Compositions for enhanced epithelial permeation of neuropeptide Y for treating obesity

• US 7,863,245 B2
• Filed: 09/19/2008
• Issued: 01/04/2011
• Est. Priority Date: 12/17/2002
• Status: Expired due to Fees

• Current Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Original Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven C.
• Primary Examiner(s): Carlson; Karen Cochrane
• Assistant Examiner(s): Kosson; Roasanne
• Application Number:
  US12/234,547
• Publication Number:
  US 20090118158A1
• Time in Patent Office: 837 Days
• Field of Search: 514/12, 530/303, 530/324, 564/293
• US Class Current: 514/5.2
• 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) or Neuropeptide Y (NPY), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) or Neuropeptide Y (NPY) 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 didecanoyl (DDPC).

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 (SEQ ID NO:

795), ([¹²⁵I]-Tyr)-neuropeptide Y (SEQ ID NO;

802), biotinyl-neuropeptide Y (SEQ ID NO;

803), (Leu³¹,Pro³⁴)-neuropeptide Y (SEQ ID NO;

804), (D-Trp³²)-neuropeptide Y (SEQ ID NO;

805), (Tyr(Me)²¹)-neuropeptide Y (SEQ ID NO;

806), (A1a³¹,Aib³²)-neuropeptide Y (SEQ ID NO;

807), (Leu³¹,Pro³⁴)-neuropeptide Y (SEQ ID NO;

808), (Pro³⁴)-neuropeptide Y (SEQ ID NO;

809), (D-Trp³²)-neuropeptide Y (SEQ ID NO;

810), neuropeptide Y_1-24 amide (SEQ ID NO;

811), (Cys²)-neuropeptide Y_1-4-8-aminooctanoyl-(D-Cys²⁷)-neuropeptide Y_25-32 (SEQ ID NO;

812), neuropeptide Y_2-36 (SEQ ID NO;

813), neuropeptide Y_3-36 (SEQ ID NO;

814), neuropeptide Y_13-36 (SEQ ID NO;

815), (Leu³¹,Pro³⁴)-neuropeptide Y_13-36 (SEQ ID NO;

816), neuropeptide Y_18-36 (SEQ ID NO;

817), pancreatic polypeptide_1-17-A1a³¹,Aib³²)-neuropeptide Y_18-36 (SEQ ID NO;

818), neuropeptide Y_22-36 (SEQ ID NO;

819), Tyr-Lys-Gly-Arg-(Glu²⁶,Lys²⁹,Pro³⁴)-neuropeptide Y_26-36 (SEQ ID NO;

820), (D-Tyr^27,36,D-Thr³²)-neuropeptide Y_27-36 (SEQ ID NO;

821), ((Cys³¹,Nva³⁴)-neuropeptide Y_27-36)₂(SEQ ID NO;

822), (Pro³⁰,Tyr³²,Leu³⁴)-neuropeptide Y_28-36 (SEQ ID NO;

823), (His³²,Leu³⁴)-neuropeptide Y_32-36 (SEQ ID NO;

824), ([¹²⁵I]-Tyr)-(Leu³¹,Pro³⁴)-neuropeptide Y (SEQ ID NO;

825), (Gly¹,Ser^3,22,Gln^4,34,Thr⁶,Ala¹⁹, Tyr²¹,Ala^23,31,Aib³²)-pancreatic polypeptide (human) (SEQ ID NO;

826), and Y2A (N-acetyl [Leu²⁸, Leu³¹]NPY_24-36) (SEQ ID NO;

827).

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, benzylalkonimum 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).