METHODS FOR ENHANCED EPITHELIAL PERMEATION OF Y2 RECEPTOR-BINDING PEPTIDES FOR TREATING AND PREVENTING OBESITY

• US 20080004218A1
• Filed: 11/27/2006
• Published: 01/03/2008
• Est. Priority Date: 12/17/2002
• Status: Abandoned Application

• Current Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Original Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven, Brandt, Gordon
• Application Number:
  US11/563,587
• Publication Number:
  US 20080004218A1
• Time in Patent Office: Days
• US Class Current: 514/12
• 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

A method for treating obesity, inducing weight-loss, or inducing satiety in a mammal comprising administering intranasally to the mammal a therapeutically effective amount of a pharmaceutical composition comprising PYY(3-36), a phosphatidylcholine or diglyceride, and a cyclodextrin, wherein the phosphatidylcholine or diglyceride and the cyclodextrin are present in an amount sufficient to enhance epithelial permeation.

Claims

1. A method for treating obesity, inducing weight-loss, or inducing satiety in a mammal comprising administering intranasally to the mammal a therapeutically effective amount of a pharmaceutical composition comprising PYY(3-36), a phosphatidylcholine or diglyceride, and a cyclodextrin, wherein the phosphatidylcholine or diglyceride and the cyclodextrin are present in an amount sufficient to enhance epithelial permeation.

2. The method of claim 1, wherein the phosphatidylcholine is L-α

-phosphatidylcholine didecanoyl (DDPC).

3. The method of claim 1, wherein the cyclodextrin is selected from the group consisting of hydroxypropyl-β

-cyclodextrin, sulfobutylether-β

-cyclodextrin, and methyl-β

-cyclodextrin.

4. The method of claim 3, wherein the cyclodextrin is methyl-β

-cyclodextrin.

5. The method of claim 1, wherein the composition is an aqueous composition having a pH of from about 3 to about 6.

6. The method of claim 5, wherein the pH is 5.0±

0.5.

7. The method of claim 1, the composition further comprising a polyol.

8. The method of claim 7, wherein the polyol is 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.

9. The method of claim 7, wherein the polyol is sorbitol.

10. The method of claim 7, further comprising a chelating agent.

11. The method of claim 10, wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).

12. The method of claim 10, wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA).

13. The method of claim 1 wherein the mammal is a human.

14. The method of claim 1, wherein the administration results in an increase in concentration of PYY(3-36) in the blood of the mammal by at least 5 pmol per liter of plasma to about 60 pmol per liter of plasma.

15. The method of claim 1, wherein the administration is from 30 to 90 minutes before a feeding of the mammal.

16. The method of claim 1, wherein the amount of PYY(3-36) is from 30 μ

g to 250 μ

g.

17. The method of claim 1, wherein the amount of PYY(3-36) is from about 0.1 pmol to about 5.0 pmol per kilogram body weight of the mammal.

18. The method of claim 1, wherein the composition is formulated for nasal mucosal delivery to a mammal.

19. The method of claim 1, wherein the composition is formulated as an intranasal spray or powder.

20. The method of claim 1, wherein the composition following mucosal administration to the mammal yields a peak concentration (C_max) of PYY(3-36) in a central nervous system (CNS) tissue or fluid or in a blood plasma of the mammal that is 25% or greater as compared to a peak concentration of PYY(3-36) in a CNS tissue or fluid or in a blood plasma following subcutaneous injection of an equivalent concentration or dose of PYY(3-36).

21. The method of claim 1, wherein the composition following mucosal administration to the mammal yields an area under concentration curve (AUC) of PYY(3-36) in a CNS tissue or fluid or in a blood plasma of the mammal that is 25% or greater compared to an AUC of PYY(3-36) in a CNS tissue or fluid or in a blood plasma following subcutaneous injection of an equivalent concentration or dose of PYY(3-36).

22. The method of claim 1, wherein the composition following mucosal administration to the mammal yields a time to maximal concentration (t_max) of PYY(3-36) in a CNS tissue or fluid or in a blood plasma of the mammal between about 0.1 to 1.0 hours.

23. The method of claim 1, further comprising one or more sustained release-enhancing agent(s).

24. The method of claim 23, wherein the sustained release-enhancing agent is polyethylene glycol (PEG).