Patent EA-004877-B1 (EA)
Title: Combinations of ileal bile acid transport inhibitors and bile acid sequestering agents for cardiovascular indications
Inventor: KELLER BRADLEY T
IPC: A61K31/56
Filed: 1999-12-17
Abstract: 1. A therapeutic combination comprising an effective amounts of first an ileal bile acid transport inhibiting compound and a second bile acid sequestering compound wherein the first amount and the second amount together comprise an anti-hyperlipidemic condition effective amount of the compounds and wherein said ileal bile acid transport inhibiting compound is represented by formula (B-5): or enantiomers, racemates or a pharmaceutically acceptable salt thereof. 2. The therapeutic combination of claim 1 wherein the bile acid sequestering compound comprises cholestyramine or a pharmaceutically acceptable salt thereof. 3. The therapeutic combination of claim 1 wherein the bile acid sequestering compound comprises colestipol or a pharmaceutically acceptable salt thereof. 4. The therapeutic combination of claim 1 wherein the bile acid sequestering compound comprises an amphiphilic copolymer having a crosslinked shell domain and an interior core domain or a pharmaceutically acceptable salt thereof. 5. The therapeutic combination of claim 1 wherein the bile acid sequestering compound comprises a polyallylamine polymer or a pharmaceutically acceptable salt thereof. 6. The therapeutic combination of claim 5, wherein the polyallylamine polymer comprises colesevelam hydrochloride or a pharmaceutically acceptable salt thereof. 7. The therapeutic combination of claim 5 wherein the polyallylamine polymer comprises OmegaGel or a pharmaceutically acceptable salt thereof. 8. A pharmaceutical composition comprising an effective amount of first an ileal bile acid transport inhibiting compound and a second bile acid sequestering compound, wherein the first amount and the second amount together comprise an anti-hyperlipidemic condition effective amount of the compounds, the first amount is about 0.01 to about 1000 mg, and the second amount is about 250 to about 30,000 mg, and wherein the ileal bile acid transport inhibiting compound has the structure of formula B-5 or an enantiomer, racemate or pharmaceutically acceptable salt thereof. 9. The pharmaceutical composition of claim 8 wherein the bile acid sequestering compound is cholestyramine or a pharmaceutically acceptable salt thereof. 10. The pharmaceutical composition of claim 8 wherein the bile acid sequestering compound is colestipol or a pharmaceutically acceptable salt thereof. 11. The pharmaceutical composition of claim 8 wherein the bile acid sequestering compound is an amphiphilic copolymer having a crosslinked shell domain and an interior core domain, or a pharmaceutically acceptable salt thereof. 12. The pharmaceutical composition of claim 8 wherein the bile acid sequestering compound is a polyallylamine, or a pharmaceutically acceptable salt thereof. 13. The pharmaceutical composition of claim 12 wherein the polyallylamine is CholestaGel or a pharmaceutically acceptable salt thereof. 14. The pharmaceutical composition of claim 12 wherein the polyallylamine is OmegaGel or a pharmaceutically acceptable salt thereof. 15. A method for the prophylaxis or treatment of a hyperlipidemic condition comprising administering to a patient in need thereof a combination in unit dosage form wherein the combination comprises an effective amounts of a first ileal bile acid transport inhibiting compound and a second bile acid sequestering compound wherein the first amount and the second amount together comprise an anti-hyperlipidemic condition effective amount of the compounds, wherein said ileal bile acid transport inhibiting compound is represented by formula (B-5): or enantiomers or racemates thereof. 16. The method of claim 15 wherein the daily dose range is from 0.01 to about 1000 mg of the first one and from about 250 to about 30,000 mg of second one. 17. The method of claim 15 wherein the hyperlipidemic condition is an atherosclerotic condition. 18. The method of claim 15 wherein the hyperlipidemic condition is hypercholesterolemia. 19. The method of claim 15 wherein the bile acid sequestering compound is cholestyramine or a pharmaceutically acceptable salt thereof. 20. The method of claim 15 wherein the bile acid sequestering compound is colestipol or a pharmaceutically acceptable salt thereof. 21. The method of claim 15 wherein me bile acid sequestering compound is an amphiphilic copolymer having a crosslinked shell domain and an interior core domain, or a pharmaceutically acceptable salt thereof. 22. The method of claim 15 wherein the bile acid sequestering compound is a polyallylamine, or a pharmaceutically acceptable salt thereof. 23. The method of claim 22 wherein the polyallylamine is CholestaGel or a pharmaceutically acceptable salt thereof. 24. The method of claim 22 wherein the polyallylamine is OmegaGel or a pharmaceutically acceptable salt thereof.