FR2897776A1 - Cosmetic composition, useful to e.g. to prevent and/or reduce skin thinning, wrinkles, lines and to stimulate cell proliferative activity of skin comprises hyaluronic acid, a protein extract of soya and an amine compound - Google Patents

Abstract

Cosmetic composition comprises: hyaluronic acid or its salts; a protein extract of soya; and an amine compound, in a medium. Cosmetic composition comprises: hyaluronic acid or its salts; a protein extract of soya; and an amine compound of (R1)(Y1=)C-N(R3)-CH(R2)-C(=O)-NH-C-C(=O)-X, in a medium. Y1 : O; R1, R2 : linear optionally saturated 1-6C, preferably 1-2C hydrocarbon or 3-6C, preferably 3-4C branched hydrocarbon; R3 : phenyl (optionally substituted by 1-3C hydrocarbon or F); X : OH (preferred) or OR4; and R4 : linear optionally saturated 1-6C hydrocarbon or 3-6C branched hydrocarbon.

Description

The present invention relates to a cosmetic composition containing

  in particular at least: - hyaluronic acid or one of its salts; - an extract of soy protein; and a compound of formula (I) as defined below, called especially pseudodipeptide in the rest of the description.

  In particular, the pseudodipeptide consists of {2- [acetyl- (3-trifluoromethylphenyl) -amino] -3-methyl-butyrylamino} acetic acid, otherwise known as N- [N-acetyl, N '- (3-trifluoromethyl) ) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, or an ester thereof with a C 1 -C 6 alcohol.

  It also relates to the use of these three active agents, as a combination intended to maintain and / or stimulate the proliferative activity of the cutaneous cells diminished with age, as well as on a cosmetic process intended to prevent and / or reduce the signs of the skin. cutaneous aging using said composition.

  Women, even men, tend to want to look young for as long as possible and therefore seek to fade the marks of aging skin, which result in particular in a loss of firmness and / or elasticity and / or tonicity and / or suppleness of the skin and by the formation of wrinkles and fine lines. In this regard, advertising and fashion mention products intended to keep as long as possible a glowing skin without wrinkles, marks of a young skin, especially as the physical aspect acts on the psyche and / or on morale.

  The human skin consists of two compartments namely a superficial compartment, the epidermis, and a deep compartment, the dermis.

  The natural human epidermis is composed mainly of three types of cells, which are the keratinocytes, a very large majority, melanocytes and Langerhans cells. Each of these cell types contributes by its own functions to the essential role played in the body by the skin.

  The dermis provides the epidermis with a solid support. It is also its nurturing element. It consists mainly of fibroblasts and an extracellular matrix. There are also leucocytes, mast cells or tissue macrophages. It is also made up of blood vessels and nerve fibers.

  The extracellular matrix of the dermis is composed of proteins belonging to several large families: collagens, matrix glycoproteins other than collagens (fibronectin, laminin), elastin, proteoglycans and glycosaminoglycans (GAGs) in free form (it is to say non-protein bound) including hyaluronic acid. These proteins are mainly synthesized by fibroblasts and it is known that the cutaneous aging process induces a decrease in these metabolic activities leading to a decrease in the proteins of the extracellular matrix of the dermis and a decrease in cell growth leading to an alteration of the tissues. mechanical properties of the skin, in particular its firmness, elasticity, tone and / or flexibility. Skin aging is a natural physiological process; it is not considered a pathological condition or a therapeutic disorder.

  There remains the need for cosmetic compositions that make it possible to prevent and / or reduce the effects of aging on the skin and / or restore the mechanical properties of a younger skin, such as its firmness and / or elasticity and / or its flexibility.

  Now the Applicant has discovered that the combination of three active ingredients, on an in vitro model of experimentally aged skin, made it possible to respond to this need by preventing the decrease and / or by restoring the protein synthesis activity of the dermis cells and / or or restoring the proliferative activity of skin cells. This specific combination comprises at least: hyaluronic acid or one of its salts; a soy protein extract; and a compound of formula (I) as defined below, especially called pseudodipeptide in the rest of the description.

  In particular, this pseudodipeptide consists of {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid, otherwise known as N- [N-acetyl, N '- ( 3-trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, or an ester thereof with a C1-C6 alcohol.

  Hyaluronic acid is known for its effect on the hydration of the skin.

  Also known from the prior art are cosmetic compositions comprising hydrolyzed extracts of soya.

  But to the knowledge of the Applicant, it has never been described or suggested hitherto to specifically associate hyaluronic acid or one of its salts, a hydrolysed soy extract and a compound of formula (I) as defined below, in particular {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} -acetic acid otherwise known as N- [N-acetyl, N '- (3 trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, or an ester thereof with a C1-C6 alcohol.

  The present invention thus relates to a composition containing, in a physiologically acceptable medium, at least: hyaluronic acid or one of its salts; - an extract of soy protein; and a compound of formula (I): (I) wherein:

the radical Y represents O,

  the radical R 1 represents a linear hydrocarbon radical, saturated or unsaturated, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, and even more preferentially from 1 to 2 carbon atoms, or a branched hydrocarbon radical; having from 3 to 6 carbon atoms, preferably from 3 to 4 carbon atoms;

  the radical R2 represents a linear hydrocarbon radical, saturated or unsaturated, having 1 to 10 carbon atoms, preferably having 2 to 6 carbon atoms, or a branched hydrocarbon radical having 3 to 10 carbon atoms, preferably having from 3 to 6 carbon atoms; the radical R 3 represents a phenyl radical optionally substituted by a hydrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 3 carbon atoms, optionally substituted with 1 or more fluorine atoms;

  the radical X represents a radical chosen from -OH, -OR4, preferably -OH, with R4 representing a linear hydrocarbon radical, saturated or unsaturated, having 1 to 6 carbon atoms, or a branched hydrocarbon radical having from 3 to 6; carbon atoms.

  In particular, the compound of formula (I) is chosen from {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid, otherwise known as N- [N-acetyl], N '- (3-trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, or an ester thereof with a C1-C6 alcohol .

  Hyaluronic acid Hyaluronic acid belongs to the family of glycosaminoglycans (GAGs). GAGs are linear chains composed of the repetition of a basic diholoside always containing a hexosamine (glucosamine or galactosamine) and another ose (glucuronic acid, iduronic acid or galactose). Glucosamine is either N-sulfated or N-acetylated. In contrast, galactosamine is still N-acetylated. In addition, there may be O-linked sulfates on hexosamine, uronic acid and galactose.

  Hyaluronic acid or hyaluronan (HA) is the main GAG of the dermis, the latter containing half of HA of the body. It is a polysaccharide of disaccharides themselves composed of D-glucuronic acid and N-acetylglucosamine, linked together by alternating glycoside bonds beta-1,4 and beta-1,3. It plays an important role in the hydration and elasticity of the skin.

  The composition according to the invention preferably contains hyaluronic acid or a salt thereof.

  As hyaluronic acid salts, mention may be made in particular of potassium hyaluronate and sodium hyaluronate.

  Preferably, it will be used according to the invention sodium hyaluronate.

  It will be possible in particular to use in the composition of the invention the sodium hyaluronate of molecular weight 1,100,000 Daltons sold by SOLIANCE under the name CRISTALHYAL. Hyaluronic acid or a salt thereof is present in the composition according to the invention in an amount ranging from 0.01 to 1% by weight (of dry matter) relative to the total weight of the composition, in particular from 0, 0.1 to 0.1% by weight (of dry matter) relative to the total weight of the composition. 15

Soy protein extract

  The soy protein extract used according to the invention may be any soy protein extract having a beneficial effect on the appearance and / or the mechanical properties of the skin, in particular on its firmness and / or its tonicity and / or its elasticity.

  Soy protein extracts that can be used in the composition according to the invention include, in particular: soy extracts stimulating the proliferation of fibroblasts, such as those sold by the company LSN under the name Eleseryl SH-VEG 8 or marketed by SILAB under the trade name Raffermine; soya extracts increasing the synthesis of collagen and / or preventing its degradation, such as the soy hydrolyzate marketed by the company COLETICA under the trade name Phytokine, or the hydrolysed extract of soy protein marketed by the company SILAB under the trade name RIDULISSE C.

  Preferably, a hydrolysed extract of soy proteins will be used to increase collagen synthesis and / or prevent degradation. The ability of a soy protein extract to increase collagen synthesis and / or prevent its degradation can be evaluated in vitro, for example by the following method: Human fibroblasts are incubated in culture in the presence or absence of control (control). an extract of soy protein to be tested or in the presence of a reference product known to increase collagen synthesis, such as vitamin C (positive control); cell supernatants are recovered; the collagens are dosed by an ELISA method; extracts are selected for which an increase in collagen synthesis is obtained with respect to the control.

  In particular, the soy protein extract used in the composition according to the invention contains a product A obtained from soybean meal and a product B obtained from soybean fibers, said products being respectively obtained by a process of extraction comprising at least one solubilization step, a protease hydrolysis, a step of separating the solubilized phase and a step of concentration of the active phase.

  A hydrolysed extract of soy protein that is preferred according to the invention is the extract prepared according to the method described in WO2004 / 096168 of SILAB and marketed by this company under the name RIDULISSE C.

  The method described in the application WO2004 / 096168 consists of combining two products A and B, obtained from soybeans, each obtained by the following succession of steps:

  A solubilization product of soybean meal at a rate of at least 50 g / l by weight, in water at acidic pH, - simultaneous or successive enzymatic hydrolyses in the presence of proteases, - filtration, decantation or centrifugation in order to separate the phase solubilized and insoluble products, and successive concentrations of the active phase by filtration, ultrafiltration, osmosis or nanofiltration; Product B -solubilization of soybean fibers in water at acidic pH, - at least one enzymatic hydrolysis using at least one protease, - filtration, decantation or centrifugation in order to separate the solubilized phase and the insoluble products and - successive concentrations of the active phase by filtration, ultrafiltration, osmosis or nanofiltration. The 2 products A and B are then combined, preferably, is associated with the product A at least 10% of the product B.

  The amount of soy protein extract used in the composition according to the invention is the amount necessary to obtain the desired beneficial effect on the skin, in particular an effect on the firmness and / or elasticity of the skin. By way of example, the composition contains from 0.01 to 5% of soy protein extract by weight relative to the total weight of the composition, preferably from 0.05 to 2% by weight relative to the total weight of the composition and even more preferably from 0.1 to 1% by weight relative to the total weight of the composition.

  Pseudodipeptide The compound used in the composition according to the invention, also called pseudodipeptide in the remainder of the description corresponds to the following formula (I): (I) in which:

the radical Y represents O,

  the radical R 1 represents a linear hydrocarbon radical, saturated or unsaturated, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, and even more preferentially from 1 to 2 carbon atoms, or a branched hydrocarbon radical; having from 3 to 6 carbon atoms, preferably from 3 to 4 carbon atoms;

  the radical R2 represents a linear hydrocarbon radical, saturated or unsaturated, having 1 to 10 carbon atoms, preferably having 2 to 6 carbon atoms, or a branched hydrocarbon radical having 3 to 10 carbon atoms, preferably having from 3 to 6 carbon atoms; the radical R 3 represents a phenyl radical optionally substituted by a hydrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 3 carbon atoms, optionally substituted with 1 or more fluorine atoms;

  the radical X represents a radical chosen from -OH, -OR4, preferably -OH, with R4 representing a linear hydrocarbon radical, saturated or unsaturated, having 1 to 6 carbon atoms, or a branched hydrocarbon radical having from 3 to 6; carbon atoms.

  These compounds are described in the patent EP 1 292 608 B1 of the Applicant.

  In particular, the compound is a derivative of glycine.

  Among the preferred compounds, mention may be made of: {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid, otherwise known as N- [N-acetyl, N'- (3-trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine; ethyl {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetate, otherwise known as ethyl ester of N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl- glycine, [2- (acetyl-benzyl-amino) -3-methyl-butyrylamino] acetic acid, [2- (acetyl-benzyl-amino) -3-methyl-butyrylamino] ethyl acetate, ethyl (2- {benzyl - [(diethoxy-phosphoryl) -acetyl] -amino} -3-methyl-butyrylamino) acetate.

  A particularly preferred compound according to the invention is chosen from {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} -acetic acid, otherwise known as N- [N-acetyl, N ' - (3-trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, and its esters with C1-C6 lower alcohols. this acid may be mentioned in particular its ethyl ester, {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} ethyl acetate otherwise known as N-acetyl-N ethyl ester. - [3- (trifluoromethyl) phenyl] valyl-glycine. These compounds are described in EP 1 292 608 B1 as elastase inhibitors and / or agents preventing the degradation of elastin.

  The composition according to the invention may contain from 0.01 to 10% by weight of compound of formula (I) relative to the total weight of the composition, and preferably from 0.1 to 2% by weight of compound of formula (I) relative to the total weight of the composition.

  According to a preferred embodiment of the invention, the composition according to the invention may furthermore comprise adenosine and a manganese salt, in particular manganese gluconate. The Applicant has actually shown on a model of contractile lattices that this combination has a dermo-decontracting effect that can be put to use in the anti-aging compositions according to the invention. This combination indeed makes it possible to prevent and / or reduce the dermo-crispations of the facial skin which are in particular at the origin of expression lines. These expression lines are produced under the effect of the stress exerted on the skin by the skin muscles which allow mimicry. Depending on the shape of the face, the frequency of mimicry and possible tics, they can appear from childhood. Age, as well as certain environmental factors such as sun exposure, do not intervene in their genesis but can dig them further and make them permanent.

  Expression lines are characterized by the presence of furrows around the orifices of the nose (nasolabial folds), the mouth (para-buccal wrinkles and so-called bitterness wrinkles) and the eyes (wrinkles of the paw d 'oie), around which are located the skin muscles, as well as between the eyebrows (glabella or lion's wrinkles) and on the forehead.5 The composition according to the invention contains from 0.01 to 1% of adenosine by weight relative to the total weight of the composition, preferably from 0.01 to 0.1% by weight relative to the total weight of the composition.

  The term "manganese salts" means the organic or inorganic salts of manganese.

  Manganese organic salts that may be mentioned include manganese gluconate or manganese carbonate or manganese acetate or manganese citrate or manganese oleate or manganese oxalate. As inorganic salts of manganese, mention may be made of inorganic salts such as manganese chloride or manganese borate or manganese nitrate or manganese phosphate or manganese sulfate.

  Preferably, the manganese gluconate will be used.

  The composition according to the invention thus contains from 0.01 to 1% of manganese salt by weight relative to the total weight of the composition, preferably from 0.01 to 0.1% by weight relative to the total weight of the composition. composition. 20

  The composition according to the invention may further comprise at least one active agent chosen from vitamins and their derivatives. In particular, the vitamins and derivatives are selected from tocopherol or tocopherol acetate.

galenic

  The composition according to the invention may be in any of the galenical forms conventionally used for topical application and in particular in the form of aqueous gels of the serum type, of aqueous or aqueous-alcoholic solutions. It may also, by addition of a fatty or oily phase, be in the form of a dispersion of the lotion or serum type, of a liquid or semi-liquid consistency emulsion of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (O / W) or conversely (W / O), or suspension or emulsion of soft, semi-solid or solid consistency of the cream or gel type, or else of multiple emulsion (W / O / W or H). / E / H), microemulsion, vesicular dispersion of ionic and / or nonionic type, or wax dispersion / aqueous phase. These compositions are prepared according to the usual methods.

  According to a preferred embodiment of the invention, the composition is in the form of an oil-in-water emulsion.

  When the composition is in emulsion form, the proportion of the oily phase of the emulsion may range, for example, from 1 to 80% by weight, and preferably from 5 to 40% by weight relative to the total weight of the composition. . The oils, the emulsifiers and the co-emulsifiers used in the composition in emulsion form are chosen from those conventionally used in the cosmetic or dermatological field. The emulsifier and the co-emulsifier are generally present in the composition, in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition. The emulsion may further contain lipid vesicles.

  As fats which can be used in the invention, it is possible to use the oils, and in particular the hydrocarbons of mineral or synthetic origin (petroleum jelly, hydrogenated polyisobutene, mineral oil), the oils of vegetable origin (shea butter, olive oil). avocado, soybean oil, apricot kernel oil), animal oils (lanolin), synthetic esters (pentaerythrityl tetraoctanoate, ethyl-2-hexyl palmitate, myristyl myristate), oils silicone (polydimethylsiloxane and cyclopentasiloxane) and fluorinated oils (perfluoropolyethers). It is also possible to use fatty alcohols such as cetyl alcohol or stearyl alcohol, fatty acids such as stearic acid, waxes such as beeswax and gums and, in particular, silicone.

  Examples of emulsifiers and co-emulsifiers that can be used in the invention include fatty acid esters of polyethylene glycol, such as PEG-100 stearate and PEG-20 stearate; optionally oxyethylenated fatty acid and alkyl glycoside esters such as oxyethylenated methylglucose sesquistearate (20 EO); fatty acid esters of polyol such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates available under the trade names Tween 20 or Tween 60, for example; and their mixtures As hydrophilic gelling agents, mention may in particular be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as copolymers of acrylates / alkylacrylates, polyacrylamides optionally in the form of inverse emulsion copolymers, such as the products sold. respectively by CLARIANT under the trade name HOSTACERIN AMPS and by SEPPIC under the trade name SEPIGEL 305, polysaccharides such as xanthan gum and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids and hydrophobic silica.

  As preservatives, mention may be made of para-hydroxybenzoic acid esters, octane 1,2-diol, 3-iodo-2-propynyl butyl carbamate, phenoxyethanol, imidazolidinyl urea and chlorhexidine digluconate.

  As fillers, mention may be made, for example, of polyamide particles (nylon); polymethyl methacrylate microspheres; ethyleneacrylate copolymer powders; expanded powders such as hollow microspheres and especially microspheres formed of a terpolymer of vinylidene chloride, acrylonitrile and methacrylate and sold under the name EXPANCEL by Kemanord Plast; powders of natural organic materials such as starch powders, especially corn starch, wheat or rice, crosslinked or otherwise, such as starch powders crosslinked with octenylsuccinic anhydride; silicone resin microbeads such as those sold under the name Tospearl by the company Toshiba Silicone; talcum; silica; metal oxides such as titanium dioxide or zinc oxide; mica; and their mixtures.

  The invention also relates to the non-therapeutic cosmetic use in a composition containing a physiologically acceptable medium, of at least: hyaluronic acid or a salt thereof; a soy protein extract; and a compound of formula (I) as defined above, said combination and / or the composition being intended to prevent and / or reduce the thinning of the skin and / or promote cell renewal. In particular, said combination and / or the composition is intended to stimulate the proliferative activity of skin cells diminished with age. Said combination and / or the composition is intended to maintain and / or stimulate the proliferation of skin cells.

  In particular, said combination and / or the composition is intended to promote the resumption of proliferation of skin cells particularly impaired during aging.

  In particular, the compound of formula (I) is chosen from {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid, otherwise known as N- [N-acetyl], N '- (3-trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, and its esters with C1-C6 lower alcohols.

  Still within the scope of the invention is the non-therapeutic cosmetic use in a composition containing a physiologically acceptable medium, of at least: hyaluronic acid or one of its salts; a hydrolyzed soy extract; and a compound of formula (I) as defined above, said combination and / or the composition being intended to maintain and / or stimulate the synthesis of collagen and / or elastin fibers of the cutaneous tissue.

  In particular, said combination and / or said composition is intended to retrace and / or repair the fibers of the skin tissue altered with age.

  Said combination and / or the composition according to the invention thus makes it possible to repair the wrinkles of the interior.

  In particular, the compound of formula (I) is chosen from {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} -acetic acid, otherwise known as N- [N-acetyl, N '- (3-trifluoromethyl) phenyl valyl] glycine or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, and its esters with C1-C6 lower alcohols.

  This combination thus makes it possible, via an effect on the synthesis of elastin and / or the prevention of its degradation and / or on the synthesis of collagen and / or the prevention of its degradation, as well as an effect on cell proliferation, of reduce wrinkles by promoting and / or improving the fibers of the cutaneous tissue altered during aging.

  According to a preferred embodiment of the invention, the use of this complex of 3 active agents is associated in the same composition with adenosine and manganese gluconate, this second combination and / or the composition being intended to prevent and / or to reduce the dermo-crispation of the skin of the face. This complementary combination also makes it possible to prevent and / or reduce expression lines in the face.

  The invention also relates to a cosmetic process for preventing and / or correcting cutaneous signs of aging, in particular wrinkles and fine lines and / or the loss of firmness and / or elasticity of the skin, comprising the topical application on the skin of a composition according to the invention comprising at least the complex of 3 active agents defined above.

  In particular, when the composition according to the invention additionally comprises adenosine and a manganese salt, the cosmetic process according to the invention also makes it possible to prevent and / or reduce dermo-crispations of the skin, and thus to prevent and / or reduce expression lines.

  The wrinkles treated according to the method of the invention are in particular lesrides arranged radially around the mouth and / or the eyes and / or horizontally on the forehead and / or located in the space inter-sourcillier. Preferably, the composition according to the invention is applied to a wrinkled skin.

  In particular, it is applied to areas of sagging skin and / or wrinkle formation, particularly on forehead areas marked by expression lines and / or on individuals with expression lines. The composition may be applied daily to the skin of the face and / or neck, particularly to the areas identified above.

  The invention will now be illustrated by the following nonlimiting examples. EXAMPLES Example 1: Anti-doping effect of the complex of 3 active agents on a skin maintained in survival and aged experimentally

  a) Protocol The effect of the mixture of three active agents according to the invention on the aging of the skin is studied. The test is performed on a model of human skin maintained in survival and experimentally aged. This experimental aging model is carried out by topical application of a Class II topical corticosteroid (Diprosone, cream containing betamethasone 0.05%) on day 0, day 1 and day 2 to obtain a reduction of the mitotic index (cellular proliferation cutaneous cells) and an alteration of fibroblast metabolism responsible for the synthesis of connective tissue macromolecules, in particular collagen and elastin.

  The mixture of the following 3 ingredients is tested: Composition of the mixture under test Final concentration tested Acetyl trifluoromethylphenyl valylglycine * 0.10% Hydrolyzed soya extract (RIDULISSE C 2.00% marketed by SILAB) 0.02% sodium hyaluronate * {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid otherwise known as N- [N-acetyl, N '- (3-trifluoromethyl) phenyl valyl] glycine or N- acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine Treatment with the combination will be carried out secondarily for 13 days, starting on D1.

  The cell proliferation assay is performed on D3 and the collagen, elastin and glycosaminoglycan (GAGs) assays at D15.

b) Results

  The epithelial proliferation is analyzed on D3 by immunohistochemistry using an anti-Ki67 antibody (cell marker in phases M, S, G1 and G2 of the cell cycle). Assays of collagen, elastin and GAGs are performed by a spectrocolorimetric assay method (Sircol Collagen Assay, Interchim). The results are related to the total amount of protein measured at 562 nm (BCA assay, Pierce); the results are expressed in ng of collagen or elastin or GAGs / mg of proteins.

  Statistical analysis is performed by the paired Student test. The results are shown in the following table: Treatment% of cells Collagen Elastin (g / mg GAGs (g / mg epithelial (g / mg protein) protein-labeled) antibody Ki67 Skin control 6.1 117.9 136.8 16.9 Skin + 1.78 92.4 84.5 14.6 dermocortocoid Skin + 6.8 122 113.4 18.7 dermocorticoid + mixture of 3 active agents 20 These results show that the treatment of human skin in survival by a dermocorticoid induces a decrease in cell proliferation, as well as in the synthesis of collagen and elastin. This treatment has no effect on the production of GAGs. This type of treatment makes it possible to age the skin experimentally. The treatment of experimentally aged human skin by mixing the active ingredients induces a resumption of cell proliferation, as well as a significant increase in the synthesis of collagen and elastin.

  This effect of the combination of the 3 active agents according to the invention on this model of aged skin can be exploited by anti-aging compositions intended to maintain and / or stimulate the proliferative and protein synthesis activity of the cells of the skin. impaired during aging.

  EXAMPLE 2 Dermo-Decontracting Effect of the Adenosine and Manganese Gluconate Association a) Principle of the Test The principle of this test consisted in studying the dermo-decontracting effect of a combination of adenosine and manganese gluconate on a equivalent dermis model consisting of a collagen matrix seeded with normal human fibroblasts. These conditions are intended to mimic in vitro the dermic contractile phenomena that occur during dermo-crispation of the face, for example during mimicry of the face. Under these conditions, the cells spontaneously express tensile forces that induce retraction of the collagen gel. This results in a decrease in the total area of the equivalent dermis over time. The measurement of this surface makes it possible to evaluate the effects of relaxation or dermo-decontracting substances previously brought into contact with the equivalent dermis. 30 b) Protocol

  Sets of three attached equivalent dermes containing normal human fibroblasts are prepared: a control series without any treatment; three series respectively treated with adenosine (0.004%), manganese gluconate (0.0005%) and the mixture of these two compounds in the proportions indicated. The experiment is repeated three times. The dermis equivalents are prepared as described in Asselineau et al., Exp. Cell. Res., 1985, 159, 536-539; Models in dermatology, 1987, vol 3 pp 1-7, in the following proportions: Medium MEM (1.76X) with or without test compound (s) 45% Fetal calf serum: 9% NaOH (0.1N) : 5% Acetic acid (1/1000): 4% Collagen: 26% Fibroblasts: II% The collagen used is collagen type I (commercial solution), but it is also possible to use collagen type III or IV. It is extracted from rat tails or calf skin by acid hydrolysis and stored in an acid medium at +4 ° C; it polymerizes naturally by warming to 37 C and by reducing the rate of acidity. Collagen is previously dialyzed against successive baths of water + acetic acid.

  The protocol is as follows: in a sterile vial tube, MEM 1.76 X medium is introduced in the presence of additives (Glutamine 1%, Non-essential amino acids 1%, Sodium pyruvate 1%, Fungizone 1% and Penicillin / Streptomycin 1%), fetal calf serum, 0.1N NaOH sodium hydroxide. Isolated fibroblasts are then added from human skin explants at the concentration of 1.4 × 10 5 cells per 1 ml of culture medium.

  A volume / volume mixture of collagen in 1/1000 acetic acid is then added slowly against the wall of the tube so as to observe the appearance of a whitish cloud.

  The whole is then carefully mixed and distributed in the wells of a 12-well culture plate (Costar type reference 3512) at a rate of 0.5 ml of mixture per cm 2. The culture plate is then placed in a 37 C incubator with 5% CO2. Once formed after polymerization of the collagen, the equivalent dermes are left adhered to the culture support for 3 days and then detached from the support so that the contraction can start. These attached equivalent dermes were taken out of the incubator to take the images for the purpose of measuring their area after 24 hours of contraction.

  The evaluation of the spontaneous contraction of the treated and control equivalent dermes is carried out by measuring their surface at 24 hours after the beginning of the spontaneous contraction. For this, a digital image is acquired for each equivalent dermis treated or untreated by means of a camera (CCD Camera Sony DXC-107P) and the area is then calculated on each image by means of a scanning system. image (Zeiss Axiovision 3.0). This surface measurement corresponds to a contraction percentage equal to the ratio of the surfaces according to the formula:% contraction = (Sp-Si) / Sp × 100

  where: Sp represents the surface of a well of the culture plate; it corresponds to the total surface of the equivalent dermis before contraction Si represents the dermal surface equivalent to the 24 h contraction time. c) Results Treatment% contraction Control 100 Manganese Gluconate (0.0005%) 89 Adenosine (0.004%) 82 Mn Gluconate (0.0005%) + Adenosine 72 (0.004%) These results show that the combination of adenosine and manganese gluconate leads to a contraction delay of 28%, greater than that obtained with each of the compounds taken separately.

  This test thus demonstrates that the combination of adenosine and manganese gluconate results in less contraction of the equivalent dermis, compared with the control and the equivalent dermis treated with these compounds separately. This dermo-decontracting effect of the adenosine and manganese gluconate combination can be put to good use in the anti-aging compositions of the invention, in particular for reducing and / or limiting the dermo-crispation of the skin of the face and thereby smoothing wrinkles, especially expression wrinkles in the face.

  Example 3: Formulation This composition is prepared in a conventional manner for the skilled person. The quantities given in this example are indicated in percentages by weight. Cream (oil-in-water emulsion) Acetyl trifluoromethylphenyl valylglycine * 0.30% Hydrolyzed Soy Protein (SILAB Ridiculisse C) 0.10% Sodium Hyaluronate (SOLIANCE Cristalhyal) 0.05% 0.05% Manganese Gluconate Adenosine 0 , 04% Talc 1,10% Silica 1,20% Octyldodecanol 0,50% Isostearyl neopentanoate 3.50% Apricot kernel oil 3.00% Vegetable oils 3.30% Squalane 0.90% Cetyl alcohol 0, 50% Stearyl alcohol 0.50% Hydrogenated polyisobutene (Perleam from NOF Corp) 6.50% Ammonium polyacryloydimethyl taurate (Hostacerin AMPS from CLARIANT) 1.00% Polyamide fibers 3.00% Cyclohexasiloxane 7.00% Silicone film-forming polymer emulsion (HMW2220 from Dow Corning) 2.00% Tocopherol Acetate 0.50% Glycerin 3.00% Triethanolamine 0.15% Emulsifiers 5.80% Perfumes 0.50% Preservatives 1, 30% Water qs 100% * = Acid { 2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid otherwise known as N- [N-acetyl, N '- (3-trifluoromethyl) phenyl valyl] glycin e or N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine or acetyl trifluoromethyl phenyl valylglycine, prepared as described in EP 1 292 608 B1.

  This cream can be applied daily on the face in the morning and / or in the evening to reduce wrinkles and reduce skin dermo-crispness.

Claims (20)

  1. Cosmetic composition containing, in a physiologically acceptable medium, at least: hyaluronic acid or one of its salts; a soy protein extract; and a compound of formula (I) wherein R is a linear hydrocarbon radical, saturated or unsaturated, having from 1 to 6 carbon atoms; preferably from 1 to 4 carbon atoms, and even more preferably from 1 to 2 carbon atoms, or a branched hydrocarbon radical having from 3 to 6 carbon atoms, preferably from 3 to 4 carbon atoms; The radical R2 represents a saturated or unsaturated, linear hydrocarbon-based radical having 1 to 10 carbon atoms, preferably having 2 to 6 carbon atoms, or a branched hydrocarbon radical having 3 to 10 carbon atoms, preferably having from 3 to 6 carbon atoms; the radical R 3 represents a phenyl radical optionally substituted by a hydrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 3 carbon atoms, optionally substituted with 1 or more fluorine atoms; and the radical X represents a radical chosen from -OH, -OR4, preferably -OH, with R4 representing a linear hydrocarbon radical, saturated or unsaturated, having 1 to 6 carbon atoms, or a branched hydrocarbon radical having from 3 to 6 carbon atoms. 25 30   2. Cosmetic composition according to claim 1, characterized in that the compound of formula (I) is chosen from N-acetyl-N- [3- (trifluoromethyl) phenyl] valyl-glycine, and an ester thereof with a C6-C6 alcohol.   3. Composition according to one of claims 1 or 2, characterized in that the hyaluronic acid salt is sodium hyaluronate.   4. Composition according to one of claims 1 to 3, characterized in that the soy protein extract contains a product A obtained from soybean meal and a product B obtained from soybean fibers, said products being respectively obtained by an extraction process comprising at least one solubilization step, a protease hydrolysis, a step of separating the solubilized phase and a concentration step of the active phase.   5. Composition according to any one of the preceding claims, characterized in that it contains from 0.01 to 1% by weight of hyaluronic acid or a salt thereof relative to the total weight of the composition.   6. Composition according to any one of the preceding claims, characterized in that it contains from 0.05 to 2% by weight of soy protein extract relative to the total weight of the composition. 25   7. Composition according to any one of the preceding claims, characterized in that it contains from 0.1 to 2% by weight of compound of formula (I) relative to the total weight of the composition.   8. Composition according to any one of the preceding claims, characterized in that it also contains adenosine and a manganese salt.   9. Composition according to claim 8, characterized in that the manganese salt is a manganese gluconate.   10. Non-therapeutic cosmetic use in a composition containing a physiologically acceptable medium, at least: hyaluronic acid or a salt thereof; - an extract of soy protein; and a compound of formula (I) as defined in one of claims 1 or 2, said combination and / or the composition being intended to prevent and / or reduce the thinning of the skin and / or promote cell renewal.   11. Use according to claim 10, characterized in that said combination and / or the composition is intended to stimulate the proliferative activity of skin cells diminished with age.   12. Non-therapeutic cosmetic use in a composition containing a physiologically acceptable medium, of at least: hyaluronic acid or one of its salts; - an extract of soy protein; and a compound of formula (I) as defined in one of claims 1 or 2, said combination and / or the composition being intended to maintain and / or stimulate the synthesis of collagen and / or elastin fibers of the tissue skin.   13. Use according to claim 12, characterized in that said association and / or said composition is intended to retrace and / or repair the fibers of the skin tissue altered with age.   14. Non-therapeutic cosmetic use according to one of claims 10 to 13, characterized in that the composition also contains adenosine and manganese gluconate, this second combination and / or the composition containing it being intended to prevent and / or to reduce the dermo-crispation of the skin of the face   15. Cosmetic process for preventing and / or reducing the cutaneous signs of aging, comprising the topical application to the skin of a composition according to any one of Claims 1 to 9.   16. The method of claim 15, characterized in that it aims to prevent and / or reduce wrinkles and fine lines and / or the loss of firmness and / or elasticity of the skin.   17. Cosmetic process for preventing and / or reducing dermo-crispation of the skin comprising the topical application to the skin of a composition according to one of claims 8 or 9.   18. The cosmetic method according to one of claims 15 to 17 for preventing and / or reducing expression lines.   19. Cosmetic process according to one of claims 15 to 18, characterized in that the wrinkles are the wrinkles arranged radially around the mouth and / or eyes and / or horizontally on the forehead and / or located in the interstitial space. - sourcillier.   20. Cosmetic process according to any one of claims 15 to 19, characterized in that the composition is applied to the areas of the face or forehead marked by expression lines and / or on persons with expression lines .