COSMETIC COMPOSITIONS CONTAINING ROBININE

Abstract

COSMETIC COMPOSITIONS COMPRISING ROBININE The present invention relates to cosmetic compositions comprising a compound of formula (I) and their use to promote and / or accelerate skin regeneration, to prevent and / or treat signs of aging, and to promote and / or accelerate wound healing. The invention also relates to cosmetic processes comprising the application of such compositions. Figure for the abstract: none

Description

Title of the invention: COSMETIC COMPOSITIONS COMPRISING ROBININE

[0001] The present invention relates to cosmetic compositions comprising a compound of formula (I) as described below, or an optical isomer thereof, or a cis-trans isomer thereof, or a tautomer or salt thereof, or a hydrate thereof, and their use to promote and / or accelerate skin regeneration, to prevent and / or treat signs of aging, and to promote and / or accelerate wound healing. The invention also relates to cosmetic processes comprising the application of such compositions.

[0002] Human skin is composed of two compartments: a deep compartment, the dermis, and a superficial compartment, the epidermis. The epidermis is in contact with the external environment and its role is to protect the body from dehydration and external chemical or mechanical aggressions.

[0003] Accelerated wound closure is an area of ​​intensive scientific research aimed at improving healing after a skin injury or within skin whose barrier function is compromised. For example, the skin barrier can be disrupted after a cosmetic procedure such as laser treatments and chemical exfoliations, or in the presence of external aggressors such as irritants (detergents, acids, bases, oxidizers, reducing agents, concentrated solvents, toxic gases or fumes), mechanical stresses (friction, shocks, abrasion, surface tearing, projection of dust, particles, shaving or waxing), thermal or climatic imbalances (cold, dryness, radiation), xenobiotics (undesirable microorganisms, allergens) or internal attacks such as psychological stress.Following such external aggressions, a healing process is triggered, aiming to rapidly and completely restore this barrier. This physiological process depends on complex biological mechanisms involving numerous molecules and enzymes.

[0004] There is a need for compositions that promote skin healing and, in particular, that accelerate skin healing.

[0005] The objective of the invention is therefore to propose a cosmetic composition that meets all these requirements.

[0006] The inventors made the surprising discovery that the natural molecules of formula (I) are capable of accelerating wound healing and are therefore potentially useful for skin regeneration.

[0007] This application proposes compositions intended to accelerate skin regeneration after a skin injury or cosmetic procedure, to promote recovery after said skin injury and / or improve the effectiveness of cutaneous cosmetic procedures. The use of the compositions will result in faster healing and recovery time from the procedure, leading to a greater willingness on the part of the patient to undergo cosmetic procedures.

[0008] Thus, the present invention relates to a cosmetic composition comprising, in a cosmetically acceptable medium:

[0009] - at least one compound of formula (I) or an optical isomer thereof, or a cis-trans isomer of the latter, or a tautomer of the latter, or a salt of the latter, or a hydrate of the latter, and

[0010] - at least one compound selected from thickeners, preservatives, perfumes, bactericides, pigments, dyes, inorganic carbon and / or silicone oils, waxes, fillers, emulsifiers, co-emulsifiers, UVA and / or UVB light protection agents also known as UV filters, polymers, gelling agents, hydrophiles and lipophiles.

[0011] For the purposes of the present invention, and unless otherwise indicated:

[0012] - a "sugar" radical is a monosaccharide or disaccharide radical. Examples Sugar radicals include sucrose (or saccharose), glucose, galactose, rhamnose, galactose, ribose, fucose, maltose, fructose, mannose, arabinose, xylose or lactose;

[0013] - a "monosaccharide" means a monosaccharide sugar comprising at least 5 carbon atoms of formula CX(H2O)X, x being an integer equal to or greater than 5, preferably x is equal to or greater than 6, in particular x is from 5 to 7, preferably x = 6; they may be of D or L configuration and of alpha or beta anomer, as well as any of its salts or solvates such as any of its hydrates;

[0014] - "disaccharide" refers to a di-ossidic sugar which is a compound made up of two sugars linked together by O-glycosidic bonds, said compounds consisting of two monosaccharides (also called mono-glycosidics) as defined above, said monosaccharide units comprising at least 5 carbon atoms, preferably 6, in particular the monosaccharide units are linked together in 1,4 or 1,6, of alpha or beta anomer, each sugar unit being of L or D configuration, as well as one of its salts or solvates such as hydrates. A disaccharide is more particularly a polymer formed from two sugars (or monosaccharides) having the general formula: [Cx(H2O)y)]2 or [(CH2O)X]2, x being an integer equal to or greater than 5, preferably x is equal to or greater than 6, in particular x is from 5 to 7, preferably x = 6, and y is an integer that represents x-1;

[0015] - "salt" means a cosmetically acceptable salt, that is to say, compatible with application to the skin, mucous membranes and / or appendages;

[0016] - in what follows and unless otherwise indicated, the limits of a range of values ​​are included in this range, in particular in the expressions "between" and "ranging from... to...";

[0017] - the expression "at least one" used in this description is equivalent to the expression "one or more".

[0018] Another object of the invention is the use of said compound or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, or a composition according to the invention, to promote and / or accelerate skin regeneration.

[0019] Another object of the invention is the use of said compound or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, or a composition according to the invention, to prevent and / or treat signs of aging.

[0020] Another object of the invention is the use of said compound or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, or a composition according to the invention, to promote and / or accelerate wound healing.

[0021] The present invention also relates to a non-therapeutic method for treating the skin comprising the step of applying to the skin said at least one compound, or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof, or a salt thereof, or a hydrate thereof, or the composition according to the invention.

[0022] Another object of the invention is a skin treatment method to promote and / or accelerate wound healing after cosmetic procedures, the method comprising:

[0023] (a) the treatment of the skin with at least one skin-modifying stimulus, and

[0024] (b) after step (a) the application of a composition according to the invention to the skin.

[0025] Other subjects, features, aspects, and advantages of the invention will become even clearer upon reading the description and examples that follow. Compositions

[0026] The composition according to the invention comprises at least one compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof: Formula (I)

[0027] in which:

[0028] - R' and R” are identical or different, preferably different, and represent a hydrogen, or an alkyl (C1-C4) such as a methyl, ethyl, propyl, isopropyl, butyl, and isobutyl, preferably a methyl, or a monosaccharide or polysaccharide comprising up to 20 sugar units, preferably up to 6 sugar units, in the form of pyranose and / or furanose and of the L and / or D series, said monosaccharide or polysaccharide being substituted by a mandatory free hydroxyl group and / or optionally one or more amine functions, optionally one or more protected amine functions, said monosaccharide or polysaccharide being optionally substituted on its -CH2OH group by a -C(O)-CO2H group and said monosaccharide or polysaccharide being optionally substituted on one or more of its hydroxyl groups by an acyl (C1-C4) group, preferably an acetyl group, or by a group hydroxycinnamyl, selected from coumaroyl, caffeoyl, feruloyl or sinapoyl;

[0029] - R' and R' are identical or different and represent a hydrogen or an alkyl (C1-C4), such as a methyl, ethyl, propyl, isopropyl, butyl and isobutyl, preferably a methyl,

[0030] - it being understood that R', R”, R” ', and R” ” cannot represent a hydrogen in same time.

[0031] Advantageously, said compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, is in the form of a plant extract.

[0032] Advantageously, R' and R” are identical or different, preferably different, and represent a monosaccharide or a polysaccharide containing up to 6 sugar units, in the form of pyranose and / or furanose and of range L and / or D, said monosaccharide or polysaccharide having at least one obligatorily free hydroxyl function and / or optionally one or more obligatorily protected amine functions.

[0033] Advantageously, the monosaccharide is chosen from D-glucose, D-allose, D-galactose, D-mannose, D-xylose, D-lyxose, L-fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine or N-acetyl-D-galactosamine and advantageously designates D-glucose, L-rhamnose, D-xylose, N-acetyl-D-glucosamine or L-fucose and more preferably L-rhamnose.

[0034] Advantageously, the polysaccharide containing up to 6 sugar units and selected from D-maltose, D-lactose, D-cellobiose, D-maltotriose, a disaccharide combining a uronic acid selected from D-iduronic acid or D-glucuronic acid with a hexosamine selected from D-galactosamine, D-glucosamine, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, a disaccharide combining L-rhamnose and D-galactose, an oligosaccharide containing at least one xylose which may advantageously be selected from xylobiose, methyl-[3-xylobioside, xylotriose, xylotetraose, xylopentaose and xylohexaose and in particular xylobiose which is composed of two xylose molecules linked by a 1-4 bond.

[0035] More preferably, R' and R'' are different and represent a monosaccharide or polysaccharide selected from D-glucose, D-allose, D-xylose, L-fucose, L-rhamnose, D-galactose, and D-maltose, preferably L-rhamnose and D-galactose as a monosaccharide or disaccharide. More preferably, R' represents a monosaccharide such as L-rhamnose and R'' represents a disaccharide such as a disaccharide combining L-rhamnose and D-galactose.

[0036] More preferably, R'” and R” ” represent a hydrogen.

[0037] The monosaccharide or polysaccharide of R' and / or R' ' can be substituted on one or more hydroxymethyl residues by a -C(O)-COOH group.

[0038] The salt of the compound of formula (I) may be an alkali or alkaline earth metal salt, preferably a calcium, magnesium, sodium or potassium salt.

[0039] Preferably, the compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof, or a salt thereof, or a hydrate thereof, is selected from robinine and its salts.

[0040] The compound of formula (I), or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof, or a salt thereof, or a hydrate thereof, preferably robinine or one of its salts, is present in solubilized form in the composition. By "in solubilized form," it is understood that the compound does not form crystals visible to the naked eye in the composition.

[0041] Robinine (C33H40O19) (or Kaempferol-3-o-gal-rham-7-o-rham or 3-[[6-o-(6-deoxy-al-mannopyranosyl)-[3-d-galactopyranosyl]oxy]-7-[(6-deoxy-al-mannopyranosyl) oxy]-5-hydroxy-2-(4-hydroxyphenyl)-4h-l-benzopyran-4-one; IUP name AC 4',5-Dihydroxy-3-[aL-rhamnopyranosyl-(l—>6)-[3-D-galactopyranosyloxy]-7-(aL-rhamnopyranosyloxy)flavone) is the compound of the following formula (II): OH OH OH

[0042] Robinine can exist in two anomer forms, a and [3. The compound of formula (II) is the [3] anomer of robinine.

[0043] Preferably, the compound of formula (I) or one of its optical isomers, cis-trans or tautomeric, or one of its salts or hydrates is chosen from robinine and its salts, more preferably in the form [3.

[0044] Robinine is a molecule derived from kaempferol. It is a flavone in the form of a yellow-orange powder. This molecule is found, for example, in the leaves and seeds of black locust (Robinia pseudoacacia).

[0045] Robinine, for example, is marketed by INTERCHIM under the name NAVQU® or by SIGMA under the name Robinin®.

[0046] Preferably, the composition comprises between 0.001% and 5% by weight relative to the total weight of the composition, more preferably between 0.01% and 4%, even more preferably between 0.02% and 3%, or between 0.03% and 1% by weight relative to the total weight of the composition, of at least one compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof.

[0047] Preferably, the composition comprises between 0.001% and 5% by weight relative to the total weight of the composition, more preferably between 0.01% and 4%, even more preferably between 0.02% and 3%, or between 0.03% and 1% by weight relative to the total weight of the composition, of the total amount of compound of formula (I) and an optical isomer thereof, and a cis-trans isomer thereof, and a tautomer thereof and a salt thereof, and a hydrate thereof.

[0048] Preferably, the composition comprises between 0.001 and 5% by weight of robinine or one of its salts relative to the total weight of the composition, preferably between 0.01 and 4% by weight, more preferably between 0.02 and 3% by weight, more preferably between 0.03 and 1% by weight.

[0049] Unless otherwise stated, percentages are expressed as a percentage of the total weight of the composition.

[0050] Finally, the composition according to the invention includes ingredients commonly used in the cosmetic field.

[0051] The composition according to the invention comprises at least one compound selected from thickeners, preservatives, perfumes, bactericides, pigments, dyes, inorganic carbon and / or silicone oils, waxes, fillers, emulsifiers, co-emulsifiers, UVA and / or UVB light-protecting agents also known as UV filters, polymers, and hydrophilic and lipophilic gelling agents. A person skilled in the art can adjust the type and quantity of these ingredients in the compositions according to the invention through routine operations, so that the desired cosmetic and stability properties of these compositions are not negatively affected. The quantities of these various ingredients are conventionally those used in the particular field, for example, from 0.01% to 20% of the total weight of the composition.

[0052] In one embodiment, the composition of the invention further comprises one or more cutaneous active agents selected from anti-aging agents and wound healing agents.

[0053] The term "anti-aging agents" refers to all cosmetic agents known to those skilled in the art suitable for reducing and / or slowing down the progression of signs of skin aging such as marked skin microrelief, fine lines, the appearance of wrinkles, loss of tone, loss of density, loss of firmness, loss of elasticity, decrease in the thickness of the dermis and / or epidermis, dryness, withered skin, loss of radiance of the skin complexion, the appearance of a dull appearance of the skin, sagging of the skin, withering of the skin and loss of the skin's regenerative capacity.

[0054] The expression "wound healing agents" refers to any cosmetic agent known to those skilled in the art and suitable for promoting and / or accelerating wound healing.

[0055] The cutaneous active agent(s) may be included in the cosmetic composition in an amount ranging from 0.001% to 5% by weight relative to the total weight of the composition, more preferably between 0.01% and 2%, even more preferably between 0.02% and 1%, or between 0.05% and 1% by weight relative to the total weight of the composition.

[0056] In another embodiment, the composition of the invention comprises only said at least one compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer of this or a salt of this or a hydrate of this, as a cutaneous active agent.

[0057] The composition according to the invention comprises a cosmetically acceptable medium.

[0058] The expression "cosmetically acceptable medium" here refers to a non-toxic carrier that can be applied to keratinous materials such as skin and mucous membranes. Thus, a cosmetically acceptable medium is compatible with the skin, integument, and / or mucous membranes; it does not induce any sensation of discomfort or, more generally, any disturbance likely to lead the user to suspend or discontinue the administration of the cosmetic composition.

[0059] More specifically, said cosmetically acceptable medium may comprise water and / or one or more water-miscible organic solvents. Said solvent may be selected from polyols and alcohols, such as glycerin, sorbitol, glycols such as butylene glycol, propylene glycol, isoprene glycol, dipropylene glycol, hexylene glycol, polypropylene glycol, ethanol or propanediol.

[0060] Preferably, the composition according to the invention has a water content ranging from 20% to 95% by weight, more preferably from 30% to 70% by weight relative to the total weight of the composition.

[0061] The composition according to the invention may include an oily phase.

[0062] The compositions according to the invention can have all the dosage forms conventionally used for topical application and in particular in the form of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) emulsions or multiple emulsions (triple: W / O / W or W / O / W emulsions), aqueous gels, or dispersions of an oily phase in an aqueous phase using spheres, these spheres potentially being ionic and / or non-ionic lipid vesicles (liposomes, niosomes, oleosomes). These compositions are prepared using routine methods.

[0063] The cosmetic compositions of this disclosure are preferably stable. The term "stable" as used here means that the cosmetic composition does not visually separate into phases or crystallize and degrade completely.

[0064] In a preferred embodiment, the compositions used in the context of the invention are intended for topical administration. In a preferred embodiment, the compositions used in the context of the invention are intended for application to the skin.

[0065] In the context of the invention, the term "skin" means any cutaneous surface of the body, preferably the skin of the face or neck or legs, and more particularly the skin of the face or neck.

[0066] Advantageously, the compositions according to the invention are in the form of a gel, or an emulsion, powder or paste. Furthermore, the composition according to the invention may be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a foaming gel, a scrub, a mask, a treatment, a toner or a mousse.

[0067] The compositions according to the invention can be applied directly to the skin or, alternatively, to occlusive or non-occlusive cosmetic carriers intended for local application to the skin. Non-limiting examples of cosmetic carriers include patches, wipes, and masks. The composition may or may not be rinsed off after application to the skin; preferably, it is not rinsed off. Uses

[0068] The present invention also relates to the use of at least one compound of formula (I) as described herein or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, to promote and / or accelerate skin regeneration.

[0069] Preferably, the compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, is chosen from robinine and its salts, it is preferably chosen from robinine and its salts in the form [3.

[0070] The present invention also relates to the use of a composition according to the invention, to promote and / or accelerate skin regeneration.

[0071] Skin regeneration is the innate ability of living organisms to repair their skin through a healing process. In the context of the invention, skin regeneration can follow skin injury, or skin whose barrier function has been compromised, for example, during or after cosmetic surgery procedures.

[0072] The term "promote" here refers to the increase in the effects of the phenomenon. For example, the action of promoting skin regeneration can lead to greater skin generation than without the use according to the invention.

[0073] Here, the term "accelerate" refers to the acceleration of the phenomenon. For example, accelerating skin regeneration can result in the same amount of regenerated skin but in less time than without the use according to the invention.

[0074] The present invention relates to the use of at least one compound of formula (I) as described herein or an optical isomer thereof, or a cis-trans isomer thereof. ci (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, according to the invention, to prevent and / or treat the signs of aging.

[0075] Preferably, the compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, is chosen from robinine and its salts, it is preferably chosen from robinine and its salts in the form [3.

[0076] The present invention relates to the use of a composition according to the invention, to prevent and / or treat the signs of aging.

[0077] Here, the term "prevent" or "prevention" refers to any action aimed at preventing the onset of discomfort or illness in a person. This term therefore covers the cessation or limitation of symptoms, but is limited to cosmetic aspects.

[0078] Here, the term "treat" or "treatment" refers to any action aimed at improving a person's comfort or well-being. This term therefore covers the alleviation, slowing, reduction, or suppression of symptoms, but is limited to cosmetic treatment.

[0079] The term "signs of aging" here refers to all the changes that occur in an elderly person. Preferably, the signs of aging according to the invention are signs of skin aging.

[0080] The term "signs of skin aging" here refers to all the changes in the skin that occur with age and that are sometimes not visible at an early stage. Signs of skin aging include marked skin microrelief, fine lines, the appearance of wrinkles, loss of tone, loss of density, loss of firmness, loss of elasticity, decreased thickness of the dermis and / or epidermis, dryness, sagging skin, loss of radiance in the skin tone, the appearance of a dull skin appearance, sagging skin, wrinkles, and loss of the skin's regenerative capacity.

[0081] The present invention relates to the use of at least one compound of formula (I) as described herein or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, to promote and / or accelerate wound healing.

[0082] Preferably, the compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, is chosen from robinine and its salts, it is preferably chosen from robinine and its salts in the form [3.

[0083] The present invention relates to the use of a composition according to the invention, to promote and / or accelerate wound healing and in particular the healing of skin wounds.

[0084] Wound healing is the innate ability of living organisms to recover from injury through a healing process. In the context of the invention, skin regeneration can follow a skin lesion or injury.

[0085] Preferably, the uses according to the invention are topical uses. Preferably, the composition is applied to the skin, more preferably to the face, legs, or body, more preferably to the face. Methods

[0086] The invention relates to a non-therapeutic, preferably cosmetic, skin treatment method comprising the step of applying the composition according to the invention to the skin.

[0087] Preferably, the application step of the composition is carried out by topical application of said composition, more preferably on the face, legs or body, more preferably on the face or neck.

[0088] Preferably, the skin exhibits at least one sign of skin aging as defined above.

[0089] Preferably, the application is carried out on the skin of a subject who needs it and in an effective quantity of the composition. Here, the term "subject" refers to a human being.

[0090] Preferably, the subject does not suffer from dermatological lesions and / or dermatological diseases, more preferably the subject does not suffer from any diseases.

[0091] Here, the term "effective quantity" refers to the quantity of composition according to the invention, which, as a whole, allows:

[0092] - to promote and / or accelerate skin regeneration, and / or

[0093] - to prevent and / or treat the signs of aging, and / or

[0094] - promote and / or accelerate wound healing.

[0095] According to the present invention, the methods are non-therapeutic methods.

[0096] The methods of the invention may include a single administration. In another embodiment, the administration is repeated, for example, 2 to 3 times a day for one day or more and generally for a prolonged period of at least 4 weeks or 4 to 15 weeks, or as long as necessary.

[0097] The invention also relates to a non-therapeutic, preferably cosmetic, method for treating the skin to promote and / or accelerate wound healing after aesthetic procedures, the method comprising:

[0098] (a) the treatment of the skin with at least one skin-modifying stimulus, and

[0099] (b) after step (a) the application of at least one compound of formula (I), or a optical isomer of it, or a cis-trans isomer of it (such as an anomer alpha or beta), or a tautomer thereof or a salt thereof, or a hydrate thereof according to the invention on the skin.

[0100] Preferably, the compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, is chosen from robinine and its salts, preferably chosen from robinine and its salts in the form [3.

[0101] By "skin-modifying stimulus" is meant an action on the skin that will induce a change in the skin, such a stimulus being able to temporarily compromise the skin's barrier function. For example, skin modification includes an exfoliating agent, a laser, radiofrequency, electrical energy, heat, low-level light, a needle, or an abrasive instrument.

[0102] The invention also relates to a non-therapeutic, preferably cosmetic, method for treating the skin to promote and / or accelerate wound healing after aesthetic procedures, the method comprising:

[0103] (a) the treatment of the skin with at least one skin-modifying stimulus, and

[0104] (b) after step (a) the application of a composition according to the invention to the skin.

[0105] In yet other embodiments, the non-therapeutic, preferably cosmetic, process according to the invention comprises:

[0106] (a) treatment of the skin with at least one type of modifying stimulus skin, for example a laser, radio frequency, electrical device, heat, low-level light, needle, or abrasive instrument; and

[0107] (b) after step (a) the application of at least one compound of formula (I), or a optical isomer of the latter, or a cis-trans isomer of the latter (such as an alpha or beta anomer), or a tautomer of the latter or a salt of the latter, or a hydrate of the latter according to the invention on the skin, in particular within about 6 hours after step (a).

[0108] Preferably, the compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof (such as an alpha or beta anomer), or a tautomer thereof or a salt thereof, or a hydrate thereof, is chosen from robinine and its salts, preferably chosen from robinine and its salts in the form [3.

[0109] In still other embodiments, the method according to the invention comprises:

[0110] (a) treatment of the skin with at least one type of modifying stimulus skin, for example a laser, radio frequency, electrical device, heat, low-level light, needle, or abrasive instrument; and

[0111] (b) after step (a) the application of a composition according to the invention to the skin, in in particular within approximately 6 hours after step (a). Brief description of the drawings

[0112] [Fig-1]: [Fig. 1]. Keratinocyte growth factor (KGF) and robinin both promote proliferation in (A) primary human keratinocytes as determined by post-treatment manual cell counting, and (B) in the HaCaT keratinocyte cell line as determined by BrdU assay. ** denotes p,0.01, **** p < 0.0001, 1-way ANOVA, Tukey post-hoc comparison. n = 3-8.

[0113] [Fig. 2]: [Fig. 2]. Robinine increases the proliferation of primary keratinocytes, as determined by the total cell count, while kaempferol reduces the cell count. *** indicates p < 0.001, **** p < 0.0001, 1-way ANOVA, Tukey post-hoc comparison. n = 3.

[0114] [Fig. 3]: [Fig. 3]. Robinine promotes keratinocyte survival after DUVR as assessed by the MTT assay. Viability is normalized to untreated keratinocytes that were not exposed to DUVR. N = 10 wells / group. One-way ANOVA, Tukey post-hoc comparison. * p<0.05, **** p<0.0001, n=8. Example#: Materials and processes Cell proliferation assays

[0115] Cell culture and processing

[0116] Primary adult human keratinocyte cells were obtained from biopsies. HaCaT keratinocytes were obtained from ATCC (Manassas, Virginia, USA). For the primary keratinocyte proliferation assays, cells were placed on a 6-well plate at 1 x 10³ cells / cm² and cultured overnight in 1X serum-free keratinocyte medium at 37°C, 5% CO₂. The cells were then treated on days 1 and 3 after seeding with either the vehicle (1:1000 DMSO), keratinocyte growth factor (KGF), robinin, or kaempferol. On day 5, the cells were trypsinized, washed, and manually counted using a trypan blue exclusion assay. The HaCaT cells used in the proliferation assays were seeded at 8 x 103 cells / well in a 96-well plate and starved overnight in serum-free DMEM.The cells were then processed as indicated for 48 hours, after which they were processed using a commercial BrdU kit according to the manufacturer's instructions. The data represent a mean standard deviation ± 6 technical replicates per state. Cell survival assay

[0117] Primary human keratinocytes were placed in 3 x 10⁴ cell / well plates in a 96-well plate for 24 hours, after which the cells were washed 3 times with PBS, with 100 µl of PBS added to the well after washing final. The cells were then exposed to daily UV radiation (DUVR) at 10 mJ / cm2. After exposure, the PBS was replaced with serum keratinocyte-free growth medium (KSFM) with the indicated treatments for 24 hours, after which cell viability was determined using the MTT cell growth assay kit. RESULTS

[0118] Promoting keratinocyte proliferation is a key mechanism by which many anti-aging and skin-regenerating molecules improve the clinical signs of skin aging, including growth factors such as KGF. To examine robinin's ability to stimulate proliferation within skin cells, primary normal human keratinocytes (NEHK) or HaCaT keratinocytes were treated with KGF or robinin as directed. Treatment with KGF resulted in an increase in cell count consistent with previous reports, as did treatment with robinin (50 pM, i.e., 0.037%) [Figure IA]. Both KGF and robinin also promoted cell proliferation in HaCaT keratinocytes [Figure IB]. These data collectively demonstrate that robin promotes this key endpoint of skin cell regeneration, consistent with KGF.

[0119] Kaempferol has been reported to possess antioxidant and photoprotective properties consistent with an anti-aging effect on the skin, but it presents considerable problems with in vitro toxicity and poor water solubility. To compare the activity of robinine and kaempferol, a proliferation assay was performed in primary keratinocytes using the same concentrations of both molecules. While robinine increased cell number as expected, cells treated with kaempferol showed a significantly reduced cell number [Fig. 2], a likely result of kaempferol toxicity in keratinocytes. These data demonstrate the biological difference between kaempferol and robinine.

[0120] One of the main biological properties of KGF is that it can promote cell survival. The inventors therefore investigated the ability of robinin to promote survival in primary keratinocytes exposed to toxic levels of UV light. Exposure of keratinocytes to daily ultraviolet radiation (DUVR) at 10 J / cm² resulted in significant cell death, which was improved by treatment with KGF [Fig. 3]. Keratinocytes treated with 5 pM (0.0037%) of robinin for 24 hours after DUVR did not alter cell survival. However, treatment with 50 pM (0.037%) increased survival to a level similar to that of KGF. These data demonstrate that robinin acts on keratinocytes in a similar way to KGF. CONCLUSION

[0121] These data demonstrate that robinin promotes keratinocyte proliferation in both primary normal human keratinocytes and HaCaT cells, which is consistent with the pro-proliferative effects of the key skin-regenerating growth factor KGF and is functionally distinct from kaempferol. Similarly, robinin promotes cell survival after high-dose UV exposure, consistent with the cell-protective effects imparted in the skin and skin cells by KGF.

Claims

Demands

1. Cosmetic composition, comprising in a cosmetically acceptable medium: - at least one compound of formula (I) or an optical isomer thereof, or a cis-trans isomer thereof, or a tautomer thereof or a salt thereof, or a hydrate thereof, r-(D ; oh in which: - R' and R” being identical or different, preferably different, and representing a hydrogen, or an alkyl (C1-C4) such as a methyl, ethyl, propyl, isopropyl, butyl and isobutyl, preferably a methyl, or a monosaccharide or polysaccharide comprising up to 20 sugar units, preferably up to 6 sugar units, in the form of pyranose and / or furanose and of the L and / or D series, said monosaccharide or polysaccharide being able to be substituted by a compulsorily free hydroxyl group and / or facultatively one or more amine functions, optionally one or more protected amine functions, said monosaccharide or polysaccharide being optionally substituted on its -CH2OH group by a -C(O)-CO2H group and said monosaccharide or polysaccharide being optionally substituted on one or more of its hydroxyl groups by an acyl (C1-C4) group, of preferably an acetyl group, or by a hydroxycinnamyl group, chosen from coumaroyl,caffeoyl, feruloyl or sinapoyl; -R'” and R”” being identical or different and representing a hydrogen or an alkyl (C1-C4), such as a methyl, an ethyl, a propyl, an isopropyl, a butyl and an isobutyl, preferably a methyl, - it being understood that R', R”, R” ', and R” ” cannot represent a hydrogen at the same time; and; - at least one compound selected from among thickeners, preservatives, perfumes, bactericides, pigments, dyes, inorganic carbon and / or silicone oils, waxes, fillers, emulsifiers, co-emulsifiers, UVA and / or UVB light protection agents also known as UV filters, polymers, gelling agents, hydrophiles and lipophiles.

2. Composition according to claim 1, said compound being robinine or one of its salts.

3. Composition according to claim 2, said robinine or one of its salts being in the form [3.

4. Composition according to any one of claims 1 to 3 further comprising one or more cutaneous active agents selected from anti-aging agents and wound-healing agents.

5. Composition according to any one of claims 1 to 4, characterized in that the concentration of said at least one compound of formula (I) is between 0.001% and 5% by weight relative to the total weight of the composition.

6. Use of at least one compound of formula (I) according to claim 1, or of an optical isomer thereof, or of a cis-trans isomer thereof, or of a tautomer thereof or of a salt thereof, or of a hydrate thereof, or of a composition according to any one of claims 1 to 5, to prevent and / or treat signs of aging.

7. Use according to claim 6, signs of aging being signs of skin aging.

8. Non-therapeutic method for treating the skin, comprising the step of applying the composition according to any one of claims 1 to 5 to the skin.

9. Method according to claim 8, the skin exhibiting at least one sign of skin aging.

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