Derivatives of GLP-1 analogs

• US 6,458,924 B2
• Filed: 09/16/1999
• Issued: 10/01/2002
• Est. Priority Date: 08/30/1996
• Status: Expired due to Term

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Nielsen, Per Franklin, Huusfeldt, Per Olaf, Knudsen, Liselotte Bjerre
• Primary Examiner(s): Low, Christopher S. F.
• Assistant Examiner(s): Lukton, David
• Application Number:
  US09/398,111
• Publication Number:
  US 20010011071A1
• Time in Patent Office: 1,111 Days
• Field of Search: 514/2, 514/12, 530/324, 530/345
• US Class Current: 530/324
• 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 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• 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: C07K 14/605 Glucagons
• CPC Class Codes: C11D 3/0063 Photo- activating compounds
• CPC Class Codes: C11D 3/168 Organometallic compounds or orgometallic complexes

Abstract

The present invention relates to a pharmaceutical composition comprising a GLP-1 derivative having a lipophilic substituent; and a surfactant.

Claims

1. A glucagon-like peptide-1 (GLP-1) derivative of formula I (SEQ ID NO:

2);

2. The GLP-1 derivative of claim 1, wherein the lipophilic substituent is linked to the ε

-amino group of Lys via a spacer.

3. The GLP-1 derivative of claim 2, wherein the spacer is is γ

-glutamyl.

4. The GLP-1 derivative of claim 2, wherein the spacer is β

-asparagyl.

5. The GLP-1 derivative of claim 2, wherein the spacer is glycyl.

6. The GLP-1 derivative of claim 2, wherein the spacer is γ

-aminobutanoyl.

7. The GLP-1 derivative of claim 2, wherein the spacer is β

-alanyl.

8. A pharmaceutical composition comprising a GLP-1 derivative of claim 1 and a pharmaceutically acceptable vehicle or carrier.

9. The pharmaceutical composition of claim 8, further comprising an isotonic agent, a preservative and a buffer.

10. The pharmaceutical composition of claim 9, wherein the isotonic agent is sodium chloride, mannitol and glycerol.

11. The pharmaceutical composition of claim 9, wherein the preservative is phenol, m-cresol, methyl p-hydroxybenzoate or benzyl alcohol.

12. The pharmaceutical composition of claim 9, wherein the buffer is sodium acetate or sodium phosphate.

13. The pharmaceutical composition of claim 8, further comprising a surfactant.

14. The pharmaceutical composition of claim 8, further comprising zinc.

15. The pharmaceutical composition of claim 8, further comprising an antidiabetic agent.

16. The pharmaceutical composition of claim 15, wherein the antidiabetic agent is human insulin.

17. The pharmaceutical composition of claim 15, wherein the antidiabetic agent is a hypoglycemic agent.

18. The pharmaceutical composition of claim 8, further comprising an antiobesity agent.

19. A method of treating diabetes, comprising adminstering to a patient a therapeutically effective amount of a GLP-1 derivative of claim 1.

20. A method of treating obesity, comprising administering to a patient a therapeutically effective amount of a GLP-1 derivative of claim 1.