Exendin pharmaceutical compositions

• US 7,521,423 B2
• Filed: 07/20/2004
• Issued: 04/21/2009
• Est. Priority Date: 08/08/1996
• Status: Expired due to Fees

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Young, Andrew A., Gedulin, Bronislava
• Primary Examiner(s): Canella; Karen A
• Application Number:
  US10/896,244
• Publication Number:
  US 20040266692A1
• Time in Patent Office: 1,736 Days
• Field of Search: None
• US Class Current: 514/1.1
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 38/26 Glucagons
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/06 Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

Methods for reducing gastric motility and delaying gastric emptying for therapeutic and diagnostic purposes are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist. Methods for treating conditions associated with elevated, inappropriate, or undesired post-prandial blood glucose levels are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist alone or in conjunction with other anti-gastric emptying agents.

Claims

1. A pharmaceutical composition comprising an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO. 2 in an amount from 0.001 mg based on a 70 kg patient to 1 mg based on a 70 kg patient;

a pharmaceutically acceptable buffer;

a pharmaceutically acceptable isotonicity agent; and

a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1, wherein the buffer is an acetate buffer.

3. The pharmaceutical composition of claim 1, wherein the isotonicity agent is mannitol, sorbitol, or a combination thereof.

4. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is water, lactose, glucose, sucrose, starch, a cellulose derivative, a gelatin, an oil, a polyethylene glycol, a physiologically compatible solvent, or a combination of two or more thereof.

5. The pharmaceutical composition of claim 1, wherein the composition is formulated to provide a single or divided daily dose of the exendin-4 peptide in an amount from 0.001 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

6. The pharmaceutical composition of claim 5, wherein the composition is formulated to provide a single daily dose.

7. The pharmaceutical composition of claim 5, wherein the composition is formulated to provide a divided daily dose.

8. The pharmaceutical composition of claim 5, in an amount from 0.01 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

9. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a subcutaneously injectable pharmaceutical composition.

10. A pharmaceutical composition comprising an exendin-4 peptide which comprises the amino acid sequence of SEQ ID NO. 2 in an amount from 0.001 mg based on a 70 kg patient to 1 mg based on a 70 kg patient;

a pharmaceutically acceptable isotonicity agent selected from the group consisting of sodium chloride, dextrose, boric acid, sodium tartrate, propylene glycol, a polyol, and a combination of two or more thereof; and

a pharmaceutically acceptable buffer.

11. The pharmaceutical composition of claim 10, wherein the composition is formulated to provide a single or divided daily dose of the exendin-4 peptide in an amount from 0.001 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

12. The pharmaceutical composition of claim 10, wherein the isotonicity agent is a polyol.

13. The pharmaceutical composition of claim 12, wherein the polyol is (i) mannitol, (ii) sorbitol, or a combination thereof.

14. The pharmaceutical composition of claim 10, wherein the buffer is an acetate buffer.

15. The pharmaceutical composition of claim 10, further comprising a pharmaceutically acceptable carrier selected from the group consisting of water, lactose, glucose, sucrose, starch, a cellulose derivative, gelatin, an oil, a polyethylene glycol, a physiologically compatible solvent, and a combination of two or more thereof.

16. The pharmaceutical composition of claim 10, wherein the composition is formulated for intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, or transmucosal administration.

17. The pharmaceutical composition of claim 10, wherein the exendin-4 peptide comprises an exendin-4 acid, an exendin-4 amide, or a combination thereof.

18. The pharmaceutical composition of claim 11, wherein the composition is formulated to provide a single daily dose.

19. The pharmaceutical composition of claim 11, wherein the composition is formulated to provide a divided daily dose.

20. The pharmaceutical composition of claim 11, in an amount from 0.01 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

21. The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is a subcutaneously injectable pharmaceutical composition.

22. A pharmaceutical composition comprising (i) an exendin-4 peptide which comprises the amino acid sequence of SEQ ID NO. 2 in an amount from 0.001 mg based on a 70 kg patient to 1 mg based on a 70 kg patient;

(ii) mannitol, sorbitol, or a combination thereof; and

(iii) an acetate buffer.

23. The pharmaceutical composition of claim 22, wherein the exendin-4 peptide comprises an exendin-4 acid, an exendin-4 amide, or a combination thereof.

24. The pharmaceutical composition of claim 22, wherein the composition is formulated to provide a single or divided daily dose of the exendin-4 peptide in an amount from 0.001 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

25. The pharmaceutical composition of claim 24, wherein the composition is formulated to provide a single daily dose.

26. The pharmaceutical composition of claim 24, wherein the composition is formulated to provide a divided daily dose.

27. The pharmaceutical composition of claim 24, in an amount from 0.01 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

28. The pharmaceutical composition of claim 22, wherein the pharmaceutical composition is a subcutaneously injectable pharmaceutical composition.

29. A subcutaneously injectable pharmaceutical composition comprising (i) an exendin-4 peptide which comprises the amino acid sequence of SEQ ID NO. 2 in an amount from 0.001 mg based on a 70 kg patient to 1 mg based on a 70 kg patient;

(ii) mannitol, sorbitol, or a combination thereof;

(iii) an acetate buffer; and

(iv) a pharmaceutically acceptable aqueous carrier.

30. The pharmaceutical composition of claim 29, wherein the composition is formulated to provide a single or divided daily dose of the exendin-4 peptide in an amount from 0.001 mg based on the 70 kg patient to 1 mg based on the 70 kg patient.

31. The pharmaceutical composition of claim 29, wherein the composition is formulated to provide a single daily dose.

32. The pharmaceutical composition of claim 29, wherein the composition is formulated to provide a divided daily dose.