COMPOSITIONS FOR ENHANCED EPITHELIAL PERMEATION OF PEPTIDE YY FOR TREATING OBESITY

• US 20070275893A1
• Filed: 11/17/2006
• Published: 11/29/2007
• 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
• Application Number:
  US11/561,331
• Publication Number:
  US 20070275893A1
• Time in Patent Office: Days
• US Class Current: 514/1.200
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents

Abstract

Pharmaceutical compositions comprising PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) is present in an amount effective to alleviate one or more symptom(s) of obesity in a subject, and the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation.

Claims

1. A pharmaceutical composition comprising PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) is present in an amount effective to alleviate one or more symptom(s) of obesity in a subject, and the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation.

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

-phosphatidylcholine didecanoyl (DDPC).

3. The pharmaceutical composition 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 pharmaceutical composition of claim 1, wherein the cyclodextrin is methyl-β

-cyclodextrin.

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

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

0.5.

7. The pharmaceutical composition of claim 1, further comprising a chelating agent.

8. The pharmaceutical composition of claim 7, wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).

9. The pharmaceutical composition of claim 7, wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA).

10. The pharmaceutical composition of claim 1, wherein the composition is formulated for nasal mucosal delivery to a mammalian subject.

11. The pharmaceutical composition of claim 10, wherein the composition is formulated as an intranasal spray or powder.

12. The pharmaceutical composition of claim 1, wherein the composition following mucosal administration to the subject 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 subject 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).

13. The pharmaceutical composition of claim 1, wherein the composition following mucosal administration to the subject yields an area under concentration curve (AUC) of PYY(3-36) in a CNS tissue or fluid or in a blood plasma of the subject 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).

14. The pharmaceutical composition of claim 1, wherein the composition following mucosal administration to the subject 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 subject between about 0.1 to 1.0 hours.

15. The pharmaceutical composition of claim 1, further comprising one or more sustained release-enhancing agent(s).

16. The pharmaceutical composition of claim 15, wherein the sustained release-enhancing agent is polyethylene glycol (PEG).

17. The pharmaceutical composition of claim 1, wherein the PYY(3-36) is formulated in an effective dosage unit of between about 30 and 250 μ

g.

18. The pharmaceutical composition of claim 1, wherein the PYY(3-36) is formulated in an effective dosage unit of between about 0.1 pmol and 5.0 pmol per kilogram body weight of the subject.