Pharmaceutical compositions containing exendins

• US 7,297,761 B2
• Filed: 07/19/2004
• Issued: 11/20/2007
• 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, Beeley, Nigel Robert Arnold, Prickett, Kathryn S., Gedulin, Bronislava, Bhavsar, Sunil
• Primary Examiner(s): Bragdon; Kathleen Kerr
• Assistant Examiner(s): LIU, SAMUEL W
• Application Number:
  US10/894,999
• Publication Number:
  US 20050215469A1
• Time in Patent Office: 1,219 Days
• Field of Search: 530/303, 530/300, 514/2, 424/278.1
• US Class Current: 530/303
• 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 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides

Abstract

Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.

Claims

1. A pharmaceutical composition comprising an exendin-4 and an acetate buffer.

2. The composition of claim 1, wherein said composition has a pH from about 3.5 to about 5.

3. The composition of claim 1, wherein said pH is about 4.5.

4. The composition of claim 1, further comprising an isotonicity agent.

5. The composition of claim 4, wherein said isotonicity agent is selected from the group consisting of sodium chloride, dextrose, boric acid, sodium tartrate, propylene glycol, polyols, and any combination thereof.

6. The composition of claim 1, further comprising a pharmaceutically acceptable carrier or excipient selected from the group consisting of calcium carbonate, calcium phosphate, lactose, glucose, sucrose, starch, cellulose derivatives, gelatin, oils, polyethylene glycol, and any combination thereof.

7. The composition of claim 1, further comprising at least one additional substance other than an exendin that reduces food intake, appetite, body weight, obesity or any combination thereof.

8. The composition of claim 7, wherein said at least one additional substance is selected from the group consisting of amylin, an amylin agonist, a leptin, a cholecystokinin (CCK), CCK-8, a calcitonin, and any combination thereof.

9. The composition of claim 7, wherein said at least one additional substance comprises human amylin.

10. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 100 μ

g/kg of said exendin in a single or divided dose.

11. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 10 μ

g/kg of said exendin in a single or divided dose.

12. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 1 μ

g/kg of said exendin in a single or divided dose.

13. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 5 mg of said exendin in a single or divided dose.

14. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 2 mg of said exendin in a single or divided dose.

15. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 1 mg of said exendin in a single or divided dose.

16. The composition of claim 1, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 0.5 mg of said exendin in a single or divided dose.

17. The composition of claim 1, wherein said composition is formulated for intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal or pulmonary administration.

18. A pharmaceutical composition comprising exendin-4, mannitol, and an acetate buffer, wherein said composition has a pH from about 3.5 to about 5.0.

19. The composition of claim 18, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 1 μ

g/kg of said exendin-4 in a single or divided dose.

20. The composition of claim 18, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 0.5 mg of said exendin-4 in a single or divided dose.

21. The composition of claim 18, further comprising at least one additional substance other than an exendin that reduces food intake, appetite, body weight, obesity or any combination thereof.

22. A pharmaceutical composition comprising a buffer and an exendin selected from at least one of the group consisting of an exendin-3, and an exendin-4, wherein said composition has a pH from about 3.5 to about 5.

23. The composition of claim 22, wherein said buffer comprises an acetate buffer.

24. The composition of claim 22, further comprising an isotonicity agent.

25. The composition of claim 22, wherein said isotonicity agent is selected from the group consisting of sodium chloride, dextrose, boric acid, sodium tartrate, propylene glycol, polyols, and any combination thereof.

26. The composition of claim 22, further comprising a pharmaceutically acceptable carrier or excipient selected from the group consisting of calcium carbonate, calcium phosphate, lactose, glucose, sucrose, starch, cellulose derivatives, gelatin, oils, polyethylene glycol, and any combination thereof.

27. The composition of claim 22, further comprising at least one additional substance other than an exendin that reduces food intake, appetite, body weight, obesity or any combination thereof.

28. The composition of claim 27, wherein said at least one additional substance is selected from the group consisting of amylin, an amylin agonist, a leptin, a cholecystokinin (CCK), CCK-8, a calcitonin, and any combination thereof.

29. The composition of claim 27, wherein said at least one additional substance comprises human amylin.

30. The composition of claim 22, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 100 μ

g/kg of said exendin in a single or divided dose.

31. The composition of claim 22, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 10 μ

g/kg of said exendin in a single or divided dose.

32. The composition of claim 22, wherein said composition is formulated to provide a daily dose of from about 0.1 μ

g/kg to about 1 μ

g/kg of said exendin in a single or divided dose.

33. The composition of claim 22, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 0.5 mg of said exendin in a single or divided dose.

34. The composition of claim 22, wherein said composition is formulated to provide a daily dose of from about 0.01 mg to about 0.5 mg of said exendin in a single or divided dose.

35. The composition of claim 22, wherein said composition is formulated for intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical, transmucosal or pulmonary administration.

36. The pharmaceutical composition of claim 22, wherein said exendin-4 is selected from the group consisting of exendin-4 (1-30), exendin-4 (1-30) amide, exendin-4 (1-28) amide, ₁₄Leu, ²⁵Phe exendin-4 amide, ¹⁴Leu, ²⁵Phe exendin-4 (1-28) amide, ¹⁴Leu, ²²Ala, ²⁵Phe exendin-4 (1-28) amide, and any combination thereof.

37. The pharmaceutical composition of claim 22, wherein said exendin is exendin-4.