What information do we collect?

We collect information from you when you register on our site, place an order, subscribe to our newsletter, respond to a survey or fill out a form.

Any data we request that is not required will be specified as voluntary or optional.

When ordering or registering on our site, as appropriate, you may be asked to enter your: name, e-mail address, mailing address, phone number or credit card information. You may, however, visit our site anonymously.

Google, as a third party vendor, uses cookies to serve ads on your site. Google’s use of the DART cookie enables it to serve ads to your users based on their visit to your sites and other sites on the Internet. Users may opt out of the use of the DART cookie by visiting the Google ad and content network privacy policy.

What do we use your information for?

Any of the information we collect from you may be used in one of the following ways:

• To improve customer service
(your information helps us to more effectively respond to your customer service requests and support needs)

• To process transactions
Your information, whether public or private, will not be sold, exchanged, transferred, or given to any other company for any reason whatsoever, without your consent, other than for the express purpose of delivering the purchased product or service requested by the customer.

• To send periodic emails

The email address you provide for order processing, may be used to send you information and updates pertaining to your order or request, in addition to receiving occasional company news, updates, promotions, related product or service information, etc.

Note: If at any time you would like to unsubscribe from receiving future emails, we include detailed unsubscribe instructions at the bottom of each email.

How do we protect your information?

We implement a variety of security measures to maintain the safety of your personal information when you place an order or access your personal information.

These security measures include: password protected directories and databases to safeguard your information, SSL (Secure Sockets Layered) technology to ensure that your information is fully encrypted and sent across the Internet securely or PCI Scanning to actively protect our servers from hackers and other vulnerabilities.

We offer the use of a secure server. All supplied sensitive/credit information is transmitted via Secure Socket Layer (SSL) technology and then encrypted into our Payment gateway providers database only to be accessible by those authorized with special access rights to such systems, and are required to keep the information confidential.

After a transaction, your private information (credit cards, social security numbers, financials, etc.) will not be stored on our servers.

Do we use cookies?

Yes (Cookies are small files that a site or its service provider transfers to your computer’s hard drive through your Web browser (if you allow) that enables the sites or service providers systems to recognize your browser and capture and remember certain information. You can opt-out of cookie tracking from your computer.

Do we disclose any information to outside parties?

We do not sell, trade, or otherwise transfer to outside parties your personally identifiable information. This does not include trusted third parties who assist us in operating our website, conducting our business, or servicing you, so long as those parties agree to keep this information confidential. We may also release your information when we believe release is appropriate to comply with the law, enforce our site policies, or protect ours or others’ rights, property, or safety. However, non-personally identifiable visitor information may be provided to other parties for marketing, advertising, or other uses.

Third party links

Occasionally, at our discretion, we may include or offer third party products or services on our website. These third party sites have separate and independent privacy policies. We therefore have no responsibility or liability for the content and activities of these linked sites. Nonetheless, we seek to protect the integrity of our site and welcome any feedback about these sites.

Policy against advertising our website using unsolicited email messages

We require that all e-mails promoting purehealthresearch.com or its subsidiaries are sent only to clients who have agreed to receive such messages. We prohibit any advertising of our brands and Web sites using unsolicited email messages. Not complying with this policy will cause partnership termination and/or affiliate account termination.

If you feel you’ve been sent unsolicited emails promoting one or more of our brands or websites and would like to register a complaint, please email support@purehealthresearch.com. We will immediately investigate all allegations made related to unsolicited messages.

California Online Privacy Protection Act Compliance

Because we value your privacy we have taken the necessary precautions to be in compliance with the California Online Privacy Protection Act. We therefore will not distribute your personal information to outside parties without your consent.

As part of the California Online Privacy Protection Act, all users of our site may make any changes to their information at anytime by logging into their control panel and going to the ‘Edit My Profile’ page.

Childrens Online Privacy Protection Act Compliance

We are in compliance with the requirements of COPPA (Childrens Online Privacy Protection Act), we do not collect any information from anyone under 13 years of age. Our website, products and services are all directed to people who are at least 13 years old or older.

CAN-SPAM Compliance

We have taken the necessary steps to ensure that we are compliant with the CAN-SPAM Act of 2003 by never sending out misleading information.

Online Privacy Policy Only

This online privacy policy applies only to information collected through our website and not to information collected offline.

Your Consent

By using our site, you consent to our privacy policy.

Changes to our Privacy Policy

If we decide to change our privacy policy, we will post those changes on this page, and/or update the Privacy Policy modification date below. Policy changes will apply only to information collected after the date of the change.

This policy was last modified on 12/16/15

Contacting Us

If there are any questions regarding this privacy policy you may contact us using the information below.

www.purehealthresearch.com
PureHealth Research
PO Box 153201 Suite #1053 Tampa,
FL 33634, United States
Contact Us, toll free (888) 558-9836

Respectfully,

PureHealth Research Team
www.purehealthresearch.com

Site Terms of Use
The Website is an Internet property of PureHealth Research (“PureHealth,” “we” or “us”). You agree to the following Website Terms of Use in their entirety, when you: (1) access or use the Website; and/or (2) purchase products or services offered on our Website (“Online Products”). The Privacy Policy (“Privacy Policy”) and any and all other applicable PureHealth Research operating rules, policies, price schedules and other supplemental terms and conditions or documents that may be published from time to time, are expressly incorporated herein by reference (collectively, the “Agreement”). Please review the Agreement carefully. If you do not agree to the terms and conditions contained within the Agreement in its entirety, you are not authorized to use the Website in any manner or form whatsoever.

1. Definitions
   The “PureHealth Sites” shall mean all areas and services offered or available on the interactive online service operated by PureHealth Research and/or its affiliates on the World Wide Web. The PureHealth sites consist of information, services and content provided by PureHealth Research and/or its affiliates and/or third parties.
2. General
   PureHealth shall have the right at any time to change or discontinue any aspect or feature of the PureHealth including, but not limited to, the content, hours of availability, and equipment needed for access or use. Such changes, modifications, additions or deletions shall be effective immediately without further notice thereof. Amendments to the terms and conditions contained herein may be given by means including but not limited to, posting on the PureHealth Sites a revised version of this Agreement or notification by electronic mail. Any use of the PureHealth Sites after such notice shall conclusively be deemed to be acceptance of such changes, modifications, additions or deletions. The user agrees to review the terms and conditions of this Agreement periodically to be aware of such revisions.
3. Use of the PureHealth Sites.
   • A. The PureHealth Sites contain copyrighted material; trademarks and other proprietary information including text, software, photos, video, graphics, music and sound, and the entire contents of the PureHealth Sites are copyrighted as a collective work under the United States copyright laws. PureHealth is the owner of the copyright in the entire PureHealth Sites. PureHealth owns a copyright in the selection, coordination, arrangement and enhancement of such content, as well as in the content original to it. Each third party content provider owns the copyright in content original to it. You may not modify, publish, transmit, display, participate in the transfer or sale, create derivative works, or in any way exploit the content of the PureHealth Sites or any portion of it. Except as otherwise expressly permitted under copyright law, you may not copy, redistribute, publish, display or commercially exploit any material from the PureHealth Sites without the express permission of PureHealth and, if applicable, the copyright owner. In the event of any permitted copying, redistribution or publication of material from the PureHealth Sites, no changes in or deletion of author attribution, trademark, legend or copyright notice shall be made. You acknowledge that you do not acquire any ownership rights by downloading or copying copyrighted material.
   • B. You hereby grant to PureHealth and its respective affiliates worldwide, royalty-free, perpetual, irrevocable, non-exclusive right and license to use, reproduce, modify, adapt, publish, translate, create derivative works from, distribute, perform and display any e-mail, video, graphic, data, or information sent by you to PureHealth (in whole or in part) and/or to incorporate it in other works in any form, media or technology now known or later developed.
   • C. You shall provide PureHealth with accurate, complete and updated information provided by you at the time of your purchase.
   • D. The PureHealth Sites contain links to other Web sites, resources and advertisers. PureHealth is not responsible for the availability of these external sites nor does it endorse or is it responsible for the contents, advertising, products or other materials made available on or through such external sites. Under no circumstances shall PureHealth be held responsible or liable, directly or indirectly, for any loss or damage caused or alleged to have been caused to a user in connection with the use of or reliance on any content, goods or services available on such external site. You should direct any concerns to such external site’s administrator or web master.
   • E. You agree not to take any action to interfere with the function or accessibility of the PureHealth Site or to take any action to restrict the access of others thereto.
   • F. The foregoing provisions of this Section 3 are for the benefit of PureHealth, its affiliates, third party content providers and licensors, and each shall have the right to assert and enforce such provisions directly on its own behalf or jointly with others.
   • G. PureHealth has carefully designed the PureHealth Site with the purpose of delivering certain content to users in a particular format and with a particular appearance. No third party shall have the right to utilize the content of the PureHealth Site in any way that interferes with that purpose. In particular, PureHealth prohibits any party from displaying the content on the PureHealth Sites in any format where third party advertising or other materials that PureHealth did not authorize in writing is viewed or viewable together with PureHealth’ proprietary content.
4. Disclaimer of Warranty; Limitation of Liability.
   • A. YOU EXPRESSLY AGREE THAT USE OF THE PureHealth SITE IS AT YOUR SOLE RISK. NEITHER PureHealth, ITS AFFILIATES NOR ANY OF THEIR RESPECTIVE EMPLOYEES, AGENTS, THIRD PARTY CONTENT PROVIDERS OR LICENSORS WARRANT THAT THE PureHealth WILL BE UNINTERRUPTED OR ERROR FREE; NOR DO THEY MAKE ANY WARRANTY AS TO THE RESULTS THAT MAY BE OBTAINED FROM USE OF THE PureHealth SITE OR AS TO THE ACCURACY, RELIABILITY OR CONTENT OF ANY INFORMATION, SERVICE OR PRODUCTS PROVIDED THROUGH THE SITES.
   • B. THE PureHealth SITES ARE PROVIDED ON AN “AS IS”, “AS AVAILABLE” BASIS WITHOUT WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO WARRANTIES OF TITLE OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OTHER THAN THOSE WARRANTIES WHICH ARE IMPLIED BY AND INCAPABLE OF EXCLUSION, RESTRICTION OR MODIFICATION UNDER THE LAWS APPLICABLE TO THIS AGREEMENT.
   • C. THE DISCLAIMERS OF LIABILITY CONTAINED IN THIS SECTION APPLY TO ANY DAMAGES OR INJURY CAUSED, DIRECTLY OR INDIRECTLY, BY ANY FAILURE OF PERFORMANCE, ERROR, OMISSION, INTERRUPTION, DELETION, DEFECT, DELAY IN OPERATION OR TRANSMISSION, COMPUTER VIRUS, COMMUNICATION LINE FAILURE, THEFT OR DESTRUCTION OR UNAUTHORIZED ACCESS TO, ALTERATION OF, OR USE OF RECORD, WHETHER FOR BREACH OF CONTRACT, TORTUOUS BEHAVIOR, NEGLIGENCE, OR UNDER ANY OTHER CAUSE OF ACTION. YOU SPECIFICALLY ACKNOWLEDGE THAT PureHealth IS NOT LIABLE FOR THE DEFAMATORY, OFFENSIVE OR ILLEGAL CONDUCT OF OTHER USERS OR THIRD PARTIES AND THAT THE RISK OF INJURY FROM THE FOREGOING RESTS ENTIRELY WITH YOU.
   • D. IN NO EVENT WILL PureHealth OR ANY PERSON OR ENTITY INVOLVED IN CREATING, PRODUCING OR DISTRIBUTING THE PureHealth SITE BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE USE OF OR INABILITY TO USE THE PureHealth OR OUT OF THE BREACH OF ANY WARRANTY. YOU HEREBY ACKNOWLEDGE THAT THE PROVISIONS OF THIS SECTION 4 SHALL APPLY TO ALL CONTENT ON THE PureHealth SITE. PureHealth’S LIABILITY TO USERS, IF ANY, SHALL IN NO EVENT EXCEED THE TOTAL AMOUNT PAID TO PureHealth.
   • E. PureHealth NEITHER ENDORSES NOR IS RESPONSIBLE FOR THE ACCURACY OR RELIABILITY OF ANY OPINION, ADVICE OR STATEMENT ON THE PureHealth SITE, NOR FOR ANY OFFENSIVE, DEFAMATORY OR OBSCENE POSTING MADE BY. UNDER NO CIRCUMSTANCES WILL PureHealth BE LIABLE FOR ANY LOSS OR DAMAGE CAUSED BY YOUR RELIANCE ON INFORMATION OBTAINED THROUGH THE CONTENT ON THE PureHealth SITE. IT IS YOUR RESPONSIBILITY TO EVALUATE THE ACCURACY, COMPLETENESS OR USEFULNESS OF ANY INFORMATION, OPINION, ADVICE OR OTHER CONTENT AVAILABLE THROUGH THE PureHealth SITES. PLEASE SEEK THE ADVICE OF PROFESSIONALS, AS APPROPRIATE, REGARDING THE EVALUATION OF ANY SPECIFIC INFORMATION, OPINION, ADVICE OR OTHER CONTENT, INCLUDING BUT NOT LIMITED TO FINANCIAL, HEALTH, OR LIFESTYLE INFORMATION, OPINION, ADVICE OR OTHER CONTENT.
   • F. PureHealth DOES NOT ENDORSE, WARRANT OR GUARANTEE ANY PRODUCTS OR SERVICES OFFERED THROUGH THE PureHealth SITES (WITH THE SOLE EXCEPTION BEING WRITTEN WARRANTIES PROVIDED IN CONNECTION WITH PureHealth PRODUCTS OR SERVICES) AND WILL NOT BE A PARTY TO OR IN ANY WAY MONITOR ANY TRANSACTION BETWEEN USERS AND THIRD PARTY PROVIDERS OF PRODUCTS OR SERVICES. AS WITH THE PURCHASE OF A PRODUCT OR SERVICE THROUGH ANY MEDIUM OR IN ANY ENVIRONMENT, YOU SHOULD USE YOUR BEST JUDGMENT AND EXERCISE CAUTION WHERE APPROPRIATE. PureHealth MAKES PRODUCTS OR SERVICES AVAILABLE ON THE PureHealth SITES WITHOUT WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO WARRANTIES OF TITLE OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OTHER THAN THOSE WARRANTIES WHICH ARE IMPLIED BY AND INCAPABLE OF EXCLUSION, RESTRICTION OR MODIFICATION UNDER THE LAWS APPLICABLE TO THIS AGREEMENT.
5. Indemnification
   You agree to defend, indemnify and hold harmless PureHealth, its affiliates and their respective directors, officers, employees and agents from and against all claims and expenses, including attorneys’ fees, arising out of the use by you of the PureHealth Sites, including claims by other users of your equipment, access or membership.
6. Termination
   PureHealth shall have the right to immediately terminate this Agreement with respect to any user which PureHealth, in its sole discretion, considers to be unacceptable, or in the event of any breach by you of this Agreement. The provisions of Sections 3, 4, 5, 6, 7, and 8 shall survive termination of this Agreement.
7. Trademarks
   All trademarks appearing on the PureHealth Sites are the property of their respective owners, including, in some instances, PureHealth, and/or affiliated companies.
8. Title & Risk of Loss
   All Online Products purchased from PureHealth are made pursuant to a shipment contract with our carriers. That means that risk of loss and title for the Online Products purchased pass to you upon our delivery to the carrier.

Miscellaneous
This Agreement and any operating rules for the PureHealth Sites established by PureHealth constitute the entire agreement of the parties with respect to the subject matter hereof, and supersede all previous written or oral agreements between the parties with respect to such subject matter. This Agreement shall be construed in accordance with the laws of the State of Texas without regard to its conflict of laws rules. Any dispute arising under or relating to this Agreement or any PureHealth Site shall be brought in state or federal courts in Austin, Texas, and you hereby irrevocably consent to the jurisdiction of such courts. No waiver by either party of any breach or default hereunder shall be deemed to be a waiver of any preceding or subsequent breach or default. You also give full permission to PureHealth to charge other accounts provided on items purchased and not paid for. The section headings used herein are for convenience only and shall not be given any legal import.

PureHealth Research wants you to be completely satisfied with your experience so we have made returning or exchanging products easy. You are backed by a 1-Year Money Back Guarantee and a 1-Year Exchange Guarantee.

Simply return the empty and unused portion of your PureHealth Research  product order within 1 year of your billing date for a full refund of the product price.

Return and Exchange Procedures:

1. Refunds/Exchanges: Contact our customer support center 24 hours a day at Support [at] PureHealthResearch .com, or call us at (888) 558-9836, M – F 9AM – 5PM EST, for a Return Merchandise Authorization Number (RMA#) or an Exchange Merchandise Number (EMA#) and the Return Address.
2. Return the empty and unused portion of your product, the original invoice and your RMA# or EMA# to ensure proper handling. If you would like to exchange your return for another quality product of equal or lesser value, please indicate what product(s) in your return.
3. Exchanges: We offer a 1-year exchange program where you can return a product and request that we send you another quality PureHealthResearch product of equal or lesser value with free shipping. All exchanges are final.
4. Important: Return postage is the responsibility of the customer and we recommend using delivery confirmation to avoid any delays. All packages returned refused or undeliverable will be refunded the cost of the product minus the shipping fees incurred by refusal of the package.
5. Returns must be received in our offices within 1 year from billing date. All charges (excluding shipping and handling fees) are fully refundable 1 year from the billing date. Exchange requests must be received by our offices within 1 year from the billing date.
6. Used/Empty product containers may only be returned if adequate time has elapsed to consume the product as directed on the label. For example, we will not accept a six-month supply of empty product containers after only one or two months.
7. All refunds will be processed within 72 hours of receiving the package. After a return has been processed, it may take up to 5 business days for the Bank to process the refund to the credit card.

Allure Cosmeceuticals

DARK SPOT CORRECTOR

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Purified Water

Rapid enumeration of physiologically active bacteria in purified water used in the pharmaceutical manufacturing process

Abstract

Physiologically active bacteria in purified water used in the manufacturing process of pharmaceutical products were enumerated in situ. Bacteria with growth potential were enumerated using the micro-colony technique and direct viable counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean Casein Digest Broth) at 30 °C. Respiring and esterase-active bacteria were detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of bacteria in purified water retained physiological activity, while most could not form colonies on conventional media. The techniques applied in this study enabled bacteria to be counted within 24 h so results could be available within one working day. These rapid and convenient techniques should be useful for the systematic monitoring of bacteria in water used for pharmaceutical manufacturing.

M. Kawai,N. Yamaguchi andM. Nasu.Journal of Applied Microbiology. Volume 86, Issue 3, pages 496–504, March 1999. DOI: 10.1046/j.1365-2672.1999.00689.x
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.1999.00689.x/full

Free radical scavenging activity of a novel antioxidative peptide purified from hydrolysate of bullfrog skin, Rana catesbeiana Shaw

Abstract

In the present study, a peptide having antioxidant properties was isolated from bullfrog skin protein, Rana catesbeiana Shaw. Bullfrog skin protein was hydrolyzed using alcalase, neutrase, pepsin, papain, α-chymotrypsin and trypsin. Antioxidant activities of respective hydrolysates were evaluated using lipid peroxidation inhibition assay and direct free radical scavenging activity by using electron spin resonance (ESR) spectrometer. Among hydrolysates, alcalase derived hydrolysate exhibited the highest antioxidant activities than those of other enzyme hydrolysates. In order to purity a peptide having potent antioxidant properties, alcalase hydrolysate was separated using consecutive chromatographic methods on a Hiprep 16/10 DEAE FF anion exchange column, Superdex Peptide 10/300 GL gel filtration column and highan octadecylsilane (ODS) C18 reversed phase column. Finally, a potent antioxidative peptide was isolated and its sequence was identified to be LEELEEELEGCE (1487 Da) by Q-TOF ESI mass spectroscopy. This antioxidant peptide from bullfrog skin protein (APBSP) inhibited lipid peroxidation higher than that of α-tocopherol as positive control and efficiently quenched different sources of free radicals: DPPH radical (IC₅₀ = 16.1 μM), hydroxyl radical (IC₅₀ = 12.8 μM), superoxide radical (IC₅₀ = 34.0 μM) and peroxyl radical (IC₅₀ = 32.6 μM). Moreover, MTT assay showed that this peptide does not exert any cytotoxicity on human embryonic lung fibroblasts cell line (MRC-5).

Zhong-Ji Qian,Won-Kyo Jung,Se-Kwon Kim.Bioresource Technology. Volume 99, Issue 6, April 2008, Pages 1690–1698.doi:10.1016/j.biortech.2007.04.005

Glycerine

Glycerol and the skin: holistic approach to its origin and functions

Summary

Glycerol is a trihydroxy alcohol that has been included for many years in topical dermatological preparations. In addition, endogenous glycerol plays a role in skin hydration, cutaneous elasticity and epidermal barrier repair. The aquaporin-3 transport channel and lipid metabolism in the pilosebaceous unit have been evidenced as potential pathways for endogenous delivery of glycerol and for its metabolism in the skin. Multiple effects of glycerol on the skin have been reported. The diverse actions of the polyol glycerol on the epidermis include improvement of stratum corneum hydration, skin barrier function and skin mechanical properties, inhibition of the stratum corneum lipid phase transition, protection against irritating stimuli, enhancement of desmosomal degradation, and acceleration of wound-healing processes. Even an antimicrobial effect has been demonstrated. Topical application of glycerol-containing products improves skin properties in diseases characterized by xerosis and impaired epidermal barrier function, such as atopic dermatitis. The increase of epidermal hydration by glycerol is critical in skin conditions aggravated by dry and cold environmental conditions, e.g. winter xerosis. This paper provides a review on effects of glycerol on the skin, the mechanisms of its action, and the potential applications of glycerol in dermatology.

Fluhr, J.W., Darlenski, R. and Surber, C. (2008), Glycerol and the skin: holistic approach to its origin and functions. British Journal of Dermatology, 159: 23–34. doi: 10.1111/j.1365-2133.2008.08643.x

A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial.

Summary

MethodsFor the patch test, commercially available test product and its vehicle were applied occluded for 12-days to photoaged forearm skin ( n = 10) prior to biopsy and immunohistochemical assessment of fibrillin-1; all-trans retinoic acid (RA) was used as a positive control. Sixty photoaged subjects were recruited to the RCT (test product, n = 30 vs. vehicle, n = 30; once daily for 6-months; face & hands) with clinical assessments performed at recruitment and following 1-, 3- & 6-months of use. Twenty-eight subjects had skin biopsies (dorsal wrist) at baseline and at 6 months of treatment for immunohistochemical assessment of fibrillin-1 (test product, n = 15; vehicle, n = 13). All subjects received test product for a further 6-months. Final clinical assessments were performed at the end of this open period; 27 subjects received test product for 12-months.

ResultsIn the 12-day patch test assay, we observed significant immunohistological deposition of fibrillin-1 in skin treated by test product and RA as compared to untreated baseline ( P = 0·005 and 0·015 respectively). In the clinical RCT, at 6 months, compared to baseline assessment, 43% of subjects on test product had an improvement in facial wrinkles (P = 0·013), whereas only 22% of subjects using vehicle had clinical improvement (P = ns). Between group comparison of test product and vehicle was non-significant (P = 0·10). After 12 months, there was a significant benefit of test product over that projected for vehicle (70% vs. 33% of subjects improving; combined Wilcoxon rank tests, P = 0·026). There was significant deposition of fibrillin-1 in skin treated for 6 months with test product (mean ± SE; vehicle, 1·84 ± 0·23; test product, 2·57 ± 0·19; P = 0·019).

ConclusionAn over-the-counter cosmetic ‘anti-ageing’ product demonstrated clear benefit over vehicle in fibrillin-1 deposition over a 6-month trial period. There was a corresponding but non-significant trend towards clinical improvement in facial wrinkles. Clinical improvements in the treated group were increased after a further 6-months of use. This study demonstrates that a cosmetic may improve the appearance of wrinkles and further supports the use of fibrillin-1 as a robust biomarker for repair of photoaged dermis.

Watson, R.E.B., Ogden, S., Cotterell, L.F., Bowden, J.J., Bastrilles, J.Y., Long, S.P. and Griffiths, C.E.M. (2009), A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial. British Journal of Dermatology, 161: 419–426. doi: 10.1111/j.1365-2133.2009.09216.x

The Euro Skin Bank: Development and Application of Glycerol-Preserved Allografts.

Mackie, David P. FRCA. The Euro Skin Bank: Development and Application of Glycerol-Preserved Allografts.ournal of Burn Care & Rehabilitation.January/February 1997 – Volume 18 – Issue 1 – ppg s7-s9.

http://journals.lww.com/burncareresearch/Citation/1997/01001/The_Euro_Skin_Bank__Development_and_Application_of.4.aspx

Stearyl Alcohol

Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol help to form emulsions and prevent an emulsion from separating into its oil and liquid components. These ingredients also reduce the tendency of finished products to generate foam when shaken. When used in the formulation of skin care products, Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol act as a lubricant on the skin surface, which gives the skin a soft, smooth appearance.

Solubilities of stearic acid, stearyl alcohol, and arachidyl alcohol in supercritical carbon dioxide at 35.degree.C

ABSTRACT The solubilities of stearic acid (octadecanoic acid), stearyl alcohol (1-octadecanol), and arachidyl alcohol (1-eicosanol) in supercritical carbon dioxide were measured by using a flow-type apparatus at 35 C up to 23.7 MPa. The solubilities of those substances and other fatty acids and higher alcohols in supercritical carbon dioxide at 35 C were correlated by a solution model based on the regular solution model coupled with the Flory-Huggins theory.

Yoshio Iwai , Yoshio Koga , Hironori Maruyama , Yasuhiko Arai. J. Solubilities of stearic acid, stearyl alcohol, and arachidyl alcohol in supercritical carbon dioxide at 35°C. Chem. Eng. Data, 1993, 38 (4), pp 506–508. DOI: 10.1021/je00012a005

http://www.researchgate.net/publication/238656304_Solubilities_of_stearic_acid_stearyl_alcohol_and_arachidyl

Effect of cetostearyl alcohol on stabilization of oil-in-water emulsion: I. Difference in the effect by mixing cetyl alcohol with stearyl alcohol

Abstract

It is known that an oil-in-water emulsion increases in consistency and stability on addition of cetostearyl alcohol. When either cetyl alcohol or stearyl alcohol was added individually, the emulsion stability decreased. On storage at room temperature, unstable emulsions decreased in consistency and many particles (not visible immediately after preparation) appeared. The particles were determined to be crystals of the alcohol added. When both alcohols were included in the formulation simultaneously in the appropriate ratio, the emulsions were stable and did not show such changes. This difference in stability can be explained in relation to polymorphism of the alcohols.

S Fukushima,M Takahashi,M Yamaguchi. Journal of Colloid and Interface Science

Volume 57, Issue 2, November 1976, Pages 201-206. doi:10.1016/0021-9797(76)90193-4

http://www.sciencedirect.com/science/article/pii/0021979776901934

Microencapsulation of a waxy solid: Wall thickness and surface appearance studies

1. L. Madan, L. A. Luzzi and J. C. Price. Journal of Pharmaceutical Sciences

Volume 63, Issue 2, pages 280–284, February 1974. DOI: 10.1002/jps.2600630224.

Contact Dermatitis From Stearyl Alcohol and Propylene Glycol in Fluocinonide Cream

Abstract

A young woman being treated for linear scleroderma became allergic to fluocinonide (Lidex) cream while using it with occlusion. She was able to continue treatment with fluocinonide ointment without an adverse reaction.

Patch testing with the ingredients of the cream demonstrated sensitization to an impurity in commercial stearyl alcohol and irritation from propylene glycol. The woman had no adverse reactions to fluocinonide ointment because this preparation contains no stearyl alcohol and very little propylene glycol.

This case reemphasizes the important role of vehicles in contact allergy and indicates that allergic sensitization may be induced despite the presence of a potent topical steroid.

Ronald N. Shore, MD; Walter B. Shelley, MD, PhD. Arch Dermatol. 1974;109(3):397-399. doi:10.1001/archderm.1974.01630030055015.

http://archderm.jamanetwork.com/article.aspx?articleid=533859

Mechanism of Formation and Structure of Micro Emulsions by Electron Microscopy

Jack H. Schulman , Walter Stoeckenius , Leon M. Prince. J. Phys. Chem., 1959, 63 (10), pp 1677–1680. DOI: 10.1021/j150580a027

Tempering influence on oxygen and water vapor transmission through a stearyl alcohol film

Abstract

Stearyl alcohol was layered on a filter paper support and tested for resistance to O₂ and water vapor transmission following tempering. Tempering at 48C for 14 or 35 days caused the resistance to O₂and water vapor transmission to increase. The resistance to O₂ and water vapor transport was increased 80% and 50% respectively, after 35 days. Likely mechanistic explanations include the healing of crystal imperfections and the development of a more extensive and better linked arrangement of lipid crystalline platelets.

1157. J. Kester, O. Fennema. Journal of the American Oil Chemists’ Society. August 1989, Volume 66, Issue 8, pp 1154-1157.

http://link.springer.com/article/10.1007/BF02670102

Phase diagram of mixtures of stearic acid and stearyl alcohol

Abstract

Stearyl alcohol (98.4%), stearic acid (96.0%) and their binary mixtures were investigated by differential scanning calorimetry (DSC) at a heating and cooling rate of 10 K min⁻¹. The phase diagrams on heating and cooling were constructed and showed a eutectic behavior for the solid–liquid equilibrium line. In the heating phase diagram, the eutectic line was not always visible due to the existence of a phase transition in the solid state. A shift in the eutectic phase composition towards the acid was observed on cooling. The cooling and heating phase diagrams further differed in the fact that only two exotherms were observed during cooling where three endotherms were observed during heating. A plot of the enthalpy of the mixtures versus the mole fraction shows that different processes are involved in the solid state.

François G Gandolfo, Arjen Bot, Eckhard Flöter. Thermochimica Acta. Volume 404, Issues 1–2, 4 September 2003, Pages 9–17. doi:10.1016/S0040-6031(03)00086-8

http://www.sciencedirect.com/science/article/pii/S0040603103000868

Ceteareth-20

Final Report on the Safety Assessment of Ceteareth-2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -13, -14, -15, -16, -17, -18,-20,-22,-23,-24,-25,-27, -28, -29, -30, -33, -34, -40, -50, -55, -60, -80, and -100.

Abstract

Ceteareths, used in a large number of cosmetics as surfactants, are the polyethylene glycol (PEG) ethers of Cetearyl Alcohol (q,v.). To supplement the limited available data on Ceteareths, previous findings from the safety assessment of Polyethylene Glycol (PEG), several fatty alcohols (Cetearyl Alcohol, Cetyl Alcohol, and Stearyl Alcohol), and Steareths were considered. These data indicate little evidence of toxicity. Although various metabolites of monoalkyl ethers of ethylene glycol are reproductive and developmental toxins, given the methods of manufacture of Ceteareth compounds, there is no likelihood of such compounds being present as impurities. Further, there would be only limited ethylene glycol monomer linked by an ether group to the Ceteareth moiety for the PEG-5 compounds, little for the PEG-10 compounds, and virtually none for the PEG-20 and higher compounds. Even if linked to ethylene glycol monomer, it was considered unlikely that the Ceteareth moieties would be metabolized (e,g., via β-oxidation) to simple methyl, ethyl, propyl, or butyl alkyl groups. As the current data indicate, such short alkyl chains are needed in order for the production of toxic alcohol or aldehyde dehydrogenase metabolites. For longer alkyl chains there is evidence of diminishing toxicity, and extrapolation to much longer chains such as expected in the Ceteareth moieties suggests that there is no reproductive or developmental hazard posed by these Ceteareth compounds. The principal clinical finding related to PEGs is based on data in bum patients— PEGs were mild irritants/sensitizers and there was evidence of nephrotoxicity. No such effects were seen in animal studies on intact skin. Cosmetic manufacturers should adjust product formulations containing Polyethylene Glycol to minimize any untoward effects when products are used on damaged skin. In the absence of specific impurities data, the possible presence of 1,4-dioxane and ethylene oxide impurities was of concern. The importance of using the necessary purification procedures to remove these impurities was stressed. Creams containing Ceteareth-20 enhanced drug absorption. Ceteareth-15 (10% in formulation) was minimally irritating to rabbits after a single dermal exposure. In ocular studies, ethoxylated Cetearyl Alcohol solution was a severe irritant to unrinsed rabbit eyes and moderately irritating to rinsed eyes. In clinical studies, Ceteareth-15 (1.5 % in formulation) produced minimal irritation when tested in both a 4- and 21-day patch test, and was not a sensitizer when tested (1.35% in formulation) in a repeat-insult patch test. Based on the limited data on Ceteareths and the extensive data on chemically related ingredients, it was concluded that these ingredients are safe as used in cosmetic formulations. These ingredients, however, should not be used on damaged skin.

49. Alan Andersen. International Journal of Toxicology April 1999 vol. 18 no. 3 suppl 41-49. doi: 10.1177/109158189901800306

Attainment of Emulsions with Liquid Crystal from Marigold Oil Using the Required HLB Method.

Abstract

Development of new formulations for topical use and cosmetic and pharmaceutical delivery agents has increased the complexity of emulsified systems. Liquid crystals, known since the nineteenth century are the third phase of an emulsion, being responsible for increasing its stability and the solubility of substances poorly soluble in water, or the oily phase, modulating the release of drugs imprisoned in its structure and promoting hydration of the skin surface. In the present work we developed oil/water emulsions, making use of Marigold oil (Calendula officinalis L) and ethoxylated fat alcohols as surfactant. The required HLB value for marigold oil was determined to be 6.0. The surfactants were associated in lipophilic/hydrophilic pairs. The lipophilic surfactants were Ceteth‐2 and Steareth‐2 and the hydrophilic surfactants were Steareth‐20, Ceteareth‐20, Ceteareth‐5, and Ceteth‐10. To identify the liquid crystalline phases, the emulsions were analyzed by polarized light microscopy. The physical stability was evaluated by rheology and zeta potential analysis. All emulsions presented lamellar liquid crystal structures. Results showed that this type of surfactant is able to produce liquid crystal in the system, with slight difference in appearance, influencing the physical stability, according to the methods applied.

Orlando David Henrique dos Santosa*, Juliana Violi Miottoa, Jacqueline Moreira de Moraisa, Pedro Alves da Rocha‐Filhoa & Wanderley Pereira de Oliveirab. Attainment of Emulsions with Liquid Crystal from Marigold Oil Using the Required HLB Method. Journal of Dispersion Science and Technology.Volume 26, Issue 2, 2005 pages 243-249.DOI:10.1081/DIS-200045610

A Guide to the Ingredients and Potential Benefits of Over-the-Counter Cleansers and Moisturizers for Rosacea Patients

Abstract:

It is difficult for rosacea patients to discern which products and ingredients will be beneficial to their skin and which products will lead to an exacerbation of the signs and symptoms of rosacea. In this paper, the authors provide a brief overview of rosacea, its pathogenesis, signs and symptoms, and the management of the two major rosacea subtypes—erythematotelangiectatic rosacea and papular pustular rosacea. Reviewed in greater detail are the common ingredients used in over-the-counter cleansers and moisturizers with discussion of how these ingredients potentially benefit or harm the skin of patients with rosacea. Clinical studies investigating the benefits of using certain over-the-counter cleansers and moisturizers in patients with erythematotelangiectatic rosacea and papular pustular rosacea with or without topical prescription therapy are also reviewed. The specific formulas used in the clinical studies include a sensitive skin synthetic detergent bar, a nonalkaline cleanser and moisturizer, polyhydroxy acid containing cleanser and moisturizer, and a ceramide-based cleanser and moisturizer formulated in a multivesicular emulsion. Based on review of available data, the authors conclude that the use of mild over-the-counter cleansers and moisturizers is beneficial for patients with erythematotelangiectatic rosacea and papular pustular rosacea. The properties of over-the-counter cleansers and moisturizers that contribute to their mildness include an acidic-neutral pH to minimize the flux in skin pH; surfactants or emulsifiers that will not strip the skin of its moisture or strip the lipids and proteins of the stratum corneum; moisturizing ingredients such as emollients, humectants, and occlusives; and formulas without potential irritants and allergens. The most consistent clinical benefits demonstrated in the reviewed studies were a subjectively perceived improvement in subjective symptoms of dryness and irritation as well as an objective improvement in dryness.

Levin J, Miller R. A Guide to the Ingredients and Potential Benefits of Over-the-Counter Cleansers and Moisturizers for Rosacea Patients. The Journal of Clinical and Aesthetic Dermatology. 2011;4(8):31-49.
Influence of hydrophilic surfactants on the properties of multiple W/O/W emulsions

Commercial applications
Study of the photostability of 18 sunscreens in creams by measuring the SPF in vitro

Abstract

The target of this research was to evaluate the photostability of various sunscreen agents incorporated into an O/W emulsion. The concept of photostability is very important in the field of solar protection. The effectiveness of the anti-solar products is quantified using a universal indicator: the sun protection factor (SPF). This number which can be found on packaging can be given in two different ways: by methods in vivo (Colipa method) and in vitro. It is this last method which was adopted for this study. According to selected filter UVB (currently directive 76/768/EEC modified authorized 18 filters UVB), we can obtain more or less effective creams. We chose the irradiation of sun lotions formulated using the authorized filters, used with their maximum amount of employment, in a Suntest, with an irradiance of 650 W/m2 throughout variable time. With interval of regular time, one carries out a measurement of SPF in order to establish for each filter the kinetics SPF = f(time). An indicator of stability (t90) is then given. In this way, we could classify the filters by order of increasing photostability.

Study of the photostability of 18 sunscreens in creams by measuring the SPF in vitro. Céline Couteau, Aurélie Faure, June Fortin, Eva Paparis, Laurence J.M. Coiffard. Journal of Pharmaceutical and Biomedical Analysis.Volume 44, Issue 1, 9 May 2007, Pages 270–273. doi:10.1016/j.jpba.2007.01.052

Porphyridium Cruentum Extract

Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum

Abstract

Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria that is widely used as a fluorescent probe and analytical reagent. In this paper, B-phycoerythrin and R-phycocyanin in native state, from the red alga Porphyridium cruentum were obtained by an inexpensive and simple process. The best results of this purification procedure were scaled up by a factor of 13 to a large preparative level using an anionic chromatographic column of DEAE cellulose. Gradient elution with acetic acid-sodium acetate buffer (pH 5.5) was used. In these conditions both 32% of B-phycoerythrin and 12% of R-phycocyanin contained in the biomass of the microalgae was recovered. B-phycoerythrin was homogeneous as determined by sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE), yielding three migrating bands corresponding to its three subunits, consistent with the (αβ)6γ subunit composition characteristic of this biliprotein and the spectroscopic characterization of B-PE (UV–visible absorption and emission spectroscopy; steady-state and polarization fluorescence), is accompanied. Finally, a preliminary cost analysis of the recovery process is presented.

Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum. R. Bermejo Román, J.M. Alvárez-Pez, F.G. Acién Fernández, E. Molina Grima.Journal of Biotechnology. Volume 93, Issue 1, 31 January 2002, Pages 73–85. doi:10.1016/S0168-1656(01)00385-6.

Preparative purification of B-phycoerythrin from the microalga Porphyridium cruentum by expanded-bed adsorption chromatography

Abstract

B-Phycoerythrin (B-PE) is a major light-harvesting pigment of microalgae. Due to its high fluorescence efficiency and its intense and unique pink color, it is widely used as a fluorescent probe and analytical reagent as well as being employed as a natural dye in foods and cosmetics. Tedious methodologies for B-PE purification have been published. In this work we present a new, fast, preparative and scaleable two-step chromatographic method for B-PE purification from the red microalga Porphyridium cruentum. Initially, phycobiliproteins were released from the microalga cells by osmotic shock and captured by applying the centrifuged cell suspension to a column containing 74 ml Streamline-DEAE equilibrated with 50 mM acetic acid–sodium acetate buffer, pH 5.5, using expanded-bed adsorption chromatography at an upward flow of 200 cm h−1. After adsorption, washing was carried out in the expanded-bed mode. Having removed unbound proteins and cellular debris, the bed was allowed to sediment and a B-PE-rich solution was eluted with a downward flow of the same 250 mM buffer. In order to obtain pure B-PE, we utilized conventional ion-exchange chromatography with a column of DEAE-cellulose loaded directly with the eluate from Streamline-DEAE and developed using a discontinuous gradient of acetic acid–sodium acetate buffer, pH 5.5. With this new methodology, 66% of B-PE contained in the biomass of the microalgae was recovered, a value significantly higher than those obtained following other methodologies. The B-PE purity was tested using sodium dodecyl sulfate–polyacrylamide gel electrophoresis and spectroscopic characterization.

Preparative purification of B-phycoerythrin from the microalga Porphyridium cruentum by expanded-bed adsorption chromatography. Ruperto Bermejo, F. Gabriel Acién, Mª.José Ibáñezb, José M. Fernández, Emilio Molina, José M. Alvarez-Pez. Journal of Chromatography B. Volume 790, Issues 1–2, 25 June 2003, Pages 317–325. Preparative Chromatography of Proteins. doi:10.1016/S1570-0232(03)00168-5

Commercial applications of microalgae

The first use of microalgae by humans dates back 2000 years to the Chinese, who used Nostoc to survive during famine. However, microalgal biotechnology only really began to develop in the middle of the last century. Nowadays, there are numerous commercial applications of microalgae. For example, (i) microalgae can be used to enhance the nutritional value of food and animal feed owing to their chemical composition, (ii) they play a crucial role in aquaculture and (iii) they can be incorporated into cosmetics. Moreover, they are cultivated as a source of highly valuable molecules. For example, polyunsaturated fatty acid oils are added to infant formulas and nutritional supplements and pigments are important as natural dyes. Stable isotope biochemicals help in structural determination and metabolic studies. Future research should focus on the improvement of production systems and the genetic modification of strains. Microalgal products would in that way become even more diversified and economically competitive.

Commercial applications of microalgae.Pauline Spolaorea, Claire Joannis-Cassan, Elie Duran, Arsène Isambert.Journal of Bioscience and Bioengineering.Volume 101, Issue 2, February 2006, Pages 87–96. doi:10.1263/jbb.101.87

Bioprocess intensification: a potential aqueous two-phase process for the primary recovery of B-phycoerythrin from Porphyridium cruentum

Abstract

A process for the primary recovery of B-phycoerythrin from Porphyridium cruentum exploiting aqueous two-phase systems (ATPS) was developed in order to reduce the number of unit operations and benefit from an increased yield of the protein product. The evaluation of system parameters such as poly(ethylene glycol) (PEG) molecular mass, concentration of PEG as well as salt, system pH and volume ratio was carried out to determine under which conditions the B-phycoerythrin and contaminants concentrate to opposite phases. PEG 1450-phosphate ATPS proved to be suitable for the recovery of B-phycoerythrin because the target protein concentrated to the top phase whilst the protein contaminants and cell debris concentrated in the bottom phase. An extraction ATPS stage comprising volume ratio (Vr) equal to 1.0, PEG 1450 24.9% (w/w), phosphate 12.6% (w/w) and system pH of 8.0 allowed B-phycoerythrin recovery with a purity of 2.9 (estimated as the relation of the 545–280 nm absorbances). The use of ATPS resulted in a primary recovery process that produced a protein purity of 2.9±0.2 and an overall product yield of 77.0% (w/w). The results reported demonstrated the practical implementation of ATPS for the design of a primary recovery process as a first step for the commercial purification of B-phycoerythrin produced by P. cruentum.

Bioprocess intensification: a potential aqueous two-phase process for the primary recovery of B-phycoerythrin from Porphyridium cruentum. Jorge Benavides, Marco Rito-Palomares. Journal of Chromatography B.Volume 807, Issue 1, 25 July 2004, Pages 33–38. doi:10.1016/j.jchromb.2004.01.028

Hydrolyzed Marine Collagen

Marine sponge collagen: isolation, characterization and effects on the skin parameters surface-pH, moisture and sebum

Abstract

A previously described isolation procedure for collagen of the marine sponge Chondrosiareniformis Nardo was modified for scaling-up reasons yielding 30% of collagen (freeze-dried collagen in relation to freeze-dried sponge). Light microscope observations showed fibrous structures. Transmission electron microscopy studies proved the collagenous nature of this material: high magnifications showed the typical periodic banding-pattern of collagen fibres. However, the results of the amino acid analysis differed from most publications, presumably due to impurities that still were present. In agreement with earlier studies, sponge collagen was insoluble in dilute acid mediums and all solvents investigated. Dispersion of collagen was facilitated when dilute basic mediums were employed. The acid–base properties of the material were investigated by titration. Furthermore, a sponge extract was incorporated in two different formulations and compared with their extract-free analogues and a commercially available collagen containing product with respect to their effects on biophysical skin parameters. None of the preparations had a noticeable influence on the physiological skin surface pH. Skin hydration increased only slightly. However, all tested formulations showed a significant increase of lipids measured by sebumetry.

Marine sponge collagen: isolation, characterization and effects on the skin parameters surface-pH, moisture and sebum.Dieter Swatscheka, Wolfgang Schatton, Josef Kellermann, Werner E.G Müller, Jörg Kreuter. European Journal of Pharmaceutics and Biopharmaceutics. Volume 53, Issue 1, January 2002, Pages 107–113.doi:10.1016/S0939-6411(01)00192-8

High-throughput quantification of hydroxyproline for determination of collagen

Abstract

An accurate and high-throughput assay for collagen is essential for collagen research and development of collagen products. Hydroxyproline is routinely assayed to provide a measurement for collagen quantification. The time required for sample preparation using acid hydrolysis and neutralization prior to assay is what limits the current method for determining hydroxyproline. This work describes the conditions of alkali hydrolysis that, when combined with the colorimetric assay defined by Woessner, provide a high-throughput, accurate method for the measurement of hydroxyproline.

High-throughput quantification of hydroxyproline for determination of collagen. Kathleen Hofman, Bronwyn Hall, Helen Cleaver, Susan Marshall. Analytical Biochemistry

Volume 417, Issue 2, 15 October 2011, Pages 289–291.doi:10.1016/j.ab.2011.06.019

Functional and bioactive properties of collagen and gelatin from alternative sources: A review.

Abstract

The rising interest in the valorisation of industrial by-products is one of the main reasons why exploring different species and optimizing the extracting conditions of collagen and gelatin has attracted the attention of researchers in the last decade. The most abundant sources of gelatin are pig skin, bovine hide and, pork and cattle bones, however, the industrial use of collagen or gelatin obtained from non-mammalian species is growing in importance. The classical food, photographic, cosmetic and pharmaceutical application of gelatin is based mainly on its gel-forming properties. Recently, and especially in the food industry, an increasing number of new applications have been found for gelatin in products such as emulsifiers, foaming agents, colloid stabilizers, biodegradable film-forming materials and micro-encapsulating agents, in line with the growing trend to replace synthetic agents with more natural ones. In the last decade, a large number of studies have dealt with the enzymatic hydrolysis of collagen or gelatin for the production of bioactive peptides. Besides exploring diverse types of bioactivities, of an antimicrobial, antioxidant or antihypertensive nature, studies have also focused on the effect of oral intake in both animal and human models, revealing the excellent absorption and metabolism of Hyp-containing peptides. The present work is a compilation of recent information on collagen and gelatin extraction from new sources, as well as new processing conditions and potential novel or improved applications, many of which are largely based on induced cross-linking, blending with other biopolymers or enzymatic hydrolysis.

Functional and bioactive properties of collagen and gelatin from alternative sources: A review. M.C. Gómez-Guillén, B. Giménez, M.E. López-Caballero, M.P. Montero.Food Hydrocolloids. Volume 25, Issue 8, December 2011, Pages 1813–1827. doi:10.1016/j.foodhyd.2011.02.007

Collagen scaffolds derived from a marine source and their biocompatibility

Abstract

The primary sources of industrial collagens are calf skin and bone. However, these carry a high risk of bovine spongiform encephalopathy or transmissible spongiform encephalopathy. In this study, a novel form of acid-soluble collagen was extracted from jellyfish in an effort to obtain an alternative and safer collagen. Porous scaffolds composed of jellyfish collagen were prepared by freeze-drying and cross-linking with 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide to be used in tissue engineering applications. Enzymatic degradation kinetics of jellyfish collagen scaffolds were controlled by EDC/NHS-cross-linking density. Results from an MTT assay indicated that jellyfish collagen exhibited higher cell viability than other naturally derived biomaterials, including bovine collagen, gelatin, hyaluronic acid, and glucan. Jellyfish collagen scaffolds also had a highly porous and interconnected pore structure, which is useful for an high-density cell seeding, an efficient nutrient and an oxygen supply to the cells cultured in the three-dimensional matrices. To determine whether jellyfish collagen evokes any specific inflammatory response compared to that induced by bovine collagen or gelatin, we measured the levels of pro-inflammatory cytokines and antibody secretions and monitored the population changes of immune cells after in vivo implantation. Jellyfish collagen was found to induce an immune response at least comparable to those caused by bovine collagen and gelatin.

Collagen scaffolds derived from a marine source and their biocompatibility. Eun Song, So Yeon Kim, Taehoon Chun, Hyun-Jung Byun, Young Moo Lee.Biomaterials. Volume 27, Issue 15, May 2006, Pages 2951–2961. doi:10.1016/j.biomaterials.2006.01.015.

Silanetriol

Structure of cyclohexylsilanetriol: The first x‐ray crystal structure of a silanetriol

The structure of cyclohexylsilanetriol C6H1 1Si(OH)3 has been determined by single‐crystal x‐ray diffraction methods. The molecule crystallizes in the monoclinic system, space group C2/m, with a=7.876(3), b=6.637(6), c=15.802(11) Å, β=95.51(3)° at −60 °C, and Z=4. The intensities of 1031 independent reflections were measured using the ω‐scan technique on a Syntex P3 diffractometer (monochromatic MoKα). The final R factor is 0.057, based on anisotropic thermal parameters for all atoms except hydrogens. The molecules pack in a head‐to‐head, tail‐to‐tail arrangement with the cyclohexyl groups forming a hydrophobic double sheet and the silanetriol groups forming a second, hydrophilic, double sheet. The structure has a distorted hydrogen bond network with the hydrogen on each oxygen having equal probability of hydrogen bonding to oxygens in two different molecules. Two types of hydrogen bonds exist in the hydrophilic double sheet; O(1)⋅⋅⋅O(2) intrasheet hydrogen bonds, 2.724(2)Å, and O(2)⋅⋅⋅O(2) intrasheet hydrogen bond, 2.722(3) Å.

Structure of cyclohexylsilanetriol: The first x‐ray crystal structure of a silanetriol. Hatsuo Ishida, Jack L. Koenig and Kenn Corwin Gardner.J. Chem. Phys. 77, 5748 (1982); http://dx.doi.org/10.1063/1.443730

Structure Determining Effect of Alcohols and Water on the Shape of the Hydrogen Bonded Network in Adducts with (9-Methyl-fluoren-9-yl)-silanetriol

Summary

(9-Methyl-fluoren-9-yl)-trichlorosilane (1) and the respective silanetriol 2 have been synthesized and characterized. In cocrystallization with 2, ethanol, methanol, and water determine the morphology of the resulting hydrogen bonded network. Thus, incorporation of ethanol/water or methanol, respectively, leads to the tubular structures 2.EtOH.H2O (2a) and 2.2MeOH (2b), whereas the incorporation of water alone results in the double sheet structure 2 . H2O (2c). The shapes of the different hydrogen bonded networks are discussed.

Structure Determining Effect of Alcohols and Water on the Shape of the Hydrogen Bonded Network in Adducts with (9-Methyl-fluoren-9-yl)-silanetriol. Manuela Schneider, Beate Neumann, Hans-Georg Stammler, Peter Jutzi.Silicon Chemistry.pp 33-44.

Glutamylamidoethyl Imidazole

Crystal Structure of Imidazole Glycerol Phosphate Synthase: A Tunnel through a (β/α)8 Barrel Joins Two Active Sites

Abstract

Background: Imidazole glycerol phosphate synthase catalyzes a two-step reaction of histidine biosynthesis at the bifurcation point with the purine de novo pathway. The enzyme is a new example of intermediate channeling by glutamine amidotransferases in which ammonia generated by hydrolysis of glutamine is channeled to a second active site where it acts as a nucleophile. In this case, ammonia reacts in a cyclase domain to produce imidazole glycerol phosphate and an intermediate of purine biosynthesis. The enzyme is also a potential target for drug and herbicide development since the histidine pathway does not occur in mammals.

Results: The 2.1 Å crystal structure of imidazole glycerol phosphate synthase from yeast reveals extensive interaction of the glutaminase and cyclase catalytic domains. At the domain interface, the glutaminase active site points into the bottom of the (β/α)8 barrel of the cyclase domain. An ammonia tunnel through the (β/α)8 barrel connects the glutaminase docking site at the bottom to the cyclase active site at the top. A conserved “gate” of four charged residues controls access to the tunnel.

Conclusions: This is the first structure in which all the components of the ubiquitous (β/α)8 barrel fold, top, bottom, and interior, take part in enzymatic function. Intimate contacts between the barrel domain and the glutaminase active site appear to be poised for crosstalk between catalytic centers in response to substrate binding at the cyclase active site. The structure provides a number of potential sites for inhibitor development in the active sites and in a conserved interdomain cavity.

Crystal Structure of Imidazole Glycerol Phosphate Synthase: A Tunnel through a (β/α)8 Barrel Joins Two Active Sites.Barnali N Chaudhuri, Stephanie C Lange, Rebecca S Myers, Sridar V Chittur, V.Jo Davisson, Janet L Smith. Structure. Volume 9, Issue 10, October 2001, Pages 987–997. doi:10.1016/S0969-2126(01)00661-X

Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase.

Abstract

Phosphate-independent glutaminase can be quantitatively solubilized from a microsomal preparation of rat kidney by treatment with papain. Subsequent gel filtration and chromatography on quaternary aminoethyl (QAE)-Sephadex and hydroxylapatite yield a 200-fold purified preparation of this glutaminase. The purified enzyme also hydrolyzes gamma-glutamylhydroxamate and exhibits substrate inhibition at high concentrations of either glutamine or gamma-glutamyhydroxamate, which is partially relieved by increasing concentrations of maleate. Rat kidney phosphate-independent glutaminase reaction is catalyzed by the same enzyme which catalyzes the gamma-glutamyltranspeptidase reaction. The ratio of glutaminase to transpeptidase activities remained constant throughout a 200-fold purification of this enzyme. The observation that the phosphate0independent glutaminase and gamma-glutamyltranspeptidase activities exhibit coincident mobilities during electrophoresis, both before and after extensive treatment with neuraminidase, strongly suggests that both reactions are catalyzed by the same enzyme. This conclusion is strengthened by the observation that maleate and various amino acids have reciprocal effects on the two activities. Maleate increases glutaminase activity and blocks transpeptidation, whereas amino acids activate the transpeptidase but inhibit glutaminase activity. In contrast, the addition of both maleate and alanine resulted in a strong inhibition of both activities. Both activities exhibit a similar distribution in the various regions of the kidney. Recovery of maximal activities in the outer stripe region of the medulla is consistent with previous quantitative microanalysis which indicated that this glutaminase activity is localized primarily in the proximal straight tubule cells. The glutaminase and transpeptidase activities have different pH optima. Examination of the product specificity suggests that decreasing pH also promotes glutaminase activity and that below pH 6.0, this enzyme functions strictly as a glutaminase. Because of the localization of this activity on the brush border membrane, these resuts are consistent with the possibility that the physiological conditions induced by metabolic acidosis could convert this enzyme from a broad specificity transpeptidase to a glutaminase. Therefore, this enzyme could contribute to the increased renal synthesis of ammonia from glutamine which is observed during metabolic acidosis.

Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase. N P Curthoys and T uhlenschmidt. March 25, 1975 The Journal of Biological Chemistry, 250, 2099-2105.

Amino Acid Metabolism

Amino Acid Metabolism.Annual Review of Biochemistry. Vol. 28: 223-256 (Volume publication date July 1959).DOI: 10.1146/annurev.bi.28.070159.001255

Alpha Arbutin

ALPHA-ARBUTIN – the more effective, faster and safer approach to skin lightening. ALPHA-ARBUTIN minimizes liver spots.

ALPHA-ARBUTIN is a pure, water soluble, biosynthetic active ingredient. ALPHA-ARBUTIN promotes lightening and an even skin tone on all skin types. ALPHA-ARBUTIN blocks epidermal melanin biosynthesis by inhibiting enzymatic oxidation of Tyrosine and Dopa. Structurally, ALPHA-ARBUTIN (IUPAC name: 4-hydroxyphenyl-α-D-glucopyranoside) is an α-glucoside. The α-glucosidic bond offers higher stability and efficacy than the β-form in the related beta-arbutin. This leads to a skin lightening active that acts faster and more efficiently than existing single components, inimizes liver spots and reduces the degree of skin tanning after UV exposure.

CHARACTERISTICS

• The more effective, faster and safer approach to skin lightening; minimize live spots.
• Promote lightening and an even skin tone on all skin types.
• Block epidermal melanin biosynthesis by inhibiting enzymatic oxidation of Tyrosine and Dopa.
• Higher stability and efficacy than β- form in the related beta-arbutin.

FUNCTION:

• Promotes lightening and an even skin tone on all skin types.
• Minimizes liver spots.
• Can reduce the degree of skin tanning after UV exposure.

Syntheses of Arbutin-α-glycosides and a Comparison of Their Inhibitory Effects with Those of α-Arbutin and Arbutin on Human Tyrosinase

Syntheses of Arbutin-α-glycosides and a Comparison of Their Inhibitory Effects with Those of α-Arbutin and Arbutin on Human Tyrosinase. Kazuhisa Sugimoto, Takahisa Nishimura, Koji Nomura, Kenji Sugimoto, Takashi Kuriki. Chemical and Pharmaceutical Bulletin. Vol. 51 (2003) No. 7 P 798-801.http://doi.org/10.1248/cpb.51.798

Inhibitory Effects of α-Arbutin on Melanin Synthesis in Cultured Human Melanoma Cells and a Three-Dimensional Human Skin Model.

Inhibitory Effects of α-Arbutin on Melanin Synthesis in Cultured Human Melanoma Cells and a Three-Dimensional Human Skin Model. Kazuhisa Sugimoto, Takahisa Nishimura, Koji Nomura, Kenji Sugimoto, Takashi Kuriki. Biological and Pharmaceutical Bulletin. Vol. 27 (2004) No. 4 P 510-514. http://doi.org/10.1248/bpb.27.510

Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: A prospective study

Abstract

Objective: To evaluate the effectiveness of a Q-switched Nd:YAG laser (MedLite C6; HOYA ConBio, Fremont, CA, USA) and 7% alpha arbutin solution (Skin Advance Laboratory, Japan) in the treatment of melasma. Methods: This was a prospective study of 35 refractory melasma cases treated with 10 weekly laser sessions, two monthly follow-up treatments and topical 7% alpha arbutin solution. Clinical photographs and severity grading on a 5-point scale were carried out by an independent observer at each visit. Results: At 6 months, 30% of study subjects received results in the excellent clearance category (> 81% reduction of melasma) and 36.7% received good (51–80% reduction) clearance. Mild and transient side effects included discomfort during treatment, erythema, whitening of fine hair and urticaria. Three cases of mottling hypo-pigmentation (8.57%) and two cases of recurrence of melasma (5.71%) were recorded. Conclusion: Combination therapy with the MedLite C6 and 7% alpha arbutin solution is an effective and well-tolerated treatment for refractory melasma.

Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: A prospective study. Niwat Polnikorn. Journal of Cosmetic and Laser Therapy.

Volume 12, Issue 3, 2010. DOI:10.3109/14764172.2010.487910

Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues

Abstract

Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with α-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of α-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues.

Yu-Ji Lim, Eunjoo H. Lee, Tong Ho Kang, Sang Keun Ha, Myung Sook Oh, Seong Min Kim, Tae-Jin Yoon, Chulhun Kang, Ji-Ho Park , Sun Yeou Kim. Research Articles Drug Actions. Archives of Pharmacal Research. March 2009, Volume 32, Issue 3, pp 367-373

Determination of alpha-arbutin, beta-arbutin and niacinamide in cosmetics by high performance liquid chromatography

A high performance liquid chromatography (HPLC) method for the determination of two optical isomers of arbutin (alpha-arbutin and beta-arbutin) and niacinamide in cosmetics was developed. The samples were extracted by the mixture of salt water and chloroform (2:1, v/v). The separation was performed on an ODS-BP column (200 mm x 4.6 mm, 5 microm, Elite) with methanol-water (10:90, v/v) as the mobile phase at a flow rate of 0.5 mL/min and 25 degrees C. The detection wavelength was set at 220 nm and the sample injection volume was 20 microL. There were good linear relationships between the mass concentration and the peak areas of alpha-arbutin, beta-arbutin and niacinamide in the ranges of 0.07-50, 0.06-50 and 0.05-50 mg/L, respectively. The relative standard deviations (RSDs, n = 7) of alpha-arbutin, beta-arbutin and niacinamide were 1.65%, 1.73% and 1.33%, respectively. The proposed method has been applied for the determination of alpha-arbutin, beta-arbutin and niacinamide in cosmetics with recoveries of 91.7%-109.6%. This method is rapid, simple and suitable for the detection of whitening ingredients in cosmetic.

Determination of alpha-arbutin, beta-arbutin and niacinamide in cosmetics by high performance liquid chromatography. Cheng P, Chen M, Zhu Y. Chinese Journal of Chromatography / Zhongguo hua xue hui [2010, 28(1):89-92]. DOI: 10.3724/SP.J.1123.2010.00089

Sodium Hyaluronate

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study.

CONCLUSIONS: This study represents the first controlled, prospective evaluation of postoperative abdominal adhesion formation and prevention after general abdominal surgery using standardized, direct peritoneal visualization. In this study, HA membrane was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions.

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study.Becker JM, Dayton MT, Fazio VW, Beck DE, Stryker SJ, Wexner SD, Wolff BG, Roberts PL, Smith LE, Sweeney SA, Moore M. Journal of the American College of Surgeons [1996, 183(4):297-306]

Intra-articular sodium yaluronate (Hyalgan®) in the treatment of patients with osteoarthritis of the knee:A randomized clinical trial.

Intra-articular sodium yaluronate (Hyalgan®) in the treatment of patients with osteoarthritis of the knee:A randomized clinical trial. R.D. Altman et al.J Rheumatol 1998; 25: 2203-12

High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.

Summary

Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks’ combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years’ duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: −35.5±26.4 mm vs −25.8±21.4, P = 0.03, Lequesne’s functional index: −3.8±4.3 vs −2.3±3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician’s overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (−4.4±5.1 vs −2.7±4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.

High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Maxime Dougados,Minh Nguyen, Véronique Listrat, Bernard Amor.Osteoarthritis and Cartilage. Volume 1, Issue 2, April 1993, Pages 97–103.doi:10.1016/S1063-4584(05)80024-X

Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies.

Abstract

The molecular weight distribution of hyaluronate (HA) in synovial fluid (SF) from 10 patients with rheumatoid arthritis (RA), from six patients with other joint disorders, and from five recently deceased persons without joint affections was investigated by a gel chromatographic procedure. A new and highly specific radioassay was used for determination of the HA concentration in the effluent from the chromatographic column, and this allowed analyses on 0.5 ml or less of untreated synovial fluid. The results confirmed the findings by others that the weight-average molecular weight (Mw) of HA in SF from patients with RA (4.8 X 10(6)) was similar to that in other joint diseases (5.0 X 10(6)) and moderately but significantly (p less than 0.001) lower than that of normal SF (7.0 X 10(6)). Furthermore, the molecular weight distribution of HA in the pathological SF was generally broad and varied considerably between individuals. The HA concentration in the pathological SF varied between 0.17 and 1.32 g/l, which is in accordance with previous reports and considerably lower than that of normal SF. Neither the nature of the arthropathy and the extent of the inflammatory process nor the pharmacological treatment had a tendency to influence the HA concentration in the SF, the mean molecular weight of HA, or its molecular weight distribution. Although the concentration of HA in SF drops in joint disease, the total amount of the polysaccharide is greatly enhanced. Also the amount of high molecular weight polysaccharide (Mw greater than 6 X 10(6)) is in excess in joint disease. The pathological state is therefore characterised not by lack of high molecular weight hyaluronate but by a dilution of it.

Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies.L B Dahl, I M Dahl, A Engström-Laurent, K Granath. Annals of the Rheumatic Diseases. The Eular Journal. Vol. 44, Issue 12, 817-822 doi:10.1136/ard.44.12.817

Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge

Abstract

This study was conducted to develop a new sponge type of biomaterial to be used for either wound dressing or scaffold for tissue engineering. We were able to prepare an insoluble matrix composed of gelatin and sodium hyaluronate (HA) by dipping the soluble sponge into 90% (w/v) acetone/water mixture containing a small amount of cross-linking agent, 1-ethyl-3-3-dimethylaminoproplycarbodiimide hydrochloride, EDC. To characterize the sponge, Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and Instron analysis were performed. The obtained results indicate that the chemically cross-linked sponge shows a cross-linking degree of 10–35%, a mean pore size of 40–160 μm, porosity of 35–67%, and a tensile strength of 10–30 gf/cm2. Especially, the porosity measured by image analysis showed a tendency to increase with HA content, resulting in an increased water uptake. The resistance to collagenase degradation in vitro increased for up to 2 days. Silver sulfadiazine (AgSD)-impregnated gelatin-HA sponge was also prepared and compared with conventional vaseline gauze by applying it onto a dorsal skin defect of wistar rat for 5, 12, and 21days. Histological results showed an enhancement of wound healing in AgSD-impregnated gelatin-HA sponge. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 48: 631–639, 1999.

Choi, Y. S., Hong, S. R., Lee, Y. M., Song, K. W., Park, M. H. and Nam, Y. S. (1999), Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge. J. Biomed. Mater. Res., 48: 631–639. doi: 10.1002/(SICI)1097-4636(1999)48:5<631::AID-JBM6>3.0.CO;2-Y

Acrylates/Steareth-20 Methacrylate

Allergic contact dermatitis to copolymers in cosmetics – case report and review of the literature

Abstract

Copolymers or heteropolymers are large molecules with high molecular weights (>1000 D). They have been underestimated for a long time as to their sensitizing capacities. Allergic contact dermatitis to 6 copolymers in cosmetics and 1 in a medical dressing has been described; however, the nature of the hapten is still unknown. We report a case of allergic contact dermatitis to polyvinylpyrrolidone (PVP)/hexadecene copolymer in a purple-colored lipstick and review the literature on allergic contact dermatitis to 7 copolymers: PVP/hexadecene, PVP/eicosene, PVP/1-triacontene, methoxy polyethyleneglycol (PEG)-22/dodecyl glycols, methoxy PEG-17/dodecyl glycols, phthalic anhydride/trimellitic anhydride/glycols, and polyvinyl methyl/maleic acid anhydride.

Quartier, S., Garmyn, M., Becart, S. and Goossens, A. (2006), Allergic contact dermatitis to copolymers in cosmetics – case report and review of the literature. Contact Dermatitis, 55: 257–267. doi: 10.1111/j.1600-0536.2006.00960.x

Polymerization of Oligo(Ethylene Glycol) (Meth)Acrylates: Toward New Generations of Smart Biocompatible Materials

ABSTRACT: Monomers composed

of a (meth)acrylate moiety

connected to a short poly(ethylene)glycol (PEG) chain are versatile building-blocks for the preparation of \smart” biorelevant materials. Many of these monomers are commercial and can be easily polymerized by either anionic, free-radical, or controlled radical polymerization. The latter approach allows synthesis of welldefined PEG-based macromolecular architectures such as amphiphilic block copolymers, dense polymer brushes, or biohybrids. Furthermore, the resulting polymers exhibit fascinating solution properties in aqueous medium.

Depending on the molecular structure of their monomer units, non linear PEG analogues can be either insoluble in water, readily soluble up to 100 8C, or thermoresponsive. Thus, these polymers can be used for building a wide variety of modern materials such as biosensors, artificial tissues, smart gels for chromatography, and drug carriers.

Polymerization of Oligo(Ethylene Glycol) (Meth)Acrylates:Toward New Generations of Smart Biocompatible Materials. JEAN-FRANC¸ OIS LUTZ. Research Group Nanotechnology for Life Science, Fraunhofer. Institute for Applied Polymer Research, 2008. DOI: 10.1002/pola.22706

Activators Regenerated by Electron Transfer for Atom-Transfer Radical Polymerization of (Meth)acrylates and Related Block Copolymers

Activators Regenerated by Electron Transfer for Atom-Transfer Radical Polymerization of (Meth)acrylates and Related Block Copolymers.Wojciech Jakubowski, Krzysztof Matyjaszewski Prof. 13 June 2006. DOI: 10.1002/ange.200600272

In-situ photopolymerization of oriented liquid-crystalline acrylates, 3. Oriented polymer networks from a mesogenic diacrylate

Abstract

Synthesis, mesomorphism, orientation and photo-initiated chain crosslinking of the liquid-crystalline diacrylate 1,4-phenylene bis{4-[6-(acryloyloxy)hexyloxy]benzoate} (1) are studied. Monomer 1 exhibits a broad nematic phase between 108 and 155°C and a monotropic smectic phase below 88°C. The monomer is uniaxially oriented in its nematic phase at a substrate which has been coated with polyimide and unidirectionally rubbed with tissue. At the transition temperature to the smectic phase the order parameter is measured to be 0,7. During polymerization, the ordering of the mesogens is frozen-in, yielding a uniaxially crosslinked network. The clear films of oriented poly(1) exhibit a birefringence Δn between 0,12 and 0,15, depending on the polymerization temperature. In the highest oriented state of 1 a small reduction of the degree of order is observed during the crosslinking reaction, whereas at higher temperatures and lower ordering of 1, the uniaxially orientation increases upon reaction. A special feature of the oriented networks is that the ordering is maintained while heating at high temperatures. The polymerization of the acrylate groups in the mesomorphic phases proceeds fast and to high conversion. Below 90°C the polymerization behaviour is similar to that of conventional isotropic diacrylates. Above 90°C the polymerization reaction of the liquid-crystalline diacrylate proceeds faster than that of an isotropic diacrylate.

Broer, D. J., Boven, J., Mol, G. N. and Challa, G. (1989), In-situ photopolymerization of oriented liquid-crystalline acrylates, 3. Oriented polymer networks from a mesogenic diacrylate. Makromol. Chem., 190: 2255–2268. doi: 10.1002/macp.1989.021900926

Atom-Transfer Radical Polymerization of Acrylates in an Ionic Liquid

Abstract

The atom-transfer radical polymerization (ATRP) of acrylates in 1-butyl-3-methylimidazolium hexafluorophosphate was investigated. The solubility of the acrylates in the ionic liquid depends on the substituent. The homogeneous polymerization of methyl acrylate gives polymers with M̄n close to the calculated value and relatively narrow polydispersity. In heterogeneous polymerizations of higher acrylates, with the catalyst present in the ionic liquid phase, deviations from ideal behavior are observed although the polymerization of butyl acrylate approaches the conditions of a controlled polymerization.

Biedroń, T. and Kubisa, P. (2001), Atom-Transfer Radical Polymerization of Acrylates in an Ionic Liquid. Macromol. Rapid Commun., 22: 1237–1242. doi: 10.1002/1521-3927(20011001)22:15<1237::AID-MARC1237>3.0.CO;2-E

Copolymer

Interaction of human skin fibroblasts with moderate wettable polyacrylonitrile–copolymer membranes

Abstract

The development of a bioartificial skin is a step toward the treatment of patients with deep burns or nonhealing skin ulcers. One possible approach is based on growing dermal cells on membranes to obtain appropriate living cellular stroma (sheets) to cover the wound. New membrane-forming copolymers were synthesized, based on acrylonitrile (AN) copolymerization with hydrophilic N-vinylpyrrolidone (NVP) monomer, in different percentage ratios, such as 5, 20, and 30% w/w, and with two other relatively high polar comonomers—namely, sodium 2-methyl-2-propene-1-sulfonic acid (NaMAS) and aminoethylmethacrylate (AeMA). All these copolymers were characterized for their bulk composition and number average molecular weight, and used to prepare ultrafiltration membranes. Water contact angles and water uptake were estimated to characterize the wettability and scanning force microscopy to visualize the morphology of the resulting polymer surface. Cytotoxicity was estimated according to the international standard regulations, and the materials were found to be nontoxic. The interaction of the membranes with human skin fibroblasts was investigated considering that these cells are among the first to colonize membranes upon implantation or with prolonged external contact. The overall cell morphology, formation of focal adhesion contacts, and cell proliferation were estimated to characterize the cell material interactions. It was found that the pure polyacrylonitrile homopolymer (PAN) membrane provides excellent conditions for seeding with fibroblasts, comparable only to a copolymer containing AeMA. In contrast, the presence of NaMAS with acidic ionic groups decreased both the attachment and proliferation of fibroblasts. Low content of NVP in the copolymer, up to about 5%, still enabled good attachment and spreading of cells, as well as subsequent proliferation of fibroblasts, but higher ratios of 20 and 30% resulted in a significant decrease of these cellular activities. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 290–300, 2002

Groth, T., Seifert, B., Malsch, G., Albrecht, W., Paul, D., Kostadinova, A., Krasteva, N. and Altankov, G. (2002), Interaction of human skin fibroblasts with moderate wettable polyacrylonitrile–copolymer membranes. J. Biomed. Mater. Res., 61: 290–300. doi: 10.1002/jbm.10191

Transdermal delivery of mixnoxidil with block copolymer nanoparticles

Abstract

We evaluated the effect of hydrodynamic size of self-assembled nanoparticles on skin penetration of minoxidil in vitro and in vivo. Self-assembled 40- and 130-nm nanoparticles, both containing minoxidil, were prepared by solvent evaporation of poly(ε-caprolactone)-block-poly(ethyleneglycol) and were applied onto the skin of both hairy and hairless guinea pigs in the Franz diffusion cell. In hairy guinea pig skin, the permeation of the minoxidil that incorporated in 40-nm nanoparticles was 1.5-fold higher in the epidermal layer and 1.7-fold higher in the receptor solution than that of 130-nm nanoparticles. Nanoparticle size dependence on the permeation behavior of minoxidil was not observed for hairless guinea pig skin in either the epidermal layer or the receptor solution.

Phospholipid liposomes and ethanol–water admixture, on the other hand, containing the same amount of minoxidil did not show differences in the amount of permeation irrespective of the existence of hair follicles. Confocal microscopy coupled with in vivo and in vitro skin permeation results demonstrated that nanoparticles containing solutes penetrated mainly via shunt routes like hair follicles, resulting in skin absorption of solutes.

Transdermal delivery of mixnoxidil with block copolymer nanoparticles. Jongwon Shim, Hyung Seok Kang, Won-Seok Park, Sang-Hun Han, Junoh Kim, Ih-Seop Chang. Journal of Controlled Release. Volume 97, Issue 3, 7 July 2004, Pages 477–484. doi:10.1016/j.jconrel.2004.03.028

Temperature-responsive shrinking kinetics of poly (N-isopropylacrylamide) copolymer gels with hydrophilic and hydrophobic comonomers

Abstract

Temperature-responsive poly(N-isopropylacrylamide) and its copolymer gels with the hydrophilic comonomer, acrylamide and the hydrophobic comonomer, butyl methacrylate, all exhibit swelling-deswelling changes in response to external temperature changes. These hydrogels show negative swelling thermosensitivities, particularly swelling at lower temperature and complete deswelling over specific phase transition temperatures (Tp). Shrinking kinetics of these gels from swollen to deswollen states at several different temperature changes have been investigated. When temperature changes are performed entirely below Tp, the shrinking process is dominated by polymer network diffusion. On the other hand, shrinking kinetics for temperature changes from below to above Tp, are dramatically influenced by gel surface structural changes and formation of a collapsed polymer skin layer. This surface skin formation prompts the accumulation of internal hydrodynamic pressure inside the gels upon shrinking by blocking the outflux of entrapped water. Both rate and magnitude of internal hydrodynamic pressure are modulated by the gel volume, the hydrophobicity of the gel polymer chains and the degree of external temperature changes. This internal pressure eventually causes convective outflow of water from the gel interior. Hydrodynamic internal pressure affects the drug release on-off pattern during gel shrinking.

Temperature-responsive shrinking kinetics of poly (N-isopropylacrylamide) copolymer gels with hydrophilic and hydrophobic comonomers. Yuzo Kaneko, Ryo Yoshida, Kiyotaka Sakai, Yasuhisa Sakurai, Teruo Okano. Journal of Membrane Science. Volume 101, Issues 1–2, 15 May 1995, Pages 13–22. doi:10.1016/0376-7388(94)00268-4

Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin

Abstract

Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen-glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 microns, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was greater than 5 x 10(4) cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physiochemical structure, functioning as a transient basal lamina during morphogenesis of skin.

Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. I V Yannas, E Lee, D P Orgill, E M Skrabut, and G F Murphy. PNAS February 1, 1989 vol. 86 no. 3 933-937.

Niacinamide

The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer

Summary. Background Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate.

Objectives To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women.

Methods Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face.

Results Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35–68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use.

Conclusions The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.

Hakozaki, T., Minwalla, L., Zhuang, J., Chhoa, M., Matsubara, A., Miyamoto, K., Greatens, A., Hillebrand, G.G., Bissett, D.L. and Boissy, R.E. (2002), The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. British Journal of Dermatology, 147: 20–31. doi: 10.1046/j.1365-2133.2002.04834.x

The Treatment of Bullous Pemphigoid With Tetracycline and Niacinamide

A Preliminary Report

Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease.

The Treatment of Bullous Pemphigoid With Tetracycline and Niacinamide – A Preliminary Report.Mark Allan Berk, MD, FRCP; Allan L. Lorincz, MD. Arch Dermatol. 1986;122(6):670-674. doi:10.1001/archderm.1986.01660180076019.

Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: A critical review of central 3-acetylpyridine neurotoxicity

Abstract

Previous studies indicate that 3-acetylpyridine (3-AP) intoxication produces discrete lesions of the inferior olive (IO) and other central structures in rats and mice. As a result, it has been widely employed in investigations of the influences of climbing fibers on cerebellar function. This study examines the central toxicity of a protocol reported to produce lesions restricted to the inferior olive in rats33. Adult male Long-Evans (n = 12) and Sprague-Dawley (n = 18) were given serial injections of 3-AP (75–80 mg/kg), harmaline (15 mg/kg) or saline, and niacinamide (300 mg/kg). Silver degeneration staining (cupric-silver method) after 6–48 h survival revealed consistent patterns of degenerating neurons in IO, nucleus ambiguus, hypoglossal nucleus, dorsal motor nucleus X, nucleus intercalatus, nucleus dorsalis raphe, medial terminal nucleus, interpeduncular nucleus, substantia nigra, ventral tegmental area, entopeduncular nucleus, hippocampus (dentate gyrus and CA 3–4), horizontal limb of the nucleus of the diagonal band, and lateral entorhinal cortex, which were not produced by control experiments with 3 saline injections or with two saline injections followed by niacinamide. These data apparently resolve conflicts in the literature regarding central 3-AP toxicity and indicate that the 3-AP-harmaline-niacinamide protocol produces degeneration that is similar to 3-AP alone. However, they also document the discrete, reproducible susceptibility of certain neuronal populations to 3-AP intoxication and suggest that the motor symptoms of intoxication are not solely due to IO destruction. Finally, they form a basis for biochemical investigations of 3-AP toxicity in susceptible central structures.

Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: A critical review of central 3-acetylpyridine neurotoxicity. Carey D. Balaban. Brain Research Reviews. Volume 9, Issue 1, April 1985, Pages 21-42. doi:10.1016/0165-0173(85)90017-7.

Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance

Background. In multiple chronic clinical studies, topical niacinamide (vitamin B3) has been observed to be well tolerated by skin and to provide a broad array of improvements in the appearance of aging facial skin (eg, reduction in the appearance of hyperpigmentated spots and red blotchiness).

Objective. To clinically determine the effect of topical niacinamide on additional skin appearance and property end points (wrinkles, yellowing, and elasticity).

Methods. Female white subjects (N = 50) with clinical signs of facial photoaging (fine lines and wrinkles, poor texture, and hyperpigmented spots) applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks (double blind, left-right randomized). Facial images and instrumental measures were obtained at baseline and at 4-week intervals.

Results. Analyses of the data revealed a variety of significant skin appearance improvement effects for topical niacinamide: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing). In addition, elasticity (as measured via cutometry) was improved. Corresponding mechanistic information is presented.

Conclusion. In addition to previously observed benefits for topical niacinamide, additional effects were identified (improved appearance of skin wrinkles and yellowing and improved elasticity).

Bissett, D. L., Oblong, J. E. and Berge, C. A. (2005), Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance. Dermatologic Surgery, 31: 860–866. doi: 10.1111/j.1524-4725.2005.31732

A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma

Josefina Navarrete-Solıs, Juan Pablo Castanedo-Cazares, Bertha Torres-Alvarez,Cuauhtemoc Oros-Ovalle, Cornelia Fuentes-Ahumada, Francisco Javier Gonzalez,Juan David Martınez-Ramırez,and Benjamin Moncada.Dermatology Research and Practice. Volume 2011, Article ID 379173, 5 pages.doi:10.1155/2011/379173

Aloe Vera Gel

Anti-inflammatory activity of extracts from Aloe vera gel

Abstract

We studied the effects of aqueous, chloroform, and ethanol extracts of Aloe vera gel on carrageenan-induced edema in the rat paw, and neutrophil migration into the peritoneal cavity stimulated by carrageenan. We also studied the capacity of the aqueous extract to inhibit cyclooxygenase activity. The aqueous and chloroform extracts decreased the edema induced in the hind-paw and the number of neutrophils migrating into the peritoneal cavity, whereas the ethanol extract only decreased the number of neutrophils. The antiinflammatory agents indomethacin and dexamethasone also decreased carrageenan-induced edema and neutrophil migration. The aqueous extract inhibited prostaglandin E2 production from [14C]arachidonic acid. The chemical tests performed in the aqueous extract for anthraglycosides, reductor sugars and cardiotonic glycosides were positive. In the ethanol extract, the chemical tests performed for saponins, carbohydrates naftoquinones, sterols, triterpenoids and anthraquinones were also positive. In the chloroform extract, the chemical tests performed for sterols type Δ5, and anthraquinones were positive. These results demonstrated that the extracts of Aloe vera gel have antiinflammatory activity and suggested its inhibitory action on the arachidonic acid pathway via cyclooxygenase.

Anti-inflammatory activity of extracts from Aloe vera gel. Beatriz Vázquez, Guillermo Avila, David Segura, Bruno Escalante. Journal of Ethnopharmacology. Volume 55, Issue 1, December 1996, Pages 69–75. doi:10.1016/S0378-8741(96)01476-6

Activation of a mouse macrophage cell line by acemannan: The major carbohydrate fraction from Aloe vera gel

Abstract

Acemannan is the name given to the major carbohydrate fraction obtained from the gel of the Aloe vera leaf. It has been claimed to have several important therapeutic properties including acceleration of wound healing, immune stimulation, anti-cancer and anti-viral effects. However, the biological mechanisms of these activities are unclear. Because of this wide diversity of effects, it is believed that they may be exerted through pluripotent effector cells such as macrophages. The effects of acemannan on the mouse macrophage cell line, RAW 264.7 cells were therefore investigated. It was found that acemannan could stimulate macrophage cytokine production, nitric oxide release, surface molecule expression, and cell morphologic changes. The production of the cytokines IL-6 and TNF-α were dependent on the dose of acemannan provided. Nitric oxide production, cell morphologic changes and surface antigen expression were increased in response to stimulation by a mixture of acemannan and IFN-γ. These results suggest that acemannan may function, at least in part, through macrophage activation.

Activation of a mouse macrophage cell line by acemannan: The major carbohydrate fraction from Aloe vera gel. Linna Zhang, Ian R. Tizard. Immunopharmacology.Volume 35, Issue 2, November 1996, Pages 119–128. doi:10.1016/S0162-3109(96)00135-X

The Stimulation of Postdermabrasion Wound Healing with Stabilized Aloe Vera Gel-Polyethylene Oxide Dressing.

Abstract. Full-face dermabrasion provided an ideal opportunity to document the effects of dressings on wound healing management. Following the procedure, the abraded face was divided in half. One side was treated with the standard polyethylene oxide gel wound dressings. The other side was treated with a polyethylene oxide gel dressing saturated with stabilized aloe vera. The polyethylene oxide dressing provided an excellent matrix for the release of aloe vera gel during the initial 5 days of wound healing. By 24–48 hours there was dramatic vasoconstriction and accompanying reduction in edema on the aloe-treated side. By the third to fourth day there was less exudate and crusting at the aloe site, and by the fifth to sixth day the reepithelialization at the aloe site was complete. Overall, wound healing was approximately 72 hours faster at the aloe site. This acceleration in wound healing is important to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. The exact mechanism of acceleration of wound healing by aloe vera is unknown.

FULTON, J. E. (1990), The Stimulation of Postdermabrasion Wound Healing with Stabilized Aloe Vera Gel-Polyethylene Oxide Dressing. The Journal of Dermatologic Surgery and Oncology, 16: 460–467. doi: 10.1111/j.1524-4725.1990.tb00065.x

Comparative antimicrobial activities of aloe vera gel and leaf.

The comparative antimicrobial activities of the gel and leaf of Aloe vera were tested against Staphylococcus aureus, Pseudomonas aeruginosa, Trichophyton mentagraphytes, T. schoeleinii,

Microsporium canis and Candida albicans. Ethanol was used for the extraction of the leaf after obtaining the gel from it. Antimicrobial effect was measured by the appearance of zones of inhibition.

Antimicrobial susceptibility test showed that both the gel and the leaf inhibited the growth of S. aureus (18.0 and 4.0 mm, respectively). Only the gel inhibited the growth of T. mentagrophytes (20.0 mm), while the leaf possesses inhibitory effects on both P. aeruginosa and C. albicans. The results of this study tend to give credence to the popular use of both Aloe vera gel and leaf.

Comparative antimicrobial activities of aloe vera gel and leaf. Agarry O.O., Olaleye M.T.and Bello-Michael, C.O.. African Journal of Biotechnology Vol. 4 (12), pp. 1413-1414, December 2005

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure

Abstract

Objective: An examination glove that delivers aloe vera (AV) gel to the gloved hand was studied in 30 adult females with bilateral occupational dry skin with or without irritant contact dermatitis (with or without erythema, fissures, and excoriations). Methods: All participants were factory assembly-line workers with repeated superficial skin trauma who attributed their dry, irritated, emollient-dependent skin to a common cause (occupational exposure). Participants were sequentially enrolled (after written informed consent, n = 29 evaluable participants) into an open, contralateral comparison study to evaluate efficacy of AV glove use 8 h/day to one hand versus no use to the opposite hand for 30 days, followed by 30 days rest, followed by 10 days of repeated use. Participant’s dorsal hands were documented by standardized photos at baseline, during, and at the end of study. Results: Unblinded investigator baseline assessment rated dry skin as mild to moderate (n = 27), or moderate to severe (n = 2). Mean time to noticeable improvement for the AV glove hand was 3.5 days (range: 2-6 days) whereas marked improvement was 10.4 days (range: 7-17 days) for the AV glove hand. No improvement was detected for nonglove hands. Blinded photo assessment was rated independently by dermatology research staff. End-of-study mean global assessment of AV glove hands versus nonglove hands was 1.3 for AV glove hand (0 = no change, 1 = good [10%-89% global improvement], 2 = marked improvement [90%-100% global improvement]) versus 0 for nonglove hand (P <.0001). Mean global end-of-study assessments by the participants = 2.0 for AV glove hand versus 0 for nonglove hand. Conclusion: Dry-coated AV gloves that provide for gradual delivery of AV gel to skin produced a uniformly positive outcome of improved skin integrity, decreased appearance of fine wrinkling, and decreased erythema in the management of occupational dry skin and irritant contact dermatitis. (Am J Infect Control 2003;31:40-2.)

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure. Dennis P. West, PhDa, Ya Fen Zhu, MSb. American Journal of Infection Control. Volume 31, Issue 1, February 2003, Pages 40–42. doi:10.1067/mic.2003.12.

Aloe vera leaf gel: a review update

Abstract

Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas. Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components. A common theme running though much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents. There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens. There are also cautionary investigations warning of possible allergic effects on some patients. Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel. Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities

Aloe vera leaf gel: a review update. T Reynolds, A.C Dweck. Journal of Ethnopharmacology. Volume 68, Issues 1–3, 15 December 1999, Pages 3–37. doi:10.1016/S0378-8741(99)00085-9

Composition and Applications of Aloe vera Leaf Gel

Abstract

Many of the health benefits associated with Aloe vera have been attributed to the polysaccharides contained in the gel of the leaves. These biological activities include promotion of wound healing, antifungal activity, hypoglycemic or antidiabetic effects antiinflammatory, anticancer, immunomodulatory and gastroprotective properties. While the known biological activities of A. vera will be briefly discussed, it is the aim of this review to further highlight recently discovered effects and applications of the leaf gel. These effects include the potential of whole leaf or inner fillet gel liquid preparations of A. vera to enhance the intestinal absorption and bioavailability of co-administered compounds as well as enhancement of skin permeation. In addition, important pharmaceutical applications such as the use of the dried A. vera gel powder as an excipient in sustained release pharmaceutical dosage forms will be outlined.

Composition and Applications of Aloe vera Leaf Gel. Josias H. Hamman. Molecules 2008, 13(8), 1599-1616; doi:10.3390/molecules13081599

Polysorbate 20

Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens?

Abstract

Multi-component organogels formed using the non-ionic surfactant sorbitan monostearate as gelator have been formulated to contain niosomes. The purpose of this study was to evaluate the potential of these vesicle-in-water-in-oil (v/w/o) gels as delivery vehicles for vaccines. Bovine serum albumin (BSA) and haemagglutinin (HA) were used as model antigens in depot and immunogenicity studies respectively. The complex gels were prepared by the addition of a hot (60°C) aqueous niosome suspension (v/w) to the sol phase (o, an organic solution of the gelator); a vesicle-in-water-in-oil (v/w/o) emulsion was produced which cools to an opaque, semi-solid, thermoreversible v/w/o gel. Light microscopy of the organogel revealed that the microstructure consists of a tubular network of surfactant aggregates in the organic medium, the niosome suspension being dispersed in these surfactant tubules. Therefore, in such gels, the vaccine is thought to be entrapped in the niosomes, themselves located within the sorbitan monostearate tubular network in the organic medium. In vivo, a depot effect was observed following intramuscular administration of the gel containing the entrapped bovine serum albumin, cleared from the injection site over a period of days. The relatively short-lived nature of the depot was thought to arise due to interactions between the gel and the local interstitial fluid which results in gel disintegration in situ. Thus, the niosomes containing antigens are believed to be released from the organic gel. Immunogenicity studies showed that the v/w/o gel as well as one of the controls, the water-in-oil (w/o) gel, possess immunoadjuvant properties and enhance the primary and secondary antibody titres (of total IgG, IgG1, IgG2a and IgG2b) to haemagglutinin antigen. As far as humoral immunity is concerned, the w/o gel showed stronger immunoadjuvant properties compared to the v/w/o gel, being effective at a lower antigen dose i.e 0.1μg HA.

Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens? Sudaxshina Murdan, Gregory Gregoriadis, Alexander T Florence. European Journal of Pharmaceutical Sciences. Volume 8, Issue 3, July 1999, Pages 177–185. doi:10.1016/S0928-0987(99)00014-7.

A new mechanism for decreasing aggregation of recombinant human interferon-γ by a surfactant: Slowed dissolution of lyophilized formulations in a solution containing 0.03% polysorbate 20

Abstract

To study the mechanisms by which Tween 20 (polysorbate 20) used in a reconstitution solution affects the aggregation of lyophilized recombinant human interferon-γ (rhIFN-γ), we used four types of buffered formulations containing 0.4–5 mg/mL rhIFN-γ in either 10 mM potassium phosphate or phosphate buffered saline: (1) without excipients, (2) with 5% sucrose, (3) with 0.03% polysorbate 20, or (4) with the combination of 5% sucrose and 0.03% polysorbate 20. After lyophilization, infrared spectroscopy was used to analyze the secondary structure of the protein in the freeze-dried solid. Each solid showed structural perturbation of the protein. Each formulation was reconstituted with water or a 0.03% polysorbate 20 solution. Aggregation of rhIFN-γ after reconstitution was measured by optical density at A350, and recovery of soluble protein was determined by high-performance liquid chromatography and ultraviolet spectroscopy. After reconstitution with a 0.03% polysorbate 20 solution, aggregation levels in all formulations were either reduced or similar to those found after reconstitution with water. These results revealed the potential for recovery of native protein using the appropriate reconstitution conditions, even though the protein is non-native in the lyophilized state. Urea-induced unfolding with and without polysorbate 20 as measured by second-derivative ultraviolet spectroscopy indicated that a concentration of 0.03% polysorbate 20 lowered the free energy of unfolding for rhIFN-γ (destabilizing). Polysorbate 20 also retarded refolding from urea solutions and increased aggregation. At a level of 0.03%, polysorbate 20 did not protect the protein against surface-induced aggregation during agitation. Dissolution times in water versus a 0.03% polysorbate 20 solution were measured using a rotating disk electrode for lyophilized formulations containing an electrochemically reactive species. The presence of 0.03% polysorbate 20 in the reconstitution solution nearly doubled the time required for dissolution of the phosphate buffered saline formulation, and the sucrose formulations dissolved 33–57% more slowly. Slowing the dissolution rates of lyophilized powders allows more time for the protein to refold while it decreases the maximum concentration of the protein at the dissolution interface, thus reducing the total amount of aggregation.

Webb, S. D., Cleland, J. L., Carpenter, J. F. and Randolph, T. W. (2002), A new mechanism for decreasing aggregation of recombinant human interferon-γ by a surfactant: Slowed dissolution of lyophilized formulations in a solution containing 0.03% polysorbate 20. J. Pharm. Sci., 91: 543–558. doi: 10.1002/jps.10033

Determination of CMC of polysorbate 20 in aqueous solution by surface tension method

Abstract

The CMC of polysorbate 20 was determined using a surface tension method; the concentration (C) of polysorbate 20 studied varied from 0.001 to 10.000 mg./ml. The results show clearly that the surface tension (γ) decreases linearly with log C up to a concentration of 0.06 mg./ml. and is practically constant for more concentrated solutions. This suggests that the CMC of polysorbate 20 is in the vicinity of 0.06 mg./ml., which is in excellent agreement with the values obtained by other methods.

Mittal, K. L. (1972), Determination of CMC of polysorbate 20 in aqueous solution by surface tension method. J. Pharm. Sci., 61: 1334–1335. doi: 10.1002/jps.2600610842

Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20

Abstract

Because the ionized species is more polar than its unionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination of pH control and complexation to pH control and micellization and to pH control and cosolvency. The total aqueous solubility is expressed as the addition of the concentration of all contributing species: free un-ionized drug [Du], free ionized drug [Di], un-ionized drug micelle [DuM], and ionized drug micelle [DiM] for surfactant, and free un-ionized drug [Dcu] and free ionized drug [Dci] for cosolvent. The equations indicate that under certain conditions the ionized species can be more important in determining the drug total solubility than the un-ionized species. Flavopiridol, a weak base, is used to test these newly generated equations. As expected, the micellar partition coefficient and solubilization power for ionized flavopiridol are both less than those of the un-ionized species. However, at acidic pH, the solubilities of the ionized drug in surfactant micelles [DiM] and in cosolvent–water [Dci] are both much greater than that of the un-ionized drug. This difference is because the solubilization of the ionized drug is proportional to its aqueous solubility, and its solubility [Di] can be as much as 24-fold greater than that of the free un-ionized species [Du].

Li, P., Tabibi, S. E. and Yalkowsky, S. H. (1999), Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20. J. Pharm. Sci., 88: 507–509. doi: 10.1021/js980433o

A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: A contribution to understand colloidal protein stabilisation

Abstract

The development of liquid therapeutic protein drugs imposes the presence of specific stabilisation agents to prevent protein degradation in order to reach shelf-lives of at least 2 years for drugs stored at 2–8 °C. Non-ionic detergents are used to avoid protein adsorption and the formation of protein aggregates. Depending on the protein and excipient (detergent) used the stabilisation effect is quite different and cannot be predicted up to now. One reason for this is the inadequate understanding of the principles that govern the stabilisation of proteins in the presence of detergents. One stabilisation mechanism discussed implicates a direct binding of detergent molecules to the hydrophobic surface area(s) of the protein in order to minimise protein–protein interactions and thus protein aggregation.

Therefore, the presented study considers the interaction and binding of polysorbate 20 and 80 to various human serum albumins and immunoglobulins of different subtypes. The interaction is analysed by means of isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). From ITC the binding constant is derived as well as the thermodynamic parameters. The thermal protein stability is obtained from DSC.

The results show that binding of the two detergents to human serum albumin is observed with binding constants of approximately ≈ 103 M− 1, with 1–3 detergent molecules binding to the albumins. The exact polysorbate–albumin ratio depends on the used albumin fraction. The interaction of the detergent is also obvious from the DSC results, showing an increase of the denaturation temperature. However, the binding of the detergent to the three investigated immunoglobulins is quite low and negligible, thus showing that for immunoglobulins a direct and strong polysorbate binding to the protein is not the reason for the colloidal stabilisation effect of immunoglobulins in solution in the presence of polysorbate 20 or 80.

A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: A contribution to understand colloidal protein stabilisation. Patrick Garidel, Claudia Hoffmann, Alfred Blume. Biophysical Chemistry. Volume 143, Issues 1–2, July 2009, Pages 70–78. doi:10.1016/j.bpc.2009.04.004

Interaction of substituted benzoic acids with polysorbate 20 micelles

Abstract

Equilibrium solubilities of a series of substituted benzoic acids in different concentrations of polysorbate 20 at controlled pH were measured. The maintenance of pH was achieved using a pH-stat assembly. A linear relationship was found between the amount of benzoic acid solubilized and surfactant concentration. As solubilizate polarity increased, the amount solubilized also increased. Solubility data were analyzed, and the interaction between solubilizate molecules and micelles was calculated in terms of partition coefficients of ionized and unionized molecules between aqueous and micellar phases. A linear relationship between π values (log partition coefficients) of functional groups and aqueous-micellar partition coefficient was found.

Collett, J. H. and Koo, L. (1975), Interaction of substituted benzoic acids with polysorbate 20 micelles. J. Pharm. Sci., 64: 1253–1255. doi: 10.1002/jps.2600640733

Phenoxyethanol

Metomidate, a better anesthetic for cod (Gadus morhua) in comparison with benzocaine, MS-222, chlorobutanol, and phenoxyethanol

Abstract

Metomidate, benzocaine, MS-222, chlorobutanol, and phenoxyethanol were tested and compared in rapid anesthesia of cod (Gadus morhua). Only metomidate and, to a lesser extent, benzocaine and MS-222 were found to be recommendable. The effective concentration for metomidate was 5 mg l−1 (9.6°C), for benzocaine 40 mg l−1 (9.5°C), and for MS-222 75 mg l−1 (8.4°C). The recovery time for metomidate was longer than for benzocaine and MS-222, but the safety margin was higher.

Metomidate, a better anesthetic for cod (Gadus morhua) in comparison with benzocaine, MS-222, chlorobutanol, and phenoxyethanol. N.S. Mattson, T.H. Riple. Aquaculture. Volume 83, Issues 1–2, 1 December 1989, Pages 89–94. doi:10.1016/0044-8486(89)90063-X

Comparative efficacy of clove oil and 2-phenoxyethanol as anesthetics in the aquaculture of European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) at different temperatures

Abstract

The efficacy of clove oil as an anesthetic was evaluated in juvenile European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata), and was compared to the commonly used 2-phenoxyethanol through a series of experiments simulating aquaculture activities. Firstly, using as a criterion the acquisition of complete anesthesia (stage A5) in < 3 min and recovery (stage R5) in < 10 min, the optimal doses at 25 °C were determined to be 40 mg l−1 of clove oil for both species, and 350 mg l−1 and 300 mg l−1 of 2-phenoxyethanol for European sea bass and gilthead sea bream, respectively. At 15 °C, the optimal doses for the European sea bass were determined to be around 30 mg l−1 clove oil and 300 mg l−1 2-phenoxyethanol, and for gilthead sea bream 55 mg l−1 clove oil and 450 mg l−1 2-phenoxyethanol. Increasing the exposure time of fish to the optimal anesthetic dose for 5, 10 or 15 min after stage A5 anesthesia prolonged recovery time (ANOVA, P < 0.001), especially in gilthead sea bream, which also suffered significant mortality (10–83%). As expected, the lower temperature resulted in significantly longer anesthesia induction and recovery times (ANOVA, P < 0.001), presumably due to the positive relationship between temperature, and opercular ventilation rates (ANOVA, P < 0.001) and metabolism. Finally, repeated exposure to anesthetics at 0 h, 3 h and 24 h increased significantly the induction time to stage A5 anesthesia (ANOVA, P < 0.001), suggesting the development of a slight tolerance, especially to the clove oil. The study demonstrated that clove oil can be used as an effective anesthetic in European sea bass and gilthead sea bream aquaculture, at almost 10-fold lower doses than 2-phenoxyethanol. The observed differences in (a) dose response, (b) anesthesia induction and recovery times, (c) ventilation rates and (d) mortality after prolonged exposure among the two species, underscore the need to undertake extensive studies with the specific fish species, anesthetic and experimental procedure employed, before clove oil or any other anesthetic is proposed for commercial use in an aquaculture species.

Comparative efficacy of clove oil and 2-phenoxyethanol as anesthetics in the aquaculture of European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) at different temperatures. Constantinos C. Mylonas, Gloriana Cardinaletti, Irini Sigelaki, Alberta Polzonetti-Magni. Aquaculture. Volume 246, Issues 1–4, 18 May 2005, Pages 467–481. doi:10.1016/j.aquaculture.2005.02.046

Phenoxyethanol: Protein Preservative for Taxonomists

Pieces of chicken heart or skeletal muscle were placed in a dilute solution of the antimicrobial agent 2-phenoxyethanol and stored at room temperature. Under these conditions, the serum albumin, lactate dehydrogenase, and malate dehydrogenase in these tissues survived in easily detectable amounts for at least 2 weeks. The surviving proteins appeared to be identical with those of fresh tissues in physical, catalytic, and immunological properties. Phenoxyethanol also preserved heart and muscle proteins of representatives of other vertebrate classes. Tissue samples collected in the analysis by biochemical taxonomists.

Phenoxyethanol: Protein Preservative for Taxonomists.

Mikiye Nakanishi, Allan C. Wilson, Richard A. Nolan, George C. Gorman, George S. Bailey. Science 14 February 1969: Vol. 163 no. 3868 pp. 681-683.DOI: 10.1126/science.163.3868.681

Cortisol and haematological response in sea bream and trout subjected to the anaesthetics clove oil and 2-phenoxyethanol

Abstract

Clove oil has been tested for anaesthesia induction and recovery time as well as for haematology and stress indicators in the gilthead sea bream and rainbow trout. The former parameters were compared with those generated by 2-phenoxyethanol. The results showed only slight differences between both anaesthetics in terms of anaesthetic efficiency and physiological effects. In addition, clove oil does not block the cortisol response to stress, as happens with other anaesthetics.

Tort, L., Puigcerver, M., Crespo, S. and Padrós, F. (2002), Cortisol and haematological response in sea bream and trout subjected to the anaesthetics clove oil and 2-phenoxyethanol. Aquaculture Research, 33: 907–910. doi: 10.1046/j.1365-2109.2002.00741.x

Comparative effects of MS 222 and 2-phenoxyethanol on gilthead sea bream (Sparus aurata L.) during confinement

Abstract

The effects of two anaesthetics, ethyl m-aminobenzoate methanosulphonate (MS 222) and 2-phenoxyethanol, at three different dosage levels, were examined on gilthead sea bream (Sparus aurata) during a confinement similar to that in transport. Changes in plasma cortisol, glucose, lactate and haematological parameters were analysed. Confinement without anaesthesia produces a smaller stress response than with the two anaesthetics. Exposure to MS 222 and 2-phenoxyethanol at a dose exceeding 25 mg 1−1 for MS 222 and 0.075 mg 1−1 for 2-phenoxyethanol, respectively, produces a stress response in gilthead sea bream. The greatest effect of anaesthetic stress in the cortisol level is found following the period of exposure. The effects on plasma glucose level and on plasma lactate continue until 24 hr of recovery time. When the anaesthetic body concentration decreases, as it is metabolically eliminated, a recovery of haematological parameters and cortisol levels is clearly noted.

Comparative effects of MS 222 and 2-phenoxyethanol on gilthead sea bream (Sparus aurata L.) during confinement. A. Molinero, J. Gonzalez. Comparative Biochemistry and Physiology Part A: Physiology. Volume 111, Issue 3, July 1995, Pages 405–414.doi:10.1016/0300-9629(95)00037-8

The use of clove oil, metomidate, tricaine methanesulphonate and 2-phenoxyethanol for inducing anaesthesia and their effect on the cortisol stress response in black sea bass (Centropristis striata L.)

Abstract

Juvenile and adult black sea bass (Centropristis striata L.) were exposed to various concentrations of four anaesthetics to determine practical dosages for handling as well as for procedures such as bleeding, ovarian biopsy or tag implantation. In experiment 1, juveniles exposed to either 2.0 mg L−1 metomidate, 15 mg L−1 clove oil, 70 mg L−1 tricaine methanesulphonate (TMS) or 200 mg L−1 2-phenoxyethanol (2-PE) reached stage II of anaesthesia in 3–5 min and could be handled for weighing and measuring. All fish had completed recovery to stage III within 6 min. In experiment 2, the established concentrations of each anaesthetic were tested on juveniles to determine their ability to prevent a reflex to a subcutaneous needle puncture. All of the fish exposed to clove oil (20 mg L−1) and 40% of the TMS-treated (70 mg L−1) fish reacted while none of the fish anaesthetized in metomidate (2.0 mg L−1) or 2-PE (200 mg L−1) responded to the needle puncture. In experiment 3, metomidate (5.0 mg L−1), clove oil (30 mg L−1) TMS (125 mg L−1) or 2-PE (300 mg L−1) were all effective for performing an ovarian biopsy or tag implantation on adults. In experiment 4, TMS (125 mg L−1) exacerbated the cortisol response to a short handling stressor during a 30 min exposure. Fish anaesthetized in 2-PE (300 mg L−1), metomidate (5.0 mg L−1) or clove oil (40 mg L−1) had increased cortisol levels associated with the handling stressor but there were no further increases during the remainder of the experimental period. The results demonstrate that these anaesthetics are effective for sedation and anaesthesia of black sea bass and that the best choice is dependant upon the procedures to be performed.

King, W., Hooper, B., Hillsgrove, S., Benton, C. and Berlinsky, D. L. (2005), The use of clove oil, metomidate, tricaine methanesulphonate and 2-phenoxyethanol for inducing anaesthesia and their effect on the cortisol stress response in black sea bass (Centropristis striata L.). Aquaculture Research, 36: 1442–1449. doi: 10.1111/j.1365-2109.2005.01365.x

Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn infants of 23–26 weeks gestation

Abstract

In preterm newborn infants, topical iodine-containing antiseptics disturb thyroid hormone regulation while alcohol-based disinfectants may cause local burns. We therefore investigated the use of an aqueous solution containing 0.1% octenidine and 2% 2-phenoxyethanol for skin disinfection during the first seven days of life in premature newborns with a gestational age <27 weeks who were consecutively admitted to our level III neonatal intensive care unit between November 1, 2000 and December 31, 2001 (N=24). In boys. (N=13) the renal excretion of absorbed 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid was quantitated by high-pressure liquid chromatography. In the most immature newborn (gestational age 23 6/7 weeks), a transient erythematous reaction was observed following application of the octenidine/phenoxyethanol solution prior to umbilical vessel catheterization. No other local reactions were observed. The urinary concentration of 2-phenoxyethanol was <2 ppm in all samples, while urinary 2-phenoxyacetic acid concentrations reached 5–95 ppm (median 24 ppm). One infant had a culture-proven septicaemia (Bacillus species) during the first seven days of life. We conclude that, in contrast to alcohol-based antiseptics, an aqueous solution of 0.1% octenidine and 2-phenoxyethanol does not cause major skin damage in premature newborn infants <27 weeks’ gestation. 2-Phenoxyethanol is readily absorbed by the newborn’s skin but apparently undergoes extensive oxidative metabolization to 2-phenoxyacetic acid.

Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn infants of 23–26 weeks gestation.C. Bührer, S. Bahr, J. Siebert, R. Wettstein, C. Geffers, M. Obladen. Journal of Hospital Infection. Volume 51, Issue 4, August 2002, Pages 305–307. doi:10.1053/jhin.2002.1249

The efficacy of 2-phenoxyethanol, metomidate, clove oil and MS-222 as anaesthetic agents in the Senegalese sole (Solea senegalensis Kaup 1858)

Abstract

The efficacy of four anaesthetic agents (2-phenoxyethanol, metomidate, clove oil and MS-222) was evaluated in the Senegalese sole (Solea senegalensis). It was assumed that stage II of anaesthesia is sufficient to carry out routine aquaculture procedures in less than 3 min, with recovery in less than 5 min. The following optimal doses were determined: 600 mg L− 1 of 2-phenoxyethanol (induction 1.50 ± 0.37 and recovery time 1.94 ± 0.56 min), 5 mg L− 1 of metomidate (induction 1.50 ± 0.22 and recovery time 3.70 ± 1.18 min), 30 mg L− 1 of clove oil (induction 3.16 ± 0.40 and recovery time 3.76 ± 1.01 min) and 75 mg L− 1 of MS-222 (induction 2.42 ± 0.20 and recovery time 0.56 ± 0.14 min). The induction times decreased with increasing doses for all of the anaesthetic agents evaluated. Finally, the ability of each anaesthetic agent to prevent a reflex reaction in less than 3 min during simulated blood sampling was evaluated in Senegalese soles of different weights (74 ± 4 g; 213 ± 15 g; 300 ± 12 g), being only achieved in the following cases: 600 mg L− 1 of 2-phenoxyethanol and 6 and 8 mg L− 1 of metomidate, with fish of 74 ± 4 g, and 600 mg L− 1 of 2-phenoxyethanol, 8 mg L− 1 of metomidate and 200 mg L− 1 of MS-222 with fish of 213 ± 15 g. The most effective of the four anaesthetic agents studied was 2-phenoxiethanol, although all were considered acceptable for use in culture of Senegalese sole.

The efficacy of 2-phenoxyethanol, metomidate, clove oil and MS-222 as anaesthetic agents in the Senegalese sole (Solea senegalensis Kaup 1858). R.A. Weber,J.B. Peleteiro, L.O. García Martín, M. Aldegunde. Aquaculture. Volume 288, Issues 1–2, 2 March 2009, Pages 147–150.doi:10.1016/j.aquaculture.2008.11.024

Imidazolidinyl Urea

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol

Abstract

Preservatives are added to many final products, such as detergents, cosmetics, pharmaceuticals and vaccines. We conducted an in vitro investigation of the apoptosis- and necrosis-inducing potential of brief applications (10 min) of four common preservatives: ethylene glycol monophenyl ether, 2-phenoxyethanol (EGPE), imidazolidinyl urea (IMU), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI), and 1,2-pentanediol, a “preservative-non-preservative” best known as pentylene glycol. Using HL60 cells, we monitored the kinetics of cell toxicity with the MTT test and analysed extranuclear end points of apoptosis, i.e. phosphatidylserine exposure and nuclear fragmentation. Preservative treatment resulted in a dose-dependent decrease of cell viability. The mode of cell death was dose-dependent: necrosis occurred at high concentrations while apoptosis, shown by DNA laddering, DNA sub-diploid peak and caspase-3 activation, occurred at lower concentrations 0–24 hr after exposure to a single dose: CMI/MI induced apoptosis at low concentrations (0.001–0.01%) and necrosis at high concentrations (0.5–0.1%); IMU and EGPE required higher concentrations to induce apoptosis (IMU 0.01–0.1% and EGPE 0.01–0.5%) or necrosis (IMU 0.5–1% and EGPE only at 1%). PG induced apoptosis only at 5%. Externalization of PS, a hallmark of apoptosis, occurred early in HL60 treated with low concentrations of CMI/MI and EGPE and was concomitant with the subdiploid peak in HL60 treated with PG. However, it did not occur in HL60 treated with IMU. In conclusion, at appropriate concentrations, each of the four preservatives modulates the apoptotic machinery by a caspase-dependent mechanism. Thus, apoptosis could be a good parameter to evaluate the cytoxicity of these chemical compounds.

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol.Cecilia Anselmi, Anna Ettorre, Marco Andreassi, Marisanna Centini, Paolo Neri, Anna Di Stefano. Biochemical Pharmacology. Volume 63, Issue 3, 1 February 2002, Pages 437–453. doi:10.1016/S0006-2952(01)00910-8

Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea

For several decades, the cosmetic preservatives imidazolidinyl urea (IU) and diazolidinyl urea (DU) have not only been poorly characterized but have also had misleading chemical structures assigned to them. The most common trade names of IU and DU are Germall 115 and Germall II, respectively. This publication gives an insight into what these 2 well-known contact allergens consist of and their degradation patterns. Approximately, 30–40% of both products can be characterized by mixtures of allantoin (synthetic starting material), (4-hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-urea (compound HU) and presumably 1-(3,4-bis-hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-1,3-bis-hydroxymethyl-urea (compound BHU). A full chemical characterization of compound HU is shown. The remaining part of both IU and DU are believed to be polymers of allantoin-formaldehyde condensation products. The analytical methods used to characterize IU and DU are capillary electrophoresis and nuclear magnetic resonance and mass spectroscopy studies.

Lehmann, S. V., Hoeck, U., Breinholdt, J., Olsen, C. E. and Kreilgaard, B. (2006), Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea. Contact Dermatitis, 54: 50–58. doi: 10.1111/j.0105-1873.2006.00735.x

Imidazolidinyl urea dermatitis

Dooms-Goossens, A., de Boulle, K., Dooms, M. and Degreef, H. (1986), Imidazolidinyl urea dermatitis. Contact Dermatitis, 14: 322–323. doi: 10.1111/j.1600-0536.1986.tb05295.x

Monitoring levels of preservative sensitivity in Europe

A 10-year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5-chloro-2-methyl-4-isothiazolin-3-one + 2-methyl-4-isothiazolin-3-one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re-evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave-on products.

Wilkinson, J. D., Shaw, S., Andersen, K. E., Brandao, F. M., Bruynzeel, D. P., Bruze, M., Camarasa, J. M. G., Diepgen, T. L., Ducombs, G., Frosch, P. J., Goossens, A., Lachappelle, J. .-M., Lahti, A., Menné, T., Seidenari, S., Tosti, A. and Wahlberg, J. E. (2002), Monitoring levels of preservative sensitivity in Europe. Contact Dermatitis, 46: 207–210. doi: 10.1034/j.1600-0536.2002.460404.x

Contact sensitivity to preservatives in the UK, 2004–2005: results of multicentre study

Preservative sensitivity in the UK was last assessed in 2000. Given the changes in preservative usage, we have re-evaluated our patch test data in order to detect any changes in the trend of sensitization. The results of patch testing using the extended British Contact Dermatitis Society Standard series were collected from 9 dermatology centres in the UK. Positive reactions to each of 10 preservative allergens were captured together with the MOAHFLA indices for each centre. In total, 6958 patients were tested during the period 2004–2005. The current data were compared with previously published data. Formaldehyde and methylchloroisothiazolinone/methyl-isothiazolinone have the highest positivity rates at 2.0% and chloroxylenol the lowest at 0.2%. Parabens mix has the highest irritancy rate. Compared with the UK data in 2000, the positivity rate of imidazolidinyl urea (0.02 < P < 0.05) has significantly increased and that of methyldibromo glutaronitrile has significantly reduced (P < 0.001).

Jong, C. T., Statham, B. N., Green, C. M., King, C. M., Gawkrodger, D. J., Sansom, J. E., English, J. S. C., Wilkinson, S. M., Ormerod, A. D. and Chowdhury, M. M. U. (2007), Contact sensitivity to preservatives in the UK, 2004–2005: results of multicentre study. Contact Dermatitis, 57: 165–168. doi: 10.1111/j.1600-0536.2007.01181.x

Allergic contact dermatitis in a girl due to several cosmetics containing diazolidinyl-urea or imidazolidinyl-urea

García-Gavín, J., González-Vilas, D., Fernández-Redondo, V. and Toribo, J. (2010), Allergic contact dermatitis in a girl due to several cosmetics containing diazolidinyl-urea or imidazolidinyl-urea. Contact Dermatitis, 63: 49–50. doi: 10.1111/j.1600-0536.2010.01736.x

EDTA

Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice

Abstract

Topical 5-aminolevulinic acid (ALA) application in three different creams was carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP) production in the tumour and in the skin overlying the tumour was studied by two methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics of PP production in the skin and in the tumour, as studied by the LIF method, was similar for all three cream preparations. The PP fluorescence intensity in the tissues reached its maximum 4–6 h after application of the creams. Quantitative analysis showed that the PP concentration after treatment was more pronounced in the skin than in the tumour. The efficiency of porphyrin production in the skin by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by ALA was observed mainly in the upper 2 mm section. However, the concentration of PP in the tumour was found to be approximately the same for the ALA-DMSO and ALA-DMSO-EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA are discussed.

Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice. Z. Malik, G. Kostenich, L. Roitman, B. Ehrenberg, A. Orenstein. Journal of Photochemistry and Photobiology B: Biology.Volume 28, Issue 3, June 1995, Pages 213–218. doi:10.1016/1011-1344(95)07117-K

Effect of EDTA and zinc-methionine complex on zinc absorption by rat intestine

The effects of zinc chelators on 65Zn uptake, absorption and tissue distribution were determined in rats using ligated duodenal loops. 65Zn was supplied as Zn-methionine complex, ZnCl2, ZnCl2 + L-methionine or ZnCl2 + EDTA. The effect of EDTA was also determined in the presence of phytic acid. Absorption of 65Zn was markedly reduced in rats given Zn-methionine complex or ZnCl2 + EDTA. The 65Zn level in tissues (liver, bone, muscle, skin, kidney, and thymus) of rats given ZnCl2 + EDTA was also significantly reduced compared to that of rats given ZnCl2. Reduced absorption due to phytic acid was not improved by EDTA, although EDTA increased mucosal 65Zn retention. High performance gel filtration chromatography showed six 65Zn-binding peaks in the mucosal cytosol of rats given ZnCl2. A seventh peak attributable to Zn-EDTA was observed in cytosol from rats given ZnCl2 + EDTA. A comparable peak in plasma was not observed. Both EDTA and Zn-methionine complex reduced 65Zn-binding to a low-molecular-weight component of mucosal cytosol that was not metallothionein. The results suggest that Zn-EDTA is transported intact from the lumen into mucosal cells but not across the basolateral membrane. The adverse effects of EDTA and Zn-methionine complex on zinc absorption were associated with reduced 65Zn-binding to a component of mucosal cytosol that may be involved in zinc absorption.

Effect of EDTA and zinc-methionine complex on zinc absorption by rat intestine.Hempe JM, Cousins RJ. Food Science and Human Nutrition Department, University of Florida, Gainesville 32611.The Journal of Nutrition [1989, 119(8):1179-1187]

The Vast Majority of CLA T Cells Are Resident in Normal Skin

There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are ∼1 × 106 T cells/cm2 normal skin and an estimated 2 × 1010 T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA+ effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.

The Vast Majority of CLA T Cells Are Resident in Normal Skin. Rachael A. Clark, Benjamin Chong, Nina Mirchandani, Nooshin K. Brinster, Kei-ichi Yamanaka, Rebecca K. Dowgiert and Thomas S. Kupper. The Journal of Immunology. April 1, 2006 vol. 176 no. 7 4431-4439. doi: 10.4049/​jimmunol.176.7.4431

Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis.

Linear IgA bullous dermatosis (LABD) is a rare blistering skin disease characterized by basement membrane zone deposition of IgA. This study identifies a tissue antigen detected by patient serum and then isolates the autoantibody using epidermis and protein bands blotted on nitrocellulose as immunoabsorbents. Sera from 10 patients (9 with cutaneous disease and 1 with cicatrizing conjunctivitis) were evaluated. Indirect immunofluorescence revealed an IgA anti-basement membrane antibody in 6 of 10 sera with monkey esophagus substrate and 9 of 10 sera with human epidermal substrate. Immunoblotting was performed on epidermal and dermal extracts prepared from skin separated at the basement membrane zone with either sodium chloride or EDTA. Saline-separated skin expressed a 97-kD band in dermal extract alone that was recognized by 4 of 10 sera. EDTA-separated skin expressed the 97-kD band in both epidermal (4 of 10 sera) and dermal (6 of 10 sera) extract. Immunoabsorption of positive sera with epidermis purified an IgA antibody that reacted uniquely with the 97-kD band. In addition, IgA antibody bound to nitrocellulose was eluted from the 97-kD band and found to uniquely bind basement membrane zone. It is likely that the 97-kD protein identified by these techniques is responsible for basement membrane binding of IgA in LABD.

Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis. J J Zone, T B Taylor, D P Kadunce, and L J Meyer. J Clin Invest. 1990 Mar; 85(3): 812–820. doi: 10.1172/JCI114508

Potassium Sorbate

Antimicrobial and physical properties of sweet potato starch films incorporated with potassium sorbate or chitosan

Abstract

Antimicrobial biodegradable films have been prepared with sweet potato starch by incorporating potassium sorbate or chitosan. Films incorporated with potassium sorbate ≥ 15% or chitosan ≥ 5% were found to have an anti-Escherichia coli effect. Staphylococcus aureus could be effectively suppressed by incorporation of chitosan at ≥10%. Whereas potassium sorbate lowers the tensile strength and elongation at break, and raises the oxygen permeability, water vapor permeability and water solubility, chitosan has the opposite effect. Fourier Transform Infrared (FT-IR) spectra analysis revealed that starch crystallinity was retarded by potassium sorbate incorporation and that hydrogen bonds were formed between chitosan and starch. This explained the modification of the mechanical and physical properties of the films by the incorporation of these two antimicrobial agents.

Antimicrobial and physical properties of sweet potato starch films incorporated with potassium sorbate or chitosan. Xiao Li Shena, Jia Min Wu, Yonghong Chen, Guohua Zhao. Food Hydrocolloids. Volume 24, Issue 4, June 2010, Pages 285–290. doi:10.1016/j.foodhyd.2009.10.003

Effect of potassium sorbate washing on the growth of Listeria monocytogenes on fresh poultry

Abstract

This work evaluated the effect of potassium sorbate washing on the growth of Listeria monocytogenes on poultry legs stored at 4 °C for 7 days. Fresh inoculated chicken legs were dipped into either a 2.5% (w/v) or 5% potassium sorbate solution or distilled water (control). Changes in mesophiles, pychrotrophic counts and sensorial characteristics (odor, color, texture and overall appearance) were also evaluated.

The shelf life of the samples washed with potassium sorbate was extended by at least 2 days over the control samples washed with distilled water. Legs washed with 5% potassium sorbate showed a significant (p < 0.05) inhibitory effect on L. monocytogenes compared to control legs, with a decrease of about 1.3 log units after 7 days of storage. Sensory quality was not adversely affected by potassium sorbate.

Effect of potassium sorbate washing on the growth of Listeria monocytogenes on fresh poultry. E. González-Fandos, J.L. Dominguez. Food Control. Volume 18, Issue 7, July 2007, Pages 842–846. doi:10.1016/j.foodcont.2006.04.008

Sorbic Acid and Potassium Sorbate Permeability of an Edible Methylcellulose-Palmitic Acid Film: Water Activity and pH Effects

ABSTRACT

The apparent permeability constants for potassium sorbate and sorbic acid through an edible film composed of methylcellulose and palmitic acid (weight ratio 3:1) were evaluated as a function of water activity (aw) and pH. For films with thickness 55–66 μm, potassium sorbate permeability increased from 2.3 × 10−10 to 2.0 × 10−8 (mg/sec cm2)(cm)/(mg/mL) as aw increased from 0.65 to 0.80. Films were not stable at aw levels above 0.80. Permeability of the film to sorbic acid at aw 0.8 decreased from 3.3 × 10−8 to 9.1 × 10−10 (mg/sec cm2)(cm)/ (mg/mL) as pH increased from 3 to 7. At pH 3 the undissociated acid was 97.5% and at pH 7 it was 0.4%.

RICO-PEÑA, D. C. and TORRES, J. A. (1991), Sorbic Acid and Potassium Sorbate Permeability of an Edible Methylcellulose-Palmitic Acid Film: Water Activity and pH Effects. Journal of Food Science, 56: 497–499. doi: 10.1111/j.1365-2621.1991.tb05312.x

Validation of HPLC Analysis of 2-Phenoxyethanol, 1-Phenoxypropan-2-ol, Methyl, Ethyl, Propyl, Butyl and Benzyl 4-Hydroxybenzoate (Parabens) in Cosmetic Products, with Emphasis on Decision Limit and Detection Capability

Abstract

The Commission Decision of August 12, 2002 on the performance of analytical methods and the interpretation of results was applied to the HPLC method for the analysis of parabens, 2-phenoxyethanol and 1-phenoxypropan-2-ol in cosmetic products. This method is published in the seventh Directive 96/45/EC of the European Commission. Non-compliant concentrations, taking into account the data distribution (CCα) and the probability of false negative values (CCβ) were determined. The repeatability and reproducibility amount to <4% and <7%, respectively. These values were obtained with blanc samples that were fortified in the laboratory. Calibration linearity was confirmed by absence of lack of fit for all seven preservatives. Matrix effects on the determinations of the preservatives in body milk or shampoo are negligible.

Validation of HPLC Analysis of 2-Phenoxyethanol, 1-Phenoxypropan-2-ol, Methyl, Ethyl, Propyl, Butyl and Benzyl 4-Hydroxybenzoate (Parabens) in Cosmetic Products, with Emphasis on Decision Limit and Detection Capability.

1. Borremans , J. Van Loco, P. Roos, L. Goeyens. Chromatographia. January 2004, Volume 59, Issue 1, pp 47-53

Tocopherol Acetate

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice

Abstract

Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115–0.23 J/cm2 results after 24–48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-α-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40–55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel noninvasive technique not previously reported for this purpose—magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p < 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p < 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p < 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the irradiation has stopped, by a derivative of d-α-tocopherol which is stable to autooxidation.

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. John R. Trevithick, Hua Xiong, Shirley Lee, David T. Shum, S.Ernest Sanford, Stephen J. Karlik, Christopher Norley, Geoffrey R. Dilworth. Archives of Biochemistry and Biophysics. Volume 296, Issue 2, 1 August 1992, Pages 575-582. doi:10.1016/0003-9861(92)90613-2

Biokinetics in humans of RRR-α-tocopherol: The free phenol, acetate ester, and succinate ester forms of vitamin E

Abstract

The bioavailability of RRR-α-tocopherol from the oral administration of RRR-α-tocopherol itself and its acetate and succinate esters was determined in healthy human subjects. Venous blood samples were withdrawn periodically over a 51-h period following oral administration of a gelatin capsule containing an equimolar mixture of RRR-α-tocopherol and RRR-α-tocopheryl acetate. In a second study, subjects received a capsule containing an equimolar mixture of RRR-α-tocopheryl acetate and RRR-α-tocopheryl succinate. In Study 1, RRR-α-tocopherol was absorbed at similar rates from both the free phenol, and the acetate ester and maximum plasma levels occurred at 12 h in most subjects. The extent of absorption of RRR-α-tocopherol varied considerably between subjects in absolute terms, but the relative absorption from the two forms was remarkably consistent, and a ratio of 1.0 was found for parameters of relative bioavailability in plasma. The concentration of RRR-α-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large inter-individual variability. In Study 2, there was no significant difference in the extent of absorption of RRR-α-tocopherol from the acetate ester and the succinate ester, although there was an apparently higher initial rate of absorption from the acetate ester.

Biokinetics in humans of RRR-α-tocopherol: The free phenol, acetate ester, and succinate ester forms of vitamin E. Kevin H. Cheeseman, Anne E. Holley, Frank J. Kelly, Mohamad Wasil, Lise Hughes, Graham Burton. Free Radical Biology and Medicine.Volume 19, Issue 5, November 1995, Pages 591–598.doi:10.1016/0891-5849(95)00083-A

A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles

Synopsis Solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system with reduced side-effects. Incorporation of the chemical sunscreen tocopherol acetate into SLN prevents chemical degradation and increases the UV-blocking capacity. Aqueous SLN dispersions were produced and incorporated into gels, followed by particle size examination, stability testing upon storage and thermoanalytical examination. Investigation of the UV-blocking capacity using different in vitro techniques revealed that the SLN dispersions produced in this study are at least twice as effective as their reference emulsions (conventional emulsions with identical lipid content). Placebo SLN even show greater UV-blocking efficacy than emulsions containing tocopherol acetate as the molecular sunscreen. Incorporation of tocopherol acetate into SLN leads to an overadditive UV-blocking effect. Furthermore, film formation of SLN on the skin and occlusivity were examined. The obtained data show that incorporation of tocopherol acetate into SLN leads to an improved sunscreen and skin care formulation.

Wissing, S. A. and Müller, R. H. (2001), A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles. International Journal of Cosmetic Science, 23: 233–243. doi: 10.1046/j.1467-2494.2001.00087.x

Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Abstract

α-Tocopherol transfer protein (αTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by αTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and α-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-α-tocopherol=100%) calculated from the degree of competition were as follows: β-tocopherol, 38%; γ-tocopherol, 9%; δ-tocopherol, 2%; α-tocopherol acetate, 2%; α-tocopherol quinone, 2%; SRR-α-tocopherol, 11%; α-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for αTTP is one of the critical determinants of their biological activity.

Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. Akihiro Hosomi, Makoto Arita, Yuji Sato, Chikako Kiyose, Tadahiko Ueda, Osamu Igarashi, Hiroyuki Arai, Keizo Inoue. FEBS Letters. Volume 409, Issue 1, 2 June 1997, Pages 105–108. doi:10.1016/S0014-5793(97)00499-7

Preparation of core-shell PAN nanofibers encapsulated alpha-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection

Preparation of core-shell PAN nanofibers encapsulated alpha-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection. Wu, Xiao-Mei; Branford-White, Christopher J.; Yu, Deng-Guang; et al. COLLOIDS AND SURFACES B-BIOINTERFACES Volume: 82 Issue: 1 Pages: 247-252

In vitro and in vivo Permeation of Vitamin E and Vitamin E Acetate from Cosmetic Formulations.

In vitro and in vivo Permeation of Vitamin E and Vitamin E Acetate from Cosmetic Formulations. Nada, Aly; Krishnaiah, Yellela S. R.; Zaghloul, Abdel-Azim; et al.MEDICAL PRINCIPLES AND PRACTICE Volume: 20 Issue: 6 Pages: 509-513 Published: 2011

Chemoprevention of Human Actinic Keratoses by Topical DL-alpha-Tocopherol.

Chemoprevention of Human Actinic Keratoses by Topical DL-alpha-Tocopherol. Foote, Janet A.; Ranger-Moore, James R.; Einspahr, Janine G.; et al. CANCER PREVENTION RESEARCH Volume: 2 Issue: 4 Pages: 394-400

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation.

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. Murray, John C.; Burch, James A.; Streilein, Robert D.; et al.JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Volume: 59 Issue: 3 Pages: 418-425

Vitamin E in human skin: Organ-specific physiology and considerations for its use in dermatology.

Vitamin E in human skin: Organ-specific physiology and considerations for its use in dermatology. Thiele, Jens J.; Ekanayake-Mudiyanselage, Swarna. MOLECULAR ASPECTS OF MEDICINE Volume: 28 Issue: 5-6 Pages: 646-667

Thyme Extract

Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels

Carvacrol, eugenol and thymol are major components of plants such as oregano, savory, clove and thyme. When applied to the tongue, these flavors elicit a warm sensation. They are also known to be skin sensitizers and allergens. The transient receptor potential channel (TRPV3) is a warm-sensitive Ca2+-permeable cation channel highly expressed in the skin, tongue and nose. Here we show that TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol. Tongue and skin epithelial cells respond to carvacrol and eugenol with an increase in intracellular Ca2+ levels. We also show that this TRPV3 activity is strongly potentiated by phospholipase C–linked, G protein–coupled receptor stimulation. In addition, carvacrol activates and rapidly desensitizes TRPA1, which may explain the pungency of oregano. Our results support a role for temperature-sensitive TRP channels in chemesthesis in oral and nasal epithelium and suggest that TRPV3 may be a molecular target of plant-derived skin sensitizers.

Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Haoxing Xu, Markus Delling, Janice C Jun & David E Clapham. Nature Neuroscience 9, 628 – 635 (2006). doi:10.1038/nn1692

Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells.

Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells. Emir Bozkurt, Harika Atmaca, Asli Kisim, Selim Uzunoglu, Ruchan Uslu & Burcak Karaca. Nutrition and CancerVolume 64, Issue 8, November 2012, pages 1245-1250.

Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy.

Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy.Margarita González-Vallinas, Guillermo Reglero & Ana Ramírez de Molina. Nutrition and CancerVolume 67, Issue 8, November 2015, pages 1223-1231

The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins.

The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins.Tea Kulišić Ph.D, Anita Kriško, Verica Dragović-Uzelac, Mladen Miloš & Greta Pifat. International Journal of Food Sciences and Nutrition. Volume 58, Issue 2, January 2007, pages 87-93

Essential Oil of Thyme (Thymus vulgaris L.) Grown in Cuba

Essential Oil of Thyme (Thymus vulgaris L.) Grown in Cuba. Jorge A. Pino, Mirna Estarrón & Victor Fuentes. Journal of Essential Oil Research. Volume 9, Issue 5, September 1997, pages 609-61.

Chemical Profile, Antioxidant and Antibacterial Activity of Thyme and Oregano Essential Oils, Thymol and Carvacrol and Their Possible Synergism.

Chemical Profile, Antioxidant and Antibacterial Activity of Thyme and Oregano Essential Oils, Thymol and Carvacrol and Their Possible Synergism. Neda Gavaric, Sonja Smole Mozina, Nebojša Kladar & Biljana Bozin. Journal of Essential Oil Bearing Plants. Volume 18, Issue 4, July 2015, pages 1013-1021

Investigation of Extracts from Thyme (Thymus vulgaris L.) for Application in Cosmetics.

Investigation of Extracts from Thyme (Thymus vulgaris L.) for Application in Cosmetics. Stanka Damianova, Stanislava Tasheva, Albena Stoyanova & Dancho Damianov. Journal of Essential Oil Bearing Plants.Volume 11, Issue 5, January 2008, pages 443-450

Identification and quantification of a major anti-oxidant and anti-inflammatory phenolic compound found in basil, lemon thyme, mint, oregano, rosemary, sage, and thyme.

Identification and quantification of a major anti-oxidant and anti-inflammatory phenolic compound found in basil, lemon thyme, mint, oregano, rosemary, sage, and thyme. Jae B. Park. International Journal of Food Sciences and Nutrition. Volume 62, Issue 6, September 2011, pages 577-584

Citric Acid

Overview of citric acid production from Aspergillus niger.

Abstract

Citric acid has high economic potential owing to its numerous applications. It is mostly produced by microbial fermentation using Aspergillus niger. In view of surges in demand and growing markets, there is always a need for the discovery and development of better production techniques and solutions to improve production yields and the efficiency of product recovery. To support the enormous scale of production, it is necessary and important for the production process to be environmentally friendly by utilizing readily available and inexpensive agro-industrial waste products, while maintaining high production yields. This article reviews the biochemistry of citric acid formation, choices of citric-acid producing microorganisms and raw materials, fermentation strategies, the effects of various fermentation conditions, citric acid recovery options and the numerous applications of citric acid, based on information drawn from the literature over the past 10 years.

Overview of citric acid production from Aspergillus niger. Pau Loke Show, Kehinde Opeyemi Oladele, Qi Yan Siew, Fitri Abdul Aziz Zakry, John Chi-Wei Lan & Tau Chuan Ling. Frontiers in Life Science. Volume 8, Issue 3, July 2015, pages 271-283

Citric Acid-Ammonium Acetate Buffer.

Abstract

A pH table is reported for citric acid-ammonium acetate buffers that are useful for horseradish peroxidase (HRP) histochemistry.

Citric Acid-Ammonium Acetate Buffer. Sharon Stegmann, Robert B. Norgren & Michael N. Lehman. biotechnic & Histochemistry.Volume 66, Issue 1, January 1991, pages 27-28

Characterization of Blue Whiting Skin Gelatines Extracted After Pretreatment with Different Organic Acids.

Abstract

Gelatines were extracted from blue whiting (Micromesistius poutassou) skins after pretreatment with different organic acids (acetic, citric, lactic, malic, and tartaric acids). The effect of the pretreatment on the chemical composition and the rheological properties of extracted gelatines were analyzed. It was observed that acetic acid pretreatment resulted in significantly (p < 0.05) higher extraction yield compared to the rest of the gelatines. All gelatines, regardless of the organic acid used in the pretreatment, had similar chemical composition (p > 0.05). The amino acid analysis showed that acetic acid pretreated skins resulted in gelatines with higher imino acid levels with respect to the other pretreatments. Acetic and tartaric acid derived gelatine gels showed highly interconnected protein networks and better viscoelastic properties, in terms of storage modulus, compared to the other pretreatments.

Characterization of Blue Whiting Skin Gelatines Extracted After Pretreatment with Different Organic Acids. Zied Khiari, Daniel Rico, Ana Belen Martin-Diana & Catherine Barry-Ryan. Journal of Aquatic Food Product Technology. Volume 24, Issue 6, August 2015, pages 546-555

The direct determination of phosphorus in citric acid soil extracts by colorimetry and direct-current plasma emission spectroscopy.

Abstract

The effect of citrate interference on the direct colorimetric determination of P in 1% citric acid soil extracts of a wide range of soils was investigated and compared to that of removing the citric acid by dry ashing. It was found that dilution of the soil extracts to ratios greater than 1:20 caused minimal interference with colour development using the molybdenum blue method. Dilutions of 1:10 and 1:5 caused a 10% and 55% reduction in absorbance values respectively. Despite this interference, the measurement of P in the presence of 1% citric acid is possible if the same concentration of this acid, present in the soil extract, is present in the calibration standards. Generally a 1:10 dilution of soil extracts provides sufficient sensitivity for the determination of P in soils with a P status < 5 mg kg−1 and can accommodate soils with a P status up to 100 mg kg−1. The effect of dry ashing the soil extracts and measuring the P colorimetrically resulted in slightly higher P values, in the order of 2 mg kg−1. Similar results were obtained when the soil extracts were aspirated into a direct-current plasma and the P was measured by emission spectrometry. It was concluded that quantities of P could be present in the soil extracts, either organically or inorganically bound, and were responsible for this difference. These forms of P were not determined by colorimetric procedures but were released by a high-temperature plasma or by dry ashing. For most practical purposes these low values can be ignored.

The direct determination of phosphorus in citric acid soil extracts by colorimetry and direct-current plasma emission spectroscopy. G. R. Thompson. South African Journal of Plant and Soil. Volume 12, Issue 4, January 1995, pages 152-157

Development and evaluation of dual controlled release microballoons containing riboflavin and citric acid: in vitro and in vivo evaluation.

Abstract

The objective of this work was to optimize the incorporation of citric acid (CA) in the gastroretentive microballoons containing riboflavin (RF) in order to achieve dual controlled release system and consequently enhance the bioavailability of RF. Microballoons of 739 ± 1.9 µm containing RF–CA were prepared by modified emulsion solvent diffusion method and were evaluated both for in vitro and in vivo performance. RF–CA microballoons with 22.8% RF and 37.2% CA entrapped in the shell matrix composed of Eudragit® S 100 and HPMCK4M and in vitro buoyancy of 86.0 ± 0.88% (RCM3) was selected for further studies. RCM3 exhibited biphasic, pH-dependent in vitro dual controlled release of RF (0.9933–0.9962) and CA (0.996–0.9984) beyond 1 h in both simulated fasted and fed state conditions. RCM3 was able to achieve higher mean plasma concentrations than reference formulation RM2 (RF microballoon) both in fed and fasted states in rabbits. The mean AUC0–24 estimate of RCM3 was 55% higher in fasted state (p < 0.01) and about 51% higher in fed state (p < 0.05) relative to mean AUC0–24 from RM2 formulation. Conclusively, enhancement in RF in the presence of CA along the entire plasma level curve suggests a possibility of reduction in dosing frequency. This controlled release drug delivery system of RF, where CA is incorporated in the microballoons can be easily encapsulated in capsule dosage form negating the need of CA solution as vehicle for administration of RF microballoons.

Development and evaluation of dual controlled release microballoons containing riboflavin and citric acid: in vitro and in vivo evaluation. Amriteshwar N. Singh & Kamla Pathak. Journal of Microencapsulation. Volume 28, Issue 5, August 2011, pages 442-454

Chamomile (Matricaria recutita) Extract

CHAMOMILE (Matricaria recutita) EXTRACT AS A CORROSION INHIBITOR FOR MILD STEEL IN HYDROCHLORIC ACID SOLUTION

Abstract

The corrosion inhibition of mild steel in hydrochloric acid solution by chamomile (Matricaria recutita) extract (CE) was investigated through electrochemical (polarization, EIS) and surface analysis (optical microscopy/AFM/SEM) techniques. The effects of inhibitor concentration, temperature, and pH were evaluated. Thermodynamic parameters were calculated and adsorption studies were carried out. Finally, the surface morphology was investigated. The electrochemical studies showed that CE acts as a mixed-type corrosion inhibitor with predominantly anodic behavior. CE was adsorbed physically on the metal surface and obeyed the Langmuir adsorption isotherm. It impeded the corrosion processes by changing the activation energy. In the presence of CE, the metal surface was more uniform than the surface in the absence of inhibitor. Maximum inhibition efficiency (IE) was 93.28%, which was obtained at 22°C in 7.2 g/L of inhibitor in 1 M HCl solution.

CHAMOMILE (Matricaria recutita) EXTRACT AS A CORROSION INHIBITOR FOR MILD STEEL IN HYDROCHLORIC ACID SOLUTION. Mahdi Nasibi, Davood Zaarei, Gholamreza Rashed & Effat Ghasemi. Chemical Engineering Communications.Volume 200, Issue 3, March 2013, pages 367-378

Chamomile Ligulate Flowers in Supercritical CO2-Extraction

Abstract

The essential oil (EO) of chamomile ligulate flowers (CLF) was extracted by supercritical carbon dioxide (SC-CO2) at 240 bar and 40°C for five hours. An empirical equation: log c = a log W + b, for defining the dependence of total extract concentration (cTE), i.e. EO concentration (cEO) in supercritical CO2, on relative mass of CO2 (W) was selected. The equations obtained fitted the experimental data very well (r1=0.9997 and r2=0.9977). In the same way, the behavior of pharmacologically active chamomile compounds [(—)-α-bisabolol, oxides A and B, (—)-α-bisabolol, cis- and trans-en-in-dicycloethers] contained in EO of CLF after SC-CO2 extraction, was investigated. For qualitative and quantitative determination of EOs the GC/MS analysis was used. The fermentation of CLF after SC-CO2 extraction was used to increase the content of spasmolytically important chamomile flavone apigenin. The procedure of obtaining the product of CLF with the best composition of pharmacologically active compounds of chamomile has been reported.

Chamomile Ligulate Flowers in Supercritical CO2-Extraction. Zoran P. Zekovic. Journal of Essential Oil Research. Volume 12, Issue 1, January 2000, pages 85-93

Antioxidant Activity, Reaction Mechanisms, and Kinetics of Matricaria recutita Extract in Commercial Blended Oil Oxidation.

Abstract

Antioxidant activity, reaction mechanisms, and kinetics of Matricaria recutita crude extract (CE; total phenolics: 41 ± 2.5 mg/g, total flavonoids: 26 ± 1.4 mg/g, IC50: 82.3 ± 2.8 µg/mL and reducing power: 10.45 ± 0.56 mmol Fe2+/mass) in comparison to tert-Butylhydroquinone during oxidation of blended vegetable oil (sunflower, soybean, and palm oil) at 120, 130, and 140°C were studied. Good correlations existed between the Rancimat oil stability index and stability indices (induction period) calculated from peroxide value, conjugated diene value, and anisidine value with no significant differences in kinetic parameters calculated from them. The temperature acceleration (Q10), activation energy (Ea), frequency factor (A), enthalpy (ΔH++), entropy (ΔS++), and free energy of activation (ΔG++) for oils containing crude extract were lower than for oils containing tert-Butylhydroquinone (0.0025, 0.005, 0.01, and 0.02%). Values were independent of crude extract or tert-Butylhydroquinone concentration. For crude extract and tert-Butylhydroquinone, Ea and A were well correlated with ΔH++ and ΔS++ values, respectively, but correlation between Ea and Q10 for crude extract compared to tert-Butylhydroquinone was poor. Furthermore, the rate of Monounsaturated:Polyunsaturated fatty acids formation did not differ significantly between crude extract and tert-Butylhydroquinone, but concentrations of them did affect Monounsaturated:Polyunsaturated ratio. Based on the results obtained, crude extract decreased the rate of the oxidation reaction due to the decrease in the concentration of the activated complex and reduction in the rate at which the activated complex dissociated into oxidation products.

Antioxidant Activity, Reaction Mechanisms, and Kinetics of Matricaria recutita Extract in Commercial Blended Oil Oxidation. Seyed Mohammad Bagher Hashemi, Mary Susan Brewer, Javad Safari, Masoud Nowroozi, Moosa Hamid Abadi Sherahi, Behrooz Sadeghi & Moslem Ghafoori. International Journal of Food PropertiesVolume 19, Issue 2, February 2016, pages 257-271

Chemical Composition and Antimicrobial Activity of Essential Oil of Matricaria recutita

Abstract

Matricaria recutita is a herbaceous plant belonging to the Asteraceae family. The present study reports the chemical composition and antimicrobial activity of M. recutita essential oil and its main compounds. The essential oil was obtained from the aerial parts of the M. recutita by hydrodistillation and analyzed by gas chromatography-mass spectrometry. The major components were α-bisabolol oxide (38%), followed by camphene (9.11%), sabinene (4.87%), limonene (6%),1,8-cineole (7.12%), camphor (6.54%), and α-pinene (6%). Essential oil of chamomile was evaluated for its antibacterial activities against three gram-positive and four gram-negative pathogenic bacteria. The essential oil and its main compounds were particularly active against Bacillus cereus, with the lowest minimum inhibitory concentration and minimum bactericidal concentration value (0.022 and 1.5 μg /mL). In conclusion, these results support the use of the essential oil and its main compounds for their antimicrobial properties.

Chemical Composition and Antimicrobial Activity of Essential Oil of Matricaria recutita. Mohsen Kazemi. International Journal of Food Properties. Volume 18, Issue 8, August 2015, pages 1784-1792

Passion Flower (Passiflora Incarnata) Extract

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques

Abstract

Passiflora is one of the 27 genera of the Passifloraceae family. Some Passiflora species are known by their edible fruits, which have a distinct flavor and aroma that favor their in natura consumption and their applicability in the food industry. Also, Passiflora leaves have therapeutical properties, such as the widely known anxiolytic and sedative effects. The quality control and the assessment of the compounds responsible for the Passiflora properties can be done by several chromatographic and electrophoretic techniques, such as planar chromatography (TLC and HTPLC), liquid chromatography (HPLC and UHPLC), gas chromatography (GC), and capillary electrophoresis (CE). The aim of this article is to review the analytical techniques used for the evaluation of the different compounds present in each part of a Passiflora plant, exploring the leaves, the fruits with their rinds and seeds, and other Passiflora parts, such as nectar and callus culture compositions, as well as to compare stability tests on several Passiflora products.

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques. Gisláine C. Silva & Carla B. G. Bottoli. Critical Reviews in Analytical Chemistry. Volume 45, Issue 1, January 2015, pages 76-95

An Evidence-Based Systematic Review of Passion Flower (Passiflora Incarnata L.) by the Natural Standard Research Collaboration

An Evidence-Based Systematic Review of Passion Flower (Passiflora Incarnata L.) by the Natural Standard Research Collaboration. Journal of Dietary SupplementsVolume 5, Issue 3, January 2008, pages 310-340. DOI:10.1080/19390210802414360

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques

Abstract

Passiflora is one of the 27 genera of the Passifloraceae family. Some Passiflora species are known by their edible fruits, which have a distinct flavor and aroma that favor their in natura consumption and their applicability in the food industry. Also, Passiflora leaves have therapeutical properties, such as the widely known anxiolytic and sedative effects. The quality control and the assessment of the compounds responsible for the Passiflora properties can be done by several chromatographic and electrophoretic techniques, such as planar chromatography (TLC and HTPLC), liquid chromatography (HPLC and UHPLC), gas chromatography (GC), and capillary electrophoresis (CE). The aim of this article is to review the analytical techniques used for the evaluation of the different compounds present in each part of a Passiflora plant, exploring the leaves, the fruits with their rinds and seeds, and other Passiflora parts, such as nectar and callus culture compositions, as well as to compare stability tests on several Passiflora products.

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques. Gisláine C. Silva & Carla B. G. Bottoli. Critical Reviews in Analytical Chemistry. Volume 45, Issue 1, January 2015, pages 76-95

Hydrolyzed Silk Protein

Long-range periodic sequence of the cement/silk protein of Stenopsyche marmorata: purification and biochemical characterisation

Abstract

The long-range periodic amino acid sequence of the bifunctional silk/cement protein from larvae of the caddisfly, Stenopsyche marmorata, is discussed in this study. The protein, named the S. marmorata silk protein (Smsp-1), was first purified to electrophoretic homogeneity. The results of Edman-based sequencing of Smsp-1 tryptic digests were consistent with the amino acid sequence deduced from a cDNA clone of the Smsp-1 gene. All undetected amino acids in the Edman-based sequencing were encoded as Ser, suggesting the presence of O-phospho-Ser. 31P-NMR and an O-phospho-amino acid analysis successfully showed that the O-phospho-Ser residue occurred in a clustered manner, serving a cement function for Smsp-1. Two patterns of non-phosphorylated repeats, –SLGPYGDPRGDXLGPYGG– (X = V, G or D) and –GVGPYGDGLGPYGG–, were enriched in Smsp-1 compared with the O-phospho-Ser cluster, and have fibre-forming functions.

Long-range periodic sequence of the cement/silk protein of Stenopsyche marmorata: purification and biochemical characterisation. Kousaku Ohkawa, Yumi Miura, Takaomi Nomura, Ryoichi Arai, Koji Abe, Masuhiro Tsukada & Kimio Hirabayashi. BiofoulingVolume 29, Issue 4, April 2013, pages 357-367

Complexation-triggerable liposome mixed with silk protein and chitosan

Abstract

Complexation-triggerable liposomes were prepared by modifying the surface of egg phosphatidylcholine (EPC) liposomes with hydrophobicized silk fibroin (HmSF) and hydrophobicized chitosan (HmCh). Maximum complexation, determined by measuring the diameter of complexation, was found when the ratio of HmSF to HmCh was 14:1, so they were immobilized on the surface of liposomes at the same ratio. The degree of fluorescence quenching of calcein in liposomal suspension was as high as 68% when the ratio of surface modifier (HmSF + HmCh) to EPC was 1:15. When the ratio was increased to 1:5, the degree of quenching decreased to 32%, indicating the inefficient formation of liposome. Liposome mixed with the surface modifier was multi-lamellar vesicle on TEM photo. And, the mean diameter was larger than those of liposome mixed with either HmSF or HmCh, possibly due to insoluble complex on the liposomal surface. The liposome exhibited a pH-sensitive release and triggered the release at pH 5.5 and 6.0. It is believed that complexation is responsible for the promoted release at those pH values.

Complexation-triggerable liposome mixed with silk protein and chitosan.Yeon-Ji Hong & Jin-Chul Kim. Journal of Biomaterials Science, Polymer Edition. Volume 26, Issue 12, August 2015, pages 766-779

High-strength silk protein scaffolds for bone repair

Abstract

Biomaterials for bone tissue regeneration represent a major focus of orthopedic research. However, only a handful of polymeric biomaterials are utilized today because of their failure to address critical issues like compressive strength for load-bearing bone grafts. In this study development of a high compressive strength (~13 MPa hydrated state) polymeric bone composite materials is reported, based on silk protein-protein interfacial bonding. Micron-sized silk fibers (10–600 µm) obtained utilizing alkali hydrolysis were used as reinforcement in a compact fiber composite with tunable compressive strength, surface roughness, and porosity based on the fiber length included. A combination of surface roughness, porosity, and scaffold stiffness favored human bone marrow-derived mesenchymal stem cell differentiation toward bone-like tissue in vitro based on biochemical and gene expression for bone markers. Further, minimal in vivo immunomodulatory responses suggested compatibility of the fabricated silk-fiber-reinforced composite matrices for bone engineering applications.

High-strength silk protein scaffolds for bone repair. Biman B. Mandala, Ariela Grinberga, Eun Seok Gila, Bruce Panilaitisa, and David L. Kaplan. PNAS. May 15, 2012 vol. 109 no. 20. doi: 10.1073/pnas.1119474109

Applications of natural silk protein sericin in biomaterials

Abstract

Silk sericin is a natural macromolecular protein derived from silkworm Bombyx mori. During the various stages of producing raw silk and textile, sericin can be recovered for other uses. Also, sericin recovery reduces the environmental impact of silk manufacture. Sericin protein is useful because of its properties. The protein resists oxidation, is antibacterial, UV resistant, and absorbs and releases moisture easily. Sericin protein can be cross-linked, copolymerized, and blended with other macromolecular materials, especially artificial polymers, to produce materials with improved properties. The protein is also used as an improving reagent or a coating material for natural and artificial fibers, fabrics, and articles. The materials modified with sericin and sericin composites are useful as degradable biomaterials, biomedical materials, polymers for forming articles, functional membranes, fibers, and fabrics.

Applications of natural silk protein sericin in biomaterials. Yu-Qing Zhang. Biotechnology Advances. Volume 20, Issue 2, May 2002, Pages 91–100. doi:10.1016/S0734-9750(02)00003-4

Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture.

We previously reported that sericin small (sericin-S), with a molecular weight that ranges from 5 to 100 kDa, is a cell culture supplement used to accelerate cell proliferation. In this study, a novel preparation method for sericin and several applications of sericin were examined. Sericin large, prepared under nonhydrolyzing conditions and ranging from 50 to 200 kDa, also accelerated cell proliferation, but its effects were inferior to those of sericin-S. Additional sericin preparations with various molecular weights that were differentially hydrolyzed were also tested but none of them was significantly superior to sericin-S, and neither were several recombinant sericin peptides. Sericin-S successfully accelerated the proliferation of hybridoma cells in various serum-free media, implying the mitogenic effect of sericin is independent from media. We also demonstrated that sericin-S successfully induced the proliferation of CTLL-2, an established T lymphocyte cell line, under IL-2 starvation conditions. These results indicate that sericin, particularly sericin-S, improves serum-free mammalian cell culture.

Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture. Satoshi Terada, Masahiro Sasaki, Kana Yanagihara, Hideyuki Yamada. Journal of Bioscience and Bioengineering. Volume 100, Issue 6, December 2005, Pages 667–671.doi:10.1263/jbb.100.667

Expression and Purification of a Spider Silk Protein: A New Strategy for Producing Repetitive Proteins

Abstract

Synthetic genes were constructed based on the known sequence of the spider dragline silk protein MaSp 2. The genes had 8, 16, or 32 contiguous units of the consensus repeat sequence of the protein. These artificial genes were constructed using a strategy involving compatible but nonregenerable restriction sites, which allowed construction of very large inserts in a precisely controlled manner. This strategy should have general utility in the controlled construction of repetitive proteins composed of identical or different repeat units. The protein from the 16-unit repeat was produced inEscherichia coliat levels up to 10 mg/g wet wt of cells although yields of 1–2 mg/g were more typical. The protein was easily purified with high recovery using an affinity column. The purified protein had the predicted amino acid composition and N-terminal sequence after cleavage of a leader sequence. The methodology described will allow production of sufficient quantities of protein for basic structure/function studies including production of synthetic fibers.

Expression and Purification of a Spider Silk Protein: A New Strategy for Producing Repetitive Proteins. Randolph V. Lewisa, Michael Hinman, Srinivas Kothakota, Maurille J. Fournier. Protein Expression and Purification. Volume 7, Issue 4, June 1996, Pages 400–406.doi:10.1006/prep.1996.0060

Retinol Palmitate (Vitamin A Palmitate).

A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy

RESULTS

Seven of ten retinol palmitate patients responded, whereas two of nine responded to placebo (P = 0.057). Mean pre-post-treatment change in Radiation Proctopathy System Assessments Scale (Δ Radiation Proctopathy System Assessments Scale) in the retinol palmitate group was 11 ± 5, whereas Δ Radiation Proctopathy System Assessments Scale in the placebo group was 2.5 ± 3.6 (P = 0.013, Mann-Whitney U test). Additionally, all five placebo nonresponders who were crossed over to treatment with retinal palmitate responded to treatment.

CONCLUSIONS

In our trial, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound-healing effects. The current results can serve as the foundation for future trials examining retinol palmitate in the multi-institutional setting.

A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy.Eli D. Ehrenpreis , Ashesh Jani, Josh Levitsky, Joseph Ahn, John Hong. Diseases of the Colon & Rectum. January 2005, Volume 48, Issue 1, pp 1-8.

Effect of Process Variables on the Microencapsulation of Vitamin A Palmitate by Gelatin-Acacia Coacervation

Abstract

Microcapsules of vitamin A palmitate were prepared by gelatin-acacia complex coacervation. The effects of colloid mixing ratio, core-to-wall ratio, hardening agent, concentration of core solution, and drying method on the coacervation process and the properties of the microcapsules were investigated. The microcapsules of vitamin A palmitate were prepared using different weight ratios of gelatin and acacia, that is, 2:3, 1:1, and 3:2 under controlled conditions. The other factors studied were 1:1, 1:2, and 1:3 core-to-wall ratios; 30, 60, and 120 min of hardening time; 2, 5, and 10 ml of formaldehyde per 280 g of coacervation system as a hardening agent; and 30%, 40%, and 50% w/w vitamin A palmitate in corn oil as a core material. The drying methods used were air drying, hot air at 40°C, and freeze-drying. The results showed that spherical microcapsules were obtained for all conditions except for 30 min of hardening time, which did not result in microcapsules. The optimum conditions for free-flowing microcapsules with a high percentage of entrapped drug were 1:1 gelatin-to-acacia ratio and 1:2 core-to-wall ratio when hardening with 2 ml formaldehyde for 60 min and using 40% w/w vitamin A palmitate in corn oil as the core concentration. In addition, drying the microcapsules by freeze-drying provided microcapsules with excellent appearance.

Effect of Process Variables on the Microencapsulation of Vitamin A Palmitate by Gelatin-Acacia Coacervation.Varaporn Buraphacheep Junyaprasert, Ampol Mitrevej, Nuttanan Sinchaipanid, Prapaporn Boonme & Dale Eric Wurster. Drug Development and Industrial PharmacyVolume 27, Issue 6, January 2001, pages 561-566. DOI:10.1081/DDC-100105181

Inclusion complexation of vitamin a palmitate with β-cyclodextrin in aqueous solution

Abstract

Study of the inclusion complex between vitamin A palmitate and β-cyclodextrin in aqueous solution was performed to determine the stoichiometry and the association constant of the complex by the phase solubility diagram and fluorescence intensity measurements.

Inclusion complexation of vitamin a palmitate with β-cyclodextrin in aqueous solution.Giovanni Filippo Palmieri, Pascal Wehrlé, Guy Duportail & AndrÉ Stamm. Drug Development and Industrial PharmacyVolume 18, Issue 19, January 1992, pages 2117-2121. DOI:10.3109/03639049209040925

#1 – Send an email to support [at] purehealthresearch.com. Remember to include your order number if inquiring about an order.

#2 – Call us toll free at (888) 558-9836, M – F 8AM – 8PM EST, Outside the US, call us at +1-863-301-4007

#3 – Mailing addresses:

Packages/Letters/Checks:
PureHealth Research
PO Box 153201 Suite #1053 Tampa,
FL 33634, United States

Allure Cosmeceuticals

DARK SPOT CORRECTOR

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Purified Water

Rapid enumeration of physiologically active bacteria in purified water used in the pharmaceutical manufacturing process

Abstract

Physiologically active bacteria in purified water used in the manufacturing process of pharmaceutical products were enumerated in situ. Bacteria with growth potential were enumerated using the micro-colony technique and direct viable counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean Casein Digest Broth) at 30 °C. Respiring and esterase-active bacteria were detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of bacteria in purified water retained physiological activity, while most could not form colonies on conventional media. The techniques applied in this study enabled bacteria to be counted within 24 h so results could be available within one working day. These rapid and convenient techniques should be useful for the systematic monitoring of bacteria in water used for pharmaceutical manufacturing.

M. Kawai,N. Yamaguchi andM. Nasu.Journal of Applied Microbiology. Volume 86, Issue 3, pages 496–504, March 1999. DOI: 10.1046/j.1365-2672.1999.00689.x
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.1999.00689.x/full

Free radical scavenging activity of a novel antioxidative peptide purified from hydrolysate of bullfrog skin, Rana catesbeiana Shaw

Abstract

In the present study, a peptide having antioxidant properties was isolated from bullfrog skin protein, Rana catesbeiana Shaw. Bullfrog skin protein was hydrolyzed using alcalase, neutrase, pepsin, papain, α-chymotrypsin and trypsin. Antioxidant activities of respective hydrolysates were evaluated using lipid peroxidation inhibition assay and direct free radical scavenging activity by using electron spin resonance (ESR) spectrometer. Among hydrolysates, alcalase derived hydrolysate exhibited the highest antioxidant activities than those of other enzyme hydrolysates. In order to purity a peptide having potent antioxidant properties, alcalase hydrolysate was separated using consecutive chromatographic methods on a Hiprep 16/10 DEAE FF anion exchange column, Superdex Peptide 10/300 GL gel filtration column and highan octadecylsilane (ODS) C18 reversed phase column. Finally, a potent antioxidative peptide was isolated and its sequence was identified to be LEELEEELEGCE (1487 Da) by Q-TOF ESI mass spectroscopy. This antioxidant peptide from bullfrog skin protein (APBSP) inhibited lipid peroxidation higher than that of α-tocopherol as positive control and efficiently quenched different sources of free radicals: DPPH radical (IC₅₀ = 16.1 μM), hydroxyl radical (IC₅₀ = 12.8 μM), superoxide radical (IC₅₀ = 34.0 μM) and peroxyl radical (IC₅₀ = 32.6 μM). Moreover, MTT assay showed that this peptide does not exert any cytotoxicity on human embryonic lung fibroblasts cell line (MRC-5).

Zhong-Ji Qian,Won-Kyo Jung,Se-Kwon Kim.Bioresource Technology. Volume 99, Issue 6, April 2008, Pages 1690–1698.doi:10.1016/j.biortech.2007.04.005

Glycerine

Glycerol and the skin: holistic approach to its origin and functions

Summary

Glycerol is a trihydroxy alcohol that has been included for many years in topical dermatological preparations. In addition, endogenous glycerol plays a role in skin hydration, cutaneous elasticity and epidermal barrier repair. The aquaporin-3 transport channel and lipid metabolism in the pilosebaceous unit have been evidenced as potential pathways for endogenous delivery of glycerol and for its metabolism in the skin. Multiple effects of glycerol on the skin have been reported. The diverse actions of the polyol glycerol on the epidermis include improvement of stratum corneum hydration, skin barrier function and skin mechanical properties, inhibition of the stratum corneum lipid phase transition, protection against irritating stimuli, enhancement of desmosomal degradation, and acceleration of wound-healing processes. Even an antimicrobial effect has been demonstrated. Topical application of glycerol-containing products improves skin properties in diseases characterized by xerosis and impaired epidermal barrier function, such as atopic dermatitis. The increase of epidermal hydration by glycerol is critical in skin conditions aggravated by dry and cold environmental conditions, e.g. winter xerosis. This paper provides a review on effects of glycerol on the skin, the mechanisms of its action, and the potential applications of glycerol in dermatology.

Fluhr, J.W., Darlenski, R. and Surber, C. (2008), Glycerol and the skin: holistic approach to its origin and functions. British Journal of Dermatology, 159: 23–34. doi: 10.1111/j.1365-2133.2008.08643.x

A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial.

Summary

MethodsFor the patch test, commercially available test product and its vehicle were applied occluded for 12-days to photoaged forearm skin ( n = 10) prior to biopsy and immunohistochemical assessment of fibrillin-1; all-trans retinoic acid (RA) was used as a positive control. Sixty photoaged subjects were recruited to the RCT (test product, n = 30 vs. vehicle, n = 30; once daily for 6-months; face & hands) with clinical assessments performed at recruitment and following 1-, 3- & 6-months of use. Twenty-eight subjects had skin biopsies (dorsal wrist) at baseline and at 6 months of treatment for immunohistochemical assessment of fibrillin-1 (test product, n = 15; vehicle, n = 13). All subjects received test product for a further 6-months. Final clinical assessments were performed at the end of this open period; 27 subjects received test product for 12-months.

ResultsIn the 12-day patch test assay, we observed significant immunohistological deposition of fibrillin-1 in skin treated by test product and RA as compared to untreated baseline ( P = 0·005 and 0·015 respectively). In the clinical RCT, at 6 months, compared to baseline assessment, 43% of subjects on test product had an improvement in facial wrinkles (P = 0·013), whereas only 22% of subjects using vehicle had clinical improvement (P = ns). Between group comparison of test product and vehicle was non-significant (P = 0·10). After 12 months, there was a significant benefit of test product over that projected for vehicle (70% vs. 33% of subjects improving; combined Wilcoxon rank tests, P = 0·026). There was significant deposition of fibrillin-1 in skin treated for 6 months with test product (mean ± SE; vehicle, 1·84 ± 0·23; test product, 2·57 ± 0·19; P = 0·019).

ConclusionAn over-the-counter cosmetic ‘anti-ageing’ product demonstrated clear benefit over vehicle in fibrillin-1 deposition over a 6-month trial period. There was a corresponding but non-significant trend towards clinical improvement in facial wrinkles. Clinical improvements in the treated group were increased after a further 6-months of use. This study demonstrates that a cosmetic may improve the appearance of wrinkles and further supports the use of fibrillin-1 as a robust biomarker for repair of photoaged dermis.

Watson, R.E.B., Ogden, S., Cotterell, L.F., Bowden, J.J., Bastrilles, J.Y., Long, S.P. and Griffiths, C.E.M. (2009), A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial. British Journal of Dermatology, 161: 419–426. doi: 10.1111/j.1365-2133.2009.09216.x

The Euro Skin Bank: Development and Application of Glycerol-Preserved Allografts.

Mackie, David P. FRCA. The Euro Skin Bank: Development and Application of Glycerol-Preserved Allografts.ournal of Burn Care & Rehabilitation.January/February 1997 – Volume 18 – Issue 1 – ppg s7-s9.

http://journals.lww.com/burncareresearch/Citation/1997/01001/The_Euro_Skin_Bank__Development_and_Application_of.4.aspx

Stearyl Alcohol

Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol help to form emulsions and prevent an emulsion from separating into its oil and liquid components. These ingredients also reduce the tendency of finished products to generate foam when shaken. When used in the formulation of skin care products, Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol act as a lubricant on the skin surface, which gives the skin a soft, smooth appearance.

Solubilities of stearic acid, stearyl alcohol, and arachidyl alcohol in supercritical carbon dioxide at 35.degree.C

ABSTRACT The solubilities of stearic acid (octadecanoic acid), stearyl alcohol (1-octadecanol), and arachidyl alcohol (1-eicosanol) in supercritical carbon dioxide were measured by using a flow-type apparatus at 35 C up to 23.7 MPa. The solubilities of those substances and other fatty acids and higher alcohols in supercritical carbon dioxide at 35 C were correlated by a solution model based on the regular solution model coupled with the Flory-Huggins theory.

Yoshio Iwai , Yoshio Koga , Hironori Maruyama , Yasuhiko Arai. J. Solubilities of stearic acid, stearyl alcohol, and arachidyl alcohol in supercritical carbon dioxide at 35°C. Chem. Eng. Data, 1993, 38 (4), pp 506–508. DOI: 10.1021/je00012a005

http://www.researchgate.net/publication/238656304_Solubilities_of_stearic_acid_stearyl_alcohol_and_arachidyl

Effect of cetostearyl alcohol on stabilization of oil-in-water emulsion: I. Difference in the effect by mixing cetyl alcohol with stearyl alcohol

Abstract

It is known that an oil-in-water emulsion increases in consistency and stability on addition of cetostearyl alcohol. When either cetyl alcohol or stearyl alcohol was added individually, the emulsion stability decreased. On storage at room temperature, unstable emulsions decreased in consistency and many particles (not visible immediately after preparation) appeared. The particles were determined to be crystals of the alcohol added. When both alcohols were included in the formulation simultaneously in the appropriate ratio, the emulsions were stable and did not show such changes. This difference in stability can be explained in relation to polymorphism of the alcohols.

S Fukushima,M Takahashi,M Yamaguchi. Journal of Colloid and Interface Science

Volume 57, Issue 2, November 1976, Pages 201-206. doi:10.1016/0021-9797(76)90193-4

http://www.sciencedirect.com/science/article/pii/0021979776901934

Microencapsulation of a waxy solid: Wall thickness and surface appearance studies

1. L. Madan, L. A. Luzzi and J. C. Price. Journal of Pharmaceutical Sciences

Volume 63, Issue 2, pages 280–284, February 1974. DOI: 10.1002/jps.2600630224.

Contact Dermatitis From Stearyl Alcohol and Propylene Glycol in Fluocinonide Cream

Abstract

A young woman being treated for linear scleroderma became allergic to fluocinonide (Lidex) cream while using it with occlusion. She was able to continue treatment with fluocinonide ointment without an adverse reaction.

Patch testing with the ingredients of the cream demonstrated sensitization to an impurity in commercial stearyl alcohol and irritation from propylene glycol. The woman had no adverse reactions to fluocinonide ointment because this preparation contains no stearyl alcohol and very little propylene glycol.

This case reemphasizes the important role of vehicles in contact allergy and indicates that allergic sensitization may be induced despite the presence of a potent topical steroid.

Ronald N. Shore, MD; Walter B. Shelley, MD, PhD. Arch Dermatol. 1974;109(3):397-399. doi:10.1001/archderm.1974.01630030055015.

http://archderm.jamanetwork.com/article.aspx?articleid=533859

Mechanism of Formation and Structure of Micro Emulsions by Electron Microscopy

Jack H. Schulman , Walter Stoeckenius , Leon M. Prince. J. Phys. Chem., 1959, 63 (10), pp 1677–1680. DOI: 10.1021/j150580a027

Tempering influence on oxygen and water vapor transmission through a stearyl alcohol film

Abstract

Stearyl alcohol was layered on a filter paper support and tested for resistance to O₂ and water vapor transmission following tempering. Tempering at 48C for 14 or 35 days caused the resistance to O₂and water vapor transmission to increase. The resistance to O₂ and water vapor transport was increased 80% and 50% respectively, after 35 days. Likely mechanistic explanations include the healing of crystal imperfections and the development of a more extensive and better linked arrangement of lipid crystalline platelets.

1157. J. Kester, O. Fennema. Journal of the American Oil Chemists’ Society. August 1989, Volume 66, Issue 8, pp 1154-1157.

http://link.springer.com/article/10.1007/BF02670102

Phase diagram of mixtures of stearic acid and stearyl alcohol

Abstract

Stearyl alcohol (98.4%), stearic acid (96.0%) and their binary mixtures were investigated by differential scanning calorimetry (DSC) at a heating and cooling rate of 10 K min⁻¹. The phase diagrams on heating and cooling were constructed and showed a eutectic behavior for the solid–liquid equilibrium line. In the heating phase diagram, the eutectic line was not always visible due to the existence of a phase transition in the solid state. A shift in the eutectic phase composition towards the acid was observed on cooling. The cooling and heating phase diagrams further differed in the fact that only two exotherms were observed during cooling where three endotherms were observed during heating. A plot of the enthalpy of the mixtures versus the mole fraction shows that different processes are involved in the solid state.

François G Gandolfo, Arjen Bot, Eckhard Flöter. Thermochimica Acta. Volume 404, Issues 1–2, 4 September 2003, Pages 9–17. doi:10.1016/S0040-6031(03)00086-8

http://www.sciencedirect.com/science/article/pii/S0040603103000868

Ceteareth-20

Final Report on the Safety Assessment of Ceteareth-2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -13, -14, -15, -16, -17, -18,-20,-22,-23,-24,-25,-27, -28, -29, -30, -33, -34, -40, -50, -55, -60, -80, and -100.

Abstract

Ceteareths, used in a large number of cosmetics as surfactants, are the polyethylene glycol (PEG) ethers of Cetearyl Alcohol (q,v.). To supplement the limited available data on Ceteareths, previous findings from the safety assessment of Polyethylene Glycol (PEG), several fatty alcohols (Cetearyl Alcohol, Cetyl Alcohol, and Stearyl Alcohol), and Steareths were considered. These data indicate little evidence of toxicity. Although various metabolites of monoalkyl ethers of ethylene glycol are reproductive and developmental toxins, given the methods of manufacture of Ceteareth compounds, there is no likelihood of such compounds being present as impurities. Further, there would be only limited ethylene glycol monomer linked by an ether group to the Ceteareth moiety for the PEG-5 compounds, little for the PEG-10 compounds, and virtually none for the PEG-20 and higher compounds. Even if linked to ethylene glycol monomer, it was considered unlikely that the Ceteareth moieties would be metabolized (e,g., via β-oxidation) to simple methyl, ethyl, propyl, or butyl alkyl groups. As the current data indicate, such short alkyl chains are needed in order for the production of toxic alcohol or aldehyde dehydrogenase metabolites. For longer alkyl chains there is evidence of diminishing toxicity, and extrapolation to much longer chains such as expected in the Ceteareth moieties suggests that there is no reproductive or developmental hazard posed by these Ceteareth compounds. The principal clinical finding related to PEGs is based on data in bum patients— PEGs were mild irritants/sensitizers and there was evidence of nephrotoxicity. No such effects were seen in animal studies on intact skin. Cosmetic manufacturers should adjust product formulations containing Polyethylene Glycol to minimize any untoward effects when products are used on damaged skin. In the absence of specific impurities data, the possible presence of 1,4-dioxane and ethylene oxide impurities was of concern. The importance of using the necessary purification procedures to remove these impurities was stressed. Creams containing Ceteareth-20 enhanced drug absorption. Ceteareth-15 (10% in formulation) was minimally irritating to rabbits after a single dermal exposure. In ocular studies, ethoxylated Cetearyl Alcohol solution was a severe irritant to unrinsed rabbit eyes and moderately irritating to rinsed eyes. In clinical studies, Ceteareth-15 (1.5 % in formulation) produced minimal irritation when tested in both a 4- and 21-day patch test, and was not a sensitizer when tested (1.35% in formulation) in a repeat-insult patch test. Based on the limited data on Ceteareths and the extensive data on chemically related ingredients, it was concluded that these ingredients are safe as used in cosmetic formulations. These ingredients, however, should not be used on damaged skin.

49. Alan Andersen. International Journal of Toxicology April 1999 vol. 18 no. 3 suppl 41-49. doi: 10.1177/109158189901800306

Attainment of Emulsions with Liquid Crystal from Marigold Oil Using the Required HLB Method.

Abstract

Development of new formulations for topical use and cosmetic and pharmaceutical delivery agents has increased the complexity of emulsified systems. Liquid crystals, known since the nineteenth century are the third phase of an emulsion, being responsible for increasing its stability and the solubility of substances poorly soluble in water, or the oily phase, modulating the release of drugs imprisoned in its structure and promoting hydration of the skin surface. In the present work we developed oil/water emulsions, making use of Marigold oil (Calendula officinalis L) and ethoxylated fat alcohols as surfactant. The required HLB value for marigold oil was determined to be 6.0. The surfactants were associated in lipophilic/hydrophilic pairs. The lipophilic surfactants were Ceteth‐2 and Steareth‐2 and the hydrophilic surfactants were Steareth‐20, Ceteareth‐20, Ceteareth‐5, and Ceteth‐10. To identify the liquid crystalline phases, the emulsions were analyzed by polarized light microscopy. The physical stability was evaluated by rheology and zeta potential analysis. All emulsions presented lamellar liquid crystal structures. Results showed that this type of surfactant is able to produce liquid crystal in the system, with slight difference in appearance, influencing the physical stability, according to the methods applied.

Orlando David Henrique dos Santosa*, Juliana Violi Miottoa, Jacqueline Moreira de Moraisa, Pedro Alves da Rocha‐Filhoa & Wanderley Pereira de Oliveirab. Attainment of Emulsions with Liquid Crystal from Marigold Oil Using the Required HLB Method. Journal of Dispersion Science and Technology.Volume 26, Issue 2, 2005 pages 243-249.DOI:10.1081/DIS-200045610

A Guide to the Ingredients and Potential Benefits of Over-the-Counter Cleansers and Moisturizers for Rosacea Patients

Abstract:

It is difficult for rosacea patients to discern which products and ingredients will be beneficial to their skin and which products will lead to an exacerbation of the signs and symptoms of rosacea. In this paper, the authors provide a brief overview of rosacea, its pathogenesis, signs and symptoms, and the management of the two major rosacea subtypes—erythematotelangiectatic rosacea and papular pustular rosacea. Reviewed in greater detail are the common ingredients used in over-the-counter cleansers and moisturizers with discussion of how these ingredients potentially benefit or harm the skin of patients with rosacea. Clinical studies investigating the benefits of using certain over-the-counter cleansers and moisturizers in patients with erythematotelangiectatic rosacea and papular pustular rosacea with or without topical prescription therapy are also reviewed. The specific formulas used in the clinical studies include a sensitive skin synthetic detergent bar, a nonalkaline cleanser and moisturizer, polyhydroxy acid containing cleanser and moisturizer, and a ceramide-based cleanser and moisturizer formulated in a multivesicular emulsion. Based on review of available data, the authors conclude that the use of mild over-the-counter cleansers and moisturizers is beneficial for patients with erythematotelangiectatic rosacea and papular pustular rosacea. The properties of over-the-counter cleansers and moisturizers that contribute to their mildness include an acidic-neutral pH to minimize the flux in skin pH; surfactants or emulsifiers that will not strip the skin of its moisture or strip the lipids and proteins of the stratum corneum; moisturizing ingredients such as emollients, humectants, and occlusives; and formulas without potential irritants and allergens. The most consistent clinical benefits demonstrated in the reviewed studies were a subjectively perceived improvement in subjective symptoms of dryness and irritation as well as an objective improvement in dryness.

Levin J, Miller R. A Guide to the Ingredients and Potential Benefits of Over-the-Counter Cleansers and Moisturizers for Rosacea Patients. The Journal of Clinical and Aesthetic Dermatology. 2011;4(8):31-49.
Influence of hydrophilic surfactants on the properties of multiple W/O/W emulsions

Commercial applications
Study of the photostability of 18 sunscreens in creams by measuring the SPF in vitro

Abstract

The target of this research was to evaluate the photostability of various sunscreen agents incorporated into an O/W emulsion. The concept of photostability is very important in the field of solar protection. The effectiveness of the anti-solar products is quantified using a universal indicator: the sun protection factor (SPF). This number which can be found on packaging can be given in two different ways: by methods in vivo (Colipa method) and in vitro. It is this last method which was adopted for this study. According to selected filter UVB (currently directive 76/768/EEC modified authorized 18 filters UVB), we can obtain more or less effective creams. We chose the irradiation of sun lotions formulated using the authorized filters, used with their maximum amount of employment, in a Suntest, with an irradiance of 650 W/m2 throughout variable time. With interval of regular time, one carries out a measurement of SPF in order to establish for each filter the kinetics SPF = f(time). An indicator of stability (t90) is then given. In this way, we could classify the filters by order of increasing photostability.

Study of the photostability of 18 sunscreens in creams by measuring the SPF in vitro. Céline Couteau, Aurélie Faure, June Fortin, Eva Paparis, Laurence J.M. Coiffard. Journal of Pharmaceutical and Biomedical Analysis.Volume 44, Issue 1, 9 May 2007, Pages 270–273. doi:10.1016/j.jpba.2007.01.052

Porphyridium Cruentum Extract

Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum

Abstract

Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria that is widely used as a fluorescent probe and analytical reagent. In this paper, B-phycoerythrin and R-phycocyanin in native state, from the red alga Porphyridium cruentum were obtained by an inexpensive and simple process. The best results of this purification procedure were scaled up by a factor of 13 to a large preparative level using an anionic chromatographic column of DEAE cellulose. Gradient elution with acetic acid-sodium acetate buffer (pH 5.5) was used. In these conditions both 32% of B-phycoerythrin and 12% of R-phycocyanin contained in the biomass of the microalgae was recovered. B-phycoerythrin was homogeneous as determined by sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE), yielding three migrating bands corresponding to its three subunits, consistent with the (αβ)6γ subunit composition characteristic of this biliprotein and the spectroscopic characterization of B-PE (UV–visible absorption and emission spectroscopy; steady-state and polarization fluorescence), is accompanied. Finally, a preliminary cost analysis of the recovery process is presented.

Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum. R. Bermejo Román, J.M. Alvárez-Pez, F.G. Acién Fernández, E. Molina Grima.Journal of Biotechnology. Volume 93, Issue 1, 31 January 2002, Pages 73–85. doi:10.1016/S0168-1656(01)00385-6.

Preparative purification of B-phycoerythrin from the microalga Porphyridium cruentum by expanded-bed adsorption chromatography

Abstract

B-Phycoerythrin (B-PE) is a major light-harvesting pigment of microalgae. Due to its high fluorescence efficiency and its intense and unique pink color, it is widely used as a fluorescent probe and analytical reagent as well as being employed as a natural dye in foods and cosmetics. Tedious methodologies for B-PE purification have been published. In this work we present a new, fast, preparative and scaleable two-step chromatographic method for B-PE purification from the red microalga Porphyridium cruentum. Initially, phycobiliproteins were released from the microalga cells by osmotic shock and captured by applying the centrifuged cell suspension to a column containing 74 ml Streamline-DEAE equilibrated with 50 mM acetic acid–sodium acetate buffer, pH 5.5, using expanded-bed adsorption chromatography at an upward flow of 200 cm h−1. After adsorption, washing was carried out in the expanded-bed mode. Having removed unbound proteins and cellular debris, the bed was allowed to sediment and a B-PE-rich solution was eluted with a downward flow of the same 250 mM buffer. In order to obtain pure B-PE, we utilized conventional ion-exchange chromatography with a column of DEAE-cellulose loaded directly with the eluate from Streamline-DEAE and developed using a discontinuous gradient of acetic acid–sodium acetate buffer, pH 5.5. With this new methodology, 66% of B-PE contained in the biomass of the microalgae was recovered, a value significantly higher than those obtained following other methodologies. The B-PE purity was tested using sodium dodecyl sulfate–polyacrylamide gel electrophoresis and spectroscopic characterization.

Preparative purification of B-phycoerythrin from the microalga Porphyridium cruentum by expanded-bed adsorption chromatography. Ruperto Bermejo, F. Gabriel Acién, Mª.José Ibáñezb, José M. Fernández, Emilio Molina, José M. Alvarez-Pez. Journal of Chromatography B. Volume 790, Issues 1–2, 25 June 2003, Pages 317–325. Preparative Chromatography of Proteins. doi:10.1016/S1570-0232(03)00168-5

Commercial applications of microalgae

The first use of microalgae by humans dates back 2000 years to the Chinese, who used Nostoc to survive during famine. However, microalgal biotechnology only really began to develop in the middle of the last century. Nowadays, there are numerous commercial applications of microalgae. For example, (i) microalgae can be used to enhance the nutritional value of food and animal feed owing to their chemical composition, (ii) they play a crucial role in aquaculture and (iii) they can be incorporated into cosmetics. Moreover, they are cultivated as a source of highly valuable molecules. For example, polyunsaturated fatty acid oils are added to infant formulas and nutritional supplements and pigments are important as natural dyes. Stable isotope biochemicals help in structural determination and metabolic studies. Future research should focus on the improvement of production systems and the genetic modification of strains. Microalgal products would in that way become even more diversified and economically competitive.

Commercial applications of microalgae.Pauline Spolaorea, Claire Joannis-Cassan, Elie Duran, Arsène Isambert.Journal of Bioscience and Bioengineering.Volume 101, Issue 2, February 2006, Pages 87–96. doi:10.1263/jbb.101.87

Bioprocess intensification: a potential aqueous two-phase process for the primary recovery of B-phycoerythrin from Porphyridium cruentum

Abstract

A process for the primary recovery of B-phycoerythrin from Porphyridium cruentum exploiting aqueous two-phase systems (ATPS) was developed in order to reduce the number of unit operations and benefit from an increased yield of the protein product. The evaluation of system parameters such as poly(ethylene glycol) (PEG) molecular mass, concentration of PEG as well as salt, system pH and volume ratio was carried out to determine under which conditions the B-phycoerythrin and contaminants concentrate to opposite phases. PEG 1450-phosphate ATPS proved to be suitable for the recovery of B-phycoerythrin because the target protein concentrated to the top phase whilst the protein contaminants and cell debris concentrated in the bottom phase. An extraction ATPS stage comprising volume ratio (Vr) equal to 1.0, PEG 1450 24.9% (w/w), phosphate 12.6% (w/w) and system pH of 8.0 allowed B-phycoerythrin recovery with a purity of 2.9 (estimated as the relation of the 545–280 nm absorbances). The use of ATPS resulted in a primary recovery process that produced a protein purity of 2.9±0.2 and an overall product yield of 77.0% (w/w). The results reported demonstrated the practical implementation of ATPS for the design of a primary recovery process as a first step for the commercial purification of B-phycoerythrin produced by P. cruentum.

Bioprocess intensification: a potential aqueous two-phase process for the primary recovery of B-phycoerythrin from Porphyridium cruentum. Jorge Benavides, Marco Rito-Palomares. Journal of Chromatography B.Volume 807, Issue 1, 25 July 2004, Pages 33–38. doi:10.1016/j.jchromb.2004.01.028

Hydrolyzed Marine Collagen

Marine sponge collagen: isolation, characterization and effects on the skin parameters surface-pH, moisture and sebum

Abstract

A previously described isolation procedure for collagen of the marine sponge Chondrosiareniformis Nardo was modified for scaling-up reasons yielding 30% of collagen (freeze-dried collagen in relation to freeze-dried sponge). Light microscope observations showed fibrous structures. Transmission electron microscopy studies proved the collagenous nature of this material: high magnifications showed the typical periodic banding-pattern of collagen fibres. However, the results of the amino acid analysis differed from most publications, presumably due to impurities that still were present. In agreement with earlier studies, sponge collagen was insoluble in dilute acid mediums and all solvents investigated. Dispersion of collagen was facilitated when dilute basic mediums were employed. The acid–base properties of the material were investigated by titration. Furthermore, a sponge extract was incorporated in two different formulations and compared with their extract-free analogues and a commercially available collagen containing product with respect to their effects on biophysical skin parameters. None of the preparations had a noticeable influence on the physiological skin surface pH. Skin hydration increased only slightly. However, all tested formulations showed a significant increase of lipids measured by sebumetry.

Marine sponge collagen: isolation, characterization and effects on the skin parameters surface-pH, moisture and sebum.Dieter Swatscheka, Wolfgang Schatton, Josef Kellermann, Werner E.G Müller, Jörg Kreuter. European Journal of Pharmaceutics and Biopharmaceutics. Volume 53, Issue 1, January 2002, Pages 107–113.doi:10.1016/S0939-6411(01)00192-8

High-throughput quantification of hydroxyproline for determination of collagen

Abstract

An accurate and high-throughput assay for collagen is essential for collagen research and development of collagen products. Hydroxyproline is routinely assayed to provide a measurement for collagen quantification. The time required for sample preparation using acid hydrolysis and neutralization prior to assay is what limits the current method for determining hydroxyproline. This work describes the conditions of alkali hydrolysis that, when combined with the colorimetric assay defined by Woessner, provide a high-throughput, accurate method for the measurement of hydroxyproline.

High-throughput quantification of hydroxyproline for determination of collagen. Kathleen Hofman, Bronwyn Hall, Helen Cleaver, Susan Marshall. Analytical Biochemistry

Volume 417, Issue 2, 15 October 2011, Pages 289–291.doi:10.1016/j.ab.2011.06.019

Functional and bioactive properties of collagen and gelatin from alternative sources: A review.

Abstract

The rising interest in the valorisation of industrial by-products is one of the main reasons why exploring different species and optimizing the extracting conditions of collagen and gelatin has attracted the attention of researchers in the last decade. The most abundant sources of gelatin are pig skin, bovine hide and, pork and cattle bones, however, the industrial use of collagen or gelatin obtained from non-mammalian species is growing in importance. The classical food, photographic, cosmetic and pharmaceutical application of gelatin is based mainly on its gel-forming properties. Recently, and especially in the food industry, an increasing number of new applications have been found for gelatin in products such as emulsifiers, foaming agents, colloid stabilizers, biodegradable film-forming materials and micro-encapsulating agents, in line with the growing trend to replace synthetic agents with more natural ones. In the last decade, a large number of studies have dealt with the enzymatic hydrolysis of collagen or gelatin for the production of bioactive peptides. Besides exploring diverse types of bioactivities, of an antimicrobial, antioxidant or antihypertensive nature, studies have also focused on the effect of oral intake in both animal and human models, revealing the excellent absorption and metabolism of Hyp-containing peptides. The present work is a compilation of recent information on collagen and gelatin extraction from new sources, as well as new processing conditions and potential novel or improved applications, many of which are largely based on induced cross-linking, blending with other biopolymers or enzymatic hydrolysis.

Functional and bioactive properties of collagen and gelatin from alternative sources: A review. M.C. Gómez-Guillén, B. Giménez, M.E. López-Caballero, M.P. Montero.Food Hydrocolloids. Volume 25, Issue 8, December 2011, Pages 1813–1827. doi:10.1016/j.foodhyd.2011.02.007

Collagen scaffolds derived from a marine source and their biocompatibility

Abstract

The primary sources of industrial collagens are calf skin and bone. However, these carry a high risk of bovine spongiform encephalopathy or transmissible spongiform encephalopathy. In this study, a novel form of acid-soluble collagen was extracted from jellyfish in an effort to obtain an alternative and safer collagen. Porous scaffolds composed of jellyfish collagen were prepared by freeze-drying and cross-linking with 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide to be used in tissue engineering applications. Enzymatic degradation kinetics of jellyfish collagen scaffolds were controlled by EDC/NHS-cross-linking density. Results from an MTT assay indicated that jellyfish collagen exhibited higher cell viability than other naturally derived biomaterials, including bovine collagen, gelatin, hyaluronic acid, and glucan. Jellyfish collagen scaffolds also had a highly porous and interconnected pore structure, which is useful for an high-density cell seeding, an efficient nutrient and an oxygen supply to the cells cultured in the three-dimensional matrices. To determine whether jellyfish collagen evokes any specific inflammatory response compared to that induced by bovine collagen or gelatin, we measured the levels of pro-inflammatory cytokines and antibody secretions and monitored the population changes of immune cells after in vivo implantation. Jellyfish collagen was found to induce an immune response at least comparable to those caused by bovine collagen and gelatin.

Collagen scaffolds derived from a marine source and their biocompatibility. Eun Song, So Yeon Kim, Taehoon Chun, Hyun-Jung Byun, Young Moo Lee.Biomaterials. Volume 27, Issue 15, May 2006, Pages 2951–2961. doi:10.1016/j.biomaterials.2006.01.015.

Silanetriol

Structure of cyclohexylsilanetriol: The first x‐ray crystal structure of a silanetriol

The structure of cyclohexylsilanetriol C6H1 1Si(OH)3 has been determined by single‐crystal x‐ray diffraction methods. The molecule crystallizes in the monoclinic system, space group C2/m, with a=7.876(3), b=6.637(6), c=15.802(11) Å, β=95.51(3)° at −60 °C, and Z=4. The intensities of 1031 independent reflections were measured using the ω‐scan technique on a Syntex P3 diffractometer (monochromatic MoKα). The final R factor is 0.057, based on anisotropic thermal parameters for all atoms except hydrogens. The molecules pack in a head‐to‐head, tail‐to‐tail arrangement with the cyclohexyl groups forming a hydrophobic double sheet and the silanetriol groups forming a second, hydrophilic, double sheet. The structure has a distorted hydrogen bond network with the hydrogen on each oxygen having equal probability of hydrogen bonding to oxygens in two different molecules. Two types of hydrogen bonds exist in the hydrophilic double sheet; O(1)⋅⋅⋅O(2) intrasheet hydrogen bonds, 2.724(2)Å, and O(2)⋅⋅⋅O(2) intrasheet hydrogen bond, 2.722(3) Å.

Structure of cyclohexylsilanetriol: The first x‐ray crystal structure of a silanetriol. Hatsuo Ishida, Jack L. Koenig and Kenn Corwin Gardner.J. Chem. Phys. 77, 5748 (1982); http://dx.doi.org/10.1063/1.443730

Structure Determining Effect of Alcohols and Water on the Shape of the Hydrogen Bonded Network in Adducts with (9-Methyl-fluoren-9-yl)-silanetriol

Summary

(9-Methyl-fluoren-9-yl)-trichlorosilane (1) and the respective silanetriol 2 have been synthesized and characterized. In cocrystallization with 2, ethanol, methanol, and water determine the morphology of the resulting hydrogen bonded network. Thus, incorporation of ethanol/water or methanol, respectively, leads to the tubular structures 2.EtOH.H2O (2a) and 2.2MeOH (2b), whereas the incorporation of water alone results in the double sheet structure 2 . H2O (2c). The shapes of the different hydrogen bonded networks are discussed.

Structure Determining Effect of Alcohols and Water on the Shape of the Hydrogen Bonded Network in Adducts with (9-Methyl-fluoren-9-yl)-silanetriol. Manuela Schneider, Beate Neumann, Hans-Georg Stammler, Peter Jutzi.Silicon Chemistry.pp 33-44.

Glutamylamidoethyl Imidazole

Crystal Structure of Imidazole Glycerol Phosphate Synthase: A Tunnel through a (β/α)8 Barrel Joins Two Active Sites

Abstract

Background: Imidazole glycerol phosphate synthase catalyzes a two-step reaction of histidine biosynthesis at the bifurcation point with the purine de novo pathway. The enzyme is a new example of intermediate channeling by glutamine amidotransferases in which ammonia generated by hydrolysis of glutamine is channeled to a second active site where it acts as a nucleophile. In this case, ammonia reacts in a cyclase domain to produce imidazole glycerol phosphate and an intermediate of purine biosynthesis. The enzyme is also a potential target for drug and herbicide development since the histidine pathway does not occur in mammals.

Results: The 2.1 Å crystal structure of imidazole glycerol phosphate synthase from yeast reveals extensive interaction of the glutaminase and cyclase catalytic domains. At the domain interface, the glutaminase active site points into the bottom of the (β/α)8 barrel of the cyclase domain. An ammonia tunnel through the (β/α)8 barrel connects the glutaminase docking site at the bottom to the cyclase active site at the top. A conserved “gate” of four charged residues controls access to the tunnel.

Conclusions: This is the first structure in which all the components of the ubiquitous (β/α)8 barrel fold, top, bottom, and interior, take part in enzymatic function. Intimate contacts between the barrel domain and the glutaminase active site appear to be poised for crosstalk between catalytic centers in response to substrate binding at the cyclase active site. The structure provides a number of potential sites for inhibitor development in the active sites and in a conserved interdomain cavity.

Crystal Structure of Imidazole Glycerol Phosphate Synthase: A Tunnel through a (β/α)8 Barrel Joins Two Active Sites.Barnali N Chaudhuri, Stephanie C Lange, Rebecca S Myers, Sridar V Chittur, V.Jo Davisson, Janet L Smith. Structure. Volume 9, Issue 10, October 2001, Pages 987–997. doi:10.1016/S0969-2126(01)00661-X

Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase.

Abstract

Phosphate-independent glutaminase can be quantitatively solubilized from a microsomal preparation of rat kidney by treatment with papain. Subsequent gel filtration and chromatography on quaternary aminoethyl (QAE)-Sephadex and hydroxylapatite yield a 200-fold purified preparation of this glutaminase. The purified enzyme also hydrolyzes gamma-glutamylhydroxamate and exhibits substrate inhibition at high concentrations of either glutamine or gamma-glutamyhydroxamate, which is partially relieved by increasing concentrations of maleate. Rat kidney phosphate-independent glutaminase reaction is catalyzed by the same enzyme which catalyzes the gamma-glutamyltranspeptidase reaction. The ratio of glutaminase to transpeptidase activities remained constant throughout a 200-fold purification of this enzyme. The observation that the phosphate0independent glutaminase and gamma-glutamyltranspeptidase activities exhibit coincident mobilities during electrophoresis, both before and after extensive treatment with neuraminidase, strongly suggests that both reactions are catalyzed by the same enzyme. This conclusion is strengthened by the observation that maleate and various amino acids have reciprocal effects on the two activities. Maleate increases glutaminase activity and blocks transpeptidation, whereas amino acids activate the transpeptidase but inhibit glutaminase activity. In contrast, the addition of both maleate and alanine resulted in a strong inhibition of both activities. Both activities exhibit a similar distribution in the various regions of the kidney. Recovery of maximal activities in the outer stripe region of the medulla is consistent with previous quantitative microanalysis which indicated that this glutaminase activity is localized primarily in the proximal straight tubule cells. The glutaminase and transpeptidase activities have different pH optima. Examination of the product specificity suggests that decreasing pH also promotes glutaminase activity and that below pH 6.0, this enzyme functions strictly as a glutaminase. Because of the localization of this activity on the brush border membrane, these resuts are consistent with the possibility that the physiological conditions induced by metabolic acidosis could convert this enzyme from a broad specificity transpeptidase to a glutaminase. Therefore, this enzyme could contribute to the increased renal synthesis of ammonia from glutamine which is observed during metabolic acidosis.

Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase. N P Curthoys and T uhlenschmidt. March 25, 1975 The Journal of Biological Chemistry, 250, 2099-2105.

Amino Acid Metabolism

Amino Acid Metabolism.Annual Review of Biochemistry. Vol. 28: 223-256 (Volume publication date July 1959).DOI: 10.1146/annurev.bi.28.070159.001255

Alpha Arbutin

ALPHA-ARBUTIN – the more effective, faster and safer approach to skin lightening. ALPHA-ARBUTIN minimizes liver spots.

ALPHA-ARBUTIN is a pure, water soluble, biosynthetic active ingredient. ALPHA-ARBUTIN promotes lightening and an even skin tone on all skin types. ALPHA-ARBUTIN blocks epidermal melanin biosynthesis by inhibiting enzymatic oxidation of Tyrosine and Dopa. Structurally, ALPHA-ARBUTIN (IUPAC name: 4-hydroxyphenyl-α-D-glucopyranoside) is an α-glucoside. The α-glucosidic bond offers higher stability and efficacy than the β-form in the related beta-arbutin. This leads to a skin lightening active that acts faster and more efficiently than existing single components, inimizes liver spots and reduces the degree of skin tanning after UV exposure.

CHARACTERISTICS

• The more effective, faster and safer approach to skin lightening; minimize live spots.
• Promote lightening and an even skin tone on all skin types.
• Block epidermal melanin biosynthesis by inhibiting enzymatic oxidation of Tyrosine and Dopa.
• Higher stability and efficacy than β- form in the related beta-arbutin.

FUNCTION:

• Promotes lightening and an even skin tone on all skin types.
• Minimizes liver spots.
• Can reduce the degree of skin tanning after UV exposure.

Syntheses of Arbutin-α-glycosides and a Comparison of Their Inhibitory Effects with Those of α-Arbutin and Arbutin on Human Tyrosinase

Syntheses of Arbutin-α-glycosides and a Comparison of Their Inhibitory Effects with Those of α-Arbutin and Arbutin on Human Tyrosinase. Kazuhisa Sugimoto, Takahisa Nishimura, Koji Nomura, Kenji Sugimoto, Takashi Kuriki. Chemical and Pharmaceutical Bulletin. Vol. 51 (2003) No. 7 P 798-801.http://doi.org/10.1248/cpb.51.798

Inhibitory Effects of α-Arbutin on Melanin Synthesis in Cultured Human Melanoma Cells and a Three-Dimensional Human Skin Model.

Inhibitory Effects of α-Arbutin on Melanin Synthesis in Cultured Human Melanoma Cells and a Three-Dimensional Human Skin Model. Kazuhisa Sugimoto, Takahisa Nishimura, Koji Nomura, Kenji Sugimoto, Takashi Kuriki. Biological and Pharmaceutical Bulletin. Vol. 27 (2004) No. 4 P 510-514. http://doi.org/10.1248/bpb.27.510

Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: A prospective study

Abstract

Objective: To evaluate the effectiveness of a Q-switched Nd:YAG laser (MedLite C6; HOYA ConBio, Fremont, CA, USA) and 7% alpha arbutin solution (Skin Advance Laboratory, Japan) in the treatment of melasma. Methods: This was a prospective study of 35 refractory melasma cases treated with 10 weekly laser sessions, two monthly follow-up treatments and topical 7% alpha arbutin solution. Clinical photographs and severity grading on a 5-point scale were carried out by an independent observer at each visit. Results: At 6 months, 30% of study subjects received results in the excellent clearance category (> 81% reduction of melasma) and 36.7% received good (51–80% reduction) clearance. Mild and transient side effects included discomfort during treatment, erythema, whitening of fine hair and urticaria. Three cases of mottling hypo-pigmentation (8.57%) and two cases of recurrence of melasma (5.71%) were recorded. Conclusion: Combination therapy with the MedLite C6 and 7% alpha arbutin solution is an effective and well-tolerated treatment for refractory melasma.

Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: A prospective study. Niwat Polnikorn. Journal of Cosmetic and Laser Therapy.

Volume 12, Issue 3, 2010. DOI:10.3109/14764172.2010.487910

Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues

Abstract

Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with α-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of α-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues.

Yu-Ji Lim, Eunjoo H. Lee, Tong Ho Kang, Sang Keun Ha, Myung Sook Oh, Seong Min Kim, Tae-Jin Yoon, Chulhun Kang, Ji-Ho Park , Sun Yeou Kim. Research Articles Drug Actions. Archives of Pharmacal Research. March 2009, Volume 32, Issue 3, pp 367-373

Determination of alpha-arbutin, beta-arbutin and niacinamide in cosmetics by high performance liquid chromatography

A high performance liquid chromatography (HPLC) method for the determination of two optical isomers of arbutin (alpha-arbutin and beta-arbutin) and niacinamide in cosmetics was developed. The samples were extracted by the mixture of salt water and chloroform (2:1, v/v). The separation was performed on an ODS-BP column (200 mm x 4.6 mm, 5 microm, Elite) with methanol-water (10:90, v/v) as the mobile phase at a flow rate of 0.5 mL/min and 25 degrees C. The detection wavelength was set at 220 nm and the sample injection volume was 20 microL. There were good linear relationships between the mass concentration and the peak areas of alpha-arbutin, beta-arbutin and niacinamide in the ranges of 0.07-50, 0.06-50 and 0.05-50 mg/L, respectively. The relative standard deviations (RSDs, n = 7) of alpha-arbutin, beta-arbutin and niacinamide were 1.65%, 1.73% and 1.33%, respectively. The proposed method has been applied for the determination of alpha-arbutin, beta-arbutin and niacinamide in cosmetics with recoveries of 91.7%-109.6%. This method is rapid, simple and suitable for the detection of whitening ingredients in cosmetic.

Determination of alpha-arbutin, beta-arbutin and niacinamide in cosmetics by high performance liquid chromatography. Cheng P, Chen M, Zhu Y. Chinese Journal of Chromatography / Zhongguo hua xue hui [2010, 28(1):89-92]. DOI: 10.3724/SP.J.1123.2010.00089

Sodium Hyaluronate

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study.

CONCLUSIONS: This study represents the first controlled, prospective evaluation of postoperative abdominal adhesion formation and prevention after general abdominal surgery using standardized, direct peritoneal visualization. In this study, HA membrane was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions.

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study.Becker JM, Dayton MT, Fazio VW, Beck DE, Stryker SJ, Wexner SD, Wolff BG, Roberts PL, Smith LE, Sweeney SA, Moore M. Journal of the American College of Surgeons [1996, 183(4):297-306]

Intra-articular sodium yaluronate (Hyalgan®) in the treatment of patients with osteoarthritis of the knee:A randomized clinical trial.

Intra-articular sodium yaluronate (Hyalgan®) in the treatment of patients with osteoarthritis of the knee:A randomized clinical trial. R.D. Altman et al.J Rheumatol 1998; 25: 2203-12

High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.

Summary

Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks’ combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years’ duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: −35.5±26.4 mm vs −25.8±21.4, P = 0.03, Lequesne’s functional index: −3.8±4.3 vs −2.3±3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician’s overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (−4.4±5.1 vs −2.7±4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.

High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Maxime Dougados,Minh Nguyen, Véronique Listrat, Bernard Amor.Osteoarthritis and Cartilage. Volume 1, Issue 2, April 1993, Pages 97–103.doi:10.1016/S1063-4584(05)80024-X

Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies.

Abstract

The molecular weight distribution of hyaluronate (HA) in synovial fluid (SF) from 10 patients with rheumatoid arthritis (RA), from six patients with other joint disorders, and from five recently deceased persons without joint affections was investigated by a gel chromatographic procedure. A new and highly specific radioassay was used for determination of the HA concentration in the effluent from the chromatographic column, and this allowed analyses on 0.5 ml or less of untreated synovial fluid. The results confirmed the findings by others that the weight-average molecular weight (Mw) of HA in SF from patients with RA (4.8 X 10(6)) was similar to that in other joint diseases (5.0 X 10(6)) and moderately but significantly (p less than 0.001) lower than that of normal SF (7.0 X 10(6)). Furthermore, the molecular weight distribution of HA in the pathological SF was generally broad and varied considerably between individuals. The HA concentration in the pathological SF varied between 0.17 and 1.32 g/l, which is in accordance with previous reports and considerably lower than that of normal SF. Neither the nature of the arthropathy and the extent of the inflammatory process nor the pharmacological treatment had a tendency to influence the HA concentration in the SF, the mean molecular weight of HA, or its molecular weight distribution. Although the concentration of HA in SF drops in joint disease, the total amount of the polysaccharide is greatly enhanced. Also the amount of high molecular weight polysaccharide (Mw greater than 6 X 10(6)) is in excess in joint disease. The pathological state is therefore characterised not by lack of high molecular weight hyaluronate but by a dilution of it.

Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies.L B Dahl, I M Dahl, A Engström-Laurent, K Granath. Annals of the Rheumatic Diseases. The Eular Journal. Vol. 44, Issue 12, 817-822 doi:10.1136/ard.44.12.817

Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge

Abstract

This study was conducted to develop a new sponge type of biomaterial to be used for either wound dressing or scaffold for tissue engineering. We were able to prepare an insoluble matrix composed of gelatin and sodium hyaluronate (HA) by dipping the soluble sponge into 90% (w/v) acetone/water mixture containing a small amount of cross-linking agent, 1-ethyl-3-3-dimethylaminoproplycarbodiimide hydrochloride, EDC. To characterize the sponge, Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and Instron analysis were performed. The obtained results indicate that the chemically cross-linked sponge shows a cross-linking degree of 10–35%, a mean pore size of 40–160 μm, porosity of 35–67%, and a tensile strength of 10–30 gf/cm2. Especially, the porosity measured by image analysis showed a tendency to increase with HA content, resulting in an increased water uptake. The resistance to collagenase degradation in vitro increased for up to 2 days. Silver sulfadiazine (AgSD)-impregnated gelatin-HA sponge was also prepared and compared with conventional vaseline gauze by applying it onto a dorsal skin defect of wistar rat for 5, 12, and 21days. Histological results showed an enhancement of wound healing in AgSD-impregnated gelatin-HA sponge. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 48: 631–639, 1999.

Choi, Y. S., Hong, S. R., Lee, Y. M., Song, K. W., Park, M. H. and Nam, Y. S. (1999), Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge. J. Biomed. Mater. Res., 48: 631–639. doi: 10.1002/(SICI)1097-4636(1999)48:5<631::AID-JBM6>3.0.CO;2-Y

Acrylates/Steareth-20 Methacrylate

Allergic contact dermatitis to copolymers in cosmetics – case report and review of the literature

Abstract

Copolymers or heteropolymers are large molecules with high molecular weights (>1000 D). They have been underestimated for a long time as to their sensitizing capacities. Allergic contact dermatitis to 6 copolymers in cosmetics and 1 in a medical dressing has been described; however, the nature of the hapten is still unknown. We report a case of allergic contact dermatitis to polyvinylpyrrolidone (PVP)/hexadecene copolymer in a purple-colored lipstick and review the literature on allergic contact dermatitis to 7 copolymers: PVP/hexadecene, PVP/eicosene, PVP/1-triacontene, methoxy polyethyleneglycol (PEG)-22/dodecyl glycols, methoxy PEG-17/dodecyl glycols, phthalic anhydride/trimellitic anhydride/glycols, and polyvinyl methyl/maleic acid anhydride.

Quartier, S., Garmyn, M., Becart, S. and Goossens, A. (2006), Allergic contact dermatitis to copolymers in cosmetics – case report and review of the literature. Contact Dermatitis, 55: 257–267. doi: 10.1111/j.1600-0536.2006.00960.x

Polymerization of Oligo(Ethylene Glycol) (Meth)Acrylates: Toward New Generations of Smart Biocompatible Materials

ABSTRACT: Monomers composed

of a (meth)acrylate moiety

connected to a short poly(ethylene)glycol (PEG) chain are versatile building-blocks for the preparation of \smart” biorelevant materials. Many of these monomers are commercial and can be easily polymerized by either anionic, free-radical, or controlled radical polymerization. The latter approach allows synthesis of welldefined PEG-based macromolecular architectures such as amphiphilic block copolymers, dense polymer brushes, or biohybrids. Furthermore, the resulting polymers exhibit fascinating solution properties in aqueous medium.

Depending on the molecular structure of their monomer units, non linear PEG analogues can be either insoluble in water, readily soluble up to 100 8C, or thermoresponsive. Thus, these polymers can be used for building a wide variety of modern materials such as biosensors, artificial tissues, smart gels for chromatography, and drug carriers.

Polymerization of Oligo(Ethylene Glycol) (Meth)Acrylates:Toward New Generations of Smart Biocompatible Materials. JEAN-FRANC¸ OIS LUTZ. Research Group Nanotechnology for Life Science, Fraunhofer. Institute for Applied Polymer Research, 2008. DOI: 10.1002/pola.22706

Activators Regenerated by Electron Transfer for Atom-Transfer Radical Polymerization of (Meth)acrylates and Related Block Copolymers

Activators Regenerated by Electron Transfer for Atom-Transfer Radical Polymerization of (Meth)acrylates and Related Block Copolymers.Wojciech Jakubowski, Krzysztof Matyjaszewski Prof. 13 June 2006. DOI: 10.1002/ange.200600272

In-situ photopolymerization of oriented liquid-crystalline acrylates, 3. Oriented polymer networks from a mesogenic diacrylate

Abstract

Synthesis, mesomorphism, orientation and photo-initiated chain crosslinking of the liquid-crystalline diacrylate 1,4-phenylene bis{4-[6-(acryloyloxy)hexyloxy]benzoate} (1) are studied. Monomer 1 exhibits a broad nematic phase between 108 and 155°C and a monotropic smectic phase below 88°C. The monomer is uniaxially oriented in its nematic phase at a substrate which has been coated with polyimide and unidirectionally rubbed with tissue. At the transition temperature to the smectic phase the order parameter is measured to be 0,7. During polymerization, the ordering of the mesogens is frozen-in, yielding a uniaxially crosslinked network. The clear films of oriented poly(1) exhibit a birefringence Δn between 0,12 and 0,15, depending on the polymerization temperature. In the highest oriented state of 1 a small reduction of the degree of order is observed during the crosslinking reaction, whereas at higher temperatures and lower ordering of 1, the uniaxially orientation increases upon reaction. A special feature of the oriented networks is that the ordering is maintained while heating at high temperatures. The polymerization of the acrylate groups in the mesomorphic phases proceeds fast and to high conversion. Below 90°C the polymerization behaviour is similar to that of conventional isotropic diacrylates. Above 90°C the polymerization reaction of the liquid-crystalline diacrylate proceeds faster than that of an isotropic diacrylate.

Broer, D. J., Boven, J., Mol, G. N. and Challa, G. (1989), In-situ photopolymerization of oriented liquid-crystalline acrylates, 3. Oriented polymer networks from a mesogenic diacrylate. Makromol. Chem., 190: 2255–2268. doi: 10.1002/macp.1989.021900926

Atom-Transfer Radical Polymerization of Acrylates in an Ionic Liquid

Abstract

The atom-transfer radical polymerization (ATRP) of acrylates in 1-butyl-3-methylimidazolium hexafluorophosphate was investigated. The solubility of the acrylates in the ionic liquid depends on the substituent. The homogeneous polymerization of methyl acrylate gives polymers with M̄n close to the calculated value and relatively narrow polydispersity. In heterogeneous polymerizations of higher acrylates, with the catalyst present in the ionic liquid phase, deviations from ideal behavior are observed although the polymerization of butyl acrylate approaches the conditions of a controlled polymerization.

Biedroń, T. and Kubisa, P. (2001), Atom-Transfer Radical Polymerization of Acrylates in an Ionic Liquid. Macromol. Rapid Commun., 22: 1237–1242. doi: 10.1002/1521-3927(20011001)22:15<1237::AID-MARC1237>3.0.CO;2-E

Copolymer

Interaction of human skin fibroblasts with moderate wettable polyacrylonitrile–copolymer membranes

Abstract

The development of a bioartificial skin is a step toward the treatment of patients with deep burns or nonhealing skin ulcers. One possible approach is based on growing dermal cells on membranes to obtain appropriate living cellular stroma (sheets) to cover the wound. New membrane-forming copolymers were synthesized, based on acrylonitrile (AN) copolymerization with hydrophilic N-vinylpyrrolidone (NVP) monomer, in different percentage ratios, such as 5, 20, and 30% w/w, and with two other relatively high polar comonomers—namely, sodium 2-methyl-2-propene-1-sulfonic acid (NaMAS) and aminoethylmethacrylate (AeMA). All these copolymers were characterized for their bulk composition and number average molecular weight, and used to prepare ultrafiltration membranes. Water contact angles and water uptake were estimated to characterize the wettability and scanning force microscopy to visualize the morphology of the resulting polymer surface. Cytotoxicity was estimated according to the international standard regulations, and the materials were found to be nontoxic. The interaction of the membranes with human skin fibroblasts was investigated considering that these cells are among the first to colonize membranes upon implantation or with prolonged external contact. The overall cell morphology, formation of focal adhesion contacts, and cell proliferation were estimated to characterize the cell material interactions. It was found that the pure polyacrylonitrile homopolymer (PAN) membrane provides excellent conditions for seeding with fibroblasts, comparable only to a copolymer containing AeMA. In contrast, the presence of NaMAS with acidic ionic groups decreased both the attachment and proliferation of fibroblasts. Low content of NVP in the copolymer, up to about 5%, still enabled good attachment and spreading of cells, as well as subsequent proliferation of fibroblasts, but higher ratios of 20 and 30% resulted in a significant decrease of these cellular activities. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 290–300, 2002

Groth, T., Seifert, B., Malsch, G., Albrecht, W., Paul, D., Kostadinova, A., Krasteva, N. and Altankov, G. (2002), Interaction of human skin fibroblasts with moderate wettable polyacrylonitrile–copolymer membranes. J. Biomed. Mater. Res., 61: 290–300. doi: 10.1002/jbm.10191

Transdermal delivery of mixnoxidil with block copolymer nanoparticles

Abstract

We evaluated the effect of hydrodynamic size of self-assembled nanoparticles on skin penetration of minoxidil in vitro and in vivo. Self-assembled 40- and 130-nm nanoparticles, both containing minoxidil, were prepared by solvent evaporation of poly(ε-caprolactone)-block-poly(ethyleneglycol) and were applied onto the skin of both hairy and hairless guinea pigs in the Franz diffusion cell. In hairy guinea pig skin, the permeation of the minoxidil that incorporated in 40-nm nanoparticles was 1.5-fold higher in the epidermal layer and 1.7-fold higher in the receptor solution than that of 130-nm nanoparticles. Nanoparticle size dependence on the permeation behavior of minoxidil was not observed for hairless guinea pig skin in either the epidermal layer or the receptor solution.

Phospholipid liposomes and ethanol–water admixture, on the other hand, containing the same amount of minoxidil did not show differences in the amount of permeation irrespective of the existence of hair follicles. Confocal microscopy coupled with in vivo and in vitro skin permeation results demonstrated that nanoparticles containing solutes penetrated mainly via shunt routes like hair follicles, resulting in skin absorption of solutes.

Transdermal delivery of mixnoxidil with block copolymer nanoparticles. Jongwon Shim, Hyung Seok Kang, Won-Seok Park, Sang-Hun Han, Junoh Kim, Ih-Seop Chang. Journal of Controlled Release. Volume 97, Issue 3, 7 July 2004, Pages 477–484. doi:10.1016/j.jconrel.2004.03.028

Temperature-responsive shrinking kinetics of poly (N-isopropylacrylamide) copolymer gels with hydrophilic and hydrophobic comonomers

Abstract

Temperature-responsive poly(N-isopropylacrylamide) and its copolymer gels with the hydrophilic comonomer, acrylamide and the hydrophobic comonomer, butyl methacrylate, all exhibit swelling-deswelling changes in response to external temperature changes. These hydrogels show negative swelling thermosensitivities, particularly swelling at lower temperature and complete deswelling over specific phase transition temperatures (Tp). Shrinking kinetics of these gels from swollen to deswollen states at several different temperature changes have been investigated. When temperature changes are performed entirely below Tp, the shrinking process is dominated by polymer network diffusion. On the other hand, shrinking kinetics for temperature changes from below to above Tp, are dramatically influenced by gel surface structural changes and formation of a collapsed polymer skin layer. This surface skin formation prompts the accumulation of internal hydrodynamic pressure inside the gels upon shrinking by blocking the outflux of entrapped water. Both rate and magnitude of internal hydrodynamic pressure are modulated by the gel volume, the hydrophobicity of the gel polymer chains and the degree of external temperature changes. This internal pressure eventually causes convective outflow of water from the gel interior. Hydrodynamic internal pressure affects the drug release on-off pattern during gel shrinking.

Temperature-responsive shrinking kinetics of poly (N-isopropylacrylamide) copolymer gels with hydrophilic and hydrophobic comonomers. Yuzo Kaneko, Ryo Yoshida, Kiyotaka Sakai, Yasuhisa Sakurai, Teruo Okano. Journal of Membrane Science. Volume 101, Issues 1–2, 15 May 1995, Pages 13–22. doi:10.1016/0376-7388(94)00268-4

Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin

Abstract

Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen-glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 microns, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was greater than 5 x 10(4) cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physiochemical structure, functioning as a transient basal lamina during morphogenesis of skin.

Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. I V Yannas, E Lee, D P Orgill, E M Skrabut, and G F Murphy. PNAS February 1, 1989 vol. 86 no. 3 933-937.

Niacinamide

The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer

Summary. Background Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate.

Objectives To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women.

Methods Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face.

Results Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35–68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use.

Conclusions The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.

Hakozaki, T., Minwalla, L., Zhuang, J., Chhoa, M., Matsubara, A., Miyamoto, K., Greatens, A., Hillebrand, G.G., Bissett, D.L. and Boissy, R.E. (2002), The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. British Journal of Dermatology, 147: 20–31. doi: 10.1046/j.1365-2133.2002.04834.x

The Treatment of Bullous Pemphigoid With Tetracycline and Niacinamide

A Preliminary Report

Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease.

The Treatment of Bullous Pemphigoid With Tetracycline and Niacinamide – A Preliminary Report.Mark Allan Berk, MD, FRCP; Allan L. Lorincz, MD. Arch Dermatol. 1986;122(6):670-674. doi:10.1001/archderm.1986.01660180076019.

Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: A critical review of central 3-acetylpyridine neurotoxicity

Abstract

Previous studies indicate that 3-acetylpyridine (3-AP) intoxication produces discrete lesions of the inferior olive (IO) and other central structures in rats and mice. As a result, it has been widely employed in investigations of the influences of climbing fibers on cerebellar function. This study examines the central toxicity of a protocol reported to produce lesions restricted to the inferior olive in rats33. Adult male Long-Evans (n = 12) and Sprague-Dawley (n = 18) were given serial injections of 3-AP (75–80 mg/kg), harmaline (15 mg/kg) or saline, and niacinamide (300 mg/kg). Silver degeneration staining (cupric-silver method) after 6–48 h survival revealed consistent patterns of degenerating neurons in IO, nucleus ambiguus, hypoglossal nucleus, dorsal motor nucleus X, nucleus intercalatus, nucleus dorsalis raphe, medial terminal nucleus, interpeduncular nucleus, substantia nigra, ventral tegmental area, entopeduncular nucleus, hippocampus (dentate gyrus and CA 3–4), horizontal limb of the nucleus of the diagonal band, and lateral entorhinal cortex, which were not produced by control experiments with 3 saline injections or with two saline injections followed by niacinamide. These data apparently resolve conflicts in the literature regarding central 3-AP toxicity and indicate that the 3-AP-harmaline-niacinamide protocol produces degeneration that is similar to 3-AP alone. However, they also document the discrete, reproducible susceptibility of certain neuronal populations to 3-AP intoxication and suggest that the motor symptoms of intoxication are not solely due to IO destruction. Finally, they form a basis for biochemical investigations of 3-AP toxicity in susceptible central structures.

Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: A critical review of central 3-acetylpyridine neurotoxicity. Carey D. Balaban. Brain Research Reviews. Volume 9, Issue 1, April 1985, Pages 21-42. doi:10.1016/0165-0173(85)90017-7.

Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance

Background. In multiple chronic clinical studies, topical niacinamide (vitamin B3) has been observed to be well tolerated by skin and to provide a broad array of improvements in the appearance of aging facial skin (eg, reduction in the appearance of hyperpigmentated spots and red blotchiness).

Objective. To clinically determine the effect of topical niacinamide on additional skin appearance and property end points (wrinkles, yellowing, and elasticity).

Methods. Female white subjects (N = 50) with clinical signs of facial photoaging (fine lines and wrinkles, poor texture, and hyperpigmented spots) applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks (double blind, left-right randomized). Facial images and instrumental measures were obtained at baseline and at 4-week intervals.

Results. Analyses of the data revealed a variety of significant skin appearance improvement effects for topical niacinamide: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing). In addition, elasticity (as measured via cutometry) was improved. Corresponding mechanistic information is presented.

Conclusion. In addition to previously observed benefits for topical niacinamide, additional effects were identified (improved appearance of skin wrinkles and yellowing and improved elasticity).

Bissett, D. L., Oblong, J. E. and Berge, C. A. (2005), Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance. Dermatologic Surgery, 31: 860–866. doi: 10.1111/j.1524-4725.2005.31732

A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma

Josefina Navarrete-Solıs, Juan Pablo Castanedo-Cazares, Bertha Torres-Alvarez,Cuauhtemoc Oros-Ovalle, Cornelia Fuentes-Ahumada, Francisco Javier Gonzalez,Juan David Martınez-Ramırez,and Benjamin Moncada.Dermatology Research and Practice. Volume 2011, Article ID 379173, 5 pages.doi:10.1155/2011/379173

Aloe Vera Gel

Anti-inflammatory activity of extracts from Aloe vera gel

Abstract

We studied the effects of aqueous, chloroform, and ethanol extracts of Aloe vera gel on carrageenan-induced edema in the rat paw, and neutrophil migration into the peritoneal cavity stimulated by carrageenan. We also studied the capacity of the aqueous extract to inhibit cyclooxygenase activity. The aqueous and chloroform extracts decreased the edema induced in the hind-paw and the number of neutrophils migrating into the peritoneal cavity, whereas the ethanol extract only decreased the number of neutrophils. The antiinflammatory agents indomethacin and dexamethasone also decreased carrageenan-induced edema and neutrophil migration. The aqueous extract inhibited prostaglandin E2 production from [14C]arachidonic acid. The chemical tests performed in the aqueous extract for anthraglycosides, reductor sugars and cardiotonic glycosides were positive. In the ethanol extract, the chemical tests performed for saponins, carbohydrates naftoquinones, sterols, triterpenoids and anthraquinones were also positive. In the chloroform extract, the chemical tests performed for sterols type Δ5, and anthraquinones were positive. These results demonstrated that the extracts of Aloe vera gel have antiinflammatory activity and suggested its inhibitory action on the arachidonic acid pathway via cyclooxygenase.

Anti-inflammatory activity of extracts from Aloe vera gel. Beatriz Vázquez, Guillermo Avila, David Segura, Bruno Escalante. Journal of Ethnopharmacology. Volume 55, Issue 1, December 1996, Pages 69–75. doi:10.1016/S0378-8741(96)01476-6

Activation of a mouse macrophage cell line by acemannan: The major carbohydrate fraction from Aloe vera gel

Abstract

Acemannan is the name given to the major carbohydrate fraction obtained from the gel of the Aloe vera leaf. It has been claimed to have several important therapeutic properties including acceleration of wound healing, immune stimulation, anti-cancer and anti-viral effects. However, the biological mechanisms of these activities are unclear. Because of this wide diversity of effects, it is believed that they may be exerted through pluripotent effector cells such as macrophages. The effects of acemannan on the mouse macrophage cell line, RAW 264.7 cells were therefore investigated. It was found that acemannan could stimulate macrophage cytokine production, nitric oxide release, surface molecule expression, and cell morphologic changes. The production of the cytokines IL-6 and TNF-α were dependent on the dose of acemannan provided. Nitric oxide production, cell morphologic changes and surface antigen expression were increased in response to stimulation by a mixture of acemannan and IFN-γ. These results suggest that acemannan may function, at least in part, through macrophage activation.

Activation of a mouse macrophage cell line by acemannan: The major carbohydrate fraction from Aloe vera gel. Linna Zhang, Ian R. Tizard. Immunopharmacology.Volume 35, Issue 2, November 1996, Pages 119–128. doi:10.1016/S0162-3109(96)00135-X

The Stimulation of Postdermabrasion Wound Healing with Stabilized Aloe Vera Gel-Polyethylene Oxide Dressing.

Abstract. Full-face dermabrasion provided an ideal opportunity to document the effects of dressings on wound healing management. Following the procedure, the abraded face was divided in half. One side was treated with the standard polyethylene oxide gel wound dressings. The other side was treated with a polyethylene oxide gel dressing saturated with stabilized aloe vera. The polyethylene oxide dressing provided an excellent matrix for the release of aloe vera gel during the initial 5 days of wound healing. By 24–48 hours there was dramatic vasoconstriction and accompanying reduction in edema on the aloe-treated side. By the third to fourth day there was less exudate and crusting at the aloe site, and by the fifth to sixth day the reepithelialization at the aloe site was complete. Overall, wound healing was approximately 72 hours faster at the aloe site. This acceleration in wound healing is important to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. The exact mechanism of acceleration of wound healing by aloe vera is unknown.

FULTON, J. E. (1990), The Stimulation of Postdermabrasion Wound Healing with Stabilized Aloe Vera Gel-Polyethylene Oxide Dressing. The Journal of Dermatologic Surgery and Oncology, 16: 460–467. doi: 10.1111/j.1524-4725.1990.tb00065.x

Comparative antimicrobial activities of aloe vera gel and leaf.

The comparative antimicrobial activities of the gel and leaf of Aloe vera were tested against Staphylococcus aureus, Pseudomonas aeruginosa, Trichophyton mentagraphytes, T. schoeleinii,

Microsporium canis and Candida albicans. Ethanol was used for the extraction of the leaf after obtaining the gel from it. Antimicrobial effect was measured by the appearance of zones of inhibition.

Antimicrobial susceptibility test showed that both the gel and the leaf inhibited the growth of S. aureus (18.0 and 4.0 mm, respectively). Only the gel inhibited the growth of T. mentagrophytes (20.0 mm), while the leaf possesses inhibitory effects on both P. aeruginosa and C. albicans. The results of this study tend to give credence to the popular use of both Aloe vera gel and leaf.

Comparative antimicrobial activities of aloe vera gel and leaf. Agarry O.O., Olaleye M.T.and Bello-Michael, C.O.. African Journal of Biotechnology Vol. 4 (12), pp. 1413-1414, December 2005

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure

Abstract

Objective: An examination glove that delivers aloe vera (AV) gel to the gloved hand was studied in 30 adult females with bilateral occupational dry skin with or without irritant contact dermatitis (with or without erythema, fissures, and excoriations). Methods: All participants were factory assembly-line workers with repeated superficial skin trauma who attributed their dry, irritated, emollient-dependent skin to a common cause (occupational exposure). Participants were sequentially enrolled (after written informed consent, n = 29 evaluable participants) into an open, contralateral comparison study to evaluate efficacy of AV glove use 8 h/day to one hand versus no use to the opposite hand for 30 days, followed by 30 days rest, followed by 10 days of repeated use. Participant’s dorsal hands were documented by standardized photos at baseline, during, and at the end of study. Results: Unblinded investigator baseline assessment rated dry skin as mild to moderate (n = 27), or moderate to severe (n = 2). Mean time to noticeable improvement for the AV glove hand was 3.5 days (range: 2-6 days) whereas marked improvement was 10.4 days (range: 7-17 days) for the AV glove hand. No improvement was detected for nonglove hands. Blinded photo assessment was rated independently by dermatology research staff. End-of-study mean global assessment of AV glove hands versus nonglove hands was 1.3 for AV glove hand (0 = no change, 1 = good [10%-89% global improvement], 2 = marked improvement [90%-100% global improvement]) versus 0 for nonglove hand (P <.0001). Mean global end-of-study assessments by the participants = 2.0 for AV glove hand versus 0 for nonglove hand. Conclusion: Dry-coated AV gloves that provide for gradual delivery of AV gel to skin produced a uniformly positive outcome of improved skin integrity, decreased appearance of fine wrinkling, and decreased erythema in the management of occupational dry skin and irritant contact dermatitis. (Am J Infect Control 2003;31:40-2.)

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure. Dennis P. West, PhDa, Ya Fen Zhu, MSb. American Journal of Infection Control. Volume 31, Issue 1, February 2003, Pages 40–42. doi:10.1067/mic.2003.12.

Aloe vera leaf gel: a review update

Abstract

Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas. Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components. A common theme running though much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents. There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens. There are also cautionary investigations warning of possible allergic effects on some patients. Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel. Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities

Aloe vera leaf gel: a review update. T Reynolds, A.C Dweck. Journal of Ethnopharmacology. Volume 68, Issues 1–3, 15 December 1999, Pages 3–37. doi:10.1016/S0378-8741(99)00085-9

Composition and Applications of Aloe vera Leaf Gel

Abstract

Many of the health benefits associated with Aloe vera have been attributed to the polysaccharides contained in the gel of the leaves. These biological activities include promotion of wound healing, antifungal activity, hypoglycemic or antidiabetic effects antiinflammatory, anticancer, immunomodulatory and gastroprotective properties. While the known biological activities of A. vera will be briefly discussed, it is the aim of this review to further highlight recently discovered effects and applications of the leaf gel. These effects include the potential of whole leaf or inner fillet gel liquid preparations of A. vera to enhance the intestinal absorption and bioavailability of co-administered compounds as well as enhancement of skin permeation. In addition, important pharmaceutical applications such as the use of the dried A. vera gel powder as an excipient in sustained release pharmaceutical dosage forms will be outlined.

Composition and Applications of Aloe vera Leaf Gel. Josias H. Hamman. Molecules 2008, 13(8), 1599-1616; doi:10.3390/molecules13081599

Polysorbate 20

Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens?

Abstract

Multi-component organogels formed using the non-ionic surfactant sorbitan monostearate as gelator have been formulated to contain niosomes. The purpose of this study was to evaluate the potential of these vesicle-in-water-in-oil (v/w/o) gels as delivery vehicles for vaccines. Bovine serum albumin (BSA) and haemagglutinin (HA) were used as model antigens in depot and immunogenicity studies respectively. The complex gels were prepared by the addition of a hot (60°C) aqueous niosome suspension (v/w) to the sol phase (o, an organic solution of the gelator); a vesicle-in-water-in-oil (v/w/o) emulsion was produced which cools to an opaque, semi-solid, thermoreversible v/w/o gel. Light microscopy of the organogel revealed that the microstructure consists of a tubular network of surfactant aggregates in the organic medium, the niosome suspension being dispersed in these surfactant tubules. Therefore, in such gels, the vaccine is thought to be entrapped in the niosomes, themselves located within the sorbitan monostearate tubular network in the organic medium. In vivo, a depot effect was observed following intramuscular administration of the gel containing the entrapped bovine serum albumin, cleared from the injection site over a period of days. The relatively short-lived nature of the depot was thought to arise due to interactions between the gel and the local interstitial fluid which results in gel disintegration in situ. Thus, the niosomes containing antigens are believed to be released from the organic gel. Immunogenicity studies showed that the v/w/o gel as well as one of the controls, the water-in-oil (w/o) gel, possess immunoadjuvant properties and enhance the primary and secondary antibody titres (of total IgG, IgG1, IgG2a and IgG2b) to haemagglutinin antigen. As far as humoral immunity is concerned, the w/o gel showed stronger immunoadjuvant properties compared to the v/w/o gel, being effective at a lower antigen dose i.e 0.1μg HA.

Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens? Sudaxshina Murdan, Gregory Gregoriadis, Alexander T Florence. European Journal of Pharmaceutical Sciences. Volume 8, Issue 3, July 1999, Pages 177–185. doi:10.1016/S0928-0987(99)00014-7.

A new mechanism for decreasing aggregation of recombinant human interferon-γ by a surfactant: Slowed dissolution of lyophilized formulations in a solution containing 0.03% polysorbate 20

Abstract

To study the mechanisms by which Tween 20 (polysorbate 20) used in a reconstitution solution affects the aggregation of lyophilized recombinant human interferon-γ (rhIFN-γ), we used four types of buffered formulations containing 0.4–5 mg/mL rhIFN-γ in either 10 mM potassium phosphate or phosphate buffered saline: (1) without excipients, (2) with 5% sucrose, (3) with 0.03% polysorbate 20, or (4) with the combination of 5% sucrose and 0.03% polysorbate 20. After lyophilization, infrared spectroscopy was used to analyze the secondary structure of the protein in the freeze-dried solid. Each solid showed structural perturbation of the protein. Each formulation was reconstituted with water or a 0.03% polysorbate 20 solution. Aggregation of rhIFN-γ after reconstitution was measured by optical density at A350, and recovery of soluble protein was determined by high-performance liquid chromatography and ultraviolet spectroscopy. After reconstitution with a 0.03% polysorbate 20 solution, aggregation levels in all formulations were either reduced or similar to those found after reconstitution with water. These results revealed the potential for recovery of native protein using the appropriate reconstitution conditions, even though the protein is non-native in the lyophilized state. Urea-induced unfolding with and without polysorbate 20 as measured by second-derivative ultraviolet spectroscopy indicated that a concentration of 0.03% polysorbate 20 lowered the free energy of unfolding for rhIFN-γ (destabilizing). Polysorbate 20 also retarded refolding from urea solutions and increased aggregation. At a level of 0.03%, polysorbate 20 did not protect the protein against surface-induced aggregation during agitation. Dissolution times in water versus a 0.03% polysorbate 20 solution were measured using a rotating disk electrode for lyophilized formulations containing an electrochemically reactive species. The presence of 0.03% polysorbate 20 in the reconstitution solution nearly doubled the time required for dissolution of the phosphate buffered saline formulation, and the sucrose formulations dissolved 33–57% more slowly. Slowing the dissolution rates of lyophilized powders allows more time for the protein to refold while it decreases the maximum concentration of the protein at the dissolution interface, thus reducing the total amount of aggregation.

Webb, S. D., Cleland, J. L., Carpenter, J. F. and Randolph, T. W. (2002), A new mechanism for decreasing aggregation of recombinant human interferon-γ by a surfactant: Slowed dissolution of lyophilized formulations in a solution containing 0.03% polysorbate 20. J. Pharm. Sci., 91: 543–558. doi: 10.1002/jps.10033

Determination of CMC of polysorbate 20 in aqueous solution by surface tension method

Abstract

The CMC of polysorbate 20 was determined using a surface tension method; the concentration (C) of polysorbate 20 studied varied from 0.001 to 10.000 mg./ml. The results show clearly that the surface tension (γ) decreases linearly with log C up to a concentration of 0.06 mg./ml. and is practically constant for more concentrated solutions. This suggests that the CMC of polysorbate 20 is in the vicinity of 0.06 mg./ml., which is in excellent agreement with the values obtained by other methods.

Mittal, K. L. (1972), Determination of CMC of polysorbate 20 in aqueous solution by surface tension method. J. Pharm. Sci., 61: 1334–1335. doi: 10.1002/jps.2600610842

Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20

Abstract

Because the ionized species is more polar than its unionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination of pH control and complexation to pH control and micellization and to pH control and cosolvency. The total aqueous solubility is expressed as the addition of the concentration of all contributing species: free un-ionized drug [Du], free ionized drug [Di], un-ionized drug micelle [DuM], and ionized drug micelle [DiM] for surfactant, and free un-ionized drug [Dcu] and free ionized drug [Dci] for cosolvent. The equations indicate that under certain conditions the ionized species can be more important in determining the drug total solubility than the un-ionized species. Flavopiridol, a weak base, is used to test these newly generated equations. As expected, the micellar partition coefficient and solubilization power for ionized flavopiridol are both less than those of the un-ionized species. However, at acidic pH, the solubilities of the ionized drug in surfactant micelles [DiM] and in cosolvent–water [Dci] are both much greater than that of the un-ionized drug. This difference is because the solubilization of the ionized drug is proportional to its aqueous solubility, and its solubility [Di] can be as much as 24-fold greater than that of the free un-ionized species [Du].

Li, P., Tabibi, S. E. and Yalkowsky, S. H. (1999), Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20. J. Pharm. Sci., 88: 507–509. doi: 10.1021/js980433o

A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: A contribution to understand colloidal protein stabilisation

Abstract

The development of liquid therapeutic protein drugs imposes the presence of specific stabilisation agents to prevent protein degradation in order to reach shelf-lives of at least 2 years for drugs stored at 2–8 °C. Non-ionic detergents are used to avoid protein adsorption and the formation of protein aggregates. Depending on the protein and excipient (detergent) used the stabilisation effect is quite different and cannot be predicted up to now. One reason for this is the inadequate understanding of the principles that govern the stabilisation of proteins in the presence of detergents. One stabilisation mechanism discussed implicates a direct binding of detergent molecules to the hydrophobic surface area(s) of the protein in order to minimise protein–protein interactions and thus protein aggregation.

Therefore, the presented study considers the interaction and binding of polysorbate 20 and 80 to various human serum albumins and immunoglobulins of different subtypes. The interaction is analysed by means of isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). From ITC the binding constant is derived as well as the thermodynamic parameters. The thermal protein stability is obtained from DSC.

The results show that binding of the two detergents to human serum albumin is observed with binding constants of approximately ≈ 103 M− 1, with 1–3 detergent molecules binding to the albumins. The exact polysorbate–albumin ratio depends on the used albumin fraction. The interaction of the detergent is also obvious from the DSC results, showing an increase of the denaturation temperature. However, the binding of the detergent to the three investigated immunoglobulins is quite low and negligible, thus showing that for immunoglobulins a direct and strong polysorbate binding to the protein is not the reason for the colloidal stabilisation effect of immunoglobulins in solution in the presence of polysorbate 20 or 80.

A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: A contribution to understand colloidal protein stabilisation. Patrick Garidel, Claudia Hoffmann, Alfred Blume. Biophysical Chemistry. Volume 143, Issues 1–2, July 2009, Pages 70–78. doi:10.1016/j.bpc.2009.04.004

Interaction of substituted benzoic acids with polysorbate 20 micelles

Abstract

Equilibrium solubilities of a series of substituted benzoic acids in different concentrations of polysorbate 20 at controlled pH were measured. The maintenance of pH was achieved using a pH-stat assembly. A linear relationship was found between the amount of benzoic acid solubilized and surfactant concentration. As solubilizate polarity increased, the amount solubilized also increased. Solubility data were analyzed, and the interaction between solubilizate molecules and micelles was calculated in terms of partition coefficients of ionized and unionized molecules between aqueous and micellar phases. A linear relationship between π values (log partition coefficients) of functional groups and aqueous-micellar partition coefficient was found.

Collett, J. H. and Koo, L. (1975), Interaction of substituted benzoic acids with polysorbate 20 micelles. J. Pharm. Sci., 64: 1253–1255. doi: 10.1002/jps.2600640733

Phenoxyethanol

Metomidate, a better anesthetic for cod (Gadus morhua) in comparison with benzocaine, MS-222, chlorobutanol, and phenoxyethanol

Abstract

Metomidate, benzocaine, MS-222, chlorobutanol, and phenoxyethanol were tested and compared in rapid anesthesia of cod (Gadus morhua). Only metomidate and, to a lesser extent, benzocaine and MS-222 were found to be recommendable. The effective concentration for metomidate was 5 mg l−1 (9.6°C), for benzocaine 40 mg l−1 (9.5°C), and for MS-222 75 mg l−1 (8.4°C). The recovery time for metomidate was longer than for benzocaine and MS-222, but the safety margin was higher.

Metomidate, a better anesthetic for cod (Gadus morhua) in comparison with benzocaine, MS-222, chlorobutanol, and phenoxyethanol. N.S. Mattson, T.H. Riple. Aquaculture. Volume 83, Issues 1–2, 1 December 1989, Pages 89–94. doi:10.1016/0044-8486(89)90063-X

Comparative efficacy of clove oil and 2-phenoxyethanol as anesthetics in the aquaculture of European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) at different temperatures

Abstract

The efficacy of clove oil as an anesthetic was evaluated in juvenile European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata), and was compared to the commonly used 2-phenoxyethanol through a series of experiments simulating aquaculture activities. Firstly, using as a criterion the acquisition of complete anesthesia (stage A5) in < 3 min and recovery (stage R5) in < 10 min, the optimal doses at 25 °C were determined to be 40 mg l−1 of clove oil for both species, and 350 mg l−1 and 300 mg l−1 of 2-phenoxyethanol for European sea bass and gilthead sea bream, respectively. At 15 °C, the optimal doses for the European sea bass were determined to be around 30 mg l−1 clove oil and 300 mg l−1 2-phenoxyethanol, and for gilthead sea bream 55 mg l−1 clove oil and 450 mg l−1 2-phenoxyethanol. Increasing the exposure time of fish to the optimal anesthetic dose for 5, 10 or 15 min after stage A5 anesthesia prolonged recovery time (ANOVA, P < 0.001), especially in gilthead sea bream, which also suffered significant mortality (10–83%). As expected, the lower temperature resulted in significantly longer anesthesia induction and recovery times (ANOVA, P < 0.001), presumably due to the positive relationship between temperature, and opercular ventilation rates (ANOVA, P < 0.001) and metabolism. Finally, repeated exposure to anesthetics at 0 h, 3 h and 24 h increased significantly the induction time to stage A5 anesthesia (ANOVA, P < 0.001), suggesting the development of a slight tolerance, especially to the clove oil. The study demonstrated that clove oil can be used as an effective anesthetic in European sea bass and gilthead sea bream aquaculture, at almost 10-fold lower doses than 2-phenoxyethanol. The observed differences in (a) dose response, (b) anesthesia induction and recovery times, (c) ventilation rates and (d) mortality after prolonged exposure among the two species, underscore the need to undertake extensive studies with the specific fish species, anesthetic and experimental procedure employed, before clove oil or any other anesthetic is proposed for commercial use in an aquaculture species.

Comparative efficacy of clove oil and 2-phenoxyethanol as anesthetics in the aquaculture of European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) at different temperatures. Constantinos C. Mylonas, Gloriana Cardinaletti, Irini Sigelaki, Alberta Polzonetti-Magni. Aquaculture. Volume 246, Issues 1–4, 18 May 2005, Pages 467–481. doi:10.1016/j.aquaculture.2005.02.046

Phenoxyethanol: Protein Preservative for Taxonomists

Pieces of chicken heart or skeletal muscle were placed in a dilute solution of the antimicrobial agent 2-phenoxyethanol and stored at room temperature. Under these conditions, the serum albumin, lactate dehydrogenase, and malate dehydrogenase in these tissues survived in easily detectable amounts for at least 2 weeks. The surviving proteins appeared to be identical with those of fresh tissues in physical, catalytic, and immunological properties. Phenoxyethanol also preserved heart and muscle proteins of representatives of other vertebrate classes. Tissue samples collected in the analysis by biochemical taxonomists.

Phenoxyethanol: Protein Preservative for Taxonomists.

Mikiye Nakanishi, Allan C. Wilson, Richard A. Nolan, George C. Gorman, George S. Bailey. Science 14 February 1969: Vol. 163 no. 3868 pp. 681-683.DOI: 10.1126/science.163.3868.681

Cortisol and haematological response in sea bream and trout subjected to the anaesthetics clove oil and 2-phenoxyethanol

Abstract

Clove oil has been tested for anaesthesia induction and recovery time as well as for haematology and stress indicators in the gilthead sea bream and rainbow trout. The former parameters were compared with those generated by 2-phenoxyethanol. The results showed only slight differences between both anaesthetics in terms of anaesthetic efficiency and physiological effects. In addition, clove oil does not block the cortisol response to stress, as happens with other anaesthetics.

Tort, L., Puigcerver, M., Crespo, S. and Padrós, F. (2002), Cortisol and haematological response in sea bream and trout subjected to the anaesthetics clove oil and 2-phenoxyethanol. Aquaculture Research, 33: 907–910. doi: 10.1046/j.1365-2109.2002.00741.x

Comparative effects of MS 222 and 2-phenoxyethanol on gilthead sea bream (Sparus aurata L.) during confinement

Abstract

The effects of two anaesthetics, ethyl m-aminobenzoate methanosulphonate (MS 222) and 2-phenoxyethanol, at three different dosage levels, were examined on gilthead sea bream (Sparus aurata) during a confinement similar to that in transport. Changes in plasma cortisol, glucose, lactate and haematological parameters were analysed. Confinement without anaesthesia produces a smaller stress response than with the two anaesthetics. Exposure to MS 222 and 2-phenoxyethanol at a dose exceeding 25 mg 1−1 for MS 222 and 0.075 mg 1−1 for 2-phenoxyethanol, respectively, produces a stress response in gilthead sea bream. The greatest effect of anaesthetic stress in the cortisol level is found following the period of exposure. The effects on plasma glucose level and on plasma lactate continue until 24 hr of recovery time. When the anaesthetic body concentration decreases, as it is metabolically eliminated, a recovery of haematological parameters and cortisol levels is clearly noted.

Comparative effects of MS 222 and 2-phenoxyethanol on gilthead sea bream (Sparus aurata L.) during confinement. A. Molinero, J. Gonzalez. Comparative Biochemistry and Physiology Part A: Physiology. Volume 111, Issue 3, July 1995, Pages 405–414.doi:10.1016/0300-9629(95)00037-8

The use of clove oil, metomidate, tricaine methanesulphonate and 2-phenoxyethanol for inducing anaesthesia and their effect on the cortisol stress response in black sea bass (Centropristis striata L.)

Abstract

Juvenile and adult black sea bass (Centropristis striata L.) were exposed to various concentrations of four anaesthetics to determine practical dosages for handling as well as for procedures such as bleeding, ovarian biopsy or tag implantation. In experiment 1, juveniles exposed to either 2.0 mg L−1 metomidate, 15 mg L−1 clove oil, 70 mg L−1 tricaine methanesulphonate (TMS) or 200 mg L−1 2-phenoxyethanol (2-PE) reached stage II of anaesthesia in 3–5 min and could be handled for weighing and measuring. All fish had completed recovery to stage III within 6 min. In experiment 2, the established concentrations of each anaesthetic were tested on juveniles to determine their ability to prevent a reflex to a subcutaneous needle puncture. All of the fish exposed to clove oil (20 mg L−1) and 40% of the TMS-treated (70 mg L−1) fish reacted while none of the fish anaesthetized in metomidate (2.0 mg L−1) or 2-PE (200 mg L−1) responded to the needle puncture. In experiment 3, metomidate (5.0 mg L−1), clove oil (30 mg L−1) TMS (125 mg L−1) or 2-PE (300 mg L−1) were all effective for performing an ovarian biopsy or tag implantation on adults. In experiment 4, TMS (125 mg L−1) exacerbated the cortisol response to a short handling stressor during a 30 min exposure. Fish anaesthetized in 2-PE (300 mg L−1), metomidate (5.0 mg L−1) or clove oil (40 mg L−1) had increased cortisol levels associated with the handling stressor but there were no further increases during the remainder of the experimental period. The results demonstrate that these anaesthetics are effective for sedation and anaesthesia of black sea bass and that the best choice is dependant upon the procedures to be performed.

King, W., Hooper, B., Hillsgrove, S., Benton, C. and Berlinsky, D. L. (2005), The use of clove oil, metomidate, tricaine methanesulphonate and 2-phenoxyethanol for inducing anaesthesia and their effect on the cortisol stress response in black sea bass (Centropristis striata L.). Aquaculture Research, 36: 1442–1449. doi: 10.1111/j.1365-2109.2005.01365.x

Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn infants of 23–26 weeks gestation

Abstract

In preterm newborn infants, topical iodine-containing antiseptics disturb thyroid hormone regulation while alcohol-based disinfectants may cause local burns. We therefore investigated the use of an aqueous solution containing 0.1% octenidine and 2% 2-phenoxyethanol for skin disinfection during the first seven days of life in premature newborns with a gestational age <27 weeks who were consecutively admitted to our level III neonatal intensive care unit between November 1, 2000 and December 31, 2001 (N=24). In boys. (N=13) the renal excretion of absorbed 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid was quantitated by high-pressure liquid chromatography. In the most immature newborn (gestational age 23 6/7 weeks), a transient erythematous reaction was observed following application of the octenidine/phenoxyethanol solution prior to umbilical vessel catheterization. No other local reactions were observed. The urinary concentration of 2-phenoxyethanol was <2 ppm in all samples, while urinary 2-phenoxyacetic acid concentrations reached 5–95 ppm (median 24 ppm). One infant had a culture-proven septicaemia (Bacillus species) during the first seven days of life. We conclude that, in contrast to alcohol-based antiseptics, an aqueous solution of 0.1% octenidine and 2-phenoxyethanol does not cause major skin damage in premature newborn infants <27 weeks’ gestation. 2-Phenoxyethanol is readily absorbed by the newborn’s skin but apparently undergoes extensive oxidative metabolization to 2-phenoxyacetic acid.

Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn infants of 23–26 weeks gestation.C. Bührer, S. Bahr, J. Siebert, R. Wettstein, C. Geffers, M. Obladen. Journal of Hospital Infection. Volume 51, Issue 4, August 2002, Pages 305–307. doi:10.1053/jhin.2002.1249

The efficacy of 2-phenoxyethanol, metomidate, clove oil and MS-222 as anaesthetic agents in the Senegalese sole (Solea senegalensis Kaup 1858)

Abstract

The efficacy of four anaesthetic agents (2-phenoxyethanol, metomidate, clove oil and MS-222) was evaluated in the Senegalese sole (Solea senegalensis). It was assumed that stage II of anaesthesia is sufficient to carry out routine aquaculture procedures in less than 3 min, with recovery in less than 5 min. The following optimal doses were determined: 600 mg L− 1 of 2-phenoxyethanol (induction 1.50 ± 0.37 and recovery time 1.94 ± 0.56 min), 5 mg L− 1 of metomidate (induction 1.50 ± 0.22 and recovery time 3.70 ± 1.18 min), 30 mg L− 1 of clove oil (induction 3.16 ± 0.40 and recovery time 3.76 ± 1.01 min) and 75 mg L− 1 of MS-222 (induction 2.42 ± 0.20 and recovery time 0.56 ± 0.14 min). The induction times decreased with increasing doses for all of the anaesthetic agents evaluated. Finally, the ability of each anaesthetic agent to prevent a reflex reaction in less than 3 min during simulated blood sampling was evaluated in Senegalese soles of different weights (74 ± 4 g; 213 ± 15 g; 300 ± 12 g), being only achieved in the following cases: 600 mg L− 1 of 2-phenoxyethanol and 6 and 8 mg L− 1 of metomidate, with fish of 74 ± 4 g, and 600 mg L− 1 of 2-phenoxyethanol, 8 mg L− 1 of metomidate and 200 mg L− 1 of MS-222 with fish of 213 ± 15 g. The most effective of the four anaesthetic agents studied was 2-phenoxiethanol, although all were considered acceptable for use in culture of Senegalese sole.

The efficacy of 2-phenoxyethanol, metomidate, clove oil and MS-222 as anaesthetic agents in the Senegalese sole (Solea senegalensis Kaup 1858). R.A. Weber,J.B. Peleteiro, L.O. García Martín, M. Aldegunde. Aquaculture. Volume 288, Issues 1–2, 2 March 2009, Pages 147–150.doi:10.1016/j.aquaculture.2008.11.024

Imidazolidinyl Urea

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol

Abstract

Preservatives are added to many final products, such as detergents, cosmetics, pharmaceuticals and vaccines. We conducted an in vitro investigation of the apoptosis- and necrosis-inducing potential of brief applications (10 min) of four common preservatives: ethylene glycol monophenyl ether, 2-phenoxyethanol (EGPE), imidazolidinyl urea (IMU), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI), and 1,2-pentanediol, a “preservative-non-preservative” best known as pentylene glycol. Using HL60 cells, we monitored the kinetics of cell toxicity with the MTT test and analysed extranuclear end points of apoptosis, i.e. phosphatidylserine exposure and nuclear fragmentation. Preservative treatment resulted in a dose-dependent decrease of cell viability. The mode of cell death was dose-dependent: necrosis occurred at high concentrations while apoptosis, shown by DNA laddering, DNA sub-diploid peak and caspase-3 activation, occurred at lower concentrations 0–24 hr after exposure to a single dose: CMI/MI induced apoptosis at low concentrations (0.001–0.01%) and necrosis at high concentrations (0.5–0.1%); IMU and EGPE required higher concentrations to induce apoptosis (IMU 0.01–0.1% and EGPE 0.01–0.5%) or necrosis (IMU 0.5–1% and EGPE only at 1%). PG induced apoptosis only at 5%. Externalization of PS, a hallmark of apoptosis, occurred early in HL60 treated with low concentrations of CMI/MI and EGPE and was concomitant with the subdiploid peak in HL60 treated with PG. However, it did not occur in HL60 treated with IMU. In conclusion, at appropriate concentrations, each of the four preservatives modulates the apoptotic machinery by a caspase-dependent mechanism. Thus, apoptosis could be a good parameter to evaluate the cytoxicity of these chemical compounds.

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol.Cecilia Anselmi, Anna Ettorre, Marco Andreassi, Marisanna Centini, Paolo Neri, Anna Di Stefano. Biochemical Pharmacology. Volume 63, Issue 3, 1 February 2002, Pages 437–453. doi:10.1016/S0006-2952(01)00910-8

Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea

For several decades, the cosmetic preservatives imidazolidinyl urea (IU) and diazolidinyl urea (DU) have not only been poorly characterized but have also had misleading chemical structures assigned to them. The most common trade names of IU and DU are Germall 115 and Germall II, respectively. This publication gives an insight into what these 2 well-known contact allergens consist of and their degradation patterns. Approximately, 30–40% of both products can be characterized by mixtures of allantoin (synthetic starting material), (4-hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-urea (compound HU) and presumably 1-(3,4-bis-hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-1,3-bis-hydroxymethyl-urea (compound BHU). A full chemical characterization of compound HU is shown. The remaining part of both IU and DU are believed to be polymers of allantoin-formaldehyde condensation products. The analytical methods used to characterize IU and DU are capillary electrophoresis and nuclear magnetic resonance and mass spectroscopy studies.

Lehmann, S. V., Hoeck, U., Breinholdt, J., Olsen, C. E. and Kreilgaard, B. (2006), Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea. Contact Dermatitis, 54: 50–58. doi: 10.1111/j.0105-1873.2006.00735.x

Imidazolidinyl urea dermatitis

Dooms-Goossens, A., de Boulle, K., Dooms, M. and Degreef, H. (1986), Imidazolidinyl urea dermatitis. Contact Dermatitis, 14: 322–323. doi: 10.1111/j.1600-0536.1986.tb05295.x

Monitoring levels of preservative sensitivity in Europe

A 10-year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5-chloro-2-methyl-4-isothiazolin-3-one + 2-methyl-4-isothiazolin-3-one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re-evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave-on products.

Wilkinson, J. D., Shaw, S., Andersen, K. E., Brandao, F. M., Bruynzeel, D. P., Bruze, M., Camarasa, J. M. G., Diepgen, T. L., Ducombs, G., Frosch, P. J., Goossens, A., Lachappelle, J. .-M., Lahti, A., Menné, T., Seidenari, S., Tosti, A. and Wahlberg, J. E. (2002), Monitoring levels of preservative sensitivity in Europe. Contact Dermatitis, 46: 207–210. doi: 10.1034/j.1600-0536.2002.460404.x

Contact sensitivity to preservatives in the UK, 2004–2005: results of multicentre study

Preservative sensitivity in the UK was last assessed in 2000. Given the changes in preservative usage, we have re-evaluated our patch test data in order to detect any changes in the trend of sensitization. The results of patch testing using the extended British Contact Dermatitis Society Standard series were collected from 9 dermatology centres in the UK. Positive reactions to each of 10 preservative allergens were captured together with the MOAHFLA indices for each centre. In total, 6958 patients were tested during the period 2004–2005. The current data were compared with previously published data. Formaldehyde and methylchloroisothiazolinone/methyl-isothiazolinone have the highest positivity rates at 2.0% and chloroxylenol the lowest at 0.2%. Parabens mix has the highest irritancy rate. Compared with the UK data in 2000, the positivity rate of imidazolidinyl urea (0.02 < P < 0.05) has significantly increased and that of methyldibromo glutaronitrile has significantly reduced (P < 0.001).

Jong, C. T., Statham, B. N., Green, C. M., King, C. M., Gawkrodger, D. J., Sansom, J. E., English, J. S. C., Wilkinson, S. M., Ormerod, A. D. and Chowdhury, M. M. U. (2007), Contact sensitivity to preservatives in the UK, 2004–2005: results of multicentre study. Contact Dermatitis, 57: 165–168. doi: 10.1111/j.1600-0536.2007.01181.x

Allergic contact dermatitis in a girl due to several cosmetics containing diazolidinyl-urea or imidazolidinyl-urea

García-Gavín, J., González-Vilas, D., Fernández-Redondo, V. and Toribo, J. (2010), Allergic contact dermatitis in a girl due to several cosmetics containing diazolidinyl-urea or imidazolidinyl-urea. Contact Dermatitis, 63: 49–50. doi: 10.1111/j.1600-0536.2010.01736.x

EDTA

Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice

Abstract

Topical 5-aminolevulinic acid (ALA) application in three different creams was carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP) production in the tumour and in the skin overlying the tumour was studied by two methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics of PP production in the skin and in the tumour, as studied by the LIF method, was similar for all three cream preparations. The PP fluorescence intensity in the tissues reached its maximum 4–6 h after application of the creams. Quantitative analysis showed that the PP concentration after treatment was more pronounced in the skin than in the tumour. The efficiency of porphyrin production in the skin by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by ALA was observed mainly in the upper 2 mm section. However, the concentration of PP in the tumour was found to be approximately the same for the ALA-DMSO and ALA-DMSO-EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA are discussed.

Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice. Z. Malik, G. Kostenich, L. Roitman, B. Ehrenberg, A. Orenstein. Journal of Photochemistry and Photobiology B: Biology.Volume 28, Issue 3, June 1995, Pages 213–218. doi:10.1016/1011-1344(95)07117-K

Effect of EDTA and zinc-methionine complex on zinc absorption by rat intestine

The effects of zinc chelators on 65Zn uptake, absorption and tissue distribution were determined in rats using ligated duodenal loops. 65Zn was supplied as Zn-methionine complex, ZnCl2, ZnCl2 + L-methionine or ZnCl2 + EDTA. The effect of EDTA was also determined in the presence of phytic acid. Absorption of 65Zn was markedly reduced in rats given Zn-methionine complex or ZnCl2 + EDTA. The 65Zn level in tissues (liver, bone, muscle, skin, kidney, and thymus) of rats given ZnCl2 + EDTA was also significantly reduced compared to that of rats given ZnCl2. Reduced absorption due to phytic acid was not improved by EDTA, although EDTA increased mucosal 65Zn retention. High performance gel filtration chromatography showed six 65Zn-binding peaks in the mucosal cytosol of rats given ZnCl2. A seventh peak attributable to Zn-EDTA was observed in cytosol from rats given ZnCl2 + EDTA. A comparable peak in plasma was not observed. Both EDTA and Zn-methionine complex reduced 65Zn-binding to a low-molecular-weight component of mucosal cytosol that was not metallothionein. The results suggest that Zn-EDTA is transported intact from the lumen into mucosal cells but not across the basolateral membrane. The adverse effects of EDTA and Zn-methionine complex on zinc absorption were associated with reduced 65Zn-binding to a component of mucosal cytosol that may be involved in zinc absorption.

Effect of EDTA and zinc-methionine complex on zinc absorption by rat intestine.Hempe JM, Cousins RJ. Food Science and Human Nutrition Department, University of Florida, Gainesville 32611.The Journal of Nutrition [1989, 119(8):1179-1187]

The Vast Majority of CLA T Cells Are Resident in Normal Skin

There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are ∼1 × 106 T cells/cm2 normal skin and an estimated 2 × 1010 T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA+ effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.

The Vast Majority of CLA T Cells Are Resident in Normal Skin. Rachael A. Clark, Benjamin Chong, Nina Mirchandani, Nooshin K. Brinster, Kei-ichi Yamanaka, Rebecca K. Dowgiert and Thomas S. Kupper. The Journal of Immunology. April 1, 2006 vol. 176 no. 7 4431-4439. doi: 10.4049/​jimmunol.176.7.4431

Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis.

Linear IgA bullous dermatosis (LABD) is a rare blistering skin disease characterized by basement membrane zone deposition of IgA. This study identifies a tissue antigen detected by patient serum and then isolates the autoantibody using epidermis and protein bands blotted on nitrocellulose as immunoabsorbents. Sera from 10 patients (9 with cutaneous disease and 1 with cicatrizing conjunctivitis) were evaluated. Indirect immunofluorescence revealed an IgA anti-basement membrane antibody in 6 of 10 sera with monkey esophagus substrate and 9 of 10 sera with human epidermal substrate. Immunoblotting was performed on epidermal and dermal extracts prepared from skin separated at the basement membrane zone with either sodium chloride or EDTA. Saline-separated skin expressed a 97-kD band in dermal extract alone that was recognized by 4 of 10 sera. EDTA-separated skin expressed the 97-kD band in both epidermal (4 of 10 sera) and dermal (6 of 10 sera) extract. Immunoabsorption of positive sera with epidermis purified an IgA antibody that reacted uniquely with the 97-kD band. In addition, IgA antibody bound to nitrocellulose was eluted from the 97-kD band and found to uniquely bind basement membrane zone. It is likely that the 97-kD protein identified by these techniques is responsible for basement membrane binding of IgA in LABD.

Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis. J J Zone, T B Taylor, D P Kadunce, and L J Meyer. J Clin Invest. 1990 Mar; 85(3): 812–820. doi: 10.1172/JCI114508

Potassium Sorbate

Antimicrobial and physical properties of sweet potato starch films incorporated with potassium sorbate or chitosan

Abstract

Antimicrobial biodegradable films have been prepared with sweet potato starch by incorporating potassium sorbate or chitosan. Films incorporated with potassium sorbate ≥ 15% or chitosan ≥ 5% were found to have an anti-Escherichia coli effect. Staphylococcus aureus could be effectively suppressed by incorporation of chitosan at ≥10%. Whereas potassium sorbate lowers the tensile strength and elongation at break, and raises the oxygen permeability, water vapor permeability and water solubility, chitosan has the opposite effect. Fourier Transform Infrared (FT-IR) spectra analysis revealed that starch crystallinity was retarded by potassium sorbate incorporation and that hydrogen bonds were formed between chitosan and starch. This explained the modification of the mechanical and physical properties of the films by the incorporation of these two antimicrobial agents.

Antimicrobial and physical properties of sweet potato starch films incorporated with potassium sorbate or chitosan. Xiao Li Shena, Jia Min Wu, Yonghong Chen, Guohua Zhao. Food Hydrocolloids. Volume 24, Issue 4, June 2010, Pages 285–290. doi:10.1016/j.foodhyd.2009.10.003

Effect of potassium sorbate washing on the growth of Listeria monocytogenes on fresh poultry

Abstract

This work evaluated the effect of potassium sorbate washing on the growth of Listeria monocytogenes on poultry legs stored at 4 °C for 7 days. Fresh inoculated chicken legs were dipped into either a 2.5% (w/v) or 5% potassium sorbate solution or distilled water (control). Changes in mesophiles, pychrotrophic counts and sensorial characteristics (odor, color, texture and overall appearance) were also evaluated.

The shelf life of the samples washed with potassium sorbate was extended by at least 2 days over the control samples washed with distilled water. Legs washed with 5% potassium sorbate showed a significant (p < 0.05) inhibitory effect on L. monocytogenes compared to control legs, with a decrease of about 1.3 log units after 7 days of storage. Sensory quality was not adversely affected by potassium sorbate.

Effect of potassium sorbate washing on the growth of Listeria monocytogenes on fresh poultry. E. González-Fandos, J.L. Dominguez. Food Control. Volume 18, Issue 7, July 2007, Pages 842–846. doi:10.1016/j.foodcont.2006.04.008

Sorbic Acid and Potassium Sorbate Permeability of an Edible Methylcellulose-Palmitic Acid Film: Water Activity and pH Effects

ABSTRACT

The apparent permeability constants for potassium sorbate and sorbic acid through an edible film composed of methylcellulose and palmitic acid (weight ratio 3:1) were evaluated as a function of water activity (aw) and pH. For films with thickness 55–66 μm, potassium sorbate permeability increased from 2.3 × 10−10 to 2.0 × 10−8 (mg/sec cm2)(cm)/(mg/mL) as aw increased from 0.65 to 0.80. Films were not stable at aw levels above 0.80. Permeability of the film to sorbic acid at aw 0.8 decreased from 3.3 × 10−8 to 9.1 × 10−10 (mg/sec cm2)(cm)/ (mg/mL) as pH increased from 3 to 7. At pH 3 the undissociated acid was 97.5% and at pH 7 it was 0.4%.

RICO-PEÑA, D. C. and TORRES, J. A. (1991), Sorbic Acid and Potassium Sorbate Permeability of an Edible Methylcellulose-Palmitic Acid Film: Water Activity and pH Effects. Journal of Food Science, 56: 497–499. doi: 10.1111/j.1365-2621.1991.tb05312.x

Validation of HPLC Analysis of 2-Phenoxyethanol, 1-Phenoxypropan-2-ol, Methyl, Ethyl, Propyl, Butyl and Benzyl 4-Hydroxybenzoate (Parabens) in Cosmetic Products, with Emphasis on Decision Limit and Detection Capability

Abstract

The Commission Decision of August 12, 2002 on the performance of analytical methods and the interpretation of results was applied to the HPLC method for the analysis of parabens, 2-phenoxyethanol and 1-phenoxypropan-2-ol in cosmetic products. This method is published in the seventh Directive 96/45/EC of the European Commission. Non-compliant concentrations, taking into account the data distribution (CCα) and the probability of false negative values (CCβ) were determined. The repeatability and reproducibility amount to <4% and <7%, respectively. These values were obtained with blanc samples that were fortified in the laboratory. Calibration linearity was confirmed by absence of lack of fit for all seven preservatives. Matrix effects on the determinations of the preservatives in body milk or shampoo are negligible.

Validation of HPLC Analysis of 2-Phenoxyethanol, 1-Phenoxypropan-2-ol, Methyl, Ethyl, Propyl, Butyl and Benzyl 4-Hydroxybenzoate (Parabens) in Cosmetic Products, with Emphasis on Decision Limit and Detection Capability.

1. Borremans , J. Van Loco, P. Roos, L. Goeyens. Chromatographia. January 2004, Volume 59, Issue 1, pp 47-53

Tocopherol Acetate

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice

Abstract

Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115–0.23 J/cm2 results after 24–48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-α-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40–55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel noninvasive technique not previously reported for this purpose—magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p < 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p < 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p < 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the irradiation has stopped, by a derivative of d-α-tocopherol which is stable to autooxidation.

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. John R. Trevithick, Hua Xiong, Shirley Lee, David T. Shum, S.Ernest Sanford, Stephen J. Karlik, Christopher Norley, Geoffrey R. Dilworth. Archives of Biochemistry and Biophysics. Volume 296, Issue 2, 1 August 1992, Pages 575-582. doi:10.1016/0003-9861(92)90613-2

Biokinetics in humans of RRR-α-tocopherol: The free phenol, acetate ester, and succinate ester forms of vitamin E

Abstract

The bioavailability of RRR-α-tocopherol from the oral administration of RRR-α-tocopherol itself and its acetate and succinate esters was determined in healthy human subjects. Venous blood samples were withdrawn periodically over a 51-h period following oral administration of a gelatin capsule containing an equimolar mixture of RRR-α-tocopherol and RRR-α-tocopheryl acetate. In a second study, subjects received a capsule containing an equimolar mixture of RRR-α-tocopheryl acetate and RRR-α-tocopheryl succinate. In Study 1, RRR-α-tocopherol was absorbed at similar rates from both the free phenol, and the acetate ester and maximum plasma levels occurred at 12 h in most subjects. The extent of absorption of RRR-α-tocopherol varied considerably between subjects in absolute terms, but the relative absorption from the two forms was remarkably consistent, and a ratio of 1.0 was found for parameters of relative bioavailability in plasma. The concentration of RRR-α-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large inter-individual variability. In Study 2, there was no significant difference in the extent of absorption of RRR-α-tocopherol from the acetate ester and the succinate ester, although there was an apparently higher initial rate of absorption from the acetate ester.

Biokinetics in humans of RRR-α-tocopherol: The free phenol, acetate ester, and succinate ester forms of vitamin E. Kevin H. Cheeseman, Anne E. Holley, Frank J. Kelly, Mohamad Wasil, Lise Hughes, Graham Burton. Free Radical Biology and Medicine.Volume 19, Issue 5, November 1995, Pages 591–598.doi:10.1016/0891-5849(95)00083-A

A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles

Synopsis Solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system with reduced side-effects. Incorporation of the chemical sunscreen tocopherol acetate into SLN prevents chemical degradation and increases the UV-blocking capacity. Aqueous SLN dispersions were produced and incorporated into gels, followed by particle size examination, stability testing upon storage and thermoanalytical examination. Investigation of the UV-blocking capacity using different in vitro techniques revealed that the SLN dispersions produced in this study are at least twice as effective as their reference emulsions (conventional emulsions with identical lipid content). Placebo SLN even show greater UV-blocking efficacy than emulsions containing tocopherol acetate as the molecular sunscreen. Incorporation of tocopherol acetate into SLN leads to an overadditive UV-blocking effect. Furthermore, film formation of SLN on the skin and occlusivity were examined. The obtained data show that incorporation of tocopherol acetate into SLN leads to an improved sunscreen and skin care formulation.

Wissing, S. A. and Müller, R. H. (2001), A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles. International Journal of Cosmetic Science, 23: 233–243. doi: 10.1046/j.1467-2494.2001.00087.x

Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Abstract

α-Tocopherol transfer protein (αTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by αTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and α-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-α-tocopherol=100%) calculated from the degree of competition were as follows: β-tocopherol, 38%; γ-tocopherol, 9%; δ-tocopherol, 2%; α-tocopherol acetate, 2%; α-tocopherol quinone, 2%; SRR-α-tocopherol, 11%; α-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for αTTP is one of the critical determinants of their biological activity.

Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. Akihiro Hosomi, Makoto Arita, Yuji Sato, Chikako Kiyose, Tadahiko Ueda, Osamu Igarashi, Hiroyuki Arai, Keizo Inoue. FEBS Letters. Volume 409, Issue 1, 2 June 1997, Pages 105–108. doi:10.1016/S0014-5793(97)00499-7

Preparation of core-shell PAN nanofibers encapsulated alpha-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection

Preparation of core-shell PAN nanofibers encapsulated alpha-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection. Wu, Xiao-Mei; Branford-White, Christopher J.; Yu, Deng-Guang; et al. COLLOIDS AND SURFACES B-BIOINTERFACES Volume: 82 Issue: 1 Pages: 247-252

In vitro and in vivo Permeation of Vitamin E and Vitamin E Acetate from Cosmetic Formulations.

In vitro and in vivo Permeation of Vitamin E and Vitamin E Acetate from Cosmetic Formulations. Nada, Aly; Krishnaiah, Yellela S. R.; Zaghloul, Abdel-Azim; et al.MEDICAL PRINCIPLES AND PRACTICE Volume: 20 Issue: 6 Pages: 509-513 Published: 2011

Chemoprevention of Human Actinic Keratoses by Topical DL-alpha-Tocopherol.

Chemoprevention of Human Actinic Keratoses by Topical DL-alpha-Tocopherol. Foote, Janet A.; Ranger-Moore, James R.; Einspahr, Janine G.; et al. CANCER PREVENTION RESEARCH Volume: 2 Issue: 4 Pages: 394-400

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation.

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. Murray, John C.; Burch, James A.; Streilein, Robert D.; et al.JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Volume: 59 Issue: 3 Pages: 418-425

Vitamin E in human skin: Organ-specific physiology and considerations for its use in dermatology.

Vitamin E in human skin: Organ-specific physiology and considerations for its use in dermatology. Thiele, Jens J.; Ekanayake-Mudiyanselage, Swarna. MOLECULAR ASPECTS OF MEDICINE Volume: 28 Issue: 5-6 Pages: 646-667

Thyme Extract

Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels

Carvacrol, eugenol and thymol are major components of plants such as oregano, savory, clove and thyme. When applied to the tongue, these flavors elicit a warm sensation. They are also known to be skin sensitizers and allergens. The transient receptor potential channel (TRPV3) is a warm-sensitive Ca2+-permeable cation channel highly expressed in the skin, tongue and nose. Here we show that TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol. Tongue and skin epithelial cells respond to carvacrol and eugenol with an increase in intracellular Ca2+ levels. We also show that this TRPV3 activity is strongly potentiated by phospholipase C–linked, G protein–coupled receptor stimulation. In addition, carvacrol activates and rapidly desensitizes TRPA1, which may explain the pungency of oregano. Our results support a role for temperature-sensitive TRP channels in chemesthesis in oral and nasal epithelium and suggest that TRPV3 may be a molecular target of plant-derived skin sensitizers.

Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Haoxing Xu, Markus Delling, Janice C Jun & David E Clapham. Nature Neuroscience 9, 628 – 635 (2006). doi:10.1038/nn1692

Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells.

Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells. Emir Bozkurt, Harika Atmaca, Asli Kisim, Selim Uzunoglu, Ruchan Uslu & Burcak Karaca. Nutrition and CancerVolume 64, Issue 8, November 2012, pages 1245-1250.

Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy.

Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy.Margarita González-Vallinas, Guillermo Reglero & Ana Ramírez de Molina. Nutrition and CancerVolume 67, Issue 8, November 2015, pages 1223-1231

The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins.

The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins.Tea Kulišić Ph.D, Anita Kriško, Verica Dragović-Uzelac, Mladen Miloš & Greta Pifat. International Journal of Food Sciences and Nutrition. Volume 58, Issue 2, January 2007, pages 87-93

Essential Oil of Thyme (Thymus vulgaris L.) Grown in Cuba

Essential Oil of Thyme (Thymus vulgaris L.) Grown in Cuba. Jorge A. Pino, Mirna Estarrón & Victor Fuentes. Journal of Essential Oil Research. Volume 9, Issue 5, September 1997, pages 609-61.

Chemical Profile, Antioxidant and Antibacterial Activity of Thyme and Oregano Essential Oils, Thymol and Carvacrol and Their Possible Synergism.

Chemical Profile, Antioxidant and Antibacterial Activity of Thyme and Oregano Essential Oils, Thymol and Carvacrol and Their Possible Synergism. Neda Gavaric, Sonja Smole Mozina, Nebojša Kladar & Biljana Bozin. Journal of Essential Oil Bearing Plants. Volume 18, Issue 4, July 2015, pages 1013-1021

Investigation of Extracts from Thyme (Thymus vulgaris L.) for Application in Cosmetics.

Investigation of Extracts from Thyme (Thymus vulgaris L.) for Application in Cosmetics. Stanka Damianova, Stanislava Tasheva, Albena Stoyanova & Dancho Damianov. Journal of Essential Oil Bearing Plants.Volume 11, Issue 5, January 2008, pages 443-450

Identification and quantification of a major anti-oxidant and anti-inflammatory phenolic compound found in basil, lemon thyme, mint, oregano, rosemary, sage, and thyme.

Identification and quantification of a major anti-oxidant and anti-inflammatory phenolic compound found in basil, lemon thyme, mint, oregano, rosemary, sage, and thyme. Jae B. Park. International Journal of Food Sciences and Nutrition. Volume 62, Issue 6, September 2011, pages 577-584

Citric Acid

Overview of citric acid production from Aspergillus niger.

Abstract

Citric acid has high economic potential owing to its numerous applications. It is mostly produced by microbial fermentation using Aspergillus niger. In view of surges in demand and growing markets, there is always a need for the discovery and development of better production techniques and solutions to improve production yields and the efficiency of product recovery. To support the enormous scale of production, it is necessary and important for the production process to be environmentally friendly by utilizing readily available and inexpensive agro-industrial waste products, while maintaining high production yields. This article reviews the biochemistry of citric acid formation, choices of citric-acid producing microorganisms and raw materials, fermentation strategies, the effects of various fermentation conditions, citric acid recovery options and the numerous applications of citric acid, based on information drawn from the literature over the past 10 years.

Overview of citric acid production from Aspergillus niger. Pau Loke Show, Kehinde Opeyemi Oladele, Qi Yan Siew, Fitri Abdul Aziz Zakry, John Chi-Wei Lan & Tau Chuan Ling. Frontiers in Life Science. Volume 8, Issue 3, July 2015, pages 271-283

Citric Acid-Ammonium Acetate Buffer.

Abstract

A pH table is reported for citric acid-ammonium acetate buffers that are useful for horseradish peroxidase (HRP) histochemistry.

Citric Acid-Ammonium Acetate Buffer. Sharon Stegmann, Robert B. Norgren & Michael N. Lehman. biotechnic & Histochemistry.Volume 66, Issue 1, January 1991, pages 27-28

Characterization of Blue Whiting Skin Gelatines Extracted After Pretreatment with Different Organic Acids.

Abstract

Gelatines were extracted from blue whiting (Micromesistius poutassou) skins after pretreatment with different organic acids (acetic, citric, lactic, malic, and tartaric acids). The effect of the pretreatment on the chemical composition and the rheological properties of extracted gelatines were analyzed. It was observed that acetic acid pretreatment resulted in significantly (p < 0.05) higher extraction yield compared to the rest of the gelatines. All gelatines, regardless of the organic acid used in the pretreatment, had similar chemical composition (p > 0.05). The amino acid analysis showed that acetic acid pretreated skins resulted in gelatines with higher imino acid levels with respect to the other pretreatments. Acetic and tartaric acid derived gelatine gels showed highly interconnected protein networks and better viscoelastic properties, in terms of storage modulus, compared to the other pretreatments.

Characterization of Blue Whiting Skin Gelatines Extracted After Pretreatment with Different Organic Acids. Zied Khiari, Daniel Rico, Ana Belen Martin-Diana & Catherine Barry-Ryan. Journal of Aquatic Food Product Technology. Volume 24, Issue 6, August 2015, pages 546-555

The direct determination of phosphorus in citric acid soil extracts by colorimetry and direct-current plasma emission spectroscopy.

Abstract

The effect of citrate interference on the direct colorimetric determination of P in 1% citric acid soil extracts of a wide range of soils was investigated and compared to that of removing the citric acid by dry ashing. It was found that dilution of the soil extracts to ratios greater than 1:20 caused minimal interference with colour development using the molybdenum blue method. Dilutions of 1:10 and 1:5 caused a 10% and 55% reduction in absorbance values respectively. Despite this interference, the measurement of P in the presence of 1% citric acid is possible if the same concentration of this acid, present in the soil extract, is present in the calibration standards. Generally a 1:10 dilution of soil extracts provides sufficient sensitivity for the determination of P in soils with a P status < 5 mg kg−1 and can accommodate soils with a P status up to 100 mg kg−1. The effect of dry ashing the soil extracts and measuring the P colorimetrically resulted in slightly higher P values, in the order of 2 mg kg−1. Similar results were obtained when the soil extracts were aspirated into a direct-current plasma and the P was measured by emission spectrometry. It was concluded that quantities of P could be present in the soil extracts, either organically or inorganically bound, and were responsible for this difference. These forms of P were not determined by colorimetric procedures but were released by a high-temperature plasma or by dry ashing. For most practical purposes these low values can be ignored.

The direct determination of phosphorus in citric acid soil extracts by colorimetry and direct-current plasma emission spectroscopy. G. R. Thompson. South African Journal of Plant and Soil. Volume 12, Issue 4, January 1995, pages 152-157

Development and evaluation of dual controlled release microballoons containing riboflavin and citric acid: in vitro and in vivo evaluation.

Abstract

The objective of this work was to optimize the incorporation of citric acid (CA) in the gastroretentive microballoons containing riboflavin (RF) in order to achieve dual controlled release system and consequently enhance the bioavailability of RF. Microballoons of 739 ± 1.9 µm containing RF–CA were prepared by modified emulsion solvent diffusion method and were evaluated both for in vitro and in vivo performance. RF–CA microballoons with 22.8% RF and 37.2% CA entrapped in the shell matrix composed of Eudragit® S 100 and HPMCK4M and in vitro buoyancy of 86.0 ± 0.88% (RCM3) was selected for further studies. RCM3 exhibited biphasic, pH-dependent in vitro dual controlled release of RF (0.9933–0.9962) and CA (0.996–0.9984) beyond 1 h in both simulated fasted and fed state conditions. RCM3 was able to achieve higher mean plasma concentrations than reference formulation RM2 (RF microballoon) both in fed and fasted states in rabbits. The mean AUC0–24 estimate of RCM3 was 55% higher in fasted state (p < 0.01) and about 51% higher in fed state (p < 0.05) relative to mean AUC0–24 from RM2 formulation. Conclusively, enhancement in RF in the presence of CA along the entire plasma level curve suggests a possibility of reduction in dosing frequency. This controlled release drug delivery system of RF, where CA is incorporated in the microballoons can be easily encapsulated in capsule dosage form negating the need of CA solution as vehicle for administration of RF microballoons.

Development and evaluation of dual controlled release microballoons containing riboflavin and citric acid: in vitro and in vivo evaluation. Amriteshwar N. Singh & Kamla Pathak. Journal of Microencapsulation. Volume 28, Issue 5, August 2011, pages 442-454

Chamomile (Matricaria recutita) Extract

CHAMOMILE (Matricaria recutita) EXTRACT AS A CORROSION INHIBITOR FOR MILD STEEL IN HYDROCHLORIC ACID SOLUTION

Abstract

The corrosion inhibition of mild steel in hydrochloric acid solution by chamomile (Matricaria recutita) extract (CE) was investigated through electrochemical (polarization, EIS) and surface analysis (optical microscopy/AFM/SEM) techniques. The effects of inhibitor concentration, temperature, and pH were evaluated. Thermodynamic parameters were calculated and adsorption studies were carried out. Finally, the surface morphology was investigated. The electrochemical studies showed that CE acts as a mixed-type corrosion inhibitor with predominantly anodic behavior. CE was adsorbed physically on the metal surface and obeyed the Langmuir adsorption isotherm. It impeded the corrosion processes by changing the activation energy. In the presence of CE, the metal surface was more uniform than the surface in the absence of inhibitor. Maximum inhibition efficiency (IE) was 93.28%, which was obtained at 22°C in 7.2 g/L of inhibitor in 1 M HCl solution.

CHAMOMILE (Matricaria recutita) EXTRACT AS A CORROSION INHIBITOR FOR MILD STEEL IN HYDROCHLORIC ACID SOLUTION. Mahdi Nasibi, Davood Zaarei, Gholamreza Rashed & Effat Ghasemi. Chemical Engineering Communications.Volume 200, Issue 3, March 2013, pages 367-378

Chamomile Ligulate Flowers in Supercritical CO2-Extraction

Abstract

The essential oil (EO) of chamomile ligulate flowers (CLF) was extracted by supercritical carbon dioxide (SC-CO2) at 240 bar and 40°C for five hours. An empirical equation: log c = a log W + b, for defining the dependence of total extract concentration (cTE), i.e. EO concentration (cEO) in supercritical CO2, on relative mass of CO2 (W) was selected. The equations obtained fitted the experimental data very well (r1=0.9997 and r2=0.9977). In the same way, the behavior of pharmacologically active chamomile compounds [(—)-α-bisabolol, oxides A and B, (—)-α-bisabolol, cis- and trans-en-in-dicycloethers] contained in EO of CLF after SC-CO2 extraction, was investigated. For qualitative and quantitative determination of EOs the GC/MS analysis was used. The fermentation of CLF after SC-CO2 extraction was used to increase the content of spasmolytically important chamomile flavone apigenin. The procedure of obtaining the product of CLF with the best composition of pharmacologically active compounds of chamomile has been reported.

Chamomile Ligulate Flowers in Supercritical CO2-Extraction. Zoran P. Zekovic. Journal of Essential Oil Research. Volume 12, Issue 1, January 2000, pages 85-93

Antioxidant Activity, Reaction Mechanisms, and Kinetics of Matricaria recutita Extract in Commercial Blended Oil Oxidation.

Abstract

Antioxidant activity, reaction mechanisms, and kinetics of Matricaria recutita crude extract (CE; total phenolics: 41 ± 2.5 mg/g, total flavonoids: 26 ± 1.4 mg/g, IC50: 82.3 ± 2.8 µg/mL and reducing power: 10.45 ± 0.56 mmol Fe2+/mass) in comparison to tert-Butylhydroquinone during oxidation of blended vegetable oil (sunflower, soybean, and palm oil) at 120, 130, and 140°C were studied. Good correlations existed between the Rancimat oil stability index and stability indices (induction period) calculated from peroxide value, conjugated diene value, and anisidine value with no significant differences in kinetic parameters calculated from them. The temperature acceleration (Q10), activation energy (Ea), frequency factor (A), enthalpy (ΔH++), entropy (ΔS++), and free energy of activation (ΔG++) for oils containing crude extract were lower than for oils containing tert-Butylhydroquinone (0.0025, 0.005, 0.01, and 0.02%). Values were independent of crude extract or tert-Butylhydroquinone concentration. For crude extract and tert-Butylhydroquinone, Ea and A were well correlated with ΔH++ and ΔS++ values, respectively, but correlation between Ea and Q10 for crude extract compared to tert-Butylhydroquinone was poor. Furthermore, the rate of Monounsaturated:Polyunsaturated fatty acids formation did not differ significantly between crude extract and tert-Butylhydroquinone, but concentrations of them did affect Monounsaturated:Polyunsaturated ratio. Based on the results obtained, crude extract decreased the rate of the oxidation reaction due to the decrease in the concentration of the activated complex and reduction in the rate at which the activated complex dissociated into oxidation products.

Antioxidant Activity, Reaction Mechanisms, and Kinetics of Matricaria recutita Extract in Commercial Blended Oil Oxidation. Seyed Mohammad Bagher Hashemi, Mary Susan Brewer, Javad Safari, Masoud Nowroozi, Moosa Hamid Abadi Sherahi, Behrooz Sadeghi & Moslem Ghafoori. International Journal of Food PropertiesVolume 19, Issue 2, February 2016, pages 257-271

Chemical Composition and Antimicrobial Activity of Essential Oil of Matricaria recutita

Abstract

Matricaria recutita is a herbaceous plant belonging to the Asteraceae family. The present study reports the chemical composition and antimicrobial activity of M. recutita essential oil and its main compounds. The essential oil was obtained from the aerial parts of the M. recutita by hydrodistillation and analyzed by gas chromatography-mass spectrometry. The major components were α-bisabolol oxide (38%), followed by camphene (9.11%), sabinene (4.87%), limonene (6%),1,8-cineole (7.12%), camphor (6.54%), and α-pinene (6%). Essential oil of chamomile was evaluated for its antibacterial activities against three gram-positive and four gram-negative pathogenic bacteria. The essential oil and its main compounds were particularly active against Bacillus cereus, with the lowest minimum inhibitory concentration and minimum bactericidal concentration value (0.022 and 1.5 μg /mL). In conclusion, these results support the use of the essential oil and its main compounds for their antimicrobial properties.

Chemical Composition and Antimicrobial Activity of Essential Oil of Matricaria recutita. Mohsen Kazemi. International Journal of Food Properties. Volume 18, Issue 8, August 2015, pages 1784-1792

Passion Flower (Passiflora Incarnata) Extract

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques

Abstract

Passiflora is one of the 27 genera of the Passifloraceae family. Some Passiflora species are known by their edible fruits, which have a distinct flavor and aroma that favor their in natura consumption and their applicability in the food industry. Also, Passiflora leaves have therapeutical properties, such as the widely known anxiolytic and sedative effects. The quality control and the assessment of the compounds responsible for the Passiflora properties can be done by several chromatographic and electrophoretic techniques, such as planar chromatography (TLC and HTPLC), liquid chromatography (HPLC and UHPLC), gas chromatography (GC), and capillary electrophoresis (CE). The aim of this article is to review the analytical techniques used for the evaluation of the different compounds present in each part of a Passiflora plant, exploring the leaves, the fruits with their rinds and seeds, and other Passiflora parts, such as nectar and callus culture compositions, as well as to compare stability tests on several Passiflora products.

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques. Gisláine C. Silva & Carla B. G. Bottoli. Critical Reviews in Analytical Chemistry. Volume 45, Issue 1, January 2015, pages 76-95

An Evidence-Based Systematic Review of Passion Flower (Passiflora Incarnata L.) by the Natural Standard Research Collaboration

An Evidence-Based Systematic Review of Passion Flower (Passiflora Incarnata L.) by the Natural Standard Research Collaboration. Journal of Dietary SupplementsVolume 5, Issue 3, January 2008, pages 310-340. DOI:10.1080/19390210802414360

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques

Abstract

Passiflora is one of the 27 genera of the Passifloraceae family. Some Passiflora species are known by their edible fruits, which have a distinct flavor and aroma that favor their in natura consumption and their applicability in the food industry. Also, Passiflora leaves have therapeutical properties, such as the widely known anxiolytic and sedative effects. The quality control and the assessment of the compounds responsible for the Passiflora properties can be done by several chromatographic and electrophoretic techniques, such as planar chromatography (TLC and HTPLC), liquid chromatography (HPLC and UHPLC), gas chromatography (GC), and capillary electrophoresis (CE). The aim of this article is to review the analytical techniques used for the evaluation of the different compounds present in each part of a Passiflora plant, exploring the leaves, the fruits with their rinds and seeds, and other Passiflora parts, such as nectar and callus culture compositions, as well as to compare stability tests on several Passiflora products.

Analyses of Passiflora Compounds by Chromatographic and Electrophoretic Techniques. Gisláine C. Silva & Carla B. G. Bottoli. Critical Reviews in Analytical Chemistry. Volume 45, Issue 1, January 2015, pages 76-95

Hydrolyzed Silk Protein

Long-range periodic sequence of the cement/silk protein of Stenopsyche marmorata: purification and biochemical characterisation

Abstract

The long-range periodic amino acid sequence of the bifunctional silk/cement protein from larvae of the caddisfly, Stenopsyche marmorata, is discussed in this study. The protein, named the S. marmorata silk protein (Smsp-1), was first purified to electrophoretic homogeneity. The results of Edman-based sequencing of Smsp-1 tryptic digests were consistent with the amino acid sequence deduced from a cDNA clone of the Smsp-1 gene. All undetected amino acids in the Edman-based sequencing were encoded as Ser, suggesting the presence of O-phospho-Ser. 31P-NMR and an O-phospho-amino acid analysis successfully showed that the O-phospho-Ser residue occurred in a clustered manner, serving a cement function for Smsp-1. Two patterns of non-phosphorylated repeats, –SLGPYGDPRGDXLGPYGG– (X = V, G or D) and –GVGPYGDGLGPYGG–, were enriched in Smsp-1 compared with the O-phospho-Ser cluster, and have fibre-forming functions.

Long-range periodic sequence of the cement/silk protein of Stenopsyche marmorata: purification and biochemical characterisation. Kousaku Ohkawa, Yumi Miura, Takaomi Nomura, Ryoichi Arai, Koji Abe, Masuhiro Tsukada & Kimio Hirabayashi. BiofoulingVolume 29, Issue 4, April 2013, pages 357-367

Complexation-triggerable liposome mixed with silk protein and chitosan

Abstract

Complexation-triggerable liposomes were prepared by modifying the surface of egg phosphatidylcholine (EPC) liposomes with hydrophobicized silk fibroin (HmSF) and hydrophobicized chitosan (HmCh). Maximum complexation, determined by measuring the diameter of complexation, was found when the ratio of HmSF to HmCh was 14:1, so they were immobilized on the surface of liposomes at the same ratio. The degree of fluorescence quenching of calcein in liposomal suspension was as high as 68% when the ratio of surface modifier (HmSF + HmCh) to EPC was 1:15. When the ratio was increased to 1:5, the degree of quenching decreased to 32%, indicating the inefficient formation of liposome. Liposome mixed with the surface modifier was multi-lamellar vesicle on TEM photo. And, the mean diameter was larger than those of liposome mixed with either HmSF or HmCh, possibly due to insoluble complex on the liposomal surface. The liposome exhibited a pH-sensitive release and triggered the release at pH 5.5 and 6.0. It is believed that complexation is responsible for the promoted release at those pH values.

Complexation-triggerable liposome mixed with silk protein and chitosan.Yeon-Ji Hong & Jin-Chul Kim. Journal of Biomaterials Science, Polymer Edition. Volume 26, Issue 12, August 2015, pages 766-779

High-strength silk protein scaffolds for bone repair

Abstract

Biomaterials for bone tissue regeneration represent a major focus of orthopedic research. However, only a handful of polymeric biomaterials are utilized today because of their failure to address critical issues like compressive strength for load-bearing bone grafts. In this study development of a high compressive strength (~13 MPa hydrated state) polymeric bone composite materials is reported, based on silk protein-protein interfacial bonding. Micron-sized silk fibers (10–600 µm) obtained utilizing alkali hydrolysis were used as reinforcement in a compact fiber composite with tunable compressive strength, surface roughness, and porosity based on the fiber length included. A combination of surface roughness, porosity, and scaffold stiffness favored human bone marrow-derived mesenchymal stem cell differentiation toward bone-like tissue in vitro based on biochemical and gene expression for bone markers. Further, minimal in vivo immunomodulatory responses suggested compatibility of the fabricated silk-fiber-reinforced composite matrices for bone engineering applications.

High-strength silk protein scaffolds for bone repair. Biman B. Mandala, Ariela Grinberga, Eun Seok Gila, Bruce Panilaitisa, and David L. Kaplan. PNAS. May 15, 2012 vol. 109 no. 20. doi: 10.1073/pnas.1119474109

Applications of natural silk protein sericin in biomaterials

Abstract

Silk sericin is a natural macromolecular protein derived from silkworm Bombyx mori. During the various stages of producing raw silk and textile, sericin can be recovered for other uses. Also, sericin recovery reduces the environmental impact of silk manufacture. Sericin protein is useful because of its properties. The protein resists oxidation, is antibacterial, UV resistant, and absorbs and releases moisture easily. Sericin protein can be cross-linked, copolymerized, and blended with other macromolecular materials, especially artificial polymers, to produce materials with improved properties. The protein is also used as an improving reagent or a coating material for natural and artificial fibers, fabrics, and articles. The materials modified with sericin and sericin composites are useful as degradable biomaterials, biomedical materials, polymers for forming articles, functional membranes, fibers, and fabrics.

Applications of natural silk protein sericin in biomaterials. Yu-Qing Zhang. Biotechnology Advances. Volume 20, Issue 2, May 2002, Pages 91–100. doi:10.1016/S0734-9750(02)00003-4

Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture.

We previously reported that sericin small (sericin-S), with a molecular weight that ranges from 5 to 100 kDa, is a cell culture supplement used to accelerate cell proliferation. In this study, a novel preparation method for sericin and several applications of sericin were examined. Sericin large, prepared under nonhydrolyzing conditions and ranging from 50 to 200 kDa, also accelerated cell proliferation, but its effects were inferior to those of sericin-S. Additional sericin preparations with various molecular weights that were differentially hydrolyzed were also tested but none of them was significantly superior to sericin-S, and neither were several recombinant sericin peptides. Sericin-S successfully accelerated the proliferation of hybridoma cells in various serum-free media, implying the mitogenic effect of sericin is independent from media. We also demonstrated that sericin-S successfully induced the proliferation of CTLL-2, an established T lymphocyte cell line, under IL-2 starvation conditions. These results indicate that sericin, particularly sericin-S, improves serum-free mammalian cell culture.

Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture. Satoshi Terada, Masahiro Sasaki, Kana Yanagihara, Hideyuki Yamada. Journal of Bioscience and Bioengineering. Volume 100, Issue 6, December 2005, Pages 667–671.doi:10.1263/jbb.100.667

Expression and Purification of a Spider Silk Protein: A New Strategy for Producing Repetitive Proteins

Abstract

Synthetic genes were constructed based on the known sequence of the spider dragline silk protein MaSp 2. The genes had 8, 16, or 32 contiguous units of the consensus repeat sequence of the protein. These artificial genes were constructed using a strategy involving compatible but nonregenerable restriction sites, which allowed construction of very large inserts in a precisely controlled manner. This strategy should have general utility in the controlled construction of repetitive proteins composed of identical or different repeat units. The protein from the 16-unit repeat was produced inEscherichia coliat levels up to 10 mg/g wet wt of cells although yields of 1–2 mg/g were more typical. The protein was easily purified with high recovery using an affinity column. The purified protein had the predicted amino acid composition and N-terminal sequence after cleavage of a leader sequence. The methodology described will allow production of sufficient quantities of protein for basic structure/function studies including production of synthetic fibers.

Expression and Purification of a Spider Silk Protein: A New Strategy for Producing Repetitive Proteins. Randolph V. Lewisa, Michael Hinman, Srinivas Kothakota, Maurille J. Fournier. Protein Expression and Purification. Volume 7, Issue 4, June 1996, Pages 400–406.doi:10.1006/prep.1996.0060

Retinol Palmitate (Vitamin A Palmitate).

A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy

RESULTS

Seven of ten retinol palmitate patients responded, whereas two of nine responded to placebo (P = 0.057). Mean pre-post-treatment change in Radiation Proctopathy System Assessments Scale (Δ Radiation Proctopathy System Assessments Scale) in the retinol palmitate group was 11 ± 5, whereas Δ Radiation Proctopathy System Assessments Scale in the placebo group was 2.5 ± 3.6 (P = 0.013, Mann-Whitney U test). Additionally, all five placebo nonresponders who were crossed over to treatment with retinal palmitate responded to treatment.

CONCLUSIONS

In our trial, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound-healing effects. The current results can serve as the foundation for future trials examining retinol palmitate in the multi-institutional setting.

A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy.Eli D. Ehrenpreis , Ashesh Jani, Josh Levitsky, Joseph Ahn, John Hong. Diseases of the Colon & Rectum. January 2005, Volume 48, Issue 1, pp 1-8.

Effect of Process Variables on the Microencapsulation of Vitamin A Palmitate by Gelatin-Acacia Coacervation

Abstract

Microcapsules of vitamin A palmitate were prepared by gelatin-acacia complex coacervation. The effects of colloid mixing ratio, core-to-wall ratio, hardening agent, concentration of core solution, and drying method on the coacervation process and the properties of the microcapsules were investigated. The microcapsules of vitamin A palmitate were prepared using different weight ratios of gelatin and acacia, that is, 2:3, 1:1, and 3:2 under controlled conditions. The other factors studied were 1:1, 1:2, and 1:3 core-to-wall ratios; 30, 60, and 120 min of hardening time; 2, 5, and 10 ml of formaldehyde per 280 g of coacervation system as a hardening agent; and 30%, 40%, and 50% w/w vitamin A palmitate in corn oil as a core material. The drying methods used were air drying, hot air at 40°C, and freeze-drying. The results showed that spherical microcapsules were obtained for all conditions except for 30 min of hardening time, which did not result in microcapsules. The optimum conditions for free-flowing microcapsules with a high percentage of entrapped drug were 1:1 gelatin-to-acacia ratio and 1:2 core-to-wall ratio when hardening with 2 ml formaldehyde for 60 min and using 40% w/w vitamin A palmitate in corn oil as the core concentration. In addition, drying the microcapsules by freeze-drying provided microcapsules with excellent appearance.

Effect of Process Variables on the Microencapsulation of Vitamin A Palmitate by Gelatin-Acacia Coacervation.Varaporn Buraphacheep Junyaprasert, Ampol Mitrevej, Nuttanan Sinchaipanid, Prapaporn Boonme & Dale Eric Wurster. Drug Development and Industrial PharmacyVolume 27, Issue 6, January 2001, pages 561-566. DOI:10.1081/DDC-100105181

Inclusion complexation of vitamin a palmitate with β-cyclodextrin in aqueous solution

Abstract

Study of the inclusion complex between vitamin A palmitate and β-cyclodextrin in aqueous solution was performed to determine the stoichiometry and the association constant of the complex by the phase solubility diagram and fluorescence intensity measurements.

Inclusion complexation of vitamin a palmitate with β-cyclodextrin in aqueous solution.Giovanni Filippo Palmieri, Pascal Wehrlé, Guy Duportail & AndrÉ Stamm. Drug Development and Industrial PharmacyVolume 18, Issue 19, January 1992, pages 2117-2121. DOI:10.3109/03639049209040925