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

Abstract

The present invention relates to the cosmetic use, in particular a topical non-therapeutic cosmetic use, of a composition comprising indole-3-pyruvic acid, an isomer thereof or a salt thereof in a physiologically acceptable medium for preventing a decrease in skin barrier function and / or enhancing skin barrier function in an individual, in particular in an individual having dry skin. The invention also relates to the use of such a composition for the prevention and / or treatment of skin disorders in sensitive skin in a subject, and the use of such a composition for the prevention and / or treatment of itching and / or inflammation in the skin of a subject. Finally, the present invention relates to a non-therapeutic cosmetic process for caring for keratin materials, in particular the skin, comprising the topical application of such a composition to these keratin materials.

Description

Technical Field

[0001] The present invention relates to the use of indole-3-pyruvic acid for improving skin barrier function and moisturizing the skin.

[0002] More specifically, the present invention aims to provide the cosmetic use, particularly local non-therapeutic cosmetic use, of a composition for preventing a decrease in skin barrier function and / or enhancing skin barrier function in an individual, especially in an individual with dry skin, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

[0003] The present invention also relates to the cosmetic use, particularly local cosmetic use, of such a composition for preventing and / or treating atopic dermatitis or eczema.

[0004] The present invention also relates to the cosmetic use, particularly local non-therapeutic cosmetic use, of such a composition for preventing and / or treating skin disorders of sensitive skin in an individual.

[0005] The present invention also relates to the cosmetic use, particularly local cosmetic use, of such a composition for preventing and / or treating itching and / or inflammation of the skin of an individual, particularly itching and inflammation of the skin of an individual present in a dermatological disorder selected from the group consisting of atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea. Background Art

[0006] The skin is a tissue in which cells are joined together and adhere to one another as a whole. The skin tissue forms an outer covering including sebaceous glands or sweat glands and hair follicles. The skin, particularly the scalp, is an epithelium that undergoes continuous renewal. Renewal or desquamation is a coordinated and finely regulated process that results in the imperceptible and invisible removal of the surface cells.

[0007] The human skin consists of two parts, namely an upper part (epidermis) and a deeper part (dermis).

[0008] The epidermis is generally divided into a basal layer of keratinized cells constituting the stratum germinativum, a spinous layer consisting of several layers of polyhedral cells located above the stratum germinativum, one to three "granular" layers consisting of flattened cells containing different cytoplasmic inclusions, keratohyalin granules, and finally a group of upper layers called the stratum corneum (or horny layer), said stratum corneum (or horny layer) being composed of keratinized cells (called corneocytes) at the end stage of differentiation.

[0009] Keratinocytes are anucleate cells mainly composed of fibrous material containing cytokeratins and are surrounded by a cornified envelope. New cornified cells are continuously produced to compensate for the continuous loss of epidermal cells in the stratum corneum through a mechanism called desquamation.

[0010] However, an imbalance between cell production in the basal layer and the desquamation rate can particularly lead to the formation of scales on the skin surface. Similarly, due to various reasons, the lack of terminal differentiation of stratum corneum cells can result in the formation of large and thick cell clusters visible to the naked eye, called "scales", or in other cases, lead to thinning of the stratum corneum.

[0011] This can lead to a weakening of the epidermal barrier properties, chronic dehydration of the stratum corneum, loss of mechanical elasticity, tightness, and loss of skin gloss and transparency.

[0012] As examples of factors promoting the deterioration of skin surface quality (which weakens the skin barrier), stress, winter periods, seborrhea or lack of moisturization can be mentioned.

[0013] Therefore, in the presence of external attack factors or internal attack factors, weakening of the skin barrier can occur. The external attack factors are particularly selected from irritants (detergents, acids, alkalis, oxidants, reductants, concentrated solvents, gases or toxic fumes, pollutants), heat or climate imbalance (cold, drought, radiation), exogenous substances (pathogenic microorganisms, allergens), and the internal attack factors such as psychological stress.

[0014] This deterioration of the skin barrier leads to skin discomfort, sensory phenomena, and obvious unpleasant phenomena. Individuals affected by this will experience a feeling of skin discomfort, which will particularly manifest as stinging, tightness, burning, and / or itching.

[0015] These skin discomfort sensations (cosmetic and non-therapeutic procedures) are more common in the most exposed areas of the body, namely the hands, feet, face, and scalp.

[0016] These skin discomfort sensations can particularly occur in areas subjected to the following activities: certain daily or frequently repeated hygiene activities (such as shaving, hair removal, cleaning with bathroom or household products, application of adhesives (dressings, patches or prosthesis attachments)), or sports or professional activities, or simply lifestyle-related activities and activities related to the use of clothes, tools or equipment that cause local friction. These skin discomfort sensations can also be amplified by psychological stress.

[0017] These skin discomfort sensations affect everyone, especially:

[0018] - People with "fragile" or "delicate" and vulnerable skin (such as baby skin) that quickly becomes unbalanced during large changes in temperature or relative humidity;

[0019] Persons with "weakened" skin, in particular including:

[0020] (i) Persons in whom the protective hydrolipidic film composed of sweat, sebum and natural moisturizing factors becomes reduced, such as the elderly over 60 years old, in particular the very elderly over at least 75 years old;

[0021] (ii) Persons in whom the composition of the hydrolipidic film is altered.

[0022] Mention may also be made of persons whose skin is "attacked" (such as skin during shaving).

[0023] One of the key steps in the terminal differentiation process of the stratum corneum is the crosslinking of the precursor proteins of the cornified envelope (CE). This phenomenon plays a crucial role in the development and maintenance of skin coherence and skin physical properties such as the barrier function and is a key step in the above-mentioned terminal differentiation process.

[0024] Conventionally used moisturizing active ingredients, such as humectants, moisturizing polymers or fatty substances (such as liquid petrolatum), temporarily alter the surface properties of the skin. These active ingredients cause mechanical softening of the stratum corneum, increase the moisturizing state of the stratum corneum and / or improve the microtexture of the skin by forming a film on the skin surface.

[0025] However, over time, these effects are not necessarily particularly long-lasting. In addition, these active ingredients can be eliminated by cleaning activities.

[0026] To overcome these drawbacks, it is advantageous to turn to active agents with a lasting beneficial effect that are not affected by cleaning when acting on biological pathways, for example by regulating the expression of certain key biomarkers when the barrier function is impaired.

[0027] It is well known that a damaged epidermal barrier causes keratinocytes to secrete chemokines such as TSLP: (thymic stromal lymphopoietin), which is known to be a key chemokine for keratinocyte communication, due to its ability to induce itching by directly activating certain types of neurons (TRPA-1+) as well as the type 2 immune response involved in atopic dermatitis.

[0028] In addition, after barrier impairment, other molecules are also involved in this reaction process, such as the proteins MCP-1 and MIP-1 that participate in the inflammatory process in type 2 immune responses, especially in patients with atopic dermatitis, where they are significantly increased (Kaburagi et al., Arch Dermatol Res. July 2001; 293(7): 350-5), and the cytokines interleukin 1α (IL-1α) and interleukin 29 (IL-29) that participate in the general mechanisms of inflammation (Malik and Kanneganti, Immunol Rev. January 2018; 281(1): 124-137), and IL-29 can be regulated by IL-4 present in type 2 immune responses and atopic dermatitis (Megjugorac et al., Blood. May 27, 2010; 115(21): 4185-90). These two interleukins increase the skin barrier's responsiveness to external attack factors.

[0029] Therefore, it is necessary to identify new active agents that can reduce the expression of these markers.

[0030] Therefore, by identifying these new active agents, it is sought:

[0031] - To prevent the reduction of skin barrier function and / or enhance skin barrier function, especially the skin barrier function of dry skin; and / or

[0032] - To prevent and / or reduce the sensations of skin discomfort, stinging, tightness, burning, and itching, especially in people with sensitive, fragile, weakened, or delicate skin (such as infants or people at least 60 years old, especially at least 75 years old), or in people with an altered composition of the hydro-lipid film; and / or

[0033] - To improve skin barrier function, especially the skin barrier function of atopic skin, and / or extend the remission period between acute crises of such conditions.

[0034] Therefore, there is also a need for an active agent that can enable the skin, especially dry and / or sensitive and / or atopic skin, to maintain its barrier function.

[0035] There is also a need for an active agent for improving skin moisturization.

[0036] In addition, there is also a need for such active agents: for improving the quality and / or skin color of the skin, especially the quality or skin color of sensitive skin; and / or for preventing and / or treating skin disorders related to sensitive skin, especially skin disorders selected from tightness, stinging, burning, and / or itching.

[0037] There is also a need for such an active agent that can prevent and / or treat itching and / or inflammation of an individual's skin, particularly inflammation of the skin affected by the following skin diseases: skin diseases selected from the group consisting of atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis, and rosacea, or skin diseases after the skin is exposed to pollutants and / or ultraviolet rays. Summary of the Invention

[0038] The object of the present invention is to solve the above technical problems.

[0039] In fact, the inventors have now found that in a skin model of atopic dermatitis, indole-3-pyruvic acid can significantly reduce the production of chemokine TSLP, cytokine IL-1α, IL-29, and proteins MCP-1 and MIP-1a.

[0040] Therefore, according to a first aspect, the present invention relates to the cosmetic use, particularly local non-therapeutic cosmetic use, of a composition for preventing a decrease in skin barrier function and / or enhancing skin barrier function in an individual, particularly in an individual with dry skin, the composition comprising indole-3-pyruvic acid, its isomers, or its salts in a physiologically acceptable medium.

[0041] According to a second aspect, the present invention also relates to the cosmetic use, particularly local non-therapeutic cosmetic use, of a composition for preventing and / or treating atopic dermatitis or eczema, the composition comprising indole-3-pyruvic acid, its isomers, or its salts in a physiologically acceptable medium.

[0042] According to a third aspect, the present invention relates to the cosmetic use, particularly local non-therapeutic cosmetic use, of a composition for preventing and / or treating skin disorders of sensitive skin in an individual, the composition comprising indole-3-pyruvic acid, its isomers, or its salts in a physiologically acceptable medium.

[0043] Such skin disorders can particularly be a feeling of discomfort, particularly tightness, tingling, burning, and / or itching.

[0044] According to a fourth aspect, the present invention relates to the cosmetic use, particularly local cosmetic use, of a composition for preventing and / or treating itching and / or inflammation of an individual's skin, the composition comprising indole-3-pyruvic acid, its isomers, or its salts in a physiologically acceptable medium.

[0045] An isomer of indole-3-pyruvic acid according to the present invention can be, for example, 3H-indole-3-pyruvic acid.

[0046] The itching and / or inflammation of an individual's skin can particularly be present in:

[0047] -selected from the group consisting of the following skin diseases: atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis, and rosacea; or

[0048] -in skin diseases after the skin is exposed to pollutants and / or ultraviolet rays.

[0049] Finally, the present invention also relates to a non-therapeutic cosmetic method for caring for keratin materials, preferably the skin, the method comprising topically applying a composition to these keratin materials, the composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

[0050] The composition used according to the present invention can be applied to fragile, weakened, dry, atopic and / or sensitive skin.

[0051] The composition used according to the present invention is particularly suitable for topical application.

[0052] Other features, aspects and advantages of the present invention will become apparent by reading the following detailed description. Detailed Description

[0053] The composition used according to the present invention

[0054] The composition used according to the present invention is preferably a cosmetic.

[0055] The composition used according to the present invention is preferably suitable for topical application to keratin materials, especially the skin, and thus comprises a physiologically acceptable medium, i.e., a medium compatible with the skin.

[0056] The term "cosmetic" refers to a composition compatible with keratin materials (especially the skin, mucous membranes and cuticle). The composition used according to the present invention is non-therapeutic.

[0057] The term "keratin material" is intended to particularly denote the skin, mucous membranes, fibers, eyelashes and skin appendages.

[0058] The term "skin" is intended to refer to all the skin of the body, preferably the skin of the face, scalp, neckline, neck, arms and forearms, or more preferably the skin of the face, face (especially the forehead, nose, cheeks and chin), neckline and neck.

[0059] The composition used according to the present invention preferably comprises a cosmetically acceptable medium, i.e., a medium having a pleasant color, odor and feel and not causing any unacceptable discomfort, i.e., stinging or tightness (which may prevent the user from applying the composition).

[0060] As used herein, the terms "treat" and "treatment" refer to alleviating and / or eliminating the symptoms associated with a particular disease or disorder, as well as the complete disappearance of the disease or disorder under discussion.

[0061] In the context of the present invention, the terms "prevent" and "prevention" denote reducing, to a lesser extent, the risk or probability of a given phenomenon occurring.

[0062] Thus, the compositions used according to the present invention can confer beneficial properties to the skin, particularly in a lasting manner, in particular conferring: an effective barrier function; a moisturizing effect; the elasticity and smooth texture of the skin; an improvement in surface morphology with low roughness, good tissue cohesion, good stratum corneum thickness, and the visual appearance of the skin.

[0063] In particular, the compositions used according to the present invention can be used on the skin of individuals who are fragile, weakened, dry, atopic, and / or sensitive.

[0064] An epidemiological study recently conducted on adult subjects from different countries (Haftek et al., Clin Cosmet Investig Dermatol. 2013; 6: 289 - 294) can show that the concept of "fragile skin" has a specific resonance in the population studied. "Fragile skin" can be defined as skin with inherent fragility, such that it is more susceptible to various aggression factors compared to non - fragile skin.

[0065] Generally speaking, fragile skin has a disrupted barrier function, leading to permeability, and thus a greater response to environmental stress or aggression compared to "normal skin" (non - fragile skin). Therefore, this type of skin has a lower resistance to stress or environmental aggression. In addition to the dysfunction of the barrier function, these stresses can also cause skin inflammation. Finally, fragile skin also recovers its basal state more slowly once exposed to such conditions.

[0066] Fragile skin refers to skin that is inherently fragile, for example, corresponding to the skin of infants, the elderly, or delicate parts of the body (eyelids, face, etc.).

[0067] Weakened skin is skin that is fragile and is termed "environmentally" or "pathologically" fragile. "Environmentally" fragile skin is, in particular, skin that is attacked by climatic stress (heat, cold, drought, etc.), mechanical stress (friction, etc.), physical stress (ultraviolet radiation, lasers, etc.), or chemical stress (surfactants, solvents, etc.). "Pathologically" fragile skin concerns, in particular, skin affected by atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis, and / or rosacea.

[0068] The term "atopic skin" is understood here to mean the skin of a patient that exhibits the same physiological and molecular characteristics as the skin of a patient with atopic dermatitis, in particular exhibiting itching or inflammation, which are chronic and interspersed with remission periods.

[0069] The expression "skin disorder" encompasses sensations of discomfort and also skin signs that are temporarily visible and objectionable and that may affect the same individual.

[0070] In general, sensitive skin is defined by the specific reactivity of the skin. This skin reactivity is usually reflected by signs of discomfort in the individual's reaction when exposed to triggering factors, which can have different origins. Triggering factors can be the application of a cosmetic product to the surface of sensitive skin, eating, exposure to sudden changes in temperature, exposure to air pollution, and / or ultraviolet or infrared rays. These signs of discomfort appear within a few minutes of the individual's exposure to the triggering factor and are one of the fundamental characteristics of sensitive skin. These are mostly sensations of allergic pain. The "dysesthetic sensation" is understood to be a sensation in the skin area, such as stinging, tightness, burning, and / or itching.

[0071] These personal signs usually exist in the absence of obvious clinical symptoms (such as peeling).

[0072] Thus, "sensitive skin" will experience sensations of discomfort much more quickly and frequently than other skin types.

[0073] Dry skin feels rough and appears to be covered with scales and is basically characterized by a feeling of tightness and / or tension. In fact, dry skin is usually accompanied by peeling. From a physiological perspective, dry skin is usually particularly related to a decrease in skin moisture and an adverse effect on the barrier function, which is determined by insensible water loss. From a sensory perspective, dry skin is particularly characterized by a feeling of skin tightness and / or tension.

[0074] Dry skin, also known as "xerosis", can occur at any age and can be unrelated to a pathological condition.

[0075] Thus, the composition according to the invention has proven to be very particularly effective in treating tightness, stinging, burning and / or itching, in particular tightness, stinging, burning and / or itching associated with fragile, weakened, dry, atopic and / or sensitive skin; very particularly effective in physiologically restoring the proper moisturized state of the stratum corneum; very particularly effective in restoring the altered thickness, in particular the thinned thickness, of the skin stratum corneum; very particularly effective in improving the comfort of fragile, weakened, dry, atopic and / or sensitive skin; or very particularly effective in counteracting the dullness and / or lacklustre appearance of such skin.

[0076] As mentioned above, the composition according to the invention comprises indole-3-pyruvic acid, its isomers or its salts.

[0077] Indole-3-pyruvic acid has the following formula I:

[0078] [Chemical formula 1]

[0079]

[0080] According to the invention, the "salt" of indole is to be understood as a salt formed from an inorganic acid or an organic acid, or an inorganic base or an organic base.

[0081] As examples of acid salts, mention may be made of sulfates, citrates, acetates, oxalates, chlorides, bromides, iodides, nitrates, hydrogen sulfates, phosphates, isonicotinates, lactates, salicylates, tartrates, oleates, tannates, pantothenates, hydrogen tartrates, ascorbates, succinates, maleates, gentisates, fumarates, gluconates, glucuronates, saccharates, formates, benzoates, glutamates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates and pamoates (i.e. 1,1'-methylene-bis(2-hydroxy-3-naphthoates)).

[0082] As examples of basic 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), ammonia and organic amines, such as unsubstituted or hydroxy-substituted monoalkylamines, dialkylamines or trialkylamines; dicyclohexylamine; tributylamine, pyridine, N-methyl-N-ethylamine; diethylamine; triethylamine; mono(2-hydroxyalkylamines), bis(2-hydroxyalkylamines) or tris(2-hydroxyalkylamines), such as mono(2-hydroxyethyl)amine, bis(2-hydroxyethyl)amine, tris(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, or tris(hydroxymethyl)methylamine, N,N-dialkyl-N-(hydroxyalkyl)amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tris(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids, such as arginine and lysine.

[0083] The salt of indole-3-pyruvic acid according to the present invention is preferably a basic salt, especially a sodium salt or a potassium salt.

[0084] The composition used according to the present invention may contain, relative to the total weight of the composition, at least 0.0001% by weight of indole-3-pyruvic acid, its isomers or its salts, preferably in an amount of 0.0001% to 5% by weight, more preferably in an amount of 0.001% to 1% by weight, and even better in an amount of 0.001% to 0.01% by weight.

[0085] The composition used according to the present invention may further contain at least one adjuvant selected from the group consisting of: liquid, paste or solid fatty substances; organic solvents selected from linear or branched C1-C6 monoalcohols, such as ethanol, isopropanol, tert-butanol; polyols, such as glycerol, propylene glycol, pentylene glycol, octylene glycol, hexylene glycol (or 2-methyl-2,4-pentanediol) and polyethylene glycol; polyol ethers, such as dipropylene glycol monomethyl ether; ionic or non-ionic, hydrophilic or lipophilic thickeners; softeners; humectants; emollients; sunscreens; stabilizers; silicones; defoamers; fragrances; preservatives; anionic, cationic, non-ionic, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing agents or acidifying agents; and mixtures thereof.

[0086] Relative to the total weight of the composition, such an adjuvant may account for 0.01% to 20% by weight, preferably 0.1% to 10% by weight, and even better 1% to 5% by weight.

[0087] Of course, those skilled in the art will take care to select such adjuvant or adjuvants and / or their amounts such that the advantageous properties of the indole-3-pyruvic acid, its isomers or its salts of the composition used according to the present invention are not or are substantially not adversely affected by the intended addition.

[0088] Preferably, the composition used according to the present invention may contain water.

[0089] In particular, relative to the total weight of the composition, the composition used according to the present invention may contain 1% to 95% by weight, preferably 20% to 80% by weight, and even better 30% to 60% by weight of water.

[0090] The pH of the composition used according to the present invention is advantageously less than or equal to 8, preferably in the range of 4 to 7, and even better in the range of 5.5 to 6.5.

[0091] Advantageously, the composition used according to the present invention may contain one or more water-soluble organic solvents.

[0092] According to the present invention, the term "water-soluble solvent" denotes a compound that is liquid at room temperature and water-soluble, in particular having a miscibility with water of greater than 50% by weight at 25 °C and atmospheric pressure.

[0093] The water-soluble organic solvents can be selected from linear or branched C1-C6 monoalcohols such as ethanol, isopropanol or tert-butanol; polyols such as glycerol, propylene glycol, pentylene glycol, octylene glycol, hexylene glycol (or 2-methyl-2,4-pentanediol) and polyethylene glycol; polyol ethers such as dipropylene glycol monomethyl ether; and mixtures thereof.

[0094] Relative to the total weight of the composition, these water-soluble organic solvents can be present in the composition used according to the invention at a concentration of 0.01% to 20% by weight, preferably 0.1% to 10% by weight, more preferably 1% to 5% by weight.

[0095] The composition used according to the invention can also comprise at least one additional cosmetic active agent.

[0096] The at least one additional cosmetic active agent can in particular be at least one active agent for caring for fragile, weakened, atopic and / or sensitive skin.

[0097] In the context of the present invention, the term "additional active agent" refers to a compound that has biological activity per se (i.e., without the intervention of an external reagent to activate it), and this biological activity can in particular be:

[0098] - sedative or anti-irritant activity; and / or

[0099] - moisturizing activity; and / or

[0100] - emollient activity.

[0101] The additional active agents that can be used in the composition used according to the invention can in particular be selected from humectants (such as glycerol and / or urea), emollients (such as liquid petrolatum), anti-irritants, and mixtures thereof in any proportion.

[0102] Relative to the total weight of the composition, the additional active agents used in the composition used according to the invention can account for 0.0001% to 20% by weight, preferably 0.01% to 10% by weight, more preferably 0.01% to 5% by weight.

[0103] Needless to say, those skilled in the art will take care to select such optional additional compound(s) and / or their amounts such that the advantageous properties of the composition used according to the invention are not or are substantially not adversely affected by the intended addition.

[0104] The compositions used according to the invention can be in any presentation form commonly used in the beauty field, in particular any presentation form that can generally be used for the selected mode of administration.

[0105] Depending on the type of composition under consideration, the carrier can have different properties.

[0106] The compositions according to the invention can be in any presentation form commonly used for topical administration, in particular the following forms: aqueous solution or water-alcohol solution, oil-in-water (O / W) emulsion, water-in-oil (W / O) emulsion or multiple (triple: W / O / W or O / W / O) emulsion, hydrogel, or dispersion of a fatty phase in an aqueous phase using spheres, which spheres can be ionic and / or non-ionic lipid vesicles (liposomes, niosomes or oleosomes). These compositions are prepared according to usual methods.

[0107] The compositions used according to the invention are preferably suitable for topical administration.

[0108] More specifically, for compositions for topical administration, i.e., compositions applied to the skin, they can be aqueous solutions, water-alcohol solutions or oil solutions, solution-type dispersions or lotion-type or serum-type dispersions, emulsions of liquid or semi-liquid consistency of the milk type, suspensions or emulsions of the cream type, hydrogels or anhydrous gels, microemulsions, microcapsules, microparticles, or dispersions of ionic and / or non-ionic vesicles.

[0109] The compositions used according to the invention can advantageously contain at least one liquid fatty substance.

[0110] The term "liquid fatty substance" refers to compounds with a melting point below about 30°C to 35°C, as opposed to solid fatty substances (such as waxes) with a melting point above about 50°C.

[0111] As oils that can be used in the compositions of the invention, for example, can be mentioned:

[0112] - hydrocarbon-based oils of animal origin;

[0113] - hydrocarbon-based oils of plant origin;

[0114] - synthetic esters and ethers, in particular synthetic esters and ethers of fatty acids, such as oils of the formula R’COOR2 and R’OR2, where R’ represents a fatty acid residue containing 8 to 29 carbon atoms and R2 represents a branched or unbranched hydrocarbon-based chain containing 3 to 30 carbon atoms;

[0115] - linear or branched hydrocarbons of mineral or synthetic origin;

[0116] - fatty alcohols containing 8 to 26 carbon atoms;

[0117] - Hydrocarbon-based and / or silicone-based fluorinated oils;

[0118] - Silicone oils;

[0119] - Their mixtures.

[0120] In the above list of oils, the term "hydrocarbon-based oil" refers to any oil that mainly comprises carbon and hydrogen atoms, and may include ester, ether, fluorine, carboxylic acid, and / or alcohol groups.

[0121] Other fatty substances that may be present in the oil phase are, for example, fatty acids containing 8 to 30 carbon atoms, waxes, silicone resins, and silicone elastomers.

[0122] Those skilled in the art can select these fatty substances in various ways to prepare a composition having desired properties (such as in terms of consistency or texture).

[0123] According to a specific embodiment of the present invention, the composition according to the present invention is a water-in-oil (W / O) or oil-in-water (O / W) emulsion. Relative to the total weight of the composition, the proportion of the oil phase of the emulsion can be in the range of 5% to 90% by weight, preferably in the range of 5% to 60% by weight. The emulsion generally contains at least one emulsifier (selected from amphoteric, anionic, cationic, and nonionic emulsifiers, which are used alone or as a mixture), and optionally a co-emulsifier. The emulsifier is appropriately selected according to the emulsion (W / O or O / W) to be obtained.

[0124] Relative to the total weight of the composition, the emulsifier and the co-emulsifier are generally present in the composition in a proportion of 0.3% to 30% by weight, preferably 0.5% to 20% by weight.

[0125] For W / O emulsions, examples of emulsifiers that may be mentioned include polydimethylsiloxane copolyols and alkyl polydimethylsiloxane copolyols. Solid organopolysiloxanes containing crosslinked elastomers having at least one oxyalkylene group can also be used as W / O emulsion surfactants.

[0126] For O / W emulsions, examples of emulsifiers that may be mentioned are nonionic emulsifiers.

[0127] Preferably, the composition used according to the present invention is different from compositions having a substantially detergent purpose for the skin, hair, and / or mucous membranes, such as soaps, shampoos, and shower gels for washing and / or cleaning.

[0128] More specifically, the composition used according to the present invention can be used for topical application, preferably can be in the form of an emulsion, preferably in the form of an oil-in-water emulsion. Preferably, such an emulsion does not need to be rinsed off after application.

[0129] The composition used according to the invention can alternatively be in the form of a product for facial and / or body care or make-up, and can 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.

[0130] Before formation, the ingredients are mixed in an order and under conditions readily determinable by a person skilled in the art.

[0131] Use and Process

[0132] As mentioned above, according to one aspect of the invention, the invention relates to the cosmetic use, in particular for improving skin hydration, of a composition for preventing a decrease in skin barrier function and / or enhancing the skin barrier function, especially in an individual having dry skin, in particular for local non-therapeutic cosmetic use, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

[0133] The invention also relates to the cosmetic use, in particular for local cosmetic use, of a composition for preventing and / or treating atopic dermatitis or eczema, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

[0134] The invention also relates to the cosmetic use, in particular for local non-therapeutic cosmetic use, of a composition for preventing and / or treating skin disorders of sensitive skin in an individual, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

[0135] The invention also relates to a non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, which method comprises topically applying a composition to these keratin materials, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

[0136] The skin which is particularly affected by this method and thus the skin to which the composition used according to the invention is applied can preferably be fragile, weakened, dry, atopic and / or sensitive skin.

[0137] As mentioned above, the composition used in the method of the invention is preferably suitable for topical application.

[0138] The cosmetic uses, methods and processes contemplated according to the invention are non-therapeutic.

[0139] The cosmetic uses and processes of the invention are preferably carried out by topically applying a composition according to the invention.

[0140] Topical application comprises externally applying the cosmetic composition to the skin according to the usual use techniques for these compositions.

[0141] For example, the cosmetic use or method according to the invention can be achieved by topical (e.g., daily) administration of at least one composition according to the invention, which can be formulated, for example, in the form of a cream, gel, serum, lotion, emulsion or makeup remover, preferably in the form of an emulsion.

[0142] The administration can be repeated, for example, one to two times a day, for one day or more days, usually for an extended period of at least 4 weeks, or even 4 to 15 weeks, with one or more stopping periods, where appropriate.

[0143] According to one embodiment, the administration is daily (once a day), usually for an extended period of at least 4 weeks, or even 4 to 15 weeks, with one or more stopping periods, where appropriate.

[0144] According to one embodiment, the cosmetic treatment method according to the invention can include a single administration.

[0145] Throughout the specification, including the claims, unless otherwise specified, the terms "between... and..." and "ranging from... to..." shall be understood to mean including the limits.

[0146] The following examples illustrate the invention but do not limit its scope.

[0147] In the examples, unless otherwise specified, the temperature is room temperature (20 °C), expressed in degrees Celsius, and the pressure is atmospheric pressure.

[0148] Examples

[0149] Example: Study on the antipruritic and anti-inflammatory effects of indole-3-pyruvic acid (I3P)

[0150] A / - Materials and methods

[0151] Thaw and culture in a T75 flask

[0152] Thaw 3T3 cells

[0153] [Table 1]

[0154] Product Supplier Number Y27632 ROCK inhibitor (10 mM) Sigma Y0503 G7F medium Episkin GR7F+

[0155] Table 1

[0156] 3T3 fibroblasts (ATCC, CRL-1658), used as a feeder for keratinocytes, were initially cultured in DMEM (No. 12491015, ThermoFisher) and treated with 0.5 mg / ml mitomycin solution (Sigma, M4287) before freezing. Then, the mitomycin-treated 3T3s were seeded at 2.1 million per flask in 30 ml of G7 and incubated in an oven at 37 °C and 5% CO2 for 2 - 3 hours.

[0157] Thaw primary cells of normal human epidermal keratinocytes (NHEK) collected from the foreskins of healthy subjects obtained after plastic surgery from Alphenyx (France).

[0158] Thaw the NHEK and seed at 150,000 in a flask. Aspirate all the medium used to seed the 3T3m, and then dispense 35 ml of G7F + Y27632 medium (see below) into each flask.

[0159] Add 65 μl of the cell suspension containing 150,000 NHEK to each flask, followed by an incubation step in an oven at 37 °C and 5% CO2. Replace the medium with 10 μM G7F + Y27632 medium at 48 hours.

[0160] Transfer to a 48-well plate for stimulation

[0161] [Table 2]

[0162] Product Supplier Number Y27632 ROCK inhibitor (10 mM) Sigma Y0503 KGM Gold Lonza 00192060 TNS PromoCell C-41120 TrypLE Express Gibco ThermoFisher 10718463

[0163] Table 2

[0164] When the flask containing the 3T3 feeder reaches 80% - 90% confluence, seed 50,000 NHEK in a 48-well plate containing 1 ml of KGM Gold medium without hydrocortisone and 1 ml of BPE (bovine pituitary extract) (instead of the 2 ml contained in the supplement of the KGMGold kit); Y27632 10 μM. Then incubate in an oven at 37 °C and 5% CO2 for 72 hours.

[0165] After 72 hours, perform the step of exposure to a stimulation cocktail as defined below to induce a phenotype similar to that observed in patients with atopic dermatitis in terms of the chemokines produced.

[0166] Stimulation cocktail:

[0167] - Poly(I:C): 1 mg / ml (used at 10 μg / ml in the wells), cat. no. P9582, Sigma; and

[0168] - IL-4: 5 μg / ml (used at 50 ng / ml in the wells), cat. no. 204-IL, RnD Systems; and

[0169] - IL-13: 5 μg / ml (used at 50 ng / ml in the wells), cat. no. 213-ILB / CF, RnD Systems; and

[0170] - TNFα: 5 μg / ml (used at 10 ng / ml in the wells), cat. no. 210-TA / CF, RnD Systems.

[0171] Molecules of interest:

[0172] Various molecules of interest were added to KGM Gold medium:

[0173] - IALD cat. no.: 129445, Sigma: Stock solution in DMSO at 10 mg / ml was diluted in the medium to final concentrations of 10 μg / ml and 25 μg / ml; or

[0174] - FICZ cat. no.: SML1489, Sigma: Stock solution in DMSO at 0.5 mg / ml was diluted in the medium to final concentrations of 0.05 μg / ml and 0.1 μg / ml; or

[0175] - I3P cat. no.: 286281, Sigma: Stock solution in DMSO at 10 mg / ml was diluted in the medium to final concentrations of 10 μg / ml and 25 μg / ml.

[0176] Determination of chemokines in the supernatant after 48 hours of culture

[0177] Chemokines in the culture supernatants were measured using Meso Scale Discovery technology according to the manufacturer's instructions.

[0178] [Table 3]

[0179]

[0180] Table 3

[0181] Statistical analysis

[0182] 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). One-way ANOVA test was used followed by Dunnett's multiple comparison test to analyze the data. Results were considered statistically significant when p < 0.05.

[0183] B / - Results

[0184] The antipruritic effects of indole-3-pyruvic acid and comparative products (indole-3-carboxaldehyde (IALD) and FICZ (5,11-dihydroindolo[3,2-b]carbazole-6-carboxaldehyde, 6-formylindolo[3,2-b]carbazole)) were investigated in a 3D model that recapitulates atopic dermatitis.

[0185] FICZ is a literature-based anti-itch and anti-inflammatory positive control.

[0186] IALD is also a positive control. In fact, in the study by Yu et al. (J Allergy Clin Immunol, June 2019; 143(6):2108-2119.e12), topical application of IALD could reduce skin inflammation in a dermatitis-like mouse model.

[0187] The results in Tables 4, 5, and 6 below are expressed as percentage differences relative to the stimulation control.

[0188] [Table 4]

[0189]

[0190] Table 4[Table 5]

[0191]

[0192] Table 5 [Table 6]

[0193]

[0194] Table 6

[0195] These represent the percentages of the expression levels of TSLP, MCP-1, IL-1α, MIP-1α, and IL-29 in the keratinocyte culture medium relative to the stimulation control 48 hours after stimulation. p-values were calculated relative to the stimulation control.

[0196] TSLP: (thymic stromal lymphopoietin) is a key chemokine for keratinocyte communication because it can induce itching by directly activating certain types of neurons (TRPA-1+) and type 2 immune responses involved in atopic dermatitis.

[0197] MCP-1 and MIP-1a are proteins involved in inflammatory processes in type 2 immune responses, especially in patients with atopic dermatitis, where they are significantly increased (Kaburagi et al., Arch Dermatol Res. July 2001; 293(7): 350-5).

[0198] These tables show that for I3P and FICZ, the production of the chemokines TSLP, IL-1a, and IL-29, and the proteins MCP-1 and MIP-1a is significantly reduced, while this reduction is not observed with IALD.

[0199] In summary, all these results indicate that I3P has a very good ability to restore the epidermal barrier function, especially compared to IALD.

Claims

1. Use of a composition for the prevention and / or treatment of atopic dermatitis or eczema, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

2. Non-therapeutic cosmetic use, in particular topical non-therapeutic cosmetic use, of a composition for the prevention and / or treatment of skin disorders of sensitive skin in an individual, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium, said skin disorders being sensations of discomfort, in particular tightness, stinging, burning and / or itching.

3. Use of a composition for the prevention and / or treatment of itching of an individual's skin, said composition comprising indole-3-pyruvic acid, its isomers or its salts in a physiologically acceptable medium.

4. Use of the composition according to claim 3, wherein, The itching of the individual's skin is present in: - skin diseases selected from the group consisting of: atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea; or - skin diseases after the skin is exposed to pollutants.

5. Use according to claim 2 or use of the composition 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 use of the composition according to any one of claims 1, 3 to 5, wherein, Relative to the total weight of the composition, the composition contains a content of at least 0.0001% by weight of indole-3-pyruvic acid, its isomers or its salts, preferably a content of 0.0001% to 5% by weight relative to the total weight of the composition, more preferably a content of 0.001% to 1% by weight, and still better a content of 0.001% to 0.01% by weight.

7. Use according to claim 2 or use of the composition according to any one of claims 1, 3 to 6, wherein, The composition further comprises at least one adjuvant selected from the group consisting of: liquid, pasty or solid fatty substances; organic solvents selected from linear or branched C1-C6 monohydric alcohols, such as ethanol, isopropanol, tert-butanol; polyhydric alcohols, such as glycerol, propylene glycol, pentylene glycol, octylene glycol, hexylene glycol (or 2-methyl-2,4-pentanediol) and polyethylene glycol; polyhydric alcohol ethers, such as dipropylene glycol monomethyl ether; ionic or non-ionic, hydrophilic or lipophilic thickeners; emollients; humectants; emollients; sunscreens; stabilizers; silicones; defoamers; fragrances; preservatives; anionic, cationic, non-ionic, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing agents or acidifying agents; and mixtures thereof.

8. Use according to claim 2 or use of the composition according to any one of claims 1, 3 to 7, said composition being suitable for topical application.

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