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
  • A61Q19/008—Preparations for oily skin
• • 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
• • 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
  • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
  • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
• • 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
  • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
  • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
  • A61K8/445—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof aromatic, i.e. the carboxylic acid directly linked to the aromatic ring
• • 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
  • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
  • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
  • A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/08—Antiseborrheics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/10—Anti-acne agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/006—Antidandruff preparations
• • 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
  • A61K2800/70—Biological properties of the composition as a whole
• • 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
  • A61Q19/10—Washing or bathing preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/02—Preparations for cleaning the hair
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring

Definitions

• the present invention relates to the use of at least one PPAR receptor activator in a cosmetic composition or for the preparation of a pharmaceutical composition, said PPAR receptor activator or said composition being intended to regulate the size of the sebaceous glands.
• said activator of PPAR receptors or said composition is intended to inhibit the production of sebum by the sebaceous glands.
• Sebum is a holocrine excretion of the cells of the sebaceous gland or sebocytes.
• the maturation of sebocytes is characterized by the production of lipids.
• Human sebum consists mainly of triglycerides, waxes, squalene, cholesterol esters, fatty acids and other lipids in lower quantities. Many factors can affect the secretion of sebum.
• the sebaceous glands are generally associated with the hair follicles and also with their function, thus forming a pilosebaceous unit. They are found all over the body and more particularly concentrated on the face, forehead and scalp. Some sebaceous glands are not associated with hair. All the sebaceous glands, whatever animal species they come from, have a similar structure. They consist of a single lobule or acinus, or a collection of lobules open on a hair canal. The sebaceous glands alone are open directly on the surface of the skin.
• the sebocytes are specialized epithelial cells which proliferate first in an undifferentiated state and then differentiate in the basal and parabasal layers (Mednieks et al., J. Invest. Dermatol., 97: 517-523, 1991). The differentiation takes place in cells loaded with lipids which, at the end of their maturity, do not break and release the sebum by holocrine secretion.
• disorders linked to the sebaceous function can also lead to dermatological disorders, in particular perioral dermatitis, pathologies linked to the sebaceous gland hyperplasia such as hereditary sebaceous hyperplasia, the overproduction of sebum linked to hormonal disorders such hyperandrogenism of endocrine origin.
• PPAR activator Peroxisome Proliferator Activated Receptor
• Patent application WO98 / 08089 by Arch Development demonstrated that PPARgamma agonists such as thiazolidinediones stimulate the production of sebum in a culture of preputial sebocytes, and therefore proposed, conversely to the present invention, the use of antagonists of these receptors to inhibit the production of sebum by the sebaceous glands.
• Peroxisomes are small organelles close to mitochondria containing a series of enzymes specific to the metabolism of hydrogen peroxide (catalase, urate-oxidase, D-amino acid oxidase) and enzymes of the ⁇ -oxidation of fatty acids.
• Peroxisome proliferators are primarily groups of chemicals that include lipid-lowering drugs, such as clofibrate, herbicides, and industrial plastics, such as phthalate esters. These peroxisome proliferators activate receptors, called PPARs, which are part of the super-family of steroid nuclear receptors.
• PPAR receptors can be activated by peroxisome proliferators, they can also be activated by natural fatty acids, they thus stimulate the expression of genes coding for enzymes involved in peroxisomal and mitochondrial ⁇ -oxidation or for P450-4A6 fatty acid ⁇ -hydroxylase.
• the PPAR receptors activate transcription by binding to DNA sequence elements, called the response elements of peroxisome proliferators (PPRE), in the form of a heterodimer with the X retinoid receptors (called RXRs).
• PPRE peroxisome proliferators
• RXRs X retinoid receptors
• Three human PPAR receptor subtypes have been identified and described: PPARalpha (ce), PPARgamma ( ⁇ ) and PPARdelta ( ⁇ ) (or NUC1).
• the subject of the present invention is the use of at least one activator of PPAR type receptors in a cosmetic composition or for the preparation of a pharmaceutical composition, said activator of PPAR receptors or said composition being intended to regulate the size sebaceous glands.
• said activator of PPAR receptors or said composition is intended to inhibit the production of sebum.
• compositions according to the invention comprise a physiologically acceptable medium.
• a physiologically acceptable medium is meant a medium compatible with the skin and optionally with its integuments (eyelashes, nails, hair) and / or mucous membranes.
• PPAR receptors means in particular the PPAR- ⁇ , PPAR- ⁇ and PPAR- ⁇ subtypes.
• the compounds according to the invention exhibit activating properties of receptors of the PPAR type. This activating activity of PPAR receptors can be measured in a transactivation test by the dissociation constant Kdapp (apparent).
• activator of PPAR type receptors is meant according to the invention in particular any agonist compound which binds to the PPAR receptor which, for at least one of the PPAR, ⁇ , or ⁇ subtypes, has a dissociation constant Kdapp less than or equal to 1 ⁇ M, in a transactivation test as described in Example 1.
• the preferred compounds of the present invention have, for at least one of the PPAR subtypes ⁇ , ⁇ , or ⁇ , a dissociation constant Kdapp less than or equal to 500 nM, and advantageously less than or equal to 100 nM.
• a PPAR activator which has, for at least the PPAR- ⁇ subtype, a dissociation constant Kdapp less than or equal to 500 nM and advantageously less than or equal to 100 nM.
• the activator of the PPAR- ⁇ type receptors is specific, that is to say that it has an R ratio of Kdapp relative to PPAR- ⁇ on the Kdapp relative to PPAR ⁇ less than or equal to 10 ⁇ 1 .
• R is less than or equal to 0.05, and more advantageously less than or equal to 0.02.
• composition according to the invention can be carried out by oral, parenteral or topical route.
• the composition is packaged in a form suitable for topical or oral application, preferably topical.
• the composition By oral route, the composition, more particularly the pharmaceutical composition, can be in the form of tablets, capsules, dragees, syrups, suspensions, solutions, powders, granules, emulsions, microspheres or nanospheres or lipid or polymeric vesicles allowing controlled release.
• the composition By the parenteral route, the composition may be in the form of solutions or suspensions for infusion or for injection.
• the compounds used according to the invention are generally administered at a daily dose of approximately 0.001 mg / kg to 100 mg / kg in body weight in 1 to 3 doses.
• the composition according to the invention is more particularly intended for the treatment of the skin and mucous membranes and may be in the form of ointments, creams, milks, ointments, powders, soaked tampons, syndets , solutions, gels, sprays, mousses, suspensions, stick lotions, shampoos, or cleansers. It can also be in the form of suspensions of microspheres or nanospheres or lipid or polymeric vesicles or of polymeric patches and of hydrogels allowing controlled release.
• This topical composition can be in anhydrous form, in aqueous form or in the form of an emulsion.
• the compounds are used topically at a concentration generally between 0.001% and 10% by weight, preferably between 0.01 and 1% by weight, relative to the total weight of the composition.
• compositions as described above can also contain inert additives, or even pharmacodynamically active as regards the pharmaceutical compositions, or combinations of these additives, and in particular:
• esters of parahydroxybenzoic acid such as esters of parahydroxybenzoic acid
• antioxidants such as ⁇ -tocopherol, butylhydroxyanisole or butylhydroxytoluene, Super Oxide Dismutase, Ubiquinol or certain metal chelating agents;
• - depigmenting agents such as hydroquinone, azelaic acid, caffeic acid or kojic acid
• - emollients such as glycerol, PEG 400, thiamorpholinone, and its derivatives or urea;
• antiseborrhoeic or anti-acne agents such as S-carboxymethylcysteine, S-benzyl-cysteamine, their salts or their derivatives, or benzoyl peroxide;
• antibiotics such as erythromycin and its esters, neomycin, clindamycin and its esters, tetracyclines;
• anti-psoriatic agents such as anthralin and its derivatives; - eicosa-5,8,11, 14-tetraynoic and eicosa-5,8,11-triynoic acids, their esters and amides; - retinoids, that is to say ligands of the RAR or RXR receptors, natural or synthetic;
• ⁇ - ⁇ -hydroxy acids and ⁇ -keto acids or their derivatives such as lactic, alic, citric, glycolic, mandelic, tartaric, glyceric, ascorbic acids, as well as their salts, amides or esters, or ⁇ -hydroxy acids or their derivatives, such as salicylic acid and its salts, amides or esters;
• agents for combating desquamative conditions of the scalp such as zinc pyrithione, piroctone olamine, selenium disulfide, climbazole, undecylenic acid, Ketoconazole, piroctone olamine (octopirox) or ciclopiroctone (ciclopirox ), in particular for 'anti-dandruff' cosmetic compositions;
• mattifying agents such as powders or agents consisting of colloidal dispersions of inorganic particles, such as silica, in particular for cosmetic 'mattifying' compositions;
• compositions in combination with drugs known to interfere with the immune system (for example, cyclosporine, FK 506, glucocorticoids, monoclonal antibodies, cytokines or growth factors. .).
• drugs known to interfere with the immune system for example, cyclosporine, FK 506, glucocorticoids, monoclonal antibodies, cytokines or growth factors. .).
• the invention relates to the use of at least one receptor activator of the PPAR type as defined above for the preparation of a pharmaceutical composition intended for the treatment of perioral dermatitis, pathologies linked to the hyperplasia of the sebaceous glands such as inherited hyperplasia of the sebaceous glands, overproduction of sebum linked to hormonal disorders such as hyperandrogenism of endocrine origin. It also relates to the cosmetic use of at least one activator of the PPAR type receptors as defined above, as a matting agent or also as an anti-dandruff agent.
• Another object of the invention is a cosmetic process for the treatment of oily skin, characterized in that a composition comprising at least one activator is administered or applied to the skin, the mucous membranes or the keratin fibers.
• PPAR type receptors as defined above.
• the invention also relates to a cosmetic process for the prevention and / or treatment of a scalp with a dandruff tendency, characterized in that one administers or that one applies to the skin, the mucous membranes or the keratin fibers. , a composition comprising at least one receptor activator of the PPAR type as defined above.
• compositions according to the invention can be administered orally or applied locally to the areas to be treated.
• the administration or the application can be carried out daily, for a period of several weeks and the treatment can be renewed periodically, depending on the individual to be treated.
• Activation of PPAR receptors by an agonist (activator) in HeLN cells leads to the expression of a reporter gene, luciferase, which, in the presence of a substrate, generates light.
• the modulation of PPAR receptors is measured by quantifying the luminescence produced after incubation of the cells in the presence of a reference agonist. The ligands will move the agonist from his site. The activity is measured by the quantification of the light produced. This measurement makes it possible to determine the modulating activity of the compounds according to the invention by determining the constant which represents the affinity of the molecule for the PPAR receptor. This value can fluctuate depending on the basal activity and the expression of the receptor, it is called apparent Kd (KdApp in nM).
• the cells are in contact with a concentration of the product to be tested and a concentration of the reference agonist, 2- (4- ⁇ 2- [3- (2,4- Difluoro-phenyl) acid). -1-heptyl-ureido] -ethyl ⁇ -phenyIsuIfanyl) -2-methyl-propionic for
• the HeLN cell lines used are stable transfectants containing the plasmids ERE- ⁇ Glob-Luc-SV-Neo (reporter gene) and PPAR ( ⁇ , ⁇ , ⁇ ) Gal-hPPAR. These cells are seeded in 96-well plates at the rate of 10,000 cells per well in 100 ⁇ l of DMEM medium without phenol red and supplemented with 10% delipidated calf serum. The plates are then incubated at 37 ° C, 7% CO 2 for 16 hours. The different dilutions of the products to be tested and of the reference ligand are added at the rate of 5 ⁇ l per well. The plates are then incubated for 18 hours at 37 ° C, 7% CO 2 . The culture medium is removed by inversion and 100 ⁇ l of a 1: 1 PBS / Luciferine mixture is added to each well. After 5 minutes, the plates are read by the luminescence reader.
• na means not active
• the activity of the compounds according to the invention is evaluated by daily topical application (1 time per day, weekend included) on the skin of the back of female Fuzzy or OFA rats for 4 weeks. 30 animals of 9/10 weeks were divided into 6 animals per group.
• the evaluation method consists of weighing the animals at the start and end of the study and evaluating the size of the sebaceous glands on epidermal sheets.
• the animals are euthanized then the treated area (back) is depilated and defatted.
• the 8 mm biopsy samples are then incubated in NaBr M. After separation of the epidermis, shots of the sebaceous glands are taken and the images obtained are then analyzed using the Tina software (quantification of the surface of the sebaceous glands, arbitrary unit area [mm 2 ]), version 2.09g sold by Raytest GmbH.
• Negative control PPAR ⁇ antagonist: 1- ⁇ 2 - [(S) -2- ⁇ 4- [2- (5-Methyl-2-phenyl-oxazol-4-yl) - ethoxy] -phenyl ⁇ -1 - ( 5-propyl- [1, 3,4] oxadiazol-2-yl) -ethylamino] -phenyl ⁇ -1 -phenyl- methanone

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• Health & Medical Sciences (AREA)
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• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Birds (AREA)
• Dermatology (AREA)
• General Chemical & Material Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Medicinal Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Engineering & Computer Science (AREA)
• Cosmetics (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Thiazole And Isothizaole Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2003
  • 2003-12-01 FR FR0314082A patent/FR2862870A1/fr not_active Withdrawn
• 2004
  • 2004-11-30 RU RU2006123436/15A patent/RU2006123436A/ru not_active Application Discontinuation
  • 2004-11-30 BR BRPI0415801-6A patent/BRPI0415801A/pt not_active IP Right Cessation
  • 2004-11-30 AU AU2004294760A patent/AU2004294760A1/en not_active Abandoned
  • 2004-11-30 KR KR1020067011169A patent/KR20060121140A/ko not_active Application Discontinuation
  • 2004-11-30 WO PCT/FR2004/003069 patent/WO2005053632A2/fr active Application Filing
  • 2004-11-30 EP EP04805593A patent/EP1722753A2/fr not_active Withdrawn
  • 2004-11-30 CA CA002545140A patent/CA2545140A1/fr not_active Abandoned
  • 2004-11-30 JP JP2006541976A patent/JP2007512386A/ja not_active Withdrawn
  • 2004-11-30 CN CNA2004800357333A patent/CN1889919A/zh active Pending
• 2006
  • 2006-06-01 US US11/444,371 patent/US20070065471A1/en not_active Abandoned
  • 2006-06-28 ZA ZA200605337A patent/ZA200605337B/en unknown

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