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EP1278509A1 - Lipochroman-6 as no-synthase inhibitor and uses - Google Patents

Lipochroman-6 as no-synthase inhibitor and uses

Info

Publication number
EP1278509A1
EP1278509A1 EP01929750A EP01929750A EP1278509A1 EP 1278509 A1 EP1278509 A1 EP 1278509A1 EP 01929750 A EP01929750 A EP 01929750A EP 01929750 A EP01929750 A EP 01929750A EP 1278509 A1 EP1278509 A1 EP 1278509A1
Authority
EP
European Patent Office
Prior art keywords
composition
lipochroman
intended
use according
skin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP01929750A
Other languages
German (de)
French (fr)
Inventor
Marie-Madeleine Cals-Grierson
Pascale Pelletier
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LOreal SA
Original Assignee
LOreal SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LOreal SA filed Critical LOreal SA
Publication of EP1278509A1 publication Critical patent/EP1278509A1/en
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61Q19/08—Anti-ageing preparations
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • 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
    • A61P17/14—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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • Lipochroman-6 as a NO-synthase inhibitor and uses
  • the subject of the present invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit NO synthase.
  • NO-synthase covers a family of enzymes which ensure the enzymatic catalysis of L-arginine into citrulline, during which catalysis is produced a gaseous mediator with multiple functions, nitrogen monoxide or NO.
  • NO-synthases exist in three forms, two constitutive forms, nomenclature grouping together neuronal NO-synthase (or NOS 1) and endothelial NO-synthase (or NOS 3), and the inducible form (or NOS 2) (Medicine / Sciences , 1992, 8, pp. 843-845).
  • NO-synthase covers all of the isoforms of the enzyme.
  • NO-synthase inhibitors is understood to mean any product which, in the end, results, notwithstanding the isoform of NO-synthase, in the reduction of the concentration of NO.
  • Nitric oxide has, by its structure, an additional electron making it extremely chemically reactive. It is well known that such compounds are harmful and we seek to limit their production as much as possible. Thus, in the case of nitric oxide, the NO-synthase inhibitors have been widely studied.
  • NO is a multifunctional signal molecule active in a wide variety of body systems and tissues.
  • cardiovascular system regulatory effect, inhibitor of platelet aggregation with effect anticoagulant
  • nervous system memory, modulation of neurotransmitter release
  • immunological system modulation immune defenses, inflammation, involvement in autoimmune pathologies.
  • NO plays a predominant role in the skin.
  • NO can be synthesized by all varieties of cells constituting the skin and as such it intervenes in multiple and complex regulatory processes such as the regulation of cell differentiation and / or proliferation, vasodilation, melanogenesis , the response to environmental variations (homeostasis. Its involvement in cell differentiation and proliferation (stimulating effect), particularly of keratinocytes, associates it as well with the growth of the epidermis and scarring as with hyperproliferative disorders ( Due to its electronic hyperreactivity which can lead to cell degradation or even destruction, NO is involved in apoptotic processes and in the intrinsic and / or extrinsic aging of the skin. It intervenes in the cutaneous immunological and inflammatory processes.
  • NO plays a role in contact hypersensitivity reactions, in allergic skin manifestations, in the skin's immune response.
  • it is the mediator between neuropeptides such as substance P and / or the peptide associated with the calcitonin gene (calcitonin gene related peptide or CGRP) in cutaneous neurogenic inflammatory processes, hence its implication in so-called sensitive skin phenomena.
  • CGRP calcitonin gene related peptide
  • NO is recognized as an intermediate in melanogenesis induced by type B ultraviolet radiation (UVB). It is also one of the factors involved in hypermelanosis-like disorders. NO also seems to be involved in the control of sweating as well as in that of lipolysis (inhibitory effect) or even in hair loss. Finally, NO is known to have an influence on the barrier function of the skin and therefore on its hydration (inhibitory effect).
  • UVB type B ultraviolet radiation
  • NMMA N G -monomethyl-L-arginine
  • NAME the methyl ester of N G -nitro-L-arginine
  • NNA N G -nitro-L-arginine
  • NAA N G - amino-L-arginine
  • ADMA diphenyleneiodonium chloride
  • 2- (4-carboxy ⁇ henyl) -4,4,5 5-tetramethylimidazoline-1-oxy-3-oxide
  • the object of the present invention is to provide a new inhibitor of NO-synthase which is moreover a natural inhibitor of NO-synthase.
  • lipochroman-6 has the property of being an inhibitor of NO synthase, particularly of inducible NO synthase (NOS 2), which makes it a good candidate for uses in applications where it proves interesting to use an inhibitor of NO-synthase, particularly in cosmetics.
  • NOS 2 inducible NO synthase
  • Lipochroman-6 is a compound corresponding to the general formula:
  • This compound is described in the prior art as an antioxidant, as a free radical scavenger, as an inhibitor of lipid peroxidation and as a cell protector against damage induced by peroxynitrite. However, it is not described as an inhibitor of NO-synthase.
  • the primary object of the invention is therefore the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman- ⁇ or the composition being intended to inhibit NO synthase.
  • physiologically acceptable medium is understood a compatible medium with the skin, mucous membranes, nails, hair.
  • a second object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the lipochroman-6 or the composition being intended for an application. in all areas in which inhibition of NO synthases is necessary, particularly in the skin and / or capillary area.
  • Lipochroman-6 or the composition containing it can be used to slow down or even inhibit cell differentiation and / or proliferation, and / or vasodilation, and or melanogenesis, and / or the response to environmental variations (homeostasis).
  • the third object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended for slow down or even inhibit cell differentiation and / or proliferation, particularly to regulate the growth of the epidermis and / or treat hyperproliferative disorders such as psoriasis.
  • a fourth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit the degradation and / or destruction of cells and to inhibit apoptotic processes, particularly of skin cells, very particularly of keratinocytes and / or to treat the intrinsic and / or extrinsic aging of cells, particularly of skin cells.
  • a fifth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit or even suppress the immunological and or inflammatory processes linked to the synthesis of NO, such as for example contact hypersensitivity reactions and / or allergic manifestations and / or the immune response, particularly in the skin.
  • lipochroman-6 or the composition are intended to decrease or even inhibit skin inflammation, particularly the neurogenic inflammatory skin processes, and therefore to treat so-called sensitive skin.
  • the sixth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to treat the rosacea and / or skin erythema, particularly erythema induced by ultraviolet radiation and / or localized or diffuse erythematous rashes on the skin such as those caused by drugs, toxins and / or viral or bacterial infections.
  • a seventh subject of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit the melanogenesis induced by ultraviolet radiation of type A and or B and / or to treat disorders of hypermelanosis type.
  • the eighth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to control the sweating and / or stimulating lipolysis and / or inhibiting hair loss and / or strengthening the barrier function of the skin and or stimulating hydration of the skin.
  • the composition comprising lipochroman-6 can be a cosmetic or dermatological composition.
  • the composition is a cosmetic composition.
  • the lipochroman-6 or the composition comprising it is applied to the skin topically.
  • the amount of lipochroman-6 extract used in the composition is of course a function of the desired effect and can therefore vary to a large extent.
  • lipochroman-6 can be used in an amount representing from 10 "4 % to 20% of the total weight of the composition and preferably in an amount representing from 5.10 " 3 % to 10% of the total weight of the composition.
  • lipochroman-6 can be combined with other NO synthase inhibitors such as plant extracts, for example an extract of at least one plant of the species Olea europaea or an extract of Ginkgo biloba or an extract of Vitis vinifera or an extract of green tea or cocoa.
  • plant extracts for example an extract of at least one plant of the species Olea europaea or an extract of Ginkgo biloba or an extract of Vitis vinifera or an extract of green tea or cocoa.
  • the ninth subject of the invention is a cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that it is used by application on the skin, on the hair, and / or on the mucous membranes , a cosmetic composition comprising at least lipochroman-6 in a physiologically acceptable medium.
  • the cosmetic treatment method of the invention aims to improve the appearance of the individual affected by the disorders due to the synthesis of NO.
  • the cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the usual technique for using these compositions.
  • the cosmetic compositions as defined above, according to the usual technique for using these compositions.
  • composition according to the invention in which the lipochroman-6 is used, it can be ingested, injected 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). Depending on the mode of administration, the composition according to the invention can be in all the dosage forms normally used.
  • 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 fatty phase 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 Ionic and / or nonionic type vesicular dispersions.
  • These compositions are prepared according to the usual methods.
  • They can also be used for the 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 may be in the form of an aqueous, oily lotion or in the form of a serum.
  • the eyes it can be in the form of drops and for ingestion, it can be in the form of capsules, granules of syrups or tablets.
  • compositions according to the invention are those conventionally used in the fields considered.
  • compositions constitute in particular cleansing, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, make-up remover creams, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, anti-sun milks, lotions, gels or foams for care of the skin, such as cleansing lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, pain relieving compositions, compositions for treating certain skin diseases such as eczema, rosacea, psoriasis, lichens, severe pruritus.
  • 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 according to the invention may also be a composition for hair care, and in particular a shampoo, a styling lotion, a treating lotion, a styling cream or gel, a composition of dyes (in particular oxidation dyes) in the form of coloring shampoos, restructuring hair lotions, a perm composition (in particular a composition for the first time of a perm), a fall prevention lotion or gel, an antiparasitic shampoo, etc.
  • 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 phase. fatty 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 which can be used in the invention, there may be mentioned, for example, glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / Glycol Stearate sold under the name Tefose ⁇ 63 by the company Gattefosse.
  • solvents which can be used in the invention mention may be made of lower alcohols, in particular ethanol and isopropanol, propylene glycol.
  • 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.
  • carboxyvinyl polymers carboxyvinyl polymers
  • acrylic copolymers such as acrylate / alkylacrylate copolymers
  • polyacrylamides polysaccharides
  • polysaccharides such as hydroxypropylcellulose
  • natural gums and clays and, as lipophilic gelling agents
  • modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica,
  • composition may contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, aliantoin, 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, aliantoin, 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 lipochroman-6 extract with other active agents intended in particular for the prevention and / or treatment of skin conditions.
  • active agents there may be mentioned by way of example: - 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, kojic acid or hydroquinone;
  • - antibacterials such as clindamycin phosphate, erythromycin or antibiotics of the tetracycline class
  • - antifungals in particular compounds belonging to the class of imidazoles such as Peconazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such as terbinafine , or octopirox; - non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid;
  • - anesthetic agents such as lidocaine hydrochloride and its derivatives
  • - antipruritic agents such as thenaldine, trimeprazine or cyproheptadine;
  • - keratolytic agents such as alpha- and beta-hydroxycarboxylic or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, acid citric and generally fruit acids, and n-octanoyl-5-salicylic acid;
  • - anti-free radical agents such as Palpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters;
  • - anti-seborrheic drugs such as progesterone
  • - anti-dandruff agents such as octopirox or zinc pyrithione
  • - anti-acne drugs such as retinoic acid or benzoyl peroxide
  • compositions illustrate the invention without limiting it in any way.
  • proportions indicated are percentages by weight.
  • Example 1 Biological activity of lipochroman-6: The activity of lipochroman-6 on inducible NO synthase was evaluated in the test described by Heck et al. (JBC, Vol. 267, No. 30, 21277-21280, October 25, 1992). The objective of this test is to show the decrease in the nitrate concentration and nitrite, in fine, after stimulation of NO-synthase 2.
  • A positive control (induction of the enzyme): mixtures of interferon- ⁇ (1000U7ml) and Interleukin 1- ⁇ (100 U / ml);
  • B negative control (maximum inhibition): N G- monomethyl-L-arginine (form L) at 200 ⁇ M; inhibition specificity control: N G -monomethyl-L-arginine (form D) at 200 ⁇ M.
  • the quantity of stable NO reaction products is measured using the “nitric colorimetric assay” kit sold by the company Boehringer under the reference 1756.28.
  • Lipochroman-6 was tested at concentrations of 0.005% and 0.01% (weight / volume) in ethanol.
  • Lipochroman-6 has an inhibitory effect on inducible NO synthase.
  • Composition 1 Face gel
  • composition 3 Lipochroman-6 gel for care 3.00%
  • Composition 4 Care cream (oil in water emulsion)
  • Composition 5 Lipochroman-6 shampoo 0.50% Hydroxypropylcellulose * 1.00% Perfume 0.50% Preservative 0.30% Water qs 100%
  • Composition 6 Care cream (oil / water emulsion) Lipochroman-6 5.00% Glycerol stearate 2.00% Polysorbate 60 ** 1.00% Stearic acid 1.40% n-Octanoyl-5-salicylic acid 0.50% Triethanolamine 0.70% Carbomer 0.40%
  • Composition 7 Pain relief gel
  • Composition 8 Sun erythema care cream (emulsioonn hhuuiillee - ddaannss- -eeaaui) Lipochroman-6 5.00%
  • composition 9 Gel for the treatment of acne
  • Composition 10 Lotion for eliminating scars due to acne
  • Example 3 Effect of composition 1 of Example 2 on sensitive skin. It has been shown that sensitive skin is characterized by a very strong neurosensory reactivity of the skin to topical application to the face of capsaicin. (Magnusson and Koskinen, Acta Derm. Venereol. (Stockh), 1996, 76, 129-132).
  • Example 2 The composition of Example 2 was therefore tested on a population (15 volunteers) of people with the characteristics of sensitive skin, in comparison with the same composition not containing Lipochroman-6.
  • composition and control are applied to the face at the angle of the cheeks, randomly double blind. 30 minutes after treatment, a 0.075% capsaicin cream is applied to the treated areas.
  • the gel containing lipochroman-6 has a protective effect against the itching sensation induced by capsaicin

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Abstract

The invention concerns the use of an efficient amount of lipochroman-6 in a physiologically acceptable medium, in a composition or for preparing a composition, the lipochroman-6 or the composition being designed to inhibit NO-synthase.

Description

Lipochroman-6 comme inhibiteur de NO-synthase et utilisations Lipochroman-6 as a NO-synthase inhibitor and uses
La présente invention a pour objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à inhiber la NO-synthase.The subject of the present invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit NO synthase.
Le terme NO-synthase recouvre une famille d'enzymes qui assurent la catalyse enzymatique de la L-arginine en citrulline, catalyse au cours de laquelle est produit un médiateur gazeux aux multiples fonctions, le monoxyde d'azote ou NO.The term NO-synthase covers a family of enzymes which ensure the enzymatic catalysis of L-arginine into citrulline, during which catalysis is produced a gaseous mediator with multiple functions, nitrogen monoxide or NO.
Les NO-synthases existent sous trois formes, deux formes constitutives, nomenclature regroupant la NO-synthase neuronale (ou NOS 1) et la NO-synthase endothéliale (ou NOS 3), et la forme inductible (ou NOS 2) (Médecine/Sciences, 1992, 8, pp. 843-845).NO-synthases exist in three forms, two constitutive forms, nomenclature grouping together neuronal NO-synthase (or NOS 1) and endothelial NO-synthase (or NOS 3), and the inducible form (or NOS 2) (Medicine / Sciences , 1992, 8, pp. 843-845).
On comprend par ailleurs dans le texte que sans indication contraire le terme NO-synthase recouvre l'ensemble des isoformes de l'enzyme.It is also understood in the text that without the contrary indication the term NO-synthase covers all of the isoforms of the enzyme.
Ainsi, selon l'invention on entend par inhibiteurs de NO-synthase, tout produit qui in fineconduit, nonobstant l'isoforme de NO-synthase, à la diminution de la concentration de NO. On peut citer à titre d'exemple les produits qui diminuent la quantité de NO-synthase active, qui bloquent l'activité enzymatique de la NO- synthase ou son induction ou qui inhibent l'activité du NO produit.Thus, according to the invention, the term NO-synthase inhibitors is understood to mean any product which, in the end, results, notwithstanding the isoform of NO-synthase, in the reduction of the concentration of NO. By way of example, mention may be made of products which reduce the amount of active NO-synthase, which block the enzymatic activity of NO-synthase or its induction or which inhibit the activity of NO produced.
Le monoxyde d'azote possède de par sa structure un électron supplémentaire le rendant extrêmement réactif chimiquement. Il est notoire que de tels composés sont nocifs et l'on cherche à limiter au mieux leur production. C'est ainsi que dans le cas du monoxyde d'azote les inhibiteurs de NO-synthase ont été largement étudiés.Nitric oxide has, by its structure, an additional electron making it extremely chemically reactive. It is well known that such compounds are harmful and we seek to limit their production as much as possible. Thus, in the case of nitric oxide, the NO-synthase inhibitors have been widely studied.
Le NO est une molécule signal multifonctioηnelle active dans une grande variété de systèmes et de tissus du corps. Outre ses effets dommageables pour les cellules liés à son hyperréactivité due à sa structure comprenant un électron supplémentaire, elle est reconnue entre autre comme intervenant particulièrement dans le système cardiovasculaire (régulateur de la pression sanguine avec effet vasodilatateur, inhibiteur de l'agrégation plaquettaire avec effet anticoagulant), dans le système nerveux (mémoire, modulation de la libération des neurotransmetteurs), dans le système immunologique (modulation des défenses immunitaires, inflammation, implication dans les pathologies auto- immunes).NO is a multifunctional signal molecule active in a wide variety of body systems and tissues. In addition to its damaging effects on cells linked to its hyperreactivity due to its structure comprising an additional electron, it is recognized, among other things, as particularly involved in the cardiovascular system (regulator of blood pressure with vasodilator effect, inhibitor of platelet aggregation with effect anticoagulant), in the nervous system (memory, modulation of neurotransmitter release), in the immunological system (modulation immune defenses, inflammation, involvement in autoimmune pathologies).
Il est maintenant bien admis que le NO joue un rôle prépondérant dans la peau. Le NO peut être synthétisé par toutes les variétés de cellules constituant la peau et à ce titre il intervient dans de multiples et complexes processus de régulation tels que la régulation de la différenciation et/ou de la prolifération cellulaire, de la vasodilatation, de la melanogenese, de la réponse aux variations environnementales (homéostasie . Son implication dans la différenciation et la prolifération cellulaire (effet stimulateur), particulièrement des kératinocytes, l'associe aussi bien à la croissance de l'épiderme et à la cicatrisation qu'aux désordres hyperprolifératifs (psoriasis). Du fait de son hyperréactivité électronique pouvant entraîner une dégradation voire une destruction des cellules, le NO est impliqué dans les processus apoptotiques et dans le vieillissement intrinsèque et/ou extrinsèque de la peau. Il intervient dans les processus immunologiques et inflammatoires cutanés. Il est en effet communément admis que le NO joue un rôle dans les réactions d'hypersensibilité de contact, dans les manifestations allergiques cutanées, dans la réponse immunitaire de la peau. De même, outre son rôle proinflammatoire direct, il est le médiateur entre les neuropeptides comme la substance P et/ou le peptide associé au gène de la calcitonine (calcitonin gène related peptide ou CGRP) dans les processus inflammatoires neurogéniques cutanés, d'où son implication dans les phénomènes de peau dite sensible. L'implication du NO dans la vasodilatation fait qu'il est associé aux érythèmes cutanés, particulièrement les érythèmes induits par les rayonnements ultra-violets, aux éruptions érythémateuses localisées ou diffuses de la peau comme celles causées par les drogues les toxines et/ou les infections virales ou bactériennes, à la rosacée. Le NO est reconnu comme intermédiaire dans la melanogenese induite par les rayonnements ultra-violets de type B (UVB). Il serait aussi un des facteurs intervenant dans les désordres de type hypermélanose. Le NO semble également impliqué dans le contrôle de la sudation ainsi que dans celui de la lipolyse (effet inhibiteur) ou encore dans la chute des cheveux. Enfin, le NO est connu pour avoir une influence sur la fonction barrière de la peau et donc sur l'hydratation de celle-ci (effet inhibiteur).It is now well recognized that NO plays a predominant role in the skin. NO can be synthesized by all varieties of cells constituting the skin and as such it intervenes in multiple and complex regulatory processes such as the regulation of cell differentiation and / or proliferation, vasodilation, melanogenesis , the response to environmental variations (homeostasis. Its involvement in cell differentiation and proliferation (stimulating effect), particularly of keratinocytes, associates it as well with the growth of the epidermis and scarring as with hyperproliferative disorders ( Due to its electronic hyperreactivity which can lead to cell degradation or even destruction, NO is involved in apoptotic processes and in the intrinsic and / or extrinsic aging of the skin. It intervenes in the cutaneous immunological and inflammatory processes. It is indeed commonly accepted that NO plays a role in contact hypersensitivity reactions, in allergic skin manifestations, in the skin's immune response. Similarly, in addition to its direct proinflammatory role, it is the mediator between neuropeptides such as substance P and / or the peptide associated with the calcitonin gene (calcitonin gene related peptide or CGRP) in cutaneous neurogenic inflammatory processes, hence its implication in so-called sensitive skin phenomena. The involvement of NO in vasodilation makes it associated with skin erythema, particularly erythema induced by ultraviolet radiation, localized or diffuse erythematous rashes of the skin such as those caused by drugs, toxins and / or viral or bacterial infections, rosacea. NO is recognized as an intermediate in melanogenesis induced by type B ultraviolet radiation (UVB). It is also one of the factors involved in hypermelanosis-like disorders. NO also seems to be involved in the control of sweating as well as in that of lipolysis (inhibitory effect) or even in hair loss. Finally, NO is known to have an influence on the barrier function of the skin and therefore on its hydration (inhibitory effect).
On comprend donc l'intérêt qui existe à disposer d'inhibiteurs des NO-synthases. A cet égard de nombreux inhibiteurs ont déjà été proposés dans l'art antérieur. On peut citer plus particulièrement la NG-monométhyl-L-arginine (NMMA), l'ester méthylé de la NG-nitro-L-arginine (NAME), la NG-nitro-L-arginine (NNA), la NG- amino-L-arginine (NAA), la NG.NG-diméthyl-arginine (la diméthylarginine asymétrique, dénommée ADMA), le chlorure de diphenyleneiodonium, le 2-(4-carboxyρhényl)-4,4,5,5-tetraméthylimidazoline-1-oxy-3-oxyde, laWe therefore understand the interest that exists in having inhibitors of NO-synthases. In this regard, numerous inhibitors have already been proposed in the prior art. Mention may more particularly be made of N G -monomethyl-L-arginine (NMMA), the methyl ester of N G -nitro-L-arginine (NAME), N G -nitro-L-arginine (NNA), N G - amino-L-arginine (NAA), N G .N G -dimethyl-arginine (asymmetric dimethylarginine, called ADMA), diphenyleneiodonium chloride, 2- (4-carboxyρhenyl) -4,4,5 , 5-tetramethylimidazoline-1-oxy-3-oxide, the
7-nitroindazole, la N(5)-(1-iminoéthyl)-L-ornithine, Paminoguanidine, la canavanine et l'ebselen. Sans mettre en doute l'efficacité de ces produits, on note qu'il s'agit de composés chimiques qui peuvent induire des désagréments chez l'utilisateur voire des effets secondaires néfastes, qui de manière générale préfère utiliser des produits naturels.7-nitroindazole, N (5) - (1-iminoethyl) -L-ornithine, Paminoguanidine, canavanine and ebselen. Without questioning the effectiveness of these products, we note that these are chemical compounds which can induce inconvenience in the user or even harmful side effects, who generally prefer to use natural products.
Le but de la présente invention est de fournir un nouvel inhibiteur de NO-synthase qui plus est un inhibiteur naturel de NO-synthase.The object of the present invention is to provide a new inhibitor of NO-synthase which is moreover a natural inhibitor of NO-synthase.
De manière surprenante et inattendue, la demanderesse a démontré que le lipochroman-6 présente la propriété d'être un inhibiteur de NO-synthase, particulièrement de la NO-synthase inductible (NOS 2) ce qui en fait un bon candidat pour des utilisations dans des applications où il s'avère intéressant d'utiliser un inhibiteur de NO-synthase, particulièrement en cosmétique.Surprisingly and unexpectedly, the Applicant has demonstrated that lipochroman-6 has the property of being an inhibitor of NO synthase, particularly of inducible NO synthase (NOS 2), which makes it a good candidate for uses in applications where it proves interesting to use an inhibitor of NO-synthase, particularly in cosmetics.
Le lipochroman-6 est un composé répondant à la formule générale :Lipochroman-6 is a compound corresponding to the general formula:
Ce composé est décrit dans l'art antérieur comme un anti-oxydant, comme piégeur de radicaux libres, comme inhibiteur de la peroxydation des lipides et comme protecteur des cellules contre les dommages induits par le peroxynitrite. Cependant, il n'est pas décrit comme inhibiteur de NO-synthase.This compound is described in the prior art as an antioxidant, as a free radical scavenger, as an inhibitor of lipid peroxidation and as a cell protector against damage induced by peroxynitrite. However, it is not described as an inhibitor of NO-synthase.
L'invention a donc pour objet premier l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-β ou la composition étant destinés à inhiber la NO-synthase.The primary object of the invention is therefore the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-β or the composition being intended to inhibit NO synthase.
Par milieu physiologiquement acceptable, on comprend un milieu compatible avec la peau, les muqueuses, les ongles, les cheveux.By physiologically acceptable medium is understood a compatible medium with the skin, mucous membranes, nails, hair.
L'invention a pour second objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à une application dans tous les domaines dans lesquels une inhibition des NO-synthases s'avère nécessaire, particulièrement dans le domaine cutané et/ou capillaire.A second object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the lipochroman-6 or the composition being intended for an application. in all areas in which inhibition of NO synthases is necessary, particularly in the skin and / or capillary area.
Le lipochroman-6 ou la composition le contenant peuvent être utilisés pour ralentir voire inhiber la différenciation et/ou la prolifération cellulaire, et/ou la vasodilatation, et ou la melanogenese, et/ou la réponse aux variations environnementales (homéostasie).Lipochroman-6 or the composition containing it can be used to slow down or even inhibit cell differentiation and / or proliferation, and / or vasodilation, and or melanogenesis, and / or the response to environmental variations (homeostasis).
Ainsi, l'invention a pour troisième objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à ralentir voire inhiber la différenciation et/ou la prolifération cellulaire, particulièrement à réguler la croissance de l'épiderme et/ou à traiter les désordres hyperprolifératifs comme par exemple le psoriasis.Thus, the third object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended for slow down or even inhibit cell differentiation and / or proliferation, particularly to regulate the growth of the epidermis and / or treat hyperproliferative disorders such as psoriasis.
L'invention a pour quatrième objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à inhiber la dégradation et/ou la destruction des cellules et a inhiber les processus apoptotiques, particulièrement des cellules de la peau, très particulièrement des kératinocytes et/ou à traiter le vieillissement intrinsèque et/ou extrinsèque des cellules, particulièrement des cellules de la peau.A fourth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit the degradation and / or destruction of cells and to inhibit apoptotic processes, particularly of skin cells, very particularly of keratinocytes and / or to treat the intrinsic and / or extrinsic aging of cells, particularly of skin cells.
L'invention a pour cinquième objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à inhiber voire supprimer les processus immunologiques et ou inflammatoires liés à la synthèse de NO, comme par exemple les réactions d'hypersensibilité de contact et/ou les manifestations allergiques et/ou la réponse immunitaire, particulièrement au niveau de la peau. Particulièrement le lipochroman-6 ou la composition sont destinés à diminuer voir inhiber l'inflammation cutanée, particulièrement les processus inflammatoires neurogéniques cutanés, et donc à traiter les peaux dites sensibles.A fifth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit or even suppress the immunological and or inflammatory processes linked to the synthesis of NO, such as for example contact hypersensitivity reactions and / or allergic manifestations and / or the immune response, particularly in the skin. Particularly the lipochroman-6 or the composition are intended to decrease or even inhibit skin inflammation, particularly the neurogenic inflammatory skin processes, and therefore to treat so-called sensitive skin.
L'invention a pour sixième objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à traiter la rosacée et/ou les érythèmes cutanés, particulièrement les érythèmes induits par les rayonnements ultra-violets et/ou les éruptions erythemateuses localisées ou diffuses de la peau comme celles causées par les drogues les toxines et/ou les infections virales ou bactériennes.The sixth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to treat the rosacea and / or skin erythema, particularly erythema induced by ultraviolet radiation and / or localized or diffuse erythematous rashes on the skin such as those caused by drugs, toxins and / or viral or bacterial infections.
L'invention a pour septième objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à inhiber la melanogenese induite par les rayonnements ultra-violets de type A et ou B et/ou à traiter les désordres de type hypermélanose.A seventh subject of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit the melanogenesis induced by ultraviolet radiation of type A and or B and / or to treat disorders of hypermelanosis type.
L'invention a pour huitième objet l'utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à contrôler la sudation et/ou à stimuler la lipolyse et/ou a inhiber la chute des cheveux et/ou à renforcer la fonction barrière de la peau et ou à stimuler l'hydratation de la peau.The eighth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to control the sweating and / or stimulating lipolysis and / or inhibiting hair loss and / or strengthening the barrier function of the skin and or stimulating hydration of the skin.
Selon l'invention, la composition comprenant le lipochroman-6 peut être une composition cosmétique ou dermatologique. Préférentiellement selon l'invention, la composition est une composition cosmétique.According to the invention, the composition comprising lipochroman-6 can be a cosmetic or dermatological composition. Preferably according to the invention, the composition is a cosmetic composition.
Préférentiellement selon l'invention, le lipochroman-6 ou la composition le comprenant est appliqué sur la peau de manière topique.Preferably according to the invention, the lipochroman-6 or the composition comprising it is applied to the skin topically.
Selon l'invention, la quantité d'extrait lipochroman-6 utilisée dans la composition est bien entendu fonction de l'effet recherché et peut donc varier dans une large mesure.According to the invention, the amount of lipochroman-6 extract used in the composition is of course a function of the desired effect and can therefore vary to a large extent.
Pour donner un ordre de grandeur, selon l'invention, le lipochroman-6 peut être utilisé en une quantité représentant de 10"4% à 20% du poids total de la composition et préférentiellement en une quantité représentant de 5.10"3% à 10% du poids total de la composition.To give an order of magnitude, according to the invention, lipochroman-6 can be used in an amount representing from 10 "4 % to 20% of the total weight of the composition and preferably in an amount representing from 5.10 " 3 % to 10% of the total weight of the composition.
Bien entendu, selon l'invention le lipochroman-6 peut être associé à d'autres inhibiteurs de NO-synthases comme des extraits végétaux comme par exemple par exemple un extrait d'au moins un végétal de l'espèce Olea europaea ou un extrait de Ginkgo biloba ou un extrait de Vitis vinifera ou encore un extrait de thé vert ou de cacao.Of course, according to the invention lipochroman-6 can be combined with other NO synthase inhibitors such as plant extracts, for example an extract of at least one plant of the species Olea europaea or an extract of Ginkgo biloba or an extract of Vitis vinifera or an extract of green tea or cocoa.
L'invention a pour neuvième objet un procédé de traitement cosmétique en vue de traiter les désordres liés à la synthèse du NO, caractérisé par le fait que l'on utilise par application sur la peau, sur les cheveux, et/ou sur les muqueuses, une composition cosmétique comprenant au moins du lipochroman-6 dans un milieu physiologiquement acceptable.The ninth subject of the invention is a cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that it is used by application on the skin, on the hair, and / or on the mucous membranes , a cosmetic composition comprising at least lipochroman-6 in a physiologically acceptable medium.
Le procédé de traitement cosmétique de l'invention vise à améliorer l'aspect de l'individu atteint par les désordres dus à la synthèse du NO.The cosmetic treatment method of the invention aims to improve the appearance of the individual affected by the disorders due to the synthesis of NO.
Le procédé de traitement cosmétique de l'invention peut être mis en œuvre notamment en appliquant les compositions cosmétiques telles que définies ci- dessus, selon la technique d'utilisation habituelle de ces compositions. Ainsi par exemple il est possible d'effectuer des applications de crèmes, de gels, de sérums, de lotions, de laits de démaquillage ou de compositions anti-solaires sur la peau ou sur les cheveux secs, des applications d'une lotion pour cheveux sur cheveux mouillés, de shampooings, ou encore des applications de dentifrice sur les gencives.The cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the usual technique for using these compositions. Thus for example it is possible to carry out applications of creams, gels, serums, lotions, cleansing milks or anti-sun compositions on the skin or on dry hair, applications of a hair lotion on wet hair, shampoos, or even toothpaste applications on the gums.
Quelque soit la forme de la composition selon l'invention dans laquelle le lipochroman-6 est utilisé, celle-ci peut être ingérée, injectée ou appliquée sur la peau (sur toute zone cutanée du corps), les cheveux, les ongles ou les muqueuses (buccale, jugale, gingivale, génitale, conjonctive). Selon le mode d'administration, la composition selon l'invention peut se présenter sous toutes les formes galéniques normalement utilisées.Whatever the form of the composition according to the invention in which the lipochroman-6 is used, it can be ingested, injected 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). Depending on the mode of administration, the composition according to the invention can be in all the dosage forms normally used.
Pour une application topique sur la peau, la composition peut avoir la forme notamment de solution aqueuse ou huileuse ou de dispersion du type lotion ou sérum, d'émulsions de consistance liquide ou semi-liquide du type lait, obtenues par dispersion d'une phase grasse dans une phase aqueuse (H/E) ou inversement (E/H), ou de suspensions ou émulsions de consistance molle du type crème ou gel aqueux ou anhydres, ou encore de microcapsules ou microparticules, ou de dispersions vésiculaires de type ionique et/ou non ionique. Ces compositions sont préparées selon les méthodes usuelles.For topical application to the skin, 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 fatty phase 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 Ionic and / or nonionic type vesicular dispersions. These compositions are prepared according to the usual methods.
Elles peuvent être également utilisées pour les cheveux sous forme de solutions aqueuses, alcooliques ou hydroalcooliques, ou sous forme de crèmes, de gels, d'émulsions, de mousses ou encore sous forme de compositions pour aérosol comprenant également un agent propulseur sous pression.They can also be used for the 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.
Pour l'injection, la composition peut se présenter sous forme de lotion aqueuse, huileuse ou sous forme de sérum. Pour les yeux, elle peut se présenter sous forme de gouttes et pour l'ingestion, elle peut se présenter sous forme de capsules, de granulés de sirops ou de comprimés.For injection, the composition may be in the form of an aqueous, oily lotion or in the form of a serum. For the eyes, it can be in the form of drops and for ingestion, it can be in the form of capsules, granules of syrups or tablets.
Les quantités des différents constituants des compositions selon l'invention sont celles classiquement utilisées dans les domaines considérés.The amounts of the various constituents of the compositions according to the invention are those conventionally used in the fields considered.
Ces compositions constituent notamment des crèmes de nettoyage, de protection, de traitement ou de soin pour le visage, pour les mains, pour les pieds, pour les grands plis anatomiques ou pour le corps, (par exemple crèmes de jour, crèmes de nuit, crèmes démaquillantes, crèmes de fond de teint, crèmes anti-solaires), des fonds de teint fluides, des laits de démaquillage, des laits corporels de protection ou de soin, des laits anti-solaires, des lotions, gels ou mousses pour le soin de la peau, comme des lotions de nettoyage, des lotions anti-solaires, des lotions de bronzage artificiel, des compositions pour le bain, des compositions désodorisantes comprenant un agent bactéricide, des gels ou lotions après-rasage, des crèmes épilatoires, des compositions contre les piqûres d'insectes, des compositions anti-douleur, des compositions pour traiter certaines maladies de la peau comme l'eczéma, la rosasée, le psoriasis, les lichens, les prurits sévères.These compositions constitute in particular cleansing, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, make-up remover creams, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, anti-sun milks, lotions, gels or foams for care of the skin, such as cleansing lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, pain relieving compositions, compositions for treating certain skin diseases such as eczema, rosacea, psoriasis, lichens, severe pruritus.
Les compositions selon l'invention peuvent également consister en des préparations solides constituant des savons ou des pains de nettoyage.The compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.
Les compositions peuvent aussi être conditionnées sous forme de composition pour aérosol comprenant également un agent propulseur sous pression. La composition selon l'invention peut aussi être une composition pour soins capillaires, et notamment un shampooing, une lotion de mise en plis, une lotion traitante, une crème ou un gel coiffant, une composition de teintures (notamment teintures d'oxydation) éventuellement sous forme de shampooings colorants, des lotions restructurantes pour les cheveux, une composition de permanente (notamment une composition pour le premier temps d'une permanente), une lotion ou un gel antichute, un shampooing antiparasitaire, etc.The compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure. The composition according to the invention may also be a composition for hair care, and in particular a shampoo, a styling lotion, a treating lotion, a styling cream or gel, a composition of dyes (in particular oxidation dyes) in the form of coloring shampoos, restructuring hair lotions, a perm composition (in particular a composition for the first time of a perm), a fall prevention lotion or gel, an antiparasitic shampoo, etc.
La composition peut aussi être à usage bucco-dentaire, par exemple une pâte dentifrice. Dans ce cas, la composition peut contenir des adjuvants et additifs usuels pour les compositions à usage buccal et notamment des agents tensioactifs, des agents épaississants, des agents humectants, des agents de polissage tels que la silice, divers ingrédients actifs comme les fluorures, en particulier le fluorure de sodium, et éventuellement des agents édulcorants comme le saccharinate de sodium.The composition can also be for oral use, for example a toothpaste. In this case, 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.
Lorsque la composition est une émulsion, la proportion de la phase grasse peut aller de 5 % à 80 % en poids, et de préférence de 5 % à 50 % en poids par rapport au poids total de la composition. Les huiles, les cires, les émulsionnants et les coemulsionnants utilisés dans la composition sous forme d'emulsion sont choisis parmi ceux classiquement utilisés dans le domaine cosmétique. L'émulsionnant et le coémulsionnant sont présents, dans la composition, en une proportion allant de 0,3 % à 30 % en poids, et de préférence de 0,5 à 20 % en poids par rapport au poids total de la composition. L'émulsion peut, en outre, contenir des vésicules lipidiques.When the composition is an emulsion, 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.
Lorsque la composition est une solution ou un gel huileux, la phase. grasse peut représenter plus de 90 % du poids total de la composition.When the composition is an oily solution or gel, the phase. fatty can represent more than 90% of the total weight of the composition.
De façon connue, la composition cosmétique peut contenir également des adjuvants habituels dans le domaine cosmétique, tels que les gélifiants hydrophiles ou lipophiles, les additifs hydrophiles ou lipophiles, les conservateurs, les antioxydants, les solvants, les parfums, les charges, les filtres, les absorbeurs d'odeur et les matières colorantes. Les quantités de ces différents adjuvants sont celles classiquement utilisées dans le domaine cosmétique, et par exemple de 0,01 % à 10 % du poids total de la composition. Ces adjuvants, selon leur nature, peuvent être introduits dans la phase grasse, dans la phase aqueuse et/ou dans les sphérules lipidiques. Comme huiles ou cires utilisables dans l'invention, on peut citer les huiles minérales (huile de vaseline), les huiles végétales (fraction liquide du beurre de karité, huile de tournesol), les huiles animales (perhydrosqualène), les huiles de synthèse (huile de Purcellin), les huiles ou cires siliconées (cyclométhicone) et les huiles fluorées (perfluoropolyéthers), les cires d'abeille, de carnauba ou paraffine. On peut ajouter à ces huiles des alcools gras et des acides gras (acide stéarique).In a known manner, 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. 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. As oils or waxes which can be used in the invention, mention may be made of mineral oils (petroleum jelly oil), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils (perhydrosqualene), synthetic oils ( Purcellin oil), silicone oils or waxes (cyclomethicone) and fluorinated oils (perfluoropolyethers), beeswax, carnauba or paraffin. Fatty alcohols and fatty acids (stearic acid) can be added to these oils.
Comme émulsionnants utilisables dans l'invention, on peut citer par exemple le stéarate de glycérol, le polysorbate 60 et le mélange de PEG-6/PEG-32/Glycol Stéarate vendu sous la dénomination de Tefose^ 63 par la société Gattefosse.As emulsifiers which can be used in the invention, there may be mentioned, for example, glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / Glycol Stearate sold under the name Tefose ^ 63 by the company Gattefosse.
Comme solvants utilisables dans l'invention, on peut citer les alcools inférieurs, notamment l'éthanol et l'isopropanol, le propylène glycol.As solvents which can be used in the invention, mention may be made of lower alcohols, in particular ethanol and isopropanol, propylene glycol.
Comme gélifiants hydrophiles utilisables dans l'invention, on peut citer les polymères carboxyvinyliques (carbomer), les copolymères acryliques tels que les copolymères d'acrylates/alkylacrylates, les polyacrylamides, les polysaccharides tels que l'hydroxypropylcellulose, les gommes naturelles et les argiles, et, comme gélifiants lipophiles, on peut citer les argiles modifiées comme les bentones, les sels métalliques d'acides gras comme les stéarates d'aluminium et la silice hydrophobe, éthylcellulose, polyéthylène.As 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.
La composition peut contenir d'autres actifs hydrophiles comme les protéines ou les hydrolysats de protéine, les acides aminés, les polyols, l'urée, l'aliantoïne, les sucres et les dérivés de sucre, les vitamines hydrosolubles, les extraits végétaux et les hydroxyacides.The composition may contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, aliantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.
Comme actifs lipophiles, on peut utiliser le rétinol (vitamine A) et ses dérivés, le tocophérol (vitamine E) et ses dérivés, les acides gras essentiels, les céramides, les huiles essentielles, l'acide salicylique et ses dérivés.As lipophilic active agents, retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives can be used.
Selon l'invention la composition peut associer au moins un extrait lipochroman-6 à d'autres agents actifs destinés notamment à la prévention et/ou au traitement des affections cutanées. Parmi ces agents actifs, on peut citer à titre d'exemple : - les agents modulant la différenciation et/ou la prolifération et/ou la pigmentation cutanée tels que l'acide rétinoïque et ses isomères, le rétinol et ses esters, la vitamine D et ses dérivés, l'acide kojique ou l'hydroquinone ;According to the invention, the composition can combine at least one lipochroman-6 extract with other active agents intended in particular for the prevention and / or treatment of skin conditions. Among these active agents, there may be mentioned by way of example: - 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, kojic acid or hydroquinone;
- les antibactériens tels que le phosphate de clindamycine, l'érythromycine ou les antibiotiques de la classe des tétracyclines ;- antibacterials such as clindamycin phosphate, erythromycin or antibiotics of the tetracycline class;
- les antiparasitaires, en particulier le métronidazole, le crotamiton ou les pyréthrinoïdes ;- antiparasitics, in particular metronidazole, crotamiton or pyrethroids;
- les antifongiques, en particulier les composés appartenant à la classe des imidazoles tels que Péconazole, le kétoconazole ou le miconazole ou leurs sels, les composés polyènes, tels que l'amphotéricine B, les composés de la famille des allylamines, tels que la terbinafine, ou encore l'octopirox ; - les agents anti-inflammatoires non-stéroïdiens tels que l'ibuprofène et ses sels, le diclofénac et ses sels, l'acide acétylsalicylique, l'acétaminophène ou l'acide glycyrrhétinique ;- antifungals, in particular compounds belonging to the class of imidazoles such as Peconazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such as terbinafine , or octopirox; - non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid;
- les agents anesthésiques tels que le chlorhydrate de lidocaïne et ses dérivés ;- anesthetic agents such as lidocaine hydrochloride and its derivatives;
- les agents antiprurigineux comme la thénaldine, la triméprazine ou la cyproheptadine ;- antipruritic agents such as thenaldine, trimeprazine or cyproheptadine;
- les agents kératolytiques tels que les acides alpha- et bêta- hydroxycarboxyliques ou bêta-cétocarboxyliques, leurs sels, amides ou esters et plus particulièrement les hydroxyacides tels que l'acide glycolique, l'acide lactique, l'acide salicylique, l'acide citrique et de manière générale les acides de fruits, et l'acide n-octanoyl-5-salicylique ;- keratolytic agents such as alpha- and beta-hydroxycarboxylic or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, acid citric and generally fruit acids, and n-octanoyl-5-salicylic acid;
- les agents anti-radicaux libres, tels que Palpha-tocophérol ou ses esters, les superoxyde dismutases, certains chélatants de métaux ou l'acide ascorbique et ses esters ;- anti-free radical agents, such as Palpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters;
- les anti-séborrhéiques tels que la progestérone ; - les antipelliculaires comme l'octopirox ou la pyrithione de zinc ;- anti-seborrheic drugs such as progesterone; - anti-dandruff agents such as octopirox or zinc pyrithione;
- les antiacnéiques comme l'acide rétinoïque ou le peroxyde de benzoyle ;- anti-acne drugs such as retinoic acid or benzoyl peroxide;
- les extraits végétaux ou d'origine microbienne,- plant or microbial extracts,
- les peptides et leur dérivés comme par exemple le tripeptide Lys-Pro-Val.- peptides and their derivatives such as for example the tripeptide Lys-Pro-Val.
Les exemples et compositions suivants illustrent l'invention sans la limiter aucunement. Dans les compositions les proportions indiquées sont des pourcentages en poids.The following examples and compositions illustrate the invention without limiting it in any way. In the compositions the proportions indicated are percentages by weight.
Exemple 1 : Activité biologique du lipochroman-6 : L'activité du lipochroman-6 sur la NO-synthase inductible a été évalué dans le test décrit par Heck et col. (J.B.C., Vol. 267, N°30, 21277-21280, 25 octobre 1992). Ce test a pour objectif de montrer la diminution de la concentration en nitrate et nitrite, in fine, après stimulation de la NO-synthase 2.Example 1: Biological activity of lipochroman-6: The activity of lipochroman-6 on inducible NO synthase was evaluated in the test described by Heck et al. (JBC, Vol. 267, No. 30, 21277-21280, October 25, 1992). The objective of this test is to show the decrease in the nitrate concentration and nitrite, in fine, after stimulation of NO-synthase 2.
Les contrôles suivants ont été introduits dans le tests :The following controls were introduced in the tests:
A : contrôle positif (induction de l'enzyme) : mélanges d'interféron-γ (1000U7ml) et d'Interleukine 1-β (100 U/ml) ;A: positive control (induction of the enzyme): mixtures of interferon-γ (1000U7ml) and Interleukin 1-β (100 U / ml);
B contrôle négatif (inhibition maximale) : NG-monométhyl-L-arginine (forme L) à 200 μM ; contrôle de spécificité de l'inhibition : NG-monométhyl-L-arginine (forme D) à 200 μM.B negative control (maximum inhibition): N G- monomethyl-L-arginine (form L) at 200 μM; inhibition specificity control: N G -monomethyl-L-arginine (form D) at 200 μM.
Pour déterminer l'activité du produit à tester on mesure la quantité de produits de réaction stables du NO (nitrites et nitrates) à l'aide du kit "nitric colorimetric assay" vendu par la société Boehringer sous la référence 1756.28.To determine the activity of the product to be tested, the quantity of stable NO reaction products (nitrites and nitrates) is measured using the “nitric colorimetric assay” kit sold by the company Boehringer under the reference 1756.28.
Le lipochroman-6 a été testé aux concentrations de 0,005% et 0,01% (poids/volume) dans Péthanol.Lipochroman-6 was tested at concentrations of 0.005% and 0.01% (weight / volume) in ethanol.
Le lipochroman-6 présente un effet inhibiteur de la NO-synthase inductible.Lipochroman-6 has an inhibitory effect on inducible NO synthase.
Exemple 2 :Example 2:
Exemples de formulations illustrant l'invention. Ces compositions ont été obtenues par simple mélange des différents composants.Examples of formulations illustrating the invention. These compositions were obtained by simple mixing of the various components.
Composition 1 : Gel pour le visageComposition 1: Face gel
Lipochroman-6 0,1 %0.1% Lipochroman-6
Methyiparaben 0,2 %0.2% Methyiparaben
Carbomer 0,7 %Carbomer 0.7%
Polyethylène glycol (80E) 10,0 % Imidazolidinyl urée 0,3 %Polyethylene glycol (80E) 10.0% Imidazolidinyl urea 0.3%
Triéthanolamine 0,58 %Triethanolamine 0.58%
Eau qsp 100 % Composition 2 : Lotion Lipochroman-6 2,00 % Antioxydant 0,05 % Isopropanol 40,00 % Conservateur 0,30 % Eau qsp100 %Water qs 100% Composition 2: Lipochroman-6 Lotion 2.00% Antioxidant 0.05% Isopropanol 40.00% Preservative 0.30% Water qs100%
Composition 3 : Gel pour le soin Lipochroman-6 3,00 %Composition 3: Lipochroman-6 gel for care 3.00%
Hydroxypropylcellulose* 1,00 %Hydroxypropylcellulose * 1.00%
Antioxydant 0,05 %Antioxidant 0.05%
Isopropanol 40,00 %Isopropanol 40.00%
Conservateur 0,30 % Eau qsp100 %Preservative 0.30% Water qs100%
Composition 4 : Crème de soin (emulsion huile dans eau)Composition 4: Care cream (oil in water emulsion)
Lipochroman-6 5,00 %Lipochroman-6 5.00%
Stéarate de glycérol 2,00 % Polysorbate 60** 1,00 %Glycerol stearate 2.00% Polysorbate 60 ** 1.00%
Acide stéarique 1,40 %Stearic acid 1.40%
Triéthanolamine 0,70 %Triethanolamine 0.70%
Carbomer 0,40 %Carbomer 0.40%
Fraction liquide du beurre de karité 12,00 % Perhydrosqualène 12,00 %Liquid fraction of shea butter 12.00% Perhydrosqualene 12.00%
Antioxydant 0,05 %Antioxidant 0.05%
Parfum 0,50 %Perfume 0.50%
Conservateur 0,30 %Preservative 0.30%
Eau qsp 100 %Water qs 100%
Composition 5 : Shampooing Lipochroman-6 0,50 % Hydroxypropylcellulose* 1,00 % Parfum 0,50 % Conservateur 0,30 % Eau qsp 100 %Composition 5: Lipochroman-6 shampoo 0.50% Hydroxypropylcellulose * 1.00% Perfume 0.50% Preservative 0.30% Water qs 100%
Composition 6 : Crème de soin (emulsion huile/eau) Lipochroman-6 5,00 % Stéarate de glycérol 2,00 % Polysorbate 60** 1 ,00 % Acide stéarique 1 ,40 % Acide n-octanoyl-5-salicylique 0,50 % Triéthanolamine 0,70 % Carbomer 0,40 %Composition 6: Care cream (oil / water emulsion) Lipochroman-6 5.00% Glycerol stearate 2.00% Polysorbate 60 ** 1.00% Stearic acid 1.40% n-Octanoyl-5-salicylic acid 0.50% Triethanolamine 0.70% Carbomer 0.40%
Fraction liquide du beurre de karité 12,00 % Perhydrosqualène 12,00 % Antioxydant 0,05 % Parfum 0,50 % Conservateur 0,30 % Eau qsp 100 %Liquid fraction of shea butter 12.00% Perhydrosqualene 12.00% Antioxidant 0.05% Perfume 0.50% Preservative 0.30% Water qs 100%
Composition 7 : Gel anti-douleurComposition 7: Pain relief gel
Lipochroman-6 5,00 %Lipochroman-6 5.00%
Hydroxypropylcellulose* 1 ,00 %Hydroxypropylcellulose * 1, 00%
Antioxydant 0,05 %Antioxidant 0.05%
Chlorhydrate de lidocaïne 2,00 % Isopropanol 40,00 %Lidocaine hydrochloride 2.00% Isopropanol 40.00%
Conservateur 0,30 %Preservative 0.30%
Eau qsp 100 %Water qs 100%
Composition 8 : Crème de soin de l'érythème solaire (emulsioonn hhuuiillee--ddaannss- -eeaaui ) Lipochroman-6 5,00 %Composition 8: Sun erythema care cream (emulsioonn hhuuiillee - ddaannss- -eeaaui) Lipochroman-6 5.00%
Stéarate de glycérol 2,00 %Glycerol stearate 2.00%
Polysorbate 60** 1 ,00 %Polysorbate 60 ** 1, 00%
Acide stéarique 1 ,40 %Stearic acid 1.40%
Acide glycyrrhétinique 2,00 % Triéthanolamine 0,70 %Glycyrrhetinic acid 2.00% Triethanolamine 0.70%
Carbomer 0,40 %Carbomer 0.40%
Fraction liquide du beurre de karité 12,00 %Liquid fraction of shea butter 12.00%
Huile de tournesol 10,00 %Sunflower oil 10.00%
Antioxydant 0,05 % Parfum 0,50 %Antioxidant 0.05% Perfume 0.50%
Conservateur 0,30 %Preservative 0.30%
Eau qsp 100 % Composition 9 : Gel pour le traitement de l'acnéWater qs 100% Composition 9: Gel for the treatment of acne
Lipochroman-6 5,00 %Lipochroman-6 5.00%
Acide tout trans rétinoïque 0,05 %0.05% all trans retinoic acid
Hydroxypropylcellulose* 1 ,00 % Antioxydant 0,05 %Hydroxypropylcellulose * 1.00% Antioxidant 0.05%
Isopropanol 40,00 %Isopropanol 40.00%
Conservateur 0,30 %Preservative 0.30%
Eau qsp 100 %Water qs 100%
Composition 10 : Lotion pour éliminer les cicatrices dues à l'acnéComposition 10: Lotion for eliminating scars due to acne
Lipochroman-6 3,00 %Lipochroman-6 3.00%
Acide glycolique 50,00 %Glycolic acid 50.00%
Hydroxypropylcellulose* 0,05 %Hydroxypropylcellulose * 0.05%
Conservateur 0,30 % NaOH qsp pH = 2,8Preservative 0.30% NaOH qs pH = 2.8
Ethanol qsp 100 %Ethanol qs 100%
* : Klucel H® vendu par la société Hercules ** : Tween 60® vendu par la société ICI*: Klucel H® sold by the company Hercules **: Tween 60® sold by the company HERE
Exemple 3 : Effet de la composition 1 de l'exemple 2 sur une peau sensible. Il a été démontré que la peau sensible se caractérise par une réactivité neurosensorielle de la peau très forte à l'application topique sur la face de capsaïcine. (Magnusson et Koskinen, Acta Derm. Venereol.(Stockh), 1996, 76, 129-132).Example 3: Effect of composition 1 of Example 2 on sensitive skin. It has been shown that sensitive skin is characterized by a very strong neurosensory reactivity of the skin to topical application to the face of capsaicin. (Magnusson and Koskinen, Acta Derm. Venereol. (Stockh), 1996, 76, 129-132).
La sensation de démangeaison est un des signes les plus prédictifs de la peau sensibleOne of the most predictive signs of sensitive skin is itching
La composition de l'exemple 2 a donc été testée sur une population (15 personnes volontaires) de personnes présentant les caractéristiques d'une peau sensible, en comparaison de la même composition ne contenant pas Lipochroman-6.The composition of Example 2 was therefore tested on a population (15 volunteers) of people with the characteristics of sensitive skin, in comparison with the same composition not containing Lipochroman-6.
La composition et le contrôle sont appliqués sur la face à l'angle des joues, de manière aléatoire en double aveugle. 30 minutes après traitement, une crème à 0,075% de capsaïcine est appliquée sur les zones traitées.Composition and control are applied to the face at the angle of the cheeks, randomly double blind. 30 minutes after treatment, a 0.075% capsaicin cream is applied to the treated areas.
La sensation de démangeaison est alors évaluée selon : 0 = aucun 1 = légerThe itching sensation is then evaluated according to: 0 = none 1 = light
2 = modéré2 = moderate
3 = fort3 = strong
Les résultats moyens sont présentés dans le tableau suivant :The average results are presented in the following table:
Le gel contenant le lipochroman-6 présente un effet protecteur contre la sensation de démangeaison induite par la capsaïcine The gel containing lipochroman-6 has a protective effect against the itching sensation induced by capsaicin

Claims

REVENDICATIONS
1. Utilisation d'une quantité efficace de lipochroman-6, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le lipochroman-6 ou la composition étant destinés à inhiber la NO-synthase.1. Use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit NO-synthase.
2. Utilisation selon la revendication précédente, caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à ralentir voire inhiber la différenciation et/ou la prolifération cellulaire.2. Use according to the preceding claim, characterized in that the lipochroman-6 or the composition are intended to slow down or even inhibit cell differentiation and / or proliferation.
3. Utilisation selon la revendication précédente, caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à ralentir voire inhiber la croissance de l'épiderme et/ou à traiter les désordres hyperprolifératifs.3. Use according to the preceding claim, characterized in that the lipochroman-6 or the composition are intended to slow down or even inhibit the growth of the epidermis and / or to treat hyperproliferative disorders.
4. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman- 6 ou la composition sont destinés à inhiber la dégradation et/ou la destruction des cellules.4. Use according to claim 1, characterized in that the lipochroman- 6 or the composition are intended to inhibit the degradation and / or destruction of cells.
5. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman- 6 ou la composition sont destinés à inhiber les processus apoptotiques cellulaires.5. Use according to claim 1, characterized in that the lipochroman- 6 or the composition are intended to inhibit cellular apoptotic processes.
6. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman- 6 ou la composition sont destinés à traiter le vieillissement intrinsèque et/ou extrinsèque.6. Use according to claim 1, characterized in that the lipochroman- 6 or the composition are intended to treat intrinsic and / or extrinsic aging.
7. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman- 6 ou la composition sont destinés à inhiber voire supprimer les processus immunologiques et/ou inflammatoires.7. Use according to claim 1, characterized in that the lipochroman- 6 or the composition are intended to inhibit or even suppress the immunological and / or inflammatory processes.
8. Utilisation selon la revendication 7, caractérisée par le fait que le lipochroman- 6 ou la composition sont destinés à traiter les réactions d'hypersensibilité de contact et/ou les manifestations allergiques et/ou la réponse immunitaire.8. Use according to claim 7, characterized in that the lipochroman- 6 or the composition are intended for treating hypersensitivity reactions of contact and / or allergic manifestations and / or the immune response.
9. Utilisation selon la revendication 7, caractérisée par le fait que le lipochroman- 6 ou la composition sont destinés à diminuer voir inhiber l'inflammation cutanée. 9. Use according to claim 7, characterized in that the lipochroman- 6 or the composition are intended to decrease or even inhibit skin inflammation.
10. Utilisation selon la revendication 9, caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à traiter les processus inflammatoires neurogéniques cutanés.10. Use according to claim 9, characterized in that the lipochroman-6 or the composition are intended for treating the neurogenic inflammatory skin processes.
11. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à traiter les peaux dites sensibles11. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating so-called sensitive skin
12. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à traiter les érythèmes, particulièrement les érythèmes induits par les rayonnements ultra-violets.12. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating erythemas, particularly erythemas induced by ultraviolet radiation.
13. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à traiter les éruptions erythemateuses localisées ou diffuses de la peau.13. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating localized or diffuse erythematous eruptions of the skin.
14. Utilisation selon la revendication 1, caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à traiter la rosacée.14. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating rosacea.
15. Utilisation selon la revendication 1 , caractérisée par le fait que le Iipochroman-6 ou la composition sont destinés à inhiber la melanogenese induite par les rayonnements ultraviolets de type A et/ou B et/ou à traiter les désordres de type hypermélanose.15. Use according to claim 1, characterized in that the Iipochroman-6 or the composition are intended to inhibit melanogenesis induced by ultraviolet radiation type A and / or B and / or to treat disorders of the hypermelanosis type.
16. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à contrôler la sudation.16. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to control sweating.
17. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à stimuler la lipolyse.17. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to stimulate lipolysis.
18. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à inhiber la chute des cheveux.18. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to inhibit hair loss.
19. Utilisation selon la revendication 1, caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à renforcer la fonction barrière de la peau.19. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to reinforce the barrier function of the skin.
20. Utilisation selon la revendication 1 , caractérisée par le fait que le lipochroman-6 ou la composition sont destinés à stimuler l'hydratation de la peau.20. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to stimulate the hydration of the skin.
21. Utilisation selon l'une quelconque des revendications précédentes, caractérisée par le fait que le lipochroman-6 est en une quantité représentant de 10"4% à 20% du poids total de la composition.21. Use according to any one of the preceding claims, characterized in that the lipochroman-6 is in an amount representing from 10 "4 % to 20% of the total weight of the composition.
22. Utilisation selon la revendication précédente, caractérisée par le fait que le lipochroman-6 est en une quantité représentant de 5.10"3% à 10% du poids total de la composition.22. Use according to the preceding claim, characterized in that the lipochroman-6 is in an amount representing from 5.10 "3 % to 10% of the total weight of the composition.
23. Procédé de traitement cosmétique en vue de traiter les désordres liés à la synthèse du NO, caractérisé par le fait que l'on utilise par application sur la peau, sur les cheveux, et/ou sur les muqueuses, une composition cosmétique comprenant au moins du lipochroman-6 dans un milieu physiologiquement acceptable. 23. Cosmetic treatment method with a view to treating disorders linked to the synthesis of NO, characterized in that use is made, by application to the skin, to the hair, and / or to the mucous membranes, of a cosmetic composition comprising at least less lipochroman-6 in a physiologically acceptable medium.
EP01929750A 2000-04-28 2001-04-27 Lipochroman-6 as no-synthase inhibitor and uses Ceased EP1278509A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0005520A FR2808189B1 (en) 2000-04-28 2000-04-28 LIPOCHROMAN-6 AS NO-SYNTHASE INHIBITOR AND USES
FR0005520 2000-04-28
PCT/FR2001/001317 WO2001082888A1 (en) 2000-04-28 2001-04-27 Lipochroman-6 as no-synthase inhibitor and uses

Publications (1)

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EP1278509A1 true EP1278509A1 (en) 2003-01-29

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EP01929750A Ceased EP1278509A1 (en) 2000-04-28 2001-04-27 Lipochroman-6 as no-synthase inhibitor and uses

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US (1) US7008630B2 (en)
EP (1) EP1278509A1 (en)
JP (1) JP2003531845A (en)
CA (1) CA2407334A1 (en)
FR (1) FR2808189B1 (en)
WO (1) WO2001082888A1 (en)

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DE10259014A1 (en) * 2002-12-16 2004-06-24 Henkel Kgaa Antioxidant combinations with 6,7-disubstituted 2,2-dialkylchromanes or chromenes
US7501136B2 (en) * 2003-09-30 2009-03-10 Kao Corporation Deodorant composition
ES2310142B1 (en) * 2007-06-15 2009-12-04 Lipotec S.A PIGMENTATION REGULATING COMPOUNDS.
GB0719202D0 (en) * 2007-10-02 2007-11-07 Boots Co Plc Compositions and methods for the skin and hair
EP2113242A1 (en) * 2008-05-02 2009-11-04 Pangaea Laboratories Limited Antioxidant for use in cosmetic, medicated and pharmaceutical preparations
FR2934490B1 (en) * 2008-08-01 2010-09-17 Lvmh Rech USE IN A COSMETIC COMPOSITION OF LIPOCHROMAN-6 TO IMPROVE THE SKIN FLASH OF THE SKIN, IN PARTICULAR THE FACE
FR2934491B1 (en) * 2008-08-01 2010-09-17 Lvmh Rech COSMETIC COMPOSITION CONTAINING AN ASSOCIATION OF LIPOCHROMAN-6 AND A LOGOZA EXTRACT AND USE THEREOF
DE102012221079A1 (en) 2012-11-19 2013-08-14 Henkel Ag & Co. Kgaa Cosmetic and non-therapeutic use of hair treatment agent comprising e.g. 6,7-disubstituted-2,2-dialkyl-chroman compounds, anionic surfactant, and amphoteric or zwitterionic surfactants, e.g. for activating keratin synthesis in hair root
WO2016131824A1 (en) * 2015-02-16 2016-08-25 Xantial Composition for prevention or treatment of cutaneous disorder
KR20180073690A (en) * 2015-11-02 2018-07-02 루브리졸 어드밴스드 머티어리얼스, 인코포레이티드 Compositions for protecting skin against the effects of pollution and uses thereof

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Also Published As

Publication number Publication date
WO2001082888A1 (en) 2001-11-08
US7008630B2 (en) 2006-03-07
JP2003531845A (en) 2003-10-28
CA2407334A1 (en) 2001-11-08
FR2808189B1 (en) 2004-03-05
FR2808189A1 (en) 2001-11-02
US20030165444A1 (en) 2003-09-04

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