"CODIF": A Revolutionary Strategy Against Stains

As anti-pollution sentiment continues to grow and skin health remains a global concern, CODIF laboratories have discovered a revolutionary molecule that helps treat skin pigmentation spots caused by environmental pollution within 2 weeks, characterized by a unique structure and a configuration that interacts with pigmentary synapses. One quarter of French consumers say they are interested in soaps or bath/shower gels that can protect their skin from environmental pollution. In China, 41% of people aged 20-49 are concerned about environmental pollution. This situation directly influences the purchasing behavior of 52% of consumers in the stated age group who prefer products that protect their skin. In the United Kingdom, one third of women view the environment as a factor affecting their hair. Anti-pollution claims are popular not only in Asia but worldwide [1]. Among products marketed with anti-pollution claims in 2015, 3% were for skincare, 1.2% for makeup, and 0.9% for hair products [2]. Recent studies conducted by leading brands have demonstrated how environmental pollution accelerates skin aging, particularly in sensitive skin. Recently, a clear connection has been observed between air pollution and the formation of skin pigmentation spots.

CODIF began work in 2014 on diesel vehicle emissions (gases and fine particles) on human skin using the original 3D model presented at IFSCC 2014 [3]. This initial study emphasized a direct link between exposure to environmental pollution and the activation of inflammatory response.

Aware that inflammation is associated with many skin disorders, including melanogenesis activation, we formulated the hypothesis of the connection between environmental pollution and the formation of pigmentation spots. This has been confirmed by two important recent studies. In the first study, conducted between two groups of volunteers living in Germany and China [4], an increase in spots on the cheeks of Chinese volunteers, who were exposed to more environmental pollution than German volunteers, was observed. In the second study, it was observed that increased soot and dust particles from traffic caused 20% more pigmentation spots on the forehead and cheeks [5]. Based on these recent studies, it appears that treating inflammation immediately is a solution in treating skin pigmentation spots caused by environmental pollution. However, CODIF laboratories have discovered a molecule that can interact with pigmentary synapses to control melanin synthesis and migration and treat inflammation.

Figure 1: Schematic representation of pigmentary synapse formation between melanocytes and keratinocytes; ExoPolysaccharide EPS White interaction in this recognition.

The "pigmentary synapse" is a term used by renowned experts in skin pigmentation [6]. It describes the area where a melanocyte comes into contact with a keratinocyte to transfer melanin. This is made possible through surface receptors present in both cells that recognize each other and thus provide the connection between melanocytes and keratinocytes (Figure 1). The receptors involved in pigmentary synapse formation belong to the lectin family. Essentially they recognize sugar residues, which explains why CODIF began researching marine sugars, specifically known as ExoPolySaccharides (ExoPolySaccharides), through its collaborative research program. The research program called Polymer covers a 4-year study supported by French authorities. It brings together a university laboratory, 3 private companies and a technology transfer center. All of them are experts in skin biology and marine biotechnology.

The aim of this program is to develop the glyco-cosmetics of the future through the discovery of new sugar polymers and, primarily, marine exopolysaccharides. These molecules are secreted by microorganisms to interact with their environment (protection, binding, nutrient supply, ...).

Each organism produces its own special exopolysaccharides with a unique sugar structure and configuration. For this reason, each EPS is different from the others. However, one of them, identified by CODIF, represents a previously undescribed structure. It is a sugar polymer prepared with two hydrophobic amino acids, alanine and serine (galacturonic acid, galactose, N-acetyl-glucosamine) [7]. Further research emphasizes the important role of both amino acids. They trigger the curling of the molecule under its vesicular shape, which will facilitate its penetration and interaction in the formation of pigmentary synapses. (Figure 2).   This revolutionary exopolysaccharide reduces recognition between keratinocyte and melanocyte receptors by up to 35% by interacting with the melanocyte receptor. This interaction in pigmentary synapse formation is combined with a reduction in melanocyte dendriticity (Figure 3). Both actions on synapses and dendrites partially explain the high spot-reducing effects obtained with this exopolysaccharide. Figure 3: Examination of brown dendritic melanocytes in the basal layer of melanized human epidermis exposed to environmental pollution for 2 weeks, 30 minutes per day (3A). Under the same conditions, with the addition of 1% exopolysaccharide to local application (3B), the dendriticity of melanocytes has visibly decreased and the epidermis appears brighter. Furthermore, when melanized human epidermis exposed to environmental pollution (car exhaust, 30 minutes per day for 2 weeks) was tested, the exopolysaccharide provided 45% protection against inflammation and 71% protection against melanin synthesis (Figure 4). It is also effective against UV radiation, the primary cause of skin pigmentation: it provides 39% protection against UV-induced inflammation and 81% protection against melanogenesis.

Figure 4: Visualization of melanin synthesis in melanized human epidermis exposed to environmental pollution for 9 days, 1 hour per day, (4A) without and (4B) with 1% local exopolysaccharide application.

At the conclusion of these in-vitro studies, the new exopolysaccharide appears to be a molecule that provides global spot-reducing strategies for all skin types, including those with sensitive skin and exposed to urban harmful effects. This was confirmed through in vivo study. The spot-reducing efficacy of the exopolysaccharide was tested on volunteers living in Bangkok, thus accumulating both factors involved in spot formation on the cheeks: sun and urbanization. Through application twice daily, after 2 weeks (formulated at 1% exopolysaccharide), spots on the cheeks decreased on average by 6%, with a maximum of 38% reduction (Figure 5). This effect continued to strengthen as long as volunteers continued to use the product: after 1 month, average reduction of 13%* with a maximum of 57%; after 2 months, average reduction of 20%* with a maximum of 60%; after 3 months, average reduction of 17%* with a maximum of 67% (*p<0.05 Student's test). In addition to these remarkable results, 96% of volunteers observed a reduction in the number of spots after 2 months of use. 92% reported that their pigmentation was more even and changed with each application. The structure and configuration of this unique exopolysaccharide has completely changed the spot-reducing strategy. The vesicular shape protects skin from UV-induced inflammation and pollution while providing interaction with pigmentary synapses for a visible and marked reduction in pigmentation spots. Gabrielle Moro / Marketing Director - CODIF Technologie Naturelle Romuald Vallée / Scientific and Industrial Director - CODIF Technologie Naturelle Ümit Erdem Işık / Business Development Manager - Chemical Engineer - Arerko Kimya Sanayi ve Ticaret A.Ş. Figure 5: Visualization of pigmented spots on the volunteer's cheek before treatment (5A); after 2 weeks (5B), 1 month (5C), 2 months (5D) and 3 months (5E).

Bibliographic References

[1] Market potential growing for anti-pollution products. Andrew McDougall. Cosmetic design, December 2nd, 2015.

[2] Les allégations anti-pollution dans les capillaires. L'Observatoire des cosmétiques. July 2015.

[3] Pentecouteau L, Gasparotto E, Vallee R, Morvan PY. Evaluation of the air pollution effects on human skin using an original 3D model. Poster IFSCC 2014, Paris.

[4] Krutmann J, Liu W, Li L, Pan X, Crawford M, Sore G, Seite S. Pollution and skin: From epidemiological and mechanistic studies to clinical implications. Journal of Dermatological Science 76 (2014) 163–168.

[5] Vierkotter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Kramer U, Krutmann J. Airborne particle exposure and extrinsic skin aging. J Invest Dermatol. 2010 Dec;130(12):2719-26.

[6] Yamaguchi Y, Hearing V.J. Physiological factors that regulate skin pigmentation. Biofactors. 2009. 35(2):193-199.

[7] Drouillard S, Jeacomine I, Buon L, Boisset C, Courtois A, Thollas B, Morvan PY, Vallee R and Helbert W. Structure of an amino acid decorated exopolysaccharide secreted by a Vibrio alginolyticus strain. Marine drugs, 13, 6723-6739, 2015.