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The facts you need to know: new FDA proposed Sunscreen Regulation

by james.runkle@drummondst.com james.runkle@drummondst.com No Comments

Sunscreen Innovation Act

The Sunscreen Innovation Act sponsored by Jack Reed was introduced to the Senate Committee Health, Education, Labor and Pensions on March 13, 2014.  It amends the Federal Food, Drug, and Cosmetic Act to establish a process for the review and approval of over-the-counter (OTC) sunscreen active ingredients.

FDA Proposes New Safety Testing for Selected Sun Filters

On February 26, 2019 the FDA published a proposed rule that would put into effect a final monograph for non-prescription OTC sunscreen drug products.  It establishes conditions under which certain OTC drugs may be marketed without approved new drug applications, indicating these products would be Generally Recognized as Safe and Effective (GRASE).  The sun care industry was hopeful that data previously submitted to the FDA would lead to the approval of additional sun filters currently used in Europe, under the FDA time and extent rule (TEA) policy.

Significance of the Proposed Safety Testing Protocol

To establish safety in use of sunscreen products, the FDA is proposing a Maximal Usage Trial study (MUsT). This is a human pharmacokinetic test that measures the amount of absorption of a drug into the body.  This study is new to the cosmetics industry and is more commonly used to study absorption of prescription drugs into the body.  The FDA believes this study will help to determine the potential effect of long-term use of an active ingredient.

 


Bio for Howard Epstein, Ph.D.

Howard Epstein is Director of Technical Services for EMD Performance Materials Corporation, Philadelphia, PA., an affiliate of Merck KGaA, Darmstadt, Germany. He was a scholar in residence at the University of Cincinnati department of dermatology and received his Ph.D. in Pharmacognasy from the Union Institute & University in Cincinnati, Ohio during that time. He has been in the cosmetics industry for many years since he began his career formulating cosmetics for Estee Lauder, Maybelline, Max Factor, Bausch & Lomb and Kao Brands. In addition to his interest in botanicals Howard previously served as editor of the Journal of the Society of Cosmetic Science and is a member of the International Academy of Dermatology. He is on the editorial board of the dermatological journals Clinics in
Dermatology and SKINmed representing the cosmetics industry to dermatologists.

Howard has authored chapters in various cosmetic technology textbooks including various chapters in Harry’s Cosmeticology, and holds eight patents and two patent applications.

Clinical Study Dos and Don’ts: Designing Safety & Claim Support Studies

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Clinical Study Dos and Don’ts:  Designing Safety & Claim Support Studies

Nothing makes an R&D director happier than providing a validated sound scientific dossier to his/her marketing team on a technology or formulation that has gone through months, if not years, of development.  From inception to market, there are endless meetings about progress, budgets, resource allocation and most of all, data generation.   When you think about all of the time and energy you have spent on this one aspect of your pipeline, validating your work becomes paramount so that it is universally accepted by not only the market place but by your management and investors as well. Ironically, this is the most crucial and usually the most expensive point of the project as a whole.  What can you do to ensure that you are efficient in your success?

In order to properly validate your mechanism of action and support your claims, an outside lab is usually brought into the fray for good reason: you want an objective 3rd party verification of all you have done to this point.   This will entail having all of your project management skills ready to go. This is akin to getting to the championship game in your favorite sport.  The whole season now rides on how well you do in the next game or series.  How do you position yourself for success?  Below you will find some do’s and don’ts that I have been faced with, both as a client and as a provider of clinical testing for personal care and cosmetic products.

Are you Ready to Test?

From the service side of the industry, I find that many clients come to the table thinking they are ready to test with a 3rd party laboratory. However, after the first meeting is over, they are usually going home with a to-do list longer than the questions they had for me.  So, ask yourself, are we ready to test?  No matter your title or level of responsibility, you must build a team to answer this question.  Having a team in place that represents all facets of the project, including where you have been and where you are going is the first step.  Understanding how you landed on the functional claims, category and target consumer/customer are going to lay the foundation of what type of 3rd party lab you will need and what type of study design is warranted, as not all testing labs are created equal.  All of your team members must bring their information and needs to the table to answer that question before you pick up the phone and ask for 3rd party commitment.  Have a timeline built and map out the approval process commensurate with your company’s policies.  There are some companies that inherently have more red tape than others.  Know and understand your internal process before bringing in outside counsel.  This will certainly convey confidence and keep you in the driver’s seat.

Represent your Stake Holders

Having a good mix of representation on your team of R&D, marketing, operations, regulatory and sales personnel, especially in the initial meetings with a 3rd party laboratory, will ensure that everyone’s needs are accounted for and visible.  This will also make for a much smoother utilization of data when it comes time to launch.  Some of the best launches are the result of this synergy alone.

Communication

Gathering, moving and analyzing information is the norm in today’s market place and is critical for success.  It is imperative that the team you build have an open channel of communication within its team members and the lab when necessary.  As the team leader/project champion, you must know who your go-to people are.   There are often cases of misplaced assumptions regarding who knows what, and who is responsible for deliverables and decisions.  Many times I work with a project team looking to perform validation studies only to find that delays are imposed from executing as planned because the test materials are not available or not delivered on time to the testing facility.  There are many reasons for this.  Some examples include delays in release from QA, test materials that have not passed physical or chemical stability, last minute changes to the formulation design and for our international clients, test materials getting stuck in customs at the border.  All of these issues can be mitigated with proper channels of information being open.  If one person is the gate keeper of all the information, that person needs to have access to all facets of the project and to includes information that the team members possess.  Establishing portals for information sharing especially when collaborations exist over multiple time zones is something to also consider. At the end of the day, proper, concise and efficient communication is paramount to keeping all stakeholders informed and abreast of the status of your project.

Understand your Goals

Have a holistic view of the expectations and goals.  I always say to prospective clients, “work your project backwards”.  Assuming that you get the best data possible, what will you say about it?  Understanding the end game allows everyone to see the goal in the detail that is needed.  Having a vague undefined goal is grounds for confusion, uncertainty and delays to market.  Having the goal in mind is also crucial for developing the protocol to get you to the desired objective.  One of the most common delays and unpredicted expenses companies incur are due to last minute protocol changes.  These cause delays in final approvals, delays in recruiting the required subjects, and ultimately delays in study execution at the 3rd party lab. There is a high risk for decisions being made before final protocols are signed by not having your team review the protocols early on. This can lead to re-works, delays and loss of access to resources, equipment and personnel needed to perform the study.

Know your Financial Limitations

Budget, budget, budget, how many times have we all heard, “we can’t do that, it’s too expensive”?  Have a deliberate budget in mind when you are ready to validate claims.  You can start off shooting for the stars but inevitably, you land back on earth holding your budget in hand saying, “we need a new plan”.  Match your needs within your budget.  So many clients come to me with a beautiful study design only to realize that it is light years beyond what they budgeted for.  Factors that drive price in any clinical study are of course the time and resources allocated by the lab; however, there are study design oversights that drive up study costs significantly.  Having time points that can be managed Monday through Friday and within a regular work day reduces overtime commitment by the lab.  Choosing technicians (or expert graders) to perform evaluations other rather than MD’s (where appropriate) is another way to save money.  IRB cost, interim data requests, expedited reports and last minute changes to the schedule once protocols are signed are huge drivers of cost, and many of these can be avoided with proper planning and good team building.

Focus on what you want to Achieve

Validation of claims or target mechanism of action is in the eyes of the beholder.  Keep in mind, in the personal care industry, consumer perception trumps all.  If your technology/finished product does not deliver on consumer perceivable results, you most likely will not get a return customer and the market will quickly lose interest in your product.  The good news is, consumer use studies are not that expensive.  Know your consumer base, ask the right questions and provide the best use instructions possible.  Many clients like to marry consumer use data with objective instrumental measures and/or expert grading.  This is the trifecta of clinical study success.  If you can show agreement with consumer perception, instrumental measures and expert assessment, you have a solid foundation for a bullet proof marketing campaign.

Understand your Consumer

Consider the consumer experience when designing your study.  Have you prepared use instructions that best represent how the product will be used?  Do you have a mechanism in place to understand off indication used of your product?  Factoring in these questions is critical to reduce the variation in consumer generated data.  People in general are variable in their recollection of experiences.  Having a way to reduce this through easy to read, easy to understand, and simple use instructions makes for a happy experience.  Consumers/subjects evaluating a product will, when asked, provide valuable negative feedback as well.  Ask for it, don’t wait for it.  It’s better to understand the short comings of using your product before it hits the market.  Is your product providing comfort and ease of use?  If so, it will be viewed in a better light.  Ask for diary comments, proof of use, have a hot line into the testing company for adverse event reporting.  All of these provide subjects on your study with a positive experience which will ultimately be reflected in your data on product performance.

Translate your Science and Check Regulatory Requirements

Marketing should play an integral role as a co-champion of the validation process.  They should be able to translate the science to consumer language which in turn should be converted to questions used for consumer perception studies.  Marketing should also understand what the competition in their particular category is saying about similar products.  3rd party labs do not make marketing claims; they provide data to support them.  Your marketing team should also have a hot line to a regulatory expert in the geographic regions of where you plan to sell your product.  So much for world harmonization, the individual regulatory requirements worldwide are ever growing further apart and complex.  Don’t spend your valuable time and resources developing a technology only to find out you can’t sell it in your target region because of regulatory hurdles, restrictions on trade, and/or miss alignment with what is culturally acceptable.

Know your Data

Finally, what to do with your data?  Chances are, you may be in charge of getting a 3rd party laboratory to perform some validation or claim support studies but you don’t remember the first thing about statistics.  Your report comes back from the lab with P values and Z scores.  Paragraphs about significant and non-significant data along with ANOVA analysis….YIKES!, what does all of this mean?

Did you set up the study to have the data be understandable or are you counting on one of your science team members to make sense of it all?  Is the data audited?  So many times as a client, I have asked for the raw data to review and “crunch” myself to better understand the relationships.  On the flip side, as a testing lab, I have had clients spend significant time and money on a study and not know what their data means or how to apply it back to the original objective of the study.

Final Remarks

No matter how you get to your goal, always keep in mind the fundamentals.  They are so easy to take for granted and in retrospect, the lack of attention to the fundamentals is the very reason why projects don’t go as planned.  So, build an effective and comprehensive team, know your budget limitation upfront, manage information in and out of the team efficiently, understand the expectations and stick to the plan. Understand the needs of your customers and translate the data in a way they understand.  Last but not least, know your market and consumer front to back and translate data so that they both understand it to the point at which they come back for more.

 

Author’s Biography:

Michael Anthonavage is the current VP of Operations and Technology at Eurofins CRL Cosmetic Testing. Michael has 20+ years of experience in personal care product development and a career spanning background in skin biology and models and methods development. He specializes in R&D to marketing translation and claims validation, both in vitro and in vivo. Michael is an engaging public speaker and product technology advocate with an ability to marry complex ideas and concepts to various consumer needs; he is also an educator in the area of herbal studies, instructing students in the study of plant chemistry and their impact on human physiology.  Michael has a number publications and patents to his name and continues to be an influential speaker in personal care, bioinstrumentation and skin testing.

 

 

Sunscreen Monograph Proposed New Rules and its Impact on Formulations-Part II

by james.runkle@drummondst.com james.runkle@drummondst.com No Comments

In my recent blog published in August, changes to the current sunscreen tentative monograph were proposed.  These changes are probably the most drastic changes to the sunscreen monograph since its inception.  In this section, I would like to tackle two key areas related to the changes requested by the FDA.  The first one is the human pharmacokinetics Maximal Usage Trial (MUsT) for sunscreens conducted by the FDA and published in the Journal of the American Medical Association in May 2019.  The second is the response from the Personal Care Product Council (PCPC) to the requests from the FDA for additional safety data.

The FDA conducted a MUsT trial on 4 sunscreen formulations.  The products consisted of 2 sprays, one lotion and one cream. A detailed description of the products used in the study and the sunscreens concentrations used is displayed in Table I below.

Table I

Concentrations of sunscreens in all treatments

Treatment Percent sunscreen contents per label
Avobenzone Oxybenzone Octocrylene Ecamsule
Spray 1 3.00 6.00 2.35 0.00
Spray 2 3.00 5.00 10.00 0.00
Lotion 3.00 4.00 6.00 0.00
Cream 2.00 0.00 10.00 2.00

Twenty-four subjects were enrolled in the study and were randomized into 4 groups.  Each treatment was studied on 6 individuals. All subjects finished the study except one.  Products were applied at a rate of 2 mg/cm2 on 75% of the body area.  Products were applied by a trained expert and were re-applied every 2 hours four times a day.  The study ran for 4 days and panelists were kept indoors.  Thirty blood samples were collected from each panelist over a period of 7 days and were analyzed for their concentration of sunscreens using a validated HPLC method.

Mean maximum plasma concentrations for all sunscreens were calculated for the four treatments and are displayed in Table II.

Table II

Geometric mean maximum plasma concentration for all treatments

Treatment Geometric Mean Maximum plasma concentration, ng/mL (%CV)
Avobenzone Oxybenzone Octocrylene Ecamsule
Spray 1 4.0 (60.9) 209.6 (66.8) 2.9 (102) Not applicable
Spray 2 3.4 (77.3) 194.9 (52.4) 7.8 (113.3) Not applicable
Lotion 4.3 (46.1) 169.3 (44.5) 5.7 (66.3) Not applicable
Cream 1.8 (32.1) Not applicable 5.7 (47.1) 1.5 (166.1)

As seen from the table, all sunscreens tested had higher blood levels than the FDA proposed threshold of 0.5 ng/mL.  These levels were also achieved on the first day of treatment.  The levels obtained triggered the FDA to request safety data not only on the sunscreens studied but also on the 12 sunscreens listed in the monograph.  In addition, the FDA requested MUsT studies to be conducted by the manufacturers on several dosage forms to establish proper guidelines for usage based on safety and efficacy.  Regardless of the results obtained, the FDA insisted on the fact that individuals should not refrain from using sunscreens.

In response to the request from the FDA, the PCPC sent a letter to describe the protocols and studies suggested by the council as well as a timeline.  The PCPC suggested to conduct, in addition to MUsT studies, several surveys on usage of sunscreen products to guide the council in designing the MUsT studies.  The timeline extends till 2023 which should give the industry some breathing room in terms of formulations.  Once the studies are received and completed, an additional timeline delineating the safety of the selected molecules will be proposed.  In the council’s response, two sunscreens were not considered for MUsT studies.  These are Cinoxate and Dioxybenzone.  The fate of these two sunscreens is not determined at this stage yet.

The sunscreen monograph has been evolving for the past 35 years to keep up with the advancement in science.  Formulators, and companies in the field of sun care will have to adjust one more time to the changes.  These changes bring a lot of new challenges and opportunities to innovate and lead.


 

Biography

Dr. Fares started his career in personal care studying the effect of solvents on sunscreen chemicals.  His interest in skin drug delivery especially from polymeric matrices grew during his graduate work at Rutgers, where he completed his Ph. D. in Pharmaceutics.

Dr. Fares worked at Block Drug and GlaxoSmithKline where he held positions in research and development in the areas of skincare and oral care.  After that, he joined L’Oreal where he held several positions of increasing responsibility leading to AVP of skincare.  He is currently the Senior Director of skincare and oral care at Ashland Specialty Ingredients.  Dr. Fares is the author of many publications, and patents and made many presentations in national and international meetings in the areas of suncare, skincare, and oral care.

 

Natural and Clean Cosmetics – The Science Behind the Ingredients

by james.runkle@drummondst.com james.runkle@drummondst.com No Comments

In recent years we have seen in the cosmetic market an increase of simplified products with fewer ingredients.

The marketing message of these products is often linked to the ingredients sourcing, functionality, and safety (including the absence of the so called no-no ingredients). Labeled as clean beauty products, they often rely on natural ingredients that, due to the identification of natural with recognized by the human body, biodegradable, and often used in traditional medicine, they easily fit into the concept of safety (and carry a nice story on sourcing). But what about efficacy? Is it possible today to develop clean beauty products, carrying the purest and most ethical sourced natural ingredients, and prove their efficacy with Science? Technology and science is available today for both developing the natural extracts and for testing them, therefore increasing their safety and efficacy while maintaining their positive image of clean, pure, eco-friendly, safe and sustainably sourced. Technologies derived from the pharma and the imaging industries are available at affordable cost and flexibility. Genomics, proteomics and metabolomics analysis are now offered to the cosmetic scientist1 as well as machines able to qualify and quantify skin characteristics in a non-invasive way. In other words, it is finally possible to verify the scientific edge and efficacy of any natural and natural derived ingredient.

Raw materials – Minimal Processing

Raw materials sourcing from sustainable supply chain are often linked to:

– Biological agriculture

– Sustainable harvesting form the wild

These raw materials seem to emerge in the food supply chain first. Initial markets are in the country of origin on a micro-scale (local green markets), following a macro-scale and industrialization step (larger distribution in retail space). Often commercialized at a continent level, they are eventually “discovered” in other continents and growing according to their commercial and marketing appeal.

Example – Pomegranate Seed Oil

Pomegranate is sourced through a sustainable model and cold pressed oil is produced. Due to its unique and elevated level of omega-5 (conjugated linolenic acid, punicic acid) (Table 1),  the oil is a strong anti-oxidant, showing protection from UV-induced protein oxidation (carbonylation) and DNA damage.2


Table 1. Omegas Fatty Acids and Vitamin E Composition of Pomegranate Seed Oil

Further research highlighted the oil’s soothing properties such as inhibition of inflammatory mediator lipoxygenase;3 but also its regenerating characteristics, like the stimulation of keratinocytes growth.4

Raw Material – Extraction and Transformation in an Active Ingredient

Raw materials are often transformed into active ingredients for personal care applications. Specific extraction by using biodegradable and natural solvents produces ingredients with specific physical-chemical characteristics and solubility for different cosmetic applications. Once ingredients are validated based on stability assays and scaled up, they can be tested for safety and efficacy in different models (in vitro, ex vivo, and clinical – non animal).

Example – Fucoidan from Seaweed

Seaweeds are rich in phenols derivatives and polysaccharides with protecting activity.5,6 Brown seaweeds also contain a compound called fucoidan that assists with protection from marine pathogens.  Fucoidan is a fucose-rich polysaccharide with anti -viral, immune modulating and matrix metalloprotease inhibiting properties.7 By isolating fucoidan from seaweeds, the formulator can use smaller concentrations of the extract. These lower levels reduce the risk of incompatibilities and material setting, color issues and scent, improving overall stability.8 Recent research highlighted the scientific added value of fucoidan as skin soothing and skin regenerating agent (reduction of Trans Epidermal Water Loss, decreased wrinkle’s depth, increase elasticity, reduction of proteases) (Figure 1).9

Figure 1. Seaweed Extract rich in Fucoidan inhibits proteases and tyrosinase (from Fitton JH et al.9)

Conclusion

Natural and Clean Beauty Products contain natural ingredients communicated through ethical sourcing and safety. Scientific tools allow to analyze and test these ingredients for efficacy, therefore helping to select the right ingredient concentration to add to the finished product for optimal functionality. Natural and Clean Beauty Brands need to start validate their ingredients efficacy through real scientific testing and/or select their suppliers based on how scientific is their ingredient offer. Natural ingredients can step up for efficacy once good science is performed to validate their benefits for cosmetic applications. There is a clear need in the market for more science and more credible claims and we can provide them both helping consumers properly chose the cosmetics they need.

References

  1. Rai A, Saito K, Yamazaki M. Integrated omics analysis of specialized metabolism in medicinal plants. Plant J 90(4):764-787, 2017
  2. Afaq F, Zaid MA, Khan N, Dreher M, Mukhtar H. Protective effect of pomegranate-derived products on UVB-mediated damage in human reconstituted skin. Exp Dermatol 18(6):553-561, 2009
  3. Schubert SY, Lansky EP, Neeman I. Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids. J Ethnopharmacol 66(1):11-17, 1999
  4. Aslam MN, Lansky EP, Varani J. Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells. J Ethnopharmacol 103(3):311-318, 2006
  5. Fernando IP, Kim M, Son KT, Jeong Y, Jeon YJ. Antioxidant activity of marine algal polyphenolic compounds: a mechanistic approach. J Med Food 19(7):615-628, 2016
  6. de Jesus Raposo MF, de Morais AM, de Morais RM. Marine polysaccharides from algae with potential biomedical applications. Mar Drugs 13(5):2967-3028, 2015
  7. Fitton JH, Stringer DN, Karpiniec SS. Therapies from fucoidan: an update. Mar Drugs 13(9):5920-5946, 2015
  8. Dell’Acqua G. Sustainable ingredient science: brown algae. Cosmet Toil 128(4): 226-229, 2013
  9. Fitton JH, Dell’Acqua G, Gardiner VA, Karpiniec SK, Stringer DN, Davis E. Topical benefits of two Fucoidan-rich extracts from marine macroalgae. Cosmetics 2(2): 66-81, 2015

 

Giorgio Dell’Acqua, PhD, is a cosmetic scientist and a consultant for the personal care industry. A graduate from the University of Rome, Italy, Dr Dell’Acqua worked for 15 years as an investigator in applied medical research in different Research Institutes and Universities, including Mount Sinai Medical School in New York and Harvard Medical School in Boston. Moving to the private sector in 2000, he has spent the last 20 years as an executive and cosmetic scientist in the personal care industry. He is specialized in skin and hair care ingredients, finished product development and technical marketing. He has helped bring more than 200 successful active ingredients and finished products to market and has authored more than 70 publications in medicine and cosmetic science. From last 10 years he has been writing and lecturing on natural cosmetic ingredients, sustainable supply chain, and helped sourcing, developing and bringing to market many natural ingredients. He is an award winning speaker on natural ingredients and a regular writer on sustainability and cosmetic science. He is also the chair of the Scientific Committee for the New York Society of Cosmetic Chemists and its scientific blogger.

 

 

 

Phyto Complexes

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As the quest for natural ingredients is growing, the interest in phyto-cosmetics is raising. Phyto in Greek means plant and phyto-cosmetics are products based on natural plant extracts or containing predominantly ingredients derived from plants such as polyphenols, vitamins, etc. Since I started working on ingredients development 15 years ago, I focused my attention on natural extract, especially those rich in active molecules, preferably from the same chemical family (1, 2). My grandfather introduced phyto-cosmetics in Italy in the early 30s and I read some of his early publications. In particular, I was intrigued by how he described the power of ingredients families or phyto-complexes when compared to single ingredients from the same family. In the late 50s he published together with my uncle, at the time a young chemist in Milano, a paper on beta carotene where he highlighted the capacity of carotenoids as a family to have a more powerful effect than single moleculebeta carotene on a series of skin benefit (beta carotene was used at the same concentration of the phyto-complex).

We know that plants are often mobilizing different isoforms, variants of same molecule to create a more effective and sophisticated response to a particular need. Molecule families are common, they often work in synergies and there are evidences that molecules belonging to the same family can protect each other against oxidation, so increasing stability of the phyto-complex. Phyto-complex is not a new definition neither a new concept, but I think the recent understanding of the importance of a multifactorial and synergetic approach when formulating a product for cosmetic applications has brought a renovated interest into this strategy and into phyto-complexes.

While in the last 50 years the approach to treatment was a reductionist approach based on single purified molecules (often compared to a plant extract with little efficacy), more recently a comprehensive approach based on plant extract fractionation and enrichment has proven to be as effective as single molecules, and often more stable in finished formulations. Phyto-complexes are also the basis of modern aromatherapy, where complex composition of essential oils showed therapeutic values to treat conditions associated to diseases (3). Moreover, studies have shown that encapsulation of polyphenols phyto-complexes were able to increase wound healing (4). Interestingly, when single molecules where combined with their phyto-complex, the complex acted as an enhancer to increase molecule bioavailability, and helping stabilizing the molecule itself (5). Numerous experiments have shown the phyto-complex superior to the single molecule in mechanisms meant to reduce inflammation, such autophagy (4) and apoptosis (5). Carotenoid such as lycopene was significant inferior in anti-oxidant activity when compared to tomato seed phyto-complex (6, 7).

Finally and intriguing, combination of phyto-complexes from different parts of the same plant was superior to single plant part extracts when used for healing (8). In conclusion, evidences exist to support the use of phyto-complexes instead of (or in combination) with single molecules from the same family. The use of phyto-cosmetics and phyto-complexes will grow in the next years as more experimental evidences on their stability and efficacy will be established.

 

Tomato Seed Oil (TSO) is superior to Purified Lycopene (Lyc) in inhibiting ROS production (Ref 8)

 

References

  1. Ebrahimi SN, Gafner F, Dell’Acqua G, Schweikert K, Hamburger M. Flavone 8-C-glycosides from Haberlea rhodopensisFriv. (Gesneriaceae). Helvetica Chimica Acta, 94 (1): 38–45, 2011.
  2. Germani F, Dell’Acqua G. An extract from blueberry processing by-product (press cake) inhibits blue light induced physiological changes and increases radiance in human skin, Poster IFSCC Milano, 2019
  3. Scuteri D, Morrone LA, Rombolà L, Avato PR, Bilia AR, Corasaniti MT, Sakurada S, Sakurada T, Bagetta G. Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: Clinical Evidence and Possible Mechanisms. Evid Based Complement Alternat Med 2017:9416305, 2017
  4. Moulaoui K, Caddeo C, Manca ML, Castangia I, Valenti D, Escribano E, Atmani D, Fadda AM, Manconi M. Identification and nanoentrapment of polyphenolic phytocomplex from Fraxinus angustifolia: in vitro and in vivo wound healing potential. Eur J Med Chem 89:179-88, 2015
  5. Hasa D, Perissutti B, Dall’Acqua S, Chierotti MR, Gobetto R, Grabnar I, Cepek C, Voinovich D. Rationale of using Vinca minor Linne dry extract phytocomplex as a vincamine’s oral bioavailability enhancer. Eur J Pharm Biopharm. 84(1):138-44, 2013
  6. Lascala A, Martino C, Parafati M, Salerno R, Oliverio M, Pellegrino D, Mollace V, Janda E. Analysis of proautophagic activities of Citrus flavonoids in liver cells reveals the superiority of a natural polyphenol mixture over pure flavones. J Nutr Biochem 58:119-130, 2018
  7. Ettorre A, Frosali S, Andreassi M, Di Stefano A. Lycopene phytocomplex, but not pure lycopene, is able to trigger apoptosis and improve the efficacy of photodynamic therapy in HL60 human leukemia cells. Exp Biol Med (Maywood) 235(9):1114-25, 2010
  8. Müller L, Catalano A, Simone R, Cittadini A, Fröhlich K, Böhm V, Palozza P. Antioxidant capacity of tomato seed oil in solution and its redox properties in cultured macrophages. J Agric Food Chem 61(2):346-54, 2013
  9. van Vuuren SF, Viljoen AM. In vitro evidence of phyto-synergy for plant part combinations of Croton gratissimus (Euphorbiaceae) used in African traditional healing. J Ethnopharmacol 119(3):700-4, 2008

 

About the Author

Giorgio Dell’Acqua, PhD, is a cosmetic scientist and a consultant for the personal care industry. A graduate from the University of Rome, Italy, he worked for 15 years as an investigator in applied medical research in Universities such as Mount Sinai Medical School in New York and Harvard Medical School in Boston. Moving to the private sector in 2000, he has spent the last 19 years as an executive and cosmetic scientist in the personal care industry. He is specialized in skin and hair care ingredients, finished product development and technical marketing. He has helped bring more than 200 successful active ingredients and finished products to market and has authored more than 60 publications in medicine and cosmetic science. From last 10 years he has been writing and lecturing on natural cosmetic ingredients, sustainable supply chain, and helped sourcing, developing and bringing to market many natural ingredients. Some of his recent product development activity has focused on food by products to cosmetics, prebiotics and postbiotics to skin, and adaptogens for skin and hair care. He is an award winning speaker on natural ingredients and a regular columnist on sustainability and cosmetic science. He is also the chair of the Scientific Committee for the New York Society of Cosmetic Chemists and its scientific blogger.

Sunscreen Monograph Proposed New Rules and its Impact on Formulations

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Introduction

In February of 2019, the FDA stunned the cosmetics industry one more time by publishing proposed rules for sunscreens in the Federal Register.  As indicated by its name, these are only proposed rules but historically companies have implemented proposed rules into their formulations to be proactive.  The FDA used the argument that since the issuance of the original Final Monograph in 1999, the use of sunscreens and exposure to UV filters substantially increased.  It was important for the Agency to re-evaluate sunscreens based on current scientific understanding and extend safety assessments for such topical products to include chronic use.

 

What are the changes

The biggest change that the proposed ruling brought was the reduction of the number of Category I (Safe and effective) approved sunscreens that can be used in the US.  The FDA reduced the number of sunscreens in Category I from 16 to 2.  These two sunscreens are Titanium Dioxide and Zinc Oxide and they are approved at a level of 25% in formulations.  In addition, the FDA classified paminobenzoic acid (PABA) and Trolamine Salicylate as Category two II (Not safe and effective) which means that these two sunscreens can no longer be used in sunscreen formulations.  The remaining 12 sunscreens namely, Cinoxate, Dioxybenzone, Ensulizole, Homosalate, Meradimate, Octinoxate, Octisalate, Octocrylene, Padimate O., Sulisobenzone, Oxybenzone, and Avobenzone were classified as Category III (Additional data needed to confirm safety and efficacy).  These 12 sunscreens can be used in formulations until the FDA categorizes them into Category I or II.  From a formulation prospective, the FDA decreased the number of sunscreens to 14 until further action.  The FDA did not address the percentage at which those sunscreens can be used specifically, but probably a good fall back would be to use them at the levels published in the 1999 Monograph.  The proposed rule does not address the sunscreen active ingredients that are being evaluated under a TEA (Time and Extent Application).

In addition, the FDA proposed changes to the types of dosage forms that can be used for sunscreen products.  For Category I, they proposed the following dosage forms: oils, lotions, creams, gels, butters, pastes, ointments and sticks.  The FDA proposed Category I status for sprays subject to testing for inhalation and flammability.  Powders were classified as Category III pending additional data.  All additional dosage forms including wipes, shampoos, body washes, towelettes and others are considered as new drugs.

Broad spectrum testing was also changed.  In most parts of the world, the Critical Wavelength is used to measure broad spectrum.  The FDA is proposing to use the UVAI/UV ratio of 0.7 or higher as a standard for all sunscreens of SPF 15 or higher.  The FDA had previously proposed to make the ratio 0.9 or higher but realized that it is impossible to achieve such ratio with the portfolio of approved Category I sunscreens available in the US.  The new ratio seems reasonable but now manufacturers must perform two tests for global products, the UVAI/UV ratio and the Critical Wavelength.

Final formulation testing and labeling requirements have changed as well.  The FDA proposed to label products with the lowest SPF number achieved in in vivo testing to eliminate the variability associated with such testing.  The FDA also raised the maximum labeled sunscreen product to SPF 60+ and they attributed their decision to the lack of evidence that higher SPF product could bring meaningful clinical benefits.  The FDA proposed to label sunscreens products with an SPF 30 or higher in increments of 10 (i.e. SPF 30, 40, 50 and 60+).  They also proposed labeling sunscreens with SPF 15 to 29 to be in increments of 5 (i.e. SPF 15, 20, and 25).  The FDA also brought attention to products that are labeled SPF2 to SPF 14 and proposed that such products be removed from the market since they do not bring any adequate protection to consumers.

Sunscreens-insect repellant combination products are proposed to be classified as Category II due to incompatibility between FDA and EPA labeling instructions.  In addition, the FDA believes that combining DEET with certain sunscreens may increase cutaneous absorption of either or both.

 

What is the impact

In this proposed ruling, the FDA addressed so many safety concerns that companies and consumers suspected for years.  Many sunscreens used in the US are no longer used in Europe, Asia and the rest of the world due to their safety profiles.  However, these markets have alternative sunscreens in their portfolio that they can use to formulate safe and effective sunscreens.  In the US, such large portfolio of approved Category I sunscreen does not exist, so I would like to urge the FDA to speed the approval of all the molecules awaiting approval in the TEA process.  This will enable US formulators to have the same tools that their counterparts in the rest of the world have.  In the meantime, I am sure that formulators will use their creativity and start adapting their new formulations to the guidelines set forth by the FDA.

 

About the Author

Dr. Hani Fares started his career in personal care studying the effect of solvents on sunscreen chemicals.  His interest in skin drug delivery especially from polymeric matrices grew during his graduate work at Rutgers, where he completed his Ph. D. in Pharmaceutics.

Dr. Fares worked at Block Drug and GlaxoSmithKline where he held positions in research and development in the areas of skincare and oral care.  After that, he joined L’Oreal where he held several positions of increasing responsibility leading to AVP of skincare.  He is currently the Senior Director of skincare and oral care at Ashland Specialty Ingredients.  Dr. Fares is the author of many publications, and patents and made many presentations in national and international meetings in the areas of suncare, skincare, and oral care.

 

Development of Color Products – From William Perkin to Urban Decay

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Russian Red. 999. Ruby Woo. Pioneer. Androgyny. No. 1.

 


What do these words call to mind?

Beauty product enthusiasts the world over will recognize these iconic shade names currently inhabiting their purse. (The author tips her hat to the product developers and marketers at Dior, MAC, L’Oreal, Chanel, and Jeffree Star.)

At the risk of taking the technology for granted, what went into creating the iconic colors?

Accidental experiments, bold defiance, an enterprising mind, good taste, shrewd manufacturing, and hours of color matching in the product development laboratories.


A Short History Lesson: Accidental Chemistry Makes Mauve

In 1856 over Easter vacation, 18-year-old William Perkin set out to isolate quinine from coal tar. Perkin was student of great German organic chemist August Wilhelm von Hofmann at London’s Royal College of Chemistry. Quinine is a valuable compound with valued anti-malarial properties. However, any chemist who knows its chemical structure would not have attempted this approach. During Perkin’s time however, the structure of benzene was not even understood.

Chemical structure of quinine and benzene

Embarking on what some might call a fool’s errand, Perkin attempted to chemically isolate the compound. With an artist’s eye, he stumbled upon mauve instead, or “aniline purple”, through a series of serendipitous experiments.

Mere luck would not have been enough to produce entire libraries of color additives manufactured today. Against his professor’s recommendation –(proof that we should always make final judgement calls for ourselves rather than obey advice without discernment)– Perkin commercialized his discovery. With the financial support of his father, a construction contractor, he developed the processes for the production and use of the new aniline purple dye. In 1857, Perkin opened his factory at Greenford Green near London. From modest beginnings, the synthetic dye industry and its relative, the pharmaceutical industry, was born.

Despite falling short of his original goal (R&D scientists and research leaders: take note!), Perkin discovered the world’s first synthetic dye, opening up an entire chemical industry and painting the mass markets with bedazzling color.

Each time we swivel up a beloved tube of lipstick for application, we pay homage to Perkin. Our ability to make style statements with color products was enabled entirely by Perkin’s accidental discovery in 1856, shrewd manufacturing, and business development.

 

Color Additives for the Consumer Packaged Goods Industry

Perhaps the most tightly regulated in the cosmetic industry, these ingredients play an important role in making products visually appealing for consumers. With the right product, it empowers the consumer to make artistic statements of her choice through color products, unencumbered.

Modern day color additives have come a long way since 1856, and safely used for more than 150 years. Color additives are used to liven up a product. As industrial research brought science into industry, the industrial colorist was a profession that developed alongside industrial design after World War I. American designers and artists worked together on the design of tasteful and attractive goods to promote culture and civility to a nation that had become overwhelmed with unsophisticated immigrants from largely rural regions of southern and eastern Europe.

For manufacturers, the mass production of different colored goods posed other challenges. The need to predict which colored products would be attractive to the masses required market research, upkeep with Parisian fashion trends, and an understanding of consumer psychology. After World War II, the epicenter of mass market fashion moved to New York, where consumers exercised -and still very much do today- the power of choice over color for self-expression.

In broader contexts in business, color is used to liven a brand or company through its logo, to create instantaneous product recognition, set the visual tone and impression, or even influence consumer psychology. As such, judicious choice and use of color in products, advertisements, and on live consumer lips and faces, can pose as effective marketing campaign strategy to increase a company’s awareness and presence in the marketplace.

 

Judicious use of color even in a company logo can make a difference to a company’s brand, by igniting consumer emotion. Image source: https://www.fastcompany.com/3028378/what-your-logos-color-says-about-your-company-infographic

 

Technology Advancements Empowers the Consumer as Artist

Since the advent of brands like Urban Decay from the 1990s, bold colors have emerged on the cosmetic market, like a relentless catwalk and lightshow of color. Greens, blues, the blackest black, pinkest pink, and everything unicorn, iridescent, pearlescent, glow-in-the-dark, and in-between have become mainstays of any cosmetic product line aiming to market itself as exciting and cutting-edge.

 

Image source: www.urbandecay.com

Owing to technological advancements, consumers no longer have to choose between long-lastingness, comfort, payoff, or value. Oftentimes, a large palette of color options accost her, with the option of layering more than one color over her lips, eyelids, lashes, or face, to achieve her desired shade and look.

 

Less is More?

Presented with the sleuth of options, studies on the paradox of choice by Professors Barry Schwartz and Sheena Iyengar come to mind. While more isn’t always better, in the world of cosmetic products and beauty trends today, more DOES mean more. The wide array of color options delights the beauty consumer.

Today, this consumer is as complex in skin tone, gender, political association, and values, and expects her beauty products to reflect her multidimensional nuanced identity just as effectively. Variety in color and shade options (particularly in skin-matching tones for foundations) have been in long-time demand. Consumers asked, and beauty companies have listened.

The market today has made progress since the era of limited shade range housed in drugstore-branded compacts, where nary a tester was in sight for the consumer to choose a shade that matched her skin tone. “Nude” can mean many different shades. Brands such as Beauty Bakerie were founded upon this very premise of inclusion, turning shade names upon its head. Where brands used to start shade naming from light to dark, Beauty Bakerie makes it a point to call its darkest shade, “1”.

 

Jackie Aina, influencer known for pushing companies towards shade diversity and racial inclusivity. She demonstrates Too Faced’s pigmented emulsion foundation product in a range of new shades. Image source: https://www.glamour.com/story/jackie-aina-too-faced

 

Advent of Color via the Chemical Industry, Social Media, and Business

The evolution of consumer tastes tracks the ubiquitous use of social media and the rise of the beauty blogger voice,, both of which continue to drive demand volumes and trends today. Continued delivery of chemical and formulation innovation is what enables the fashionistas’ envelope-pushing on what is considered wearable and trendy. Contrapuntal to the international beauty companies’ main-stream product development approach, the rise of indie brands and the use of direct selling (e.g. Glossier) have sprung up to fill market whitespaces from the supply side. From the formulator’s standpoint, innovation has liberated what is possible in performance and payoff to meet the ever-growing consumer demands for “new”. Consumer force and industry innovation, very much lubricated by social media, has progressed hand in hand dramatically in the last decade.

The consumer voice has gained a significant amount of power in the beauty and consumer products industry today. The onslaught of small beauty brands has forced larger beauty conglomerates to innovate, push daring and imaginative color products, or buy up these small brands in an effort to be more competitive.

Development of technology by material suppliers continues to facilitate the creative explosion of color products. Raw ingredient suppliers in Europe, Asia, and the Americas push the boundaries of surface functionalization, particle, colloidal, material and formulation development, designing polymers and optimizing production capabilities to enable supply and production of novel raw ingredients. The advancement of technology and manufacture production has put high-performing value products directly into the consumers’ hands, democratizing beauty and lowering the cost of self-expression.

With the glut of products and trends, it remains to be seen where the push-pull conversation between consumer and company will take us. It is an exciting time to observe how raw ingredient suppliers and product development companies big and small will respond to market forces.

 

References

[1] https://www.sciencehistory.org/historical-profile/william-henry-perkin

[2] Rydzewski, R. M., Real World Drug Discovery

[3] https://www.sciencehistory.org/distillations/magazine/colors-run-riot

[4] https://medium.com/marketing-and-entrepreneurship/the-psychology-of-logo-color-in-how-consumers-view-your-brand-d3afe84f2bdb

[5] https://www.fastcompany.com/3028378/what-your-logos-color-says-about-your-company-infographic

[6] https://hbr.org/2006/06/more-isnt-always-better

[7] https://www.glamour.com/story/jackie-aina-too-faced

[8] https://www.wsj.com/articles/celebrities-like-kylie-jenner-are-upending-the-52-billion-beauty-industry-1543401001

[9] https://blogs.wsj.com/cmo/2015/06/09/bethany-mota-overtakes-michelle-phan-as-youtubes-top-beauty-producer/

[10]  https://www.huffingtonpost.co.uk/sophie-bianchi/beauty-bloggers-zoella_b_11566248.html

[11] https://www.wsj.com/articles/small-cosmetics-brands-make-over-the-beauty-market-by-targeting-millennials-11556296365

[12] https://www.wsj.com/articles/glossier-tops-billion-dollar-valuation-with-latest-funding-11552993200

 

About the Author

A polymer chemist in the personal care industry, Dr. Diane Lye is a product developer and formulator, translating novel raw materials into stable color, SPF, and skin care actives-containing consumer products. She studies the physicochemical properties of raw ingredients and finished formulas to map the consumer experience onto quantifiable entities.

Dr. Lye cut her fundamental scientific teeth by working on the design, synthesis, and bulk property characterization of main-chain block copolymer materials with supramolecular self-recognition end groups with the Weck Lab at the NYU Molecular Design Institute. She has 10 academic publications in her time in academic institutions, and developed a market commercialization assessment and plan for a dermal technology in conjunction with NYU Stern and NYU Langone.

Protection from Artificial Visible Light (and not just Blue Light)

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One of the most relevant cosmetic-industry trends in recent years – “blue light protection” – is also one of the most widely misunderstood; this article will help dispel some of the mysteries surrounding the concept of skin damage from exposure to digital screens.

 

Blue light is not the whole story

“Blue light” is a catchy phrase that is easily recognized, probably because ambient light from TV screens tends to appear “bluish”. According to Esther Ingliss-Arkell (Gizmodo, 2012), “As you go down a dark street at night, you won’t just see televisions lighting up windows and making them blue. You’ll also see a light bulbs lighting up windows to make them yellow. Have you ever noticed those light bulbs making every room you enter at night a deep shade of yellow? No, of course not. Your eyes adjust and see it as more white. Light bulbs are about 3200° K, and so are yellow when looked at briefly from someone who has other things to compare them to. TVs, on the other hand, give off shades of red, green, and blue which combine to have a color temperature in the 5500° to 6500° K range. That’ll make them look bluish for someone walking on the street and comparing them to yellow streetlights and yellow house lights. It will also make them blue if someone is sitting in a room illuminated by a light bulb and looking at a room illuminated by a television.”

A recent study by Gattefossé examined eight different devices (Apple iPhone 4S, Apple iPhone 5S, Samsung Galaxy S4, Apple iPad 2, Samsung Galaxy Tab, Samsung Galaxy Note2, DELL screen U2312MHT, DELL screen E7440) with a high spectral resolution spectrophotometer, and found that the artificial visible light (AVL) from all of these screens is composed of three distinct peaks in the spectrum, corresponding to blue, green and red light in equal parts (See Figure 1).

Figure 1. Peaks represent the dominant wavelengths emitted by the devices tested.

Therefore, any study of potential damage from artificial visible light (AVL) must cover the full spectrum of blue, green and red, not just “blue light” alone.

 

AVL is not like sunlight, and does not cause the same damage to the skin

As we all know, sunlight produces UV radiation that can damage the skin via the generation of free radicals; we protect ourselves against UVA and UVB rays by using sunscreens (with organic and/or inorganic filters) that act to prevent DNA damage that can result in age spots, deep wrinkles, dry skin and potentially skin cancer. But AVL is in the visible spectrum and does not carry the same potential for damage – so it cannot be treated in the same manner! In other words, while AVL causes some generation of free radicals in the skin, these free radicals are NOT the main driver of damage (see below), so a simple sunscreen or free radical scavenging ingredient (antioxidant) will not sufficiently protect your skin from AVL-induced damage.

 

So what does AVL actually do?

Gattefossé conducted a human genome microarray-based gene expression analysis, and found that the pathways related to mitochondria and cell cytoskeleton were significantly affected (down-regulated) (See Figure 2). These pathways are critical to the normal function of the skin:

Mitochondria are responsible for cellular respiration (taking in glucose and oxygen, and releasing energy in the form of ATP)

The cytoskeleton is a network of filaments which not only supports the plasma membrane and gives the cell an overall shape, but also allows the cell to move and mediates communication across the entire cell

Figure 2. The expression of genes related to mitochondria and cytoskeleton is significantly decreased in fibroblasts exposed to AVL (*** p<0.001)

Therefore, exposure to AVL damages the energetic machinery of skin cells and weakens their mobility and communication properties, resulting in increased cellular fatigue. Exhausted and isolated, fibroblasts are less able to produce key matrix components and less functional to interact with their environment, hindering proper matrix remodeling process. In plain English, your skin will look duller, faded, with less vitality and “glow”.

 

Protection against AVL – This is not a passing trend!

Protection against AVL, also referred to as “digital pollution”, is becoming a critical part of today’s personal care routine. Gattefossé’s Lauren DelDotto said, According to a recent study, the time spent on smartphones by millennials is estimated at 3.2 hours a day = 22 hours a week = 49 days a year1. Another report records that US consumers own 4 digital devices on average and spend 60 hours a week consuming content through digital media2.” And these figures are only for leisure activities and do NOT count time spent in front of screens for work activities.

(1)  http://www.tns-sofres.com/publications/les-millennials-passent-un-jour-par-semaine-sur-leur-smartphone

(2) http://www.nielsen.com/us/en/insights/reports/2014/the-us-digital-consumer-report.html

The use of digital screens is a permanent part of our lives and will only increase. Think about what you do as soon as your alarm goes off in the morning – before eating, showering, dressing or preparing for work, you pick up your smartphone and check out what’s been happening, thus receiving an immediate and direct dose of AVL before you even get out of bed. Consumers are beginning to be concerned about this, and are looking for ways to protect themselves.

A recent Gattefossé consumer study conducted in both Thailand (to gauge consumer reaction from the Asia Pacific/Eastern market) and in France (for reaction from the European/Western market) found over 80% of the subjects found the concept of screen-light protection “seducing”, and over 90% of the subjects found the concept “brings novelty and differentiation to the facial care offer”.

Figure 3. Consumer test conclusions on the AVL concept and novelty.

 

Conclusions

If you are developing a product line with “blue light protection”, you need to keep these important facts in mind:

  1. Blue light is not the whole story – you must test against the full spectrum of artificial visible light (AVL), equal parts blue, green and red wavelengths.
  2. AVL is not sunlight – and you cannot protect against AVL the same way you protect against the sun’s rays. UV filters and antioxidants will not be effective against digital pollution; you need an active that protects against the actual effects of AVL – disruption of the mitochondrial network and disorganization of the cellular cytoskeleton.
  3. The “trend” is here to stay – screens are getting larger (100 inch TV, anyone?), more prevalent, and most people use multiple screens at the same time. Consumers are receptive, and eager, to incorporate AVL-protection into their normal skin care routine.

 

 

About the Author

Ben Blinder – Senior Director, Gattefossé

Ben Blinder is the Senior Director for Gattefossé USA – Personal Care Division, where he is responsible for the strategic direction and performance of the cosmetic business for Gattefossé in the US and Mexico. Ben holds a chemical engineering degree from Lehigh University and has been working in the personal care industry for 32 years, with extensive experience in strategic and long-range planning, sales and technical management, and new technology search/discovery.  Ben also serves on the NYSCC Scientific Committee.

Basis for and Clinical Importance of Stratum Corneum Acidification

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While long suspected to be an important regulator of cutaneous antimicrobial defense, the ‘acid mantle’ of the stratum corneum is also a critical regulator of three additional, critical functions – permeability barrier homeostasis, integrity/cohesion (desquamation), and restriction of pro-inflammatory cytokine signaling (i.e., dampening of inflammation) (1,2). The pH of normal human stratum corneum ranges from 4.5-5.5, with the lowest levels occurring in darkly-pigmented individuals (3).

 

The epidermis renewal time is about 28 days, during which a pH gradient is formed. For several decades, it was assumed that the low pH of the stratum corneum resulted from the deposition of sebaceous gland-derived free fatty acids (FFA) on the skin surface. But it is now evident that secreted sebaceous gland products are not required for stratum corneum acidification, and may have limited impact on pH, as it has been observed that sebaceous gland-impoverished skin sites are as acidic as adjacent, sebaceous gland-enriched sites (4). Instead, pH acidification is achieved by several endogenous pathways including by-products of keratinization (filaggrin processing accounting for 0.5 unit of the bulk pH of the stratum corneum) (5), synthesis of FFA from phospholipids by the secretory phospholipase A2 (contributing to »one unit of SC bulk pH) (6,7), and the sodium-proton exchanger NHE1. In addition, the contribution of melanosome transfer in reducing skin pH, further increases skin acidic mantle in dark pigmented skin compared to light pigmented skin (3).

 

Skin surface pH is an essential component for a functional skin barrier. It provides antimicrobial defense, and regulates stratum corneum desquamation (8). Indeed, the upper layers of the epidermis carry several enzymes which activity is pH-dependent such as lipid generating enzymes, working best at acidic pH, that supply the lipid envelope of the stratum corneum (ceramides and phospholipids), or extracellular serine proteases, which are responsible for corneocytes shedding, that work best at neutral to alkaline pH (9). In addition, these proteases also play a role in skin inflammation, as they can process and activate inflammatory precursors such as IL-1α and IL-1β (10,11).

 

The importance of skin pH has also been highlighted in pathologies like ichthyosis vulgaris or atopic dermatitis, which depict dramatic barrier function impairment. In both diseases, the stratum corneum pH is increased by approximately 0.5 unit compared to healthy skin.  This increase has been correlated with: 1. mutations in the Filaggrin protein, impairing its degradation in smaller components associated with pH reduction) and, 2. excessive serine protease activity, leading to excessive desquamation, cytokine cascade and inflammation) (5,11,12).

 

Age also seems to play a role in stratum corneum pH. Aged human stratum corneum (50-60 years old) displays a higher pH than in a younger skin, with proven adverse consequences for both barrier function and stratum corneum cohesion. This age difference has been linked to decreased expression/activity of the sodium-proton exchanger NHE1 and the secretory phospholipase A2 in aged individuals (13).

 

In all cases, providing exogenous acidification has shown clinical benefits. Several rat and mouse models mimicking atopic dermatitis, fragile neonatal skin or an aged phenotype have been employed to demonstrate that defects in the barrier function maturity and stratum corneum cohesion can be corrected through restoring a normal skin pH (13–15). Moreover, in the case of atopic dermatitis, exogenous stratum corneum acidification has also been reported as beneficial in further preventing the ‘atopic March’ associated with aeroallergen-induced asthma (16).

 

In conclusion, the importance and clinical benefits of maintaining a low skin surface pH are becoming increasingly evident, especially in inflammatory dermatoses such as atopic dermatitis as well as aged skin, where the use of reduced pH emollients and cleansers should be strongly recommended to maintain a skin barrier in good condition.

 

References

  1. Chuong CM, Nickoloff BJ, Elias PM, Goldsmith LA, Macher E, Maderson PA, et al. What is the « true » function of skin? Exp Dermatol. 11(2):159‑87, 2002
  2. Elias PM. Stratum corneum acidification: how and why? Exp Dermatol 24(3):179‑80, 2015
  3. Gunathilake R, Schurer NY, Shoo BA, Celli A, Hachem J-P, Crumrine D, et al. pH-regulated mechanisms account for pigment-type differences in epidermal barrier function. J Invest Dermatol 129(7):1719‑29, 2009
  4. Man MQ, Xin SJ, Song SP, Cho SY, Zhang XJ, Tu CX, et al. Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population. Skin Pharmacol Physiol 22(4):190‑9, 2009
  5. Gruber R, Elias PM, Crumrine D, Lin T-K, Brandner JM, Hachem J-P, et al. Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function. Am J Pathol 178(5):2252‑63, 2011
  6. Mao-Qiang M, Feingold KR, Jain M, Elias PM. Extracellular processing of phospholipids is required for permeability barrier homeostasis. J Lipid Res 36(9):1925‑35, 1995
  7. Ilic D, Bollinger JM, Gelb M, Mauro TM. sPLA2 and the epidermal barrier. Biochim Biophys Acta 1841(3):416‑21, 2014
  8. Elias PM. Structure and function of the stratum corneum extracellular matrix. J Invest Dermatol 132(9):2131‑3, 2012
  9. Hachem J-P, Roelandt T, Schürer N, Pu X, Fluhr J, Giddelo C, et al. Acute acidification of stratum corneum membrane domains using polyhydroxyl acids improves lipid processing and inhibits degradation of corneodesmosomes. J Invest Dermatol 130(2):500‑10, 2010
  10. Hansson L, Bäckman A, Ny A, Edlund M, Ekholm E, Ekstrand Hammarström B, et al. Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis. J Invest Dermatol 118(3):444‑9, 2002
  11. Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, et al. New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J Allergy Clin Immunol 118(1):3‑21; quiz 22‑3, 2006
  12. Hatano Y, Man M-Q, Uchida Y, Crumrine D, Scharschmidt TC, Kim EG, et al. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. J Invest Dermatol 129(7):1824‑35, 2009
  13. Choi E-H, Man M-Q, Xu P, Xin S, Liu Z, Crumrine DA, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 127(12):2847‑56, 2007
  14. Fluhr JW, Man M-Q, Hachem J-P, Crumrine D, Mauro TM, Elias PM, et al. Topical peroxisome proliferator activated receptor activators accelerate postnatal stratum corneum acidification. J Invest Dermatol 129(2):365‑74, 2009
  15. Fluhr JW, Crumrine D, Mao-Qiang M, Moskowitz DG, Elias PM, Feingold KR. Topical liver x receptor activators accelerate postnatal acidification of stratum corneum and improve function in the neonate. J Invest Dermatol 125(6):1206‑14, 2005
  16. Lee H-J, Lee NR, Kim B-K, Jung M, Kim DH, Moniaga CS, et al. Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy. Exp Dermatol 26(1):66‑72, 2017

 

About the Authors

Carine Mainzer, PhD – Scientific Support Manager, Silab

Before joining Silab in 2016, Dr Mainzer was a postdoctoral scholar in the Department of Dermatology at University of California San Francisco under the supervision of Dr. Peter Elias and Dr. Yoshikazu Uchida, where her work focused on the communication between inflammatory cells and cutaneous cells under bacterial challenges. She obtained her Ph.D. from the University of Lyon (France) in 2014 with work focused on the involvement of the Insulin-like growth factor (IGF)-1 on epidermal differentiation and aging. Dr. Carine Mainzer has been within the cosmetic industry since several years now, working notably with Johnson & Johnson Consumer France, Natura and Silab. Her current position offers her the opportunity to continue applying her scientific expertise to the research problematics of the cosmetic industry in various domain around skin.

 

Peter M Elias, MD. – Dermatology Service, Department of Veterans Affairs Medical Center and Department of Dermatology, University of California

Dr. Elias, Staff Physician, San Francisco VA Medical Center and Professor Emeritus, University of California San Francisco, is in part responsible for the present wealth of knowledge on the structure and myriad functions of mammalian stratum corneum.  His pioneering research since the 1970’s has dispelled the myth of the stratum corneum as a “dead, keratinized, basket-weave” structure, to establish the iconic “brick and mortar” model.  The stratum corneum is now viewed as a metabolically active, two-compartment composite that functions as a biosensor. The resultant “outside-in” concept of the barrier as a prime mover in the pathogenesis of cutaneous disease has also been a highlight of his work, with the paramount role of skin barrier dysfunction in disease pathogenesis now widely recognized. Over the past 40 years, his lab has been the destination for over 100 young investigators from around the world, a trend that continues to enrich the field of academic dermatology with an armamentarium of techniques and disciplines on epidermal structure and function.  Dr. Elias mentors his vast network of associates and postdoctoral fellows, past and present, several of whom have achieved leadership roles in academia and industry the world over.  His oeuvre comprises over 650 scientific publications, including several books that he has either edited or co-edited.

Naturality

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In a world becoming increasingly eco-conscious, the word naturality has become part of our regular if not daily vocabulary. But this word, that may sound trivial at first sight, harbors different meanings and applicability, depending on the individual employing it.

 

In the last few years, nature has been in the center of the conversations especially from an environmental perspective with climate change issues being a worldwide concern. In an effort to improve our impact on the planet but also on ourselves, consumers have started to shift their habits with an increasing demand for naturalness, locally sourced beauty products that are respectful of the environment and of human health.

 

This phenomenon is not just a trend, it has become a lifestyle, synonymous of healthiness, that has been observed in industrialized countries for some years now not only at the personal care level (1), but also in the food industry, textile, automotive, etc.….

Most of the established personal care companies now carry a sustainability program. To name a few: J&J with their citizenship and sustainability approach; L’Oréal with their Sharing beauty with all (SBWA) program; or Natura Brasil, founding member of the Union for Bioethical Trade (2-4). In the past years, new brands have appeared with a strong imprint in naturality, that is not only reflected in their actions and products but also in their name: Yarok, which means “green” or “pure” in Hebrew, develops organic and sustainable hair care products; Ajali, a brand from Nigeria, which name means “red earth” or “sand” in the local language, produces handmade natural cosmetics with local ingredients from West Africa and in tight partnerships with local farmers (Mintel 2018). China is also joining this movement with companies sourcing natural ingredients (Maysu) pushing for a change in consumer’s habits. According to a Mintel survey, 45% of Chinese women are planning to use in the next few years products with natural herbs or plants (1).

 

Similarly to the brands, cosmetic ingredients suppliers with a chemical, biotechnological or natural ingredients profile have joined the movement and communicate more and more about the implementation of naturality in their products. As explained recently by Monique Simmonds from the Kew Royal Botanical Gardens (5), plants have an aura that have fascinated individuals for years, especially because plants are very clever and have developed several ways to adapt and protect themselves from harmful situations, making them attractive materials for consumers.

In the quest of mastering nature and offering natural materials that would bear the strength of Mother Nature, but be safe and respectful of our planet, suppliers have to follow some specifications and be knowledgeable about local and global cosmetic regulations, which can sometimes alter the choice of the raw material. For instance, in some countries, certain plants are considered as medical drugs and thus cannot be used to develop a cosmetic ingredient. Additionally, sourcing natural resources is also subjected to local laws on biodiversity preservation (the Nagoya protocol) (6-7).

A great example for sourcing naturally-derived products is the Amazon forest that carries exotic plants with a variety of beneficial actions, but which supply needs close monitoring to avoid both plant toxicity and species disappearance. Interestingly, one approach followed more and more, and advertised by companies and raw material suppliers, is the collaboration with local populations to cultivate and/or supply local plants in a respectful way.

Lastly, another aspect associated with naturally-derived products is the variability they can present. Unlike chemically synthesized molecules, easily reproduced from one batch to another, products coming from nature evolve and change according to environmental challenges. This applies for any supplier elaborating naturally-derived raw materials and it is especially true for those developing natural active ingredients.

Mastering nature requires some tricks to guaranty the efficacy, the safety and the reproducibility of naturally-sourced ingredients. Thus, the right questions should be asked from the beginning: which plant has been selected? It is important to carefully identify the plant of interest, starting with its correct name (often Latin based). What is special about this plant? Does it bear specific features that could help with its identification and could perhaps relate to its functionality? Botanical and chemical-physical analyses can be helpful to assist answer these questions and avoid confusion or falsification. This is the case for Ophiopogon japonicus and Liriope spicata, two plants that look alike when non-flowering, but that bear a specific analytical profile. Another question to address is the origin of the plant. Where does the plant come from? How has it been sourced? Is the plant coming from a wild harvest or has it has been cultivated? And finally, is the plant available in large quantities enabling an industrial scale production? All considerations that have to be acknowledged when working with natural raw material sourcing.

 

Today, naturality is one essential criteria of a cosmetic product that is pushed by eco-conscious consumers and offered by most of the actors in our field. Mastering Nature requires rigor with a long list of requirements to be considered to deliver high-quality and effective products. As the number of naturally-derived products keeps on growing, one major challenge that remains will be to sustain constant innovation while developing naturally-based products.

 

 

References:

(1) Mintel Global Tends 2018

(2) Johnson & Johnson (2017). Citizenship & Sustainability Reporting. Retrieved from https://www.jnj.com/caring/citizenship-sustainability

(3) L’Oreal (2015): Sharing Beauty with all, the L’Oreal Sustainability Commitment. Retrieved from https://www.loreal.com/sustainability/sbwa

(4) Williams, T. (2015). Natura Cosmetics gets a sustainability makeover. Retrieved from https://www.businessforhome.org/2015/02/natura-cosmetics-gets-a-sustainability-makeover/

(5) Hollis, L. (2018). Trends in natural beauty. Retrieved from https://www.cosmeticsdesign-europe.com/Article/2018/10/10/Advances-in-Botanical-Actives-naturals-opportunity-interview-part-I

(6) Dorato, S. (2018). Chapter 1 – General concepts: current legislation on cosmetics in various countries. Analysis of Cosmetic Products (Second edition), p3-37

(7) CBD. Retrieved from https://www.cbd.int/abs/about/default.shtml/

 

Dr. Carine Mainzer joined Silab in 2016 as a Scientific Support Manager. Before joining Silab, Dr. Carine Mainzer was a postdoctoral scholar in the Department of Dermatology at University of California San Francisco under the supervision of Dr. Peter Elias and Dr. Yoshikazu Uchida, where her work focused on the communication between inflammatory cells and cutaneous cells under bacterial challenges. She obtained her Ph.D. from the University of Lyon (France) in 2014 with work focused on the involvement of the Insulin-like growth factor (IGF)-1 on epidermal differentiation and aging. Dr. Carine Mainzer has been within the cosmetic industry since several years now, working notably with Johnson & Johnson Consumer France, Natura and Silab. Her current position offers her the opportunity to continue applying her scientific expertise to the research problematics of the cosmetic industry in various domain around skin.

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