FR3030250A1 - AQUEOUS COMPOSITION COMPRISING A 4- (HETEROCYCLOALKYL) -BENZENE-1,3-DIOL COMPOUND AND A HYDROTROPE - Google Patents

Abstract

The invention relates to a composition comprising; at least one 4- (heterocycloalkyl) -benzene-1,3-diol compound; at least one nonionic hydrotrope; - some water. Application to the care, makeup and / or cleaning of keratin materials, especially the skin.

Description

An aqueous composition comprising a 4- (heterocycloalkyl) -benzene-1,3-diol compound and a hydrotrope The subject of the present invention is a composition, preferably a cosmetic composition, comprising a 4- (heterocycloalkyl) -benzene-1,3-diol compound , and at least one nonionic hydrotrope. The 4- (heterocycloalkyl) -benzene-1,3-diol derivatives are compounds used for the treatment of cutaneous signs of aging and more particularly as a depigmenting agent for keratin materials. However, these compounds, which are in solid form at room temperature and have a high melting point (> 210 ° C.), are difficult to solubilize. They are in particular poorly soluble in water and glycerin. However, it is necessary for this compound to be formulated in a solubilized form, and in particular at a high content, such as greater than or equal to 0.50% by weight, in order to make the best use of its activity and it is also preferable that its solubilization is maintained over time to avoid any recrystallization phenomenon during the storage of compositions comprising such a compound. In fact the solubilized forms lead to a better bioavailability in the skin than crystallized forms whose crystal size is poorly controlled. For the purposes of this application, the term "bioavailability" refers to the molecular penetration of the active agent into the living layers of the skin and in particular of the epidermis. It will be sought that the penetrated concentration is as high as possible, so as to increase the rate of asset reaching the living layers of the skin. By "solubilized form" is meant a dispersion of the derivatives according to the invention in a liquid, in the free molecular state, in particular in uncomplexed form. No crystallization of 4- (heterocycloalkyl) -benzene-1,3-diol derivatives is visible in the open eye or in cross-polarized light microscopy. Compositions containing a high level of glycols provide a sticky and greasy feel of the skin. It is therefore sought to increase the solubility of these active ingredients but using limited quantities of solvents which reduce the cosmetic properties of the compositions. The object of the present invention is precisely to propose a new galenic formulation of the 4- (heterocycloalkyl) -benzene-1,3-diol compounds making it possible to overcome the abovementioned disadvantages, and thus to incorporate these compounds in a solubilized and durable form. over time, these compounds being in particular present at a high content (such as a content greater than or equal to 0.20% by weight relative to the total weight of the composition). This new galenic formulation of the compounds 4- (heterocycloalkyl) -benzene-1,3-diol makes it possible in particular to improve the efficacy of the active ingredient for the treatment of keratin materials such as the skin. The compositions according to the invention make it possible to use lower amounts of glycols. The inventors have, in fact, unexpectedly discovered that the combination of at least one 4- (heterocycloalkyl) -benzene-1,3-diol compound with at least one nonionic hydrotrope makes it possible to improve the solubility of these compounds. while avoiding their recrystallization, especially after storage for at least 1 week, or even 1 month, 2 months or more at room temperature (25 ° C) and / or at 4 ° C and / or 45 ° C. More specifically, the subject of the invention is a composition, in particular a cosmetic composition, comprising a composition comprising; at least one 4- (heterocycloalkyl) -benzene-1,3-diol compound; at least one nonionic hydrotrope; water, as defined below.

The 4- (heterocycloalkyl) benzene-1,3-diol compounds according to the invention have the following general formula (I): ## STR3 ## in which R 1, R 2, R 3 and R 4, which may be identical or different, represent: a hydrogen, a C1-C4 alkyl radical, a hydroxymethyl, a hydroxyethyl, a C1-C4 alkoxy carbonyl, a C1-C4 alkoxy, a hydroxyl or R2 R1 and R2 are interconnected and form a ring. carbon containing 5 or 6 carbon atoms with the carbon atom to which they are bonded and R3 and R4, identical or different, represent: - a hydrogen - a C1-C4 alkyl radical OR R1 and R4 are connected to each other and form a chain - (CH2) 2- or - (CH2) 3- and R2 and R3, identical or different, represent: - a hydrogen - a C1-C4 alkyl radical represents an oxygen atom, or a sulfur atom Y represents a hydrogen, a chlorine atom or a fluorine atom m can take the values 1 or 2 and n can take the values 0 or 1 and when n = 0, then m = 1 o u 2, and when n = 1, then m = 1. as well as the salts of the compounds of general formula (I), and their isomeric and enantiomeric forms.

Among the salts of the compounds of general formula (I), there may be mentioned preferably salts with an organic base or with an inorganic base. Suitable inorganic bases are, for example, potassium hydroxide, sodium hydroxide or calcium hydroxide.

Suitable organic bases are, for example, morpholine, piperazine, arginine, lysine. The compounds of general formula (I) may also exist in the form of hydrates or solvates.

Suitable solvents for forming solvates are, for example, alcohols such as ethanol or iso-propanol. According to the present invention, C 1 -C 4 alkyl denotes a saturated hydrocarbon chain, linear or branched, comprising from 1 to 4 carbon atoms.

According to the present invention, C 1 -C 4 alkoxycarbonyl denotes a carboxy radical substituted by an alkyl radical comprising from 1 to 4 carbon atoms. According to the present invention, C 1 -C 4 alkoxy denotes an oxygen atom substituted with a linear or branched saturated hydrocarbon-based chain containing from 1 to 4 carbon atoms.

According to the present invention, the isomers are the cis and trans forms relating to the substituents on the heterocycloalkyl at the 4-position of the benzene-1,3-diol.

According to the present invention, the compounds of general formula (1) which are particularly preferred are those for which: R 1 represents a hydrogen, a C 1-4 alkyl radical or a hydroxymethyl radical, R 2 represents a hydrogen, R 3 represents a hydrogen, - R4 represents a hydrogen, - X represents an oxygen atom - Y represents a hydrogen or a fluorine atom -m = 1 and n = 1, as well as the salts of these compounds of general formula (1), and their forms isomers and enantiomers. Among the compounds of formula (1) within the scope of the present invention, there may be mentioned in particular: 1: 4- (tetrahydro-pyran-4-yl) -benzene-1,3-diol 2: 4- ( tetrahydro-thiopyran-4-yl) -benzene-1,3-diol 3: 4- (cis-2,6-dimethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 4: trans-4 (2-methyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 5: cis-4- (2-methyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 6 trans-4- (2-Ethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 7: cis-4- (2-ethyl-tetrahydro-pyran-4-yl) -benzene-1, 3-Diol 8: trans-4- (2-Hydroxymethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 9: 4- (2,2,6,6-tetramethyl-tetrahydro-pyran-4) 1H-benzene-1,3-diol 10: 4- (tetrahydro-furan-3-yl) -benzene-1,3-diol 11: 4- (tetrahydro-thiophen-3-yl) -benzene-1, 3-Diol 12: 4- (6-Oxa-spiro [4.5] dec-9-yl) -benzene-1,3-diol 13: 4-chloro-6- (tetrahydro-pyran-4-yl) -benzene- 1,3-diol 14: 4-Fluoro-6- (tetrahydro-pyran-4-yl) -benzene-1,3-diol 15: 4- (2,2-Diethyl-tetrahydro-pyran-4-yl) - be Nzene-1,3-diol 16: 4- (tetrahydro-pyran-3-yl) -benzene-1,3-diol 17: trans-4- (5-Hydroxymethyl-tetrahydro-furan-3-yl) -benzene- 1,3-diol 18: cis-4- (5-Hydroxymethyl-tetrahydro-furan-3-yl) -benzene-1,3-diol 19: trans-4-Fluoro-6- (5-hydroxymethyl-tetrahydro-furan) -3-yl) -benzene-1,3-diol 20: cis-4-Fluoro-6- (5-hydroxymethyl-tetrahydro-furan-3-yl) -benzene-1,3-diol 21: trans-4- Fluoro-6- (2-hydroxymethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 22: cis-4-fluoro-6- (2-hydroxymethyl-tetrahydro-pyran-4-yl) -benzene 1,3-diol 23: cis-4- (8-Oxa-bicyclo [3.2.1] oct-3-yl) -benzene-1,3-diol 24: trans-4- (8-Oxa-bicyclo [ 3.2.1] oct-3-yl) -benzene-1,3-diol 25: 4-Fluoro-6- (tetrahydro-thiopyran-4-yl) -benzene-1,3-diol These compounds can be prepared according to procedures described in application WO2010063773. The compound 1: 4- (tetrahydro-pyran-4-yl) -benzene-1,3-diol is particularly preferred. compound 1 The compound of formula (I) may be present in the composition according to the invention, in a content ranging from 0.001% to 10% by weight, relative to the total weight of the composition, more particularly in a content ranging from From 5% to 5% by weight, and preferably from 0.1% to 2% by weight, and preferably from 0.2% to 1.5% by weight.

The composition according to the invention comprises at least one nonionic hydrotrope. The nonionic hydrotropes are in particular chosen from: - caffeine, - niacinamide derivatives, for example vitamin B3, - urea and its derivatives, especially (C1-C6) alkyl urea and hydroxy (C1-C6) alkyls. )urea. - and their mixtures. The nonionic hydrotropes are selected from caffeine, urea, hydroxyethyl urea, N, N-diethylnicotinamide, N-picolylnicotinamide, N-allylnicotinamide, 2-methacryloyloxyethyl phosphorylcholine, butylurea, pyrogallol, N- picolylacetamide 3.5, nicotinamide (vitamin B3), pyridine, 3-picolylamine, ethyl carbamate, pyridoxal hydrochloride, 2-pyrrolidone, ethylurea, N, N-dimethylacetamide, N-methylacetamide, and isoniazid and mixtures thereof. Hydrotropes can be found in Lee Jet et al., "Hydrotropic Solubilization of Paclitaxel: Analysis of Chemical Structures for Hydrotropic Property", Pharmaceutical Research, Vol. 20, No. 7, 2003; and Lee S. et al., "Hydrotropic Polymers: Synthesis and Characterization of PolymersContaining Picolylnicotinamide Moieties", Macromolecules, 36, 2248-2255,2003. The preferred nonionic hydrotropes are in particular chosen from: caffeine, niacinamide derivatives such as vitamin B3, and mixtures thereof.

The non-ionic hydrotropic agent (s) may be present in a content ranging from 0.01% to 15% by weight, preferably ranging from 0.1% to 10% by weight, relative to the weight total of the composition.

According to a preferred embodiment, the mass ratio of said nonionic hydrotrope (s) / compound (s) of formula (1) present in the composition according to the invention is greater than or equal to 1, preferably greater than or equal to equal to 2, for example ranging from 2.5 to 30, and preferably ranging from 3 to 15.

According to a particular embodiment of the invention, the composition according to the present invention further comprises at least one glycol. By glycol according to the invention is meant a hydrocarbon chain comprising at least 2 carbon atoms, preferably 2 to 50 carbon atoms, preferably 2 to 20 carbon atoms, preferably having 2 to 10 carbon atoms, and preferably having from 2 to 6 carbon atoms, and bearing two hydroxyl groups. The glycols used in the present invention may have a weight average molecular weight less than or equal to 1000, preferably between 60 and 500.

The glycol may be a natural or synthetic glycol. The glycol may have a linear, branched or cyclic structure. The glycol may be chosen from diethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, 1,3-propanediol, 1,5-pentanediol and polyethylene glycols, in particular having 5 to 50 ethylene oxide groups, and mixtures thereof. More particularly, the glycol may be chosen from the group consisting of dipropylene glycol, propylene glycol, propanediol-1, 3, butylene glycol, and their mixture, and more particularly dipropylene glycol. The said glycol (s) may be present in a content ranging from 0.50% to 50% by weight, relative to the total weight of the composition, preferably ranging from 3% to 30% by weight. % by weight, and preferably ranging from 5% to 20% by weight, relative to the total weight of the composition. According to the invention, the composition according to the present invention comprises water. The amount of water is not limited, and may range from 50% to 99% by weight, preferably from 55% to 95% by weight, and more preferably from 70% to 90% by weight, based on total weight of the composition.

According to a particular embodiment of the invention, the composition according to the present invention further comprises at least one 02-04 monoalcohol. The 02-04 monohydric alcohols comprise a hydroxy group and 2 to 4 carbon atoms. Ethanol, propanol, isopropanol, butanol-1, isobutanol and mixtures thereof can be used. The 02-04 monohydric alcohol is preferably ethanol. The concentration of 02-04 monohydric alcohol can range from 0.1% to 30% by weight, preferably from 0.5% to 15% by weight, preferably from 1% to 10% by weight relative to the total weight of the composition. The compositions used according to the invention may comprise a physiologically acceptable medium, that is to say a medium which is suitable for the topical administration of a composition, that is to say compatible with the keratinous substances of the present invention. human beings such as the skin, the scalp, the hair, the nails. According to the invention a physiologically acceptable medium is preferably a cosmetically acceptable medium, that is to say without odor, or unpleasant appearance, and which is perfectly compatible with the topical route of administration.

The term "keratin materials" according to the invention is understood to mean the skin, the body, the face and / or the contour of the eyes, the lips, the nails, the mucous membranes, the eyelashes, the eyebrows, the hairs, the scalp and / or the hair, or any other skin area of the body. More particularly, the keratin materials according to the invention are the scalp, the hair, and / or the skin. Preferably, the keratin materials according to the invention are the scalp and / or the hair. Preferably, the keratin materials according to the invention are the skin. By "skin" is meant all of the skin of the body, and preferably, the skin of the face, décolleté, neck, arms and forearms, or even more preferably, the skin of the skin. face, including forehead, nose, cheeks, chin, eye area. As specified below, the compound of formula (I) is advantageously present in the compositions according to the invention in a solubilized form.

By way of example, the composition according to the invention may be intended to be administered topically, that is to say by surface application of the keratin material in question, such as the skin under consideration.

The composition of the invention may be a cosmetic composition (either intended for cosmetic use) or dermatological. Preferably, according to the invention, the composition is a cosmetic composition and even more preferentially a cosmetic composition for topical application. The term "cosmetic composition" is understood to mean a substance or a preparation intended to be brought into contact with the various superficial parts of the human body, in particular the epidermis, the hair and hair systems, the nails, the lips and the oral mucosa, in particular view, exclusively or mainly, to clean, embellish, perfume, change the appearance, protect, maintain or repair body odors.

The compositions according to the invention may be in the form of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O) emulsions. E or H / E / H), aqueous gels. These compositions are prepared according to the usual methods.

The composition may comprise at least one oil. Suitable oils that may be mentioned include, for example: hydrocarbon oils of vegetable origin, such as liquid triglycerides of fatty acids containing from 4 to 10 carbon atoms, for example triglycerides of heptanoic or octanoic acids or, for example, sunflower, corn, soy, squash, grape seed, sesame, hazelnut, apricot, macadamia, arara, castor oil, avocado, caprylic / capric acid triglycerides those sold by the company Stéarineries Dubois or those sold under the names "Miglyol 810", "812" and "818" by the company Dynamit Nobel, jojoba oil, shea butter oil; esters and synthetic ethers, in particular of fatty acids, such as the oils of formulas R 1 COOR 2 and R 1 OR 2 in which R 1 represents the residue of a fatty acid comprising from 8 to 29 carbon atoms, and R 2 represents a hydrocarbon-based chain, branched or unbranched, containing from 3 to 30 carbon atoms, such as, for example, purcellin oil, isononyl isononanoate, isopropyl myristate, ethyl-2-hexyl palmitate, octyl stearate, -2-dodecyl, octy1-2-dodecyl erucate, isostearyl isostearate; hydroxyl esters such as isostearyl lactate, octyl hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate; heptanoates, octanoates, decanoates of fatty alcohols; polyol esters, such as propylene glycol dioctanoate, neopentyl glycol diheptanoate and diethylene glycol diisononanoate; and pentaerythritol esters such as pentaerythrityl tetraisostearate; linear or branched hydrocarbons of mineral or synthetic origin, such as paraffin oils, volatile or not, and their derivatives, petroleum jelly, polydecenes, hydrogenated polyisobutene such as parleam oil; fatty alcohols having from 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetylstearyl alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, oleic alcohol or linoleic alcohol; silicone oils such as volatile or non-volatile polymethylsiloxanes (PDMS) with a linear or cyclic silicone chain, which are liquid or pasty at room temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenyl silicones such as phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl-dimethicones, diphenylmethyldiphenyltrisiloxanes, 2-phenylethyltrimethylsiloxysilicates, and polymethylphenylsiloxanes; - their mixtures.

The term "hydrocarbon-based oil" in the list of oils mentioned above, any oil predominantly comprising carbon and hydrogen atoms, and optionally ester, ether, fluoro, carboxylic acid and / or alcohol groups. The composition according to the invention may comprise solid bodies at ambient temperature (25 ° C.), for example fatty acids containing from 8 to 30 carbon atoms, such as stearic acid, lauric acid and palmitic acid. and oleic acid; waxes such as lanolin, beeswax, carnauba or candelilla wax, paraffin waxes, microcrystalline waxes, ceresin or ozokerite, synthetic waxes such as polyethylene waxes, Fischer waxes, Tropsch.

These fatty substances may be chosen in a varied manner by those skilled in the art in order to prepare a composition having the desired properties, for example of consistency or textures. According to a particular embodiment of the invention, the composition according to the invention is a water-in-oil (W / O) or oil-in-water (O / W) emulsion. The proportion of the oily phase of the emulsion may range from 1% to 80% by weight, and preferably from 5% to 50% by weight relative to the total weight of the composition. The emulsions generally contain at least one emulsifier, especially chosen from amphoteric, anionic, cationic or nonionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are suitably selected according to the emulsion to be obtained (W / O or O / W). The emulsifier and the co-emulsifier are generally present in the composition, in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

For the W / O emulsions, examples of emulsifiers that may be mentioned include dimethicone copolyols such as the mixture of cyclomethicone and dimethicone copolyol, sold under the name "DC 5225 C" by the company Dow Corning, and the alkyl-dimethicone copolyols such as Laurylmethicone copolyol sold under the name "Dow Corning 5200 Formulation Aid" by the company Dow Corning and Cetyl dimethicone copolyol sold under the name "Abil EM 90®" by the company Goldschmidt. For O / W emulsions, mention may be made, for example, as emulsifiers, of nonionic emulsifiers such as oxyalkylenated (more particularly polyoxyethylenated) fatty acid esters of glycerol; oxyalkylenated fatty acid and sorbitan esters; oxyalkylenated fatty acid esters (oxyethylenated and / or oxypropylenated); oxyalkylenated fatty alcohol ethers (oxyethylenated and / or oxypropylenated); sugar esters such as sucrose stearate; and mixtures thereof such as the mixture of glyceryl stearate and PEG-100 stearate.

The composition may be an aqueous gel, and in particular comprise conventional aqueous gelling agents. In a known manner, the composition according to the invention may also contain adjuvants which are customary in the cosmetic or dermatological field, such as gelling agents, thickeners, film-forming polymers, preservatives, perfumes, fillers, UV filters, bactericidal agents, odor absorbers, dyestuffs, plant extracts, vitamins, polyols such as glycerin, diglycerin, sugars such as sorbitol, cosmetic and dermatological active ingredients, and salts. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.001 to 20% of the total weight of the composition. Advantageously, the composition according to the invention has a pH ranging from 3 to 7. Preferably, the pH of the composition ranges from 4 to 6.

More particularly, the subject of the invention is also a process for the cosmetic treatment of skincare, makeup, and / or cleaning of keratinous substances, in particular the skin, comprising the application on said keratin materials, in particular the skin, of a composition according to the invention as described above.

Said method of cosmetic treatment of care, makeup, and / or cleansing of the skin is non-therapeutic. The subject of the invention is also a cosmetic process for the depigmentation, lightening and / or bleaching of keratin materials, in particular human skin, hair or hair, comprising the application to said keratin materials of a composition according to the invention. invention as described above.

The subject of the invention is also a cosmetic process for preventing and / or treating cutaneous signs of aging, comprising at least one step of topical application to keratin materials, such as the skin, of a composition according to the invention as previously described.

The cutaneous signs of the aging to be prevented and / or treated in the cosmetic process according to the invention may be chosen from the lines and wrinkles, and / or to fight against the skin withered, soft and / or thinned. The invention also relates to the cosmetic use of a composition according to the invention as defined above, for the care, makeup and / or cleaning of keratin materials. In another embodiment, the invention relates to a cosmetic treatment method for the care, makeup, and / or cleaning of keratinous substances, in particular the skin, comprising the administration, topically, to an individual, of a composition as defined above. The expressions "between ... and ..." and "from ... to ...", or "at least ..", or "at least .." must be understood as inclusive, unless the opposite is specified. The following examples of compositions according to the invention are given by way of illustration and without limitation. The compounds are indicated in chemical name or INCI name. The contents of the ingredients are expressed in percentage by weight.

Example 1: Solubility test The solubility tests were carried out with the compound 1 4- (tetrahydro-pyran-4-yl) -benzene-1,3-diol. Compound 1 was added in excess in the following solutions: Water Water + 5% vitamin B3 Water + 2% caffeine Water + 5% caffeine + 5% vitamin B3 Water / Dipropylene glycol (90/10 by weight) Water / Dipropylene glycol (90/10 by weight) + 5% caffeine + 5% vitamin B3 The solutions were brought to thermodynamic equilibrium with magnetic stirring for 24 hours. The soluble fraction was extracted by filtration (PTFE filters 0.45pm) and the active content assayed by HPLC / UV.

We let stand between 1 hour and 24 hours. The mixture was then heated to about 50 ° C and allowed to cool to room temperature (25 ° C) for 24 hours. It was then observed whether the amount of compound 1 introduced recrystallizes or remains solubilized. In this way, the amount of compound 1 which can be solubilized in the hydrotropic mixture + water tested was determined in this way. The maximum value corresponds to that of the amount from which the compound 1 begins not to solubilize in the evaluated solvent. The following results were obtained: Medium% by weight of solubilized compound 1 Water 0.08 Invention Water + 5% vitamin B 3 0.21 Invention Water + 2% caffeine 0.25 Invention Water + 5% caffeine + 5% vitamin B 3 0 , 55 Water / Dipropylene glycol (90/10 by weight) 0.17 Invention Water / Dipropylene glycol (90/10 by weight) + 5% caffeine + 5% vitamin B3 0.82 It was thus found that the solubility of the compound 1 was improved by the presence of a hydrotrope. EXAMPLE 2 Composition According to the Invention A skin care composition (oil-in-water emulsion) having the following composition was prepared:% MA 2 Vitamin B3 3 Caffeine 3 Compound 1 0.5 Dipropylene Glycol 6 INULIN LAURYL CARBAMATE (CREACHEM INUTEC SP1) 0.49 Xanthan gum 0.2 AMMONIUM POLYACRYLOYLDIMETHYL TAU RATE (Hostacerin AMPS® from Clariant) 0.49 DIMETHICONE (and) DIMETHICONOL (MIRASIL D-DML LV from BLUESTAR) 3 PENTAERYTHRITYL 1 TETRAETHYLHEXANOATE POLYSILICONE- 11 (GRANSIL RPS-D6 from GRANT INDUSTRIES) DIMETHICONE 5 Cst 4 Ethanol 5 Glycerine 5 Preservatives 0.75 Water Qsp 100% The composition is stable and homogeneous after storage for 2 months at 45 ° C. This composition can be applied regularly to the skin of the face to reduce the signs of skin aging and lighten the skin.

Claims (16)

CLAIMS1.Composition comprising: a) at least one nonionic hydrotrope; (b) water; c) at least one 4- (heterocycloalkyl) -benzene-1,3-diol compound of the following general formula (I): wherein R1, R2, R3, R4, which may be identical or different, represent: hydrogen, - a C1-C4 alkyl radical, - a hydroxymethyl, a hydroxyethyl, - a C1-C4 alkoxycarbonyl, - a C1-04 alkoxy, - a hydroxyl, OR R1 and R2 are connected to each other and form a carbon-based ring. at 5 or 6 carbon atoms with the carbon atom to which they are bonded and R3 and R4, which are identical or different, represent: - a hydrogen - a C1-C4 alkyl radical or R1 and R4 are connected to each other and form a chain - (CH2) 2- or - (CH2) 3- and R2 and R3, which may be identical or different, represent: - a hydrogen 30 - a C1-C4 alkyl radical represents an oxygen atom, or an atom of sulfur. Y represents a hydrogen, a chlorine atom or a fluorine atom. m can take the values 1 or 2 and n can take the values 0 or 1 and when n = 0, 35 then m = 1 or 2, and when n = 1, then m = 1. as well as the salts of the compounds of general formula (I), and their isomeric and enantiomeric forms, hydrates and solvates. R3 R4 (X R1 R2 2 - Compound according to claim 2 characterized in that in the compound d) of formula (I): - R1 represents a hydrogen, a C1-C4 alkyl radical or a hydroxymethyl radical, - R2 represents a hydrogen, - R3 represents a hydrogen, - R4 represents a hydrogen, - X represents an oxygen atom - Y represents a hydrogen or a fluorine atom -m = 1 and n = 1, as well as the salts of these compounds and their isomeric and enantiomeric forms, the hydrates and the solvates. 3 - Compound according to one of claims 1 to 2 characterized in that the compound or compounds d) of formula (1) are chosen from the group consisting of: 1: 4- (tetrahydro-pyran-4-yl) -benzene-1,3-diol 2: 4- (tetrahydro-thiopyran-4-yl) -benzene-1,3-diol 3: 4- (cis-2,6) Dimethyl tetrahydro-pyran-4-yl) -benzene-1,3-diol 4: trans-4- (2-methyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 5: cis- 4- (2-methyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 6: trans-4- (2-ethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 7: cis-4- (2-Ethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 8: trans-4- (2-Hydroxymethyl-tetrahydro-pyran-4-yl) -benzene-1 9: 4- (2,2,6,6-tetramethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 10: 4- (tetrahydro-furan-3-yl) -benzene, 3-diol; -1,3-Diol 11: 4- (tetrahydro-thiophen-3-yl) -benzene-1,3-diol 12: 4- (6-Oxa-spiro [4.5] dec-9-yl) -benzene-1 3-Diol 13: 4-Chloro-6- (tetrahydro-pyran-4-yl) -benzene-1,3-diol 14: 4-Fluoro-6- (tetrahydro-pyran-4-yl) -benzene-1 3-Diol 15: 4- (2,2-Diethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 16: 4- (tetrahydro-pyran-3-yl) -benzene-1,3 -diol 17: trans-4- (5-Hydroxymethyl-tetrahydro-furan-3-yl) -benzen e-1,3-diol 18: cis-4- (5-Hydroxymethyl-tetrahydro-furan-3-yl) -benzene-1,3-diol 19: trans-4-Fluoro-6- (5-hydroxymethyl-tetrahydro) -furan-3-yl) -benzene-1,3-diol 20: cis-4-Fluoro-6- (5-hydroxymethyl-tetrahydro-furan-3-yl) -benzene-1,3-diol 21: trans 4-Fluoro-6- (2-hydroxymethyl-tetrahydro-pyran-4-yl) -benzene-1,3-diol 22: cis-4-fluoro-6- (2-hydroxymethyl-tetrahydro-pyran-4-yl) benzene-1,3-diol 23: cis-4- (8-Oxa-bicyclo [3.2.1] oct-3-yl) -benzene-1,3-diol 24: trans-4- (8-Oxa) bicyclo [3.2.1] oct-3-yl) -benzene-1,3-diol 25: 4-Fluoro-6- (tetrahydro-thiopyran-4-yl) -benzene-1,3-diol 4 - compound according to one of claims 1 to 3 characterized in that the compound of formula (I) is 4- (tetrahydro-pyran-4-yl) -benzene-1,3-diol. 5. Composition according to one of claims 1 to 4, characterized in that the compound or compounds a) are present in a content ranging from 0.001% to 10% by weight, relative to the total weight of the composition, more particularly in a content ranging from 0.05% to 5% by weight, and preferably ranging from 0.1% to 2% by weight, and preferably ranging from 0.2% to 1.5% by weight. 6. Composition according to any one of the preceding claims, characterized in that the said nonionic hydrotrope (s) is chosen from: - caffeine - derivatives of niacinamide such as vitamin B3, - urea and its derivatives such as (hydroxy) alkyl (C1C6) urea, and mixtures thereof. 7. Composition according to any one of the preceding claims, characterized in that the (or) hydrotropes are present at a content ranging from 0.01% to 15% by weight, preferably ranging from 0.1% to 10%. by weight, based on the total weight of the composition. 8. Composition according to any one of the preceding claims, wherein the mass ratio of (said) nonionic hydrotropes (s) / compound of formula (I) is greater than or equal to 1, preferably greater than or equal to 2. for example from 2.5 to 30, and preferably from 3 to 15. 9. Composition according to any one of the preceding claims, characterized in that the composition further comprises at least one glycol. 30 10. Composition according to the preceding claim, characterized in that (s) said polyol a) is chosen from among propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol, 1,3-propanediol, 1,5-pentanediol, polyethylene glycol, and a mixture thereof. 35 11. Composition according to any one of claims 9 to 10, characterized in that the (s) said glycol (s) is present (s) in a content ranging from 0.50% to 50% by weight, relative to total weight of the composition, preferably ranging from 3% to 30% by weight, and preferably ranging from 5% to 20% by weight. % by weight, relative to the total weight of the composition. 40 12. Composition according to any one of the preceding claims, characterized in that it is in the form of a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. 13. Composition according to any one of the preceding claims, characterized in that it is a cosmetic composition. 14. A process for the cosmetic treatment of keratin materials comprising the application to keratin materials, such as the skin, of a composition according to any one of the preceding claims. 15. Process for the cosmetic treatment of skincare and / or make-up and / or cleaning of keratinous substances, in particular the skin, comprising the application on said keratin materials, in particular the skin, of a composition as defined according to one of the following: any of claims 1 to 13. 16. A cosmetic process for the depigmentation, lightening and / or bleaching of keratin materials, in particular human skin, hair or hair, comprising the application to said keratin materials of a composition as defined according to any one of the following: Claims 1 to 13.