COSMETIC COMPOSITIONS COMPRISING ROBININE

Abstract

COSMETIC COMPOSITIONS COMPRISING ROBININ The present invention relates to cosmetic compositions comprising a compound of formula (I) and their use for promoting and / or accelerating skin regeneration, for preventing and / or treating signs of aging and for promoting and / or accelerating wound healing. The invention also relates to cosmetic methods comprising the application of such compositions. Figure for 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 thereof or a salt thereof, or a hydrate thereof, and their use for promoting and / or accelerating skin regeneration, for preventing and / or treating signs of aging and for promoting and / or accelerating wound healing. The invention also relates to cosmetic methods 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 skin injury or within skin whose barrier function is compromised. For example, the skin barrier may become unbalanced after a cosmetic procedure such as laser treatments and chemical exfoliations, or in the presence of external aggressors such as irritants (detergents, acids, bases, oxidants, reducing agents, concentrated solvents, toxic gases or fumes), mechanical stresses (friction, shocks, abrasion, surface tearing, projection of dust, particles, shaving or hair removal), thermal or climatic imbalances (cold, dryness, radiation), xenobiotics (unwanted microorganisms, allergens) or internal attacks such as psychological stress.Following such external aggressions, a healing process is triggered, aimed at quickly and completely restoring this barrier. This physiological process depends on complex biological mechanisms involving numerous molecules and enzymes.

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

[0005] The objective of the invention is therefore to propose a cosmetic composition which 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] The present application provides compositions for accelerating skin regeneration after skin injury or after a cosmetic procedure, for promoting recovery after said skin injury and / or improving the effectiveness of cosmetic skin procedures. Use of the compositions will result in faster healing and recovery time from the procedure, resulting in a greater patient willingness 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 thereof, or a tautomer thereof or a salt thereof, or a hydrate thereof, and

[0010] - at least one compound chosen 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 called UV filters, polymers, gelling agents, hydrophilic and lipophilic agents.

[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 are sucrose (or saccharose), glucose, galactose, rhamnose, galactose, ribose, fucose, maltose, fructose, mannose, arabinose, xylose or lactose;

[0013] - a “monosaccharide” means a monosidic 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 one of its salts or solvates such as one of its hydrates;

[0014] - “disaccharide” means a di-ossidic sugar which is a compound consisting of two oses linked together by O-osidic bonds, said compounds consisting of two monosaccharides (also called mono-osidics) 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 osidic 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 oses (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 which represents x-1;

[0015] - “salt” means a cosmetically acceptable salt, i.e. compatible with application to the skin, mucous membranes and / or appendages;

[0016] - in the following 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 the present 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, for promoting and / or accelerating 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, for preventing and / or treating the 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, for promoting and / or accelerating 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 method of treating the skin to promote and / or accelerate the healing of wounds after aesthetic procedures, the method comprising:

[0023] (a) treating the skin with at least one skin-altering stimulus, and

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

[0025] Other subjects, characteristics, aspects and advantages of the invention will appear even more clearly on reading the description and the examples which 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 hydrogen, or an alkyl (C1-C4) such as methyl, ethyl, propyl, isopropyl, butyl and isobutyl, preferably 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 L and / or D series, said monosaccharide or polysaccharide being able to be substituted by an obligatorily 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 a acyl group (C1-C4), preferably an acetyl group, or by a group hydroxycinnamyl, selected from coumaroyl, caffeoyl, feruloyl or sinapoyl;

[0029] - R' ” and R” ” are the same or different and represent a hydrogen or an alkyl (C1-C4), such as methyl, ethyl, propyl, isopropyl, butyl and isobutyl, preferably 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 L and / or D range, said monosaccharide or polysaccharide having at least one hydroxyl function which is obligatorily free and / or optionally one or more amine functions which are obligatorily protected.

[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 denotes 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 be advantageously 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 a 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 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' ' may 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 a salt thereof, is present in solubilized form in the composition. By "in solubilized form" is meant that the compound does not form crystals visible to the naked eye in the composition.

[0041] Robinine (C33H4oOi9) (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, α 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, cis-trans or tautomeric isomers, 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] Robinin, 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 the 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, the percentages are expressed by weight of the total weight of the composition.

[0050] Finally, the composition according to the invention comprises ingredients usual in the cosmetic field.

[0051] The composition according to the invention comprises at least one compound chosen from thickeners, preservatives, perfumes, bactericides, pigments, dyes, inorganic carbon and / or silicone oils, waxes, fillers, emulsifiers, coemulsifiers, UVA and / or UVB light protection agents also called UV filters, polymers, 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 by means of routine operations, so that the desired cosmetic properties and stability properties of these compositions are not adversely affected. The amounts of these various ingredients are conventionally the amounts 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 chosen from anti-aging agents and wound healing agents.

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

[0054] The expression “wound healing agents” designates any cosmetic agent known to those skilled in the art and suitable for promoting and / or accelerating the healing of wounds.

[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 thereof or a salt thereof or a hydrate thereof, as a skin active agent.

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

[0058] The expression "cosmetically acceptable medium" here designates a non-toxic support which can be applied to keratinous materials such as the skin and mucous membranes. Thus, a cosmetically acceptable medium is compatible with the skin, the integuments and / or the mucous membranes, it does not induce any sensation of discomfort or, more generally, any disorder likely to cause the user to suspend or stop the administration of the cosmetic composition.

[0059] More particularly, said cosmetically acceptable medium may comprise water and / or one or more water-miscible organic solvents. Said solvent may be chosen 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 comprise an oily phase.

[0062] The compositions according to the invention may 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 (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 lipid vesicles of ionic and / or non-ionic type (liposomes, niosomes, oleosomes). W / O / W or O / W / O) emulsions, aqueous gels, or dispersions of an oily phase in an aqueous phase using spheres, these spheres potentially being lipid vesicles of ionic and / or non-ionic type (liposomes, niosomes, oleosomes). These compositions are prepared using routine methods.

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

[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" designates 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 have the form of a gel, or an emulsion, powder or paste. In addition, 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 tonic or a mousse.

[0067] The compositions according to the invention may be applied directly to the skin or, alternatively, to cosmetic supports of the occlusive or non-occlusive type, intended to be applied locally to the skin. As non-limiting examples of cosmetic supports, mention may be made of a patch, a wipe, a mask on a support. The composition may or may not be rinsed after being applied to the skin, preferably it is not rinsed. 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, for promoting and / or accelerating 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 selected from robinine and its salts, it is preferably selected 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 the regeneration of the skin.

[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 may follow skin injury, skin whose barrier function has been compromised, for example during or after cosmetic surgery procedures.

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

[0073] Here, the term "accelerate" refers to accelerating the phenomenon. For example, accelerating skin regeneration may 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, for preventing and / or treating 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 selected from robinine and its salts, it is preferably selected from robinine and its salts in the form [3.

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

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

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

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

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

[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, for promoting and / or accelerating 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 selected from robinine and its salts, it is preferably selected 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 the healing of wounds 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 may follow skin injury or skin 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, method for treating the skin comprising the step of applying the composition according to the invention to the skin.

[0087] Preferably, the step of applying the composition is carried out by the 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 in need thereof and in an effective amount of the composition. Here, the term "subject" designates a human being.

[0090] Preferably, the subject does not suffer from a dermatological lesion and / or dermatological disease, more preferably the subject does not suffer from any disease.

[0091] Here, the term “effective amount” designates the amount of composition according to the invention, which, as a whole, makes it possible to:

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

[0093] - 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 comprise a single administration. In another embodiment, the administration is repeated, for example, 2 to 3 times per day for one or more days and generally for an extended 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 of treating the skin to promote and / or accelerate the healing of wounds after aesthetic procedures, the method comprising:

[0098] (a) treating the skin with at least one skin-altering stimulus, and

[0099] (b) after step (a) the application of at least one compound of formula (I), or a optical isomer thereof, or a cis-trans isomer thereof (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 selected from robinine and its salts, it is preferably selected 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 modification of the skin, such stimulus being able to temporarily compromise the barrier function of the skin. For example, the skin modification includes a peeling agent, a laser, a radio frequency, an electrical energy, heat, a low level light, a needle or an abrasive instrument.

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

[0103] (a) treating the skin with at least one skin-altering stimulus, and

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

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

[0106] (a) treating the skin with at least one type of skin-altering 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 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 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 selected from robinine and its salts, it is preferably selected from robinine and its salts in the form [3.

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

[0110] (a) treating the skin with at least one type of skin-altering 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 particular within approximately 6 hours after step (a). Brief description of the drawings

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

[0113] [Fig.2]: [Fig.2]. Robinine increases the proliferation of primary keratinocytes, as determined by total cell number, while kaempferol reduces cell number. *** 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 with 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 treatment

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

[0117] Primary human keratinocytes were plated at 3 x 104 cells / well 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. Cells were then exposed to daily UV radiation (DUVR) at 10 mJ / cm2. After exposure, 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] Promotion of 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 the ability of robinin to stimulate proliferation within skin cells, primary normal human keratinocytes (NEHK) or HaCaT keratinocytes were treated with KGF or robinin as indicated. KGF treatment resulted in an increase in cell number consistent with previous reports, as did robinin treatment (50 pM, i.e., 0.037%) [Figure 1A]. Both KGF and robinin also promoted cell proliferation with HaCaT keratinocytes [Figure 1B]. These data collectively demonstrate that robin promotes this key criterion 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 has considerable problems with in vitro toxicity and poor water solubility. To compare the activity of robinin and kaempferol, a proliferation assay was performed in primary keratinocytes using the same concentrations of both molecules. While robinin increased cell numbers as expected, cells treated with kaempferol showed significantly reduced cell numbers [Fig. 2], a likely result of kaempferol toxicity in keratinocytes. These data demonstrate the biological difference between kaempferol and robinin.

[0120] One of the key biological properties of KGF is that it can promote cell survival. The inventors therefore examined 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 ameliorated by KGF treatment [Fig. 3]. Keratinocytes treated with 5 µM (0.0037%) of robinin for 24 hours after DUVR did not alter cell survival. However, treatment with 50 µM (0.037%) increased survival to a level similar to that of KGF. These data demonstrate that robinin acts on keratinocytes in a manner similar to KGF. CONCLUSION

[0121] These data demonstrate that robinine 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 different from kaempferol. Similarly, robinine promotes cell survival after high-dose UV exposure, consistent with the cellular protective effects imparted in skin and skin cells by KGF.

Claims

Claims

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, an ethyl, a propyl, an isopropyl, a butyl and an isobutyl, preferably a methyl, or a monosaccharide or a polysaccharide comprising up to 20 sugar units, preferably up to 6 sugar units, in the form of pyranose and / or furanose and of L and / or D series, said monosaccharide or polysaccharide being able to be substituted by a hydroxyl group which is obligatorily free 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 group (C1-C4), 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 chosen 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 called UV filters, polymers, gelling agents, hydrophilic agents and lipophilic agents.

2. A 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 skin active agents chosen 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 an optical isomer thereof, or a cis-trans isomer thereof, or a tautomer thereof or a salt thereof, or a hydrate thereof, or a composition according to any one of claims 1 to 5, for preventing and / or treating the signs of aging.

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

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

9. The method of claim 8, the skin exhibiting at least one sign of skin aging.

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