WO2008064815A2 - Préparation pour l'administration transdermique de galanthamine - Google Patents

Préparation pour l'administration transdermique de galanthamine Download PDF

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Publication number
WO2008064815A2
WO2008064815A2 PCT/EP2007/010112 EP2007010112W WO2008064815A2 WO 2008064815 A2 WO2008064815 A2 WO 2008064815A2 EP 2007010112 W EP2007010112 W EP 2007010112W WO 2008064815 A2 WO2008064815 A2 WO 2008064815A2
Authority
WO
WIPO (PCT)
Prior art keywords
galanthamine
preparation
transdermal
lecithin
oleic acid
Prior art date
Application number
PCT/EP2007/010112
Other languages
German (de)
English (en)
Other versions
WO2008064815A3 (fr
Inventor
Thomas Hille
Original Assignee
Becher, Frank
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 Becher, Frank filed Critical Becher, Frank
Publication of WO2008064815A2 publication Critical patent/WO2008064815A2/fr
Publication of WO2008064815A3 publication Critical patent/WO2008064815A3/fr

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Classifications

    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Definitions

  • the present invention relates to a preparation in the form of a cream, a gel, a lotion, a suppository, an ointment or a transdermal therapeutic system (TTS) for the transdermal administration of the active ingredient galanthamine or one of its pharmaceutically active salts for the treatment of Alzheimer's dementia.
  • TTS transdermal therapeutic system
  • the invention relates to a preparation, the permeation of the active ingredient galanthamine (4 a, 5, 9, 10, 11, 12-hexahydro-3-methoxy-11-methyl-6H-benzofuro (3 a, 3, 2-e, f ) (2) benzazepine-6-ol) or one of its pharmaceutically-acceptable salts through the skin to such an extent as to enable the treatment of Alzheimer's dementia by transdermal administration of galanthamine.
  • galanthamine belongs to the group of reversible cholinesterase inhibitors and, in addition to the inhibition of AChE, has a further mechanism of action with specific modulation of the nicotinic part of cholinergic neurotransmission.
  • Galanthamine has a 3 to 6 times greater therapeutic index, as it does not have the toxicity of physostigmine or neostigmine. This advantage outweighs its dose-covered somewhat lower cholinesterase inhibitory activity.
  • the main applications of galanthamine are the treatment of narrow-angle glaucoma and its use as an antidote to curare applications.
  • Galanthamine has also recently been disclosed for the treatment of alcohol dependence (DE 40 10 079 C2) and nicotine dependence (DE 43 01 782 C1).
  • a daily dose of 24 mg galanthamine hydrobromide corresponds to about 22 mg galanthamine base.
  • a TTS represents the preferred dosage form, it has still not been able to transdermal to bring galanthamine in the required amount for absorption. Since the skin is not a resorptive organ, but primarily has the function of preventing the ingress of foreign bodies, such a high dose is currently not transdermally absorbable with a TTS of acceptable size. There is therefore a need for formulations in the transdermal therapy, with which galanthamine can be administered in these daily doses of up to 22 mg per day, without having to cover in the application skin of 100 cm 2 and more.
  • the object of the invention was therefore to provide a preparation for the transdermal administration of galanthamine, which meets these requirements.
  • This object is achieved in a surprisingly simple manner with a preparation according to claim 1.
  • This solution is all the more astonishing since the administration of lecithin, oleic acid and cholesterol by no means attempted to increase the transdermal absorption of galanthamine. Rather, the starting point of the development was that Alzheimer's dementia is known to be characterized by a deficiency of acetylcholine.
  • the use of galanthamine to treat Alzheimer's dementia follows the idea that galanthamine inhibits acetylcholinesterase. The lack of acetylcholine should be compensated by inhibiting the degradation of the enzyme acetylcholinesterase.
  • the invention was therefore based on the consideration that one compensates for the lack of acetylcholine not only by preventing its degradation, but also that acetylcholine is increasingly produced. This is achieved by adding lecithin in addition.
  • lecithin is particularly suitable so as to reduce the amount of galanthamine required. This not only has the particular advantage of reducing the side effects of galanthamine, but also allows the now reduced dose of galanthamine transdermally applied by a plaster system of acceptable size.
  • the preparation is relatively easy and inexpensive to produce.
  • the preparation according to the invention thus contains as essential constituents lecithin and galanthamine.
  • composition was tested under in vitro conditions on excised human skin in the Franz's diffusion cell known to those skilled in the art.
  • lecithin oleic acid
  • cholesterol a combination of lecithin, oleic acid and cholesterol is capable of reabsorbing galanthamine to the extent that the delivery of 22 mg of galanthamine across the skin is possible through a patch system of acceptable size.
  • the invention is illustrated by the following example:
  • a siliconized polyester film is coated with a solution of a pressure-sensitive adhesive medically acceptable polyacrylate in organic solvent in such a way that, after evaporation of the solvents, a surface weight of about 100 g / m 2 results.
  • the two-layer laminate consisting of siliconized polyester film and solvent-free pressure-sensitive adhesive layer is covered with a non-siliconized 15 ⁇ m thick polyester film.
  • the three-layer laminate, consisting of siliconized polyester film, polyacrylate adhesive layer and non-siliconized polyester film, is cut into 6 cm wide rolls.
  • the siliconized polyester film is removed, and a sheet of 30 cm 2 tea towel paper is placed on the polyacrylate pressure-sensitive adhesive layer.
  • the round plate is now mixed with the preparation Covered on a pressure-sensitive adhesive coated carrier with a removable film. Subsequently, the drug form is punched into a format that the Ronde is surmounted on all sides by pressure-sensitive adhesive. After removing the removable protective layer, the non-oil emulsion soaked Ronde is glued and fixed on the skin of a patient.
  • Table 1 Comparison of galanthamine absorption rates under in vitro conditions to galanthamine absorption rates from a TTS.
  • galanthamine from the non-oil emulsion penetrates, in approximately twice as much, excised human skin.
  • the preparation must be tested in a second step in patients with Alzheimer's dementia in a clinical trial. With this system it should even be possible to bring galanthamine quantities above 20 mg in 24 hours with plaster systems of acceptable size to absorb.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une préparation pour l'administration transdermique de galanthamine, caractérisée en ce que la galanthamine, ou l'un de ses sels pharmaceutiquement acceptable, est amené en l'état de résorption transdermique dans une émulsion non huileuse.
PCT/EP2007/010112 2006-12-01 2007-11-22 Préparation pour l'administration transdermique de galanthamine WO2008064815A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006056783A DE102006056783A1 (de) 2006-12-01 2006-12-01 Zubereitung zur transdermalen Verabreichung von Galanthamin
DE102006056783.8 2006-12-01

Publications (2)

Publication Number Publication Date
WO2008064815A2 true WO2008064815A2 (fr) 2008-06-05
WO2008064815A3 WO2008064815A3 (fr) 2008-07-17

Family

ID=39247230

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/010112 WO2008064815A2 (fr) 2006-12-01 2007-11-22 Préparation pour l'administration transdermique de galanthamine

Country Status (2)

Country Link
DE (1) DE102006056783A1 (fr)
WO (1) WO2008064815A2 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004002402A2 (fr) * 2002-05-21 2004-01-08 Nastech Pharmaceutical Company Inc. Administration d'inhibiteurs d'acetylcholinesterase au liquide cephalorachidien spinal
US20040185170A1 (en) * 2003-03-21 2004-09-23 Shubha Chungi Method for coating drug-containing particles and formulations and dosage units formed therefrom
US20050074487A1 (en) * 1999-12-16 2005-04-07 Tsung-Min Hsu Transdermal and topical administration of drugs using basic permeation enhancers
WO2005039531A1 (fr) * 2003-10-10 2005-05-06 Antares Pharma Ipl Ag Formulation pharmaceutique transdermique visant a reduire les residus sur la peau
WO2005102268A2 (fr) * 2004-04-22 2005-11-03 Sanochemia Pharmazeutika Ag Inhibiteurs de la cholinesterase inclus dans des liposomes, leur production et leur utilisation
WO2007016766A1 (fr) * 2005-08-05 2007-02-15 Nuvo Research Inc. Formulation pour l'administration transdermique de medicaments

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9007052D0 (en) * 1990-03-29 1990-05-30 Skua Investments Ltd Pharmaceutical formulations
US5945409A (en) * 1995-03-10 1999-08-31 Wilson T. Crandall Topical moisturizing composition and method
HU227182B1 (en) * 2000-03-06 2010-09-28 Andras Javor Lecitin-ascorbic acid combination

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050074487A1 (en) * 1999-12-16 2005-04-07 Tsung-Min Hsu Transdermal and topical administration of drugs using basic permeation enhancers
WO2004002402A2 (fr) * 2002-05-21 2004-01-08 Nastech Pharmaceutical Company Inc. Administration d'inhibiteurs d'acetylcholinesterase au liquide cephalorachidien spinal
US20040185170A1 (en) * 2003-03-21 2004-09-23 Shubha Chungi Method for coating drug-containing particles and formulations and dosage units formed therefrom
WO2005039531A1 (fr) * 2003-10-10 2005-05-06 Antares Pharma Ipl Ag Formulation pharmaceutique transdermique visant a reduire les residus sur la peau
WO2005102268A2 (fr) * 2004-04-22 2005-11-03 Sanochemia Pharmazeutika Ag Inhibiteurs de la cholinesterase inclus dans des liposomes, leur production et leur utilisation
WO2007016766A1 (fr) * 2005-08-05 2007-02-15 Nuvo Research Inc. Formulation pour l'administration transdermique de medicaments

Also Published As

Publication number Publication date
WO2008064815A3 (fr) 2008-07-17
DE102006056783A1 (de) 2008-06-05

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