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

• US 7,186,691 B2
• Filed: 12/23/2003
• Issued: 03/06/2007
• Est. Priority Date: 12/17/2002
• Status: Expired due to Fees

• 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.
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): Kosson; Rosanne
• Application Number:
  US10/745,069
• Publication Number:
  US 20040157777A1
• Time in Patent Office: 1,169 Days
• Field of Search: 514/12, 530/324, 530/303
• US Class Current: 514/4.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 38/2271 Neuropeptide Y
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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

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 method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a mammal comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the mammal wherein the PYY formulation is comprised of a solubilizing agent, a chelating agent, a polyol, L-α

-phosphatidylcholine didecanoyl (DDPC) and a PYY peptide wherein the PYY peptide is comprised of the amino acid sequence of SEQ ID NO;

2.

2. The method of claim 1 wherein the formulation is an aqueous PYY formulation.

3. The method of claim 2 wherein the aqueous PYY formulation has a pH of about of about 3–

6.

4. The method of claim 3 wherein the pH of the aqueous PYY formulation is 5.0±

0.3.

5. The method of claim 1 wherein a dose containing 50 μ

g to 800 μ

g of a PYY peptide is administered to the mammal.

6. The method of claim 5 wherein a dose containing 100 μ

g to 400 μ

g is administered to the mammal.

7. The method of claim 6 wherein a dose containing 150 μ

g to 200 μ

g is administered to the mammal.

8. The method of claim 1 wherein the mammal is a human.

9. The method for inducing appetite suppression of claim 1 wherein the formulation is further comprised of at least two polyols.

10. The method for inducing appetite suppression of claim 9 wherein the polyols are 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.

11. The method of claim 10 wherein the polyols are lactose and sorbitol.

12. The method of claim 1 wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).

13. The method of claim 12 wherein the chelating agent is ethylenediamine tetraacetic acid (EDTA).

14. The method of claim 1 wherein the solubilizing agent is selected from the group consisting of a cyclodextran, hydroxypropyl-β

-cyclodextran, sulfobutylether-β

-cyclodextran and methyl-β

-cyclodextrin.

15. The method of claim 14 wherein the solubilizing agent is a cyclodextrin.

16. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a mammal comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the mammal wherein the PYY formulation is comprised of methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and a PYY peptide wherein the PYY peptide is comprised of the amino acid sequence of SEQ ID NO;

2.

17. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a human comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the human wherein the PYY formulation is comprised of water, sodium citrate, citric acid, methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and PYY(3–

36) (SEQ ID NO;

     2), wherein the formulation has a pH of about 5.0±

0.3.

18. The method of claim 17 wherein the human is administered a dose containing from 50 μ

g to about 800 μ

g of PYY(3–

36) (SEQ ID NO;

     2).

19. The method of claim 17 wherein the human is administered a dose containing from 100 μ

g to about 400 μ

g of PYY(3–

36) (SEQ ID NO;

     2).

20. The method of claim 17 wherein the human is administered a dose containing from 150 μ

g to about 200 μ

g of PYY(3–

36) (SEQ ID NO;

     2).

21. The method of claim 17, wherein the formulation is further comprised of a preservative selected from the group consisting of chlorobutanol and benzalkonium chloride.

22. The method of claim 21 wherein the preservative is chlorobutanol.

23. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a human comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the human wherein the PYY formulation is comprised of water, sodium citrate, citric acid, methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and PYY(3–

36) (SEQ ID NO;

     2), wherein the formulation has a pH of about 5.0±

0.3 and wherein the human is administered 150 μ

g to about 200 μ

g of PYY(3–

36) (SEQ ID NO;

     2).

24. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a human comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the human wherein the PYY formulation is comprised of water, chlorobutanol, sodium citrate, citric acid, methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and PYY(3–

36) (SEQ ID NO;

     2), wherein the formulation has a pH of about 5.0±

0.3 and wherein the human is administered 150 μ

g to about 200 μ

g of PYY(3–

36) (SEQ ID NO;

     2).

25. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a human comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the human wherein the PYY formulation is comprised of water, benzalkonium chloride, sodium citrate, citric acid, methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and PYY(3–

36) (SEQ ID NO;

     2), wherein the formulation has a pH of about 5.0±

0.3 and wherein the human is administered 150 μ

g to about 200 μ

g of PYY(3–

36) (SEQ ID NO;

     2).

26. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a human comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the human wherein the PYY formulation is comprised of water, chlorobutanol, sodium citrate, citric acid, methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and PYY(3–

36) (SEQ ID NO;

     2), wherein the formulation has a pH of about 5.0±

0.3.

27. A method for treating obesity, inducing weight-loss, inducing satiety or inducing appetite suppression in a human comprising administering intranasally a therapeutically effective amount of a peptide YY (PYY) formulation to the human wherein the PYY formulation is comprised of water, benzalkonium chloride, sodium citrate, citric acid, methyl-β

-cyclodextrin, EDTA, lactose, sorbitol, L-α

-phosphatidylcholine didecanoyl and PYY(3–

36) (SEQ ID NO;

     2), wherein the formulation has a pH of about 5.0±

0.3.