Pharmaceutical formulations of amyloid inhibiting compounds

• US 8,835,500 B2
• Filed: 01/30/2009
• Issued: 09/16/2014
• Est. Priority Date: 06/23/2003
• Status: Active Grant

• Current Assignee: BELLUS Health, Inc.
• Original Assignee: BHI Limited Partnership
• Inventors: Laurin, Julie, Garceau, Denis
• Primary Examiner(s): Rao, Savitha
• Assistant Examiner(s): Polansky, Gregg
• Application Number:
  US12/362,971
• Publication Number:
  US 20090182056A1
• Time in Patent Office: 2,055 Days
• Field of Search: None
• US Class Current: 514/578
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Therapeutic formulations and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Therapeutic formulations and methods for preventing or treating amyloidosis and/or amyloid-related disease are also described.

Claims

1. An oral formulation comprising an effective amount of 3-amino-1-propanesulfonic acid to treat amyloidosis, inhibit amyloid deposition and/or treat an amyloid deposition-related disease, a pharmaceutically acceptable vehicle and an enteric coating, wherein the formulation results in lesser gastrointestinal intolerance in comparison to an immediate release dosage form comprising 3-amino-1-propanesulfonic acid.

2. An oral formulation comprising an effective amount of 3-amino-1-propanesulfonic acid, a pharmaceutically acceptable vehicle and an enteric coating,

wherein the formulation results in lesser gastrointestinal intolerance in comparison to an immediate release dosage form comprising 3-amino-1-propanesulfonic acid.

3. A formulation of claim 2 wherein the amount of 3-amino-1-propanesulfonic acid is effective for stabilizing cognitive function or decreasing the rate of decline in cognitive function.

4. A formulation of claim 2 wherein the amount of 3-amino-1-propanesulfonic acid is effective for inhibiting neurodegeneration or cellular toxicity induced by amyloid-β

.

8. A method for stabilizing cognitive function or decreasing the rate of decline in cognitive function in a subject in need thereof comprising administering a formulation of claim 3.

9. A method for inhibiting neurodegeneration or cellular toxicity induced by amyloid in a subject in need thereof comprising administering a formulation of claim 4.

10. The method of claim 9 wherein said amyloid is amyloid-β

.

11. A method for treating amyloidosis in a subject in need thereof comprising administering a formulation of claim 4.

12. A method for inhibiting amyloid deposition in a subject in need thereof comprising administering a formulation of claim 4.

13. A method for treating an amyloid-related diseases or conditions in a subject in need thereof comprising administering a formulation of claim 4.

14. The method of claim 13 wherein said amyloid-related disease or condition is an amyloid-β

-related disease or condition.

15. The method of claim 8 wherein said subject is an elderly individual.

16. The method of claim 14 wherein said amyloid-related disease or condition is selected from Alzheimer'"'"'s disease, cerebral amyloid angiopathy, Down'"'"'s syndrome, and mild cognitive impairment.

17. The method of claim 14 wherein said amyloid-related disease or condition is Alzheimer'"'"'s disease or mild cognitive impairment.

18. A method for treating an amyloid-related disease in a human with brain amyloidosis comprising administering to the subject a therapeutic amount of a formulation of claim 3, such that cognitive function is improved or stabilized or further deterioration in cognitive function is slowed.

5. An oral formulation comprising 3-amino-1-propanesulfonic acid, a pharmaceutical acceptable carrier and an enteric coating wherein the formulation results in lesser gastrointestinal intolerance in comparison to an immediate release dosage form comprising 3-amino-1-propane sulfonic acid.

6. The formulation of claim 5 wherein 20% or less dissolution of 3-amino-1-propanesulfonic acid occurs in the acidic environment of the stomach but dissolution occurs in the more neutral or alkaline environments of the GI tract.

7. The formulation of claim 5 wherein less than or equal to 10% dissolution of the active ingredient occurs within 2 hours.