EP2515652A1 - Compositions et méthodes de traitement du vitiligo - Google Patents

Compositions et méthodes de traitement du vitiligo

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Publication number
EP2515652A1
EP2515652A1 EP10840093A EP10840093A EP2515652A1 EP 2515652 A1 EP2515652 A1 EP 2515652A1 EP 10840093 A EP10840093 A EP 10840093A EP 10840093 A EP10840093 A EP 10840093A EP 2515652 A1 EP2515652 A1 EP 2515652A1
Authority
EP
European Patent Office
Prior art keywords
composition
skin
rapamycin
effective amount
cosmeceutically
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP10840093A
Other languages
German (de)
English (en)
Other versions
EP2515652A4 (fr
Inventor
Sarah Bacus
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
0901911 B. C. UNLIMITED LIABILITY COMPANY
Original Assignee
0901911 B C UNLIMITED LIABILITY Co
B C UNLIMITED LIABILITY Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 0901911 B C UNLIMITED LIABILITY Co, B C UNLIMITED LIABILITY Co filed Critical 0901911 B C UNLIMITED LIABILITY Co
Publication of EP2515652A1 publication Critical patent/EP2515652A1/fr
Publication of EP2515652A4 publication Critical patent/EP2515652A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/133—Amines having hydroxy groups, e.g. sphingosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1825—Fibroblast growth factor [FGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y111/00—Oxidoreductases acting on a peroxide as acceptor (1.11)
    • C12Y111/01—Peroxidases (1.11.1)
    • C12Y111/01006—Catalase (1.11.1.6)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y111/00—Oxidoreductases acting on a peroxide as acceptor (1.11)
    • C12Y111/01—Peroxidases (1.11.1)
    • C12Y111/01009—Glutathione peroxidase (1.11.1.9)

Definitions

  • the present invention relates to a novel skin composition that stops progression of vitiligo.
  • the invention further relates to a composition containing a compound functioning to inhibit T-cell killing in the melanocytes. More specifically, the invention relates to a composition containing rapamycin as an active ingredient.
  • the invention can contain fibroblast growth factor as an active ingredient.
  • the invention further relates to a composition for promoting the formation of collagen in the skin, wherein the composition comprises the aforementioned compound or compounds.
  • the invention also relates to a method of treating related skin signs of aging (hollowing or sagging of skin) through use of the composition.
  • the aging process has multiple effects on the overall thickness and elasticity of the cells which comprise the skin.
  • the amount of collagen produced is decreased and the type of collagen changes.
  • the elastin in the skin decreases, the melanin granules collect into areas of dark-colored blemishes, the cells of the skin become older and the layers of expired cells increases.
  • retin-A is used to increase collagen production, decrease elastin loss, decrease production of metalloproteases (which may cause oxidative damage to the skin), disperse melanin granules and exfoliate the layers of dead skin cells from the skin.
  • retin-A has some undesirable side effects and requires monitoring of sun exposure while treating skin.
  • treatments for aging skin such as hydroquinone (bleaches skin and slows melanin production), alpha hydroxy acid (acts similar to retin-A), anti-oxidants (e.g. Cellex-C, Prevage or Revale).
  • hydroquinone bleaches skin and slows melanin production
  • alpha hydroxy acid acts similar to retin-A
  • anti-oxidants e.g. Cellex-C, Prevage or Revale
  • Vitiligo is an autoimmune disease presenting with progressive loss of skin pigmentation.
  • Vitiligo is a cutaneous disease in which the melanocytes are destroyed in discrete patches, resulting in lightened areas of variable size and location distributed throughout the skin of the body.
  • Melanocytes are cells located in the stratum basale (bottom layer) of the skin's epidermis. They are also located in the eye, ear, meninges, bones and heart. Melanocytes produce a pigment called melanin, a derivative of the amino acid tyrosine, through the process of melanogenesis. Variations in the activity of melanocytes and the production of melanin is a primary determinant of human skin color.
  • the condition of vitiligo can also affect eye pigmentation and ear function, as melanin is expressed in both the ear and the uveal tract of the eye.
  • the lightened lesions of the skin are immunocompromised and generally have greater susceptibility to the damaging effects of the sun, premature aging and possible cancer of the skin.
  • the disease strikes about 1% of the world population, generally during teenage years.
  • the progressive loss of melanocytes from depigmenting vitiligo skin is accompanied by cellular infiltrates containing T lymphocytes. Infiltrating cytotoxic T cells with high affinity T cell receptors have likely escaped clonal deletion in the thymus, allowing such T cells to enter the circulation.
  • T cells home to the skin where they express type 1 -cytokine profiles and mediate melanocyte apoptosis via the granzyme/perforin pathway.
  • This condition affects the skin and is readily visible to the public eye, there are many psychological and social problems that can result.
  • treatments that can be used to minimize the visible consequences of a condition such as vitiligo, as well as other conditions which manifest themselves as discolorations of the skin (aging spots, liver spots, etc.).
  • compositions are disclosed for cosmeceuticals that aid in the retardation of the progression of vitiligo.
  • Methods for preparing cosmeceutical compositions for treating vitiligo are also disclosed. More specifically, the methods herein disclose the use of rapamycin for preventing the progression of vitiligo and the use of rapamycin and fibroblast growth factor for promoting collagen formation.
  • methods for preparing cosmeceutical compositions resulting in a promotion of collagen are also disclosed. More specifically, the methods herein disclose the use of rapamycin and fibroblast growth factor for promoting collagen formation.
  • the composition contains rapamycin in a cosmeceutically acceptable medium/vehicle that functions to reduce T-cell degradation of melanocytes and lessen the visual signs of vitiligo.
  • the composition contains additional ingredients, such as fibroblast growth factor to aid in collagen formation.
  • the composition contains vitamin E.
  • the composition contains tromethamine, glutathione peroxidase, and catalase.
  • the invention is adminstered topically.
  • the compositions is formulated as a leave-on product.
  • the composition contains about 0.001 to 0.5% by weight rapamycin.
  • the composition contains about 0.1 to 0.2% by weight rapamycin
  • the composition contains about 0.15% by weight rapamycin.
  • composition is used in a method of treating vitiligo involving topical administration of one of the rapamycin compositions disclosed.
  • the composition is used in a method of promoting collagen production involving topical administration of one of the rapamycin compositions disclosed
  • Another embodiment is a method of inhibiting T cells in melanocytes by administering an about 0. luM to 100 uM of rapamycin composition to the cells.
  • FIG. 1 Western blot of protein expression in Human Hepatocarcinoma, HH, (T- cell lymphoma) cells treated with increasing doses of rapamycin (0.1 - 100 uM).
  • the present invention is based on the discovery that drugs, such as rapamycin, actively inhibit T-cells and inhibit the process of T-cell maturation in the melanocytes. It has been further discovered that the use of rapamycin in cosmeceutical medium is an effective topical treatment for vitiligo. The response of vitiligo skin cells to treatment with rapamycin over a course of treatment (twice a day application of 2.5 uM cosmeceutical rapamycin composition) has shown response via reduction of the discoloration and reduction in the progression of the disease. In another aspect of the present invention, the use of rapamycin and fibroblast growth factor (FGF) promotes the production of collagen and reduces the visible effects of aging.
  • drugs such as rapamycin
  • FGF fibroblast growth factor
  • Rapamycin also called sirolimus
  • IL-2 interleukin-2
  • Rapamycin binds to the cytosolic protein F -binding protein 12 (FKBP12) and inhibits the mammalian target of rapamycin (mTOR) pathway by directly binding the mTOR Complex 1 (mTORCl).
  • the treatment of vitiligo and the production of collagen with a rapamycin composition, an FGF composition or a rapamycin and FGF composition of the present invention has many desired effects in management of skin and skin disorders, including anti-ageing, anti- wrinkle and/or an anti-cellulite effects, minimizing the appearance of wrinkles, blemishes, skin lines, oily skin, acne, dry skin, xerosis, ichthyosis, dandruff, brownish spots, keratoses, melasma, lentigines, age spots, dark circles around eyes, skin pigmentation, topical inflammation, liver spots, pigmented spots, wrinkles, blemishes, skin lines, oily skin, acne, warts, eczema, pruritic skin, psoriasis, inflammatory dermatoses, disturbed keratinization, dandruff, bacterial infection, fungal infection, wound healing, body odor, and skin changes associated with aging
  • composition according to the invention also comprises a dermatologically/cosmetically acceptable vehicle to act as a diluent, dispersant or carrier for the rapamycin.
  • vehicle can comprise materials commonly employed in skin care products such as water, liquid or solid emollients, silicone oils, emulsifiers, solvents, humectants, thickeners, powders, propellants and the like.
  • agents which can be employed in the present application as the dermatologically acceptable vehicle include fibroblast growth factor (FGF), tromethamine, glutathione peroxides, catalase, sphingoid and phospholipid derivatives, antioxidants and vitamins, antiinflammatories, botanical agents, moisturizing agents, skin whitening agents, peptides, caffeine and sunscreens and UV absorbers.
  • FGF fibroblast growth factor
  • tromethamine glutathione peroxides
  • catalase catalase
  • sphingoid and phospholipid derivatives antioxidants and vitamins
  • antiinflammatories botanical agents
  • moisturizing agents moisturizing agents
  • skin whitening agents peptides
  • peptides peptides
  • sunscreens and UV absorbers UV absorbers
  • vehicle ingredients include water, glycerin, hydrogenated polyisobutene, cetearyl alcohol, ceteareth-20, macadamia integrifolia seed oil (macademia nut oil), dimethicone, tocopheryl acetate, stearoxytrimethylsilane, stearyl alcohol, panthenol, farnesol, benzyl alcohol, phenoxyethanol, acrylates/C 10-30 alkyl acrylate crosspolymer, sodium hydroxide, citric acid for lotions or water, petrolatum, glyceryl polymethacrylate, dicaprylyl ether, glycerin, dimethicone, glyceryl stearate, cetyl alcohol, prunus amygdalus dulcis (sweet almond) oil, PEG-30 glyceryl stearate, tocopheryl acetate, benzyl alcohol, phenoxyethanol, sodium hydroxide, acrylates/C 10-30 alkyl
  • a preferred vehicle is Cetaphil®.
  • agents that can be added to the vehicle include: sphingoid and phospholipid derivatives (e.g. ceramides, phytosphingosine, sphingosine, pseudoceramides, phospholipids, lysophospholipids); antioxidants and vitamins (e.g. tocopherol and derivatives, ascorbic acid and derivatives, niacinamide and derivatives, vitamin complexes, alpha-lipoic acid, retinol and derivatives, panthenol); antiinflammatories (e.g.
  • the cosmeceutically effective amount of rapamycin that is used in the cosmeceutically acceptable composition has a concentration of about 0.5% to 0.00001% rapamycin preferably from about 0.5% to 0.1%.
  • the cosmeceutically effective amount of rapamycin is partially dependent on the cells or the individual being treated and higher concentrations may be necessary to achieve desired results, in addition higher concentrations may result in increased side effects.
  • the Formulation Table shows exemplary calculations for producing products of 0.01% and 0.005% rapamycin, similar calculations can be used to produce a cosmeceutically acceptable composition at the desired concentration.
  • ingredients that may be used in any combination in the composition with 10 gms of vehicle are indicated: addition of about 15 mgs of rapamycin is preferred (about 0.15% by weight), addition of about 0.5 ugm to about 1.5 ugm of fibroblast growth factor is preferred (about 0.00005% to 0.00015% by weight), addition of about 0.5 gms of tromethamine is preferred (about 0.5% by weight), addition of about 30 mgs of glutathione peroxides is preferred (about 0.3% by weight), addition of about 30 mgs of catalase is preferred (about 0.3% by weight), and addition of about 500 mgs of vitamin E is preferred (about 0.5% by weight).
  • the dermatologically acceptable vehicle will usually form from about 80% to about 99.999%, preferably from about 95% to about 99.985% and most preferably about 99.985% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the balance of the composition.
  • the rapamycin is maintained at a concentration of about 0.15% by weight in a cosmeceutically acceptable medium.
  • the fibroblast growth factor is maintained at a therapeutically effective concentration of about 0.000015% to about 0.00005% in a cosmeceutically acceptable medium.
  • the rapamycin and FGF together comprise about 0.15% by weight in a cosmeceutically acceptable medium.
  • the skin care formulation can be an aqueous solution, a water-in-oil (w/o) emulsion, an oil-in-water (o/w) emulsion, a dispersion of lipids, an aqueous, water-alcohol, oil or oil-alcohol gel, a solid stick, a wet-wipe or an aerosol.
  • a dermatologically acceptable vehicle itself is an (w/o) or (o/w) emulsion, it can contain 5 to 50% of an oilphase and 47 to 94.95% water, with respect to the weight of the whole formulation.
  • compositions Preparation, Form, Use and Packaging
  • the active components are generally incorporated in a dermatologically acceptable carrier in conventional manner.
  • the active components can suitably be dissolved or dispersed in a portion of the water or another solvent or liquid to be incorporated in the composition.
  • the preferred compositions are oil-in-water or water-in-oil emulsions.
  • the composition may be in the form of conventional skin-care products such as a cream, gel or lotion or the like.
  • the composition can also be in the form of a so-called "rinse-off 1 product, e.g., a bath or shower gel, possibly containing a delivery system for the actives to promote adherence to the skin during rinsing.
  • the product is a "leave-on” product; a product to be applied to the skin without a deliberate rinsing step soon after its application to the skin.
  • composition may be packaged in any suitable manner such as in ajar, a bottle, tube, roll-ball, or the like, in the conventional manner.
  • the active ingredients described in the present invention may be applied one or more times daily to the portion of skin requiring treatment.
  • the improvement in skin appearance will usually become visible after two weeks of treatment, depending on the status of the initial skin condition, the concentration of the active components used in the composition, the volume of composition used and the frequency of application.
  • a small quantity, about 0.25 ml, of the composition is applied to the skin from a suitable container or applicator and spread over and/or rubbed into the skin using the hands or fingers or a suitable device.
  • the composition is formulated as a "leave-on" product and does not require any gloves or special applicators for effective use. Once applied to the skin in the affected area, the composition will begin to elicit the desired effects for treating vitiligo and promoting collagen production.
  • Fig. 1 Human Hepatocarcinoma, HH, cells were treated with increasing doses of rapamycin (0.1 - 100 u ) and the protein expression profile was analyzed by Western blot.
  • the rapamycin treatment resulted in increased expression of pAcc (phosphorylated acetyl-CoA carboxylase), slightly increased expression of peEF2 (phosphorylated eukaryotic elongation factor 2) and decreased expression of pS6 (phosphorylated ribosomal protein S6).
  • pAcc phosphorylated acetyl-CoA carboxylase
  • peEF2 phosphorylated eukaryotic elongation factor 2
  • pS6 phosphorylated ribosomal protein S6
  • Vitilogstop is not a cure, but provides a noticeable diminishment of discoloration and enlargement of vitiligo spots usually after three months. Combined with other active ingredients, stimulation of new melanin occurs over time. Apply twice a day on affected sites. The cream may oxidize and darken with time but will remain effective throughout use.
  • a 0.4 mg/ul Rapamycin composition is made in DMSO as a stock solution, from which an aliquot of 187.5 uls of the stock solution is added to 200 gms of lotion or cosmeceutically acceptable medium and mixed thoroughly.
  • An FGF composition is made following a similar protocol for a cosmeceutically acceptable medium and mixed thoroughly. Additional concentrations can be made from a concentrated stock solution by methods known to one of ordinary skill in the art.
  • the cosmeceutical formulation (lotion) can be stored at ambient temperature for topical use on those areas of the skin wherein additional lipid production is desired.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Birds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne des compositions et méthodes pour traiter le vitiligo et favoriser la formation de collagène.
EP10840093.8A 2009-12-21 2010-12-21 Compositions et méthodes de traitement du vitiligo Withdrawn EP2515652A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US28868809P 2009-12-21 2009-12-21
US31567210P 2010-03-19 2010-03-19
PCT/US2010/061661 WO2011079154A1 (fr) 2009-12-21 2010-12-21 Compositions et méthodes de traitement du vitiligo

Publications (2)

Publication Number Publication Date
EP2515652A1 true EP2515652A1 (fr) 2012-10-31
EP2515652A4 EP2515652A4 (fr) 2014-11-26

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP10840093.8A Withdrawn EP2515652A4 (fr) 2009-12-21 2010-12-21 Compositions et méthodes de traitement du vitiligo

Country Status (3)

Country Link
EP (1) EP2515652A4 (fr)
CA (1) CA2822746A1 (fr)
WO (1) WO2011079154A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10493020B2 (en) 2016-04-14 2019-12-03 The Procter & Gamble Company Method of improving the appearance of periorbital dyschromia

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2671583A4 (fr) * 2011-01-31 2014-09-03 Univ Osaka Médicament à usage externe pour traiter un trouble cutané et procédé pour produire celui-ci
CN102552253A (zh) * 2012-01-17 2012-07-11 唯美度科技（北京）有限公司 一种祛痘用皮肤外用剂
CN104324367A (zh) * 2014-10-20 2015-02-04 广西壮族自治区花红药业股份有限公司 鱼鳞提取物在制备治疗和/或预防白癜风药物方面的新用途
JP2018528236A (ja) 2015-09-24 2018-09-27 ドレクセル ユニバーシティ 真皮障害を治療または予防するための新規組成物および方法

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WO1999024036A1 (fr) * 1997-11-07 1999-05-20 Aberdeen University Composants ameliorant la penetration dans la peau
US20030022911A1 (en) * 2000-10-06 2003-01-30 Smith Terry J. Detection of antibody mediated inflammatory auto-immune disorders
WO2009118191A2 (fr) * 2008-03-27 2009-10-01 Clinuvel Pharmaceuticals Limited Thérapie pour le vitiligo

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* Cited by examiner, † Cited by third party
Title
Lisa B Travis ET AL: "Successful Treatment of Vitiligo With 0.1% Tacrolimus Ointment The Cutting Edge: Challenges in Medical and Surgical Therapeutics REPORT OF CASES", Arch Dermatol, May 2003 (2003-05), pages 571-574, XP55146413, DOI: 10.1001/archderm.139.5.571 Retrieved from the Internet: URL:http://archderm.jamanetwork.com/data/Journals/DERM/11722/DCE20005.pdf [retrieved on 2014-10-14] *
PASSERON ET AL: "Physiopathology and genetics of vitiligo", JOURNAL OF AUTOIMMUNITY, LONDON, GB, vol. 25, 2005, pages 63-68, XP005176440, ISSN: 0896-8411, DOI: 10.1016/J.JAUT.2005.10.001 *
See also references of WO2011079154A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10493020B2 (en) 2016-04-14 2019-12-03 The Procter & Gamble Company Method of improving the appearance of periorbital dyschromia

Also Published As

Publication number Publication date
CA2822746A1 (fr) 2011-06-30
EP2515652A4 (fr) 2014-11-26
WO2011079154A1 (fr) 2011-06-30

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