Cosmetic use of composition for caring for keratin materials, comprising at least indole-3-acetamide

Abstract

The present invention relates to the cosmetic use of a composition for caring for keratin materials comprising at least indole-3-acetamide. The present invention relates to a composition comprising indole-3-acetamide, an isomer thereof or a salt thereof in a physiologically acceptable medium for use in the treatment of keratin materials in an individual, the present invention relates to cosmetic use, in particular topical non-therapeutic cosmetic use, for preventing and / or enhancing skin barrier function, in particular in individuals with dry skin. The invention also relates to the non-therapeutic use of such a composition for preventing and / or treating skin disorders of sensitive skin in a subject, and also to the use of such a composition for preventing and / or treating itching and / or inflammation of 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

Field of the Invention

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

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

[0003] The present invention further relates to the cosmetic use, particularly for 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 for 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 additionally relates to the cosmetic use, particularly for local cosmetic use, of such a composition for preventing and / or treating itching and / or inflammation of the skin of an individual, particularly in dermatological disorders selected from atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea. Prior Art

[0006] The skin is a tissue whose cells are joined together and adhere to each other as a whole. The skin tissue forms an external covering containing sebaceous glands or sweat glands and hair follicles. The skin (and especially 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 surface cells.

[0007] The human skin is composed of two compartments, namely, an upper compartment (epidermis) and a deeper compartment (dermis).

[0008] The epidermis is customarily divided into the basal layer of keratinocytes that make up the germinative layer of the epidermis; the spinous layer composed of several layers of polygonal cells located above the germinative layer; one to three "granular" layers composed of flattened cells containing different cytoplasmic inclusions (keratohyalin granules); and a final group of upper layers called the stratum corneum (or horny layer), which is composed of keratinocytes (called corneocytes) in their final stage of differentiation.

[0009] Corneocytes are anucleate cells mainly composed of fibrous material containing cytokeratins and are surrounded by a cornified envelope. New keratinocytes are constantly produced to compensate for the epidermal cells continuously lost at the stratum corneum by a mechanism called desquamation.

[0010] However, an imbalance between cell production and desquamation rate at the basal layer can particularly lead to the formation of scales on the skin surface. Similarly, a lack of terminal differentiation of stratum corneum cells for various reasons can result in the formation of large thick cell clusters visible to the naked eye and called "squamae", 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 also loss of skin gloss and transparency.

[0012] As examples of factors that promote a decrease in skin surface quality (which weakens the skin barrier), mention may be made of stress, winter, excessive sebum or lack of moisturization.

[0013] Thus, weakening of the skin barrier can occur in the presence of external attack factors especially selected from irritants (detergents, acids, alkalis, oxidizing agents, reducing agents, concentrated solvents, gases or toxic fumes, pollutants), heat or climatic imbalances (cold, drought, radiation), biological xenobiotics (undesirable microorganisms, allergens), or internal attack factors such as psychological stress.

[0014] This deterioration of the skin barrier can lead to skin discomfort, sensory phenomena and especially unpleasant phenomena. Individuals affected by it can then experience a feeling of skin discomfort, which can be particularly manifested as stinging, tightness, heat and / or itching.

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

[0016] They can occur particularly in areas subjected to certain daily or frequently repeated hygiene actions such as shaving, hair removal, cleaning with toiletry or household products, application of adhesives (attachment of dressings, patches or prostheses), or in cases of sports or professional activities, or simply actions related to lifestyle and clothing worn, or use of tools or equipment that cause local friction. They can also be amplified by psychological stress.

[0017] These feelings of skin discomfort affect everyone, and especially:

[0018] - people with "fragile" or "delicate" and vulnerable skin that rapidly becomes imbalanced during large changes in temperature or relative humidity (for example in the case of baby skin);

[0019] - people with "weakened" skin, especially including:

[0020] (i) those in whom the protective hydrolipidic film, which consists of sweat, sebum and natural moisturizing factors, is reduced, as is the case for people over 60 years old, and particularly in the case of the elderly (at least 75 years old);

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

[0022] Mention may also be made of people with "attacked" skin (such as shaved skin).

[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 an important role in the development and maintenance of skin cohesion 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 can cause mechanical softening of the stratum corneum, improve its moisturizing state and / or improve the microrelief of the skin by forming a film on the skin surface. However, these effects do not necessarily last very long. In addition, these active ingredients can be removed by the cleaning action.

[0025] To overcome these drawbacks, it is advantageous to turn to active ingredients that have a lasting beneficial effect that is not affected by cleaning when acting on biological pathways.

[0026] Recently, Chng et al. (Microbiol July 11, 2016; 1(9):16106.doi:10.1038 / nmicrobiol.2016.106) have demonstrated that the tryptophan metabolic pathway (i.e., the aryl hydrocarbon receptor (AhR) pathway) is reduced in the skin microbiota of patients with atopic dermatitis. AhR is a transcription factor involved in skin homeostasis (Di Meglio et al., Immunity. June 19, 2014; 40(6):989-1001; Haas et al., J Invest Dermatol. November 2016; 136(11), 2260-2269).

[0027] The best-known ligands that bind to AhR include bioheterogeneous substances, such as polycyclic aromatic hydrocarbons (HAP), such as benzo[a]pyrene, polychlorinated biphenyls (PCB); and halogenated aromatic hydrocarbons (related to air pollution), such as dioxins. AhR is particularly recognized for its role in the metabolism of these bioheterogeneous substances and their detoxification (Furue et al., Acta DermVenereol. November 5, 2018; 98(10):918-923).

[0028] Certain members of the cytochrome P450 family, such as CYP1A1, and also other detoxifying enzymes such as glutathione S-transferases (GSTs) can be induced by AhR. Metabolites of AhR xenobiotic ligands, especially polycyclic aromatic hydrocarbons, cause barrier dysfunction by accelerating the terminal differentiation of keratinocytes and also by inducing the release of type 2 inflammatory cytokines (Hidaka et al., Nat Immunol. January 2017; 18(1): 64-73). This exacerbates the inflammation in patients with atopic dermatitis. This is because CYP1A1 activity can be harmful as it can generate reactive oxygen species in keratinocytes. Nevertheless, other AhR ligands can also have beneficial antioxidant effects via the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) (Schafer et al., EMBO Mol Med. May 2012; 4(5): 364–379).

[0029] Therefore, there is a need to identify new active ingredients that make it possible to very weakly induce the harmful biological pathways mediated by cytochrome P450 (CYP1A1) in the AhR pathway while activating the beneficial biological detoxification pathways mediated by NRF2 within the same AhR pathway.

[0030] By identifying these new active ingredients, it is thus attempted to:

[0031] - Prevent the reduction of the skin barrier function (especially the skin barrier function of dry skin) and / or enhance the skin barrier function (especially the skin barrier function of dry skin); and / or

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

[0033] - Prevent and / or treat atopic dermatitis or eczema and / or extend the remission period between acute episodes of this type of condition.

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

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

[0036] In addition, there is a need for active ingredients for improving the quality and / or complexion of the skin (especially the quality and / or complexion of sensitive skin); and / or for preventing and / or treating skin disorders associated with sensitive skin (especially selected from tightness, stinging, heat, and / or itching).

[0037] It is also necessary to have active ingredients that can prevent and / or treat the following disorders: itching and / or inflammation of the individual's skin, in particular skin inflammation affected by a dermatological disorder selected from atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis, and rosacea, or skin inflammation affected by a dermatological disorder after the skin is exposed to pollutants and / or UV rays.

[0038] Disclosure of the invention

[0039] The object of the present invention is to solve the above technical problems.

[0040] In fact, the inventors have now found in a skin model of atopic dermatitis that indole-3-acetamide makes it possible to significantly reduce (in particular to a greater extent than known active ingredients) the production of thymic stromal lymphopoietin (TSLP) in keratinocytes. In fact, TSLP is a key chemokine for keratinocyte communication because it can induce itching by directly activating certain types of neurons (TRPA-1+) and also by involving the type 2 immune response involved in atopic dermatitis. As exemplified, for example, in Si-Hang Wang and Ya-Gang Zuo (Front Immunol. June 24, 2021: 12:698522) and Zsolt Dajnoki et al. (J Invest Dermatol. May 2017; 137(5):1114-1125), it is well known that there is a link between TSLP markers and certain skin disorders, including atopic dermatitis, psoriasis, rosacea, chronic spontaneous urticaria, and systemic sclerosis. In addition, the inventors have also observed that indole-3-acetamide can reduce the production of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) in the keratinocytes of this same model. TRAIL is a protein involved in the apoptosis pathway and is produced in large amounts during the stimulation used to reproduce the atopic dermatitis model.

[0041] It has also been observed that, unlike other active ingredients available in the prior art, indole-3-acetamide only very weakly induces or does not induce the Cyp1a1 pathway, the activity of which can be harmful (because it produces reactive oxygen species in keratinocytes), which is different from indole-3-carboxaldehyde (IALD), which is an undesirable strong inducer, as shown in the following examples.

[0042] Finally, the inventors have demonstrated that indole-3-acetamide makes it possible to restore the control thickness of the epidermal stratum corneum in a skin model of atopic dermatitis and to do so in a manner superior to that of compounds known from the prior art. Summary of the Invention

[0044] Thus, according to a first aspect, the present invention relates to the cosmetic use, in particular local non-therapeutic cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing a decrease in skin barrier function and / or enhancing skin barrier function in an individual, particularly in an individual with dry skin.

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

[0046] According to a second aspect, the present invention relates to the cosmetic use, particularly local cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing and / or treating atopic dermatitis or eczema.

[0047] According to a third aspect, the present invention relates to the cosmetic use, particularly local non-therapeutic cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing and / or treating skin disorders of sensitive skin in an individual.

[0048] Such skin disorders can in particular be a feeling of discomfort and in particular tightness, stinging, heat and / or itching.

[0049] According to a fourth aspect, the present invention relates to the cosmetic use, particularly local cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing and / or treating itching and / or inflammation of an individual's skin.

[0050] The itching and / or inflammation of an individual's skin can in particular be present in the following disorders:

[0051] - dermatological disorders selected from atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea; or

[0052] - dermatological disorders after the skin has been exposed to pollutants and / or UV rays.

[0053] Finally, the present invention also relates to a non-therapeutic cosmetic method for caring for keratin materials, particularly the skin, which comprises topically applying a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium to these keratin materials.

[0054] The composition used according to the present invention can be applied to fragile, weakened, dry, atopic and / or sensitive skin.

[0055] The composition used according to the present invention can be particularly suitable for topical application.

[0056] Other features, aspects, and advantages of the present invention will become apparent upon reading the following detailed description. Detailed Description of the Invention

[0058] Compositions for Use in Accordance with the Invention

[0059] The compositions for use in accordance with the invention are preferably cosmetic.

[0060] The compositions for use in accordance with the invention are preferably suitable for topical application to keratin materials (especially the skin), and thus comprise a physiologically acceptable medium, i.e., a medium compatible with the skin.

[0061] The term "cosmetic" denotes a composition compatible with keratin materials (especially the skin, mucous membranes, and skin appendages). The compositions for use in accordance with the invention are non-therapeutic.

[0062] The term "keratin material" particularly denotes the skin, mucous membranes, fibers, eyelashes, and skin appendages.

[0063] The term "skin" denotes all the skin of the body, and preferably the skin of the face, scalp, décolletage, neck, arms, and forearms, or still more preferably the skin of the face (especially the forehead, nose, cheeks, and chin), the skin of the décolletage, and the skin of the neck.

[0064] The compositions for use in accordance with the invention preferably comprise 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) that would tend to prevent the user from applying the composition.

[0065] As used herein, the term "treat" means alleviating and / or eliminating the symptoms associated with a particular disorder or condition and also causing the mentioned disorder or condition to disappear completely.

[0066] In the context of the present invention, the term "prevent" means reducing the risk or probability of a given phenomenon occurring to a lesser degree.

[0067] Thus, the compositions for use in accordance with the invention make it possible to confer (especially in a lasting manner) beneficial properties on the skin, especially the following beneficial properties: an effective barrier function; a moisturizing effect; the elasticity and smooth texture of the skin; a surface morphology with low roughness, good tissue cohesion, a good stratum corneum thickness, and an improvement in the visual appearance of the skin.

[0068] In particular, the compositions for use in accordance with the invention can be used on the fragile, weakened, dry, atopic, and / or sensitive skin of an individual.

[0069] Recent epidemiological studies (Haftek et al., Clin Cosmet Investig Dermatol. 2013;6:289–294) in adult subjects from various countries have made it possible to establish that the concept of "sensitive skin" has a specific resonance among the studied populations. "Sensitive skin" can be defined as skin with intrinsic fragility such that it is more vulnerable to various aggressors than non-sensitive skin.

[0070] Generally speaking, compared to "normal skin" (non-sensitive skin), sensitive skin has a disrupted barrier function, which leads to increased permeability and thus greater reactivity to environmental stressors or aggressors. Consequently, this type of skin has a lower tolerance to stress or environmental aggressors. In addition to the dysfunction of the barrier function, these stressors can also cause skin inflammation. Finally, once exposed to such conditions, sensitive skin also takes longer to return to its basal state.

[0071] Sensitive skin is called constitutively sensitive skin and corresponds to, for example, the skin of infants, the elderly, or delicate areas of the body (eyelids, face, etc.).

[0072] Weakened skin is sensitive skin called "environmental" sensitive skin or "pathological" sensitive skin. "Environmental" sensitive skin is especially skin attacked by climatic stress (heat, cold, drought, etc.), mechanical stress (friction, etc.), physical stress (UV radiation, lasers, etc.) or chemical stress (surfactants, solvents, etc.). "Pathological" sensitive skin concerns skin particularly affected by atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis or rosacea.

[0073] The term "atopic skin" here denotes the skin of patients presenting the same physiological and molecular characteristics as the skin of patients with atopic dermatitis, in particular skin presenting itching or inflammation, these manifestations being chronic and interspersed with remission periods.

[0074] The expression "skin disorder" encompasses the feeling of discomfort as well as also temporary visible and unaesthetic skin signs liable to affect the same individual.

[0075] In general, sensitive skin is defined by a specific reactivity of the skin. This skin reactivity is usually reflected by the manifestation of discomfort signs in response to the contact of an individual with triggering factors, which can have multiple sources. It can be the application of a cosmetic product to the surface of sensitive skin, the consumption of food, exposure to sudden temperature changes, air pollution and / or ultraviolet or infrared rays. The appearance of these discomfort signs (which occur within a few minutes of the individual's contact with the triggering factor) is one of the fundamental characteristics of sensitive skin. Most of these are dysesthetic sensations. "Dysesthetic sensations" denote sensations felt in a skin area, such as stinging, tightening, heat and / or itching.

[0076] These subjective signs are usually present in the absence of visible clinical signs such as redness and desquamation.

[0077] Therefore, this skin type will present discomfort sensations much faster and more frequently than other skin types.

[0078] Dry skin feels rough to the touch, appears covered with scales, and basically exhibits a feeling of tightness and / or tension. In fact, dry skin is usually accompanied by desquamation.

[0079] At the physiological level, dry skin is usually particularly associated with a decrease in skin hydration and an impaired barrier function (measured by imperceptible water loss). At the sensory level, it is particularly characterized by a feeling of skin tightness and / or tension.

[0080] Dry skin (also called "xerosis") can occur at any age and may be unrelated to a pathological condition.

[0081] Therefore, it has been proven that the composition according to the invention is very particularly effective for treating tightness, stinging, heat and / or itching (especially related to fragile, weakened, dry, atopic and / or sensitive skin), very particularly effective for physiologically restoring the appropriate moisturized state of the stratum corneum, very particularly effective for restoring the thickness of the skin stratum corneum that has been adversely affected (and especially thinned), and very particularly effective for improving the comfort of fragile, weakened, dry, atopic and / or sensitive skin.

[0082] As indicated above, the composition according to the invention comprises indole-3-acetamide, its isomers or its salts.

[0083] Indole-3-acetamide (also called 1H-indole-3-acetamide) has the following formula I:

[0084] [Chemical formula 1]

[0085]

[0086] The "salt" of indole according to the present invention refers to a salt formed by an inorganic acid or an organic acid, or an inorganic base or an organic base.

[0087] The composition used according to the present invention may contain indole-3-acetamide, its isomers or its salts in an amount of at least 0.0001% by weight, preferably between 0.0001% and 5% by weight, more preferably between 0.001% and 1% by weight, still more preferably between 0.001% and 0.01% by weight, based on the total weight of the composition.

[0088] The composition used according to the present invention may further contain at least one adjuvant selected from the following: liquid fatty substances, pasty fatty substances 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, caprylyl 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; softeners; humectants; emollients; sunscreen agents; stabilizers; silicones; defoamers; fragrances; preservatives; anionic surfactants, cationic surfactants, non-ionic surfactants, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing agents or acidifying agents; and mixtures thereof.

[0089] Such adjuvants may account for 0.01% to 20% by weight, preferably 0.1% to 10% by weight and still more preferably 1% to 5% by weight, based on the total weight of the composition.

[0090] Of course, those skilled in the art will carefully select such adjuvant or adjuvants and / or their amounts so that the beneficial properties of indole-3-acetamide, its isomers or its salts in the composition used according to the present invention are not or are substantially not adversely affected by the envisaged addition.

[0091] Preferably, the composition used according to the present invention may contain water.

[0092] The composition may contain 1% to 95% by weight, preferably 20% to 80% by weight, still more preferably 30% to 60% by weight of water, based on the total weight of the composition used according to the present invention.

[0093] 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, still more preferably in the range of 5.5 to 6.5.

[0094] Advantageously, the composition used according to the present invention may contain one or more water-miscible organic solvents.

[0095] According to the present invention, the term "water-miscible solvent" means a compound that is liquid at room temperature and miscible with water (in particular, having a miscibility with water greater than 50% by weight at 25 °C and atmospheric pressure).

[0096] The water-miscible organic solvents can be selected from linear or branched C1-C6 monohydric alcohols such as ethanol, isopropanol or tert-butanol; polyhydric alcohols such as glycerol, propylene glycol, pentylene glycol, caprylyl glycol, hexylene glycol (or 2-methyl-2,4-pentanediol) and polyethylene glycol; polyhydric alcohol ethers such as dipropylene glycol monomethyl ether; and mixtures thereof.

[0097] Relative to the total weight of the composition used according to the present invention, the concentration of these water-miscible organic solvents present in the composition can range from 0.01% to 20% by weight, preferably from 0.1% to 10% by weight and still more preferably from 1% to 5% by weight.

[0098] The composition used according to the present invention may further comprise at least one additional cosmetic active ingredient.

[0099] This can be, in particular, at least one active ingredient for caring for dry skin.

[0100] In the context of the present invention, the term "additional active ingredient" means a compound that inherently (i.e., without the need for external reagent intervention to activate it) has biological activity, and the biological activity can particularly be:

[0101] - Soothing or anti-irritant activity, and / or

[0102] - Moisturizing activity; and / or

[0103] - Emollient activity.

[0104] The additional active ingredients that can be used in the composition used according to the present invention can particularly be selected from humectants (such as urea and / or glycerol), soothing agents, anti-irritant agents, emollients (such as liquid petrolatum) and mixtures thereof in any proportion.

[0105] Relative to the total weight of the composition used according to the present invention, the additional active ingredients used in the composition can account for 0.0001% to 20% by weight, preferably 0.01% to 10% by weight and still more preferably 0.01% to 5% by weight.

[0106] Needless to say, those skilled in the art will carefully select such optional additional compound(s) and / or its / their amount(s) such that the advantageous properties of the composition used according to the present invention are not or are substantially not adversely affected by the envisaged addition.

[0107] The compositions used according to the invention can be in particular in any form of presentation commonly used in the cosmetic field and more particularly in any form of presentation generally suitable for the chosen mode of application.

[0108] Depending on the type of composition considered, the vehicle can have various properties.

[0109] The compositions according to the invention can be in any form of presentation conventionally used for topical application and more particularly in the following forms: aqueous or hydroalcoholic solutions, oil-in-water (O / W) emulsions, water-in-oil (W / O) emulsions or multiple (triple: W / O / W or O / W / O) emulsions, hydrogels, or dispersions of a fatty phase in an aqueous phase using spheres, which spheres can be ionic lipid vesicles and / or non-ionic lipid vesicles (liposomes, niosomes or oleosomes). These compositions are prepared according to usual methods.

[0110] The compositions used according to the invention are preferably suitable for topical application.

[0111] More particularly, with regard to compositions intended for topical application (i.e., application on the skin), they can be aqueous solutions, hydroalcoholic solutions or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, liquids of the milk type or emulsions of semi-liquid consistency, suspensions or emulsions of the cream type, hydrogels or anhydrous gels, microemulsions, microcapsules, microparticles, or dispersions of ionic vesicles and / or non-ionic vesicles.

[0112] The compositions used according to the invention can advantageously contain at least one liquid fatty substance.

[0113] The term "liquid fatty substance" denotes compounds with a melting point below about 30 - 35 °C, as opposed to solid fatty substances (such as waxes) with a melting point above about 50 °C.

[0114] As oils that can be used in the compositions of the invention, mention may be made, for example, of:

[0115] - hydrocarbon-based oils of animal origin;

[0116] - hydrocarbon-based oils of plant origin;

[0117] - 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 from 8 to 29 carbon atoms and R2 represents a branched or linear hydrocarbon-based chain containing from 3 to 30 carbon atoms;

[0118] - linear or branched hydrocarbons of mineral or synthetic origin;

[0119] - fatty alcohols containing from 8 to 26 carbon atoms;

[0120] - Hydrocarbon- and / or silicone-based fluorinated oils;

[0121] - Silicone oils;

[0122] - Their mixtures.

[0123] In the list of oils mentioned above, the term "hydrocarbon-based oil" means any oil mainly containing carbon atoms and hydrogen atoms and possibly ester groups, ether groups, fluorine groups, carboxylic acid groups, and / or alcohol groups.

[0124] 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.

[0125] These fatty substances can be selected in various ways by those skilled in the art to facilitate the preparation of a composition having the desired properties (such as in terms of consistency or texture).

[0126] According to a specific embodiment of the present invention, the composition according to the present invention is a water-in-oil (W / O) emulsion or an oil-in-water (O / W) emulsion. The proportion of the oil phase of the emulsion can range from 5% to 90% by weight, and preferably from 5% to 60% by weight, based on the total weight of the composition. The emulsion usually contains at least one emulsifier selected from amphoteric emulsifiers, anionic emulsifiers, cationic emulsifiers, and nonionic emulsifiers, 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.

[0127] The proportion of the emulsifier and the co-emulsifier present in the composition usually ranges from 0.3% to 30% by weight, and preferably from 0.5% to 20% by weight, based on the total weight of the composition.

[0128] For W / O emulsions, examples of emulsifiers that can be mentioned include polydimethylsiloxane copolyols and alkyl polydimethylsiloxane copolyols. Crosslinked elastomeric solid organopolysiloxanes containing at least one oxyalkylene group can also be used as W / O emulsion surfactants.

[0129] For O / W emulsions, examples of emulsifiers that can be mentioned are nonionic emulsifiers.

[0130] Preferably, the composition used according to the present invention is different from compositions having an essentially detergent use for the skin, hair, and / or mucous membranes, such as soaps, shampoos, and shower gels for washing and / or cleaning.

[0131] More particularly, the compositions 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.

[0132] Alternatively, the compositions used according to the invention may be in the form of a facial and / or body care product or a cosmetic product and may be packaged, for example, in a jar in the form of a cream or in a tube or a pump bottle or a dropper bottle in a fluid form.

[0133] Use and method

[0134] As mentioned above, according to one of its aspects, the invention relates to the cosmetic use, in particular non-therapeutic topical cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing a decrease in skin barrier function and / or enhancing skin barrier function, in particular for improving skin hydration, in an individual, particularly in an individual with dry skin.

[0135] The invention also relates to the cosmetic use, in particular topical cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing and / or treating atopic dermatitis or eczema.

[0136] The invention additionally relates to the cosmetic use, in particular non-therapeutic topical cosmetic use, of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for preventing and / or treating skin disorders of sensitive skin in an individual.

[0137] The invention additionally relates to a non-therapeutic cosmetic method for caring for keratin materials (in particular the skin), which comprises topically applying to these keratin materials a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium.

[0138] The skin particularly affected by such a method and thus the skin on which the composition used according to the invention is applied may preferably be fragile, weakened, dry, atopic and / or sensitive skin.

[0139] In particular, the composition used in the method according to the invention may comprise indole-3-acetamide in a content of at least 0.0001% by weight, preferably between 0.0001% by weight and 5% by weight, more preferably between 0.001% by weight and 1% by weight, still more preferably between 0.001% by weight and 0.01% by weight, relative to the total weight of the composition.

[0140] In addition, the composition used in the method according to the invention may comprise at least one adjuvant selected from the following: liquid fatty substances; organic solvents selected from ethanol, isopropanol, tert-butanol, propylene 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; opacifiers; stabilizers; silicones; defoamers; fragrances; preservatives; anionic surfactants, cationic surfactants, non-ionic surfactants, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing or acidifying agents; and mixtures thereof.

[0141] As indicated above, the composition used in the method of the invention is preferably suitable for topical application.

[0142] The cosmetic uses, methods and processes contemplated according to the invention are non-therapeutic.

[0143] The cosmetic uses and methods of the invention are preferably carried out by topical application of the composition according to the invention.

[0144] Topical application consists of externally applying these compositions to the skin by the usual techniques for using cosmetic compositions.

[0145] By way of illustration, the cosmetic use or method according to the invention can be carried out by topical (e.g. daily) application of at least one composition according to the invention, which can be formulated, for example, in the form of a cream, gel, serum, lotion, milk or make-up remover, preferably in the form of a lotion.

[0146] The application can be repeated, for example one to two times a day, for one or more days, and is generally applied for an extended period of at least 4 weeks or even 4 to 15 weeks, with one or more stopping periods where appropriate.

[0147] According to one embodiment, it is applied daily (once a day) and is generally applied for an extended period of at least 4 weeks or even 4 to 15 weeks, with one or more stopping periods where appropriate.

[0148] According to one embodiment, the cosmetic treatment method according to the invention may comprise a single application.

[0149] Throughout the specification (including the claims), unless otherwise specified, the terms "between... and..." and "ranging from... to..." shall be understood to mean including the upper and lower limits.

[0150] The following examples illustrate the invention without limiting its scope.

[0151] 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

[0152] Materials and methods

[0153] Stimulate RHE with a mixture mimicking atopic dermatitis

[0154] Reconstructed human epidermis is used, in which keratinocytes exhibit reduced FLG gene expression. This model is described in particular in "Knockdown of filaggrin in a three-dimensional reconstructed human epidermis impairs keratinocyte differentiation", Valérie Pendaries et al., December 2014; 134(12):2938 - 2946. The reconstructed epidermis is placed on an inert non-submerged polycarbonate surface of 0.5 cm 2 and cultured in cell culture medium (Episkin). In our study, filaggrin (FLG)-deficient keratinocytes are used to generate RHE. This is because FLG is greatly reduced in patients with atopic skin. This FLG-deficient line is generated using short hairpin RNA (shFLG) targeting FLG. The application of RHE-shFLG in the 3D RHE model has been disclosed (see Madiedo-Podvrsan et al., Sci Rep. March 18, 2021; 11(1):6217).

[0155] To generate a phenotype similar to that observed in patients with atopic dermatitis in terms of the chemokines produced and histology, it is necessary to stimulate the RHE with a mixture consisting of:

[0156] - 10 μg / ml of polyinosinic acid - polycytidylic acid (poly(I:C)) (label P9582, Sigma);

[0157] - 50 ng / ml of interleukin 4 (IL-4) (label BMS337, Invitrogen) and interleukin 13 (IL-13) (label 213-ILB, R&D Systems); and

[0158] - 10 ng / ml of TNF (tumor necrosis factor, label 210-TA / CF, R&D Systems).

[0159] While in contact with various molecules to be tested:

[0160] -IALD Label: 129445, Sigma: Stock solution in DMSO (10 mg / ml), diluted to a final concentration of 10 μg / ml in RHE (Episkin) medium;

[0161] -FICZ Label: SML1489, Sigma: Stock solution in DMSO (0.5 mg / ml), diluted to a final concentration of 100 ng / ml in RHE (Episkin) medium; and

[0162] -I3A Label: 286281, Sigma: Stock solution in DMSO (10 mg / ml), diluted to a final concentration of 10 μg / ml in RHE (Episkin) medium.

[0163] Measure chemokines in the culture medium supernatant and qPCR

[0164] The inflammatory mixture as defined above, along with the various molecules to be tested (I3A, IALD, and FICZ), was added simultaneously to the appropriate cell culture medium in which the RHE was placed. The culture plates were then incubated at 37 °C for 48 hours. The culture medium supernatant was then recovered, and various chemokines were measured (kits in Table 1 below). The RHE was ground using ceramic beads, and RNA was extracted according to the manufacturer's instructions (kits in the table below). The expression of target genes (Table 1 below) was measured by qPCR.

[0165] [Table 1]

[0166]

[0167] Measure the thickness of the stratum corneum and the non-viable layer

[0168] After culturing RHE for 48 hours under different stimulation conditions, the tissues were fixed in 4% paraformaldehyde (w / v) at pH 6.9 (Carlo Erba Reagents, France) and kept at 4 °C for 24 to 48 hours. The tissues were then dehydrated in a series of baths of 70% ethanol, 100% ethanol, and xylene, and then embedded in paraffin blocks. The blocks were cut into 5-μm sections using a microtome, and the sections were collected on SuperFrost Plus slides (ThermoFisher, USA). The sections were then subjected to deparaffinization (a series of baths of ethanol, xylene, and water). H&E staining was then performed in a first hematoxylin (ThermoFisher) bath for 2 minutes, followed by a 2-minute wash in water and finally a bath in 1% eosin (ThermoFisher) (staining), followed by a final wash. The sections were dehydrated again and mounted using Coverquick 2000Q (VWR). The slides were scanned using a Nanozoomer S60 (Hamamatsu, Japan), and the images were analyzed using NDP view software. The images were analyzed using the GeoLower algorithm and DHisTo-Skin software (Digital Histological Tools for Skin).

[0169] Statistical analysis

[0170] All experiments were performed with at least three biological replicates. Data were presented as mean ± SEM. GraphPad Prism (version 7.0; GraphPad Software, La Jolla, California). The data were analyzed using one-way ANOVA followed by Duncan's multiple comparison test. Results were considered statistically significant when p < 0.05.

[0171] Example 1: Study on the antipruritic and anti-inflammatory effects of indole-3-acetamide (I3A)

[0172] The antipruritic effects of indole-3-acetamide 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 on a 3D model reproducing atopic dermatitis.

[0173] Based on the literature, FICZ is our positive control for itch relief and anti-inflammation. It is also a strong inducer of the Cyp1a1 pathway, which can have detrimental effects in certain inflammatory conditions (see Deeba N Syed and Hasan Mukhtar, J Invest Dermatol. June 2015;135(6):1478-1481). This is because CYP1A1 activity can be harmful as it can generate reactive oxygen species in keratinocytes.

[0174] 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 made it possible to reduce skin inflammation in a dermatitis-like mouse model. IALD is alleged to inhibit the production of TSLP (thymic stromal lymphopoietin) in keratinocytes, and this phenomenon is alleged to depend on the aryl hydrocarbon receptor (AhR) pathway. TSLP is a key chemokine for keratinocyte communication as it can induce itch by directly activating certain types of neurons. TSLP production can cause itch (one of the factors that can deteriorate the quality of life of patients) and inflammatory damage (see S.R. Wilson et al., Cell. October 10, 2013, 155(2), 285-95).

[0175] The metabolite alone cannot induce TSLP or the various chemokines measured. Stimulation of the shFLG model with a mixture as mentioned above (poly(I:C), TNFa, IL-13, IL-4) resulted in TSLP production that was on average 10-fold greater than the control condition in the culture supernatant, and other chemokines measured that were 20 to 30-fold greater than the control condition in the culture supernatant.

[0176] The results in Table 2 below are expressed as percentage differences relative to the stimulated control in the RHE shFLG model.

[0177] [Table 2]

[0178]

[0179] Table 2

[0180] This Table 2 shows the percentage expression levels of TSLP and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) in the RHE medium relative to the stimulated control 48 hours after stimulation. p-values were calculated relative to the stimulated control.

[0181] Table 2 shows a significant reduction in TSLP production for IALD, I3A, and FICZ. This reduction for I3A is slightly greater than that for IALD or FICZ.

[0182] TRAIL is a protein involved in the apoptosis pathway and is produced in large amounts during stimulation used to reproduce the atopic dermatitis model (PMID: 18813321). A reduction in TRAIL production was observed with I3A and FICZ, but not in the case of IALD.

[0183] Example 2: Study on the effects of indole-3-acetamide on the harmful AhR pathway (mediated by CYP1A1) and on the beneficial anti- oxidant AhR pathway (mediated by NRF2, HMOX and NQO1)

[0184] qPCR was performed to examine the expression of certain target genes induced in the context of the AhR pathway after stimulation with a mixture that mimics certain phenotypes of atopic dermatitis as defined above. FICZ is known to be a strong inducer of the Cyp1a1 pathway, which is confirmed by the results shown in Table 3 below.

[0185] [Table 3]

[0186]

[0187] Table 3

[0188] In contrast, a weaker induction of Cyp1a1 by I3A was observed compared to the case of FICZ. Thus, by restricting the induction of Cyp1a1 and hence the xenobiotic pathway, I3A induces fewer or even no adverse effects compared to FICZ. The induction of the antioxidant pathway was monitored using the expression of the genes Nrf2, Hmox1, and Nqo1. Under atopic conditions, I3A slightly induces the antioxidant pathway.

[0189] To evaluate the overall effect of the metabolites under stimulating conditions, the morphology of the RHE was analyzed.

[0190] Example 3: I3A improves the quality of the epidermis

[0191] Treatment with the mixture that mimics atopic dermatitis as defined above induced epidermal tissue disassembly compared to the control (Ctr), which could be observed on H&E histological images (not shown). Contraction of the keratinocyte layer in the stratum corneum and basal layer was observed. Clusters of undifferentiated / dedifferentiated keratinocytes appeared in the RHE shFLG model.

[0192] It was observed that, unlike FICA, I3A was able to reduce the surface area and / or number of undifferentiated / dedifferentiated keratinocytes (data not shown).

[0193] The use of the software DHisTo-skin made it possible to measure the thickness of the stratum corneum. These values are reported in Table 4 and represent the average thickness (μm) of the stratum corneum of the RHE epidermis.

[0194] [Table 4]

[0195]

[0196] Table 4

[0197] Contraction of the stratum corneum (SC) was observed under the stimulation conditions relative to the unstimulated control. The ability of I3A to restore the control thickness of the SC was superior to that of FICZ.

[0198] In summary, all these results demonstrate that I3A has a better ability to restore the epidermal barrier function compared to FICZ.

Claims

1. Use of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for non-cosmetic therapeutic use, particularly topical non-therapeutic cosmetic use, in an individual, particularly in an individual with dry skin, for preventing a decrease in skin barrier function and / or enhancing skin barrier function.

2. A composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium, for its use in preventing and / or treating atopic dermatitis or eczema.

3. Use of a composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium for non-cosmetic therapeutic use, particularly topical non-therapeutic cosmetic use, in an individual for preventing and / or treating skin disorders of sensitive skin, said skin disorders being sensations of discomfort, particularly tightness, tingling, heat and / or itching.

4. A composition comprising indole-3-acetamide, its isomers or its salts in a physiologically acceptable medium, for its use in preventing and / or treating itching and / or inflammation of an individual's skin.

5. The composition for its use according to claim 4, wherein the itching and / or inflammation of the individual's skin is present in the following disorders: - Dermatological disorders selected from atopic dermatitis or eczema, psoriasis, prurigo nodularis, seborrheic dermatitis, acne, folliculitis and rosacea; or - Dermatological disorders after the skin has been exposed to pollutants and / or UV rays.

6. The use according to claim 1 or 3, or the composition for its use according to any one of claims 2, 4 and 5, wherein the composition is applied to fragile, weakened, dry, atopic and / or sensitive skin.

7. The use according to claim 1 or 3, or the composition for its use according to any one of claims 2 and 4 to 6, wherein the composition comprises indole-3-acetamide, its isomers or its salts in a content of at least 0.0001% by weight, preferably between 0.0001% and 5% by weight, more preferably between 0.001% and 1% by weight, still more preferably between 0.001% and 0.01% by weight, based on the total weight of the composition.

8. Use according to claim 1 or 3, or composition for use according to claim 2 and any one of claims 4 to 7, wherein the composition further comprises at least one adjuvant selected from the following: liquid fatty substances, pasty fatty substances 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, caprylyl 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; softeners; humectants; emollients; opacifiers; stabilizers; silicones; antifoaming agents; fragrances; preservatives; anionic surfactants, cationic surfactants, non-ionic surfactants, zwitterionic or amphoteric surfactants; fillers; polymers; propellants; alkalizing agents or acidifying agents; and mixtures thereof.

9. Use according to claim 1 or 3, or composition for use according to claim 2 and any one of claims 4 to 8, the composition being suitable for topical application.

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