WO2002102345A2 - Deferoxamine as an no synthase inhibitor and uses thereof - Google Patents

Deferoxamine as an no synthase inhibitor and uses thereof Download PDF

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Publication number
WO2002102345A2
WO2002102345A2 PCT/FR2002/002065 FR0202065W WO02102345A2 WO 2002102345 A2 WO2002102345 A2 WO 2002102345A2 FR 0202065 W FR0202065 W FR 0202065W WO 02102345 A2 WO02102345 A2 WO 02102345A2
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composition
deferoxamine
intended
use according
skin
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PCT/FR2002/002065
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French (fr)
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WO2002102345A3 (en
Inventor
Marie-Madeleine Cals-Grierson
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L'oreal
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Publication of WO2002102345A3 publication Critical patent/WO2002102345A3/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/005Preparations for sensitive skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/75Anti-irritant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/78Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782Enzyme inhibitors; Enzyme antagonists

Definitions

  • the subject of the present invention is the use of an effective amount of Deferoxamine (Desferal) in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit NO-synthase .
  • Desferal Deferoxamine
  • NO-synthase covers a family of enzymes which ensure the enzymatic transformation of L-arginine into citrulline, a reaction during which a gaseous mediator with multiple functions is produced, 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 means any product which ultimately leads, notwithstanding the isoform of NO-synthase, to 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 of immune defenses, inflammation, involvement in autoimmune pathologies.
  • 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, response to environmental variations (homeostasis).
  • NO is involved in apoptotic processes and in intrinsic and / or extrinsic aging of the skin. It is involved in the skin's 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 the skin reaction processes of neurogenic origin, d 'where its involvement in so-called sensitive skin phenomena.
  • Application WO97 / 15280 has thus demonstrated the advantage of using a NO-synthase inhibitor in the treatment of sensitive skin. NO is also involved in the reduction of the barrier effect of the skin, as well as in the reduction of skin hydration.
  • 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 infections viral or bacterial, with rosacea.
  • UVB type B ultraviolet radiation
  • NMMA N G -monomethyl-L-arginine
  • NAME ester methylated N G -nitro-L-arginine
  • NNA N G -nitro-L-arginine
  • NAA N G - amino-L-arginine
  • ADMA diphenyleneiodonium chloride
  • 2- (4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide 7-nitroindazole
  • N ( 5) - (1 -iminoethyl) -L-ornithine, aminoguanidine canavanine and ebselen.
  • the object of the present invention is to provide a new inhibitor of NO-synthase which is moreover a natural inhibitor of NO-synthase.
  • Desferal 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 is interesting to use a NO-synthase inhibitor, particularly in cosmetics.
  • NOS 2 inducible NO-synthase
  • Desferal or Deferoxamine is an iron chelator sold by the company NOVARTIS.
  • a primary object of the invention is therefore the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit NO-synthase .
  • physiologically acceptable medium a medium compatible with the skin, mucous membranes, nails, hair.
  • a second object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended for application in all fields in which inhibition of NO synthases proves necessary, particularly in the cutaneous and or capillary field.
  • Desferal 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 response to environmental variations (homeostasis).
  • the third object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to slow down or even inhibit the cell differentiation and / or proliferation, particularly to regulate, slow down or even inhibit the growth of the epidemic and / or to treat hyperproliferative disorders such as psoriasis.
  • a fourth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit the degradation and / or the destruction of cells and to inhibit apoptotic processes, particularly skin cells, very particularly keratinocytes and or to treat the intrinsic and / or extrinsic aging of cells, particularly skin cells.
  • a fifth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit or even eliminate the related symptoms to immunological and / or inflammatory phenomena 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.
  • the Desferal or the composition are intended to reduce or even inhibit skin irritation, caused by external agents, the skin irritant effect is a response of the skin most often resulting in redness, pain or tingling , this response being generated by chemicals of natural or synthetic origin applied topically to the skin.
  • This irritation is accompanied by an alteration in the function and or in the epithelial structure, directly linked to the effect of the irritant product.
  • the desferal or the composition containing it are particularly suitable in the case of skin reactions linked to processes of neurogenic origin such as certain skin rednesses, and therefore to treat decrease or suppress the manifestations of so-called sensitive skin. These are aspecific reactions, distinguished from the mechanisms of allergy or inflammation.
  • dysesthetic sensations is meant more or less painful sensations felt in a skin area such as tingling, tingling, itching or itching, heating, discomfort, tightness, etc.
  • Sensitive skin can be divided into two main clinical forms, irritable and / or reactive skin, and intolerant skin.
  • Irritable and / or reactive skin is skin that reacts with pruritus, that is, itching or tingling, to various factors such as the environment, emotions, food, wind, friction, razor, soap, surfactants, hard water with a high concentration of limestone, temperature variations or wool.
  • these signs are associated with dry skin with or without sores or with skin that presents with erythema, which is non-inflammatory.
  • Intolerant skin is skin that reacts with sensations of heating, tightness, tingling and / or redness, to various factors such as the environment, emotions, food and certain cosmetic products.
  • these signs are associated with hyperseborrheic or acneic skin with or without sores and erythema.
  • “Sensitive” scalps have a more unequivocal clinical semiology: the sensations of pruritus and / or tingling and / or overheating are essentially triggered by local factors such as friction, soap, surfactants, hard water with a high concentration of limestone, shampoos or lotions. These sensations are also sometimes triggered by factors such as the environment, emotions and or food. Erythema and hyperseborrhea of the scalp and dandruff are frequently associated with the above signs.
  • the sixth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to increase the barrier effect of skin or skin hydration.
  • the seventh subject of the invention is the use of an effective amount of Desferal in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to treat rosacea and / or skin erythema, particularly erythema induced by ultraviolet radiation and or localized or diffuse erythematous rashes of the skin such as those caused by drugs toxins and / or viral or bacterial infections.
  • the eighth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit melanogenesis induced by ultraviolet radiation of type A and or B and or to treat type disorders hypermelanosis.
  • the ninth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to control sweating and / or to decrease or inhibit hair loss.
  • the composition comprising Desferal can be a cosmetic or dermatological composition.
  • the composition is a cosmetic composition.
  • the Desferal or the composition comprising it is applied to the skin topically.
  • the amount of Desferal extract used in the composition is of course a function of the desired effect and can therefore vary to a large extent.
  • Desferal 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.
  • Desferal 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 V / ' f / s 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 V / ' f / s vinifera or an extract of green tea or cocoa.
  • the tenth subject of the invention is a cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that, by application to the skin, to the hair, and or to the mucous membranes, a cosmetic composition comprising at least Desferal 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.
  • composition according to the invention in which Desferal 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).
  • 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 phase fatty 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. 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 cleaning, protection creams, treatment or care 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, anti-aging creams sunscreen), fluid foundations, cleansing milks, body protection or care milks, anti-sun milks, lotions, gels or foams for skin care, such as cleansing lotions, anti-sun lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, anti-aging compositions pain, compositions for treating certain skin diseases such as eczema, rosacea, psoriasis, lichens, severe pruritus.
  • skin care such as cleansing lotions, anti-sun lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, after
  • 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.
  • 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 coemulsifiers 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.
  • emulsiorinants 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 R 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.
  • the 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.
  • retinol and its derivatives
  • tocopherol vitamin E
  • essential fatty acids ceramides
  • essential oils ceramides
  • the composition can combine at least one Desferal 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, perythromycin or antibiotics of the tetracycline class
  • - antiparasitics in particular metronidazole, crotamiton or pyrethroids
  • - antifungals in particular compounds belonging to the class of t imidazoles such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such that terbinafine, or even octopirox;
  • non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophene 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 alpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters
  • anti-dandruff drugs 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 Desferal: The activity of Desferal on inducible NO-synthase was evaluated in the test described by Heck et al. (J.B.C., Vol. 267, N ° 30, 21277-21280, October 25, 1992). The objective of this test is to show the decrease in the concentration of nitrate and nitrite, in fine, after stimulation of NO-synthase 2.
  • A positive control (induction of the enzyme): mixtures of interferon- ⁇ (1000u / ml) and interleukin 1- ⁇ (100 u / ml);
  • B negative control (maximum inhibition): N g -monomethyl-L-arginine (form L) at 200 ⁇ m;
  • C specificity control of the inhibition: N 9 -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.
  • Desferal was tested at concentrations of 0.1 mM, 0.5 mM and 1 mM in ethanol.
  • Composition 1 Desferal face gel 3.0% Methylparaben 0.2% Carbomer 0.7%
  • Composition 2 Lotion Desferal 0.10% Antioxidant 0.05% Isopropanol 40.00% Preservative 0.30% Water qs 100%
  • Composition 3 Desferal care gel 2.00%
  • Composition 4 Care cream (oil-in-water emulsion) Desferal 5.00 o // o
  • Composition 5 Shampoo
  • Composition 6 Care cream (oil / water emulsion)
  • Composition 7 Pain relief gel
  • Composition 8 Sun erythema care cream (oil-in-water emulsion)
  • Composition 9 Gel for the treatment of acne
  • Composition 10 Lotion for eliminating scars due to acne

Abstract

The invention relates to the use of an effective quantity of deferoxamine (desferal) in a physiologically acceptable medium, in a composition or in the preparation of a composition, the desferal or composition being used to inhibit NO synthase.

Description

Deferoxamine comme inhibiteur de NO-synthase et utilisations Deferoxamine as a NO-synthase inhibitor and uses
La présente invention a pour objet l'utilisation d'une quantité efficace de Deferoxamine (Desferal) dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à inhiber la NO-synthase.The subject of the present invention is the use of an effective amount of Deferoxamine (Desferal) in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit NO-synthase .
Le terme NO-synthase recouvre une famille d'enzymes qui assurent la transformation enzymatique de la L-arginine en citrulline, réaction 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 transformation of L-arginine into citrulline, a reaction during which a gaseous mediator with multiple functions is produced, 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 fine conduit, 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” means any product which ultimately leads, notwithstanding the isoform of NO-synthase, to 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 multifonctionnelle 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). 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 mélanogenèse, de la réponse aux variations environnementales (homéostasie).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 of immune defenses, inflammation, involvement in autoimmune pathologies). 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, response to environmental variations (homeostasis).
Son implication dans la différenciation et la prolifération cellulaire (effet stimulateur), particulièrement des kératinocytes, l'associe aussi bien à la croissance de Pépiderme et à la cicatrisation qu'aux désordres hyperprolifératifs (psoriasis).Its involvement in cell differentiation and proliferation (stimulatory effect), particularly in keratinocytes, associates it with the growth of the epidermis and scarring as well as with hyperproliferative disorders (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 de réaction cutanée d'origine neurogène, d'où son implication dans les phénomènes de peau dite sensible. La demande WO97/15280 a ainsi démontré l'intérêt d'utiliser un inhibiteur de NO-synthase dans le traitement des peaux sensibles. Le NO est également impliqué dans la diminution de l'effet barrière de la peau, ainsi que dans la diminution de l'hydratation cutanée.Due to its electronic hyperreactivity which can lead to degradation or even destruction of cells, NO is involved in apoptotic processes and in intrinsic and / or extrinsic aging of the skin. It is involved in the skin's 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 the skin reaction processes of neurogenic origin, d 'where its involvement in so-called sensitive skin phenomena. Application WO97 / 15280 has thus demonstrated the advantage of using a NO-synthase inhibitor in the treatment of sensitive skin. NO is also involved in the reduction of the barrier effect of the skin, as well as in the reduction of skin hydration.
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.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 infections viral or bacterial, with rosacea.
Le NO est reconnu comme intermédiaire dans la mélanogenèse induite par les rayonnements ultra-violets de type B (UVB). Il serait aussi un des facteurs intervenant dans les désordres de type hypermélanose. Enfin, le NO semble impliqué dans le contrôle de la sudation ainsi que dans la chute des cheveux.NO is recognized as an intermediary in melanogenesis induced by type B ultraviolet radiation (UVB). It is also one of the factors involved in hypermelanosis-like disorders. Finally, NO seems to be involved in the control of sweating as well as in hair loss.
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 NΘ.NG-diméthyl-arginine (la diméthylarginine asymétrique, dénommée ADMA), le chlorure de diphénylèneiodonium, le 2-(4-carboxyphényl)-4,4,5,5-tetraméthylimidazoline-1-oxy-3-oxyde, la 7-nitroindazole, la N(5)-(1 -iminoéthyl)-L-ornithine, l'aminoguanidine, la canavanine et l'ebselen.We 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 ester methylated N G -nitro-L-arginine (NAME), N G -nitro-L-arginine (NNA), N G - amino-L-arginine (NAA), N Θ .N G -dimethyl- arginine (asymmetric dimethylarginine, called ADMA), diphenyleneiodonium chloride, 2- (4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide, 7-nitroindazole, N ( 5) - (1 -iminoethyl) -L-ornithine, aminoguanidine, canavanine and 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. Le but de la présente invention est de fournir un nouvel inhibiteur de NO-synthase qui plus est un inhibiteur naturel de NO-synthase.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. 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 Desferal 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 Desferal 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 is interesting to use a NO-synthase inhibitor, particularly in cosmetics.
Le Desferal ou encore Deferoxamine est un chelateur de fer vendu par la société NOVARTIS.Desferal or Deferoxamine is an iron chelator sold by the company NOVARTIS.
A la connaissance de la Demanderesse, il n'est pas décrit comme inhibiteur de NO- synthase.To the knowledge of the Applicant, it is not described as an inhibitor of NO-synthase.
L'invention a donc pour objet premier l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à inhiber la NO-synthase.A primary object of the invention is therefore the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal 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 medium compatible with the skin, mucous membranes, nails, hair.
L'invention a pour second objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné 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 Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended for application in all fields in which inhibition of NO synthases proves necessary, particularly in the cutaneous and or capillary field.
Le Desferal ou la composition le contenant peut être utilisé pour ralentir voire inhiber la différenciation et/ou la prolifération cellulaire, et/ou la vasodilatation, et/ou la mélanogenèse, et ou la réponse aux variations environnementales (homéostasie).Desferal 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 response to environmental variations (homeostasis).
Ainsi, l'invention a pour troisième objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à ralentir voire inhiber la différenciation et/ou la prolifération cellulaire, particulièrement à réguler, ralentir voire inhiber la croissance de l'épidémie 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 Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to slow down or even inhibit the cell differentiation and / or proliferation, particularly to regulate, slow down or even inhibit the growth of the epidemic and / or to treat hyperproliferative disorders such as psoriasis.
L'invention a pour quatrième objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné 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 Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit the degradation and / or the destruction of cells and to inhibit apoptotic processes, particularly skin cells, very particularly keratinocytes and or to treat the intrinsic and / or extrinsic aging of cells, particularly skin cells.
L'invention a pour cinquième objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à inhiber voire supprimer les symptômes liés à des phénomènes 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.A fifth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit or even eliminate the related symptoms to immunological and / or inflammatory phenomena 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.
Selon un autre aspect, le Desferal ou la composition sont destinés à diminuer voire inhiber l'irritation cutanée, provoquée par des agents externes, l'effet irritant cutané est une réponse de la peau se traduisant le plus souvent par des rougeurs, douleurs ou picotements, cette réponse étant engendrée par des produits chimiques d'origine naturelle ou synthétique appliqués de manière topique sur la peau. Cette irritation s'accompagne d'une altération de la fonction et ou de la structure épithéliale, directement liée à l'effet du produit à caractère irritant. Le desferal ou la composition le contenant sont particulièrement adaptés dans le cas des réactions cutanées liées à des processus d'origine neurogène telles que certaines rougeurs cutanées , et donc à traiter diminuer ou supprimer les manifestations des peaux dites sensibles. Il s'agit de réactions aspécifiques, se distinguant des mécanismes d'allergie ou d'inflammation. Ces symptômes sont en particulier des signes subjectifs, qui sont essentiellement des sensations dysesthésiques. On entend par sensations dysesthésiques des sensations plus ou moins douloureuses ressenties dans une zone cutanée comme les picotements, fourmillements, démangeaisons ou prurits, échauffements, inconforts, tiraillements, etc. Les peaux sensibles peuvent être scindées en deux grandes formes cliniques, les peaux irritables et/ou réactives, et les peaux intolérantes.According to another aspect, the Desferal or the composition are intended to reduce or even inhibit skin irritation, caused by external agents, the skin irritant effect is a response of the skin most often resulting in redness, pain or tingling , this response being generated by chemicals of natural or synthetic origin applied topically to the skin. This irritation is accompanied by an alteration in the function and or in the epithelial structure, directly linked to the effect of the irritant product. The desferal or the composition containing it are particularly suitable in the case of skin reactions linked to processes of neurogenic origin such as certain skin rednesses, and therefore to treat decrease or suppress the manifestations of so-called sensitive skin. These are aspecific reactions, distinguished from the mechanisms of allergy or inflammation. These symptoms are in particular subjective signs, which are essentially sensations dysaesthesic. By dysesthetic sensations is meant more or less painful sensations felt in a skin area such as tingling, tingling, itching or itching, heating, discomfort, tightness, etc. Sensitive skin can be divided into two main clinical forms, irritable and / or reactive skin, and intolerant skin.
Une peau irritable et/ou réactive est une peau qui réagit par un prurit, c'est-à-dire par des démangeaisons ou par des picotements, à différents facteurs tels que l'environnement, les émotions, les aliments, le vent, les frottements, le rasoir, le savon, les tensioactifs, l'eau dure à forte concentration de calcaire, les variations de température ou la laine. En général, ces signes sont associés à une peau sèche avec ou sans dartres ou à une peau qui présente un érythème, non inflammatoire. Une peau intolérante est une peau qui réagit par des sensations d'échauffement, de tiraillements, de fourmillements et/ou de rougeurs, à différents facteurs tels que l'environnement, les émotions, les aliments et certains produits cosmétiques. En général, ces signes sont associés à une peau hyperseborrheique ou acneique avec ou sans dartres et à un érythème.Irritable and / or reactive skin is skin that reacts with pruritus, that is, itching or tingling, to various factors such as the environment, emotions, food, wind, friction, razor, soap, surfactants, hard water with a high concentration of limestone, temperature variations or wool. In general, these signs are associated with dry skin with or without sores or with skin that presents with erythema, which is non-inflammatory. Intolerant skin is skin that reacts with sensations of heating, tightness, tingling and / or redness, to various factors such as the environment, emotions, food and certain cosmetic products. In general, these signs are associated with hyperseborrheic or acneic skin with or without sores and erythema.
Les cuirs chevelus "sensibles" ont une sémiologie clinique plus univoque : les sensations de prurit et ou de picotements et/ou d'échauffements sont essentiellement déclenchés par des facteurs locaux tels que frottements, savon, tensioactifs, eau dure à forte concentration de calcaire, shampooings ou lotions. Ces sensations sont aussi parfois déclenchées par des facteurs tels que l'environnement, les émotions et ou les aliments. Un érythème et une hyperséborrhée du cuir chevelu ainsi qu'un état pelliculaire sont fréquemment associés aux signes précédents."Sensitive" scalps have a more unequivocal clinical semiology: the sensations of pruritus and / or tingling and / or overheating are essentially triggered by local factors such as friction, soap, surfactants, hard water with a high concentration of limestone, shampoos or lotions. These sensations are also sometimes triggered by factors such as the environment, emotions and or food. Erythema and hyperseborrhea of the scalp and dandruff are frequently associated with the above signs.
L'invention a pour sixième objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à augmenter l'effet barrière de la peau ou l'hydratation cutanée.The sixth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to increase the barrier effect of skin or skin hydration.
L'invention a pour septième objet l'utilisation d'une quantité efficace de Desferal dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à traiter la rosacée et/ou les érythèmes cutanés, particulièrement les érythèmes induits par les rayonnements ultra-violets et ou les éruptions érythémateuses localisées ou diffuses de la peau comme celles causées par les drogues les toxines et/ou les infections virales ou bactériennes.The seventh subject of the invention is the use of an effective amount of Desferal in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to treat rosacea and / or skin erythema, particularly erythema induced by ultraviolet radiation and or localized or diffuse erythematous rashes of the skin such as those caused by drugs toxins and / or viral or bacterial infections.
L'invention a pour huitième objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destinés à inhiber la mélanogenèse induite par les rayonnements ultra-violets de type A et ou B et ou à traiter les désordres de type hypermélanose.The eighth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit melanogenesis induced by ultraviolet radiation of type A and or B and or to treat type disorders hypermelanosis.
L'invention a pour neuvième objet l'utilisation d'une quantité efficace de Desferal, dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à contrôler la sudation et/ou à diminuer ou inhiber la chute des cheveux.The ninth object of the invention is the use of an effective amount of Desferal, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to control sweating and / or to decrease or inhibit hair loss.
Selon l'invention, la composition comprenant le Desferal peut être une composition cosmétique ou dermatologique. Préférentiellement selon l'invention, la composition est une composition cosmétique.According to the invention, the composition comprising Desferal can be a cosmetic or dermatological composition. Preferably according to the invention, the composition is a cosmetic composition.
Préférentiellement selon l'invention, le Desferal ou la composition le comprenant est appliqué sur la peau de manière topique.Preferably according to the invention, the Desferal or the composition comprising it is applied to the skin topically.
Selon l'invention, la quantité d'extrait Desferal 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 Desferal 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 Desferal 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, Desferal 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 Desferal 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 V/'f/s vinifera ou encore un extrait de thé vert ou de cacao.Of course, according to the invention, Desferal 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 V / ' f / s vinifera or an extract of green tea or cocoa.
L'invention a pour dixième 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 Desferal dans un milieu physiologiquement acceptable.The tenth subject of the invention is a cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that, by application to the skin, to the hair, and or to the mucous membranes, a cosmetic composition comprising at least Desferal 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. 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 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. 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 applications of toothpaste on the gums.
Quelque soit la forme de la composition selon l'invention dans laquelle le Desferal 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 Desferal 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. 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.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 phase fatty 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. 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 cleaning, protection creams, treatment or care 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, anti-aging creams sunscreen), fluid foundations, cleansing milks, body protection or care milks, anti-sun milks, lotions, gels or foams for skin care, such as cleansing lotions, anti-sun lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, anti-aging compositions pain, 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.The compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.
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 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 emulsion, 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 coémulsionnants utilisés dans la composition sous forme d'émulsion 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 coemulsifiers 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 fatty phase 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.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.
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 (perhydrosqualene), les huiles de synthèse (huile de Purcellin), les huiles ou cires siliconées (cyclométhicone) et les huiles fluorées (perfluoropolyéthers), les cires d'abeille, de camauba ou paraffine. On peut ajouter à ces huiles des alcools gras et des acides gras (acide stéarique).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, camauba or paraffin. Fatty alcohols and fatty acids (stearic acid) can be added to these oils.
Comme émulsiorinants 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 TefoseR 63 par la société Gattefosse.As emulsiorinants 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 R 63 by the company Gattefosse.
Comme solvants utilisables dans l'invention, on peut citer les alcools inférieurs, notamment l'éthanol et Pisopropanol, 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. La composition peut contenir d'autres actifs hydrophiles comme les protéines ou les hydrolysats de protéine, les acides aminés, les polyols, l'urée, l'allantoïne, les sucres et les dérivés de sucre, les vitamines hydrosolubles, les extraits végétaux et les hydroxyacides.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. The 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.
Comme actifs lipophiles, on peut utiliser le rétinol (vitamine A) et ses dérivés, le tocopherol (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 Desferal 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 :According to the invention, the composition can combine at least one Desferal 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:
- 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 ;- 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, Pérythromycine ou les antibiotiques de la classe des tétracyclines ;- antibacterials such as clindamycin phosphate, perythromycin or antibiotics of the tetracycline class;
- les antiparasitaires, en particulier le métronidazole, le crotamiton ou les pyréthrinoïdes ; - les antifongiques, en particulier les composés appartenant à la classe dest imidazoles tels que l'éconazole, 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 ;- antiparasitics, in particular metronidazole, crotamiton or pyrethroids; - antifungals, in particular compounds belonging to the class of t imidazoles such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such that terbinafine, or even octopirox;
- les agents anti-inflammatoires non-stéroïdiens tels que l'ibuprofène et ses sels, le diclofenac et ses sels, l'acide acétylsalicylique, l'acetaminophene ou l'acide glycyrrhétinique ;- non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophene 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 ; - 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 ; - les agents anti-radicaux libres, tels que l'alpha-tocophérol ou ses esters, les superoxyde dismutases, certains chélatants de métaux ou l'acide ascorbique et ses esters ;- 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 alpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters;
- ! les anti-séborrhéiques tels que la progestérone ;-! anti-seborrheics such as progesterone;
- les antipelliculaires comme l'octopirox ou la pyrithione de zinc ; - les antiacnéiques comme l'acide rétinoïque ou le peroxyde de benzoyle ;- anti-dandruff drugs such as octopirox or zinc pyrithione; - 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 (KPV).- peptides and their derivatives such as for example the tripeptide Lys-Pro-Val (KPV).
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 Desferal : L'activité du Desferal 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 Desferal: The activity of Desferal on inducible NO-synthase was evaluated in the test described by Heck et al. (J.B.C., Vol. 267, N ° 30, 21277-21280, October 25, 1992). The objective of this test is to show the decrease in the concentration of nitrate 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 (1000u/ml) et d'interleukine 1-β (100 u/ml) ; B : contrôle négatif (inhibition maximale) : Ng-monométhyl-L-arginine (forme L) à 200 μm ; C : contrôle de spécificité de l'inhibition : N9-monométhyl-L-arginine (forme D) à 200 μm.A: positive control (induction of the enzyme): mixtures of interferon-γ (1000u / ml) and interleukin 1-β (100 u / ml); B: negative control (maximum inhibition): N g -monomethyl-L-arginine (form L) at 200 μm; C: specificity control of the inhibition: N 9 -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 Desferal a été testé aux concentrations de 0,1 mM, 0,5 mM et 1 mM dans l'éthanol.Desferal was tested at concentrations of 0.1 mM, 0.5 mM and 1 mM in ethanol.
Figure imgf000012_0001
Figure imgf000012_0001
Le Desferal présente un effet inhibiteur de la NO-synthase inductible. Exemple 2 :Desferal has an inhibitory effect on inducible NO synthase. 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 visage Desferal 3,0 % Methylparaben 0,2 % Carbomer 0,7 %Composition 1: Desferal face gel 3.0% Methylparaben 0.2% Carbomer 0.7%
Polyethylène glycol (80 E) 10,0 % Imidazolidinyl urée 0,3 % Triéthanolamine 0,58 % Eau qsp 100 %Polyethylene glycol (80 E) 10.0% Imidazolidinyl urea 0.3% Triethanolamine 0.58% Water qs 100%
Composition 2 : Lotion Desferal 0,10 % Antioxydant 0,05 % Isopropanol 40,00 % Conservateur 0,30 % Eau qsp 100 %Composition 2: Lotion Desferal 0.10% Antioxidant 0.05% Isopropanol 40.00% Preservative 0.30% Water qs 100%
Composition 3 : Gel pour le soin Desferal 2,00 %Composition 3: Desferal care gel 2.00%
Hydroxypropylcellulose* 1 ,00 o/Hydroxypropylcellulose * 1, 00 o /
/o Antioxydant 0,05 0/ /o Isopropanol 40,00 % Conservateur 0,30 % Eau qsp 100 /o/ o Antioxidant 0.05 0 / / o Isopropanol 40.00% Preservative 0.30% Water qs 100 / o
Composition 4 : Crème de soin (emulsion huile dans eau) Desferal 5,00 o //oComposition 4: Care cream (oil-in-water emulsion) Desferal 5.00 o // o
Stéarate de glycérol 2,00 /oGlycerol stearate 2.00 / o
Polysorbate 60** 1 ,00 o //oPolysorbate 60 ** 1, 00 o // o
Acide stéarique 1 ,40 0 //oStearic acid 1, 40 0 // o
Triéthanolamine 0,70 0 //o Carbomer 0,40 /oTriethanolamine 0.70 0 // o Carbomer 0.40 / o
Fraction liquide du beurre de karité 12,00 0 //oLiquid fraction of shea butter 12.00 0 // o
Perhydrosqualene 12,00 %Perhydrosqualene 12.00%
Ahtioxydant 0,05 %0.05% antioxidant
Parfum 0,50 % Conservateur 0,30 %Perfume 0.50% Preservative 0.30%
Eau qsp 100 %Water qs 100%
Composition 5 : ShampooingComposition 5: Shampoo
Desferal 0,50 %Desferal 0.50%
Hydroxypropylcellulose* 1 ,00 %Hydroxypropylcellulose * 1, 00%
Parfum 0,50 %Perfume 0.50%
Conservateur 0,30 %Preservative 0.30%
Eau qsp 100 %Water qs 100%
Composition 6 : Crème de soin (emulsion huile/eau)Composition 6: Care cream (oil / water emulsion)
Desferal 5,00 %Desferal 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 n-octanoyl-5-salicylique 0,50 %N-octanoyl-5-salicylic acid 0.50%
Triéthanolamine 0,70 %Triethanolamine 0.70%
Carbomer 0,40 %Carbomer 0.40%
Fraction liquide du beurre de karité 12,00 %Liquid fraction of shea butter 12.00%
Perhydrosqualene 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 7 : Gel anti-douleurComposition 7: Pain relief gel
Desferal 5,00 %Desferal 5.00%
Hydroxypropylcellulose* 1 ,00 %Hydroxypropylcellulose * 1, 00%
Antioxydant 0,05 %Antioxidant 0.05%
Chlorhydrate de lidocaïne 2,00 %Lidocaine hydrochloride 2.00%
Isopropanol 40,00 %Isopropanol 40.00%
Conservateur 0,30 %Preservative 0.30%
Eau qsp 100 %Water qs 100%
Composition 8 : Crème de soin de l'érythème solaire (emulsion huile-dans-eau)Composition 8: Sun erythema care cream (oil-in-water emulsion)
Desferal 3,00 /oDesferal 3.00 / o
Stéarate de glycérol 2,00 %Glycerol stearate 2.00%
Polysorbate 60** 1 ,00 %Polysorbate 60 ** 1, 00%
Acide stéarique 1 ,40 % Acide glycyrrhétinique 2,00 %Stearic acid 1.40% Glycyrrhetinic acid 2.00%
Triéthanolamine 0,70 %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 %Antioxidant 0.05%
Parfum 0,50 %Perfume 0.50%
Conservateur 0,30 %Preservative 0.30%
Eau qsp " 100 %Water qs " 100%
Composition 9 : Gel pour le traitement de l'acnéComposition 9: Gel for the treatment of acne
Desferal 5,00 %Desferal 5.00%
Acide tout trans rétinoïque 0,05 %0.05% all trans retinoic acid
Hydroxypropylcellulose* 1 ,00 %Hydroxypropylcellulose * 1, 00%
Antioxydant 0,05 %Antioxidant 0.05%
Isopropanol 40,00 %Isopropanol 40.00%
Conservateur 0,30 %Preservative 0.30%
Eau qsp " I00 %Water qs " I00%
Composition 10 : Lotion pour éliminer les cicatrices dues à l'acnéComposition 10: Lotion for eliminating scars due to acne
Desferal 3,00 %Desferal 3.00%
Acide glycolique 50,00 %Glycolic acid 50.00%
Hydroxypropylcellulose* 0,05 %Hydroxypropylcellulose * 0.05%
Conservateur 0,30 %Preservative 0.30%
NaOH qsp pH = 2,8NaOH 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

Claims

REVENDICATIONS
1. Utilisation d'une quantité efficace de Deferoxamine (Desferal), dans un milieu physiologiquement acceptable, dans une composition ou pour la préparation d'une composition, le Desferal ou la composition étant destiné à inhiber la NO-synthase.1. Use of an effective amount of Deferoxamine (Desferal), in a physiologically acceptable medium, in a composition or for the preparation of a composition, the Desferal or the composition being intended to inhibit NO-synthase.
2. Utilisation selon la revendication précédente, caractérisée par le fait que la Deferoxamine ou la composition sont destinées à ralentir voire inhiber la différenciation et/ou la prolifération cellulaire.2. Use according to the preceding claim, characterized in that the Deferoxamine 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 la Deferoxamine ou la composition sont destinées 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 Deferoxamine 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 la Deferoxamine ou la composition sont destinées à inhiber la dégradation et/ou la destruction des cellules.4. Use according to claim 1, characterized in that the Deferoxamine 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 la Deferoxamine , ou la composition sont destinées à inhiber les processus apoptotiques cellulaires.5. Use according to claim 1, characterized in that the Deferoxamine, or the composition are intended to inhibit cellular apoptotic processes.
6. Utilisation selon la revendication 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à traiter le vieillissement intrinsèque et/ou extrinsèque.6. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended for treating intrinsic and / or extrinsic aging.
7. Utilisation selon la revendication 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à inhiber voire supprimer les processus immunologiques et/ou inflammatoires.7. Use according to claim 1, characterized in that the Deferoxamine 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 la Deferoxamine ou la composition sont destinées 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 Deferoxamine 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 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à traiter les réactions cutanées d'origine neurogène..9. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended for treating skin reactions of neurogenic origin.
10. Utilisation selon la revendication 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à traiter les peaux dites sensibles10. Use according to claim 1, characterized in that Deferoxamine or the composition are intended for treating so-called sensitive skin
11. Utilisation selon la revendication 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à augmenter l'effet barrière de la peau ou l'hydratation cutanée.11. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended to increase the barrier effect of the skin or the skin hydration.
12. Utilisation selon la revendication 1, caractérisée par le fait que là Deferoxamine ou la composition sont destinées à traiter les érythèmes, particulièrement les érythèmes induits par les rayonnements ultra-violets.12. Use according to claim 1, characterized in that there Deferoxamine or the composition are intended to treat erythemas, particularly erythemas induced by ultraviolet radiation.
13. Utilisation selon la revendication 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à traiter les éruptions érythémateuses localisées ou diffuses de la peau.13. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended for treating localized or diffuse erythematous rashes of the skin.
14. Utilisation selon la revendication 1, caractérisée par le fait que la Deferoxamine ou la composition sont destinées à traiter la rosacée.14. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended for treating rosacea.
15. Utilisation selon la revendication 1, caractérisée par le fait que la Deferoxamine ou la composition sont destinées à inhiber la mélanogenèse 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 Deferoxamine or the composition are intended to inhibit melanogenesis induced by type A and / or B ultraviolet radiation and / or to treat disorders of hypermelanosis type.
16. Utilisation selon la revendication 1, caractérisée par le fait que la Deferoxamine ou la composition sont destinées à contrôler la sudation.16. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended to control sweating.
17. Utilisation selon la revendication 1 , caractérisée par le fait que la Deferoxamine ou la composition sont destinées à inhiber la chute des cheveux.17. Use according to claim 1, characterized in that the Deferoxamine or the composition are intended to inhibit hair loss.
18. Utilisation selon l'une quelconque des revendications précédentes, caractérisée par le fait que la Deferoxamine est en une quantité représentant de 10"4% à 20% du poids total de la composition.18. Use according to any one of the preceding claims, characterized in that the Deferoxamine is in an amount representing from 10 "4 % to 20% of the total weight of the composition.
19. Utilisation selon la revendication précédente, caractérisée par le fait que la Deferoxamine est en une quantité représentant de 5.10"3% à 10% du poids total de la composition.19. Use according to the preceding claim, characterized in that the Deferoxamine is in an amount representing from 5.10 "3 % to 10% of the total weight of the composition.
20. 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 de la Deferoxamine dans un milieu physiologiquement acceptable. 20. Cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that a cosmetic composition comprising, by application to the skin, to the hair, and / or to the mucous membranes at least Deferoxamine in a physiologically acceptable medium.
PCT/FR2002/002065 2001-06-15 2002-06-14 Deferoxamine as an no synthase inhibitor and uses thereof WO2002102345A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0107876A FR2825920B1 (en) 2001-06-15 2001-06-15 DESFERAL AS INHIBITOR OF NO-SYNTHASE AND USES
FR01/07876 2001-06-15

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US10751304B2 (en) 2008-10-10 2020-08-25 The Board Of Trustees Of The Leland Stanford Junior University Topical and transdermal delivery of HIF-1 modulators to prevent and treat chronic wounds
US11331288B2 (en) 2017-09-14 2022-05-17 The Board Of Trustees Of The Leland Stanford Junior University Conditioning irradiated tissue for increasing vascularity

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US9737511B2 (en) * 2004-05-24 2017-08-22 Geoffrey C. GURTNER Method of treating or preventing pathologic effects of acute increases in hyperglycemia and/or acute increases of free fatty acid flux
US10751304B2 (en) 2008-10-10 2020-08-25 The Board Of Trustees Of The Leland Stanford Junior University Topical and transdermal delivery of HIF-1 modulators to prevent and treat chronic wounds
US11160775B2 (en) 2008-10-10 2021-11-02 The Board Of Trustees Of The Leland Stanford Junior University Topical and transdermal delivery of HIF-1 modulators to prevent and treat chronic wounds
WO2011021203A3 (en) * 2009-08-19 2011-04-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Desferrioxamine-metal complexes for the treatment of immune-related disorders
US8975294B2 (en) 2009-08-19 2015-03-10 Hadasit Medical Research Services And Development Ltd. Desferrioxamine-metal complexes for the treatment of immune-related disorders
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US11331288B2 (en) 2017-09-14 2022-05-17 The Board Of Trustees Of The Leland Stanford Junior University Conditioning irradiated tissue for increasing vascularity

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