e n ta d i n e Photoprotection Anti-photoaging the most natural way to reinforce skin natural defenses against outdoor and indoor radiations

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eno p r e se rvativ e n ta d i n e Photoprotection Anti-photoaging the most natural way to reinforce skin natural defenses against outdoor and indoor radiations Anti-oxidation Anti-inflammation Anti-immunosuppression Protection against sun and domestic radiations i v e ac t n at u r a l c h i na compliant EXSYMOL MONACO

entadine Sun radiations vs. skin natural defenses Light radiation and skin premature aging Luminous radiations: environmental and domestic lights, are composed of different wavelengths, from UV to IR through visible lights. All luminous radiations participate to skin premature aging with more or less skin depth and damages. UV are the most noxious sunrays that can strongly affect skin and cause major damages and premature aging. Among UV, UV-B and UV-A have been at the center of attention since science identified their noxious effects. Sun radiations (UV, IR, visible...) UV-B UV-A UV, skin s archenemies UV have direct and indirect damaging impacts: 1. UV radiations can directly affect DNA and cause mutations. These mutations may lead to three different outcomes: reparation if the damage is low, cell death if the damage is beyond repair, skin cancer if key genes were mutated. 2. UV generate free radicals, especially (reactive oxygen species) that will in turn affect: DNA, skin proteins (enzymes and strutural proteins), skin cell metabolisms. UV + Sunburn cell condensed nucleus (apoptosis) Skin defenses against UV Skin developed several natural protections against UV among which urocanic acid and melanin. Urocanic acid barrier function defense Urocanic acid (UCA) is the 2 nd most common skin natural defense system: chromophore, and absorbs UV-B. It is mainly located in the stratum corneum. Melanin keratinocytes defense Melanin is the most common mechanism of defense against UV and strongly absorbs UV. It is mainly located within living cells of the epidermis. Melanin HN N CO Trans-UCA HN production DNA mutations Inflammation N CO Cis-UCA Immunosuppression Overwhelmed skin defenses Skin natural protections against UV are not foolproof. Radiation overexposure degrades the protective potential of these natural defenses. Urocanic acid UCA isomerization generates and inflammation. In addition cis-uca induces skin immunosuppression as galectin-7 is overexpressed. Melanin While absorbing UV, melanin generate. Intense and recurrent exposure to luminous radiations leads to skin premature aging Intensive sun radiation exposure Skin defenses degradation Sun burning Instant visible degradations Reccurent light radiations exposure Premature skin aging Photoaging

entadine Cosmetic characteristics «To reduce sun-induced skin damages by boosting skin natural defenses, and to prevent both sunburn consequences and skin premature aging «Cosmetic applications Sun protection Anti-photoaging Anti-inflammation Hydration and firming Photo-induced spots prevention Beauty promises UV noxious effects negation Soothing effect Skin dryness prevention Even complexion Anti-wrinkles Atopic skin prevention Cosmetic concepts UV protection by absorbance: reinforce skin natural defense Anti-photoaging: - avoids consequences of immunosuppression - avoids toxic forms accumulation Anti-photoimmunosuppression: - fights sun-induced immunosuppression - prevents galectin-7 overexpression Prevents atopic skin sensitization Long lasting UV absorbance: self recycling active ingredient Metabolic targets Anti-oxidant properties Limits the isomerization of trans-uca into the noxious and immunosuppressive cis form Prevents dermic matrix degradation: MMP-1 inactivation DNA protection Prevents sunburn cells formation Limits inflammation, inhibiting of IL-8 and TNF-a expression Limits immunosuppression, inhibiting galectin-7 expression

EntadINE Sunburn prevention Skin defenses degradation DNA and metabolic damages Inflammation + Immunosuppression Instant visible degradations Sun burning UV Cell and metabolic degradations induced by sun overexposure lead to visible skin damages such as: edema, dryness, sensitivity and redness, mainly due to UV-B rapid effects. Optimized skin cell survival DNA damages Barrier function degradation Inflammation Immunosuppression Among the most noxious effects of sun radiations over cells are DNA damages (CPD) that may lead to cell apoptosis. These dying cells are characterized by a dense nucleus and described as sunburn cells. Dna protection Anti-cell s death (Sunburn cells) CPD staining UV-B (300 mj/cm 2 ) 8% 2.5% prevents CPD formation by 92%, therefore prevents DNA damages induced by UV-B direct absorbance or. (Evaluation model: RHE) protects skin against sun radiations-induced -92% 9% cell damages and metabolic disorders, that induce cell death and generate inflammation and immunosuppression. Number of sunburn cells Solar irradiation (40 J/cm 2 ) -91% 2.5% prevents sunburn cells formation by 91%, therefore protects your skin under sun irradiation (UV, IR, VIS) (Evaluation model: skin explant) Prevention of sunburn noxious and visible effects Immunosuppression and inflammation are generated by mediators following sun overexposure. Both mechanisms induce visible consequences: dryness and redness. Anti-skin sensitivity and redness Prevents inflammation Anti-skin dehydration Prevents Barrier Function degradation IL-8 released UV-B (300 mj/cm 2 ) 19% -81% 2.5% prevents IL-8 synthesis by 81%, as damages are limited. (Evaluation model: RHE) prevents the synthesis of specific mediators induced by sunburn situations and prevents skin damages. Galectin-7 released UV-B (300 mj/cm 2 ) 28% -72% 2.5% prevents galectin-7 expression by 72%, therefore protects barrier function (Evaluation model: RHE) 's benefits against sun burning: Extends skin natural defenses efficacy for delayed erythema Limits immunosuppression and skin dryness Prevents inflammation, redness and sensitivity Limits sunburn visible effects consequences

EntadINE Anti-photoaging Irritated and dry skin Dull complexion Skin structural collapse Skin premature aging Photoaging UV Over a life time, recurrent exposure to luminous radiations leads to an accumulation of inflammation and immunosuppression. These will induce deep skin disorders and premature aging. Protection against environmental radiations DNA mutation Disrupted barrier function Immunosuppression Inflammation Wrinkles, age spots Loss of elasticity Life time sun exposure is known to induce skin premature aging, slowly but globaly disorganizing skin metabolisms and structure. EPIDERMAL HOMEOSTASIS protection of genetic capital DNA protection Anti-skin collapse Anti-inflammatory effect Control Irradiated Gal-7 expression Solar irradiation (40 J/cm 2 ) 2% -98% CPD staining Solar irradiation (40 J/cm 2 ) 38% -62% TNF-a released UV-B (300 mj/cm 2 ) 72% -28% + Entadine (2.5%) 2.5% decreases galectin-7 expression by 98%, therefore ensuring skin homeostasis (Evaluation model: skin explant) 2.5% prevents DNA damages by 62%, therefore preventing metabolic disorders (Evaluation model: skin explant) 1.5% prevents TNF-a release by 28%, therefore preventing collagen synthesis inhibition (Evaluation model: HRE) protects skin barrier function, prevents DNA damages, skin collapse, and therefore limits sun-induced photoaging. Protection against domestic radiations Artificial lights and multimedia electromagnetic radiations, known as the feared blue light are representative of domestic light pollution. It was reported to cause skin hyperpigmentation, to delay skin barrier recovery and to produce leading to an overexpression of MMP-1. Collagen matrix protection prevents artificial radiations to slowly and deeply deconstruct skin structure and organization. MMP-1 released (% vs domestic light) Domestic light (30J/cm 2 ) 26% -74% 0.025% prevents MMP-1 activity by -74%, therefore preventing collagen degradation (Evaluation model: fibroblasts) 's benefits against photoaging: Protects against environmental (sun) and domestic (artificial) radiations Prevents loss of immunity Prevents metabolic disorders, source of dull complexion and age spots Limits inflammation participating to skin structural collapse Prevents premature aging

entadine Mechanism of action: Global natural luminous radiations protector Identified and quantified active molecules is obtained by a patented extraction method from the seeds of Entada phaseoloides. This innovative extraction method relies on the self activation of endogenous enzymes to induce specific hydrolysis. Entada phaseoloides is a large vine climbing into tropical and coastal forests of the intertropical zones. Its seeds have been used as traditional medecine to treat different skin deseases. Anti-inflammatory and anti-oxidant activities are also reported in the litterature. S O N H Entadamide A Standardized content 0.25% Limits urocanic acid isomerization Prevents inflammation and immunosuppression Photoprotector HO HO O O O Phaseoloidin Standardized content > 3% Multi-potent anti-oxidant Photoprotector Natural skin defense booster Complements urocanic acid isomerisation activity is rich in Entadamide A that limits UVinduced trans-uca isomerization into noxious cis-uca. Trans-UCA Cis-UCA No irradiation + UV-B 37% 3 % 56% +51% Complements melanin activity is rich in anti-oxidants such as phaseoloidin. As a result, has chromophore properties and can efficiently support melanin scavenging activity. Overwhelmed melanin by UV evaluation can generate UV-B Purified synthetic melanin suspension Long lasting benefits is a natural source of Entadamide A, a completely safe natural UV absorber. By absorbing UV, it has the ability to be recycled into and from Solexyl, one of our latest released biomimetic active ingredient for long lasting benefits. Entadamide A UV SOLEXYL Anti-oxidant properties As expected, is endowed with significant anti-oxidant activities, mainly due to phaseoloidin, a major constituent of the extract. The activity is confirmed thanks to the DPPH and ABTS usual procedures. entadine Vit. C (1%) DPPH IC 50 = 0.84 IC 50 = 0.42 ABTS IC 50 = 0.074 IC 50 = 0.43

eno p r e se rvativ entadine INCI NAME Entada phaseoloides bark/seed extract ANALYTICAL COMPOSITION Entada phaseoloides bark/seed extract 13% including Entadamide A 0.25% Phaseoloidin >3% Propanediol 50% Water (sq) PHYSICO-CHEMICAL CHARACTERISTICS Limpid to slightly opalescent liquid, orange to red Miscible with water and glycols ph 4.5 PRESERVATIVES No preservative system TOLERANCE AND TOXICITY STUDIES Entadine does not show any toxicity, and tolerance studies show that it is perfectly tolerated FORMULATION Advised doses: 1.5 to 4% Availabilities Entadine is available in 5kg and 30kg drums i v e ac t n at u r a l c h i na compliant

EXSYMOL S.A.M. 4 avenue Albert II MC 98000 MONACO Tél: +377 92 05 66 77 exsymol@exsymol.com EXSYMOL MONACO P8_1545GB1806E