Pharmaceutical compositions for reducing amyloid deposition, amyloid neurotoxicity, and microgliosis

• US 8,236,347 B2
• Filed: 02/01/2010
• Issued: 08/07/2012
• Est. Priority Date: 10/05/2007
• Status: Active Grant

• Current Assignee: Alzheimer's Institute Of America
• Original Assignee: Alzheimer's Institute Of America
• Inventors: Mullan, Michael J., Paris, Daniel, Ivey, Robert A. III
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Palenik, Jeffrey T
• Application Number:
  US12/697,436
• Publication Number:
  US 20100183711A1
• Time in Patent Office: 918 Days
• Field of Search: None
• US Class Current: 424/456
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• 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
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives

Abstract

The present invention provides methods for reducing Aβ deposition, Aβ neurotoxicity and microgliosis in an animal or human afflicted with a cerebral amyloidogenic disease, such as Alzheimer'"'"'s disease (AD), by administering therapeutically effective amounts of the (R)-enantiomer of the dihydropyridine compound nilvadipine, also known as (−)-nilvadipine, to the animal or human. Further provided are methods for reducing the risk of Aβ deposition, Aβ neurotoxicity and microgliosis in animals or humans suffering from traumatic brain injury by administering (−)-nilvadipine after the traumatic brain injury and continuing treatment for a prescribed period of time thereafter.

Claims

1. A pharmaceutical composition comprising optically active nilvadipine and a pharmaceutically acceptable carrier, the pharmaceutical composition comprising an excess of (−

)-nilvadipine relative to (+)-nilvadipine.

2. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition has an enantiomeric excess of (−

)-nilvadipine relative to (+)-nilvadipine of at least 90%.

3. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition has an enantiomeric excess of (−

)-nilvadipine relative to (+)-nilvadipine of at least 95%.

4. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition has an enantiomeric excess of (−

)-nilvadipine relative to (+)-nilvadipine of at least 98%.

5. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition contains no detectible (+)-nilvadipine.

6. The pharmaceutical composition of any of claims 1-5 wherein the pharmaceutical composition is in unit dosage form.

7. The pharmaceutical composition of any of claims 1-5 wherein the pharmaceutical composition is in dosage unit form enclosed in hard or soft gelatin capsules or compressed into tablets.

8. The pharmaceutical composition of any of claims 1-5 wherein the pharmaceutical composition is in unit dosage form suitable for parenteral, oral or interperitoneal administration.