PHARMACEUTICAL COMBINATIONS FOR LIPID MANAGEMENT AND IN THE TREATMENT OF ATHEROSCLEROSIS AND HEPATIC STEATOSIS

• US 20080103122A1
• Filed: 08/29/2007
• Published: 05/01/2008
• Est. Priority Date: 09/05/2006
• Status: Abandoned Application

• Current Assignee: Schering Corporation (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Veltri, Enrico
• Application Number:
  US11/846,575
• Publication Number:
  US 20080103122A1
• Time in Patent Office: Days
• US Class Current: 514/210.02
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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

A pharmaceutical combination comprising an effective amount of at least one cholesterol absorption inhibitor and at least one microsomal triglyceride transfer protein inhibitor (MTP).

Claims

1. A pharmaceutical combination comprising an effective amount of at least one cholesterol absorption inhibitor and at least one microsomal triglyceride transfer protein inhibitor (MTP).

2. The pharmaceutical combination according to claim 1, wherein the cholesterol absorption is a sterol or 5-α

-stanol absorption inhibitor.

3. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (I);

4. The pharmaceutical combination according to claim 3, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (II);

5. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (III);

6. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (IV);

7. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (V);

8. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula;

9. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula by formulae (VIIA) or (VIIB);

10. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (VIII);

11. The pharmaceutical combination according to claim 2, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (IX);

12. The pharmaceutical combination according to claim 2, wherein the MTP inhibitor is selected from the group consisting of implitapide, mitratapide, T-0126, CP-346086, BMS 201038 and CP-395919.

13. The pharmaceutical combination according to claim 12, wherein the sterol or 5-α

-stanol absorption inhibitor is a compound of formula (I);

14. The pharmaceutical combination according to claim 13, wherein the sterol or 5-α

-stanol absorption inhibitor is ezetimibe.

15. The pharmaceutical combination according to claim 14, which further comprises simastatin.

16. The pharmaceutical combination according to claim 1, which further comprises an effective amount of an HMG-CoA reductase inhibitor.

17. The pharmaceutical combination according to claim 16, wherein the HMG-CoA reductase inhibitor is selected from the group consisting of lovastatin, pravastatin fluvastatin, simvastatin, atorvastatin, cerivastatin, pitavastatin, and rosuvastatin.

18. The pharmaceutical combination according to claim 17, which further comprises an effective amount of an HMG-CoA reductase inhibitor wherein said inhibitor is simvastatin.

19. The pharmaceutical combination according to claim 1, which further comprises a PPAR activator, nicotinic acid and/or a nicotinic acid receptor agonist or a bile acid sequestrant.

20. A method for lipid management in a mammal in need thereof which comprises administering an effective amount of the pharmaceutical combination according to claim 1 to said mammal.

21. The method according to claim 20, wherein the cholesterol absorption inhibitor is ezetimibe and the MTP is selected from the group consisting of implitapide, mitratapide, T-0126, CP-346086, BMS 201038 and CP-395919.

22. The method according to claim 21, wherein the pharmaceutical combination further comprises a cholesterol lowering agent which is a HMG-CoA reductase inhibitor is selected from the group consisting of lovastatin, pravastatin fluvastatin, simvastatin, atorvastatin, cerivastatin, pitavastatin, and rosuvastatin.

23. The method according to claim 22, wherein the HMG Co-A reductase inhibitor is simvastatin.

24. A method for the treatment, prevention or ameliorating the symptoms atherosclerosis in a mammal in need thereof which comprises administering an effective amount of the therapeutic combination according to claim 1 to said mammal.

25. The method according to claim 24, wherein the cholesterol absorption inhibitor is ezetimibe and the MTP is selected from the group consisting of implitapide, mitratapide, T-0126, CP-346086, BMS 201038 and CP-395919.

26. The method according to claim 25, wherein the pharmaceutical combination further comprises a cholesterol lowering agent which is a HMG-CoA reductase inhibitor is selected from the group consisting of lovastatin, pravastatin fluvastatin, simvastatin, atorvastatin, cerivastatin, pitavastatin, and rosuvastatin.

27. The method according to claim 26, wherein the HMG Co-A reductase inhibitor is simvastatin.

28. A method for the prevention or amelioration of the symptoms or the development of hepatic steatosis in a mammal in need thereof comprising administering an effective amount of the pharmaceutical combination according to claim 1 to said mammal.

29. The method according to claim 28, wherein the cholesterol absorption inhibitor is ezetimibe and the MTP is selected from the group consisting of include implitapide, mitratapide, T-0126, CP-346086, BMS 201038 and CP-395919.

30. The method according to claim 29, wherein the pharmaceutical combination further comprises a cholesterol lowering agent which is a HMG-CoA reductase inhibitor is selected from the group consisting of lovastatin, pravastatin fluvastatin, simvastatin, atorvastatin, cerivastatin, pitavastatin, and rosuvastatin.

31. The method according to claim 30, wherein the HMG-CoA reductase inhibitor is simvastatin.