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WO1996037193A1 - Agents a appliquer localement pour le traitement et la prophylaxie de l'alopecie - Google Patents

Agents a appliquer localement pour le traitement et la prophylaxie de l'alopecie Download PDF

Info

Publication number
WO1996037193A1
WO1996037193A1 PCT/EP1996/002195 EP9602195W WO9637193A1 WO 1996037193 A1 WO1996037193 A1 WO 1996037193A1 EP 9602195 W EP9602195 W EP 9602195W WO 9637193 A1 WO9637193 A1 WO 9637193A1
Authority
WO
WIPO (PCT)
Prior art keywords
vitamin
liposome
liposomes
topically applicable
treating
Prior art date
Application number
PCT/EP1996/002195
Other languages
German (de)
English (en)
Inventor
Ralph Lipp
Jutta Riedl
Andreas Sachse
Georg Rössling
Original Assignee
Schering Aktiengesellschaft
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 Schering Aktiengesellschaft filed Critical Schering Aktiengesellschaft
Priority to JP8535377A priority Critical patent/JPH11505262A/ja
Priority to AU58199/96A priority patent/AU5819996A/en
Priority to EP96919796A priority patent/EP0827395A1/fr
Publication of WO1996037193A1 publication Critical patent/WO1996037193A1/fr

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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K8/67—Vitamins
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • Topical agents for the treatment and prophylaxis of alopecia Topical agents for the treatment and prophylaxis of alopecia
  • the invention relates to topically applicable agents for the treatment and prophylaxis of alopecia, which is characterized by a content of vitamin D analogs encapsulated in liposomes.
  • vitamin D analogues can be used to treat various forms of alopecia.
  • GB-A 2 260 903 and WO 93/00079 describe topically administrable compositions which contain vitamin D analogues in ointments, creams, gels or lotions. Since these previously known formulations, in particular if they additionally contain penetration-enhancing agents such as ethanol or propylene glycol, also have a systemic activity, they also develop undesirable side effects in addition to the desired therapeutic effect. In particular, they also influence calcium metabolism, which can lead to hypercalcemia and hypercalcuria.
  • topically administrable agents according to the invention which contain vitamin D analogs encapsulated in liposomes, are extremely effective in treating various forms of alopecia, but in contrast to the previously known agents, undesirable systemic side effects are not observed in them.
  • Vitamin D analogs which are suitable for the preparation of the agents according to the invention are, for example, calcitriol (l ⁇ , 25-dihydroyvitamin D3), calcifediol (25-hydroxyvitamin D3), calcipotriol (CAS-1128-00-9) and colecalciferol (Vitamin Ds) and the tacalcitol (CAS-57333-96-7).
  • the vitamin D analogs mentioned in the abovementioned GB-A 2 260 903 and WO 93/00079 are also suitable for producing the agents according to the invention.
  • the compounds described in WO 94/07853 are also suitable as suitable vitamin D analogs, such as, for example, the (5Z, 7E, 22E) - (1S, 3, 24R) -1, 3,24-trihydroxy-9, 10-secocholesta-5,7, 10 (19), 22-tetraen-25-carboxylic acid isopropyl ester.
  • Suitable liposome-forming substances are in particular phospholipids, such as the sphingomyeline, the plasmalogens, the phosphatidylcholines, the phosphatidylethanolamines, the phosphatidylserines, the phosphatidylinosites and the cardiolipins, or else mixtures of these lipids (Dr. Otto-Albert Neumüller: Römpps Chemie-Lexikon; Franksche Verlag Stuttgart, Franksche Verlag Stuttgart (DE), 9th edition, 1991, 3383f) and mixtures of these phospholipids with cholesterol and / or charge carriers, such as, for example, stearylamine, stearic acid or diacetyl phosphate.
  • phospholipids such as the sphingomyeline, the plasmalogens, the phosphatidylcholines, the phosphatidylethanolamines, the phosphatidylserines, the phosphatidylinosites and
  • phospholipid or lipid mixture based on the aqueous phase, is usually used to prepare the liposome suspensions.
  • Suitable mixtures can contain up to 60 percent by weight of cholesterol and up to 30 percent by weight of charge carriers.
  • Ethanol, methanol, isopropanol, diethyl ether, acetone, chloroform and mixtures of these solvents are preferably used as solvents.
  • the process is advantageously carried out under an inert gas atmosphere, such as nitrogen or argon, and the aqueous liposome solutions obtained are stabilized by adding antioxidants, such as sodium ascorbate, tocopherol or sodium bisulfite.
  • aqueous liposome solutions can also contain additional active ingredients, such as bactericides, preservatives and / or buffer substances.
  • the encapsulation of the vitamin D analogs in liposomes can be carried out under the same conditions as the previously known methods of this type (pharmacy in our time ü, 1982, 97-108; Pure Appl. Chem., 53, 1981, 2241-2254) .
  • the encapsulation of the vitamin D analogs can take place both in multilamellar liposomes and in unilamellar liposomes.
  • the active substance-containing liposome suspensions prepared in this way can be diluted with water if necessary and / or thickeners, such as, for example, hydroxyethyl cellulose, methyl cellulose, Aerosil® (Herseller Degussa AG, DE), Carbopol® (BFGoodrich Chem., USA) etc. can be added to make them spreadable To produce gels.
  • thickeners such as, for example, hydroxyethyl cellulose, methyl cellulose, Aerosil® (Herseller Degussa AG, DE), Carbopol® (BFGoodrich Chem., USA) etc.
  • the optimal concentration of active substance in the finished pharmaceutical preparations naturally depends on the type of active substance and the galenical preparation and must be determined in individual cases using the usual preliminary tests. As a rule, it will be sufficient to use pharmaceutical preparations which use 0.001 to 1 mg and preferably 0.005 to 0.1 mg of vitamin D analogs per g of preparation.
  • the liposome suspension obtained contains liposomes with an average size of 112 nm.
  • the phosphatidylcholine content is 9 mg per g; the content of encapsulated! Active ingredient is 0.1 mg per g.
  • the solution is then evaporated to dryness in a 500 ml round-bottom flask on a rotary evaporator, a lipid film forming on the glass wall. This lipid film is removed with 98.9 g of double-distilled water.
  • the suspension obtained is then subjected to high-pressure extrusion, as described in PCT / DE93 / 00997, using Nucleopore® membranes with a decreasing pore size of 5.0, 1.0, 0.4, 0.2, 0.1 and 0.05 ⁇ m is used.
  • the liposome suspension obtained contains liposomes with an average size of 94 nm and otherwise has the same properties as the preparation described in Example 1.
  • the liposome suspension thus obtained contains liposomes with an average size of 106 nm.
  • the phosphatidylcholine content is 9.0 mg per g, the active ingredient content is 0.04 mg per g.
  • the liposome suspension obtained contains liposomes with an average size of 220 nm.
  • the phosphatidylcholine content is 10 mg per g; the content of encapsulated! Active ingredient is 0.2 mg per g.
  • the liposome suspensions prepared according to Examples 1 and 3 are mixed with 0.18%
  • the liposomes are still suspended in the aqueous phase. You are intact.
  • the liposome suspensions prepared according to Examples 1 and 3 are freeze-dried.
  • BHT 2,6-di tert-butyl-4-methylphenol

Landscapes

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

Abstract

L'invention a pour objet des agents à appliquer localement pour le traitement et la prophylaxie de l'alopécie, caractérisés par une teneur en analogues de vitamine D encapsulés en liposomes.
PCT/EP1996/002195 1995-05-22 1996-05-22 Agents a appliquer localement pour le traitement et la prophylaxie de l'alopecie WO1996037193A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP8535377A JPH11505262A (ja) 1995-05-22 1996-05-22 脱毛治療及び脱毛予防のための局所適用可能な薬剤
AU58199/96A AU5819996A (en) 1995-05-22 1996-05-22 Topically applicable agents for treating and preventing alopecia
EP96919796A EP0827395A1 (fr) 1995-05-22 1996-05-22 Agents a appliquer localement pour le traitement et la prophylaxie de l'alopecie

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19519273A DE19519273A1 (de) 1995-05-22 1995-05-22 Topisch applizierbare Mittel zur Behandlung und Prophylaxe der Alopezie
DE19519273.7 1995-05-22

Publications (1)

Publication Number Publication Date
WO1996037193A1 true WO1996037193A1 (fr) 1996-11-28

Family

ID=7762883

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/002195 WO1996037193A1 (fr) 1995-05-22 1996-05-22 Agents a appliquer localement pour le traitement et la prophylaxie de l'alopecie

Country Status (7)

Country Link
EP (1) EP0827395A1 (fr)
JP (1) JPH11505262A (fr)
KR (1) KR19990021864A (fr)
AU (1) AU5819996A (fr)
CA (1) CA2222061A1 (fr)
DE (1) DE19519273A1 (fr)
WO (1) WO1996037193A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997037637A1 (fr) * 1996-04-04 1997-10-16 Ortho Pharmaceutical Corporation Formulation topique de vitamine d a base de liposomes
WO2003028674A3 (fr) * 2001-10-02 2003-12-11 Cedars Sinai Medical Center Procede pour stimuler la repousse des cheveux par l'administration des analogues de la vitamine d
EP2464357A4 (fr) * 2009-08-14 2013-08-14 Berg Pharma Llc Vitamine d3 et ses analogues pour le traitement de l'alopécie
EP3969005A4 (fr) * 2019-05-17 2023-10-04 The Trustees of The University of Pennsylvania Procédés et compositions pour le traitement de l'obésité et/ou de troubles cutanés

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030219465A1 (en) * 2002-05-23 2003-11-27 Suresh Kumar Gidwani Composition for delivery of dithranol
US9375388B2 (en) 2011-09-23 2016-06-28 Indian Institute Of Technology, Bombay Nanoparticle based cosmetic composition
FR3017290B1 (fr) * 2014-02-10 2017-05-12 Dermaconcept Jmc Composition pour lutter contre la chute des cheveux
CN113498344A (zh) 2018-12-06 2021-10-12 脂康生命科学有限公司 维生素d纳米乳液及其用途

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5116605A (en) * 1989-03-09 1992-05-26 Alt John P Composition and skin treatment method therewith for mitigating acne and male-pattern baldness
US5190935A (en) * 1989-07-10 1993-03-02 Leo Pharmaceutical Products Ltd. Vitamin d analogues
US5374629A (en) * 1990-03-30 1994-12-20 Leo Pharmaceutical Products Ltd. A/S Lovens Kemiske Fabrik Produktionsaktieselskab Vitamin D analogues
US5401731A (en) * 1989-06-29 1995-03-28 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Productionsaktieselskab) Vitamin D analogues
EP0664287A1 (fr) * 1994-01-20 1995-07-26 Duphar International Research B.V Dérivés de vitamine D et leur procédé de préparation
US5447924A (en) * 1990-08-15 1995-09-05 Leo Pharmaceutical Products Ltd. Vitamin D analogues

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5116605A (en) * 1989-03-09 1992-05-26 Alt John P Composition and skin treatment method therewith for mitigating acne and male-pattern baldness
US5401731A (en) * 1989-06-29 1995-03-28 Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik Productionsaktieselskab) Vitamin D analogues
US5190935A (en) * 1989-07-10 1993-03-02 Leo Pharmaceutical Products Ltd. Vitamin d analogues
US5374629A (en) * 1990-03-30 1994-12-20 Leo Pharmaceutical Products Ltd. A/S Lovens Kemiske Fabrik Produktionsaktieselskab Vitamin D analogues
US5447924A (en) * 1990-08-15 1995-09-05 Leo Pharmaceutical Products Ltd. Vitamin D analogues
EP0664287A1 (fr) * 1994-01-20 1995-07-26 Duphar International Research B.V Dérivés de vitamine D et leur procédé de préparation

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997037637A1 (fr) * 1996-04-04 1997-10-16 Ortho Pharmaceutical Corporation Formulation topique de vitamine d a base de liposomes
US5834016A (en) * 1996-04-04 1998-11-10 Cilag Ag Liposome-based topical vitamin D formulation
WO2003028674A3 (fr) * 2001-10-02 2003-12-11 Cedars Sinai Medical Center Procede pour stimuler la repousse des cheveux par l'administration des analogues de la vitamine d
EP2464357A4 (fr) * 2009-08-14 2013-08-14 Berg Pharma Llc Vitamine d3 et ses analogues pour le traitement de l'alopécie
AU2010282731B2 (en) * 2009-08-14 2015-08-13 Berg Llc Vitamin D3 and analogs thereof for treating alopecia
AU2010282731C1 (en) * 2009-08-14 2016-04-21 Berg Llc Vitamin D3 and analogs thereof for treating alopecia
AU2015238850B2 (en) * 2009-08-14 2017-08-24 Berg Llc Vitamin D3 and analogs thereof for treating alopecia
US9901637B2 (en) 2009-08-14 2018-02-27 Berg Llc Vitamin D3 and analogs thereof for treating alopecia
US11305016B2 (en) 2009-08-14 2022-04-19 Berg Llc Vitamin D3 and analogs thereof for treating alopecia
EP3969005A4 (fr) * 2019-05-17 2023-10-04 The Trustees of The University of Pennsylvania Procédés et compositions pour le traitement de l'obésité et/ou de troubles cutanés

Also Published As

Publication number Publication date
AU5819996A (en) 1996-12-11
DE19519273A1 (de) 1996-11-28
KR19990021864A (ko) 1999-03-25
EP0827395A1 (fr) 1998-03-11
JPH11505262A (ja) 1999-05-18
CA2222061A1 (fr) 1996-11-28

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