Cosmetic use of at least urolithin C on sensitive skin

Abstract

Cosmetic use of at least urolithin C on sensitive skin. The present invention relates to the cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates, such as hydrates, to prevent and / or treat a skin reaction on sensitive skin. Figure for the abstract: none

Description

Title of the invention: Cosmetic use of at least urolithin C on sensitive skin

[0001] The present invention relates to the cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates for preventing and / or treating a cutaneous manifestation in sensitive skin.

[0002] The skin has the ability to respond to external physicochemical and mechanical stimuli, generating alert sensations such as tingling and itching. These stimuli are of varied origin.

[0003] In particular, subjects with sensitive skin are more sensitive to such stimuli. Sensitive skin is defined as non-pathological skin, which may present undesirable cutaneous manifestations.

[0004] Generally speaking, undesirable skin manifestations can manifest themselves in two ways, namely sensations of discomfort felt at the skin level and / or the appearance of visible skin signs.

[0005] As for feelings of discomfort, these can typically include itching, heating, tingling and / or tightness. Examples of visible skin signs include redness.

[0006] These skin manifestations are more frequent in the most exposed areas of the body, namely the hands, feet, face and scalp.

[0007] This skin reactivity is classically expressed by the manifestation of signs of discomfort in response to the subject coming into contact with a triggering element which can have various origins.

[0008] These skin reactions can occur in particular in areas subject to certain daily or frequently repeated hygiene procedures such as shaving, hair removal, cleansing with toiletries or household products, the application of adhesives (dressings, patches, fixing of prostheses) or in the case of sporting, professional or simply lifestyle-related actions and the use of clothing, tools or equipment generating localized friction when eating certain foods. They can also be amplified by temperature variations, wind and psychological stress.

[0009] It is also known that the risk of these skin reactions occurring is increased in the case of sensitive skin.

[0010] Thus, the appearance of signs of discomfort, which appear in the minutes following the subject's contact with the triggering element, is one of the characteristics essential characteristics of sensitive skin. These are mainly dysesthetic sensations. Dysesthetic sensations are understood to be more or less painful sensations felt in an area of ​​skin such as tingling, pins and needles, itching, heating, discomfort, tightness, etc. These subjective signs most often exist in the absence of visible clinical signs such as redness or scaling.

[0011] The reactivity of sensitive skin is not a process leading to an inflammatory response.

[0012] It is therefore completely distinct from skin showing inflammatory reactions such as dermatosis, eczema and / or ichthyosis, and for which a certain number of treatments have already been proposed.

[0013] For obvious reasons, it would be advantageous to have compositions capable of preventing and / or treating these undesirable skin manifestations.

[0014] The present invention aims precisely to meet this need.

[0015] The present invention thus aims at the cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates, to prevent and / or treat a cutaneous manifestation in sensitive skin.

[0016] Urolithin C, or 3,8,9-trihydroxy-6H-benzo[c]chromen-6-one, is the compound of the following general formula (I):

[0017] [Chem.l] (I).

[0018] Urolithin C is a microbial metabolite produced by enzymatic catabolism in commensal bacteria from ellagic acid and ellagitannins with low bioavailability. Ellagic acid and ellagitannins are derived from edible plants such as berries, tropical fruits like pomegranate and medicinal plants like Camellia sinensis.

[0019] For example, we can cite urolithin C marketed by the company Sigma-Aldrich under the commercial reference SML3047-50mg.

[0020] The term “salt” of a urolithin C according to the invention means a salt formed by an inorganic or organic base.

[0021] Examples of basic salts include alkali metal hydroxides such as sodium, potassium and lithium; alkaline earth metal hydroxides such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia and organic amines such as unsubstituted or hydroxy-substituted mono-, di- or tri-alkylamines; dicyclohexylamines; tributyl amines; pyridine; N-methyl-N-ethylamine; diethylamine; triethylamine; mono-, bis- or tris-(2-hydroxy-alkylamines) such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, tris-(hydroxymethyl)methylamine, N,N-di-alkyl-N-(hydroxyalkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine and lysine.

[0022] A salt of urolithin C according to the invention is preferably a basic salt, and in particular a sodium or potassium salt.

[0023] For the purposes of the invention, the expression “cutaneous manifestation” covers sensations of discomfort, in a subject in particular with sensitive skin, as well as temporary visible and unsightly cutaneous signs likely to affect this same subject. Thus, preferably, the cutaneous manifestation is a sensation of discomfort.

[0024] The subject (or person) is a subject with sensitive skin, preferably a human subject.

[0025] By "the skin" is meant the whole of the skin of the body, and preferably the skin of the face, scalp, décolleté, neck, arms and forearms, or even more preferably, the skin of the face (in particular the forehead, nose, cheeks, chin), décolleté and neck.

[0026] As previously stated, the sensations of discomfort may be itching, heating, tingling and / or tightness.

[0027] These undesirable manifestations particularly concern people with so-called sensitive skin, who have a lowered reactivity threshold; this skin will therefore present these sensations and clinical signs much more quickly and frequently than other skin types.

[0028] Preferably, the cutaneous manifestation at the level of sensitive skin according to the invention results in the manifestation of one or more visible cutaneous signs such as redness and scaling.

[0029] According to another of its aspects, the present invention relates to the cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates, as a soothing agent.

[0030] By "soothing agent" is meant an agent capable of reducing a cutaneous manifestation in sensitive skin, in particular capable of reducing redness and / or a feeling of discomfort.

[0031] According to another of its aspects, it aims at the cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates. such as moisturizers to prevent and / or treat the manifestations of dysesthetic sensations in sensitive skin.

[0032] The invention therefore aims in particular to prevent and / or reduce sensations of skin discomfort, such as for example tingling, prickling, itching, heating, discomfort and / or tightness, in particular in people with sensitive skin.

[0033] Preferably, urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as the hydrates according to the invention is administered topically.

[0034] According to another of its aspects, the invention relates to a cosmetic treatment method comprising the topical application to sensitive skin of a subject of a cosmetic composition comprising at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates.

[0035] Such a process is cosmetic, therefore non-therapeutic. The same applies to the various uses covered by the present application.

[0036] For the purposes of the present invention, “prevent” means reducing the risk of manifestation of a phenomenon.

[0037] For the purposes of the present invention, the term “treat” means to compensate for a physiological dysfunction and more generally to reduce, or even eliminate, an undesirable disorder, the manifestation of which is in particular a consequence of this dysfunction.

[0038] For obvious reasons, the absence of visible signs makes it difficult to diagnose sensitive skin. Most often, this diagnosis is based on questioning the subject.

[0039] Consequently, the development of "sensitive skin" products required tools for evaluating the sensory reaction of the skin. The first tools were inspired from their design by the essential characteristic of sensitive skin, namely the presence of signs of discomfort induced by topical application. Thus, the lactic acid "stinging test" was the first test proposed. It is carried out by recording the tingling sensations reported by a volunteer after application of a 10% lactic acid solution to the wings of the nose. Subjects reporting moderate or severe tingling sensations are called "stingers" and considered to have sensitive skin. Because of this skin sensitivity to topical product application, these subjects are then selected to test so-called sensitive skin products.

[0040] Other tools, particularly in vitro, exist for identifying compounds of interest for treating sensitive skin. Indeed, it has been demonstrated in the literature that this sensitive skin condition can be associated with an exacerbated response of the TRPV1 (transient receptor potential vanilloid 1) calcium channel by its activation indirect. This indirect activation can result in particular from the binding of histamine to the H1R and H4R receptors and / or from the binding of a protease such as SLIGRL to the PAR2 receptor (Protease-Activated Receptor-2), both belonging to the GPCR family of transmembrane receptors, and from their activation. Once this receptor(s) is / are activated, there follows an activation of the PKC / PLC pathway, which itself will activate certain calcium channels, including TRPV1 (Gouin, O., et al., TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization. Protein Cell, 2017. 8(9): p. 644-661). The activation of these channels results in the genesis of an intracellular calcium flux, the release of neurotransmitters and the activation of a signaling cascade at the origin of the sensation of discomfort.Thus, reducing this signaling cascade by limiting intracellular calcium fluxes generated by indirect activation of these channels on the surface of keratinocytes via an action on H1R and H4R receptors and / or the PAR2 receptor, constitutes a particularly useful tool for the identification of compounds of interest for treating sensitive skin.

[0041] For the purposes of the present invention, the expression “sensitive skin” covers reactive skin and intolerant skin.

[0042] Intolerant skin is skin that reacts at least with sensations of heating, tightness, tingling and / or redness, to various factors such as the application of cosmetic or dermatological products or soap. In general, these signs are associated with hyper-seborrheic skin.

[0043] Reactive skin is skin that reacts with itching or tingling to various factors such as the environment, emotions, food, wind, friction, razors, hard water with a high concentration of limestone, temperature variations, humidity or wool.

[0044] It is understood that these sensations can also be associated with the manifestation of cutaneous signs. Thus, generally speaking, this type of skin can be associated with dry skin or skin that presents redness. Dry skin is essentially manifested by a feeling of tightness and / or tension. It is also rough to the touch and appears covered in scales. When the skin is slightly dry, these scales are abundant but barely visible to the naked eye. They are less and less numerous but increasingly visible to the naked eye when this disorder worsens.

[0045] In the context of the present invention, the sensitive skins considered do not show any inflammatory character.

[0046] Urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates may be formulated in a composition at a rate of at least 0.00001% by weight, in particular at a rate of 0.0001 to 20% by weight and more per particularly at a rate of 0.001 to 2% by weight relative to the total weight of the composition.

[0047] The compositions according to the invention may be presented in all the galenic forms normally available for the chosen method of administration. The support may be of a diverse nature depending on the type of composition considered.

[0048] Preferably, urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as the hydrates according to the invention is administered topically, that is to say to the surface of the skin. As topical compositions, mention may be made of aqueous, hydroalcoholic or oily solutions, dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, suspensions or emulsions of the cream, aqueous or anhydrous gel type, microemulsions, microcapsules, microparticles or vesicular dispersions of the ionic and / or non-ionic type. These compositions are prepared according to the usual methods.

[0049] These compositions may in particular constitute cleansing, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, make-up remover creams, foundation creams, sun creams), make-up products such as fluid foundations, make-up remover milks, protective or care body milks, after-sun milks, lotions, gels or mousses for skin care, such as cleansing or disinfecting lotions, sun lotions, artificial tanning lotions, bath compositions, deodorant compositions containing a bactericidal agent, after-shave gels or lotions, hair removal creams or compositions against insect bites.

[0050] The compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.

[0051] They can also be used for the scalp in the form of solutions, creams, gels, emulsions, mousses or even in the form of aerosol compositions also containing a pressurized propellant.

[0052] The compositions according to the invention may comprise one or more adjuvants usual in the cosmetic field, such as organic solvents, hydrophilic or lipophilic gelling agents, preservatives, fatty substances such as oils, emulsifiers, antioxidants, solvents, perfumes, fillers, sunscreens, odor absorbers, coloring materials and mixtures thereof.

[0053] The quantities of these different adjuvants are those conventionally used in the fields considered, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase or into the aqueous phase. These adjuvants, as well as their concentrations, must be such that they do not do not harm the beneficial properties of urolithin C and / or any of its salts and / or any of its isomers and / or any of its solvates such as hydrates.

[0054] As organic solvents which can be used in the composition of the invention, mention may be made of organic solvents miscible in water.

[0055] By "water-miscible solvent" according to the present invention is meant a compound which is liquid at room temperature and miscible with water, in particular having a miscibility in water greater than 50% by weight at 25°C and atmospheric pressure.

[0056] The water-miscible organic solvents may be selected from lower monoalcohols having 1 to 5 carbon atoms such as ethanol and isopropanol, glycols having 2 to 8 carbon atoms such as ethylene glycol, hexylene glycol, propylene glycol, 1,3-butylene glycol, pentylene glycol, dipropylene glycol, and glycerin.

[0057] As oils which can be used in the composition of the invention, we can cite for example:

[0058] - hydrocarbon oils of animal origin;

[0059] - hydrocarbon oils of vegetable origin;

[0060] - synthetic esters and ethers, in particular of fatty acids, such as oils of formulas R1COOR2 and R1OR2 in which RI represents the residue of a fatty acid containing from 8 to 29 carbon atoms, and R2 represents a hydrocarbon chain, branched or not, containing from 3 to 30 carbon atoms;

[0061] - linear or branched hydrocarbons, of mineral or synthetic origin;

[0062] - fatty alcohols having from 8 to 26 carbon atoms;

[0063] - partially hydrocarbon and / or silicone fluorinated oils;

[0064] - silicone oils;

[0065] - their mixtures.

[0066] In the list of oils cited above, the term hydrocarbon oil means any oil comprising mainly carbon and hydrogen atoms, and possibly ester, ether, fluorine, carboxylic acid and / or alcohol groups.

[0067] Other fatty substances which may be present in the oily phase are, for example, fatty acids containing 8 to 30 carbon atoms; waxes; silicone resins; and silicone elastomers.

[0068] These fatty substances can be chosen in a variety of ways by those skilled in the art in order to prepare a composition having the desired properties, for example consistency or texture.

[0069] According to a particular embodiment of the invention, the composition used in the context of the invention is anhydrous.

[0070] By "anhydrous" is meant a composition comprising less than 5% by weight of water relative to the total weight of the composition, preferably less than 3% by weight, even better less than 1% by weight relative to the total weight of the composition, or even completely free of water (0%).

[0071] According to a particular embodiment of the invention, the composition used in the context of the invention is a water-in-oil (W / O) or oil-in-water (O / W) emulsion. The proportion of the oily phase of the emulsion can range from 5 to 90% by weight, and preferably from 5 to 60% by weight relative to the total weight of the composition.

[0072] The emulsions generally contain at least one emulsifier chosen from amphoteric, anionic, cationic or non-ionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are chosen appropriately depending on the emulsion to be obtained (W / O or O / W). The emulsifier and the co-emulsifier are generally present in the composition, in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

[0073] As emulsifiers and co-emulsifiers which can be used in the invention, mention may be made, for example, of O / W emulsifiers, in particular non-ionic emulsifiers such as fatty acid and polyethylene glycol esters, fatty acid and glycerin esters, as well as W / O emulsifiers such as dimethicone copolyols, alkyl-dimethicone copolyols, crosslinked solid elastomeric organopolysiloxanes comprising at least one oxyalkylenated group.

[0074] As hydrophilic gelling agents, mention may be made in particular of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides, natural gums and clays; as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes.

[0075] As fillers which may be used in the composition of the invention, mention may be made, in addition to pigments, of silica powder; talc; starch; polyamide particles; polyethylene powders; microspheres based on acrylic copolymers; expanded powders such as hollow microspheres; silicone resin microbeads; and mixtures thereof. These fillers may be present in amounts ranging from 0.1 to 20% by weight and preferably from 1 to 10% by weight relative to the total weight of the composition or preparation according to the invention.

[0076] The invention also relates to a cosmetic treatment method comprising the topical application to sensitive skin of a subject of a cosmetic composition comprising at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates.

[0077] The cosmetic treatment method of the invention can be implemented in particular by administering cosmetic and / or dermatological compositions such as as defined above, according to the usual technique of use of these compositions. For example: applications of creams, gels, serums, lotions, cleansing milks or after-sun compositions on the skin or on the dry scalp, application of a hair lotion or shampoos on the wet scalp, as regards topical application.

[0078] The cosmetic treatment method according to the invention can thus be implemented by topical administration, daily for example, of urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates.

[0079] The method according to the invention may comprise a single administration. According to another embodiment, the administration is repeated for example 2 to 3 times daily over one day or more, and generally over a prolonged period of at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of interruption.

[0080] The invention is now illustrated by the following non-limiting examples. Example 1: Soothing effect of urolithin C

[0081] Principle of the method for measuring the soothing effect

[0082] Monitoring the activation of certain calcium channel receptors (whether direct or indirect) is made possible by measuring the calcium influx into the cytoplasm of skin cells.

[0083] A soothing effect is obtained if an inhibition of intracellular calcium flux is observed.

[0084] In this case, the calcium channel receptors studied are those of the histamine pathway, i.e. H1R and H4R, and those of the PAR2 pathway. H1 (H1R) and H4 (H4R) receptors (histamine pathway)

[0085] Four histamine receptors have been described today, including the H1 and H4 receptors expressed by keratinocytes. These are transmembrane receptors belonging to the GPCR family and coupled to a calcium channel; they are directly activated by endogenous histamine. At the keratinocyte level, the binding of histamine to these specific receptors activates the PLC and PIP2 pathway, and these mechanisms result in vivo in itching sensations that can sometimes be accompanied by tingling and / or redness. In the case of sensitive skin and with a soothing aim, neutralizing this pathway could result in mainly reducing itching. PAR2 receiver (PAR2 channel)

[0086] PAR2 (Protease-Activated Receptor-2) is also a transmembrane receptor of the GPCR family widely expressed in the skin and more particularly by keratinocytes. Its activation by serine protease-type proteases (eg kallikrein family) leads to the opening of TRP (VI and V3) and the genesis of a calcium influx. Also activated by itching (mucosaine), it is involved in itching reactions. Inhibition of PAR2 could clinically reduce itching, tingling, but also contribute to a better skin barrier function in sensitive skin.

[0087] Cell culture protocol for preparing intracellular calcium flux measurement 1. Keratinocyte cells of the corneal epidermis

[0088] The cells were isolated from the epidermal tissue according to the Mat'Tek protocol described in 2006 (Development of a method for assessing micronucleus induction in a 3D human skin model (Epiderm), Rodger D. Curren et al, Volume 607, Issue 2, 5 September 2006, Pages 192-204). The HCE cells (Human Corneal Epithelial cells) are seeded in sterile black 96-well Advanced TC plates (Greiner) at a cell density of 20,000 cells / well / 0.2ml for carrying out the test 48 hours after seeding, and at 10,000 cells / well / 0.2ml for carrying out the test 72 hours after seeding. 1. Measurement of intracellular ICa^l & Expression of results

[0089] The molecules tested are Turolithine A from Sigma Aldrich (SML-1791), and Turolithine C. a. Solubility of the molecules to be evaluated

[0090] The solubility of each molecule is primarily tested in HBSS buffer (Gibco-Invitrogen) supplemented with 20mM HEPES (Gibco-Invitrogen) and adjusted to pH 7.4. For non-water-soluble molecules, DMSO (Sigma-Aldrich) is used first, then ethanol (Prolabo). For a molecule soluble in DMSO, the final concentration of DMSO administered to the keratinocytes is 2%, whereas for a molecule soluble in ethanol, the final concentration of ethanol must not exceed 1%. Each molecule is tested in the agonist version of the test to ensure non-activation of the receptors by the molecule before proceeding with the evaluation of its soothing properties. The maximum dose tested is determined according to the non-activation of the receptors but also the solubility of the molecules and / or their cytotoxicity on the cells. At least three concentrations are tested per molecule and are carried out by successive dilutions.

[0091] For soluble, non-agonistic and non-cytotoxic molecules, the maximum dose tested on HCE keratinocyte cells is 1 mg / ml. a. Preparation of the fluorescent calcium probe

[0092] Calcium concentration is measured using the fluorescent probe fura-2AM Ester (Molecular Probes) at 5 pM. The probe is previously solubilized in DMSO. An equal volume of 10% Pluronic F-127 surfactant (Molecular Probes) is added for better solubilization of the probe. a. Cell treatment

[0093] After 48 or 72 hours of seeding, the cells are washed twice in HBSS buffer and then incubated for 30 minutes at 37°C in the presence of the previously prepared calcium probe. 2 washes in HBSS buffer are carried out before then treating the cells for 30 minutes at room temperature and away from light with the solutions of molecules to be evaluated at the determined concentrations. a. Preparation of the reference agonist solution

[0094] In parallel, the solutions of reference agonists of the H1R and H4R pathway, and of the PAR2 pathway, are prepared extemporaneously then deposited in a 96-well plate allowing automatic injection into the cells in order to carry out real-time monitoring of the calcium influx.

[0095] The reference agonist of the H1R and H4R pathway is histamine (Sigma-Aldrich), soluble in HBSS buffer, used at 4.5 mM.

[0096] The reference agonist of the PAR2 pathway is SLIGRL (R&D Systems), soluble in HBSS buffer, used at 75 pM. a. Real-time monitoring of calcium influx

[0097] Fluorescence is measured on a FlexStation 3 microplate reader (Molecular Devices) at a double excitation wavelength: 340 nm (bound Ca2+), 380 nm (free Ca2+) and at an emission wavelength of 510 nm. Measurements are carried out for 30 seconds - basal level - and for 3 minutes after automatic injection by the Flexstation of the reference agonists (agonists or HBSS or DMSO or ethanol buffer, volume of 50 μl / well). 7 controls are carried out in parallel: HBSS control; DMSO and ethanol control if necessary, and Activation control for each of the 2 channels. Each condition is replicated on at least 2 independent tests with 6 wells per condition and per test. Results

[0098] The results are expressed as a ratio of the fluorescence intensity of 2 wavelengths (340nm / 380nm) and used as a % variation of the ratio over a kinetics of 10 to 300 seconds.

[0099] The response peak obtained with the molecule to be evaluated in combination with the corresponding agonist is compared with that of the agonist alone, and the percentage of inhibition is then determined. 1. Effect of rurolithin C greater than rurolithin A on histamine receptors (H1R and H4R)

[0100] For each urolithin, a capacity to reduce the calcium flux induced by the agonist of the H1R and H4R histamine receptors is observed at the concentrations tested compared to the 0 pM control (Table 1). The percentages of inhibition are then observed. of normalized calcium flux relative to the 0 pM condition (Table 2).

[0101] Urolithin C has a percentage inhibition of calcium flux after activation of H1R and H4R which is 79% at 4 pM, whereas urolithin A shows an inhibition which amounts to only 65% ​​at 4.4 pM and 80% at 22 pM (Table 2).

[0102] Urolithin C has H1R and H4R inhibition capacities that are 5 times greater than urolithin A. Urolithin C therefore has strong potential to reduce itching in sensitive skin.

[0103] Percentage change in calcium flux in response to histamine and after addition of different concentrations of urolithin A and urolithin C

[0104] The percentage variation of the calcium flux of Table 1 is calculated as follows:

[0105] % Variation in calcium flux = ((fluorescence intensity at 340nm for x second(s) / fluorescence intensity at 380nm for x second(s)) - (fluorescence intensity at 340nm tO / fluorescence intensity at 380nm t0)) / (fluorescence intensity at 340nm tO / fluorescence intensity at 380nm tO).

[0106] [Tables 1] Histamine R pg / ml pM Mean percentage variation in calcium flux (%) Urolithin A (outside the invention) 0 0 101 1 4.4 38 5 22 20 Urolithin C (according to the invention) 0 0 124.7 0.5 2 39.0 5 4 25.7

[0107] Percentage inhibition of calcium flux in response to histamine and after addition of different concentrations of urolithin A and urolithin C

[0108] The percentage inhibition of Table 2 is calculated as follows:

[0109] % inhibition = 100 - ((% Variation of calcium flux compound “X” x 100) / % Variation in calcium flux of the H1R and H4R receptor agonist, histamine)

[0110] [T ables 2] Histamine R pg / ml pM Mean percentage inhibition of calcium flux variation (%) Urolithin A (not in the invention) 1 4.4 65.1 5 22 80.6 Urolithin C (in the invention) 0.5 2 68.7 5 4 79.4 1. Effect of urolithins on PAR2

[0111] For each of urolithins A and C, an inhibitory capacity of the calcium flux induced by the PAR2 agonist is observed at the concentrations tested compared to the 0 pM control (Table 4).

[0112] Urolithin C exhibits a higher effect at 4 pM (36.7% inhibition) compared to urolithin A at equivalent molar concentration (30.2% inhibition).

[0113] Urolithin C, by inhibiting PAR2 activation, is therefore a compound that can reduce itching and tingling, but also contribute to a better barrier function of the skin in sensitive skin.

[0114] Percentage change in calcium flux in response to SLIGRL (PAR2 agonist) and after addition of different concentrations of urolithin A and urolithin C

[0115] The percentage variation of the calcium flux of Table 3 is calculated as follows:

[0116] % Variation in calcium flux = ((fluorescence intensity at 340nm for x second(s) / fluorescence intensity at 380nm for x second(s)) - (fluorescence intensity at 340nm tO / fluorescence intensity at 380nm t0)) / (fluorescence intensity at 340nm tO / fluorescence intensity at 380nm tO).

[0117] [Tables3] PAR2 pg / ml pM Mean percentage variation in calcium flux (%) Urolithin A (outside the invention) 0 0 165.3 1 4.4 113.7 Urolithin C (according to the invention) 0 0 178.7 5 4 113.7

[0118] Percentage inhibition of calcium flux in response to SL1GRL (PAR2 agonist) and after adding different concentrations of urolithin A and urolithin C

[0119] The percentage inhibition of Table 4 is calculated as follows:

[0120] % inhibition = 100 - ((% Variation of calcium flux compound “X” x 100) / % Variation in calcium flux of the PAR2 receptor agonist, SLIGRL protease)

[0121] [Tables4] PAR2 pg / ml pM Mean percentage inhibition of calcium flux variation (%) Urolithin A (not in the invention) 1 4.4 30.2 Urolithin C (in the invention) 5 4 36.7 Conclusion

[0122] Urolithin C has the ability to reduce itching and tingling by targeting the 2 main pathways through the initial activation of PAR2 and H1R and H4R. It appears that urolithin C has a greater inhibitory effect than urolithin A on H1R and H4R, suggesting a stronger antagonistic effect of urolithin C on H1R and H4R than that observed with urolithin A. On PAR2, urolithin C has, at a lower molar concentration, a greater effect than urolithin A, suggesting a stronger antagonistic effect of urolithin C on PAR2 (at a lower molar concentration) than that observed with urolithin A.

[0123] Urolithin C has a soothing effect and could be used on the following skin conditions: tingling, tightness, discomfort, itching, redness and / or feeling of heat of the skin (including the scalp).

Claims

Claims

1. Cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates for preventing and / or treating a cutaneous manifestation in sensitive skin.

2. Use according to claim 1, wherein the cutaneous manifestation is a feeling of discomfort.

3. Use according to claim 2, wherein the discomfort sensation is itching, warming, tingling, and / or pulling.

4. Use according to any one of the preceding claims, in which the cutaneous manifestation results in the manifestation of one or more visible cutaneous signs.

5. Use according to any one of the preceding claims, in which urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates, is intended to prevent and / or treat the manifestations of dysaesthetic sensations in sensitive skin.

6. Cosmetic use of at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates as a soothing agent.

7. Use according to any one of the preceding claims, wherein urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates is administered topically.

8. Use according to any one of the preceding claims in which urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates is formulated in a composition in a proportion of at least 0.00001% by weight, in particular in a proportion of 0.0001 to 20% by weight and more particularly in a proportion of 0.001 to 2% by weight relative to the total weight of the composition.

9. Use according to any one of the preceding claims in which urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates is formulated in a composition chosen from aqueous, hydroalcoholic or oily solutions, dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, suspensions or emulsions of the cream, aqueous or anhydrous gel type, microemulsions, microcapsules, microparticles and vesicular dispersions of the ionic and / or non-ionic type.

10. Cosmetic treatment method comprising the topical application to sensitive skin of a subject of a cosmetic composition comprising at least urolithin C and / or one of its salts and / or one of its isomers and / or one of its solvates such as hydrates.