Indole and its uses in cosmetics

Abstract

Indole and its uses in cosmetics The present invention relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates and / or isomers for the care of keratin materials, in particular the skin, preferably for improving the signs of cutaneous aging. The present invention relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates and / or isomers as an anti-aging active agent. It also relates to a cosmetic composition which comprises at least one such compound or one of its salts, and / or solvates and / or isomers. Figure for abstract: none

Description

Title of the invention: Indole and its uses in cosmetics

[0001] The present invention relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates and / or isomers for the care of keratin materials, in particular the skin, preferably for improving the cutaneous signs of aging.

[0002] The present invention relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates and / or isomers as an anti-aging active agent.

[0003] It also relates to a cosmetic composition which comprises at least one such compound or one of its salts, and / or solvates and / or isomers.

[0004] The outer layer of the skin, the epidermis, is stratified and composed mainly of three types of cells which are keratinocytes, which are the vast majority, melanocytes and Langerhans cells. Each of these cell types contributes through its own functions to the essential role played in the body by the skin, in particular the role of protecting the body against external aggressions (climate, ultraviolet rays, tobacco, pollution, etc.).

[0005] The alterations associated with skin aging can manifest themselves in different ways, among which we can cite:

[0006] - a microrelief characterized in particular by the appearance of fine wrinkles or fine lines, or also by the presence of visible pores in significant density, by a roughness altering the surface appearance of the skin;

[0007] - loss of radiance, which leads to uneven skin tone;

[0008] - a loss of elasticity, suppleness, firmness, density, tone of the skin, a sagging and / or wilting of the skin;

[0009] - a slowdown in epidermal renewal leading to thinning of the horny layer of the skin and a papery appearance of the skin; and

[0010] - skin dryness resulting from a reduction in the barrier function of the layer skin horniness.

[0011] Among the anti-aging active ingredients available, retinol is unanimously known to be effective on the signs of skin aging, and thus, used to treat a wide range of skin problems, including wrinkles and fine lines, and more generally to improve radiance.

[0012] However, the use of retinol can be limited by its instability, its sensitivity to oxidation, light, heat, but also its spontaneous degradation over time. The instability of retinol thus requires special precautions for good formulation and good use.

[0013] There is therefore a need to provide new active ingredients effective on the signs of skin aging, stable and easier to formulate.

[0014] The present invention meets this need. Indeed, as demonstrated in particular by example, the Applicant has identified that the compound of formula (I) is effective in stimulating cell proliferation and epidermal cell renewal. Summary of the invention

[0015] The present invention thus relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers:

[0016] [Chem.l] (I)

[0017] in which - RI, R2, R3, R4, independently denote a hydrogen atom or a C1-C4 alkyl radical, preferably RI to R4 are identical and preferably denote a hydrogen atom; - R5 and R6 independently denote a hydrogen atom or a monovalent hydrocarbon radical Cl-CIO, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2; - R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl, or R7 and R8 together with the carbon atom which carries them form a heterocycle of 3 to 8 members, preferably of 5 or 6 members, said heterocycle being optionally substituted by one or more hydroxy radicals;

[0018] for the care of keratin materials, in particular the skin.

[0019] The present invention also relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers as an anti-aging active agent.

[0020] The present invention also relates to a cosmetic treatment process for the care of keratin materials, preferably the skin, comprising the application to keratin materials, preferably skin, more preferably skin showing signs of cutaneous aging, of a cosmetic composition comprising in a physiologically acceptable medium, at least one compound of formula (I) or one of their salts, and / or solvates, and / or isomers.

[0021] The present invention also relates to a cosmetic composition comprising in a physiologically acceptable medium at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers. Definitions

[0022] “Keratin materials” means the skin of the body or face, the lips, the mucous membranes, the eyelashes, the nails, and the hair of a human being.

[0023] By "skin" is meant the entire skin of the body and the scalp of a human being and preferably, the skin of the face, décolleté, neck, arms and forearms, hands or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, lips, chin), décolleté and neck.

[0024] By "solvated" is meant the mixture of a compound of formula (I) with one or more molecules of water or organic solvent.

[0025] By "isomer" is meant in particular the optical isomers or any positional isomer, or any geometric isomer of a compound of formula (I).

[0026] The term “unsaturated monovalent hydrocarbon radical” means an unsaturated monovalent hydrocarbon radical comprising at least one unsaturation, preferably conjugated or unconjugated ethylenic, preferably comprising an ethylenic unsaturation.

[0027] The term “salt” of a compound of formula (I) according to the invention means a salt formed by an inorganic or organic acid.

[0028] Examples of acid salts include sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, isonicotinate, lactate, salicylate, citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e. 1,1'-methylene-bis-(2-hydroxy-3-naphthoate). Detailed description

[0029] The present invention thus relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers:

[0030] [Chem.l] (I)

[0031] in which - RI, R2, R3, R4, independently denote a hydrogen atom or a C1-C4 alkyl radical, preferably RI to R4 are identical and preferably denote a hydrogen atom; - R5 and R6 independently denote a hydrogen atom or a monovalent hydrocarbon radical Cl-CIO, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2; - R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl, or R7 and R8 together with the carbon atom which carries them form a heterocycle of 3 to 8 members, preferably of 5 or 6 members, said heterocycle being optionally substituted by one or more hydroxy radicals;

[0032] for the care of keratin materials, in particular the skin.

[0033] Preferably RI, R2, R3, R4, are identical and denote a hydrogen atom.

[0034] Preferably R5 and R6 independently denote a hydrogen atom or a monovalent hydrocarbon radical C1-C10, linear or branched, saturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH. More preferably, R5 and R6 independently denote a hydrogen atom or a monovalent hydrocarbon radical C1-C10, linear or branched, saturated, substituted by at least one radical -CO-NR7R8. Even more preferably, R5 and R6 independently denote a hydrogen atom or a monovalent hydrocarbon radical C1-C6, better still C1-C4, linear or branched, saturated, substituted by a radical -CO-NR7R8.

[0035] Preferably R5 and / or R6 denotes a hydrogen atom.

[0036] Preferably, R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl; more preferably R7 and R8 denote a hydrogen atom.

[0037] Preferably, R7 and R8 together with the carbon atom which carries them form a heterocycle of 3 to 8 members, preferably of 5 or 6 members, said heterocycle being optionally substituted by one or more hydroxy radicals.

[0038] According to a particular embodiment, R5 denotes a hydrogen atom and R6 denotes a monovalent hydrocarbon radical C1-C10, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2.

[0039] According to another embodiment, R6 denotes a hydrogen atom and R5 denotes a monovalent hydrocarbon radical C1-C10, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2.

[0040] According to a preferred embodiment, - RI, R2, R3, R4, are identical and denote a hydrogen atom; - R5 and R6 independently denote a hydrogen atom or a monovalent C1-C6, better still C1-C4, linear or branched, saturated hydrocarbon radical substituted by a -CO-NR7R8 radical; preferably R6 denotes a hydrogen atom; and - R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl; more preferably R7 and R8 denote a hydrogen atom.

[0041] According to a particularly preferred embodiment, the compound(s) of formula (I) are chosen from the compounds of formula (IA) and (IB) as well as salts, and / or solvates, and / or isomers:

[0042] [Chem.2] (IA)

[0043] or

[0044] [Chem. 3]

[0045]

[0046]

[0047]

[0048]

[0049]

[0050] (IB). The present invention relates in particular to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers, for improving the cutaneous signs of aging. The present invention also relates to the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers, as an anti-aging active agent. As mentioned above, the compound of formula (I) is in particular chosen from compounds of structure (IA) or (IB) as well as their salts, and / or solvates, and / or isomers: [Chem. 2] (IA) Or [Chem. 3]

[0051]

[0052]

[0053] (IB). The compound (IA) is also known as indole and can be identified by the following CAS number: CAS 120-72-9. Compound (IB) is also known as indole-3-acetamide and can be identified by the following CAS number: CAS 879-37-8. These compounds (IA) and / or (IB) are commercially available.

[0054] For the purposes of the present invention and unless otherwise indicated, the term "compound of formula (I)" means a compound of formula (I) as well as one of its salts, and / or solvates, and / or isomers.

[0055] The cosmetic use of at least one compound of formula (I) aims at the care of keratin materials and in particular of the skin.

[0056] More particularly, the cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers according to the invention aims to improve the cutaneous signs of aging. Preferably, the compound of formula (I) according to the invention is used as an anti-aging active agent.

[0057] All uses according to the invention are cosmetic, i.e. non-therapeutic.

[0058] As mentioned above, the present invention aims to improve the cutaneous signs of aging.

[0059] By “improving the cutaneous signs of aging” is meant in particular preventing and / or reducing the cutaneous signs of aging.

[0060] By "skin signs of aging" is meant all changes in the external appearance of the skin due to aging.

[0061] The cutaneous signs of aging targeted by the invention may be chosen from an appearance of a microrelief of the skin, a formation and / or a presence of fine wrinkles or fine lines, an appearance of roughness, an alteration of the surface appearance of the skin, an alteration of the radiance of the complexion of the skin, a heterogeneity of the complexion, a loss of elasticity, a loss of suppleness, a loss of firmness, a loss of density, or a loss of tone of the skin, sagging and / or wilting of the skin, a thinning of the horny layer of the skin and a papery appearance of the skin, skin dryness.Preferably, the cutaneous signs of aging targeted by the invention are chosen from the appearance of a microrelief of the skin, the formation and / or the presence of fine wrinkles or fine lines, the appearance of roughness, the alteration of the surface appearance of the skin, the thinning of the horny layer of the skin and the papery appearance of the skin, skin dryness.

[0062] More preferably, the cutaneous signs of aging targeted by the invention are chosen from the appearance of a microrelief of the skin, the formation and / or the presence of fine wrinkles, fine lines, the appearance of roughness, the alteration of the surface appearance of the skin, the thinning of the horny layer of the skin, and skin dryness.

[0063] The skin is in particular the skin of a mammal, preferably human. Preferably, the skin is aged. By "aged skin" is meant a general aesthetic condition of the skin resulting from aging.

[0064] Preferably, the compound(s) of formula (I) according to the invention is (are) used in an amount of between 0.0001 and 10%, preferably between 0.001% and 5%, more preferably between 0.002% and 1%.

[0065] The present invention also relates to a cosmetic treatment process (non-therapeutic) comprising the application to the skin of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers according to the invention. In particular, said process is a cosmetic process for caring for keratin materials, in particular the skin. Said process therefore comprises at least one step of topical application to the skin of said compound(s).

[0066] The present invention also relates to a cosmetic composition comprising at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers, in a physiologically acceptable medium.

[0067] By "physiologically acceptable medium" is meant a medium compatible with keratin materials, in particular the skin. The physiologically acceptable medium is generally adapted to the nature of the support on which the composition is to be applied, as well as to the form in which the composition is to be packaged.

[0068] The physiologically acceptable medium of the composition used is advantageously an aqueous medium.

[0069] It may for example consist of water or a mixture of water and at least one physiologically acceptable organic solvent.

[0070] According to a preferred embodiment, the compositions of the invention comprise at least 20% by weight of water, in particular at least 40% by weight of water relative to the total weight of said composition.

[0071] Preferably, the composition according to the invention has a water content ranging from 20% to 95% by weight, even better from 40% to 90% by weight relative to the total weight of the composition.

[0072] As organic solvents which can be used in the composition of the invention, mention may be made of organic solvents miscible in water.

[0073] By "water-miscible solvent" according to the present invention is meant a compound which is liquid at room temperature and miscible with water, in particular having a miscibility in water greater than 50% by weight at 25°C and atmospheric pressure.

[0074] As organic solvent, mention may be made, for example, of (C2-C4) alcohols such as ethanol and isopropanol; polyols, in particular those having from 2 to 6 carbon atoms such as glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol; polyol ethers such as 2-butoxyethanol, propylene glycol monomethyl ether, monoethyl ether and diethylene glycol monomethyl ether; and mixtures thereof.

[0075] The water-miscible organic solvent(s) may be present in a concentration of 0.01% to 30% by weight, preferably 0.1% to 20% by weight and more preferably 1% to 10% by weight, relative to the total weight of the com- position.

[0076] In particular, the cosmetic composition according to the invention further comprises at least one cosmetic adjuvant.

[0077] Thus, preferably, the composition according to the invention comprising, in a physiologically acceptable medium, at least one compound of formula (I), may also comprise one or more usual cosmetic adjuvants, in particular chosen from hydrophilic or lipophilic gelling agents, preservatives, cosmetic active agents such as anti-aging active agents other than the compound of formula (I), fatty substances such as oils, emulsifiers, antioxidants, vitamins, perfumes, fillers, sunscreens, odor absorbers, desquamating active agents, moisturizing active agents, emollients, and coloring matters, and mixtures thereof.

[0078] The quantities of these different adjuvants are those conventionally used in the fields considered, and for example from 0.01 to 80% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase or into the aqueous phase. These adjuvants, as well as their concentrations, must be such that they do not harm the advantageous properties of the compound of formula (I).

[0079] In the context of the present invention, said cosmetic active agents are preferentially chosen from anti-aging cosmetic active agents other than the compound of formula (I).

[0080] Preferably, the cosmetic composition has a pH of between 6 and 8, preferably between 6.5 and 7.5, even more preferably around 7.

[0081] Preferably, the composition according to the invention comprises the compound(s) of formula (I) according to the invention, in an amount of between 0.0001 and 10%, preferably between 0.001% and 5%, more preferably between 0.002% and 1%.

[0082] As oils which can be used in the composition of the invention, we can cite for example:

[0083] - hydrocarbon oils of animal origin;

[0084] - hydrocarbon oils of vegetable origin;

[0085] - synthetic esters and ethers, in particular of fatty acids, such as oils of formulas R1COOR2 and R1OR2 in which RI represents the residue of a fatty acid containing from 8 to 29 carbon atoms, and R2 represents a hydrocarbon chain, branched or not, containing from 3 to 30 carbon atoms;

[0086] - linear or branched hydrocarbons, of mineral or synthetic origin;

[0087] - fatty alcohols having from 8 to 26 carbon atoms;

[0088] - partially hydrocarbon and / or silicone fluorinated oils;

[0089] - silicone oils;

[0090] - their mixtures.

[0091] Oil means any fatty substance in liquid form at room temperature. (20-25°C) and at atmospheric pressure. These oils can be of vegetable, mineral or synthetic origin.

[0092] In the list of oils cited above, the term hydrocarbon oil means any oil comprising mainly carbon and hydrogen atoms, and possibly ester, ether, fluorine, carboxylic acid and / or alcohol groups.

[0093] Other fatty substances that may be present in the oily phase are, for example, fatty acids containing 8 to 30 carbon atoms; waxes; silicone resins; and silicone elastomers.

[0094] These fatty substances can be chosen in a variety of ways by those skilled in the art in order to prepare a composition having the desired properties, for example consistency or texture.

[0095] According to a particular embodiment of the invention, the composition used in the context of the invention is a water-in-oil (W / O) or oil-in-water (O / W) emulsion. The proportion of the oily phase of the emulsion can range from 5 to 90% by weight, and preferably from 5 to 60% by weight relative to the total weight of the composition.

[0096] The composition may comprise at least one emulsifier. The emulsions generally contain at least one emulsifier chosen from amphoteric, anionic, cationic or non-ionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are chosen appropriately depending on the emulsion to be obtained (W / O or O / W). 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.

[0097] As coloring matter, we can cite pigments and / or nacres.

[0098] A composition used according to the invention comprises in particular at least one compound of formula (I) described above or one of its salts, and / or solvates, and / or isomers and can be presented in all the galenic forms normally used in the cosmetic field.

[0099] It may be in particular in the form of an anhydrous composition, an aqueous, hydroalcoholic, optionally gelled solution, a dispersion of the lotion type, optionally two-phase, an oil-in-water or water-in-oil or multiple emulsion, an aqueous gel, a dispersion of oils in an aqueous phase, in particular using spherules, these spherules being able to be polymeric particles or better, lipid vesicles of ionic and / or non-ionic type, or even in the form of a powder, a serum, a paste or a flexible stick or even a stick. It may be of solid, pasty, or more or less fluid liquid consistency. It may be optionally applied to the skin in the form of an aerosol. It may also be in solid form, and for example in the form of a stick.

[0100] Thus, the composition may comprise all the constituents usually employed in the topical application and administration envisaged.

[0101] A composition according to the invention may advantageously be in the form of an emulsion, in particular obtained by dispersing an aqueous phase in a fatty phase (W / O) or a fatty phase in an aqueous phase (O / W), of liquid or semi-liquid consistency of the milk type, or of soft, semi-solid or solid consistency of the cream or gel type, or even of multiple emulsion (W / O / W or O / W / O). These compositions are prepared according to the usual methods.

[0102] Said compound(s) of formula (I) or one of its salts, and / or solvates, and / or isomers, or said composition containing them are used, within the framework of a use or a method according to the invention, by topical route.

[0103] 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 in particular be made of a patch, a wipe, a roll-on and a pen.

[0104] The composition may or may not be rinsed off after being applied to the skin.

[0105] The invention is now illustrated by the following examples. Examples

[0106] The indole used is supplied by Sigma-Aldrich, ref. 13408, CAS 120-72-9, purity greater than or equal to 99%, and corresponds to the formula (IA) mentioned in the context of the present invention.

[0107] The indole-3-acetamide used is supplied by Sigma-Aldrich, ref. 286281, CAS 879-37-8, purity 98%, and corresponds to the formula (IB) mentioned in the context of the present invention. Example 1: Epidermal proliferation test Principle:

[0108] The aim of this study is to evaluate the potential of indole and indole-3-acetamide to modulate the expression of a gene involved in the physiology of normal human epidermal keratinocytes, in particular epidermal renewal such as epidermal proliferation, by quantitative RT-PCR.

[0109] Indole is estimated at 0.1 g / L (i.e. 0.01%) in DMSO.

[0110] Indole-3-acetamide is estimated at 0.17 g / L (i.e. 0.017%) in DMSO.

[0111] Indole and indole-3-acetamide are compared to retinoic acid at 10-7 M (i.e. 3.10-5 g / L) in DMSO.

[0112] The most significant marker studied is the epidermal renewal gene HBEGF (Heparin-binding EGF-like growth factor, Gene ID No. 1839). HBEGF is a growth factor that binds to the EGF receptor and stimulates epithelial cell growth. The effects of retinoic acid on hyperplasia (in vitro and in vivo) have been shown to be mediated by an increase in the expression of this factor (Retinoid-Induced Epidermal Hyperplasia Is Mediated by Epidermal Growth Factor Receptor Activation Via Specifies Induction of its Ligands Heparin-Binding EGF and Amphiregulin in Human Skin In Vivo. Rittié L. et al. 2006. Journal of Investigative Dermatology, Vol 126, Issue 4, 732-739). The housekeeping gene GAPDH serves as a normalizing gene for the results. Protocol (experimental conditions): Cytotoxicity

[0113] Normal human keratinocytes were seeded into 96-well plates and cultured for 24 hours in medium dosage. The culture medium was then replaced with culture medium containing or not (control) the test compounds. After 72 hours of incubation, cell viability was measured according to a standard measure of mitochondrial activity using MTT.

[0114] Expression of transcripts in human keratinocytes

[0115] Human epidermal keratinocytes were seeded in a 24-well culture plate and cultured for 72 hours at 37°C and 5% CO2 in culture medium with renewal of the culture medium after the first 24 hours. At the end of the incubation, the culture medium was replaced with assay medium (supplemented with 1.5 mM CaCl2) containing or not (control) the starting material or reference (retinoic acid) and the cells were incubated for another 24 hours.

[0116] All experimental conditions were performed in n=2. At the end of treatment, cells were washed twice in PBS (without CaCl2, without MgCl2) and RNA extraction was performed using TriPure Isolation Reagent® according to the manufacturer's recommendations. The relative expression of the selected markers was measured by two-step RT-qPCR.

[0117] First, reverse transcription was performed using Transcriptor Reverse Transcriptase (ROCHE) according to the manufacturer's recommendation. Then, PCR experiments were performed using a LightCycler® 480 real-time PCR system by a SYBR®Green incorporation measurement system (Roche). Results and conclusions:

[0118] The results are expressed as a modulation factor (Fc, fold change) compared to the untreated control after normalization of the relative expressions compared to the expression of a housekeeping gene (GAPDH). The Fc value of the housekeeping gene GAPDH is therefore equal to 1. The expression of a gene is considered to be stimulated when it is multiplied by at least 1.5.

[0119] Effects of indole and indole-3-acetamide on the expression of the HBEGE gene involved in the physiology of normal human epidermal keratinocytes. The constitutive GAPDH gene serves as a normalizing gene.

[0120] [Tables 1] Retinoic acid (ref R2625, Sigma, CAS 302-79-4) Indole (ref13408, Sigma, CAS 120-72-9) Indole-3-acetami (ref286281, Sigma, CAS 879-37-8) GENE l,00E-07 l,00E-01 g / L 0.17 g / L or 0.017% M or 0.01% Gene membership gene symbol DMSO DMSO DMSO Epidermal renewal HBEGF 2.64 3.59 3.57 Housekeeping gene GAPDH 1.01 0.97 1.00

[0121] Retinoic acid, tested at 10 7 M (i.e. 3.10-5 g / L), significantly increases (Fc = 2.64) the expression of the HBEGF marker involved in epidermal renewal (Rittié et al. 2006). This result was expected and validates the assay.

[0122] Indole, tested at 0.1 g / L, also significantly increases (Fc = 3.59) the expression of the HBEGF marker involved in epidermal renewal.

[0123] Indole-3-acetamide, tested at 0.17 g / L, also significantly increases (Fc = 3.57) the expression of the HBEGF marker involved in epidermal renewal.

[0124] These results show that indole and rindole-3-acetamide are effective in improving epidermal renewal.

[0125] Example 2: Functional test of epidermal renewal in reconstructed model Principle:

[0126] The aim of this study is to evaluate the efficacy of indole, under systemic conditions, in stimulating epidermal renewal by modulating the thickness and / or quality of the epidermis. tological analysis of a 3D reconstructed model of epidermal tissue between 10 and 14, or 10 and 17 days of maturation.

[0127] Indole is estimated at 30 and 100 pg / mL (i.e. 0.03 and 0.10 g / L) in DMSO.

[0128] Indole is compared to Retinol at 3 pM (i.e. 8.6.10-4 g / L) in DMSO. Protocols (experimental conditions):

[0129] The epidermal thickness evaluation test is carried out to evaluate the effectiveness of the raw materials, in systemic application, on the reconstruction of the epidermis in the 3D in vitro SkinEthic RHE® model for 4 or 7 days. The effects of the active ingredients are determined by an evaluation of the quality of the reconstructed epidermis based on its thickness and morphology. Materials

[0130] - Classic material for biological tests (pipettes, tubes, etc.) - 6-well plates - Optical coherence tomography equipment with Newtone® software (EPISKIN acquisition and EpiSkin RHEV2 processing) - Classic material for histological study (fixing samples, etc.) - 96-well 2 ml Depp plates (if analytical biochemistry tests) Reagents

[0131] - RHE culture medium (SGM) - Retinol DMSO - Formaldehyde - Coloring reagent for HE Biological model

[0132] The experiments are carried out on the reconstructed epidermal model SkinEthic RHE®.

[0133] The tissues are received on medium at D10 and stored at 37°C (95% humidity and 5% carbon dioxide) until the end of the treatments at D14 or D17. RH3E TEST METHOD Solubilization

[0134] For compounds solubilized in DMSO, the 1000X solutions are first vortexed for 1 minute and stored at room temperature.

[0135] For compounds solubilized in water, 10X solutions are prepared in the same manner in the media.

[0136] The solubility aspect is evaluated visually.

[0137] The solutions are then diluted in a medium to obtain the final solution IX and stored at 4°C. Treatment

[0138] Systemic treatments are carried out on D10, D12 and harvest on D14 (Short-term protocol).

[0139] Tissues are cultured with 2 ml of treatment solution (raw material (RM) in SGM medium) in a 6-well plate and stored at 37°C (95% humidity and 5% carbon dioxide) between treatments.

[0140] For all conditions, the MP (Raw Materials) are tested in triplicate (n = 3).

[0141] For MPs of interest, if no toxicity and good histological quality are observed at D14, it is possible to treat the tissues at D14 with 3mL of treatment solution and harvest at D17 in a long-term protocol. Viability

[0142] No specific viability study is carried out in this test. Cell viability is monitored during the first treatment by histological analysis which makes it possible to verify the capacity of the tissue to generate a good quality epidermis. OCT acquisition and analysis

[0143] OCT (Optical Coherence Tomography) is a non-invasive imaging technique, based on the analysis of infrared light reflected by tissues and the creation of an interference signal.

[0144] OCT allows surface aspects to be visualized, the 2D structures of the RHE® model are followed during epidermal reconstruction.

[0145] This also makes it possible to determine, by acquisition and segmentation with Newtone® algorithms, the epidermal thickness of the tissue after reconstruction.

[0146] Image acquisition and analysis are carried out on D10, D12, and D14 under all tested conditions.

[0147] A variation in thickness on the first day of treatment is carried out to observe the evolution of thickness for all tissues.

[0148] In a second step, the thickness variations are rationalized with the vehicle (untreated control or DMSO). Histology

[0149] A histological analysis is carried out on all the conditions tested and on all the tissues to evaluate the impact of the treatment on the quality of the reconstruction.

[0150] The histological process and hematoxylin and eosin staining are performed according to the Episkin histology platform protocol.

[0151] Analysis of treatment cytotoxicity and histological qualities is performed and compared to untreated or vehicle conditions.

[0152] INTERPRETATION CRITERIA References

[0153]

[0154]

[0155]

[0156]

[0157]

[0158]

[0159]

[0160]

[0161]

[0162] The test has 3 references to guarantee the good quality of the tissue batch and the good response of the treatments: - Untreated control, as a negative reference, - DMSO, as a vehicle without effect, - Retinol, a positive reference for tissue quality with an increase in cell proliferation (epidermal thickness) and a reduction in differentiation (histological quality). The expected results for these references are: - Untreated Control (= Untreated Tissue): good and homogeneous overall quality with an epidermal thickness of up to 80 pm on D10 (or on the first day of treatment), - DMSO: good overall quality close to the untreated control without negative impact on the thickness of the epidermis on the day of harvest. - Retinol: a decrease in differentiation compared to the vehicle with better stratification and epidermal thickness up to 15% compared to DMSO from variation D10 to D14. Molecules tested For each molecule tested, the interpretation criteria are based on: - Epidermal thickness, - Histological quality at the end of treatment. Each condition is compared to the vehicle (untreated control or DMSO control). Raw data (OCT measurements) - E10 (pm): Thickness of the epidermis at D10 - E14 (pm): Thickness of the epidermis at D14 Calculations VAR (%): Variation in epidermal thickness between D10 and D14 With VAR (in %) = [(E14 / E10) x 100] - 100 VAR_normalized (%): Variation in epidermal thickness between D10 and D14, normalized: - compared to solvent (DMSO) for Retinol and Indole - and compared to untreated fabric for untreated fabrics and solvent With normalized VAR (%) = VAR (%) - (average of the VARs of the 3 biological replicates (%)) Considering: - biological replicates of DMSO for retinol and indole, - biological replicates of untreated Tissue for untreated Tissues and for the Solvent (DMSO).

[0163] Average_VAR_normalized (%): Average of the Variations in the Thickness of the epidermis between D10 and D14, normalized for the 3 biological replicates

[0164] With Average_normalized_VAR (%) = (normalized_VAR replicate 1 + normalized_VAR replicate 2 + normalized_VAR replicate 3) / 3

[0165] EC_ VAR_normalized (%): Standard deviation of the Variations in the Thickness of the epidermis between D10 and D14, normalized for the 3 biological replicates,

[0166] With EC_ VAR_normalized (%) = Results and conclusions:

[0167] The results of the untreated tissues and DMSO are expressed as the average variation in the thickness of the epidermis of the reconstructed model tissue, between D10 and D14, normalized compared to the untreated tissues.

[0168] The results for retinol and indole are expressed as the mean variation in the thickness of the epidermis of the reconstructed model tissue, between D10 and D14, normalized to the solvent (DMSO).

[0169] These standardized average variations are expressed as a percentage and are considered significant when they are greater than or equal to 10%.

[0170] Variation in thickness (in pm) of the reconstructed epidermal model between D10 and D14. Calculations of the percentages of variation compared to the vehicle. TNT: Untreated tissues

[0171] [Tables2] MP Concentr Biological replicate E10 (pm) (1) E14 (pm) (2) VAR (%) (3) VAR_normalized (%) (4) Mean _VAR_normalized (%) (5) EC_ VAR_normalized (%) (6) ation MP ue TNT na 1 84.04 114.63 36.40 3.84 0.00 3.38 2 91.08 118.46 30.06 -2.50 3 89.85 117.90 31.22 -1.34 DMSO 0.1% 1 90.19 117.16 29.90 -2.66 -3.55 0.78 2 90.06 115.70 28.48 -4.08 3 87.77 112.91 28.64 -3.92 Retino 1 in DMSO 3 pM 1 76.81 127.24 65.66 36.66 37.13 2.68 2 76.08 128.60 69.03 40.02 3 77.09 126.23 63.73 34.72 Indole in DMSO 30 pg / mL 1 84.14 118.02 40.28 11.27 12.85 2.02 2 82.09 115.88 41.16 12.16 3 81.13 116.94 44.13 15.12 Indole in DMSO 100 pg / mL 1 89.34 123.68 38.43 9.43 10.00 3.06 2 84.07 119.64 42.31 13.31 3 89.14 121.48 36.27 7.27

[0172] (1) Thickness OCT J10

[0173] (2) Thickness OCT J14

[0174] (3) Thickness variation between J10_J14

[0175] (4) Thickness variation between J10_J14, normalized

[0176] (5) Average for the 3 biological replicates of the thickness variations between J10_J14, normalized

[0177] (6) Standard deviation for the 3 biological replicates of the thickness variations between J10_J14, normalized

[0178] Retinol, tested at 3 pM (i.e. 8.6.10 4 g / L), significantly increases epidermal thickness with a variation greater than 30%. This result was expected and validates the dosage.

[0179] Indole, tested at 30 and 100 pg / mL (i.e. 0.03 and 0.10 g / L), shows a significant positive effect on epidermal renewal compared to retinol (with respectively 13% and 10% more variation compared to the solvent) under the conditions of carrying out this test.

Claims

Claims

1. Cosmetic use of at least one compound of formula (I) or one of its salts, and / or solvates, and / or isomers: [Chem.l] (I) in which - RI, R2, R3, R4, independently denote a hydrogen atom or a C1-C4 alkyl radical, preferably RI to R4 are identical and preferably denote a hydrogen atom; - R5 and R6 independently denote a hydrogen atom or a monovalent hydrocarbon radical Cl-CIO, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2; - R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl, or R7 and R8 together with the carbon atom which carries them form a heterocycle of 3 to 8 members, preferably of 5 or 6 members, said heterocycle being optionally substituted by one or more hydroxy radicals; for the care of keratin materials, particularly the skin.

2. Use according to claim 1 in which the compound(s) of formula (I) are characterized in that: - RI, R2, R3, R4, are identical and designate an atom hydrogen; and / or - R5 and R6 independently denote a hydrogen atom or a linear or branched, saturated monovalent hydrocarbon radical C1-C10, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH, preferably, R5 and R6 independently denote a hydrogen atom or a linear or branched, saturated monovalent hydrocarbon radical C1-C10, substituted by at least one radical -CO-NR7R8, more preferably, R5 and R6 independently denote a hydrogen atom or a linear or branched, saturated monovalent hydrocarbon radical C1-C6, better still C1-C4, substituted by a radical -CO-NR7R8, even more preferably R5 and / or R6 denotes a hydrogen atom; and / or - R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl; preferably R7 and R8 denote a hydrogen atom; or R7 and R8 together with the carbon atom which carries them form a heterocycle of 3 to 8 members, preferably of 5 or 6 members, said heterocycle being optionally substituted by one or more hydroxy radicals.

3. Use according to claim 1 or 2, in which the compound(s) of formula (I) are characterized in that: - R5 denotes a hydrogen atom and R6 denotes a monovalent hydrocarbon radical Cl-CIO, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2; or - R6 denotes a hydrogen atom and R5 denotes a monovalent hydrocarbon radical Cl-CIO, linear or branched, saturated or unsaturated, substituted by at least one radical -CO-NR7R8, said monovalent hydrocarbon radical being optionally substituted by one or more radicals chosen from -OH and / or -NH2.

4.

5. Use according to any one of the preceding claims, in which the compound(s) of formula (I) are characterized in that: - RI, R2, R3, R4, are identical and denote a hydrogen atom; - R5 and R6 independently denote a hydrogen atom or a monovalent C1-C6, better still C1-C4, linear or branched, saturated hydrocarbon radical substituted by a -CO-NR7R8 radical; preferably R6 denotes a hydrogen atom; and - R7 and R8 independently denote a hydrogen atom; a C1-C4 alkyl radical optionally substituted by one or more hydroxy radicals such as methyl; more preferably R7 and R8 denote a hydrogen atom. Use according to any one of the preceding claims, in which the compound(s) of formula (I) are chosen from the compounds of formula (IA) and (IB) as well as their salts, and / or solvates, and / or isomers: [Chem. 2] (IA) Or [Chem. 3]

6. (IB). Use according to any one of the preceding claims, for improve the skin's signs of aging.

7. Use according to any one of the preceding claims, as an anti-aging active ingredient.

8. Use according to any one of the preceding claims, for preventing and / or reducing at least one cutaneous sign of aging chosen from an appearance of a microrelief of the skin, a formation and / or a presence of fine wrinkles or fine lines, an appearance of roughness, an alteration of the surface appearance of the skin, an alteration of the radiance of the skin complexion, a heterogeneity of the complexion, a loss of elasticity, a loss of suppleness, a loss of firmness, a loss of density, or a loss of tone of the skin, sagging and / or wilting of the skin, a thinning of the horny layer of the skin and a papery appearance of the skin, skin dryness.

9. Use according to any one of the preceding claims, in which the compound(s) of formula (I) is (are) used in an amount of between 0.0001 and 10%, preferably between 0.001% and 5%, more preferably between 0.002% and 1%.

10. Cosmetic composition comprising at least one compound of formula (I) as defined in any one of claims 1 to 5 in a physiologically acceptable medium.

11. Cosmetic composition according to claim 10, further comprising at least one cosmetic adjuvant.

12. Cosmetic composition according to claim 11, wherein said at least one cosmetic adjuvant is chosen from hydrophilic or lipophilic gelling agents, preservatives, cosmetic active agents such as anti-aging active agents other than the compound of formula (I), fatty substances such as oils, emulsifiers, antioxidants, vitamins, perfumes, fillers, sunscreens, odor absorbers, desquamating active agents, moisturizing active agents, emollients, and coloring agents, and mixtures thereof.

13. Cosmetic composition according to claim 12, in which said cosmetic active agents are chosen from anti-aging cosmetic active agents.

14. Composition according to any one of claims 10 to 13, which has a pH of between 6 and 8, preferably between 6.5 and 7.5, more preferably around 7.

15. Method for cosmetic treatment, in particular for the care of keratin materials, in particular the skin, comprising the application to the skin, of at least one compound of formula (I) or of one of its salts, and / or solvates, and / or isomers as defined according to any one of claims 1 to 5.