Formulations and their use in the treatment of neurological diseases

• US 5,540,938 A
• Filed: 10/24/1994
• Issued: 07/30/1996
• Est. Priority Date: 11/02/1990
• Status: Expired due to Term

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Elan Corporation PLC (Perrigo Company PLC)
• Inventors: Myers, Michael, Masterson, Joseph G.
• Primary Examiner(s): Page, Thurman
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/328,165
• Time in Patent Office: 645 Days
• Field of Search: 424/445, 424/449, 424/451, 424/452, 424/458, 424/460, 424/461, 424/464, 424/465, 424/474, 424/475, 424/480, 424/484, 424/489, 424/494, 424/495, 424/497, 424/498, 424/499
• US Class Current: 424/490
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 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

Abstract

Pharmaceutical formulations comprise a mono- or di-aminopyridine active agent for administration on a once- or twice-daily basis for use in the treatment of neurological diseases, in particular multiple sclerosis and Alzheimer'"'"'s disease. The formulations, which are suitable for oral or percutaneous administration of the active agent, include the active agent in a carrier effective to permit release of the mono- or di-aminopyridine at a rate allowing controlled absorption thereof over, on the average, not less than a 12 hour period and at a rate sufficient to achieve therapeutically effective blood levels over a period of 12-24 hours following administration.

Claims

1. A method for the treatment of a neurological disease where the disease is characterised by a slowing of nerve impulse transmission, which comprises administering to a patient in need thereof a medicament containing a mono- or di-aminopyridine active agent, said medicament being effective to permit sustained release of said mono- or di-aminopyridine active agent at a rate allowing controlled absorption thereof which achieves therapeutically effective blood levels over a 12-24 hour period when administered on a once- or twice-daily basis.

2. A method according to claim 1, wherein the neurological disease is characterised by demyelination of the central nervous system.

3. A method according to claim 1 or 2, wherein the neurological disease is multiple sclerosis.

4. A method according to claim 1, wherein the neurological disease is Alzheimer'"'"'s disease.

5. A method according to claim 1, wherein the medicament is administered to a subject at a dose and for a period sufficient to allow said subject to reach a tolerable state such that said subject is able to tolerate said dose without showing any adverse effects and thereafter increasing the dose of said mono- or di-aminopyridine active agent at selected intervals of time until a therapeutic dose is achieved.

6. A method according to claim 5, wherein at the commencement of treatment the mono- or di-aminopyridine active agent is administered at a dose of less than 15 mg/day until a tolerable state is reached.

7. A method according to claim 5, wherein at the commencement of treatment the mono- or di-aminopyridine active agent is administered at a dose of less than 15 mg/day until a tolerable state is reached and when said tolerable state is reached, the dose administered is increased by amounts of at least 5-15 mg/day until said therapeutic dose is reached.

8. A method according to claim 1, wherein the active agent is 4-aminopyridine.