WO2018210933A1 - Utilisation cosmétique de dérivés du résorcinol - Google Patents

Utilisation cosmétique de dérivés du résorcinol Download PDF

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WO2018210933A1
WO2018210933A1 PCT/EP2018/062742 EP2018062742W WO2018210933A1 WO 2018210933 A1 WO2018210933 A1 WO 2018210933A1 EP 2018062742 W EP2018062742 W EP 2018062742W WO 2018210933 A1 WO2018210933 A1 WO 2018210933A1
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hydrocarbon
branched
agents
mmol
radical
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Xavier Marat
Chunyu MA
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LOreal SA
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LOreal SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4056—Esters of arylalkanephosphonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3882—Arylalkanephosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
    • C07F9/657181—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative

Definitions

  • the present invention relates to the cosmetic use of novel resorcinol derivatives, to compositions, especially cosmetic compositions, containing same and to the use thereof for depigmenting and/or bleaching the skin.
  • compositions especially cosmetic compositions, containing same and to the use thereof for depigmenting and/or bleaching the skin.
  • Some people develop darker and/or more coloured blemishes on their skin, and more especially on the hands and the face, which give the skin heterogeneity.
  • These blemishes are especially due to a high concentration of melanin in the keratinocytes located at the surface of the skin.
  • the mechanism of formation of the pigmentation of the skin i.e. of the formation of melanin, is particularly complex and involves, schematically, the following main steps:
  • Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this sequence of reactions. It especially catalyses the reaction for converting tyrosine into dopa (dihydroxyphenylalanine), by virtue of its hydroxylase activity, and the reaction for converting dopa into dopaquinone, by virtue of its oxidase activity. This tyrosinase acts only when it is in mature form under the effect of certain biological factors.
  • a substance is acknowledged as being depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis takes place, and/or if it interferes with one of the steps of melanin biosynthesis, either by inhibiting one of the enzymes involved in melanogenesis, or by inserting itself as a structural analogue of one of the chemical compounds of the melanin synthesis chain, which chain can then be blocked, thus ensuring depigmentation.
  • Arbutin and kojic acid are known as skin depigmenting agents. Substances with efficient depigmenting action, especially better than that of arbutin and kojic acid, have been sought.
  • a subject of the invention is a composition comprising, in a physiologically acceptable medium, at least one compound of formula (I) as defined below.
  • the invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below, as an agent for bleaching, lightening and/or depigmenting keratin materials, especially the skin.
  • a subject of the invention is also a non-therapeutic cosmetic treatment process for depigmenting, lightening and/or bleaching keratin materials, especially the skin, comprising the application to the skin of at least one compound of formula (I) as defined below or of a composition containing same.
  • a subject of the invention is also the compounds of formula (I) as defined below for their dermatological use for depigmenting the skin.
  • the compounds of formula (I) in accordance with the invention make it possible to depigment and/or lighten efficiently, or even bleach, human skin. They are especially intended to be applied to the skin of individuals bearing brownish pigmentation blemishes or senescence spots, or to the skin of individuals wishing to combat the appearance of a brownish colour caused by melanogenesis.
  • keratin materials means human keratin materials, and in particular human skin, bodily hair, the eyelashes, head hair, the lips and the nails.
  • the compounds of formula (I) in accordance with the invention may also make it possible to depigment and/or lighten bodily hair, the eyelashes, head hair, and also the lips and/or the nails.
  • keratin materials denotes human skin.
  • Rl denotes:
  • R5 denotes a saturated linear or branched C1-C20 hydrocarbon-based radical, an unsaturated linear or branched C2-C20 hydrocarbon-based radical, or a C3-C8 cycloalkyl radical optionally substituted with one or more C1-C10 alkyl radicals
  • R2 denotes:
  • R3 and R4 independently denote
  • R3 and R4 may form, together with each oxygen atom that bears them and the phosphorus atom, a 5- to 8-membered heterocycle optionally substituted with one or more C1-C10 hydrocarbon-based chains; and also the salts thereof, the solvates thereof and the optical and/or geometrical isomers thereof, including enantiomers and diastereoisomers, and the racemic mixtures thereof, alone or as a mixture.
  • the salts of the compounds of formula (I) comprise the conventional non-toxic salts of said compounds such as those formed from acid or base.
  • a base which may be organic or mineral.
  • the base may thus be a mineral base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithium hydroxide, or sodium, potassium or calcium carbonate or hydrogen carbonate, for example.
  • the base may also be an organic base such as a primary, secondary or tertiary alkylamine, for example triethylamine or butylamine.
  • This primary, secondary or tertiary alkylamine may comprise one or more nitrogen and/or oxygen atoms and may thus comprise, for example, one or more alcohol functions; mention may be made in particular of 2-amino-2- methylpropanol, ethanolamine, triethanolamine, 2-dimethylaminopropanol, 2-amino-2- (hydroxymethyl)- 1 ,3-propanediol and 3-(dimethylamino)propylamine.
  • the salts may also denote salts of addition with amino acids, for instance lysine, arginine or guanidine.
  • the salts of the compounds of formula (I) may be chosen from alkali metal or alkaline-earth metal salts such as sodium, potassium, calcium or magnesium salts; ammonium salts.
  • the solvates comprise conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents. Examples that may be mentioned include solvates due to the presence of water or of linear or branched alcohols, such as ethanol or isopropanol.
  • optical isomers are especially enantiomers and diastereoisomers.
  • a "Cx-Cy hydrocarbon-based radical” denotes an alkyl group comprising from x to y carbon atoms.
  • Such a hydrocarbon-based radical may be linear and saturated and typically contain from 1 to 20 carbon atoms or from 1 to 10 carbon atoms. It may also be linear and unsaturated (ethylenic double bond) and typically contain from 2 to 20 carbon atoms or from 2 to 10 carbon atoms. It may also be branched and typically contain from 3 to 20 carbon atoms or from 3 to 10 carbon atoms.
  • a hydrocarbon-based radical may also be cyclic: it is then a cycloalkyl group which may typically contain from 3 to 8 carbon atoms.
  • Cx-Cy hydrocarbon-based radical denotes a saturated linear alkyl group comprising from x to y carbon atoms.
  • the saturated linear or branched hydrocarbon-based radicals are chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, 2-ethylhexyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl and eicosyl.
  • the saturated linear or branched hydrocarbon-based radicals are chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, 2-ethylhexyl and octyl, and even more preferentially from methyl, ethyl, propyl, butyl and hexyl.
  • the cycloalkyl group is chosen from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
  • Cx-Cy alkyl radical denotes a saturated Cx-Cy hydrocarbon-based radical.
  • Such a hydrocarbon-based radical may be linear and saturated and typically contain from 1 to 20 carbon atoms or from 1 to 10 carbon atoms. It may also be branched and typically contain from 3 to 20 carbon atoms or from 3 to 10 carbon atoms.
  • Cx-Cy alkyl radical denotes a saturated linear alkyl group comprising from x to y carbon atoms.
  • An x- to y-membered heterocycle denotes a hydrocarbon-based cyclic radical containing in its ring x to y atoms also referred to as x to y members, and of which at least one of these atoms is a heteroatom which may be chosen, for example, from O and P.
  • This heterocycle may be monocyclic or bicyclic, preferably monocyclic. It may be saturated or unsaturated, preferably saturated. When the heterocycle contains several heteroatoms, these heteroatoms may be identical or different.
  • heterocycle when the heterocycle contains several different heteroatoms, these heteroatoms may be adjacent or non- adjacent.
  • the 5- to 8-membered heterocycle may denote a cyclic radical of 5 to 8 atoms containing the sequence - O-P-0 -.
  • the compounds of formula (I) and also the salts thereof, the solvates thereof and the optical and/or geometrical isomers thereof, including enantiomers and diastereoisomers, and the racemic mixtures thereof, alone or as a mixture are such that:
  • Rl denotes:
  • R5 denotes a saturated linear or branched Cl- C4 hydrocarbon-based radical
  • R2 denotes:
  • R3 and R4 independently denote
  • R3 and R4 possibly forming, together with the oxygen that bears them and the phosphorus atom, a 5- to 8-membered heterocycle optionally substituted with one or more C1-C10 alkyl radicals.
  • the compounds of formula (I) and also the salts thereof, the solvates thereof and the optical and/or geometrical isomers thereof, including enantiomers and diastereoisomers, and the racemic mixtures thereof, alone or as a mixture are such that:
  • Rl denotes a hydrogen atom H
  • R2 denotes:
  • R3 and R4 independently denote
  • R3 and R4 possibly forming, together with each oxygen atom that bears them and the phosphorus atom, a 5- to 6-membered heterocycle optionally substituted with one or more C1-C10 hydrocarbon-based chains.
  • the compounds of formula (I) and also the salts thereof, the solvates thereof and the optical and/or geometrical isomers thereof, including enantiomers and diastereoisomers, and the racemic mixtures thereof, alone or as a mixture are such that:
  • Rl denotes a hydrogen atom H
  • R2 denotes:
  • R3 and R4 independently denote
  • R3 and R4 possibly forming, together with each oxygen atom that bears them and the phosphorus atom, a 5- to 6-membered and preferably 6-membered heterocycle, said heterocycle being optionally substituted with one or more Ci-C 6 and more particularly C1-C4 alkyl radicals.
  • the compounds of formula (I) are such that the radicals R3 and R4 are identical.
  • the compounds of formula (I) are such that the radicals R3 and R4 form, together with each oxygen atom that bears them and the phosphorus atom, a 5- to 8-membered heterocycle optionally substituted with one or more C1-C10 hydrocarbon-based chains.
  • the compounds of formula (I) of the invention denote compounds 1 to 11 mentioned in table 1 below.
  • the compounds of formula (I) of the invention denote compounds 1, 5, 6, 7, 8, 9, 10 and 11.
  • the compounds of the invention may be prepared according to scheme 1 below involving methods that are known and described for those skilled in the art concerning phosphonate chemistry. See, for example, Modern Phosphonate Chemistry by Philippe Savignac, Bogdan Iorga CRC Press 2003, ISBN 0-8493-1099-7.
  • Rhodium-Catalyzed Enantioselective Hydrogenation of Unsaturated Phosphonates by ClickFerrophos Ligands by Konno, Takashi; Shimizu, Kenta; Ogata, Kenichi; Fukuzawa, Shin-ichi from Journal of Organic Chemistry (2012), 77(7), 3318-3324.
  • the adjustment of the radicals R3 and R4 may be made at the end of the reaction by standard modification of phosphonate esters.
  • Production of the derivatives of the compounds of formula (I) may be performed especially in the presence of an organic solvent, which may be chosen from toluene, tetrahydrofuran, heptane, isooctane, methyltetrahydrofuran, methyl ethyl ketone, methyl isobutyl ketone, dioxane, ethyl acetate, isopropyl acetate and isododecane, and mixtures thereof, especially at a temperature of between 15 and 200°C, optionally in the presence of a catalyst (acidic or basic) as described in the publications.
  • an organic solvent which may be chosen from toluene, tetrahydrofuran, heptane, isooctane, methyltetrahydrofuran, methyl ethyl ketone, methyl isobutyl ketone, dioxane, ethyl acetate, isopropyl
  • the compounds of formula (I) for which Rl denote a group COR5 may be obtained by acetylation/esterification.
  • the acetylation/esterification reaction may be performed with an anhydride R5COOCOR5 such as acetic anhydride or an acid chloride R5COC1 such as acetyl chloride, especially in the presence of an aprotic solvent such as toluene, pyridine or tetrahydrofuran.
  • the acetylation reaction may be selective by employing protecting groups on the functions that do not need to be acetylated and by performing a deprotection reaction after acetylation, according to the known techniques of organic synthesis.
  • the reactions described to obtain the compound of formula (I) as described above may optionally be performed in the presence of an organic solvent, especially tetrahydrofuran, dioxane, dimethylformamide, 2-methyltetrahydrofuran or toluene; optionally in the presence of a catalyst chosen from Lewis or Bronsted acid catalysts and basic catalysts, such as potassium carbonate, triethylamine, diisopropylethylamine or butyllithium; optionally by heating to a temperature of between 15°C and 200°C, especially between 20°C and 150°C, or by cooling to temperatures of between -78°C and 0°C.
  • an organic solvent especially tetrahydrofuran, dioxane, dimethylformamide, 2-methyltetrahydrofuran or toluene
  • a catalyst chosen from Lewis or Bronsted acid catalysts and basic catalysts, such as potassium carbonate, triethylamine, diisopropylethylamine or butyllith
  • the final compounds (I) in which the radicals R3 and/or R4 denote a hydrogen atom may be obtained by saponification of the compounds for which R3 and/or R4 denote an alkyl radical using mineral bases, for instance NaOH or LiOH, in the presence of protic or aprotic solvents, for instance ethanol or tetrahydrofuran or water, at temperatures ranging between 0 and 100°C.
  • the salts obtained are then reacidified in the presence of standard mineral or organic acids, for instance hydrochloric acid or citric acid.
  • a subject of the invention is also a composition containing at least one compound of formula (I), in particular a composition containing at least one compound chosen from compounds 1 to 11 described previously, and even more preferentially at least one compound chosen from compounds 1, 9, 7, 6, 8, 5, 11 and 10.
  • composition according to the invention is advantageously a cosmetic composition.
  • composition according to the invention is advantageously a composition intended for topical application.
  • composition according to the invention advantageously comprises, in a physiologically acceptable medium, at least one compound of formula (I) as described previously, in particular at least one compound chosen from compounds 1 to 11 described previously, and even more preferentially at least one compound chosen from compounds 1, 9, 7, 6, 8, 5, 11 and 10.
  • physiologically acceptable medium means a medium that is compatible with human keratin materials such as bodily or facial skin, the lips, mucous membranes, the eyelashes, the nails, the scalp and/or the hair.
  • the compound of formula (I) may be present in the composition according to the invention in an amount that may be between 0.01% and 10% by weight, preferably between 0.1 % and 5% by weight, especially from 0.5%> to 3% by weight relative to the total weight of the composition.
  • composition according to the invention is advantageously a cosmetic composition: it may comprise adjuvants usually used in the cosmetic field.
  • These optional cosmetic adjuvants may be present in the composition in a proportion of from 0.001% to 80% by weight and especially from 0.1% to 40% by weight relative to the total weight of the composition. In any case, these adjuvants, and the proportions thereof, will be chosen by those skilled in the art such that the advantageous properties of the compounds according to the invention are not, or are not substantially, adversely affected by the envisaged addition.
  • composition according to the invention may in particular be in any presentation form normally used in the cosmetic field, and especially in the form of an aqueous or aqueous-alcoholic solution, which is optionally gelled, a dispersion of the lotion type, which is optionally a two-phase lotion, an oil-in-water or water-in-oil or multiple (for example W/O/W or 0/W/O) emulsion, an aqueous gel, a dispersion of oil in an aqueous phase by means of spherules, these spherules possibly being polymer nanoparticles such as nanospheres and nanocapsules or, better still, lipid vesicles of the ionic and/or nonionic type; aqueous or oily gels.
  • an aqueous or aqueous-alcoholic solution which is optionally gelled
  • a dispersion of the lotion type which is optionally a two-phase lotion, an oil-in-water or water-in-oil or
  • compositions are prepared according to the usual methods.
  • the composition according to the invention may constitute a skincare composition, and especially a cleansing, protecting, treating or care cream for the face, the hands, the feet, the major anatomical folds or the body (for example day creams, night creams, makeup-removing creams, foundation creams or antisun creams); a fluid foundation, a makeup-removing milk, a protective or care body milk or an antisun milk; a skincare lotion, gel or foam, such as a cleansing lotion.
  • a subject of the invention is also a non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, especially the skin, comprising the application of the composition described previously.
  • the invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined previously, and more particularly of at least one compound chosen from compounds 1 to 11 described previously, and even more preferentially at least one compound chosen from compounds 1, 9, 7, 6, 8, 5, 11 and 10, as an agent for bleaching, lightening and/or depigmenting keratin materials, especially the skin.
  • Figure 1 Evaluation of the dose effect on a KHN/MHN coculture of compound 7 (circle: percentage of depigmentation, triangle: percentage of cytotoxicity)
  • Step 1 2,4-Dihydroxybenzaldehyde A (5 g, 0.036 mol) and sodium carbonate (20 g, 0.145 mol) are stirred in 35 ml of DMF. The reaction medium is left stirring at room temperature for 1 hour. Benzyl bromide (24.8 g, 0.145 mol) is added and the mixture is refiuxed for 3 hours. After cooling to room temperature, 200 ml of ice-water are poured into the reaction medium. After filtering off the precipitate, it is recrystallized from MeOH to obtain the expected B in the form of a beige-coloured powder in a yield of 88%.
  • Step 2 The diphosphonate B (15.6 g, 0.054 mol) and sodium carbonate (9 g, 0.065 mol) are stirred in 10 ml of water. The mixture is heated to a nominal temperature of 50°C. After dissolution, the benzyl derivative is added (6.9 g, 0.022 mol) and the reaction mixture is heated at a nominal temperature of 100°C for 24 hours. After cooling, a large volume of water is added and the mixture is then extracted twice with dichloromethane. The organic phases are combined and then concentrated to dryness. After triturating the crude product in a small volume of water, the solid is washed with diisopropyl ether. Product C is obtained after filtration in the form of a beige-coloured powder in a yield of 81%.
  • the unsaturated derivative C (7 g, 0.015 mol) is placed in contact with 10% Pd/C (1.65 g, 0.015 mol) in 140 ml of a 50/50 cyclohexene/MeOH mixture and refluxed for 22 hours. After concentrating the reaction medium under vacuum, the crude product is purified on a chromatography column on silica gel with a CH2Cl2/MeOH system. Compound 1 is obtained in the form of a light brown oil in a yield of 77%.
  • Example 4 Synthesis of compound 5 (in all the synthetic examples, the intermediates should be renamed as in the preceding examples so as not to reuse numbers 1 to 11, which are reserved for the compounds of formula (I)).
  • Synthesis of b-8 A mixture of 2,4-dihydroxyacetophenone (3.04 g, 20.0 mmol), K2C03 (6.9 g, 50.0 mmol) and BnBr (7.5 g, 43.9 mmol) in 80 ml of MeCN was refluxed for 15 hours. After cooling, the mixture was filtered to remove the K2C03. The filtrate was concentrated to dryness to give 6.0 g of b-8 in the form of a white solid in a yield of 90%.
  • Synthesis of c-8 3.8 ml of 2.0 M LDA in THF were added to a solution of b-8 (1.14 g, 7.5 mmol) in 50 ml of THF at -78°C.
  • the measurement of the depigmenting activity (reduction of melanin production) of compounds of formula (I) was performed by assaying normal human melanocytes in vitro as follows.
  • the IC50 value is 18.7 ⁇ .
  • the IC50 value is 63.1 ⁇ .
  • the compounds of formula (I) showed a strong depigmenting effect.
  • the melanogenesis-modulating effect of compound 7 was measured according to the method described in patent FR-A-2734825, and also in the article by R. Schmidt, P. Krien and M. Regnier, Anal. Biochem., 235(2), 113-18, 1996. This test is performed on a coculture of keratinocytes and melanocytes.
  • the inhibitory activity on melanin synthesis by estimating the melanin optical density.
  • IC50 values concentration for which 50% of the melanin synthesis is inhibited
  • the test was also performed with arbutin, niacinamide and kojic acid, which are known depigmenting compounds.
  • the melanin present in the PRE is stained (Fontana-Masson staining) and then quantified by image analysis. Each epidermis image is scanned using Nanozoomer®. For each epidermis, about 10 ⁇ 15 images are extracted (white light, magnification x20). The zone occupied by melanin is quantified using the Histolab® software.
  • Compound 1 has higher depigmenting efficiency than lucinol on pigmented reconstructed epidermis.
  • a skin depigmenting composition comprising (in grams):
  • composition applied to the skin makes it possible to attenuate brown spots.
  • a skin depigmenting gel comprising (% by weight): Compound 7 0.25%
  • Carbomer (Carbopol 981 from Lubrizol) 1 %
  • composition applied to the skin makes it possible to attenuate brown

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Abstract

L'invention concerne des dérivés de résorcinol de formule (I) ainsi que leurs sels, leurs solvates et leurs isomères optiques et/ou géométriques, y compris des énantiomères et des diastéréoisomères, et leurs mélanges racémiques, seuls ou en mélange. L'invention concerne également un procédé cosmétique de dépigmentation, d'éclaircissement et/ou de décoloration de matières kératiniques, en particulier de la peau, à l'aide de ces composés (I).
PCT/EP2018/062742 2017-05-16 2018-05-16 Utilisation cosmétique de dérivés du résorcinol Ceased WO2018210933A1 (fr)

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FR1754295A FR3066492B1 (fr) 2017-05-16 2017-05-16 Derives de resorcinol pour leur utilisation cosmetique
FR1754295 2017-05-16

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0623339A1 (fr) 1993-04-29 1994-11-09 L'oreal Utilisation de dérivés de la resorcine substitués en position(s)4,4 et 5 ou 4 et 6 dans des compositions cosmétiques ou dermopharmaceutiques à action dépigmentante
FR2734825A1 (fr) 1995-05-31 1996-12-06 Oreal Procede de separation de la melanine presente dans des cellules
JPH11255638A (ja) 1998-03-13 1999-09-21 Kansai Kouso Kk チロシナーゼ活性阻害剤及び化粧料

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0623339A1 (fr) 1993-04-29 1994-11-09 L'oreal Utilisation de dérivés de la resorcine substitués en position(s)4,4 et 5 ou 4 et 6 dans des compositions cosmétiques ou dermopharmaceutiques à action dépigmentante
FR2734825A1 (fr) 1995-05-31 1996-12-06 Oreal Procede de separation de la melanine presente dans des cellules
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