Compositions and methods for enhanced mucosal delivery of Y2 receptor-binding peptides and methods for treating and preventing obesity

• US 20040214772A1
• Filed: 02/17/2004
• Published: 10/28/2004
• Est. Priority Date: 12/17/2002
• Status: Active Grant

• Current Assignee: Mdrna Inc. (Adhera Therapeutics, Inc.)
• Original Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven C., Kleppe, Mary S., Brandt, Gordon, MacEvilly, Conor J.
• Granted Patent: US 7,229,966 B2
• Time in Patent Office: Days
• US Class Current: 514/12
• 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

Pharmaceutical compositions and methods are described comprising at least one Y2 receptor-binding peptide, such as peptide YY(PYY), Neuropeptide Y (NPY) or Pancreatic Peptide (PP) and one or more mucosal delivery-enhancing agents for enhanced nasal mucosal delivery of the peptide YY, for treating a variety of diseases and conditions in mammalian subjects, including obesity.

Claims

1. A pharmaceutical composition product comprising:

a. an aqueous solution formulation of a Y2 receptor binding compound at a concentration sufficient to produce therapeutically effective plasma concentrations and;

b. an actuator able to produce an aerosol of said solution, wherein the spray pattern ellipticity ratio of said aerosol is between 1.00 and 1.40 when measured at a height of between 0.5 cm and 10 cm distance from the actuator tip.

2. The Y2 receptor binding compound of claim 1 comprising PYY(3-36).

3. The aqueous solution of claim 2 wherein said PYY(3-36) is at a concentration of at least 200 ug/mL.

4. The product of claim 1 wherein said actuator produces an ellipticity of between 1.00 and 1.30.

5. The product of claim 1 comprising an aerosol of between 20 and 200 microliters per actuation.

6. The product of claim 3 wherein said ellipticity is between 1.15 and 1.25.

8. The Y2 receptor binding compound of claim 6 comprising PYY(3-36).

7. A pharmaceutical composition product comprising:

a. an aqueous solution of a Y2 receptor binding compound;

b. an actuator to produce an aerosol of said solution, wherein the spray pattern major and minor axes of said aerosol are between 10 and 50 mm when measured at a height of between 0.5 cm and 10 cm distance from the actuator tip.

9. The aqueous solution of claim 7 wherein said PYY(3-36) is at a concentration of at least 200 ug/mL.

10. The product of claim 7 comprising an aerosol of between 20 and 200 microliters per actuation.

12. The product of claim 9 wherein less than 5% of the droplets are smaller than 10 microns in size.

13. The product of claim 9 wherein less than 1% of the droplets are smaller than 10 microns in size.

11. A pharmaceutical composition product comprising:

a. an aqueous solution formulation of a Y2 receptor binding compound at a concentration sufficient to produce therapeutically effective plasma concentrations and;

b. an actuator to produce an aerosol of said solution, wherein less than 10% of the droplets are smaller than 10 microns in size.

14. The product of claim 11 comprising an aerosol of between 20 and 200 microliters per actuation.

15. A pharmaceutical composition product comprising:

a. an aqueous solution formulation of a Y2 receptor binding compound at a concentration sufficient to produce therapeutically effective plasma concentrations and;

b. an actuator selected to produce an aerosol of said solution, wherein droplets between 25 and 700 microns are produced.

16. The product of claim 15 comprising an aerosol of between 20 and 200 microliters per actuation.