Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
  • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
  • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
  • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
  • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
  • C07D233/60—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• • 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
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
  • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/04—Antipruritics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/08—Antiseborrheics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P23/00—Anaesthetics
  • A61P23/02—Local anaesthetics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/20—Hypnotics; Sedatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/04—Antibacterial agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/10—Antimycotics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/12—Antivirals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/10—Anthelmintics
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
  • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
  • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/74—Biological properties of particular ingredients
  • A61K2800/75—Anti-irritant

Definitions

• the present invention relates to new compounds of the family of 3-Alkyl- (4,5 diphenyl-imidazol-1-yl), to their process of synthesis and to the cosmetic, hygienic or pharmaceutical compositions containing them.
• Another subject of the invention relates to the use, in a physiologically acceptable medium, in or for the preparation of a soothing composition, of at least one compound of the family of 3-Alkyl- (4,5 diphenyl -imidazol-1 -yl).
• Another subject of the invention relates to the use, in a physiologically acceptable medium, in or for the preparation of a composition, of at least one compound of the family of 3-Alkyl- (4,5 diphenyl- imidazol-1-yl), the compound or composition being intended to soothe skin disturbances such as sensitive skin, discomfort, tightness, itching, irritation, redness, sensations of heat and / or warming, advantageously the symptoms of skin and / or scalp and / or sensitive and / or irritable and / or reactive and / or intolerant mucous membranes.
• Another subject of the invention relates to a soothing cosmetic process using such a composition.
• skin disturbances means the sensations of heating, discomfort, tightness, itching, irritation, redness, the sensation of heat, symptoms of the skin and / or scalp and / or sensitive and / or irritable and / or reactive and / or intolerant mucous membranes, scabs. Sensitive and / or irritable and / or reactive and / or intolerant skin and / or scalp and / or mucous membranes have been defined and characterized by the Applicant in patent EP 0 680 749.
• the purpose of the present invention is therefore to be able to have new products, easily accessible from a synthetic point of view, having a soothing activity while not presenting any significant side effects.
• the first subject of the invention relates to new compounds of the family of 3- Alkyl- (4,5 diphenyl-imidazol-1-yl) corresponding to the following formula (I):
• - n is equal to 3, 4 or 5
• R ⁇ and R 2 represent a linear or branched alkyl radical in 0, -0 4 , - an aryl or alkylaryl radical or arylalkyl or a heterocycle, optionally substituted by at least one alkyl radical and / or a hydroxy radical (-OH) and / or a radical -OR !
• R, and R 2 represent a linear or branched alkyl radical in C, ⁇ ., a phenyl radical or a benzyl radical.
• the invention also relates to the optical and / or geometric isomers as well as the physiologically acceptable salts of the compounds corresponding to formula (I), alone or as a mixture in all proportions.
• linear or branched alkyl radical in and in is understood according to the invention the acyclic radicals originating from the removal of a hydrogen atom in the molecule of a hydrocarbon, linear or branched having from 1 to 4, respectively from 1 to 8 carbon atoms and in particular the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl radicals and their corresponding position isomers.
• heterocycle is understood according to the invention a chain of atoms closed on itself and comprising at least one link (hetero atom) different from the others. According to the invention, the heterocycle can be aromatic or not.
• - n is equal to 3 or 4;
• the formation of the compounds of the family of 3-Alkyl- (4,5 diphenyl-imidazol-1-yl) of formula (I) results from the nucleophilic substitution of a halogen, originating from an alkyl halide, by pennant of 4,5-diphenyl imidazole.
• a second subject of the invention relates to a process for the preparation of the compounds of formula (I) as defined above, from 4,5-diphenyl imidazole.
• the process for preparing the compounds of formula (I) is characterized in that it essentially consists of the steps: a) dissolving 4,5-diphenyl imidazole in an aprotic organic solvent, preferably chosen from acetonitrile, acetone, tetrahydrofuran (THF), dimethylformamide (DMF), advantageously acetonitrile; b) adding an organic or inorganic base, preferably an inorganic base, advantageously chosen from potassium carbonate (K 2 CO 3 ), sodium carbonate (Na 2 CO 3 ), calcium carbonate (Ca 2 CO 3 ), very preferably K 2 CO 3 , in an amount between 1 and 10 equivalents, preferably between 1 and 3 equivalents, advantageously 2 equivalents of base; c) adding an alkyl halide in an amount of 1 and 5 equivalents, advantageously 1.5 equivalents; d) heating to a temperature between 50 ° C and 85 ° C, preferably between 70 ° C and 85 ° C, for
• the process for preparing the compounds of formula (I) is characterized in that it essentially consists of the steps: a) dissolving 4,5-diphenyl imidazole in a dipolar aprotic solvent, preferably chosen from dimethylformamide (DMF), dimethylsulfoxide (DMSO), dimethylacetamide (DMAc), advantageously DMF; b) adding, under an inert atmosphere, an organic or inorganic base, preferably an inorganic base, advantageously chosen from sodium hydride (NaH), butyl lithium (BuLi), very preferably NaH, in an amount of between 0.9 and 1, 5 equivalents, preferably between 1.0 and 1.1 equivalents, advantageously 1.0 equivalent; c) stir the reaction medium at a temperature between 25 ° C and 100 ° C, preferably between 40 ° C and 60 ° C, advantageously at 50 ° C, for a period between 30 min and 10h, advantageously between 1 and 2h, preferably for 1h; d)
• inert atmosphere argon or nitrogen and by ambient temperature is meant a temperature between 15 ° C and 25 ° C.
• a third subject of the invention relates to a composition which comprises at least one of the compounds corresponding to formula (I) defined above.
• composition according to the invention can comprise the compounds of formula (I) alone or in mixtures in all proportions.
• the amount of compounds of formula (I) contained in the composition according to the invention is clearly understood as a function of the desired effect and can therefore vary to a large extent.
• the composition of the invention may contain at least one compound of formula (I) in an amount representing from 0.001% to 20% of the total weight of the composition and preferably in an amount representing from 0.01 % to 5% of the total weight of the composition.
• composition according to the invention can be intended for a cosmetic or pharmaceutical application, particularly dermatological.
• composition according to the invention is intended for cosmetic application.
• composition can be ingested or applied to the skin (on any cutaneous zone of the body), the hair, the nails or the mucous membranes (buccal, jugale, gingival, genital, conjunctiva).
• composition according to the invention can be in all the galenical forms normally used, particularly in cosmetology.
• a preferred composition according to the invention is a cosmetic composition intended for topical application.
• composition according to the invention contains a physiologically acceptable medium, that is to say compatible with the skin, the lips, the scalp, the mucous membranes, the eyes and / or the hair.
• At least one compound of the family of 3-Alkyl- (4,5 diphenyl-imidazol-1-yl) corresponding to formula (I), as described previously in the text, can be associated with irritant side effect products commonly used in the cosmetic or pharmaceutical field, products which are sometimes cosmetic or pharmaceutical active ingredients.
• a compound of formula (I) in a cosmetic or pharmaceutical composition comprising a product having an irritant effect makes it possible to greatly attenuate, or even to eliminate this irritant effect.
• the invention relates more particularly to a cosmetic composition, characterized in that it comprises, in a cosmetically or pharmaceutically acceptable medium, at least one product with irritant side effect and at least compound of the family of 3-Alkyl- (4 , 5 diphenyl-imidazol-1-yl) corresponding to formula (I).
• surfactants ionic or nonionic
• preservatives organic solvents or active agents
• organic solvents or active agents such as ⁇ -hydroxy acids (citric, malic, glycolic, tartaric, mandelic acid, lactic), ⁇ -hydroxy acids (salicylic acid and its derivatives), ⁇ -keto acids, ⁇ -keto acids, retinoids (retinol, retinal, retinoic acid), anthralins (dioxyanthranol), anthranoids , peroxides (especially benzoyl), lithium salts, antimetabolites, certain dyes or certain hair dyes (paraphenylenediamine and its derivatives, aminophenols), alcoholic perfuming solutions (perfumes, eau de toilette, after shaving, deodorants), antiperspirants (certain aluminum salts), depilatory or permanent active ingredients (thiols), depigmenting active ingredients (hydroquinone).
• surfactants ionic or nonionic
• the comparative test which is presented in the examples of the present invention shows that the percentage of inhibition measured (inhibition of the response of superficial epidermal cells to an irritant agent by assaying interleukin-8 secreted by NHEK cells after stimulation with PMA as an irritant), is better for the compounds according to the invention compared to the reference compounds of the prior art. Due to this anti-irritant effect, it is easy to understand the advantage of using the compounds according to the invention as soothing.
• the present invention also relates to the use in a physiologically acceptable medium, in or for the preparation of a soothing composition, of at least one compound of the family of 3-Alkyl- (4,5 diphenyl-imidazol -1-yl) corresponding to formula (I) as defined above.
• the compounds of the family of 3-Alkyl- (4,5 diphenyl-imidazol-1-yl) corresponding to formula (I) also have the advantage of having very low cytotoxicity (less than 20%).
• the evaluation of the cytotoxicity of the compounds was carried out on normal human keratinocytes in culture in vitro by the addition for 2 hours in the culture medium of 3- (4,5-dimethylthiazol-2-yl) -2.5 -diphenyl) tetrazolium bromide (MTT, 0.5mg / ml) followed by the spectrophotometric measurement of the formazan incorporated into the cells after 24 h according to the classical technique described by T. Mosmann (J. Immunological Methods; 65 (1983) 55-63).
• Another advantage of the present invention is to now be able to have compounds which make it possible to gently soothe skin disturbances such as sensitive skin, discomfort, tightness, itching, irritation, redness, sensations of heat. and / or heating, which makes the use of these compounds compatible in cosmetic compositions, particularly topical.
• physiologically acceptable medium a medium compatible with the skin and / or mucous membranes and / or the nails and / or the hair.
• Another subject of the invention relates to the use in a physiologically acceptable medium, in or for the manufacture of a composition, of at least one compound of the family of 3-Alkyl- (4,5 diphenyl-imidazol -1-yl) of formula (I) as defined above, the compound or composition being intended to soothe the skin disturbances chosen from sensitive skin, discomfort, tightness, itching, irritation, redness, feelings of heat and / or heating, advantageously the symptoms of skin and / or scalp and / or sensitive and / or irritable and / or reactive and / or intolerant mucous membranes, particularly tingling, tingling, itching or pruritus, overheating, discomfort and / or tightness.
• Some alopecias are associated with irritations of the scalp and / or symptoms such as discomfort, tightness, itching or itching, redness, feelings of heat and / or heating. This is particularly the case of androgenetic alopecia which results from a process generating irritations. Therefore, it is understood that the reduction of irritation in the scalp, may represent a means of reducing and / or stabilizing the natural fall of hair in humans.
• another subject of the invention relates to the use in a physiologically acceptable medium, in a cosmetic composition or for the preparation of a pharmaceutical composition, of at least one compound of the family of 3-Alkyl- ( 4.5 diphenyl-imidazol-1-y
• the compounds of the family of 3-Alkyl- (4,5 diphenyl-imidazol-1-yl) corresponding to formula (I) used preferentially according to the invention are those defined as preferential previously in the text .
• the compounds of the family of 3-Alkyl- (4,5 diphenylimidazol-1-yl) corresponding to formula (I) can be used alone or as a mixture, in any proportion.
• the cosmetic composition according to the invention is apply to the areas to be treated of an individual suffering from at least one of the said skin disturbances and / or symptoms and is possibly left in contact for several minutes to several hours and is optionally rinsed; this for uses that can be repeated or renewed over treatment periods ranging from a few days to several months or even years.
• another subject of the present invention is a method of cosmetic treatment of the skin and / or scalp and / or mucous membranes, intended to soothe at least one of the skin disturbances and / or one of the symptoms mentioned above, characterized by the fact that it consists in applying to the skin and / or the scalp and / or the mucous membranes, a cosmetic composition comprising at least one compound corresponding to formula (I), to leaving it in contact with the skin and / or mucous membranes and / or scalp, and possibly rinse.
• the cosmetic treatment process of the invention advantageously applies to natural hair loss in humans, to skin and / or scalps and / or sensitive and / or irritable and / or reactive and / or intolerant mucous membranes.
• the treatment process has the characteristics of a cosmetic process in the measure as it improves the aesthetics or comfort of the skin and / or mucous membranes and / or scalp.
• the composition may take the form in particular of an aqueous or oily solution or of a dispersion of the lotion or serum type, of emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a phase oily in an aqueous phase (O / W) or vice versa (W / O), or of suspensions or emulsions of soft consistency of the aqueous or anhydrous cream or gel type, or of microcapsules or microparticles, or of vesicular dispersions of the ionic type and / or non-ionic.
• These compositions are prepared according to the usual methods.
• composition according to the invention obviously comprises a cosmetically acceptable support and can be in all the galenical forms normally used for a topical application, in particular in the form of an aqueous, hydroalcoholic or oily solution, of an oil-in-emulsion.
• water or water-in-oil or multiple, of an aqueous or oily gel, of a liquid, pasty or solid anhydrous product, of an oil dispersion in an aqueous phase using spherules these spherules possibly be polymeric nanoparticles such as nanospheres and nanocapsules or better lipid vesicles of ionic and / or nonionic type.
• This composition can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a foam. . It can optionally be applied to the skin in the form of an aerosol. It can also be in solid form, and for example in the form of a stick or a patch. It can be used as a care product, as a cleaning product, as a makeup product or even as a simple deodorant product.
• hair in the form of aqueous, alcoholic or hydroalcoholic solutions, or in the form of creams, gels, emulsions, foams or also in the form of aerosol compositions also comprising a propellant under pressure.
• the composition according to the invention can also be a composition for hair care, and in particular a shampoo, a styling lotion, a treating lotion, a cream or a styling gel, a composition of dyes (in particular oxidation dyes) optionally in the form of coloring shampoos, a restructuring hair lotion, a composition of perm (in particular a composition for the first time of a perm), a lotion or hair loss gel, pest control shampoo, etc.
• a composition for hair care and in particular a shampoo, a styling lotion, a treating lotion, a cream or a styling gel, a composition of dyes (in particular oxidation dyes) optionally in the form of coloring shampoos, a restructuring hair lotion, a composition of perm (in particular a composition for the first time of a perm), a lotion or hair loss gel, pest control shampoo, etc.
• the eyes For the eyes, it can be in the form of drops and for ingestion, it can be in the form of capsules, granules, syrups or tablets.
• compositions according to the invention are those conventionally used in the fields considered.
• compositions constitute in particular cleansing, protective 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, makeup remover creams, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, after-sun milks, lotions, gels or foams for skin care , such as cleansing lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, anti-hair loss compositions, aftershave gels or lotions, depilatory creams.
• compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.
• compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.
• the composition can also be for oral use, for example a toothpaste.
• the composition may contain adjuvants and additives customary for compositions for oral use and in particular surfactants, thickening agents, humectants, polishing agents such as silica, various active ingredients such as fluorides, in particular particularly sodium fluoride, and optionally sweetening agents such as sodium saccharinate.
• the proportion of the fatty phase can range from 5% to 80% by weight, and preferably from 5% to 50% by weight relative to the total weight of the composition.
• the oils, waxes, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetic field.
• the emulsifier and the coemulsifier are 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.
• the emulsion may, in addition, contain lipid vesicles.
• the fatty phase can represent more than 90% of the total weight of the composition.
• the cosmetic composition may also contain adjuvants customary in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters, odor absorbers and coloring matters.
• adjuvants customary in the cosmetic field such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters, odor absorbers and coloring matters.
• the amounts of these various adjuvants are those conventionally used in the cosmetic field, and for example from 0.01% to 10% of the total weight of the composition.
• These adjuvants depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid spherules.
• emulsifiers used in the invention there may be mentioned for example glycerol stearate, polysorbate 60 and the PEG-6 / PEG-32 / glycol stearate sold under the name Tefose ® 63 by the company Gattefosse.
• hydrophilic gelling agents which can be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose, polyethylene.
• composition may contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.
• hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.
• retinol and its derivatives
• tocopherol vitamin E
• essential fatty acids ceramides
• essential oils ceramides
• the composition can combine at least one compound of formula (I) with other active agents.
• active agents there may be mentioned by way of example: agents which improve the activity on regrowth and / or on the braking of hair loss, and which have already been described for this activity, for example the esters of nicotinic acid, including in particular tocopherol nicotinate, benzyl nicotinate and C ⁇ -CQ alkyl nicotinates such as methyl or hexane nicotinates, pyrimidine derivatives, such as those described by the Applicant in the Patent EP 0 540 629, particularly 2,4-diamino pyrimidine 3-oxide or "Aminexil", those described in patents US 4,139,619 and US 4,596,812, particularly 2,4-diamino 6-piperidinopyrimidine 3-oxide or "Minoxidil", agents promoting hair regrowth such as those described by the Applicant in patents EP-
• agents modulating differentiation and / or proliferation and / or skin pigmentation such as retinoic acid and its isomers, retinol and its esters, vitamin D and its derivatives, estrogens such as estradiol, kojic acid or hydroquinone;
• - antibacterials such as clindamycin phosphate, erythromycin or tetracycline class antibiotics
• - antifungals in particular compounds belonging to the class of imidazoles such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such as terbinafine, or octopirox;
• anti-inflammatory agents different from the compounds of formula (I) according to the invention, chosen for example from the so-called “steroidal” anti-inflammatory agents, such as hydrocortisone, betamethasone valerate or clobetasol propionate, or other anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetaminophen or glycyrrhizic acid or peptides such as for example a peptide containing the chain of amino acids Lysine-Proline-Valine described in particular by the Applicant in patent EP 0 759 292; and / or prostaglandin-H Synthase inhibitors (PGHS-1 and / or PGHS-2 also called respectively Cox-1 and Cox-2), chosen essentially from the so-called “non-steroidal” anti-inflammatory drugs (NSAIDs) such as salycilates, p-aminophenols, indoles, heteroarylacetic acids, aryl
• Lix lipoxygenase inhibitors
• hydroxamic acid and hydroxamates such as hydroxamic acid and hydroxamates, alkylhydroxyamino acids, N-hydroxyurea derivatives and more particularly Zyleuton and nordihydroguaiaretic acid (NDGA) as described in the documents Biochemistry 1994, 33, 13391-13400 and Pharmaceurtical Research, Vol. 9, NM 1, 1992;
• - anesthetic agents such as lidocaine hydrochloride and its derivatives
• - antipruritic agents such as thenaldine, trimeprazine or cyproheptadine;
• keratolytic agents such as ⁇ - and ⁇ -hydroxycarboxylic or ⁇ - and ⁇ -ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, citric acid and generally fruit acids, and n-octanoyl-5-salicylic acid;
• - anti-free radical agents such as ⁇ -tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters;
• - antiseborrheics such as progesterone
• - anti-dandruff agents such as octopirox or zinc pyrithione
• - anti-acne drugs such as retinoic acid or benzoyl peroxide
• the composition according to the invention also comprises at least one agent chosen from antibacterial agents, antiparasitics, antifungals, antivirals, anti-inflammatories, antipruritics, anesthetics, keratolytics, anti -free radicals, anti-seborrhoeics, anti-dandruff, anti-acne and / or agents decreasing differentiation and / or proliferation and / or skin pigmentation, agents improving activity on regrowth and / or braking hair loss, extracts of plant and / or bacterial origin.
• at least one agent chosen from antibacterial agents, antiparasitics, antifungals, antivirals, anti-inflammatories, antipruritics, anesthetics, keratolytics, anti -free radicals, anti-seborrhoeics, anti-dandruff, anti-acne and / or agents decreasing differentiation and / or proliferation and / or skin pigmentation, agents improving activity on regrowth and / or
• composition comprising at least one compound as defined above is in liposomal form, as described in particular in patent application WO 94/22468 filed on October 13, 1994 by the company Anti Cancer Inc.
• the compound encapsulated in liposomes can be delivered selectively to the hair follicle.
• a sodium salt solution of 4,5-diphenyl imidazole is prepared by reacting 4,5-diphenyl imidazole with an equivalent of sodium hydride in dimethylformamide (DMF) under argon at 50 ° C for 1 h. The solution is then distributed in the tubes of a multi-well reaction block at the rate of 3 mmol per tube. 1.2 molar equivalents of alkyl halide and potassium iodide in solution in DMF are then added to each tube and the whole is heated at 50 ° C. for 15 h. Each reaction mixture is taken up in dichloromethane and washed twice with water and with bicarbonate. The organic phases are dried over sodium sulfate and evaporated to dryness.
• DMF dimethylformamide
• NHEK Normal human epidermal keratinocytes sold by the company Clonetics and distributed in France by the company TEBU are incubated in the presence of 160 nM of PMA for 24 hours at 37 ° C.
• the production of the chemotactic agent Interleukin 8 (IL-8) is measured by enzymatic assay by means of an assay kit (Elisa D8050) marketed by the company R&D.
• the absorbance values are measured with a microplate reader (MRX / Dynatech) according to the procedures supplied with the assay kit.
• MRX / Dynatech microplate reader
• the results are expressed as a percentage of the control values after subtracting the background noise and as a percentage of inhibition of these values obtained in the presence of the compounds.
• the results of the comparative test show that the percentage of inhibition measured (inhibition of the response of superficial epidermal cells to an irritant agent by assaying the interleukin-8 secreted by NHEK cells after stimulation with PMA as an irritant agent) , is better for the compound according to the invention compared to the reference compounds of the prior art (US 3,759,946).
• compositions were obtained by simple mixing of the various components.
• This gel is applied to the skin, once or twice a day.
• Anti-irritant hair loss lotion
• This lotion is applied once or twice a day, at a rate of 1 ml per application.
• Thickened lotion - 3-benzyloxy-propyl- (4,5 diphenyl-imidazol) 1-yl 1.0%
• This lotion is applied once or twice a day, at the rate of 1 ml per application.
• This thickened lotion is applied at a rate of 1 ml per application.

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• 2001
  • 2001-04-24 FR FR0105497A patent/FR2823747B1/fr not_active Expired - Fee Related
• 2002
  • 2002-04-24 WO PCT/FR2002/001411 patent/WO2002085863A1/fr not_active Application Discontinuation
  • 2002-04-24 KR KR1020067005892A patent/KR100667647B1/ko not_active IP Right Cessation
  • 2002-04-24 CN CNB02812099XA patent/CN1330637C/zh not_active Expired - Fee Related
  • 2002-04-24 JP JP2002583390A patent/JP2004528333A/ja not_active Withdrawn
  • 2002-04-24 US US10/475,652 patent/US20040192928A1/en not_active Abandoned
  • 2002-04-24 KR KR1020037013961A patent/KR100602826B1/ko not_active IP Right Cessation
  • 2002-04-24 EP EP02726274A patent/EP1385827A1/de not_active Withdrawn

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