Novel formulations

• US 20030232748A1
• Filed: 04/24/2003
• Published: 12/18/2003
• Est. Priority Date: 05/07/2002
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Langkjaer, Liselotte
• Application Number:
  US10/422,239
• Publication Number:
  US 20030232748A1
• Time in Patent Office: Days
• US Class Current: 530/303
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/62 Insulins

Abstract

Stable, soluble insulin formulations having both a fast and a long action.

Claims

1. A pharmaceutical formulation comprising insulin aspart and insulin detemir, wherein the ratio between insulin aspart and insulin detemir is in the range from 15:

85 to 85;

15, on a unit (U) to unit (U) basis.

2. The formulation according to claim 1, said formulation further comprising an isotonicity agent, an antimicrobial preservative, a pH-buffering agent, and a suitable zinc salt.

3. The formulation according to claim 2, wherein the formulation has a pH value from about 7 to about 8.

4. The formulation according to claim 1, wherein the insulin is present in a concentration of from about 10 U/ml to about 1500 U/ml.

5. The formulation according to claim 1, wherein the insulin is present in a concentration of from about 40 U/ml to about 1000 U/ml.

6. The formulation according to claim 1, wherein the insulin is present in a concentration of from about 100 U/ml to about 500 U/ml.

7. The formulation according to claim 2, wherein the preservative is phenol, m-cresol or a mixture of phenol and m-cresol.

8. The formulation according to claim 7, wherein the phenol and/or m-cresol is present in a total concentration of from about 20 mM to about 50 mM.

9. The formulation according to claim 7, wherein the phenol and/or m-cresol is present in a total concentration of from about 30 mM to about 45 mM.

10. The formulation according to claim 2, wherein said formulation contains from about 2.3 to about 4.5 Zn²⁺ per insulin hexamer.

11. The formulation according to claim 2, wherein the zinc salt is zinc chloride, zinc oxide or zinc acetate.

12. The formulation according to claim 2, wherein said formulation further contains halogenide ions.

13. The formulation according to claim 12, wherein the halogenide ion is sodium chloride in a concentration of from about 1 to about 100 mM.

14. The formulation according to claim 12, wherein the halogenide ion is sodium chloride in a concentration of from about 5 to about 40 mM.

15. The formulation according to claim 2, wherein the isotonicity agent is glycerol, mannitol, sorbitol, or a mixture thereof in a concentration in a concentration range of from about 100 to about 250 mM.

16. The formulation according to claim 2, wherein the pH-buffer is sodium phosphate, TRIS (trometamol), N-glycylglycine, or L-arginine.

17. The formulation, according to claim 16, wherein the pH-buffer is a physiologically acceptable buffer in a concentration of from about 3 mM to about 20 mM.

18. The formulation, according to claim 16, wherein the pH-buffer is a physiologically acceptable buffer in a concentration of from about 5 mM to about 15 mM.

20. The use, according to any one of the two preceding claims, which is characterized by any of the features mentioned specifically in any of the above sub claims to pharmaceutical compositions.

21. A method of treating diabetes in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a pharmaceutical formulation according to claim 1.

19. The use of insulin aspart in an amount in the range from about 15% to about 85%, of the total amount of insulin component calculated on a unit to unit basis to prepare a solution having both a fast-acting and a long-acting insulin component.