Sustained release glp-1 receptor modulators

• US 20100022457A1
• Filed: 11/08/2006
• Published: 01/28/2010
• Est. Priority Date: 05/26/2006
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Burton, Lori S., Ni, Nina, Martinez, Rogelio L., Haque, Tasir Shamsul, Naringrekar, Vijay, Sulsky, Richard B., Ewing, William R., Qian, Feng, Zhu, Yeheng, Lee, Ving G., Riexinger, Douglas James, Mapelli, Claudio
• Application Number:
  US12/227,780
• Publication Number:
  US 20100022457A1
• Time in Patent Office: Days
• US Class Current: 514/10.300
• 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 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/32 Manganese; Compounds thereof
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• 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: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• 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 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
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

The present invention provides novel pharmaceutical compositions comprising a human glucagon-like peptide-1 (GLP-1)-receptor modulator as an active ingredient in a sustained release formulation.

Claims

1-32. -32. (canceled)

33. A pharmaceutical composition or a pharmaceutically-acceptable salt thereof, wherein said pharmaceutical composition comprises:

(a) an effective amount of a glucagon-like peptide-1 (GLP-1) receptor modulator, or salt thereof, as an active ingredient, wherein said GLP-1 receptor modulator comprises at least one phenyl-heteroaryl-alanine analog; and

(b) a metal ion, or a protamine vehicle, or a combination thereof.

34. The pharmaceutical composition of claim 33 wherein said GLP-1 receptor modulator is a peptide selected from the group consisting of SEQ ID NO.s 1-166.

35. The pharmaceutical composition of claim 33 wherein said GLP-1 receptor modulator is a peptide selected from the group consisting of SEQ ID NO.s 9, 15, 118, 151, and 158.

36. The pharmaceutical composition of claim 33 wherein said metal ion is a divalent cation.

37. The pharmaceutical composition of claim 33, wherein said pharmaceutical composition comprises a protamine vehicle.

38. The pharmaceutical composition of claim 33, wherein said composition is prepared by spray drying, precipitation, or lyophilization.

39. The pharmaceutical composition of claim 33, wherein said metal ion is a divalent metal cation selected from the group consisting of zinc, manganese, and iron.

40. The pharmaceutical composition of claim 38 wherein said divalent metal cation is zinc.

41. The pharmaceutical composition of claim 34 further comprising a co-precipitated, lyophilized, or spray dried zinc adduct, in a Zn:

GLP-1 receptor modulator ratio of from about 1;

10 to about 50;

1.

42. The pharmaceutical composition of claim 34 further comprising a co-precipitated, lyophilized, or spray dried zinc adduct, in a Zn:

GLP-1 receptor modulator ratio of from about 1;

10 to about 50;

1, with a weight to volume ratio of surfactants, suspending agents, and/or thickening agents, of 0% to about 30%.

43. The pharmaceutical composition of claim 42 wherein the Zn:

GLP-1 receptor modulator ratio is about 1.5;

1 to about 5;

1 and the weight to volume ratio of surfactants is 0% to about 1%, suspending agents is 0% to about 5%, and/or thickening agents is 0% to about 1%.

44. The pharmaceutical composition of claim 33 further comprising a co-precipitated, lyophilized, or spray dried zinc adduct, in a Zn:

GLP-1 receptor modulator ratio of from about 1;

10 to about 50;

1, with a weight to volume ratio of surfactants, suspending agents, and/or thickening agents, of 0% to about 30%.

45. A method for making a pharmaceutical composition comprising:

a) obtaining a GLP-1 receptor modulator comprising at least one phenyl-heteroaryl-alanine analog;

b) suspending said GLP-1 receptor modulator to form a GLP-1 suspension;

c) adjusting the pH of the GLP-1 suspension to about 8.5 to obtain a GLP-1 solution;

d) dissolving zinc acetate in a solution to obtain a zinc acetate solution;

e) adding the zinc acetate solution drop wise, with stirring, to the GLP-1 solution; and

f) obtaining a composition having a molar ratio of zinc;

GLP-1 receptor modulator of about 3;

1, and having a final pH of about 6.0.

46. The method of claim 45 wherein said GLP-1 receptor modulator is selected from the group consisting of SEQ ID NOs:

1-166.

47. The method of claim 45 wherein said GLP-1 receptor modulator is selected from the group consisting of SEQ ID NOs:

9, 15, 118, 151, and 158.