FR3143325A1 - Cosmetic use of a composition for the care of keratin materials comprising at least indole-3-pyruvic acid - Google Patents

Abstract

Cosmetic use of a composition for the care of keratin materials comprising at least indole-3-pyruvic acid The present invention relates to the cosmetic, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, to prevent a reduction in the skin barrier function and/or strengthen the skin barrier function in an individual, in particular dry skin. It also relates to the use of such a composition to prevent and/or treat a skin disorder on sensitive skin in an individual as well as the use of such a composition to prevent and/or treat pruritus and/or inflammation of an individual's skin. 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. Figure for abstract: None

Description

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

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 propose the cosmetic use, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, to prevent a reduction in the skin barrier function and/or to strengthen the skin barrier function in an individual, in particular dry skin.

It also concerns the cosmetic use, particularly topical, of such a composition to prevent and/or treat atopic dermatitis or eczema.

It also concerns the cosmetic use, in particular topical, non-therapeutic use of such a composition to prevent and/or treat a skin disorder of sensitive skin in an individual.

It further relates to the cosmetic use, in particular topical, of such a composition to prevent and/or treat pruritus and/or inflammation of the skin of a particular individual present in a dermatological disorder chosen from the group consisting of atopic dermatitis or eczema, psoriasis, nodular prurigo, seborrheic dermatitis, acne, folliculitis, rosacea.

The skin is a tissue whose cells are joined together and attached to each other. The skin tissue forms an external covering including sebaceous or sweat glands and hair follicles. The skin, and in particular the scalp, are epithelia with continuous renewal. Renewal, or desquamation, is a coordinated and finely regulated process resulting in the elimination of superficial cells, in a way that is imperceptible and invisible.

Human skin is made up of two compartments, namely a superficial compartment, the epidermis, and a deep compartment, the dermis.

The epidermis is conventionally divided into a basal layer of keratinocytes constituting the germinal layer of the epidermis, a so-called spinous layer consisting of several layers of polyhedral cells arranged on the germinal layers, one to three so-called granular layers consisting of flattened cells containing distinct cytoplasmic inclusions, the keratohyalin grains and finally, a set of upper layers called horny layers (or stratum corneum ), consisting of keratinocytes in the terminal stage of their differentiation called corneocytes.

Corneocytes are anucleated cells mainly composed of a fibrous material containing cytokeratins, surrounded by a horny envelope. There is a constant production of new keratinocytes to compensate for the continuous loss of epidermal cells at the level of the horny layer according to a mechanism called desquamation.

However, an imbalance between the production of cells in the basal layer and the rate of desquamation can lead to the formation of scales on the surface of the skin. Similarly, a deficit in terminal differentiation of cells in the stratum corneum , for various reasons, can lead to the formation of large, thick, visible to the naked eye, clumps of cells called "scales", or in other situations, to a thinning of the stratum corneum .

This can result in a fragility of the barrier properties of the epidermis, chronic dehydration of the stratum corneum , a loss of mechanical elasticity, tightness, as well as a lack of radiance and transparency of the skin.

Examples of factors that promote a reduction in the quality of the skin's surface, which weakens the skin barrier, include stress, winter, excess sebum or a lack of hydration.

Thus, a fragility of the skin barrier can occur in the presence of external aggressions, notably chosen from irritants (detergents, acids, bases, oxidants, reducers, concentrated solvents, harmful gases or fumes, pollutants), thermal or climatic imbalances (cold, dryness, radiation), xenobiotics (undesirable microorganisms, allergens) or internal aggressions such as psychological stress.

This alteration of the skin barrier can result in skin discomfort, sensory phenomena and in particular unpleasant phenomena. The individual affected may then experience a sensation of skin discomfort which may manifest itself in particular by tingling, tightness, warming and/or itching.

These feelings of skin discomfort, of a cosmetic and not therapeutic nature, are more frequent in the most exposed areas of the body, namely the hands, feet, face, and scalp.

They can occur in particular in areas subject to certain daily or frequently repeated hygiene procedures such as shaving, hair removal, cleansing with toiletries or household products, the application of adhesives (bandages, patches, fixing prostheses) or in the case of sporting, professional or simply lifestyle-related gestures and the use of clothing, tools or equipment generating localized friction. They can also be amplified by psychological stress.

These feelings of skin discomfort affect everyone, and in particular:
- people with so-called “fragile” or “delicate” and vulnerable skin that quickly becomes unbalanced when there are large variations in temperature or relative humidity (e.g. babies’ skin);
- people with so-called “fragile” skin, including in particular:
(i) persons whose protective hydrolipidic film composed of sweat, sebum and natural moisturizing factors is becoming scarce, as is the case for persons aged over 60 and in particular in the elderly (at least 75 years);
(ii) persons whose hydrolipidic film composition is modified.

We can also talk about people with “damaged” skin for shaved skin for example.

One of the critical steps in the terminal differentiation process of the stratum corneum is the cross-linking of the protein precursors of the corneal envelope (CE). This phenomenon plays an essential role in the development and maintenance of skin cohesion, physical properties of the skin such as barrier function, and is a crucial step in the terminal differentiation process mentioned above.

Conventionally used moisturizing active ingredients, such as humectants, moisturizing polymers or fatty substances such as petroleum jelly, temporarily modify the surface properties of the skin. These active ingredients can lead to mechanical softening of the stratum corneum , an increase in its hydration state and/or an improvement in the microrelief of the skin by forming a film on the surface of the skin.

However, these effects are not necessarily very long-lasting. In addition, these active ingredients can be eliminated by cleaning actions.

To overcome these drawbacks, it is interesting to turn to active ingredients with a beneficial action that lasts over time and is not affected by cleaning by acting on biological pathways, for example by modulating the expression of certain key biological markers in alterations of the barrier function.

It is known that an altered epidermal barrier leads to the secretion by keratinocytes of chemokines such as TSLP: (Thymic Stromal LymphoPoietin) which is known to be a key chemokine in keratinocyte communication through its ability to induce itching by directly activating certain types of neurons (TRPA-1+) as well as type 2 immune responses involved in atopic dermatitis.

In addition, other molecules are involved in this response process following the alteration of the barrier such as the proteins MCP-1 and MIP-1 involved in inflammatory processes in type 2 immune responses, particularly in patients with atopic dermatitis where they are found to be significantly increased (Kaburagi et al., Arch Dermatol Res. 2001 Jul;293(7):350-5), as well as the cytokines interleukin 1 alpha (IL-1a) 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 possibly being regulated by 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 capacity of the skin barrier to respond to external aggressions.

Thus, there is a need to identify new active ingredients that can reduce the expression of these markers.

By identifying these new assets, we are therefore seeking to:
- prevent a decrease in and/or strengthen the skin barrier function, particularly of dry skin; and/or
- prevent and/or reduce feelings of skin discomfort, tingling, tightness, warming and itching, particularly in people with sensitive, fragile, weakened or delicate skin (for example babies or people aged at least 60 and in particular people aged at least 75), or people whose hydrolipidic film composition is modified, and/or
- improve the skin barrier function, particularly of atopic skin, and/or prolong the remission phases between acute attacks of this type of condition.

There is also a need for an active ingredient that allows the skin, particularly dry and/or sensitive and/or atopic skin, to maintain its role as a barrier function.

There is also a need for an active ingredient to improve skin hydration.

There is also a need for active ingredients for improving the quality and/or complexion of skin, in particular the quality and/or complexion of sensitive skin; and/or for preventing and/or treating skin disorders associated with sensitive skin, in particular chosen from tightness, tingling, heating and/or itching.

There is also a need for active ingredients for preventing and/or treating pruritus and/or inflammation in an individual's skin, in particular inflammation in skin affected by a dermatological disorder selected from the group consisting of atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea, or by a dermatological disorder following exposure of the skin to pollutants and/or UV rays.

The present invention aims to solve the above-mentioned technical problems.

Indeed, the inventors have now discovered that indole-3-pyruvic acid, in a skin model of atopic dermatitis, significantly reduces the production of the chemokine TSLP, the cytokines IL-1a, IL-29 as well as the proteins MCP-1 and MIP-1a.

Thus, according to a first aspect, the present invention relates to the cosmetic, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, to prevent a reduction in the skin barrier function and/or to strengthen the skin barrier function in an individual, in particular with dry skin.

According to a second aspect, the present invention relates to the cosmetic, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, for preventing and/or treating atopic dermatitis or eczema.

According to a third aspect, the present invention relates to the cosmetic, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, for preventing and/or treating a skin disorder of sensitive skin, in an individual.

Such a skin disorder can include a feeling of discomfort, and in particular tightness, tingling, warming and/or itching.

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

Itching and/or inflammation of an individual's skin may particularly be present:
- in a dermatological disorder selected from the group consisting of atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea; or
- in a dermatological disorder following exposure of the skin to pollutants and/or UV rays.

Finally, the invention also relates to a non-therapeutic cosmetic process 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, one of its isomers or one of its salts.

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

A composition implemented according to the invention may in particular be suitable for topical administration.

Other features, aspects and advantages of the invention will become apparent upon reading the detailed description which follows.

Detailed description Composition implemented according to the invention

A composition implemented according to the invention is preferably cosmetic.

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

By " cosmetic " is meant a composition compatible with keratin materials, in particular the skin, mucous membranes and appendages. The composition used according to the invention is non-therapeutic.

By " keratin materials " we mean in particular the skin, mucous membranes, fibres, eyelashes and appendages.

By “ skin ” is meant all of the skin of the body, and preferably the skin of the face, scalp, décolleté, neck, arms and forearms, or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, chin), décolleté and neck.

A composition implemented according to the invention preferably comprises a cosmetically acceptable medium, that is to say which has a pleasant color, odor and feel and does not generate unacceptable discomfort, such as tingling, tightness, likely to discourage the user from applying this composition.

As used herein, the terms " treat " and " treatment " are intended to mean the alleviation of symptoms associated with a specific disorder or condition and/or the elimination of such symptoms and the complete disappearance of the disorder or condition in question.

In the context of the present invention, the terms " prevent " and " prevention " mean reducing to a lesser degree the risk or probability of occurrence of a given phenomenon.

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

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

A recent epidemiological study of adult subjects from different countries (Haftek et al ., Clin Cosmet Investig Dermatol. 2013; 6: 289–294) established that the notion of “fragile skin” had a specific resonance with the populations studied. “Fragile skin” can be defined as skin with an intrinsic fragility, such that it is more receptive to aggressions of all kinds than non-fragile skin.

Generally speaking, fragile skin has a disruption of the barrier function leading to greater permeability and therefore reactivity to stress or environmental aggressions compared to “ normal” (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. Finally, fragile skin is also less quick to recover its basal state once exposed to such conditions.

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

Fragile skin is fragile skin called " environmental " or " pathological ". Fragile " environmental " skin is in particular skin that has been attacked by climatic stress (hot, cold, dryness, etc.), mechanical (friction, etc.), physical (UV, laser, etc.) or chemical (surfactants, solvents, etc.). Fragile " pathological " skin concerns skin suffering in particular from atopic dermatitis or eczema, psoriasis, nodular prurigo, seborrheic dermatitis, acne, folliculitis, and/or rosacea.

By " atopic skin " is meant here the skin of a patient presenting the same physiological and molecular characteristics as the skin of a patient suffering from atopic dermatitis, in particular presenting pruritus, inflammation, these manifestations being chronic and interspersed with periods of remission.

The term "skin disorder" covers feelings of discomfort as well as temporary visible and unsightly skin signs that may affect the same subject.

Generally speaking, sensitive skin is defined by a particular reactivity of the skin. This skin reactivity generally results in the manifestation of signs of discomfort in response to the subject coming into contact with a triggering element that can have various origins. This may involve the application of a cosmetic product to the surface of sensitive skin, food intake, exposure to sudden changes in temperature, atmospheric pollution and/or ultraviolet or infrared rays. The appearance of these signs of discomfort, which appear within minutes of the subject coming into contact with the triggering element, is one of the essential characteristics of sensitive skin. These are essentially dysesthetic sensations. Dysesthetic sensations are sensations in an area of skin such as tingling, tightness, warming and/or itching.

These subjective signs most often exist in the absence of visible signs such as redness and flaking.

“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 covered in scales and is mainly manifested by a feeling of tightness and/or tension. Dry skin is generally accompanied by flaking. On a physiological level, dry skin is often associated with a drop in the skin's hydration level and an alteration of the barrier function, measured by transepidermal water loss. On a sensory level, it is characterized by feelings of tightness and/or skin tension.

Dry skin, also called xerosis, can appear at any age and may not be related to a pathological condition.

A composition according to the invention thus proves to be particularly effective for treating tightness, tingling, heating and/or itching, in particular associated with fragile, weakened, dry, atopic and/or sensitive skin, for physiologically restoring a suitable state of hydration to the stratum corneum , for restoring an altered, 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 atonic appearance of such skin.

As previously indicated, a composition according to the invention comprises indole-3-pyruvic acid, one of its isomers or one of its salts.

Indole-3-pyruvic acid has the following formula I:

(I)

The term “ salt ” of an indole according to the invention means a salt formed by an inorganic or organic acid or an inorganic or organic base.

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).

Examples of basic salts include alkali metal hydroxides such as sodium, potassium and lithium; alkaline earth metal hydroxides such as calcium and magnesium; other metal hydroxides such as aluminium and zinc; ammonia and organic amines such as unsubstituted or hydroxy-substituted mono-, di- or tri-alkylamines; dicyclohexylamines; tributyl amines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris-(2-hydroxy-alkylamines) 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 basic 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, of one of its isomers or of one of its salts, of at least 0.0001% by weight relative to the total weight of the composition, preferably a content of between 0.0001% to 5% by weight, more preferably a content of between 0.001% to 1% by weight, even better 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 also comprise at least one adjuvant chosen from the group consisting 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, capylyl 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; anti-foaming agents; fragrances; preservatives; anionic, cationic, nonionic, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing 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, the person skilled in the art will take care to choose this or these adjuvants and/or their quantity in such a way that the advantageous properties of indole-3-pyruvic acid, one of its isomers or one of its salts of the composition used according to the invention are not, or not substantially, altered by the envisaged addition.

Preferably, a composition implemented according to the invention can 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, even better 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, even better ranging from 5.5 to 6.5.

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

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.

The water-miscible organic solvents may be 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; and mixtures thereof.

These water-miscible organic solvents may be present in a composition used according to the invention at 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 ingredient.

In particular, this may involve at least one active ingredient for the care of fragile, weakened, atopic and/or sensitive skin.

By the expression "additional active", we mean, in the context of the present invention, a compound which has by itself, that is to say not requiring the intervention of an external agent to activate it, a biological activity which can be in particular:
- a soothing or anti-irritant activity, and/or
- a humectant activity; and/or
- an emollient activity.

The additional active agent usable in the compositions used according to the invention may in particular be chosen from humectants such as glycerol and/or urea, emollient agents such as petroleum jelly, anti-irritant agents, and their mixtures in all proportions.

The additional active ingredient used in the composition implemented 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.

Of course, the person skilled in the art will take care to choose this or these possible additional compounds and/or their quantity in such a way that the advantageous properties of the composition used according to the invention are not, or not substantially, altered by the envisaged addition.

A composition implemented according to the invention may be presented in all the galenic forms normally used in the cosmetic field, and in particular all the galenic forms normally available for the chosen method of administration.

The support can be of various nature depending on the type of composition considered.

The compositions according to the invention may be in all the galenic forms conventionally used for topical application and in particular in the form of aqueous, hydroalcoholic solutions, oil-in-water (O/W) or 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, these spherules possibly being lipid vesicles of ionic and/or non-ionic type (liposomes, niosomes, oleosomes). These compositions are prepared according to the usual methods.

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

With regard more particularly to compositions intended for topical administration, that is to say on the skin, these may be aqueous, hydroalcoholic or oily solutions, 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 gel, microemulsions, microcapsules, microparticles, or vesicular dispersions of the ionic and/or non-ionic type.

A composition used according to the invention may advantageously comprise at least one liquid fatty substance.

By "liquid fat" is meant a compound having a melting point below about 30-35°C, as opposed to solid fats, such as waxes, which have a melting point above about 50°C.

As oils which can be used in the composition of the invention, we can cite for example:
- hydrocarbon oils of animal origin;
- hydrocarbon oils of vegetable origin,
- synthetic esters and ethers, in particular of fatty acids, such as oils of formulas R'COOR2 and R'OR2 in which R' 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;
- linear or branched hydrocarbons, of mineral or synthetic origin;
- fatty alcohols having 8 to 26 carbon atoms;
- partially hydrocarbon and/or silicone fluorinated oils;
- silicone oils;
- their mixtures.

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

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

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.

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 can 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 or nonionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are chosen appropriately according to 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.

For W/O emulsions, examples of emulsifiers that may be used include dimethicone copolyols and alkyl-dimethicone copolyols. A crosslinked solid elastomeric organopolysiloxane comprising at least one oxyalkylenated group may also be used as a surfactant for W/O emulsions.

For H/W emulsions, examples of emulsifiers that can be mentioned are non-ionic emulsifiers.

Preferably, a composition implemented according to the invention is distinguished from compositions intended essentially as detergents for the skin, hair and/or mucous membranes, such as soaps, shampoos and shower gels for washing and/or cleaning.

More particularly, a composition implemented 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 after application.

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

The ingredients are mixed before being shaped, in the order and under conditions easily determined by those skilled in the art.

Uses and methods

As previously mentioned, according to one of its aspects, the present invention relates to the cosmetic use, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, to prevent a reduction in the skin barrier function and/or to strengthen the skin barrier function in an individual, in particular with dry skin, in particular to improve skin hydration.

It further relates to the cosmetic use, in particular topical, of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, to prevent and/or treat atopic dermatitis or eczema.

The present invention further relates to the cosmetic use, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, for preventing and/or treating a skin disorder of sensitive skin, in an individual.

The present invention further 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 a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts.

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

As previously indicated, a composition implemented 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 methods of the invention are preferably implemented 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 of use of these compositions.

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

The application can be repeated for example 1 to 2 times daily over a day or more and generally over a prolonged period of at least 4, or even 4 to 15 weeks, with one or more periods of interruption where appropriate.

According to one embodiment, the application is daily (once a day) and generally over a prolonged period of at least 4, or even 4 to 15 weeks, with, where appropriate, one or more periods of interruption.

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

Throughout the description, including the claims, the expressions "between ... and ..." and "ranging from ... to ..." must be understood inclusively, unless otherwise specified.

The following examples illustrate the present invention without limiting its scope.

In the examples, unless otherwise indicated, the temperature is ambient (20°C), and expressed in degrees Celsius, and the pressure is atmospheric pressure.

Examples

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

A/- MATERIALS AND METHODS Thawing culture in T75 flask Thawing 3T3 cells

Products Supplier Reference Rock Inhibitor Y27632 (10mM) Sigma Y0503 G7F Culture Medium Episkin GR7F+

Table 1

3T3 fibroblasts (ATCC, CRL-1658), used as feeders for keratinocytes, were initially cultured in DMEM (Ref 12491015, ThermoFisger) and treated with a solution of 0.5mg/mL of Mitomycin (Sigma, M4287) before freezing. The mitomycin-treated 3T3s were then seeded at 2.1 million per flask in 30mL of G7 and incubated in an incubator at 37°C, 5% _CO2 (2-3 hours).

Thawing of primary normal human epidermal keratinocyte (NHEK) cells collected from foreskins of healthy subjects obtained after plastic surgery at Alphenyx (France).

NHEKs 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 in each puddle.

65µL of cell suspension at 0.15 million NHEK are added to each flask, followed by an incubation step in an incubator at 37°C, 5% _CO2 . The medium is changed at 48h with 10 µM of G7F + Y27632 medium.

Passage in 48-well plate for stimulation

Products Supplier Reference Rock Inhibitor Y27632 (10mM) Sigma Y0503 KGM gold Lonza 00192060 TNS Promocell C-41120 Tryple express Gibco Thermofisher 10718463

Table 2

When the flasks with 3T3 feeder are at 80-90% confluence, 50,000 NHEK are seeded in 48-well plates with 1 mL of KGM gold medium without hydrocortisone and 1 mL BPE (bovine pituitary extract) (instead of 2 mL contained in the KGM gold kit supplements); Y27632 10 µM. This is followed by an incubation step in an incubator for 72 hours at 37°C, 5% CO ₂ .

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

Stimulation cocktail:

- Poly (I:C): 1 mg/mL (use at 10 µg/mL in the well) ref P9582 Sigma; and
- IL-4: 5 µg/mL (use at 50 ng/mL in the well) ref 204-IL rndsystems; and
- IL-13: 5 µg/mL (use at 50 ng/mL in the well) ref 213-ILB/CF rndsystems; and
- TNFa: 5 µg/mL (use at 10 ng/mL in the well) ref 210-TA/CF rndsystems.

Molecules of interest:

The different 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 µg/mL and 25 µg/mL; or
- FICZ ref: SML1489 Sigma: stock solution 0.5 mg/mL in DMSO diluted in the culture medium to the final concentration of 0.05 and 0.1 µg/mL; or
- I3P ref 286281 Sigma: stock solution 10 mg/mL in DMSO diluted in the culture medium to the final concentration of 10 µg/mL and 25 µg/mL.

Measurement of chemokines in the supernatant after 48 hours of culture

Use of Meso Scale Discovery technology for measurement of chemokines in culture supernatants following manufacturer's instructions.

Product Reference + supplier U-PLEX Metabolic Group 1 (hu) Assays, SECTOR (1 PL), MSD Meso Scale Discovery

Table 3

Statistical analysis

All experiments were performed with at least three biological replicates. Data are presented as mean ± SEM. GraphPad Prism (version 7.0; GraphPad Software, La Jolla, CA). Data were analyzed with the one-way anova test followed by Dunnett's multiple comparison test. Results were considered statistically significant when p < 0.05.

B/- RESULTS

The anti-pruritus effect of indole-3-pyruvic acid and comparatives (Indole-3-Aldehyde (IALD) and FICZ (5,11-Dihydro-indolo[3,2-b]carbazole-6-carboxaldehyde, 6-Formylindolo[3,2-b]carbazole)) on 3D models reproducing Atopic Dermatitis was studied.

FICZ is a literature-based anti-pruritus and anti-inflammation positive control.

IALD is also a positive control. Indeed, in the study by Yu et al . (J Allergy Clin Immunol, 2019 Jun;143(6):2108-2119.e12), topical application of IALD reduced skin inflammation in a dermatitis-like mouse model.

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

IALD 10 µg/ml IALD 25 µg/ml average standard deviation p-value average standard deviation p-value TSLP -16.38184 2.33661221 0.2201 22,7388594 6,73744044 0.0514 MCP-1 -14.247764 15.8621346 0.7414 -4.7779716 10,0122588 0.9961 IL-1a -46.110998 4,06096458 0.0009 -51.824122 2,01626723 0.0003 MIP-1a -7.3177166 13,6181252 0.9958 72.9587581 18,0260873 0.0035 IL-29 -29.474118 9.86424417 0.357 -8.9199235 7.81179246 0.9885

Table 4

FICZ 0.05 µg/ml FICZ 0.1 µg/ml average standard deviation p-value average standard deviation p-value TSLP -40.646136 2.79184986 0.0006 -50.780226 2,69490693 <0.0001 MCP-1 -56.546417 9,12736272 0.0032 -51.485305 9,09595406 0.0067 IL-1a -67.017405 3.26210117 <0.0001 -69.590533 4.77972139 <0.0001 MIP-1a -96.486222 0.6368101 0.0003 -96.408505 0.6979015 0.0003 IL-29 -71.283831 3,15839094 0.0033 -77.919043 2,41739189 0.0015

Table 5

Indole-3-pyruvic acid 10 µg/ml Indole-3-pyruvic acid 25 µg/ml average standard deviation p-value average standard deviation p-value TSLP -46.987218 6.69572694 0.0001 -70.858371 3.15223595 <0.0001 MCP-1 -61.493266 7.5912511 0.0016 -72.995249 4,7522178 0.0003 IL-1a -57.775648 1,78526117 0.0001 -53.358746 5.56352483 0.0002 MIP-1a -94.758177 1,39000401 0.0003 -96.959254 0.566884 0.0003 IL-29 -76.219802 4.89726954 0.0018 -89.398342 1,38461009 0.0004

Table 6

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

TSLP: (Thymic Stromal LymphoPoietin) is a key chemokine in keratinocyte communication through its ability to induce itch by directly activating certain types of neurons (TRPA-1+) as well as type 2 immune responses involved in atopic dermatitis.

MCP-1 and MIP-1a are proteins involved in inflammatory processes in type 2 immune responses, particularly in patients with atopic dermatitis where they are found to be significantly increased (Kaburagi et al ., Arch Dermatol Res. 2001 Jul;293(7):350-5).

These tables show a significant decrease in the production of chemokines TSLP, IL-1a, and IL-29 as well as the proteins MCP-1 and MIP-1a for I3P and FICZ, a decrease which is not observable with IALD.

In conclusion, all of these results demonstrate that I3P has a very good capacity to restore the barrier function of the epidermis, particularly in relation to IALD.

Claims (9)

Cosmetic use, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, to prevent a reduction in the skin barrier function and/or to strengthen the skin barrier function in an individual, in particular dry skin. Composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, for use in the prevention and/or treatment of atopic dermatitis or eczema. Cosmetic use, in particular topical, non-therapeutic use of a composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, for preventing and/or treating a skin disorder of sensitive skin, in an individual, the skin disorder being a feeling of discomfort, in particular tightness, tingling, warming and/or itching. Composition comprising, in a physiologically acceptable medium, indole-3-pyruvic acid, one of its isomers or one of its salts, for use in the prevention and/or treatment of pruritus and/or inflammation of the skin of an individual. Composition for use according to claim 4, wherein the pruritus and/or inflammation in the skin of an individual is present:
- in a dermatological disorder selected from the group consisting of atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea; or
- in a dermatological disorder following exposure of the skin to pollutants and/or UV rays. Use according to claim 1 or 3, or composition for its use according to any one of claims 2, 4 and 5, in which the composition is applied to fragile, weakened, dry, atopic and/or sensitive skin. Use according to claim 1 or 3, or composition for its use according to any one of claims 2 and 4 to 6, in which the composition comprises a content of indole-3-pyruvic acid, of one of its isomers or of one of its salts, 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 preferably a content of between 0.001% and 1% by weight, even better a content of between 0.001% and 0.01% by weight relative to the total weight of the composition. Use according to claim 1 or 3, or composition for its use according to any one of claims 2 and 4 to 7, in which the composition further comprises at least one adjuvant chosen from the group consisting 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, capylyl 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; antifoaming agents; fragrances; preservatives; anionic, cationic, nonionic, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing or acidifying agents; and mixtures thereof. Use according to claim 1 or 3, or composition for its use according to any one of claims 2 and 4 to 8, the composition being suitable for topical administration.