EP0494995A1 - Methode cosmetique pour la prevention de la formation de cicatrices - Google Patents

Methode cosmetique pour la prevention de la formation de cicatrices

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Publication number
EP0494995A1
EP0494995A1 EP90916599A EP90916599A EP0494995A1 EP 0494995 A1 EP0494995 A1 EP 0494995A1 EP 90916599 A EP90916599 A EP 90916599A EP 90916599 A EP90916599 A EP 90916599A EP 0494995 A1 EP0494995 A1 EP 0494995A1
Authority
EP
European Patent Office
Prior art keywords
bond
hydrogen
proviso
vitamin
double bond
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Withdrawn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
EP90916599A
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German (de)
English (en)
Other versions
EP0494995A4 (en
Inventor
Michael F. Holick
Xiao Tian
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Boston University
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Boston University
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Publication date
Application filed by Boston University filed Critical Boston University
Publication of EP0494995A1 publication Critical patent/EP0494995A1/fr
Publication of EP0494995A4 publication Critical patent/EP0494995A4/en
Withdrawn legal-status Critical Current

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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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention is in the field of medicinal chemistry.
  • the present invention relates to novel methods for
  • Skin Human skin is a complex integration of different types of cells and tissues which form an organ. Skin is also the primary seat of the sense of touch and creates a covering for the protection of th ⁇ deeper tissues. The skin also plays an important role in the regulation of body temperature and is also an excretory and absorbing organ. Skin consists primarily of a layer of vascular tissue and an external covering of epithelium known as the epidermis. On the surface layer are the sensitive papillae and alongside or imbedded beneath it are certain specialized organs, specifically the sweat glands, hair follicles, and sebaceous glands.
  • wounds which are caused by physical means, result in a disruption of the normal continuity of the structures of the skin. Examples of wounds include cuts, punctures, lacerations, etc.
  • stomach lining is also composed of internal epithelium (endotheliu ).
  • Gastric ulcers are a result of damage or erosion of the stomach lining. Gastric ulcers occur along the lesser curvature of the stomach where the pyloric glands border the oxyntic gland. They are usually 1 to 2.5 cm in diameter; however, they can vary from a few mm to several cm. Ulcers are usually round, oval or elliptical, with sharply defined margins. The surrounding mucosa is often hyperemic and edematous. Ulcers penetrate into the submucosa or muscular layer.
  • a thin layer of gray or white exudate usually covers the base of the ulcers; this layer is composed of fibrinoid, granulation and fibrous tissue layers.
  • fibrous tissue in the base contracts the ulcer and may distort the surrounding tissue.
  • healing continues as granulation tissue fills the base and epithelium from the ulcer edges cover its surface.
  • the mechanism of epithelial wound healing is a complex process involving ultrastructural changes of epithelial cells. These changes allow for detachment from neighboring cells, migration and subsequent reattachment.
  • the migration of epithelial cells has been found to depend on a suitable matrix composed of fibrin, fibronectin or basement membrane which traverse the wound. Clark, R., J. Am. Acid Derm.. 13:701-718 (1985); Zitelli, J., Adv. Dermatol . 2:243-268 (1987).
  • the process involves clotting and formation of a crust or scab to seal the wound; an acute inflammatory reaction; reepithelialization of the surface and fibrous bridging due to fibrin followed by complete sealing of the wound by an epithelial covering. Thereafter, hair follicles, sebaceous glands and sweat glands may subsequently regenerate.
  • the process of second intention healing requires the removal of necrotic debris. The gap in the wound then fills in with fibrous materials.
  • carbenoxolene is used to treat gastric ulcers.
  • Carbenoxolene is a hydrolytic product of glycyrrhizic acid (derivativ of licorice); it has been shown to increase the rate of gastric ulce healing. Braunwald, E., Harrison's Principles of Internal Medicin 11th ed. p. 1247. It appears to increase the life span of gastri mucosal epithelial cells and increase the secretion and viscosity o gastric mucus.
  • carbenoxolene has aldosterone-like effects, therefore it tends to increase the rate at which the body retain sodium and water. These effects may be blocked by aldosterone antagonists, however the antagonists obliterate the healing effects o the carbenoxolene. There is a need for therapies which can promot healing without the negative side effects.
  • the skin may be a targe tissue for 1,25-(0H) -D3 (Stumpf, W.E. et al.. Science. 201:1188-119 (1979)).
  • Cells isolated from the skin of rats, mice, and humans, an from cultured human skin fibroblasts and keratinocytes contain a hig affinity (1.0 x 10 "10 M) low capacity receptor-like protein for 1,25 dihydroxyvitamin D3 (Franceschi, et al .. Arch. Biochem. Biophys. 210: 1-13 (1979); Simpson, R. U. et al., P.N.A.S. (USA). 77: 582 (1980); Colston, K. et al..
  • Holick, U.S. Patent No. 4,410,545 discloses vitamin D glycosides and their use in the regulation of calcium metabolism and phosphorous homeostasis.
  • Holick, U.S. Patent No. 4,521,410 discloses water-soluble glycosyl orthoesters of vitamin D and their use in the regulation of calcium metabolism and phosphorous homeostasis.
  • Calciphylaxis is a hypersensitivity reaction resulting from the administration of or endogenous production of a sensitizing calcifier in combination with a challenger.
  • Sensitizing calcifiers include, inter alia, vitamins D2 and D3.
  • Dikstein U.S. Patent No. 4,610,478, and European Patent Application No. 0 129003 (1984), discloses compositions containing 1- alpha-hydroxycholecalciferol or 1-alpha,25-dihydroxycholecalciferol for the topical treatment of skin disorders, such as dermatitis, psoriasis, eczema, solar keratosis and certain stages of wound healing and alopecia.
  • Dikstein also teaches that low dosages are required, from about 0.03 ⁇ g to 1.0 ⁇ g per gram of composition, to minimize the risk of undesired side effects and systemic effects.
  • Dikstein does not teach that vitamin D compounds are useful for the treatment of wounds caused by lacerations, punctures or cuts.
  • the invention relates to a method of enhancing the healing of wounds in a patient comprises administering to said patient an effective amount of a vitamin D compound, wherein said vitamin D compound has the Formula (I):
  • Y 1 is hydrogen, F, CH 3 , CH 2 CH 3 or X 1 ;
  • U is hydrogen, -OH or -0-(C2-C4 alkyl)-0H;
  • Zl is F, H or X 1 ;
  • Q a is CF 3 or CH2X 1 ;
  • Q b is CF 3 or CH 3 ;
  • R is a double bond or an epoxy group; wherein ⁇ l is selected from the group consisting of hydrogen and -OH; W is CH-CH3 or 0; and V is CH2 or 0; with the proviso that both W and V are not both 0; and
  • the invention also relates to a method of enhancing the healing of wounds in a patient which comprises administering to said patient an effective amount of a vitamin D compound, wherein said vitamin D compound has the
  • Y 2 is hydrogen, fluorine, methyl, ethyl or OR*;
  • Z 2 is F, H or X 2 ;
  • U is hydrogen, -OH or -0-(C -C4 alkyl)-0H;
  • Q a is CF 3 or CH 2 X 2 ;
  • Q b is CF 3 or CH3;
  • R is a double bond or an epoxy group
  • X 2 is selected from the group consisting of hydrogen
  • R! is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue, or R! is an orthoester glycoside moiety of the Formula (III):
  • A represents a glucofuranosyl or glucopyranosyl ring
  • R 2 is hydrogen, lower alkyl, aralkyl, or aryl, with the proviso that aryl is phenyl or phenyl substituted by chloro, fluoro, bromo, iodo, lower C1-C4 alkyl, C1-C4 alkoxy; or naphthyl; and
  • R3 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue, with the proviso that at least one of the R! is either a glycosidic residue or an orthoester glycoside moiety;
  • W is CH-CH3 or 0
  • V is CH 2 or 0; with the proviso that both W and V are not both 0;
  • the invention also relates to a method of inhibiting scar formation in a patient arising from cuts, lacerations, puncture wounds and abrasions which comprises administering to said patient a pharmaceutical composition comprising an effective amount of a vitamin D compound and a pharmaceutically acceptable carrier, wherein said vitamin D compound has the Formula (I):
  • Y 1 is hydrogen, F, CH 3 , CH 2 CH 3 or X 1 ;
  • U is hydrogen, -OH or -0-(C2-C4 alkyl)-OH;
  • Z 1 is F, H or X 1 ;
  • Q a is CF 3 or CH 2 X ;
  • Q b is CF 3 or CH 3 ;
  • R is a double bond or an epoxy group; wherein ⁇ is selected from the group consisting of hydrogen and -OH;
  • W is CH-CH3 or 0; and with the proviso that both W and V are not both 0; and
  • the invention also relates to a method for inhibiting scar formation in a patient arising from cuts, lacerations, puncture wounds and abrasions which comprises topically administering to said patient a pharmaceutical composition comprising an effective amount of a vitamin D compound and a pharmaceutically acceptable carrier, wherein said vitamin D compound has the Formula (II):
  • Y 2 is hydrogen, fluorine, methyl, ethyl or OR 1 ;
  • U is hydrogen, -OH or -0-(C2-C4 alkyl)-OH;
  • Z 2 is F, H or X 2 ;
  • Q a is CF 3 or CH 2 X 2 ;
  • Q b is CF 3 or CH 3 ;
  • R is a double bond or an epoxy group
  • X 2 is selected from the group consisting of hydrogen, and
  • R 1 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue, or R 1 is an orthoester glycoside moiety of the Formula (III):
  • A represents a glucofuranosyl or glucopyranosyl ring
  • R 2 is hydrogen, lower alkyl, aralkyl, or aryl, with the proviso that aryl is phenyl or phenyl substituted by chloro, fluoro, bromo, iodo, lower C1-C4 alkyl, C1-C4 alkoxy; or naphthyl; and
  • R3 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue;
  • W is CH-CH3 or 0
  • V is CH2 or 0; with the proviso that both W and V are not both 0;
  • the invention also relates to a method of treating gastric, duodenal, esophageal , decubitus, diabetic foot and genito-urinary ulcers in a patient which comprises administering to said patient a pharmaceutical composition comprising an effective amount of a vitamin D compound and a pharmaceutically acceptable carrier, wherein said vitamin D compound has the Formula (I):
  • Y 1 is hydrogen, F, CH 3 , CH 2 CH 3 or X 1 ;
  • U is hydrogen, -OH or -0-(C2-C4 alkyl)-0H;
  • Z 1 is F, H or X 1 ;
  • Q a is CF 3 or CH2X 1 ;
  • Q b is CF 3 or CH 3 ;
  • R is a double bond or an epoxy group; wherein X 1 is selected from the group consisting of hydrogen and -OH;
  • W is CH-CH3 or 0
  • V is CH2 or 0; with the proviso that both W and V are not both 0;
  • the invention also relates to a method for treating gastric, duodenal, esophageal, decubitus, diabetic foot, genito-urinary ulcers and ulcerative keratitis in a patient which comprises topically or ophthalmically administering to said patient a pharmaceutical composition comprising an effective amount of a vitamin D compound and a pharmaceutically acceptable carrier, wherein said vitamin D compound has the Formula (II):
  • Y 2 is hydrogen, fluorine, methyl, ethyl or ORl
  • U is hydrogen, -OH or -0-(C 2 -C4 alkyl)-OH;
  • Z 2 is F, H or X 2 ;
  • Q a is CF 3 or CH 2 X 2 ;
  • Q b is CF 3 or CH 3 ;
  • R is a double bond or an epoxy group
  • X 2 is selected from the group consisting of hydrogen, and
  • R 1 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue, or R 1 is an orthoester glycoside moiety of the Formula (III):
  • A represents a glucofuranosyl or glucopyranosyl ring
  • R 2 is hydrogen, lower alkyl, aralkyl, or aryl, with the proviso that aryl is phenyl or phenyl substituted by chloro, fluoro, bromo, iodo, lower 1-C4 alkyl, C1-C4 alkoxy; or naphthyl; and
  • R3 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue;
  • W is CH-CH3 or 0
  • V is CH 2 or 0; with the proviso that both W and V are not both 0;
  • Figure 1 depicts a graph showing the effect of vehicle and 5 ⁇ g, 10 ⁇ g, 27 ⁇ g and 54 ⁇ g of 1,25-dihydroxyvitamin D per gram of oil on the percentage of wound healing on days 1, 2, 3, 4, 5 and 6 in rats with experimental wounds.
  • Figure 2 depicts a graph showing the effect of vehicle and 27 ⁇ g 1,25-dihydroxyvitamin D3/gram oil on the percentage of wound healing on days 1, 2, 3, 4, 5 and 9 in rats with experimental wounds.
  • the present invention provides for a method of healing wounds and inhibiting scar formation.
  • Wounds to the external epithelium include cuts, punctures and lacerations, including corneal lacerations.
  • Wounds of the internal epithelium include peptic ulcers, esophageal mucosa injury, oral mucosa injuries and periodontal disease.
  • the invention also provides for the treatment of ulcers such as diabetic ulcers of the feet, decubitus ulcers (bed sores), genito-urinary ulcers, peptic ulcers and ulcerative keratitis. Ulcerative keratitis is caused, for example, by extended wear of contact lenses.
  • peptic ulcer includes both duodenal and gastric ulcers.
  • Peptic ulcers are a group of ulcerative disorders of the upper gastrointestinal tract; the primary forms of peptic ulcer are duodenal and gastric ulcer.
  • Normally gastric mucosa has the ability to resist the corrosive effects of acid-pepsin. This is a trait which is unique to the gastric mucosa; areas such as the esophagus do not have this ability.
  • Injury to the esophageal mucosa occurs from exposure to refluxed gastric juice and ulceration which occurs in the small intestine at the site of surgical attachment to actively secreting gastric mucosa.
  • Genito-urinary ulcers treatable with the vitamin D compounds of the invention ⁇ include those caused by, for example, herpes simplex virus as well as other viral, fungal and bacterial infections. See Harrison's Principles of Internal Medicine. E. Braunwald et al . (eds.); McGraw-Hill Book Co., New York, N.Y., 1987, pp. 514-516.
  • the vitamin D compounds of the invention may also be administered for the treatment of periodontal disease.
  • This disease begins as a marginal inflammation of the gingivae (gingivitis) which slowly spreads to involve the underlying alveolar bone and periodontal ligament.
  • the vitamin D compounds may be applied topically, for example, as part of a tooth paste formulation, or may be administered orally or part of a thin film implant between the teeth and gums to give sustained release of the vitamin D compound.
  • the film comprises a cellulose polymer. See U.S. Patent No. 4,315,779 to Heyd.
  • Y 1 is hydrogen, F, CH 3 , CH 2 CH 3 or X 1 ;
  • U is hydrogen, -OH or -0-(C 2 -C4 alkyl)-OH;
  • Z 1 is F, H or X 1 ;
  • R is a double bond or an epoxy group
  • X 1 is selected from the group consisting of hydrogen and -OH;
  • W is CH-CH3 or 0
  • V is CH2 or 0; with the proviso that both W and V are not both 0;
  • the compounds of Formula (I) When the compounds of Formula (I) have a double bond at position C-22, they are derivatives of vitamin D2, whereas if the bond at that position is single, and there is a lack of C24 alkyl, they are derivatives of vitamin D3. The latter are preferred.
  • vitamins D3 or D2 are vitamins D3 or D2; 1-hydrox vitamins D3 or D2; and 1,25-dihydroxyvitamins D3 or D2, 5,6-epoxy derivatives of vitamin D and its metabolites, 2- ⁇ -(3-hydroxypropoxy)-l alpha,25- dihydroxyvitamin D3, as well as the side chain fluoro derivatives of 1,25-(0H)2 vitamin D and 1-(0H) vitamin D.
  • 20- and 22-oxa vitamin D derivatives including 20-oxa-l ⁇ (0H)D, 20-oxa- l ⁇ ,25(0H) 2 D 3 , 22-oxa-l ⁇ (0H)D 3 and 22-oxa-l ⁇ ,25(0H)D 3 as well as pseudo-1-alpha-hydroxyvitamin D derivatives such as dihydrotachysterol and 5,6-trans vitamin D3 and their 25-hydroxy derivatives.
  • water soluble derivatives of the aforementioned compounds of Formula (I) obtained by solubilizing such compounds by attaching thetato glycosidic residues such as those disclosed in Holick, U.S. Patent 4,410,515.
  • Alternative methods of solubilization are by conjugating compounds of Formula (I) to glycosyl orthoester residues, as disclosed in copending U.S. S.N. 607,117 by Holick et al.. filed May 3, 1984.
  • the disclosures of the aforemen tioned patent and application are herein incorporated by reference an made a part hereof.
  • Y 2 is hydrogen, fluorine, methyl, ethyl or ORl
  • Z 2 is F, H or X 2 ;
  • U is hydrogen, -OH or -0-(C 2 -C4 alkyl)-OH;
  • R is a double bond or an epoxy group
  • X 2 is selected from the group consisting of hydrogen an OR 1 ;
  • R 1 is hydrogen or a straight or branched chain glycosidi residue containing 1-20 glycosidic units per residue, or R 1 is a orthoester glycoside moiety of the Formula (III):
  • A represents a glucofuranosyl or glucopyranosyl ring
  • R 2 is hydrogen, lower alkyl (C1-C4), aralkyl (C7-C10), or aryl, with the proviso that aryl is phenyl or phenyl substituted by chloro, fluoro, bromo, iodo, lower C1-C4 alkyl, C1-C4 alkoxy; or naphthyl ;
  • R 3 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue;
  • W is CH-CH3 or 0
  • V is CH2 or 0; with the proviso that both W and V are not both 0;
  • the vitamin D compounds are prepared or obtained according to the disclosures of the aforementioned references.
  • the 5,6- epoxy derivatives of vitamin D3 are obtained as described in Jpn. Kokai Tokkvo Koho JP 58,216,178 [83,216,178], Dec. 15, 1983.
  • the fluoro derivatives are made or obtained as described in Shiina, et al.. Arch. Biochem. Bioohvs 220:90 (1983).
  • Methods for preparing the 20- and 22-oxa vitamin D derivatives are disclosed by Abe, J., et al.. Vitamin D Molecular. Cellular and Clinical Endocrinology, p. 310-319, Walter de Gruyter & Co., Berlin (1988).
  • the compounds of the invention can be administered in any appropriate pharmaceutically acceptable carrier for oral, parenteral, or topical administration. They can be administered by any means that enhances wound healing, ulcer healing, amelioration of periodontal disease, and inhibition of scar formation in animals, especially humans.
  • the dosage administered will be dependent upon the age, health and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment and the nature of the effect desired.
  • systemic daily dosage of 1,25-dihydroxyvitamin D3 will be from about 0.001 micrograms/kg to 100 micrograms/kg preferably 0.01 to 1.0 micrograms per kg of body weight.
  • Dosage forms for topical administration include about 3 to 100 micrograms of 1,25-dihydroxyvitamin D3 per gram of carrier.
  • the dosage form contains about 5 ⁇ g to 3 mg of 1,25-dihydroxyvitamin D3 per gram of carrier. More preferably, the dosage form contains about 10 to 30 micrograms of 1,25-dihydroxyvitamin D3 per gram of carrier. A most preferred dosage form contains about 15 ug of 1,25-dihydroxyvitamin D3 per gram of carrier.
  • the compounds can be employed in dosage forms such as tablets, capsules, powder packets, or liquid solutions, suspensions or elixirs for oral administration, sterile liquid for formulations such as solutions or suspensions for parenteral use.
  • a pharmacologically inert topical carrier such as one comprising a gel, an ointment or a cream, including such carriers as water, glycerol, alcohol, propylene glycol, fatt alcohols, triglycerides, fatty acid esters or mineral oils.
  • liquid petroleum isopropylpalirritate, polyethy ⁇ lene glycol ethanol 95%, polyoxyethylene monolaurate 5% in water, sodium lauryl sulfate 5% in water, and the like.
  • Materials such as anti-oxidants, humectants, viscosity stabilizers and the like may be added, if necessary.
  • the compounds may also be present as part of a cosmetic formulation which may be formulated according to methods known to those of skill in the art. The compounds can also be administered by means of pumps, tapes or patches.
  • Rats were anesthetized with ether. Their backs were prepared by clipping and shaving. Two cutaneous wounds were made on each rat by punching on the right and left sides of the back with a sterile biopsy punch (diameter 4mm, wound thickness: full thickness of skin).
  • Control rats received vehicle only on wounds (20 ⁇ l vegetable oil/two wounds/day for 4 days).
  • the other four groups of rats (5 rats per group) were used to study the effect of 1,25(0H)2D3 on wound healing at different doses (5 ⁇ g l,25(0H)2D3/g oil, 10 ⁇ g/g oil, 27 ⁇ g/g oil and 54 ⁇ g/g oil 1,25 (0H)2D3). Treatment continued for up to 4 days.
  • Wound area was estimated by planimetry. For this purpose, the wound was covered with a transparent plastic film and wound outlines were drawn with a marker. Wound shape was then magnified, was cut out, and weighed.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

On a mis au point des procédés améliorant la cicatrisation de plaies, améliorant la cicatrisation d'ulcères gastriques, duodénaux, oesophagiens, de décubitus et génito-urinaires, et de la kératite ulcérative; inhibant la formation de cicatrices; et de traitement de maladies périodontiques chez l'animal par administration locale, orale, parentérale, transdermique ou ophtalmique d'un composé de vitamine D.
EP19900916599 1989-10-04 1990-10-04 Method of accelerating wound and ulcer healing and treating periodontal disease Withdrawn EP0494995A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41678189A 1989-10-04 1989-10-04
US416781 1989-10-04

Publications (2)

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EP0494995A1 true EP0494995A1 (fr) 1992-07-22
EP0494995A4 EP0494995A4 (en) 1993-03-17

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EP (1) EP0494995A4 (fr)
JP (1) JPH05503922A (fr)
WO (1) WO1991005537A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69331833T2 (de) * 1992-12-29 2002-11-14 Michael F. Holick Verwendung von vitamin d-glykosiden zur behandlung oder prävention von osteoporose
TW422696B (en) * 1995-03-20 2001-02-21 Katsuhiko Mukai Ophthalmic composition containing active vitamin D
JP3738450B2 (ja) * 1995-11-20 2006-01-25 喜代司 喜多 ビタミンｄ類やビタミンｋ類を配合した外用剤
JP3221884B2 (ja) * 1997-05-26 2001-10-22 株式会社ニュービジョン ビタミンｄ類を配合した点眼抗アレルギー剤
CA2292879A1 (fr) * 1997-06-10 1998-12-17 New Vision Co., Ltd. Agents prophylactiques et/ou remedes contenant de la vitamine d pour prevenir et/ou traiter le xerosis conjonctival/corneen
US6187331B1 (en) 1997-06-10 2001-02-13 New Vision Co., Ltd. Composition for prophylaxis and/or treatment of dry syndrome comprising vitamin D
US20070299041A1 (en) * 2004-05-26 2007-12-27 Cedars-Sinai Medical Center Induction of innate immunity by vitamin d3 and its analogs
EP1781302A4 (fr) * 2004-07-28 2010-02-17 Lipopeptide Ab Nouvelle utilisation

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3622668A (en) * 1969-08-27 1971-11-23 Joe B Moss Method of promoting scar-free healing of skin lacerations
DE2249414A1 (de) * 1972-10-09 1974-04-25 Georg Dr Rueckheim Brand- und wundsalbe
WO1984002845A1 (fr) * 1983-01-21 1984-08-02 Advanced Drug Tech Onguent pour les soins de la peau contenant des vitamines
DE3800972A1 (de) * 1988-01-15 1989-07-27 Asche Karl W Salbe

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655881A (en) * 1970-01-22 1972-04-11 Commercial Solvents Corp Method of treating burned skin
US4410515A (en) * 1981-04-01 1983-10-18 Massachusetts General Hospital Vitamin D glycosides and a method of use
US4610978A (en) * 1983-03-22 1986-09-09 Yissum Research Development Company Of The Hebrew University Of Jerusalem Compositions containing 1α-hydroxycholecalciferol for topical treatment of skin disorders and methods employing same
US4521410A (en) * 1984-05-03 1985-06-04 The General Hospital Corporation Vitamin D glycosyl orthoesters
US4728643A (en) * 1984-11-02 1988-03-01 The General Hospital Corporation Method of treating psoriasis

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3622668A (en) * 1969-08-27 1971-11-23 Joe B Moss Method of promoting scar-free healing of skin lacerations
DE2249414A1 (de) * 1972-10-09 1974-04-25 Georg Dr Rueckheim Brand- und wundsalbe
WO1984002845A1 (fr) * 1983-01-21 1984-08-02 Advanced Drug Tech Onguent pour les soins de la peau contenant des vitamines
DE3800972A1 (de) * 1988-01-15 1989-07-27 Asche Karl W Salbe

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 96, 1982, page 150, abstract 194070y, Columbus, Ohio, US; T. SAITOH et al.: "Effect of 1alpha-hydroxycholecalciferol and anabolic steroids on the healing of experimental extraction wounds, studied by microradiogram and calcium-45 autoradiogram" & SHIGAKU, 1982, 69(5), 864-897 *
CLINICAL RESEARCH, vol. 38, no. 2, April 1990 page 640A; X.A. TIAN et al.: "1,25-dihydroxyvitamin D3: A novel agent for wound healing" *
See also references of WO9105537A1 *

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