MATRIGENICS.14 G. Re-activates 14 genes to recover the Triangle of Beauty in 14 days only

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1 MATRIGENICS.14 G Re-activates 14 genes to recover the Triangle of Beauty in 14 days only

2 Matrigenics.14 G: extract of fertile bases of Undaria Matrigenics.14 is a concentrate obtained from the fertile bases of the alga Undaria pinnatifida. This fertile bases, also known has Mekabu contain the spores that are responsible for the species reproduction and are considered as a life concentrate, having precious rejuvenation virtues. Rich in Wakamic ester, a sulfated galactofucane this life concentrate reactivates 14 genes implicated in the redensification of the extra-cellular matrix of the dermis for a rejuvenating effect. Wakamic ester

3 Undaria, Spores and Fertile Bases... Undaria pinnatifida, from the Latin "unda", a wave, and pinnatififa, feather-shaped, is also commonly known as Wakame in Japan. It is a brown macro-algae attaining up to 2m. When mature, the edges of the stipe become broader and wavy. These new tissues, known as fertile bases or even Mekabu, contain the reproductive cells of the alage. The Undaria reproductive cells are released into the environment before the adult plant dies off at the end of the summer. Each reproductive cell will then germinate into a new alga, ensuring the reproduction and the perennity of the species. Fertile bases, Mekabu are much appreciated in Japanese food. Fertile base, full of reproductive cells

4 From Undaria to Matrigenics.14 G Matrigenics.14 G is an aqueous extract of fertile bases of Undaria pinnatifida. In collaboration with local partners, Codif R&N cultivates the alga in Brittany (France) in a protected area of the Rance. Culture of the alga: Initially collected in the sea Placed in hatcheries Germination, formation of small alga Transfer to the open sea for growth on a longline system Harvest: Adult algae are collected 1 year after Fertile bases are isolated and used to produce Matrigenics.14 G Other parts of the algae are used for food applications Cultivation site Hatcheries MATRIGENICS.14 G is a natural and ecofriendly active ingredient. Longline system

5 What contributes to the face ageing? In youth the cheekbones are high and well defined, and the jaw line is also well defined, yet soft. This is called The Triangle of Beauty. With ageing appear wrinkles, but also a descent of the brow, a loss of elasticity of the skin (jowls develop), a drooping of the lip edges The Triangle of Beauty is lost which is less attractive and make look permanently unhappy and sad.

6 What is the main concern of women in terms of ageing? A study realized by Arcane Research (French Poll) on 4400 women in 2011 reveals that: 29% of women are concerned by the wrinkles between the eyebrows 32% of women are concerned by the nasal furrows wrinkles 37% of women are concerned by the lines and furrows around the mouth

7 What is the role of the ExtraCellular Matrix in the formation of lines, furrows and wrinkles? DÉRÈGLEMENT DES ADIPOCYTES ET DES FIBROBLASTES : UNE ORIGINE GÉNÉTIQUE The Extracellular Matrix (ECM) is the largest component of normal skin and gives the skin its unique properties of elasticity, tensile strength and compressibility. These properties are due to the combination of two main classes of molecules, which are secreted by fibroblasts and epidermal cells: structural proteins: collagens, elastin proteoglycans: like hyaluronic acid, which are large and highly hydrated. These molecules are assembled and organized in a specific way into the Extracellular Matrix in order to ensure the structural integrity of the skin

8 What is the role of the ExtraCellular Matrix in the formation of lines, furrows and wrinkles? DÉRÈGLEMENT DES ADIPOCYTES ET DES FIBROBLASTES : UNE ORIGINE GÉNÉTIQUE The apparition of lines, furrows and wrinkles is due to a disorganisation of the ECM directly linked to the quantity and the quality of its main components: collagen, elastin and proteoglycan. The synthesis of these molecules is regulated by our genes. A gene is a code which orders the manufacture of a specific protein. With age, genes are less active and the quantity and quality of protein synthesised is lower. The solution: awaking the activity of genes responsible for the synthesis of the components of the ECM.

9 Action mechanism of Matrigenics.14 G Goal: Re-building the Extracellular Matrix (ECM) Action mechanism: Re-activation of 14 genes implicated in the synthesis, the maturation, the assembling and the anchoring of collagen, elastin and hyaluronic acid Forehead wrinkles Results: Decrease of forehead wrinkles Decrease of nasal furrows Decrease of lines around the lips Nasal furrows Mouth wrinkles

10 In-Vitro Test: 2% Matrigenics.14 G stimulates genes implicated in collagen synthesis, maturation and anchoring. (2% Matrigenics.14 G, Human Dermal Fibroblasts, Minichips) Genes involved in the synthesis of collagen fibres Fibroblast +15% COL I (Collagen I) + 20% COL IV (Collagen IV) +37% COL VIII (Collagen VIII) Genes involved in the maturation of collagen fibres +61% P4HA1 (Proline Hydrolase 1) +30% P4HA2 (Proline Hydrolase 2) Genes involved in the assembling of collagen fibres +50% LOX (Lysyl oxydase) +43% LOXL2 (Lysyl oxydase L2) Genes involved in the anchoring of collagen fibres SYNTHESIS & MATURATION ASSEMBLING ANCHORING COLs P4HA1 P4HA2 LOX LOXL2 LUMICANE DECORINE +72% LUMICANE +23% DECORINE Dermis Epidermis

11 In-Vitro Test : Illustration of the Collagen I booster effect of 2% Matrigenics.14 G Method: Human Dermal Fibroblasts incubated with 2% Matrigenics.14 G for 48 hours. Observation of collagen fibres using immunolabelling Without Matrigenics.14 G Low level of intracellular labelling, collagen fibres are immature and not assembled With Matrigenics.14 G High level of extracellular labelling, collagen fibres are mature and assembled

12 In-Vitro Test: 2% Matrigenics.14 G stimulates genes implicated in elastin synthesis, maturation and anchoring. (2% Matrigenics.14 G, Human Dermal Fibroblasts, Minichips) Fibroblast Genes involved in the synthesis of elastin fibres + 21% ELAST (Elastin) Genes involved in the maturation of elastin fibres +36% FBN1 (Fibrilline 1) Genes involved in the assembling of elastin fibres +50% LOX (Lysyl oxydase) +43% LOXL2 (Lysyl oxydase L2) SYNTHESIS & MATURATION ASSEMBLING ELAST FBN1 LOX LOXL2 Genes involved in the strengthening and protection of elastin fibres +18% TIMP2 (Tissue Inhibitor MetalloProteinase 2) Dermis Epidermis

13 In-Vitro Test : Illustration of the Elastin booster effect of 2% Matrigenics.14 G Method: Human Dermal Fibroblasts incubated with 2% Matrigenics.14 G for 48 hours. Observation of (Tropo)Elastin fibres using immunolabelling Without Matrigenics.14 G Low level of intracellular labelling, elastin fibres are immature and not assembled With Matrigenics.14 G High level of extracellular labelling, elastin fibres are mature and assembled

14 In-Vitro Test: 2% Matrigenics.14 G stimulates gene implicated in Hyaluronic acid synthesis and fibroblast mobility (2% Matrigenics.14 G, Human Dermal Fibroblasts, Minichips) Genes implicated in the synthesis of Hyaluronic acid +68% HAS (Hyaluronic Acid Synthase) Genes implicated in the mobility of fibroblasts +31% CD44 (Cluster of Differentiation 44) Hyaluronic acid CD44 Fibroblast HAS Glucuronic acid + N- acetyl-glucosamin CD44 is a transmembraneous proteins which helps to maintain a balance between Hyaluronic acid synthesis and degradation into the matrix. In addition, via CD44, fibroblasts binds hyaluronic acid to migrate into the dermis, thus ensuring an homogenous repartition of cells and fibres in this layer. Dermis Epidermis

15 Conclusion on In-Vitro tests Matrigenics.14 G re-activates 14 genes Genes linked to collagen Genes linked to elastin COL1 ELAST COL2 COL8 P4HA1 P4HA2 LUM DCN Genes linked to collagen & elastin FBN1 TIMP2 Genes linked to hyaluronic acid HS CD44 to restructure the ExtraCellular Matrix Dermis Epidermis LOX LOXL2

16 Clinical studies PROTOCOLE Application: Cream containing 2% Matrigenics.14 G applied twice daily for 14 and 28 days versus placebo 2 groups of 22 volunteers Age: years Analysis: At T0, T14 days, T28 days Analysis of forehead wrinkles, nasal furrows mouth wrinkles Method: innovative analytic method of fringe projection in 3D.

17 In-Vivo test: effect on wrinkles and lines of the forehead 2% Matrigenics.14.G Matrigenics.14 G sigificantly decreases the lines and wrinkles of the forehead after 14 days of treatment. Average and significant decreases : -23.8%* of the volume of wrinkles -14.4%* of the area of wrinkles A prolongation of the treatment to 28 days does not induce a siginificant variation of volume and area of wrinkles, compared to D14. Average variation versus placebo (in %) Volume of wrinkles -23,8%* Area of Wrinkle -14,4%* *p<0.05 Student test

18 In-Vivo test: effect on wrinkles and lines of the forehead 2% Matrigenics.14.G Visible effect after 14 days of treatment Before treatment After 14 days treatment

19 In-Vivo test: effect on nasal furrows and mouth wrinkles 2% Matrigenics.14.G Matrigenics.14 G decreases nasal furrows and mouth wrinklesafter 14 days of treatment. Results are improved by prolonging the treatment to 28 days: Nasal furrows -8% of the volume -9% of the area Mouth wrinkles -18% of the volume -16% of the area Average variation versus placebo (in %) Nasal furrows Mouth wrinkles Volume Area Volume Area -2% -3% -4% -6% -8% -9% -16% -18% 14 days 28 days

20 In-Vivo test: 2% Matrigenics.14.G Visualisation of the anti-wrinkle effect on the nasal furrows and mouth wrinkle Visible effect after 14 days of treatment Before treatment After 14 days of treatment Nasal furrows and mouth wrinkles are visibly reduced

21 In-Vivo test: 2% Matrigenics.14.G Visualisation of the global anti-aging effect Both depth and length of nasal furrows are visibly reduced Before After Before After The forehead is smoother and the negative expression of the mouth is soften

22 Conclusion on Matrigenics.14 G Concentrate of fertile bases of the alga Undaria pinnatifida Rich in Wakamic ester Cosmetic Effects Re-activation of 14 genes implicated in: - collagen synthesis and anchoring - elastin synthesis and anchoring - hyaluronic acid synthesis and fibroblasts mobility Clinical results after 14 days only on: - volume and area of the wrinkles between the eyebrows - volume and area of the nasal furrows - volume and area of the mouth wrinkles Fights against the inversion of the Triangle of Beauty INCI Name (compliant with Chinese regulation) Glycerin (and) Water (and) Undaria pinnatifida extract Recommended use: 2%

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