COMPOSITIONS FOR ENHANCED EPITHELIAL PERMEATION OF PEPTIDE YY FOR TREATING OBESITY

• US 20090118158A1
• Filed: 09/19/2008
• Published: 05/07/2009
• Est. Priority Date: 12/17/2002
• Status: Active Grant

• Current Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Original Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven C.
• Granted Patent: US 7,863,245 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• 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 composition comprising a Y2-receptor selective agonist a solubilizing agent, a chelating agent, and L-α

-phosphatidylcholine.

2. The composition of claim 1, wherein the Y2-receptor selective agonist is PEGylated.

3. The composition of claim 1, wherein the Y2-receptor selective agonist is selected from the group consisting of neuropeptide Y, ([¹²⁵I]-Tyr)-neuropeptide Y, biotinyl-neuropeptide Y, (Leu³¹,Pro³⁴)-neuropeptide Y, (D-Trp³²)-neuropeptide Y, (Tyr(Me)²¹)-neuropeptide Y, (Ala³¹,Aib³²)-neuropeptide Y, (Leu³¹,Pro³⁴)-neuropeptide Y, (Pro 34)-neuropeptide Y, (D-Trp³²)-neuropeptide Y, neuropeptide Y_1-24 amide, (Cys²)-neuropeptide Y_1-4-8-aminooctanoyl-(D-Cys²⁷)-neuropeptide Y_25-32, neuropeptide Y_2-36, neuropeptide Y_3-36, neuropeptide Y_3-36, neuropeptide Y_13-36, (Leu³¹,Pro³⁴)-neuropeptide Y_13-36, neuropeptide Y_18-36, pancreatic polypeptide_1-17-(Ala³¹,Aib³²)-neuropeptide Y_18-36, neuropeptide Y_22-36, Tyr-Lys-Gly-Arg-(Glu²⁶,Lys²⁹,Pro³⁴)-neuropeptide Y_26-36, (D-Tyr^27,36,D-Thr³²)-neuropeptide Y_27-36, ((Cys³,Nva³⁴)-neuropeptide Y_27-36)₂, (Pro³⁰,Tyr³²,Leu³⁴)-neuropeptide Y_28-36, (His³²,Leu³⁴)-neuropeptide Y_32-36, ([¹²⁵I]-Tyr)-(Leu³¹,Pro³⁴)-neuropeptide Y, (Gly¹,Ser^3,22,Gln^4,34,Thr⁶,Ala¹⁹,Tyr²¹,Ala^23,31,Aib³²)-pancreatic polypeptide (human), and Y2A (N-acetyl [Leu, Leu] NPY_24-36).

4. The composition of claim 1, wherein the solubilizing agent is selected from the group consisting of hydroxypropyl-β

-cyclodextrin, sulfobutylether-β

-cyclodextrin, and methyl-β

-cyclodextrin.

5. The composition of claim 1, wherein the chelating agent is selected from the group consisting of ethylene diamine tetraacetic acid (EDTA) and ethylene glycol tetraacetic acid (EGTA).

6. The composition of claim 1, wherein the composition is a dry powder.

7. The composition of claim 1, further comprising a pH control agent.

8. The composition of claim 7, wherein the pH control agent is selected from the group consisting of arginine, sodium hydroxide, glycine, hydrochloric acid, and citric acid.

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

10. The composition of claim 1, wherein the composition is an aqueous composition having a pH of about 5.

11. The composition of claim 1, wherein the composition is an aqueous composition having a pH of about 4.

12. The composition of claim 1, further comprising a preservative.

13. The composition of claim 12, wherein the preservative is selected from the group consisting of methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, phenol, methyl paraben, paraben, m-cresol, thiomersal, benzylalkonium chloride, and chlorobutanol.

14. The composition of claim 1, further comprising a release-enhancing agent.

15. The composition of claim 14, wherein the release-enhancing agent is polyethylene glycol (PEG).