Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors

• US 7,053,080 B2
• Filed: 09/19/2002
• Issued: 05/30/2006
• Est. Priority Date: 09/21/2001
• Status: Expired due to Fees

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Veltri, Enrico P., Strony, John T., Davis, Harry R., Ress, Rudyard J.
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Krishnan, Ganapathy
• Application Number:
  US10/247,397
• Publication Number:
  US 20030119428A1
• Time in Patent Office: 1,349 Days
• Field of Search: 514/25, 514/23, 514/210.02, 514/449, 536/17.4
• US Class Current: 514/210.02
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07H 15/26 Acyclic or carbocyclic radicals, substituted by hetero rings

Abstract

The present invention provides methods for the treatment of obesity using sterol or 5α-stanol absorption inhibitors and compositions and therapeutic combinations including sterol or 5α-stanol absorption inhibitors and at least one obesity control medication.

Claims

1. A composition comprising:

(a) at least one obesity control medication; and

(b) at least one sterol absorption inhibitor or at least one 5α

-stanol absorption inhibitor or a pharmaceutically acceptable salt thereof or a solvate thereof.

2. The composition according to claim 1, wherein the at least one sterol or 5α

-stanol absorption inhibitor is represented by Formula (I);

3. The composition according to claim 2, wherein the sterol or 5α

-stanol absorption inhibitor is represented by Formula (II) below;

4. The composition according to claim 1, wherein the at least one sterol absorption inhibitor is represented by Formula (III):

5. The composition according to claim 1, wherein the at least one sterol absorption inhibitor is represented by Formula (IV):

6. The composition according to claim 1, wherein the at least one sterol absorption inhibitor is represented by Formula (V):

7. The composition according to claim 1, where the at least one sterol absorption inhibitor is represented by Formula (VI):

8. The composition according to claim 1, wherein the at least one sterol absorption inhibitor is represented by Formula (VIIA) or (VIIB):

9. The composition according to claim 1, wherein the at least one sterol absorption inhibitor is represented by Formula (VIII):

10. The composition according to claim 1, wherein the at least one sterol absorption inhibitor is represented by Formula (IX):

11. The composition according to claim 1, wherein the at least one obesity medication is selected from the group consisting of noradrenergic agents, serotonergic agents, thermogenic agents and combinations thereof.

12. The composition according to claim 11, wherein the noradrenergic agent is selected from the group consisting of diethylpropion, mazindol, phenylpropanolamine, phentermine, phendimetrazine, phendamine tartrate, methamphetamine, phendimetrazine tartrate and combinations thereof.

13. The composition according to claim 11, wherein the serotonergic agent is selected from the group consisting of sibutramine, fenfluramine, dexfenfluramine, fluoxetine, fluvoxamine, paroxtine and combinations thereof.

14. The composition according to claim 11, wherein the thermogenic agent is selected from the group consisting of ephedrine, caffeine, theophylline, selective β

3-adrenergic agonists and combinations thereof.

15. The composition according to claim 1, wherein the at least one obesity control medication is administered to a mammal in an amount ranging from about 1 to about 1000 milligrams of obesity medication per day.

16. The composition according to claim 1, wherein the at least one sterol or 5α

-stanol absorption inhibitor is administered to a mammal in an amount ranging from about 0.1 to about 1000 milligrams of sterol or 5α

-stanol absorption inhibitor per day.

17. The composition according to claim 1, wherein the at least one obesity control medication is an alpha-blocking agent.

18. The composition according to claim 1, wherein the at least one obesity control medication is a kainite or D,L-a-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor antagonist.

19. The composition according to claim 1, wherein the at least one obesity control medication is a leptin-lipolysis stimulated receptor.

20. The composition according to claim 1, wherein the at least one obesity control medication is a phosphodiesterase enzyme inhibitor.

21. The composition according to claim 1, wherein the at least one obesity control medication is a compound having nucleotide sequences of the mahogany gene.

22. The composition according to claim 1, wherein the at least one obesity control medication is a fibroblast growth factor-10 polypeptide.

23. The composition according to claim 1, wherein the at least one obesity control medication is a monoamine oxidase inhibitor.

24. The composition according to claim 23, wherein the monoamine oxidase inhibitor is selected from the group consisting of befloxatone, moclobemide, brofaromine, phenoxathine, esuprone, befol, toloxatone, pirlindol, amiflamine, sercloremine, bazinaprine, lazabemide, milacemide, caroxazone and combinations thereof.

25. The composition according to claim 1, wherein the at least one obesity control medication is a compound for increasing lipid metabolism.

26. The composition according to claim 1, wherein the at least one obesity control medication is a lipase inhibitor.

27. A pharmaceutical composition for the treatment or of obesity or lowering a concentration of a sterol or 5α

-stanol in plasma of a mammal, comprising a therapeutically effective amount of the composition of claim 1 and a pharmaceutically acceptable carrier.

28. A method of treating or obesity or lowering a concentration of a sterol or 5α

-stanol in plasma of a mammal, comprising the step of administering to a mammal in need of such treatment an effective amount of the composition of claim 1.

29. A therapeutic combination comprising:

(a) a first amount of at least one obesity control medication, and

(b) a second amount of at least one sterol absorption inhibitor or 5α

-stanol absorption inhibitor;

wherein the first amount and the second amount together comprise a therapeutically effective amount for the treatment or of obesity or lowering a concentration of a sterol or 5α

-stanol in plasma of a subject.

30. The therapeutic combination of claim 29, wherein the at least one sterol or 5α

-stanol absorption inhibitor is represented by Formula (I);

31. The therapeutic combination according to claim 29, wherein the at least one obesity medication is administered concomitantly with the at least one sterol or 5α

-stanol absorption inhibitor.

32. The therapeutic combination according to claim 29, wherein the at least one obesity medication and the at least one sterol or 5α

-stanol absorption inhibitor are present in separate treatment compositions.

33. A method of treating or obesity or lowering a concentration of a sterol in plasma of a subject, comprising the step of administering to a subject in need of such treatment an effective amount of the composition of claim 29.

34. A method of treating or obesity comprising the step of administering to a subject in need of such treatment an effective amount of a composition comprising at least one sterol or 5α

-stanol absorption inhibitor.

35. A method of treating or obesity comprising the step of administering to a subject in need of such treatment an effective amount of a composition comprising at least one sterol absorption inhibitor represented by Formula (II) below: