Combined use of glp-1 agonists and gastrin for regulating blood glucose levels

• US 20090202494A1
• Filed: 01/28/2005
• Published: 08/13/2009
• Est. Priority Date: 01/30/2004
• Status: Abandoned Application

• Current Assignee: Waratah Pharmaceuticals, Inc. (Opko Health, Inc.)
• Original Assignee: Waratah Pharmaceuticals, Inc. (Opko Health, Inc.)
• Inventors: Hew, Yin, Cruz, Antonio, Pastrak, Aleksandra
• Application Number:
  US10/587,529
• Publication Number:
  US 20090202494A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• 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 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• 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
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The invention relates generally to novel compositions and methods comprising a gastrin compound. The compositions and methods provide beneficial effects, in particular sustained beneficial effects, in particular sustained beneficial effects, in particular sustained beneficial effects, in the treatment of diabetes.

Claims

1. A pharmaceutical composition comprising a GLP-1 agonist and a gastrin compound that provides beneficial effects relative to each compound alone, and a pharmaceutically acceptable carrier, excipient, or vehicle.

6. A pharmaceutical composition as claimed in claim 1 wherein the ratio of a GLP-1 agonist to a gastrin compound is from about 1:

1 to 1;

110, 1;

1 to 1;

100, 1;

1 to 1;

75, 1;

1 to 1;

50, 1;

1 to 1;

25, 1;

1 to 1;

10, 1;

1 to 1;

5, and 1;

1.

9. A pharmaceutical composition as claimed in claim 1 wherein the GLP-1 agonist and the gastrin compound are present in doses that are at least about 1.1 to 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold lower than the doses of each compound alone required to treat a condition and/or disease.

10. A pharmaceutical composition as claimed in claim 1 comprising an additive amount of the GLP-1 agonist and the gastrin compound in a pharmaceutically acceptable excipient, carrier, or vehicle.

11. A pharmaceutical composition as claimed in claim 1 comprising a synergistically effective amount of the GLP-1 agonist and the gastrin compound in a pharmaceutically acceptable excipient, carrier, or vehicle.

12. A pharmaceutical composition as claimed in claim 1 comprising between 0.1 to 20, 0.1 to 30, 0.1 to 40, 0.1 to 50, and 0.1 to 60 micrograms/kg/day GLP-1 agonist and 0.1 to 20, 0.1 to 30, 0.1 to 40, 0.1 to 50, and 0.1 to 60 micrograms/kg/day gastrin compound.

19. A pharmaceutical composition as claimed in claim 1 wherein the beneficial effect is a decrease in blood glucose levels for a period of at least 2, 4, 6, 8, or 10 weeks, 2 to 4 weeks, 2 to 6 weeks, 2 to 8 weeks, 2 to 12 weeks, 2 to 24 weeks, 2 weeks to 12 months, and 2 weeks to 18 months following treatment.

20. A pharmaceutical composition as claimed in claim 1 wherein the GLP-1 agonist is a GLP-1(1-37), GLP-1(7-36) amide, fragments, analogues, and derivatives thereof, and active metabolites and prodrugs of GLP-1.

24. A pharmaceutical composition as claimed in claim 1 wherein the gastrin compound is gastrin 71 [SEQ ID NO. 15], gastrin 52 [SEQ ID NO. 16], gastrin 34 (big gastrin) [SEQ ID NO. 11 or 12], gastrin 17 (little gastrin) [SEQ ID NO. 13 or 14], gastrin 14 [SEQ ID NO. 17], gastrin 8, gastrin 6 [SEQ ID NO.18 or 19], pentagastrin, and tetragastrin, or a fragment, analog, or derivative thereof.

27. A pharmaceutical composition of claim 1 wherein the GLP-1 agonist is Arg34Lys26(Ne(g-Glu(Na-hexadecanoyl)))-GLP-1(7-37) and the gastrin compound is 15Leu gastrin 17 [SEQ ID NO. 14].

34. A method of treatment comprising administering to a subject a therapeutically effective amount of a composition according to claim 1 or at least one GLP-1 agonist in combination with administration of at least one gastrin compound which upon administration to a subject with symptoms of diabetes provides sustained beneficial effects.

36. A method as claimed in claim 34 wherein therapeutically effective amounts of the GLP-1 agonist and the gastrin compound are combined prior to administration to the subject.

37. A method as claimed in claim 34 wherein therapeutically effective amounts of the GLP-1 agonist and the gastrin compound are administered to the subject sequentially.

40. A method of treating diabetes comprising administering a composition of claim 1 with a plurality of cells to a subject in need thereof to thereby produce beneficial effects.

52. A pharmaceutical composition according to claim 24 wherein the GLP-1 agonist is an exendin or analog, derivative or fragment thereof.

53. A method according to claim 34 wherein the GLP-1 agonist is an exendin or analog, derivative or fragment thereof.

2-5. -5. (canceled)

7-8. -8. (canceled)

13-18. -18. (canceled)

21-23. -23. (canceled)

25-26. -26. (canceled)

28. (canceled)

29. A method for preparing a stable pharmaceutical composition of a GLP-1 agonist comprising mixing a GlP-1 agonist, a gastrin compound, and a pharmaceutically acceptable carrier, excipient, or vehicle effective to physically stabilize the GLP-1 agonist and adapted to provide beneficial effects.

30-33. -33. (canceled)

35. (canceled)

38-39. -39. (canceled)

41-51. -51. (canceled)

54. A method according to claim 54 wherein the GLP-1 agonist is exendin-3 or exendin-4.

55. A method according to claim 54 wherein the GLP-1 agonist is exenatide.