EP4633627A1

EP4633627A1 - Cosmetic use of a composition for caring for keratin materials comprising at least indole-3-pyruvic acid

Info

Publication number: EP4633627A1
Application number: EP23833085.6A
Authority: EP
Inventors: Amélie PREVOT-GUEGUINIAT; Magali MOREAU; Amina BOUSLIMANI; Okan ALTUNCU; Samira TAMOUTOUNOUR
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2022-12-16
Filing date: 2023-12-15
Publication date: 2025-10-22
Also published as: CN120417898A; KR20250107257A; JP2025541866A; FR3143325A1; WO2024126794A1; FR3143325B1

Abstract

The present invention relates to the cosmetic use, notably topical non-therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole-3- pyruvic acid, an isomer thereof or a salt thereof, for preventing a reduction in the skin barrier function and/or reinforcing the skin barrier function in an individual, in particular of dry skin The invention also relates to the use of such a composition for preventing and/or treating a skin disorder in sensitive skin in an individual and also to the use of such a composition for preventing and/or treating pruritus and/or inflammation in the skin of an individual. Finally, the invention relates to a non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of such a composition.

Description

Title: Cosmetic use of a composition for caring for keratin materials comprising at least indole-3-pyruvic acid

Technical field

The present invention relates to the use of indole-3-pyruvic acid for improving the skin barrier function and moisturizing the skin.

More particularly, the present invention aims to provide the cosmetic use, notably topical non-therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole- 3 -pyruvic acid, an isomer thereof or a salt thereof, for preventing a reduction in the skin barrier function and/or reinforcing the skin barrier function in an individual, in particular of dry skin.

The invention further relates to the cosmetic use, notably topical cosmetic use, of such a composition for preventing and/or treating atopic dermatitis or eczema.

The invention also relates to the cosmetic use, notably topical non-therapeutic cosmetic use, of such a composition for preventing and/or treating a skin disorder of sensitive skin, in an individual.

The invention additionally relates to the cosmetic use, notably topical cosmetic use, of such a composition for preventing and/or treating pruritus and/or inflammation of the skin of an individual, in particular present in a dermatological disorder, chosen from the group constituted of atopic dermatitis or eczema, psoriasis, nodular prurigo, seborrhoeic dermatitis, acne, folliculitis and rosacea.

Prior art

The skin is a tissue of which the cells are joined together and integrally attached to each other. The skin tissue forms an outer covering comprising sebaceous or sweat glands, and hair follicles. The skin, and in particular the scalp, are epithelia which undergo continual renewal. The renewal, or desquamation, is a coordinated and finely regulated process resulting in the imperceptible and invisible removal of the superficial cells.

Human skin is constituted of two compartments, namely an upper compartment, the epidermis, and a deep compartment, the dermis. The epidermis is conventionally divided into a basal layer of keratinocytes that constitutes the germinal layer of the epidermis, a spinous layer constituted of several layers of polyhedral cells positioned on the germinal layers, one to three "granular" layers constituted of flattened cells containing distinct cytoplasmic inclusions, keratohyalin granules, and finally a set of upper layers referred to as the cornified layers (or stratum comeum), constituted of keratinocytes at the terminal stage in their differentiation, referred to as corneocytes.

Comeocytes are anucleated cells mainly constituted of a fibrous material containing cytokeratins, surrounded by a cornified envelope. New keratinocytes are constantly being produced to compensate for the continuous loss of epidermal cells at the cornified layer by a mechanism referred to as desquamation.

Nevertheless, an imbalance between the production of cells at the basal layer and the rate of desquamation may particularly lead to the formation of scales on the surface of the skin. Similarly, a lack of terminal differentiation of the cells of the stratum comeum, for various reasons, can result in the formation of large, thick cell clusters which are visible to the naked eye and are referred to as "squamae", or in other situations, in a thinning of the stratum comeum.

This may lead to a weakness in the barrier properties of the epidermis, to chronic dehydration of the stratum corneum, to a loss of mechanical elasticity, to tautness, and also to a loss of radiance and transparency of the skin.

As examples of factors that promote a reduction in skin surface quality, which weakens the skin barrier, mention may be made of stress, the winter period, excess sebum or a lack of moisturization.

Thus, weakening of the skin barrier can occur in the presence of external attacking factors, notably chosen from irritants (detergents, acids, bases, oxidizing agents, reducing agents, concentrated solvents, gases or noxious fumes, pollutants), thermal or climatic imbalances (cold, drought, radiation), xenobiotics (undesirable microorganisms, allergens) or internal attacking factors such as psychological stress.

This deterioration of the skin barrier may result in skin discomfort, sensory phenomena and notably unpleasant phenomena. The individual who is affected thereby may then experience a feeling of skin discomfort, which may be manifested in particular by stinging, tautness, hotness and/or itching. These feelings of skin discomfort, of cosmetic and non-therapeutic order, are more common in the most exposed areas of the body, namely the hands, the feet, the face and the scalp.

They may occur especially on areas subjected to certain daily or frequently repeated hygiene actions such as shaving, hair removal, cleaning with toiletry products or household products, the application of adhesives (dressings, patches, or the attachment of prostheses) or in the case of sporting or professional actions, or simply actions associated with lifestyle and with the use of clothing, tools or equipment that give rise to localized friction. They may also be amplified by psychological stress.

These feelings of skin discomfort affect everyone, and in particular:

- people with "fragile" or "delicate" and vulnerable skin which becomes rapidly imbalanced during large-amplitude variations in temperature or relative humidity (for example in the case of baby skin);

- people with "weakened" skin, notably including:

(i) people whose protective hydrolipidic film composed of sweat, sebum and natural moisturizing factors becomes diminished, as is the case for elderly people over 60 years old and notably in the case of the very elderly (at least 75 years old);

(ii) people for whom the composition of the hydrolipidic film is modified.

Mention may also be made of people with "attacked" skin, for example shaved skin.

One of the critical steps in the process of terminal differentiation of the stratum corneum is the crosslinking of the precursor proteins of the cornified envelope (CE). This phenomenon has an essential role in the development and maintenance of skin cohesion, of the physical properties of the skin such as the barrier function, and is a crucial step in the abovementioned process of terminal differentiation.

The moisturizing active ingredients conventionally used, such as humectants, moisturizing polymers or fatty substances such as liquid petroleum jelly, temporarily modify the surface properties of the skin. These active ingredients may lead to mechanical softening of the stratum corneum, to an increase in the state of moisturization thereof and/or an improvement in the skin’s microrelief by the formation of a film at the surface of the skin. However, these effects are not necessarily particularly persistent over time. Moreover, these active ingredients can be eliminated by cleansing actions. To overcome these drawbacks, it is advantageous to turn to active agents with a long- lasting beneficial action which is not affected by cleansing while acting on biological pathways, for example by modulating the expression of certain key biological markers in the impairment of the barrier function.

It is known that an impaired epidermal barrier causes keratinocytes to secrete chemokines such as TSLP: (thymic stromal lymphopoietin) which is known to be a key chemokine of keratinocyte communication due to its ability to induce itching by directly activating certain types of neurons (TRPA-1+) and also the type 2 immune responses involved in atopic dermatitis.

In addition, other molecules are involved in this response process following the impairment of the barrier, such as the proteins MCP-1 and MIP-1 involved in inflammatory processes in type 2 immune responses, in particular in patients suffering from atopic dermatitis where they are markedly increased (Kaburagi et al., Arch Dermatol Res. 2001 Jul; 293(7): 350- 5), and also the cytokines interleukin 1 alpha (IL- la) and interleukin 29 (IL-29) which are involved in the general mechanisms of inflammation (Malik and Kanneganti, Immunol Rev. 2018 Jan; 281(1): 124-137), with IL-29 being able to be regulated by the IL-4 present in type 2 immune responses and atopic dermatitis (Megjugorac et al. Blood. 2010 May 27; 115 (21): 4185-90). These two interleukins increase the ability of the skin barrier to respond to external attacking factors.

Thus, there is a need to identify new active agents which make it possible to reduce the expression of these markers.

By identifying these new active agents, it is therefore sought to:

- prevent a reduction in, and/or to reinforce, the skin barrier function, in particular of dry skin; and/or

- prevent and/or reduce feelings of skin discomfort, stinging, tautness, hotness and itching, in particular in people with sensitive, fragile, weakened or delicate skin (for example babies or people aged at least 60 years old and in particular people aged at least 75 years old), or people for whom the composition of the hydrolipidic film is modified, and/or

- improve the skin barrier function, notably of atopic skin, and/or prolong the remission phases between acute crises of this type of condition.

There is thus also a need for an active agent that enables the skin, in particular dry and/or sensitive and/or atopic skin, to maintain its barrier function. There is also a need for an active agent for improving skin moisturization.

There is furthermore a need for active agents for improving the quality and/or complexion of the skin, in particular the quality and/or complexion of sensitive skin; and/or preventing and/or treating skin disorders associated with sensitive skin, in particular chosen from tautness, stinging, hotness and/or itching.

There is also a need for active agents that enable the prevention and/or treatment of pruritus and/or inflammation of the skin of an individual, in particular inflammation of skin affected by a dermatological disorder chosen from the group constituted of atopic dermatitis or eczema, psoriasis, nodular prurigo, seborrhoeic dermatitis, acne, folliculitis and rosacea, or by a dermatological disorder following exposure of the skin to pollutants and/or UV rays.

Disclosure of the invention

The aim of the present invention is to solve the abovementioned technical problems.

Indeed, the inventors have now discovered that indole- 3 -pyruvic acid, in a cutaneous model of atopic dermatitis, makes it possible to significantly reduce the production of the chemokine TSLP, the cytokines IL- la, IL-29 and the proteins MCP-1 and MIP-la.

Summary of the invention

Thus, according to a first aspect, the present invention relates to the cosmetic use, notably topical non-therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for preventing a reduction in the skin barrier function and/or reinforcing the skin barrier function in an individual, in particular of dry skin.

According to a second aspect, the present invention also relates to the cosmetic use, notably topical non-therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for preventing and/or treating atopic dermatitis or eczema.

According to a third aspect, the present invention relates to the cosmetic use, notably topical non-therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for preventing and/or treating a skin disorder of sensitive skin, in an individual. Such a skin disorder may notably be a feeling of discomfort, and in particular tautness, stinging, hotness and/or itching.

According to a fourth aspect, the present invention relates to the cosmetic use, notably topical cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole- 3 -pyruvic acid, an isomer thereof or a salt thereof, for preventing and/or treating pruritus and/or inflammation of the skin of an individual.

An isomer of indole- 3 -pyruvic acid according to the present invention may for example be 3H-indole-3-pyruvic acid.

Pruritus and/or inflammation of the skin of an individual may in particular be present:

- in a dermatological disorder chosen from the group constituted of atopic dermatitis or eczema, psoriasis, nodular prurigo, seborrhoeic dermatitis, acne, folliculitis and rosacea; or

- in a dermatological disorder following exposure of the skin to pollutants and/or UV rays. Lastly, the invention also relates to a non-therapeutic cosmetic method for caring for keratin materials, preferably the skin, comprising the topical application to these keratin materials of a composition comprising, in a physiologically acceptable medium, indole-3- pyruvic acid, an isomer thereof or a salt thereof.

A composition used according to the invention may be applied to fragile, weakened, dry, atopic and/or sensitive skin.

A composition used according to the invention may notably be suitable for topical administration.

Other characteristics, aspects and advantages of the invention will become apparent on reading the detailed description that follows.

Detailed description

Composition used according to the invention

A composition used according to the invention is preferably cosmetic.

A composition used according to the invention is preferentially suitable for topical application to keratin materials, in particular to the skin, and thus comprises a physiologically acceptable medium, i.e. a medium that is compatible with the skin.

The term “cosmetic” means a composition that is compatible with keratin materials, in particular the skin, mucous membranes and the integuments. The composition used according to the invention is non-therapeutic. The term “keratin materials” is intended to denote in particular the skin, mucous membranes, fibres, eyelashes and skin appendages.

The term "skin" is intended to mean all of the skin of the body, and preferably the skin of the face, scalp, neckline, neck, arms and forearms, or more preferably still the skin of the face, the skin of the face (in particular of the forehead, nose, cheeks and chin), of the neckline and of the neck.

A composition used according to the invention preferably comprises a cosmetically acceptable medium, i.e. one which has a pleasant colour, odour and feel and which does not cause any unacceptable discomfort, i.e. stinging or tautness, liable to discourage the user from applying this composition.

As used herein, the terms “treat” and “treatment” mean the alleviation of the symptoms associated with a specific disorder or condition and/or the elimination of said symptoms and also the complete disappearance of the disorder or condition in question.

In the context of the present invention, the terms “prevent” and “prevention” denote the reduction, to a lesser degree, of the risk or probability of occurrence of a given phenomenon.

A composition used according to the present invention thus makes it possible to confer beneficial properties on the skin, notably in a long-lasting manner, in particular: effective barrier function; moisturizing effect; elasticity and smooth texture of the skin; surface morphology with low roughness, good tissue cohesion, good thickness of the stratum comeum and an improvement in the visual appearance of the skin.

In particular, a composition used according to the invention may be used on fragile, weakened, dry, atopic and/or sensitive skin of an individual.

A recent epidemiological study in adult subjects from various countries (Haftek et al., Clin Cosmet Investig Dermatol. 2013; 6: 289-294) made it possible to establish that the concept of "fragile skin" had a specific resonance among the populations studied. "Fragile skin" can be defined as skin having an intrinsic fragility, such that it is more receptive to attacking factors of all kinds than a non-fragile skin.

In general, fragile skin has a disruption of the barrier function leading to permeability and therefore greater reactivity to environmental stresses or aggressions compared with "normal skin" (non-fragile skin). This type of skin is therefore less resistant to stress or environmental aggressions. In addition to the dysfunction of the barrier function, these stresses can also lead to skin inflammation. Lastly, fragile skin is also slower to recover its basal state once exposed to such conditions.

Fragile skin is referred to as constitutionally fragile skin, and corresponds, for example, to baby skin, to the skin of an elderly person, or else to the skin of delicate areas of the body (eyelids, face, etc.).

Weakened skin is fragile skin referred to as "environmentally" or "pathologically" fragile skin. "Environmentally" fragile skin is notably skin which has been attacked by climatic stress (heat, cold, drought, etc.), mechanical stress (friction, etc.), physical stress (UV radiation, laser, etc.) or chemical stress (surfactants, solvents, etc.). "Pathologically" fragile skin relates to skin suffering notably from atopic dermatitis or eczema, psoriasis, nodular prurigo, seborrhoeic dermatitis, acne, folliculitis and/or rosacea.

The term "atopic skin" is understood here to mean skin of a patient exhibiting the same physiological and molecular characteristics as skin of a patient suffering from atopic dermatitis, in particular exhibiting pruritus or inflammation, these manifestations being chronic and interspersed with periods of remission.

The expression "skin disorder" covers feelings of discomfort and also the temporary visible and unattractive cutaneous signs liable to affect this same individual.

In general, sensitive skin is defined by a particular reactivity of the skin. This skin reactivity is generally reflected by the manifestation of signs of discomfort in response to an individual coming into contact with a triggering factor, which may have diverse origins. It may be the application of a cosmetic product to the surface of sensitive skin, the taking of food, the exposure to sudden variations in temperature, to atmospheric pollution and/or to ultraviolet or infrared rays. The appearance of these signs of discomfort, which appear within minutes of the individual coming into contact with the triggering factor, is one of the essential characteristics of sensitive skin. These are mostly dysesthetic sensations. "Dysesthetic sensations" is understood to mean sensations in a cutaneous zone such as stinging, tautness, hotness and/or itching.

These subjective signs usually exist in the absence of visible clinical signs such as desquamations.

“Sensitive skin” will therefore present feelings of discomfort much more quickly and frequently than other skin types. Dry skin appears rough to the touch and appears to be covered with squamae and manifests essentially in a feeling of tautness and/or tension. Indeed, dry skin is generally accompanied by desquamation. In physiological terms, dry skin is often particularly associated with a decrease in the degree of skin moisturization and with an adverse effect on the barrier function, measured by the insensible water loss. In sensory terms, it is particularly characterized by feelings of skin tautness and/or tension.

Dry skin, also known as "xerosis", may appear at any age, and may be unrelated to a pathological condition.

A composition according to the invention thus proves to be very particularly effective for treating tautness, stinging, hotness and/or itching, notably associated with fragile, weakened, dry, atopic and/or sensitive skin, for physiologically restoring a suitable state of moisturization of the stratum corneum, for restoring an altered thickness, and in particular thinned thickness, of the stratum corneum of the skin, for improving the comfort of fragile, weakened, dry, atopic and/or sensitive skin, or for combating the dull and/or lifeless appearance of such skin.

As indicated above, a composition according to the invention comprises indole-3-pyruvic acid, an isomer thereof or a salt thereof.

The indole-3-pyruvic acid is of formula I below:

[Chem 1]

A “salt” of an indole according to the invention is understood to mean a salt formed by an inorganic or organic acid or else an inorganic or organic base.

As examples of acid salts, mention may be made of the sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, isonicotinate, lactate, salicylate, 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) salts . As examples of base salts, mention may be made of hydroxides of alkali metals such as sodium, potassium and lithium; hydroxides of alkaline earth metals such as calcium and magnesium; hydroxides of other metals such as aluminium and zinc, aqueous ammonia and organic amines such as unsubstituted or hydroxy-substituted mono-, di- or trialkylamines; dicyclohexylamines; tributylamines, pyridine, N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris(2-hydroxyalkylamines) such as mono-, bis- or tris(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine or tris(hydroxymethyl)methylamine, N,N-di-alkyl-N-(hydroxyalkyl)amines, such as N,N- dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine; N-methyl-D- glucamine; and amino acids such as arginine and lysine.

A salt of indole-3-pyruvic acid according to the invention is preferably a base salt, and in particular a sodium or potassium salt.

A composition used according to the invention may comprise a content of indole-3-pyruvic acid, an isomer thereof or a salt thereof, of at least 0.0001% by weight relative to the total weight of the composition, preferably a content of between 0.0001% and 5% by weight, more preferentially a content of between 0.001% and 1% by weight, better still a content of between 0.001% and 0.01% by weight relative to the total weight of the composition.

A composition used according to the invention may further comprise at least one adjuvant chosen from the group constituted of liquid, pasty or solid fatty substances; organic solvents chosen from linear or branched C1-C6 monoalcohols such as ethanol, isopropanol, tert-butanol; polyols such as glycerol, propylene glycol, pentylene glycol, caprylyl glycol, hexylene glycol (or 2-methyl-2,4-pentanediol) and polyethylene glycols; polyol ethers such as dipropylene glycol monomethyl ether; ionic or nonionic, hydrophilic or lipophilic, thickeners; softeners; humectants; emollients; opacifiers; stabilizers; silicones; antifoams; fragrances; preservatives; anionic, cationic, nonionic, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; basifying or acidifying agents; and mixtures thereof.

Such an adjuvant may represent from 0.01% to 20%, preferably from 0.1% to 10% and better still from 1% to 5% by weight relative to the total weight of the composition.

Of course, those skilled in the art will take care to select this or these adjuvant(s), and/or the amount thereof, such that the advantageous properties of the indole-3-pyruvic acid, an isomer thereof or a salt thereof of the composition used according to the invention are not, or are not substantially, adversely affected by the envisaged addition.

Preferably, a composition used according to the invention may comprise water.

In particular, a composition used according to the invention may comprise from 1% to 95% by weight, preferably from 20% to 80% by weight of water, better still from 30% to 60% by weight, relative to the total weight of the composition.

The pH of a composition used according to the invention is advantageously less than or equal to 8, preferably ranging from 4 to 7, better still ranging from 5.5 to 6.5.

Advantageously, the composition used according to the invention may comprise one or more water-miscible organic solvents.

According to the present invention, the term “water-miscible solvent” denotes a compound that is liquid at room temperature and water-miscible notably having a miscibility with water of greater than 50% by weight at 25°C and atmospheric pressure.

The water- miscible organic solvents can be chosen from linear or branched C1-C6 monoalcohols, such as ethanol, isopropanol or tert-butanol; polyols such as glycerol, propylene glycol, pentylene glycol, caprylyl glycol, hexylene glycol (or 2-methyl-2,4- pentanediol) and polyethylene glycols; polyol ethers, for instance dipropylene glycol monomethyl ether; and mixtures thereof.

These water-miscible organic solvents may be present in a composition used according to the invention in a concentration ranging from 0.01% to 20% by weight, preferably from 0.1% to 10% by weight and better still from 1% to 5% by weight, relative to the total weight of the composition.

The composition used according to the invention may also comprise at least one additional cosmetic active agent.

It may in particular be at least one active agent for caring for fragile, weakened, atopic and/or sensitive skin.

In the context of the present invention, the term “additional active agent” means a compound which has, by itself, that is to say not requiring the intervention of an external agent in order to activate it, a biological activity which may in particular be:

- a calmative or anti-irritant activity, and/or

- a humectant activity; and/or

- an emollient activity. The additional active agent which can be used in the compositions used according to the invention may in particular be chosen from humectants such as glycerol and/or urea, emollients such as liquid petroleum jelly, anti-irritant agents, and mixtures thereof in any proportion.

The additional active agent used in the composition used according to the invention may represent from 0.0001% to 20%, preferably from 0.01% to 10% and better still from 0.01% to 5% by weight relative to the total weight of the composition.

Needless to say, a person skilled in the art will take care to select this or these optional additional compound(s), and/or the amount thereof, such that the advantageous properties of the composition used according to the invention are not, or are not substantially, adversely affected by the envisioned addition.

A composition used according to the invention may in particular be in any presentation form normally used in the cosmetic field, and in particular any presentation form normally available for the selected mode of administration.

The support may be of diverse nature according to the type of composition considered.

The compositions according to the invention may be in any presentation form conventionally used for topical application and notably in the form of aqueous or aqueous- alcoholic solutions, oil-in-water (O/W), water-in-oil (W/O) or multiple (triple: W/O/W or O/W/O) emulsions, aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, it being possible for these spherules to be lipid vesicles of ionic and/or nonionic type (liposomes, niosomes or oleosomes). These compositions are prepared according to the usual methods.

A composition used according to the invention is preferentially suitable for topical administration.

As more particularly regards compositions intended for topical administration, i.e. on the skin, they may be aqueous, aqueous-alcoholic or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, suspensions or emulsions of the cream type, aqueous or anhydrous gels, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and/or nonionic type. A composition used according to the invention may advantageously comprise at least one liquid fatty substance.

The term “liquid fatty substance” means a compound with a melting point below about 30- 35°C, as opposed to solid fatty substances, such as waxes, which have a melting point above about 50 °C.

As oils which may be used in the composition of the invention, mention may for example be made of:

- hydrocarbon-based oils of animal origin;

- hydrocarbon-based oils of plant origin;

- synthetic esters and ethers, notably of fatty acids, for instance oils of formulae R’COOR2 and R’OR2 in which R’ represents a fatty acid residue including from 8 to 29 carbon atoms and R2 represents a branched or unbranched hydrocarbon-based chain containing from 3 to 30 carbon atoms;

- linear or branched hydrocarbons of mineral or synthetic origin;

- fatty alcohols containing from 8 to 26 carbon atoms;

- fluoro oils which are partially hydrocarbon-based and/or silicone -based;

- silicone oils;

- mixtures thereof.

In the list of oils mentioned above, the term “hydrocarbon-based oil” means any oil mainly including carbon and hydrogen atoms, and possibly ester, ether, fluoro, carboxylic acid and/or alcohol groups.

The other fatty substances that may be present in the oily phase are, for example, fatty acids including from 8 to 30 carbon atoms, waxes, silicone resins and silicone elastomers.

These fatty substances may be chosen in a varied manner by those skilled in the art in order to prepare a composition having the desired properties, for example in terms of consistency or texture.

According to a particular embodiment of the invention, the composition according to 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 may range from 5% to 90% by weight and preferably from 5% to 60% by weight relative to the total weight of the composition. The emulsions generally contain at least one emulsifier chosen from amphoteric, anionic, cationic and nonionic emulsifiers, used alone or as a mixture, and optionally a coemulsifier. The emulsifiers are appropriately chosen according to the emulsion to be obtained (W/O or O/W).

The emulsifier and the coemulsifier 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, with respect to the total weight of the composition.

For the W/O emulsions, examples of emulsifiers that may be mentioned include dimethicone copolyols and alkyldimethicone copolyols. A crosslinked elastomeric solid organopoly siloxane including at least one oxyalkylene group may also be used as W/O emulsion surfactant.

For the O/W emulsions, examples of emulsifiers that may be mentioned are nonionic emulsifiers.

Preferentially, a composition used according to the invention differs from compositions having an essentially detergent purpose with regard to the skin, hair and/or mucous membranes, such as soaps, shampoos and shower gels for washing and/or cleansing.

More particularly, a composition used according to the invention may be intended for topical application and may preferably be in the form of an emulsion, preferably an oil-in- water emulsion. Preferably, such an emulsion is not intended to be rinsed off after application.

A composition used according to the invention may alternatively be in the form of a face and/or body care or makeup product, and may be packaged, for example, in the form of a cream in a jar or a fluid in a tube or a pump bottle or a dropper bottle.

The ingredients are mixed before forming, in the order and under conditions readily determined by a person skilled in the art.

Uses and processes

As mentioned above, according to one of its aspects, the present invention relates to the cosmetic use, notably topical non-therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole- 3 -pyruvic acid, an isomer thereof or a salt thereof, for preventing a reduction in the skin barrier function and/or reinforcing the skin barrier function in an individual, in particular of dry skin, notably for improving skin moisturization. The invention also relates to the cosmetic use, notably topical cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for preventing and/or treating atopic dermatitis or eczema.

The present invention additionally relates to the cosmetic use, notably topical non- therapeutic cosmetic use, of a composition comprising, in a physiologically acceptable medium, indole- 3 -pyruvic acid, an isomer thereof or a salt thereof, for preventing and/or treating a skin disorder of sensitive skin, in an individual.

The invention additionally relates to a non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, comprising the topical application to these keratin materials of a composition comprising, in a physiologically acceptable medium, indole-3- pyruvic acid, an isomer thereof or a salt thereof.

The skin in particular affected by such a method, and thus the skin on which a composition used according to the invention is applied, may preferably be fragile, weakened, dry, atopic and/or sensitive skin.

As indicated above, a composition used in a method of the present invention is preferably suitable for topical administration.

The cosmetic uses, methods and processes considered according to the invention are non- therapeutic.

The cosmetic uses and processes of the invention are preferentially performed by topically administering a composition according to the invention.

Topical administration consists of the external application to the skin of cosmetic compositions according to the usual techniques for the use of these compositions.

By way of illustration, the cosmetic use or method according to the invention may be implemented by topical, for example daily, application of at least one composition according to the invention, which may be formulated, for example, in the form of a cream, gel, serum, lotion, emulsion, or makeup-removing milk, preferably in the form of an emulsion.

The application can be repeated, for example, once to twice daily for one or more days and generally over an extended period of at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage. According to one embodiment, the application is daily (once a day) and generally over an extended period of at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage.

According to one embodiment, the cosmetic treatment method according to the invention may comprise a single application.

Throughout the description, including the claims, the terms “between ... and ...”, and “ranging from ... to ...” should be understood as meaning limits included, unless otherwise specified.

The examples that follow illustrate the present invention without limiting the scope thereof. In the examples, unless otherwise specified, the temperature is room temperature (20°C) and is expressed in degrees Celsius, and the pressure is atmospheric pressure.

Examples

Example: Study of the anti-pruritic and anti-inflammatory effect of indole-3-pyruvic acid (I3P)

A/- MATERIALS AND METHODS

Culturing with thawing in T75 flask

Thawing the 3T3 cells

[Table 1]

Table 1

The 3T3 fibroblasts (ATCC, CRL-1658), used as feeders for the keratinocytes, were initially cultured in DMEM (Ref 12491015, ThermoFisher) and treated with a 0.5 mg/ml solution of mitomycin (Sigma, M4287) before freezing. The mitomycin-treated 3T3 are then inoculated at 2.1 million per flask in 30 ml of G7 and incubated in an oven at 37°C, 5% CO2 (2-3 hours).

Thawing of primary cells of normal human epidermal keratinocytes (NHEK) collected from prepuces of healthy subjects obtained after plastic surgery at Alphenyx (France). The NHEK are thawed and inoculated at 0.15 million in flasks. All of the medium used to inoculate the 3T3m is aspirated and then 35 ml of G7F + Y27632 medium (see below) is distributed into each flask.

65 pl of cell suspension with 0.15 million NHEK are added to each flask, followed by an incubation step in an oven at 37°C, 5% CO2. The medium is changed at 48 h with 10 pM of the G7F + Y27632 medium.

Transfer to 48-well plate for stimulation

[Table 2]

Table 2

When the flasks with 3T3 feeder are at 80-90% confluence, 50 000 NHEK are seeded in a 48-well plate with 1 ml of KGM Gold medium without hydrocortisone and 1 ml BPE (bovine pituitary extract) (instead of the 2 ml contained in the supplements of the KGM Gold kit); Y27632 10 pM. This is followed by an incubation step in an oven for 72 h at 37°C, 5% CO₂.

After 72 h, a step of exposure to a stimulation cocktail as defined below is carried out in order to induce a phenotype similar to that observed in patients with atopic dermatitis in terms of chemokines produced.

Stimulation cocktail:

- Poly (EC): 1 mg/ml (used at 10 pg/ml in the well) ref. P9582, Sigma; and

- IL-4: 5 pg/ml (used at 50 ng/ml in the well) ref. 204-IL, RnDSystems; and

- IL-13: 5 pg/ml (used at 50 ng/ml in the well) ref. 213-ILB/CF RnDSystems; and

- TNFa: 5 pg/ml (used at 10 ng/ml in the well) ref. 210-TA/CF RnDSystems.

Molecules of interest:

The various molecules of interest are added to the KGM Gold culture medium:

- IALD ref: 129445, Sigma: stock solution 10 mg/ml in DMSO diluted in the culture medium to the final concentration of 10 pg/ml and 25 pg/ml; or - FICZ ref: SML1489, Sigma: stock solution 0.5 mg/ml in DMSO diluted in culture medium at the final concentration of 0.05 and 0.1 |Jg/ml; or

- I3P ref: 286281, Sigma: stock solution 10 mg/ml in DMSO diluted in the culture medium to the final concentration of 10 |Jg/ml and 25 |jg/ml.

Measurement of chemokines in the supernatant after 48 h of culture

Use of Meso Scale Discovery technology to measure chemokines in culture supernatants according to the manufacturer's instructions.

[Table 3]

Table 3

Statistical analysis

All experiments were performed with at least three biological replicates. The data is presented in the form of mean ± SEM. GraphPad Prism (version 7.0; GraphPad Software, La Jolla, California). The data was analysed with the one-way ANOVA test followed by Dunnett’ s multi-comparison test. The results are considered to be statistically significant when p < 0.05.

B/- RESULTS

The anti-pruritic effect of indole- 3 -pyruvic acid and of comparative products (indole-3- aldehyde (IALD) and FICZ (5,l l-dihydroindolo[3,2-b]carbazole-6-carboxaldehyde, 6- formy lindolo [3, 2-b] carbazole)) on 3D models reproducing atopic dermatitis was studied. FICZ is an anti-pruritus and anti-inflammation positive control based on the literature.

IALD is also a positive control. Indeed, in the study by Yu et al. (J Allergy Clin Immunol, 2019 Jun;143(6):2108-2119.el2), topical application of IALD made it possible to reduce skin inflammation in a dermatitis-like mouse model.

The results in Tables 4, 5 and 6 below are expressed as percentage difference with respect to the stimulated control.

[Table 4]

Table 4

[Table 5]

Table 5

[Table 6]

Table 6

These tables represent the percentage of the level of expression of TSLP, MCP-1, IL- la, MIP-la and IL-29 relative to the stimulated control in the keratinocyte culture medium 48 h after stimulation. The p-values are calculated with respect to the stimulated control.

TSLP: (thymic stromal lymphopoietin) is a key chemokine of keratinocyte communication due to its ability to induce itching by directly activating certain types of neurons (TRPA- 1+) and also the type 2 immune responses involved in atopic dermatitis.

MCP-1 and MIP-la are proteins involved in inflammatory processes in type 2 immune responses, in particular in patients suffering from atopic dermatitis where they are markedly increased (Kaburagi et al., Arch Dermatol Res. 2001 Jul;293(7):350-5). These tables show a significant reduction in the production of the chemokines TSLP, IL- la, and IL-29 and also of the proteins MCP-1 and MIP-la for I3P and FICZ, which reduction cannot be observed with IALD. In conclusion, all of these results demonstrate that I3P has a very good ability to restore the barrier function of the epidermis, notably compared to IALD.

Claims

1. Composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for the use thereof in the prevention and/or treatment of atopic dermatitis or eczema.

2. Cosmetic non-therapeutic use, in particular topical cosmetic non-therapeutic use, of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for preventing and/or treating a skin disorder of sensitive skin, in an individual, the skin disorder being a feeling of discomfort, notably tautness, stinging, hotness and/or itching.

3. Composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, an isomer thereof or a salt thereof, for the use thereof in the prevention and/or treatment of pruritus of the skin of an individual.

4. Composition for the use thereof according to Claim 3, wherein pruritus of the skin of an individual is present:

- in a dermatological disorder following exposure of the skin to pollutants.

5. Use according to Claim 2, or composition for the use thereof according to any one of Claims 1, 3 and 4, wherein the composition is applied to fragile, weakened, dry, atopic and/or sensitive skin.

6. Use according to Claim 2, or composition for the use thereof according to any one of Claims 1 and 3 to 5, wherein the composition comprises a content of indole-3-pyruvic acid, an isomer thereof or a salt thereof, of at least 0.0001% by weight relative to the total weight of the composition, preferably a content of between 0.0001% and 5% by weight, more preferentially a content of between 0.001% and 1% by weight, better still a content of between 0.001% and 0.01% by weight relative to the total weight of the composition.

7. Use according to Claim 2, or composition for the use thereof according to any one of Claims 1 and 3 to 6, wherein the composition further comprises at least one adjuvant chosen from the group constituted of liquid, pasty or solid fatty substances; organic solvents chosen from linear or branched C1-C6 monoalcohols such as ethanol, isopropanol, tertbutanol; polyols such as glycerol, propylene glycol, pentylene glycol, caprylyl glycol, hexylene glycol (or 2-methyl-2,4-pentanediol) and polyethylene glycols; polyol ethers such as dipropylene glycol monomethyl ether; ionic or nonionic, hydrophilic or lipophilic, thickeners; softeners; humectants; emollients; opacifiers; stabilizers; silicones; antifoams; fragrances; preservatives; anionic, cationic, nonionic, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; basifying or acidifying agents; and mixtures thereof.

8. Use according to Claim 2, or composition for the use thereof according to any one of Claims 1 and 3 to 7, the composition being suitable for topical administration.