A DEVICE FOR ENHANCED EPITHELIAL PERMEATION OF Y2 RECEPTOR-BINDING PEPTIDES

• US 20070161563A1
• Filed: 11/22/2006
• Published: 07/12/2007
• 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, Brandt, Gordon, MacEvilly, Conor, Kleppe, Mary
• Application Number:
  US11/562,913
• Publication Number:
  US 20070161563A1
• Time in Patent Office: Days
• US Class Current: 514/5.200
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A pharmaceutical device comprising a composition comprising an aqueous solution of PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation, and wherein the composition is present in a container; and an actuator fluidly connected to the container, wherein the actuator has a tip which defines a passage through which the solution is ejected to produce a spray of the solution.

Claims

1. A pharmaceutical device comprising:

a. a composition comprising an aqueous solution of PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation, and wherein the composition is present in a container;

b. an actuator fluidly connected to the container, wherein the actuator has a tip which defines a passage through which the solution is ejected to produce a spray of the solution.

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

-phosphatidylcholine didecanoyl (DDPC).

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

-cyclodextrin.

5. The device of claim 1, wherein the solution has a pH of from about 3 to about 6.

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

0.5.

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

8. The device 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 device of claim 7, wherein the polyol is sorbitol.

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

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

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

13. The device of claim 7, further comprising one or more sustained release-enhancing agent(s).

14. The device of claim 13, wherein the sustained release-enhancing agent is polyethylene glycol (PEG).

15. The device of claim 1, wherein the PYY(3-36) is present in solution at a concentration of at least 200 μ

g/mL.

16. The device of claim 1, wherein the actuator produces a spray having a volume of between 20 and 200 microliters per actuation.

17. The device of claim 1, wherein the spray is comprised of droplets, and wherein less than 10% of the droplets are smaller than 10 microns in size.

18. The device of claim 17, wherein less than 5% of the droplets are smaller than 10 microns in size.

19. The device of claim 17, wherein less than 1% of the droplets are smaller than 10 microns in size.

20. The device of claim 17, wherein the droplets are between 25 and 700 micrometers in size.

21. The device of claim 1, wherein each spray from the actuator contains at least 100 micrograms of PYY(3-36).

22. The device of claim 1, wherein the spray has a spray pattern having major and minor axes of from 10 to 50 mm when measured at a height of from 0.5 cm to 10 cm from the actuator tip.

23. The device of claim 1, wherein the spray is an aerosol with a spray pattern ellipticity ratio of from 1.00 to 1.40 when measured at a height of from 0.5 cm to 10 cm from the actuator tip.

24. The device of claim 23, wherein the ellipticity ratio is from 1.00 to 1.30.

25. The device of claim 23, wherein the ellipticity ratio is from 1.15 to 1.25.