SKINPERF LWG. Skin resurfacing action AHAs Performance

SKINPERF LWG Skin resurfacing action AHAs Performance

SKINPERF LWG AHAs PERFORMANCE WITHOUT IRRITATIONS WHAT IT IS New tool for Corneotherapy, SKINPERF LWG is a green biomaterial forming a lamellar gel which behaves like an intracutaneous reservoir of AHAs. WHAT IT IS DEVELOPED TO DO SKINPERF LWG was designed to diffuse AHAs in a progressive and controlled way while avoiding inflammation. Exfoliation performance equals conventional AHAs within 2 weeks. After 4 weeks treatment, the skin is brighter, pigmentation spots, blackheads and acne scars disappear without any stinging sensation. HOW TO USE Dispersible gel to use at 2% in: Resurfacing serum Smoothing glow cream Anti blemishes treatments Acne/blackheads gel COMPOSITION Water (and) glycolic acid (and) lactic acid (and) sodium magnesium silicate (and) citric acid (and) xanthan gum. 28% AHAs (15% glycolic / 7% lactic / 6% citric acid)

LWG technology delivers a progressive and controled diffusion of AHAs into the skin. It allows working with lower % of AHAs while maintaining an exfoliating performance similar to classical AHAs treatments. EX VIVO BENEFITS Exfoliating action: +50%* versus 59%* with treatment AHAs 8% Weak inflammation: 15% versus 68%*** with treatment AHAs 8% Performance Index: 3.33 versus 0.86% with treatment AHAs 8% IN VIVO BENEFITS 100% cellular exfoliation in less than 2 weeks*** Skin velvety: +20%*** Skin bright: +31%*** Skin uniformity: +15%*** Acne scars: 8%** Pigmentation spots: 11%*** Number of blackheads: 43%*** No impact on skin ph Irritation scorage: grade 0.5/10

SKINPERF LWG IS A UNIQUE DELIVERY TECHNOLOGY OF AHAs THAT ANSWERS THE CONCEPT OF SKIN PERFECTIONISTS THE CONCEPT THE CUTANEOUS TARGET THE BIOLOGICAL ANSWER SKIN PERFECTIONISTS In the search for Perfect Skin, AHAs are still one of the mainstays. Their only problem is the fairly frequent irritation or cutaneous burns they cause. STRATUM CORNEUM AHAs weaken the cohesion of the stratum corneum to increase desquamation and in the same way accelerate cellular renewal. But if the exfoliating treatment is too aggressive, corneocytes initiate inflammatory answer. CORNEOTHERAPY OUTSIDE IN THERAPY DESCRIBES NEW MODELS OF RELEASING AN ACTIVE TO IMPROVE ITS DIFFUSION IN A PROGRESSIVE AND CONTROLLED WAY INTO THE SKIN. CORNEOTHERAPY & OUTSIDE IN THERAPY Corneotherapy is a science which was largely developed by Dr Albert Kligman. It is the link between cosmetics and dermatology and may represent the skin care concept of the future. Exfoliation techniques are of course part of this since their prime target is the stratum corneum. Kligman designed a treatment centred on renovation of the corneal layer to correct the entire skin which he called outside in therapy. OUTSIDE IN THERAPY ALSO DESCRIBES NEW MODELS OF RELEASING AN ACTIVE TO IMPROVE ITS DIFFUSION IN A PROGRESSIVE AND CONTROLLED WAY INTO THE SKIN. SKINPERF LWG WAS DEVELOPED ON THE BASIS OF THIS MODEL OF CUTANEOUS THERAPY.

SKINPERF LWG NEW AHAs OUTSIDE IN THERAPY SKINPERF LWG (Lamellar Water Gel) was designed to diffuse AHAs in a progressive and controlled way into the skin. Lamellar biomaterial AHAs This is a completely new way of releasing AHAs. Indeed, LWG technology allows working with low quantities of AHAs able to equal the performance of conventional AHAs treatment while avoiding the problems of burns and inflammation. It consists of: A biomaterial developed using green chemistry, forming a lamellar gel which behaves like an intra cutaneous reservoir of AHAs. A synergy of alpha hydroxy acids: 15% glycolic, 7% lactic and 6% citric acids adsorbed onto the lamellar biomaterial. THIS NEW SYSTEM MEANS THAT LOW CONCENTRATIONS OF AHAs CAN BE USED WHILE MAINTAINING ITS EXFOLIATING PERFORMANCE. BENEFITS OF SKINPERF LWG FOR OUTSIDE IN THERAPY? A PROGRESSIVE AND CONTROLLED DIFFUSION OF AHAs Lamellar Water Gel (LWG) technology has been compared to a conventional Carboxy Methyl Cellulose (CMC) gel. Both structures contain 28% AHAs. They were deposited on the surface of an agarose gel in which AHAs diffusion is measured thanks to infrared spectroscopy. The kinetics of AHAs diffusion show a stationary step (diffusion equilibrium) reached after: 5h 25 min for the CMC technology. 9h 12 min for the LWG technology. This means that the AHAs are released 2 times more slowly with LWG technology but also in a more progressive and continuous manner. AHAs (g%) 0,300 0,275 0,250 0,225 0,200 0,175 0,150 Skinperf LWG CMC gel WE CAN THEREFORE EXPECT 2 TYPES OF BENEFITS WITH LWG TECHNOLOGY: EXTENDED CONTACT TIME GIVING HIGH PERFORMANCE EXFOLIATION OF THE SKIN. A MORE PROGRESSIVE SUPPLY OF AHAs WHICH IS THEREFORE LESS AGGRESSIVE FOR THE SKIN. 0,125 0,100 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time (H)

EVALUATION OF AHAs PERFORMANCE THROUGH THE DEFINITION OF A PERFORMANCE INDEX AHAs are characterized by two major properties. Exfoliation Inflammation It is important to maintain a balance between both effects. Indeed, a cocktail of AHAs cannot be used for powerful exfoliation if it is going to generate severe irritation or even burns. The Performance Index (PI) defined by our laboratories is inspired by the therapeutic index previously developed by Dr Smith in 1994 (1). The PI of an AHA or combination of AHAs is the ratio of its exfoliating performance to the inflammation it generates. Performance Index PI % exfoliation % inflammatory mediator A PI GREATER THAN 1 IS CHARACTERISTIC OF A GOOD EXFOLIATION WITH A MINIMUM OF INFLAMMATION. PERFORMANCE INDEX OF SKINPERF LWG COMPARED TO CONVENTIONAL AHAs TREATMENTS The PI of a formulation containing 2% SKINPERF LWG was calculated and compared to formulations containing 8% and 15% AHAs. The exfoliating action of the three formulations was evaluated by stripping and counting scale (exfoliation) while the level of inflammation was evaluated by assaying the inflammation mediator COX2. Only SKINPERF LWG has a PI > 1, characteristic of a good exfoliation without irritation. The lack of inflammation is explained by a very low concentration of AHAs in the SKINPERF LWG formulation. Nevertheless the following studies show that even though its AHAs concentration is lower, its exfoliating properties are as effective as the 8% and 15% AHAs formulations. THE PROGRESSIVE AND CONTINUOUS DIFFUSION GENERATED BY LWG TECHNOLOGY MEANS THAT LOWER AHAs CONCENTRATIONS CAN BE USED LEADING TO LESS INFLAMMATION WHILE MAINTAINING AN EFFECTIVE LEVEL OF SKIN RENEWAL. CREAM AHAs 15 15% AHAs Performance Index 0.91 CREAM AHAs 8 8% AHAs Performance Index 0.86 CREAM SKINPERF LWG 2% 0,56% AHAs Performance Index 3.33

EX VIVO TEST EXFOLIATION PERFORMANCE OF SKINPERF LWG COMPARED TO CONVENTIONAL AHAs TREATMENTS Protocol: Human skin explants (39 year old donor). Application of preparations at D0, D1 and D2. Analysis of desquamating effectiveness at D5 by stripping and counting of scales obtained on the strip. Exfoliation performance of AHAs treatments is evaluated through the number and aspect of scales obtained by stripping after AHAs treatment. CREAM SKINPERF 2% (0.56% AHAs) CREAM AHAs 8 (8% AHAs) CREAM AHAs 15 (15% AHAs) TWO PARAMETERS ARE ANALYSED 1 The number of scales (% variation versus untreated explant). 2 The heterogeneity index of the scales: indeed, treatment which is too aggressive causes deep desquamation and eliminates a clump of epidermal cells. This phenomenon is visible on the strips with the AHAs 8 and 15 creams. The exfoliation then damages the cohesion of the skin below the stratum corneum and may be accompanied by burns. Number of scales +50%* Number of scales +59% Number of scales +75%* ONLY SKINPERF LWG PROVIDES BOTH SIGNIFICANT AND UNIFORM EXFOLIATION CHARACTERISTIC OF A GOOD DESQUAMATION, LESS AGGRESSIVE THAN THOSE OBTAINED WITH AHAs 8 AND AHAs 15 FORMULATIONS. Heterogeneity Index 487 Heterogeneity Index 956 Heterogeneity Index 1181** EX VIVO TEST EFFECT OF SKINPERF LWG ON SKIN INFLAMMATION COMPARED TO CONVENTIONAL AHAs TREATMENTS Protocol: Human skin explants (39 year old donor). Application of preparations at D0, D1 and D2 after stripping. Analysis of inflammation inducing effect by quantification of COX2 (purple pink) by immunohistochemistry. The quantification of the enzyme COX2 (green band), responsible for the production of Prostaglandin mediators, is first performed in the epidermis (see opposite pictures). An additional analysis showed that the 8% and 15% AHAs formulations also caused significant inflammation of the dermis. The data is characteristic of an aggressive action. WHILE SKINPERF LWG DOES NOT GENERATE ANY SIGNIFICANT INFLAMMATION, THE AHAs 8 AND 15 FORMULATIONS ACTIVATE A SIGNIFICANT AND HIGH INFLAMMATORY RESPONSE OF MORE THAN 60%. THESE RESULTS CORRELATE WITH THE AGGRESSIVENESS OF THEIR EXFOLIATING ACTION PREVIOUSLY OBSERVED. CREAM SKINPERF 2% (0.56% AHAs) Good epidermal cohesion. 15% inflammation CREAM AHAs 8 (8% AHAs) Damaged cohesion 68%***inflammation CREAM AHAs 15 (15% AHAs) Damaged cohesion 82%***inflammation

IN VIVO TEST EFFECT OF SKINPERF LWG ON SKIN EXFOLIATION Protocol Cream containing SKINPERF LWG at 2% Twice daily applications on the forearm for 14 days 17 volunteers aged 21 to 50. Analytical Method: On D0, skin is colored with DHA. Skin pigmentation is then measured using chromametry. Skin depigmentation is directly linked to the rate of cellular exfoliation. DUE TO ITS EXFOLIATING PERFORMANCE SKINPERF LWG LEADS TO TOTAL CELLULAR EXFOLIATION IN LESS THAN 2 WEEKS. After 3 days use, the exfoliation level obtained with SKINPERF LWG is significantly 3 TIMES HIGHER than the exfoliation obtained on untreated skin. Rate of cellular renewal (%) 120 100 80 60 40 20 0 Untreated skin Skin treated with SKINPERF LWG IN VIVO TEST EVALUATION OF THE ABSENCE OF IRRITANT EFFECTS Protocol Cream containing SKINPERF LWG at 2% Twice daily applications for 28 days on the whole face. 24 volunteers aged 34 to 64. Sensory evaluation by the volunteers on a structured scale of 1 to 10. The cumulative evaluation of 3 irritation parameters reached a maximum score of 0.5 points on a scale of 0 to 10. USE OF SKINPERF LWG TWICE A DAY DOES NOT LEAD TO REDNESS OR FEELINGS OF HEATING OR STINGING WHICH ARE USUALLY NOTED WITH CLASSICAL AHAs TREATMENTS. A complementary study has demonstrated that by opposition to formulation with 8 or 15% AHAs, SKINPERF LWG does not impact at all skin ph demonstrating the benefits of the LWG technology for the natural physiological barrier of the skin. Scorage of irratation parameters 10 9 8 7 6 5 4 3 2 1 0 Cumulative evaluation of irritation parameters within the first week of treatment Redness Heating Stinging 0 1 2 3 4 5 6 7 Treatment duration (in day)

IN VIVO TEST PERFECTING EFFECT OF SKINPERF LWG ON SKIN BRIGHT & IMPERFECTIONS Protocol Cream containing SKINPERF LWG at 2% Twice daily applications for 28 days on the whole face. 24 volunteers aged 34 to 64. Analytical Method Scarring blemishes: clinician scorage on a structured scale of 0 to 10. Blackheads: counted by a clinician Skin bright: sensory evaluation by a jury of 5 persons on a nonstructured scale of 0 to 15. 140 120 Average variation Maximal variation 131% SKINPERF LWG IMPROVES SKIN COMPLEXION WITHIN 14 DAYS The action of SKINPERF LWG on cellular renewal leads to a visible improvement in skin quality. More velvety skin grain: +20%*** on average More luminous skin tone: +31%*** on average More uniform skin tone: +15%*** on average SKINPERF LWG provides a resurfacing effect on the skin within 2 weeks. % variation versus T0 100 80 60 40 20 0 20 %*** 59% Skin velvety 31%*** 88% Skin bright 15%*** Skin uniformity SKINPERF LWG DIMINISHES BLEMISHES AFTER 28 DAYS The action of SKINPERF LWG on cellular renewal is also accompanied by a significant reduction in cutaneous blemishes after 4 weeks treatment. Acne scars: 8%** on average Pigmentation spots: 11%*** on average Number of blackheads: 43%*** on average SKINPERF LWG removes cutaneous blemishes and refines skin grain. % variation versus T0 0-10 -20-30 -40-50 -60-70 -80-90 Intensity of acne scars -8%** -25% Intensity of pigmentary spots -11%*** Average variation -33% Maximal variation Number of blackheads -43*** -80% IN VIVO TEST VISUALISATION OF THE EFFECT OF SKINPERF LWG ON ACNE SCARS DO D14 D28

FORMULATION GUIDELINE HD PERFECT CREAM This cream has been formulated with SKINPERF LWG and AROLEAT SAMPHIRA: retinoid like vegetable oil that smoothens skin relief and treats crow s feet wrinkles. Phase Raw material / Trade name INCI name % NIKKOMULESE LC (1) Behenyl Alcohol & Stearyl Alcohol & PEG 20 Phytosterol & Cetyl Alcohol & Phytosterols & Glyceryl Stearate & Hydrogenated Lecithin & Caprylic/Capric Triglyceride & Tocopherol 5 CRODAMOL GTCC / MIGLYOL 812 / WAGLINOL (2) Caprylic/Capric Triglyceride 2 SILICONE (DIMETHICONE (100CS)) (3) Dimethicone 0,5 A PHENOXYETHANOL (4) Phenoxyethanol 0,8 ARLAMOL HD (5) Isohexadecane 3 LANOL 99 (6) Isononyl Isononanoate 4 LANETTE O (2) Cetearyl Alcohol 2 ALCOOL CETYLIQUE / LANETTE 16 (2) Cetyl Alcohol 1 B AROLEAT SAMPHIRA (7) Caprylic/Capric Triglyceride & Hydrogenated Vegetable Oil & Crithmum Maritimum & Benzyl Alcohol & Limonene 1 C DEMINERALISED WATER Aqua 64.918 ELESTAB CPN (2) Chlorphenesin 0.27 D SEPIPLUS 400 (6) Polyacrylate 13 & Polyisobutene & Polysorbate 20 & Sorbitan Isostearate & Aqua 0.15 E DEMINERALISED WATER Aqua 10 SKINPERF LWG (7) Aqua & Glycolic Acid & Lactic Acid & Sodium Magnesium Silicate & Citric Acid & Xanthan Gum 2 F PARFUM FLEUR D EAU R21886 (8) Parfum 0,1 G SOUDE (SOLUTION 5 N) (9) Aqua & Sodium Hydroxide 0,262 H STRUCTURE XL STARCH (5) Hydroxypropyl Starch Phosphate & Aqua 3 (1) IMCD, (2) AMI, (3) Quimdis, (4) Laserson, (5) Quimasso, (6) Seppic, (7) CODIF Recherche et Nature, (8) Parfex, (9) Brenntag Protocol : Warm A up to 75 C. Just before the emulsion add B in the oily phase (A). Warm C up to 75 C. Disperse Sepiplus 400 under mulsifier 1500 rpm for 10 min. Realize the emulsion by slowly introducing the oily phase (A+B) in the aqueous phase (C+D) under emulsifier 2500 rpm for 10 minutes. Cool down to 35 C under agitation. Add the pre mix E. Add F and G. Add the Structure XL Starch under emulsifier 2500 rpm for 15 minutes.

BIBLIOGRAPHIC REFERENCES (1) Smith WP; Hydroxy acids and skin aging. Cosmetic & Toiletries 109 (9) 41 44, 46 48 (1994)

SKINPERF LWG: RESURFACING ACTION, AHAS PERFORMANCE COSMETIC ACTIVITY Exfoliating action: +50%* versus 59%* with treatment AHAs 8% Weak inflammation: 15% versus 68%*** with treatment AHAs 8% Performance Index: 3.33 versus 0.86% with treatment AHAs 8% IN VIVO BENEFITS 100% cellular exfoliation in less than 2 weeks*** Skin velvety: +20%*** Skin bright: +31%*** Skin uniformity: +15%*** Acne scars: 8%** Pigmentation spots: 11%*** Number of blackheads: 43%*** No impact on skin ph Irritation scorage: grade 0.5/10 INCI NAME: Water (and) glycolic acid (and) lactic acid (and) sodium magnesium (and) citric acid (and) xanthan gum. RECOMMENDED % OF USE: 2% CHARACTERISTICS: dispersible gel www.codif recherche et nature.com RPDOC142GB