Compositions and methods for enhanced mucosal delivery and non-infused administration of Y2 receptor-binding peptides and methods for treating and preventing obesity

• US 7,186,692 B2
• Filed: 06/16/2004
• Issued: 03/06/2007
• Est. Priority Date: 12/17/2002
• Status: Expired due to Fees

• Current Assignee: Mdrna Inc. (Adhera Therapeutics, Inc.)
• Original Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven C., Brandt, Gordon
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): Kosson; Rosanne
• Application Number:
  US10/869,649
• Publication Number:
  US 20050002927A1
• Time in Patent Office: 993 Days
• Field of Search: 514/12, 530/324, 530/303
• US Class Current: 514/4.8
• CPC Class Codes: A61K 38/2271 Neuropeptide Y
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents

Abstract

Pharmaceutical compositions and methods are described comprising at least one Y2 receptor-binding peptide, such as peptide YY(PYY), Neuropeptide Y (NPY) or Pancreatic Peptide (PP) and one or more mucosal delivery-enhancing agents for enhanced nasal mucosal delivery of the peptide YY, for treating a variety of diseases and conditions in mammalian subjects, including obesity.

Claims

1. A method for treating a mammal for obesity, inducing weight-loss or to induce satiety in the mammal comprised of intranasally administering to said mammal a therapeutically effective amount of a composition comprising a Y2 receptor-binding peptide, and L-α

-phosphatidylcholine didecanoyl (DDPC), resulting in an increase in concentration of the Y2 receptor-binding peptide in the mammal by at least 5 pmol per liter of plasma to about 60 pmol per liter of plasma.

2. The method of claim 1 wherein the mammal is human.

3. The method of claim 2 wherein the Y2 receptor-binding peptide is a PYY peptide.

4. The method of claim 3 wherein the Y2 receptor binding peptide is administered from 30 to 90 minutes prior to when the human eats food.

5. The method of claim 4 wherein the Y2 receptor-binding peptide is a PYY(3–

36) peptide comprised of the amino acid sequence of SEQ ID NO;

2.

28. The method of claim 1 wherein the composition is further comprised of at least two polyols.

29. The method of claim 28 wherein the polyols are selected from the group consisting of sucrose, mannitol, sorbitol, lactose, L-arabinose, D-erythrose, D-ribose, D-xylose, D-mannose, trehalose, D-galactose, lactulose, cellobiose, gentibiose, glycerin and polyethylene glycol.

30. The method of claim 29 wherein the polyols are lactose and sorbitol.

31. The method of claim 1 wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).

32. The method of claim 31 wherein the chelating agent is ethylenediamine tetraacetic acid (EDTA).

33. The method of claim 1 wherein the solubilizing agent is selected from the group consisting of a cyclodextran, hydroxypropyl-β

-cyclodextran, sulfobutylether-β

-cyclodextran and methyl-β

-cyclodextrin.

34. The method of claim 33 wherein the solubilizing agent is a methyl-β

-cyclodextrin.

35. The method of claim 1 wherein the composition is an aqueous PYY composition.

36. The method of claim 35 wherein the aqueous PYY composition has a pH from about 3 to about 6.

37. The method of claim 36 wherein the aqueous PYY composition has a pH of about 5.0±

0.3.

48. The method of claim 35 wherein the aqueous PYY composition is free of a protein stabilizer.

49. The method of claim 35 wherein the aqueous PYY composition is an emulsion.

50. The method of claim 35 wherein the aqueous PYY composition is a solution.

6. A method for treating a mammal for obesity, inducing weight-loss or to induce satiety in the mammal comprised of intranasally administering to said mammal 40 μ

g to 200 μ

g of a Y2 receptor binding peptide.

7. The method of claim 6 wherein the mammal is human.

8. The method of claim 7 wherein the Y2 receptor-binding peptide is a PYY peptide.

9. The method of claim 8 wherein the Y2 receptor binding peptide is administered from 30 to 90 minutes prior to when the human eats food.

10. The method of claim 9 wherein the Y2 receptor-binding peptide is a PYY(3–

36) peptide comprised of the amino acid sequence of SEQ ID NO;

2.

11. A method for treating a mammal for obesity, inducing weight-loss or to induce satiety in the mammal comprised of intranasally administering to said mammal 45 μ

g to 150 μ

g of a composition comprising a Y2 receptor-binding peptide, and L-α

-phosphatidylcholine didecanoyl (DDPC).

12. The method of claim 11 wherein the mammal is human.

13. The method of claim 12 wherein the Y2 receptor-binding peptide is a PYY peptide.

14. The method of claim 13 wherein the Y2 receptor binding peptide is administered from 30 to 90 minutes prior to when the human eats food.

15. The method of claim 14 wherein the Y2 receptor-binding peptide is a PYY(3–

36) peptide comprised of the amino acid sequence of SEQ ID NO;

2.

38. The method of claim 11 wherein the composition is further comprised of at least two polyols.

39. The method of claim 38 wherein the polyols are selected from the group consisting of sucrose, mannitol, sorbitol, lactose, L-arabinose, D-erythrose, D-ribose, D-xylose, D-mannose, trehalose, D-galactose, lactulose, cellobiose, gentibiose, glycerin and polyethylene glycol.

40. The method of claim 39 wherein the polyols are lactose and sorbitol.

41. The method of claim 11 wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).

42. The method of claim 41 wherein the chelating agent is ethylenediamine tetraacetic acid (EDTA).

43. The method of claim 11 wherein the solubilizing agent is selected from the group consisting of a cyclodextran, hydroxypropyl-β

-cyclodextran, sulfobutylether-β

-cyclodextran and methyl-β

-cyclodextrin.

44. The method of claim 43 wherein the solubilizing agent is a methyl-β

-cyclodextrin.

45. The method of claim 11 wherein the composition is an aqueous PYY composition further comprised of water.

46. The method of claim 45 wherein the aqueous PYY composition has a pH from about 3 to about 6.

47. The method of claim 46 wherein the aqueous PYY composition has a pH of about 5.0±

0.3.

16. A method for treating a mammal for obesity, inducing weight-loss or to induce satiety in the mammal comprised of intranasally administering to said mammal 50 μ

g to 100 μ

g of a composition comprising a Y2 receptor-binding peptide, and L-α

-phosphatidylcholine didecanoyl (DDPC).

17. The method of claim 16 wherein the mammal is human.

18. The method of claim 17 wherein the Y2 receptor-binding peptide is a PYY peptide.

19. The method of claim 18 wherein the Y2 receptor binding peptide is administered from 30 to 90 minutes prior to when the human eats food.

20. The method of claim 19 wherein the Y2 receptor-binding peptide is a PYY(3–

36) peptide comprised of the amino acid sequence of SEQ ID NO;

2.

21. A method for treating a mammal for obesity, inducing weight-loss or to induce satiety in the mammal comprised of intranasally administering to said mammal about 55 μ

g to about 85 μ

g of a composition comprising a Y2 receptor-binding peptide and L-α

-phosphatidylcholine didecanoyl (DDPC).

22. The method of claim 21 wherein the mammal is human.

23. The method of claim 22 wherein the Y2 receptor-binding peptide is a PYY peptide.

24. The method of claim 23 wherein the Y2 receptor binding peptide is administered from 30 to 90 minutes prior to when the human eats food.

25. The method of claim 24 wherein the Y2 receptor-binding peptide is a PYY(3–

36) peptide comprised of the amino acid sequence of SEQ ID NO;

2.

26. A method for treating a mammal for obesity, inducing weight-loss or to induce satiety in the mammal comprised of intranasally administering to said mammal 65 μ

g to 75 μ

g of a composition comprising a Y2 receptor-binding peptide, and L-α

-phosphatidylcholine didecanoyl (DDPC).

27. The method of claim 26 wherein the mammal is human.