WO1994014453A1 - Composes hydroxy de vitamine d3 destines au traitement de l'atrophie cutanee - Google Patents

Composes hydroxy de vitamine d3 destines au traitement de l'atrophie cutanee Download PDF

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Publication number
WO1994014453A1
WO1994014453A1 PCT/DK1993/000426 DK9300426W WO9414453A1 WO 1994014453 A1 WO1994014453 A1 WO 1994014453A1 DK 9300426 W DK9300426 W DK 9300426W WO 9414453 A1 WO9414453 A1 WO 9414453A1
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WO
WIPO (PCT)
Prior art keywords
hydroxy
triene
dihydroxy
seco
formula
Prior art date
Application number
PCT/DK1993/000426
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English (en)
Inventor
Jørgen Vedelskov SERUP
Original Assignee
Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab)
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 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) filed Critical Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab)
Priority to AU58088/94A priority Critical patent/AU678800B2/en
Priority to EP94903742A priority patent/EP0675722A1/fr
Priority to JP6514698A priority patent/JPH08504776A/ja
Publication of WO1994014453A1 publication Critical patent/WO1994014453A1/fr

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    • 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
    • A61P17/00—Drugs for dermatological disorders

Definitions

  • Hydroxy vitamin D3 compounds for treating skin atrophy are Hydroxy vitamin D3 compounds for treating skin atrophy.
  • This invention relates to the use of vitamin D ana ⁇ logues for prevention and/or treatment of steroid induced skin atrophy, and to the use of such compounds in the preparation of pharmaceutical compositions for the prevention and/or treatment of steroid induced skin atrophy and in the preparation of steroid containing pharmaceutical compositions without the potential of causing skin atrophy.
  • the induction of skin atrophy by treatment with ste- roids is a well known phenomenon 1 3 .
  • Steroid induced skin atrophy is mostly due to a decrease in collagen synthesis as a consequence of in ⁇ teraction of the steroid-receptor complex with certain specific regions in DNA to give a downregulation of mRNA and a reduced activity of enzymes involved in collagen bio ⁇ synthesis.
  • vita ⁇ min D analogues can prevent and/or treat skin atrophy induced by topical steroid treatment, despite the fact that these analogues have been shown not to interact with the steroid receptor and are known not to enhance collagen synthesis in skin cells, but in fact to inhibit collagen synthesis in a number of cell types 9 10 11 12 13 .
  • An enhanced inhibition of collagen synthesis is for instance observed in vi tro when dexamethasone and the natural active form of vitamin D- , l ⁇ , 25-dihydroxy vitamin D 3 (1, 25 (OH) 2 3 ) are used in combination 14 .
  • Examples 9 and 10 describe the prevention and the treatment, respectively, of corticosteroid induced atrophy.
  • Topical application of the natural form of ac ⁇ tive vitamin D, i.e. 1, 25- (OH) _D_ represents one possi- bility for such treatment, but because of its potent cal- cemic activity there will be a risk that, through transder- al absorption, it will give rise to undesired systemic effects leading to hypercalcemia.
  • a vitamin D analogue is chosen which has a more favourable potency ratio between the above described throphic effect and the effect on calcium metabolism compared to 1, 25- (OH) _D g , whereby it is possible to prevent and/or treat steroid induced skin atrophy successfully without having the risk of inducing hypercalcemia.
  • Examples of such vitamin D analogues for use in the present pharmaceutical preparations are
  • formula X stands for hydrogen, C. -C -alkyl, halogen or hydroxy
  • Y stands for hydrogen or hydroxy
  • R 1 and R2 which may be the same or different, stand for C.-C,-alkyl, optionally substituted with halogen or hydroxy, with the proviso that R 1 and R2 cannot both be methyl when X is other than C. -C,-alkyl, or R 1 and R2, when taken together with the carbon atom numbered 25, can form a saturated or unsaturated
  • R stands for hydrogen or C.-Cg,- R 4 and R5 represent either each hydrogen, or when taken together constitute a bond with the result that a double bond connects carbon atoms numbered 22 and 23 ; and bio- reversible derivatives thereof,
  • R and R 4 represent either both hydrogen, or when taken together constitute a bond, such double bond (either in the Z or E configuration) connecting carbons numbered 22 and 23; and derivatives of the compounds of formula I in which one or more hydroxy groups have been transformed into -O-acyl or -O-glycosyl or phos ⁇ phate ester groups, such masked groups being hydro- lyzable in vivo, or derivatives of the compounds of formula I in which the hydroxyl group at the starred carbon atom is lacking, these compounds being converted to active compounds of formula I by enzyma ⁇ tic hydroxylation after administration,
  • formula R stands for an alkyl group contain ⁇ ing from 7 to 12 carbon atoms optionally substituted with a hydroxy group; and derivatives of the compounds of formula I in which one or more hydroxy groups have been transformed into -O-acyl or -O-glycosyl or phosphate ester groups, such masked groups being hydrolyzable in vivo,
  • formula R stands for an alkyl group contain ⁇ ing from 4 to 12 carbon atoms optionally substituted with a hydroxy group; and derivatives of the compounds of formula I in which one or more hydroxy groups have been transformed into -O-acyl or -O-glycosyl or phosphate ester groups, such masked groups being hydrolyzable in vivo,
  • KH 1060 (example 5 in said patent application, 1 (S) , 3 (R) -di- hydroxy-20 (R) - (4' -hydroxy-4' -ethyl-1' -hexyloxy) -9, 10- -seco-pregna-5 (Z) , 7 (E) , 10 (19) -triene (confer also Hansen, K., Calverley, M.J. and Binderup, L., Syn ⁇ thesis and biological activity of 22-oxa vitamin D analogues. In: Vitamin D. Gene Regulation, Structure- Function Analysis and Clinical Application (Eds. Nor ⁇ man, A.W. , Bouillon, R. and Thomasset, M.) , pp. 161- 62. Walter de Gruyter, Berlin, 1991.)
  • n 0 or 1
  • m is O or an integer from 1 - 7
  • R 1 - and R (which may be the same or dif ⁇ ferent) stand for hydrogen or C- ⁇ -Cg-hydrocarbyl, hydrocarbyl indicating the residue after removal of a hydrogen atom from a straight, branched or cyclic saturated or unsaturated hydrocarbon, or, taken together with the carbon bearing the hydroxyl group (starred in formula I) , R 1 and R 2 can form a satu ⁇ rated or unsaturated C 3 -C Q carbocyclic ring; in addi ⁇ tion, R 1 and/or R and/or one of the m carbons desig ⁇ nated by the "°" may be optionally substituted with a hydroxyl group or one or more chlorine or fluorine atom(s) ; and finally one of the carbons designated "°” may optionally be substituted by one or two C ⁇ - C2 alkyl group (s) ,* and derivatives of
  • n is 2 or 3
  • m is 0 or an integer from 1 - 4
  • R 1 and R 2 (which may be the same or dif ⁇ ferent) stand for hydrogen or C- ⁇ -C -hydrocarbyl, hydrocarbyl indicating the residue after removal of a hydrogen atom from a straight, branched or cyclic saturated or unsaturated hydrocarbon, or taken together with the carbon bearing the hydroxyl group (starred in formula I) , R 1 and R 2 can form a satu ⁇ rated or unsaturated C 2 ⁇ Q carbocyclic ring,- in addi ⁇ tion, R 1 and/or R and/or one of the m carbons desig ⁇ nated by the "°” may be optionally substituted with one or more chlorine or fluorine atom(s); and finally one of the carbons designated "°” may optionally be substituted by one or two C 1 -C 2 alkyl group(s) ,* and derivatives of the com- pounds of formula I in which
  • R and R may be the same or different and stand for hydrogen, C- ⁇ -C ⁇ -alkyl, C3-C 7 -cycloalkyl, or taken together with the carbon atom (starred in for- mula I) , bearing the groups X, Ri and R_? , can form a
  • formula X is hydrogen or hydroxy
  • Y is oxy ⁇ gen or sulphur or oxidized sulphur (S(O) or S(0 2 ))
  • R and R which may be the same or different, stand for hydrogen or C- ⁇ Cg hydrocarbyl; or R 1 and R 2 , taken together with the carbon atom (starred in for ⁇ mula I) bearing the group X, can form a C 3 -C carbo- cyclic ring
  • Q is a C- ⁇ -Cg hydrocarbylene diradical
  • R 3 is hydrogen or C- ⁇ -Cg hydrocarbyl
  • R 1 , R 2 and/or Q may be optionally substituted with one or more deu ⁇ terium or fluorine atoms
  • n is 0 or 1
  • R 1 and R2 which may be the same or different, stand for hydrogen or C 1 -C 8 hydrocarbyl; or R 1 and R2, taken together with the carbon atom (starred in formula I) bearing the group X, can form a C 3 -C_ carbocyclic ring;
  • Q is a single bond or a C. -C R hydrocarbylene diradical, the expression hydrocarbyl radical
  • hydrocarbylene diradical indicating the residue after removal of 1 (2) hydrogen atom(s) from a straight, branched or cyclic saturated or unsaturated hydrocarbon; m is 0, 1 or 2; R 1, R2 and/or Q may be optionally substituted with one or more deuterium or fluorine atoms,- in addition, one of the m carbons designated by the "°” may be optionally substituted with one or more deuterium or fluorine atom(s), or one or two C.-C_ alkyl group(s) ; and derivatives of the compounds of formula I in which one or more hydroxy groups have been transformed into -O-acyl or
  • formula X is hydrogen or hydroxy; R 1 and R2, which may be the same or different, stand for hydrogen or a C " ' 1. --CC6, hydrocarbyl radical; or R and
  • R stands for hydrogen or a C_.-C_. Q hydrocarbyl radical or for YR , in which Y stands for the radicals -CO-, -CO-0-, -CO-S-, -CS-, -CS-0-,
  • R stands for hydrogen or a C.-C. n hydrocarbyl radical
  • Q is a single bond or a
  • R , R , R and/or Q may be optionally substituted with one or more deuterium or fluorine atoms,
  • Particularly preferred compound for use according to the invention are compounds selected from the group consisting of
  • steroids examples include alklo etason, klobetason, desonid, flumetason, fluprednidin, desoximetason, diflorason, fluocinolonacetonid, fluokortolon, mometason, klobetasol, fluticasone, halobetasol propionate, halometasone, methylprednisolone aceponate, mometasone furoate, tipredane, amcinonide, budesonide, betamethasone, dexamethasone, prednicarbate, and esters thereof.
  • the mentioned compounds shall form part of pharmaceu ⁇ tical preparations, in particular for topical use, such as a liniment, a lotion, a cream or a gel, either in a combi- nation product containing both the steroid used in the treatment of human disorders as described above and the vitamin D analogue, or alone and then used alternating with the steroid treatment or the same time as the steroid application.
  • concentration of the active ingredients will depend upon the choice of vitamin D analogues but will generally be between 1 and 100 ⁇ g/g.
  • the formulations will be applied once or more times daily, depending on the regimen of the steroid treatment, for prolonged periods of time.
  • the formulations prepared according to the present invention comprise an active compound in association with a pharmaceutically acceptable vehicle therefore and option- ally other therapeutic ingredient (s) .
  • the vehicle (s) must be "acceptable” in the sense of being compatible with the other ingredients of the preparations and not deleterious to the recipient thereof.
  • Preparations suitable for topical administration include liquid or semi-liquid preparations such as lini ⁇ ments, lotions, applicants, oil-in-water or water-in-oil emulsions such as creams, ointments, pastes or gels; or solutions or suspensions.
  • the preparations of this invention may include one or more ad ⁇ ditional ingredients such as diluents, buffers, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti- -oxidants) , emulsifying agents and the like.
  • ad ⁇ ditional ingredients such as diluents, buffers, binders, surface active agents, thickeners, lubricants, preservatives, e.g. methyl hydroxybenzoate (including anti- -oxidants) , emulsifying agents and the like.
  • ointments, creams, gels, or lotions containing from 1-100 ⁇ g/g of the vitamin D ana ⁇ logues or metabolites, possibly in a mixture with a steroid in usually applied concentrations are administered.
  • the present invention further concerns a method for preventing and/or treating atrophy in patients undergoing treatment with steroids, said method consisting of ad ⁇ ministering topically to the said patient in need of treat ⁇ ment an effective amount of one or more of the above men- tioned vitamin D analogues, alone or in combination with the steroid applied in the said treatment.
  • the treatment with a formulation containing a vitamin D analogue as the only active ingredient may be undertaken simultaneously or separately with the steroid treatment.
  • Example 2 Cream containing 22-oxa-lo..25-dihydroxy- vitamin D-,
  • Cetomacrogol 1000 30 g Cetostearyl alcohol 60 g
  • Example 8 Lotion containing MC 903 and betamethasone 17-valerate
  • KH1060 thus can prevent Corticosteroid-induced atro ⁇ phy of murine skin during simultaneous application of KH106 and the corticoid for a four week period.
  • Example 10 Treatment of established Corticosteroid induced atrophy with KH1060

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

Abstract

Utilisation de certains analogues de vitamine D dans la préparation d'une préparation pharmaceutique destinée à la prophylaxie et/ou au traitement de l'atrophie cutanée stéroïdienne.
PCT/DK1993/000426 1992-12-23 1993-12-17 Composes hydroxy de vitamine d3 destines au traitement de l'atrophie cutanee WO1994014453A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU58088/94A AU678800B2 (en) 1992-12-23 1993-12-17 Hydroxy vitamin D3 compounds for treating skin atrophy
EP94903742A EP0675722A1 (fr) 1992-12-23 1993-12-17 Composes hydroxy de vitamine d3 destines au traitement de l'atrophie cutanee
JP6514698A JPH08504776A (ja) 1992-12-23 1993-12-17 皮膚萎縮を処置するためのヒドロキシビタミンｄ３化合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB929226860A GB9226860D0 (en) 1992-12-23 1992-12-23 Novel treatment
GB9226860.6 1992-12-23

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WO1994014453A1 true WO1994014453A1 (fr) 1994-07-07

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EP (1) EP0675722A1 (fr)
JP (1) JPH08504776A (fr)
AU (1) AU678800B2 (fr)
CA (1) CA2150827A1 (fr)
GB (1) GB9226860D0 (fr)
NZ (1) NZ259318A (fr)
WO (1) WO1994014453A1 (fr)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0667166A1 (fr) * 1993-09-01 1995-08-16 Teijin Limited Composition d'emulsion a base de 1-alpha, 24-dihydroxy-vitamine d3
EP0711558A1 (fr) * 1994-10-21 1996-05-15 Unilever Plc Des compositions pour application topique sur la peau, les cheveux et les argles
DE19744127A1 (de) * 1997-10-01 1999-04-15 Schering Ag Neue Vitamin D-Derivate mit Cyclopropylringen in den Seitenketten, Verfahren und Zwischenprodukte zu ihrer Herstellung sowie ihre Verwendung zur Herstellung von Arzneimitteln
EP0979654A1 (fr) * 1998-03-04 2000-02-16 Teijin Limited Lotions de vitamines d 3? activees sous forme d'emulsion
WO2000064450A1 (fr) * 1999-04-23 2000-11-02 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) Composition pharmaceutique
WO2002017932A1 (fr) * 2000-08-30 2002-03-07 Chugai Seiyaku Kabushiki Kaisha Preparations d'oct
WO2002034235A1 (fr) * 2000-10-27 2002-05-02 Leo Pharma A/S Composition topique contenant au moins une vitamine d ou un analogue de vitamine d et au moins un corticosteroide
WO2007036802A2 (fr) * 2005-07-07 2007-04-05 Teva Pharmaceutical Industries Limited Forme dosifiee
US7279477B2 (en) 2001-01-26 2007-10-09 Chugai Seiyaku Kabushiki Kaisha Malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US7285562B2 (en) 2003-08-01 2007-10-23 Chugai Seiyaku Kabushiki Kaisha Cyanoamide compounds useful as malonyl-CoA decarboxylase inhibitors
US7385063B2 (en) 2001-01-26 2008-06-10 Chugai Seiyaku Kabushiki Kaisha Method for preparing imidazole derivatives
US7449482B2 (en) 2003-08-01 2008-11-11 Chugai Seiyaku Kabushiki Kaisha Piperidine compounds useful as malonyl-CoA decarboxylase inhibitors
US7524969B2 (en) 2001-01-26 2009-04-28 Chugai Seiyaku Kabushiki Kaisha Malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
EP2056791A2 (fr) * 2006-08-29 2009-05-13 Teva Pharmaceutical Industries Ltd. Compositions pharmaceutiques à base de vitamine d et de corticostéroïdes
US7696365B2 (en) 2003-08-01 2010-04-13 Chugai Seiyaku Kabushiki Kaisha Heterocyclic compounds useful as malonyl-CoA decarboxylase inhibitors
US7709510B2 (en) 2001-02-20 2010-05-04 Chugai Seiyaku Kabushiki Kaisha Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US7723366B2 (en) 2001-02-20 2010-05-25 Chugai Seiyaku Kabushiki Kaisha Azole compounds as malonyl-CoA decarboxylase inhibitors for treating metabolic diseases
US7786145B2 (en) 2003-08-01 2010-08-31 Chugai Seiyaku Kabushiki Kaisha Cyanoguanidine-based azole compounds useful as malonyl-CoA decarboxylase inhibitors
EP2222635A2 (fr) * 2007-11-20 2010-09-01 Abbott Laboratories Nouveaux activateurs du récepteur de la vitamine d et procédés de fabrication
WO2016182258A3 (fr) * 2015-05-08 2017-01-12 (주)동구바이오제약 Composition pharmaceutique présentant une stabilité et une pénétration cutanée améliorées

Families Citing this family (1)

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JP4511639B2 (ja) * 1997-12-09 2010-07-28 中外製薬株式会社 ビタミンｄ３誘導体を含有するクリーム剤

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WO1992001454A1 (fr) * 1990-07-18 1992-02-06 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) Utilisation d'analogues de 20(r)-22-oxavitamine d pour le traitement du vieillissement de la peau
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WO1994001398A1 (fr) * 1992-07-03 1994-01-20 Bretting, Claus, Aage, Svensgaard Analogues de la vitamine d

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992001454A1 (fr) * 1990-07-18 1992-02-06 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) Utilisation d'analogues de 20(r)-22-oxavitamine d pour le traitement du vieillissement de la peau
WO1992003414A1 (fr) * 1990-08-15 1992-03-05 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) Nouveaux analogues de la vitamine d
WO1994001398A1 (fr) * 1992-07-03 1994-01-20 Bretting, Claus, Aage, Svensgaard Analogues de la vitamine d

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SUGIMOTO T. ET AL.: "Combined effects of dexamethasone and 1,25-Dihydroxyvitamin D3 on parathyroid hormone secretion in cultured bovine parathyroid cells", ENDOCRINOLOGY, vol. 125, no. 2, 1989, pages 638 - 641 *

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0667166A4 (fr) * 1993-09-01 1995-11-02 Teijin Ltd COMPOSITION D'EMULSION A BASE DE 1-g(a),24-(OH) 2?-VITAMINE D 3?.
US5612327A (en) * 1993-09-01 1997-03-18 Teijin Limited 1α,24-(OH)2 -cholecalciferol emulsion composition and method for treating psoriasis
EP0667166A1 (fr) * 1993-09-01 1995-08-16 Teijin Limited Composition d'emulsion a base de 1-alpha, 24-dihydroxy-vitamine d3
EP0711558A1 (fr) * 1994-10-21 1996-05-15 Unilever Plc Des compositions pour application topique sur la peau, les cheveux et les argles
US7071344B1 (en) 1997-10-01 2006-07-04 Schering Ag Vitamin D derivatives with cyclopropyl rings in the lateral chains, a method and intermediate products for the production thereof and the utilization thereof for producing medicaments
DE19744127A1 (de) * 1997-10-01 1999-04-15 Schering Ag Neue Vitamin D-Derivate mit Cyclopropylringen in den Seitenketten, Verfahren und Zwischenprodukte zu ihrer Herstellung sowie ihre Verwendung zur Herstellung von Arzneimitteln
DE19744127B4 (de) * 1997-10-01 2006-10-05 Schering Ag Neue Vitamin D-Derivate mit Cyclopropylringen in den Seitenketten, Verfahren und Zwischenprodukte zu ihrer Herstellung sowie ihre Verwendung zur Herstellung von Arzneimitteln
EP0979654A1 (fr) * 1998-03-04 2000-02-16 Teijin Limited Lotions de vitamines d 3? activees sous forme d'emulsion
CZ298971B6 (cs) * 1998-03-04 2008-03-26 Teijin Limited Lotion na bázi emulze aktivního vitamínu D3
EP0979654A4 (fr) * 1998-03-04 2002-05-08 Teijin Ltd Lotions de vitamines d 3 activees sous forme d'emulsion
US6753013B1 (en) 1999-04-23 2004-06-22 Leo Pharmaceutical Products, Ltd. A/S Pharmaceutical composition
CZ303142B6 (cs) * 1999-04-23 2012-05-02 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Produktionsaktieselskab) Farmaceutický prostredek pro dermální použití
EP2450043A1 (fr) * 1999-04-23 2012-05-09 Leo Pharma A/S Composition pharmaceutique pour le traitement dermique du psoriasis, du sébopsoriasis ou de la dermatite séborrhéique comprenant une vitamine D et une corticostéroïde
EP2450043B1 (fr) 1999-04-23 2016-08-17 Leo Pharma A/S Composition pharmaceutique pour le traitement dermique du psoriasis comprenant du calcipotriol et de la bétaméthasone
HRP20010779B1 (en) * 1999-04-23 2011-02-28 Leo Pharmaceutical Products Ltd. A/S (Loevens Kemiske Fabrik Produktionsaktieselskab) Pharmaceutical composition
KR100694526B1 (ko) * 1999-04-23 2007-03-13 레오 파마 에이/에스 약제학적 조성물
EP1178808B2 (fr) † 1999-04-23 2019-06-12 Leo Pharma A/S Composition pharmaceutique non aqueuse a usage dermique pour le traitement du psoriasis a base d'une vitamine d, d'une corticosteroide et d'un composant solvant
EP3146969B1 (fr) 1999-04-23 2018-06-20 Leo Pharma A/S Pommade pour le traitement topique du psoriasis
EP2455083A1 (fr) * 1999-04-23 2012-05-23 Leo Pharma A/S Composition pharmaceutique pour application dermique comprenant du calcipotriol et une corticostéroïde
EP3146969A1 (fr) * 1999-04-23 2017-03-29 Leo Pharma A/S Pommades pour le traitement topique du psoriasis
WO2000064450A1 (fr) * 1999-04-23 2000-11-02 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) Composition pharmaceutique
EP2915534A1 (fr) * 1999-04-23 2015-09-09 Leo Pharma A/S Composition pharmaceutique pour le traitement dermique du psoriasis comprenant une vitamine D et une corticostéroïde
WO2002017932A1 (fr) * 2000-08-30 2002-03-07 Chugai Seiyaku Kabushiki Kaisha Preparations d'oct
AU2001282521B2 (en) * 2000-08-30 2005-12-15 Chugai Seiyaku Kabushiki Kaisha OCT preparations
CZ305984B6 (cs) * 2000-10-27 2016-06-08 Leo Pharma A/S V podstatě nevodná farmaceutická gelová kompozice pro aplikaci na kůži obsahující vitamin D nebo jeho analog a kortikosteroid
US6787529B2 (en) 2000-10-27 2004-09-07 Leo Pharmaceutical Products Ltd. A/S Topical composition
WO2002034235A1 (fr) * 2000-10-27 2002-05-02 Leo Pharma A/S Composition topique contenant au moins une vitamine d ou un analogue de vitamine d et au moins un corticosteroide
US7524969B2 (en) 2001-01-26 2009-04-28 Chugai Seiyaku Kabushiki Kaisha Malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US7385063B2 (en) 2001-01-26 2008-06-10 Chugai Seiyaku Kabushiki Kaisha Method for preparing imidazole derivatives
US7279477B2 (en) 2001-01-26 2007-10-09 Chugai Seiyaku Kabushiki Kaisha Malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US8119819B2 (en) 2001-01-26 2012-02-21 Chugai Seiyaku Kabushiki Kaisha Malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US8110686B2 (en) 2001-02-20 2012-02-07 Chugai Seiyaki Kabushiki Kaisha Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US7723366B2 (en) 2001-02-20 2010-05-25 Chugai Seiyaku Kabushiki Kaisha Azole compounds as malonyl-CoA decarboxylase inhibitors for treating metabolic diseases
US7709510B2 (en) 2001-02-20 2010-05-04 Chugai Seiyaku Kabushiki Kaisha Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
US7696365B2 (en) 2003-08-01 2010-04-13 Chugai Seiyaku Kabushiki Kaisha Heterocyclic compounds useful as malonyl-CoA decarboxylase inhibitors
US7786145B2 (en) 2003-08-01 2010-08-31 Chugai Seiyaku Kabushiki Kaisha Cyanoguanidine-based azole compounds useful as malonyl-CoA decarboxylase inhibitors
US7897615B2 (en) 2003-08-01 2011-03-01 Chugai Sciyaku Kabushiki Kaisha Cyanoamide compounds useful as malonyl-CoA decarboxylase inhibitors
US8080665B2 (en) 2003-08-01 2011-12-20 Chugai Seiyaku Kabushiki Kaisha Piperidine compounds useful as malonyl-CoA decarboxylase inhibitors
US7449482B2 (en) 2003-08-01 2008-11-11 Chugai Seiyaku Kabushiki Kaisha Piperidine compounds useful as malonyl-CoA decarboxylase inhibitors
US7285562B2 (en) 2003-08-01 2007-10-23 Chugai Seiyaku Kabushiki Kaisha Cyanoamide compounds useful as malonyl-CoA decarboxylase inhibitors
WO2007036802A3 (fr) * 2005-07-07 2007-08-30 Teva Pharma Forme dosifiee
WO2007036802A2 (fr) * 2005-07-07 2007-04-05 Teva Pharmaceutical Industries Limited Forme dosifiee
EP2056791A2 (fr) * 2006-08-29 2009-05-13 Teva Pharmaceutical Industries Ltd. Compositions pharmaceutiques à base de vitamine d et de corticostéroïdes
EP2222635A2 (fr) * 2007-11-20 2010-09-01 Abbott Laboratories Nouveaux activateurs du récepteur de la vitamine d et procédés de fabrication
WO2016182258A3 (fr) * 2015-05-08 2017-01-12 (주)동구바이오제약 Composition pharmaceutique présentant une stabilité et une pénétration cutanée améliorées

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AU678800B2 (en) 1997-06-12
AU5808894A (en) 1994-07-19
NZ259318A (en) 1997-08-22
JPH08504776A (ja) 1996-05-21
EP0675722A1 (fr) 1995-10-11
CA2150827A1 (fr) 1994-07-07
GB9226860D0 (en) 1993-02-17

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