LONG-ACTING FORMULATIONS OF INSULINS

• US 20120122774A1
• Filed: 12/02/2011
• Published: 05/17/2012
• Est. Priority Date: 05/19/2010
• Status: Abandoned Application

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Becker, Reinhard, Frick, Annke, Boderke, Peter, Fürst, Christiane, Müller, Werner, Tertsch, Katrin, Werner, Ulrich, Loos, Petra, Schöttle, Isabell
• Application Number:
  US13/310,118
• Publication Number:
  US 20120122774A1
• Time in Patent Office: Days
• US Class Current: 514/6.2
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• 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 47/26 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 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: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

The application relates to an aqueous pharmaceutical formulation comprising 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine.

Claims

1. An aqueous pharmaceutical formulation comprising 300 U/mL of insulin glargine [equimolar to 300 IU human insulin].

2. The aqueous pharmaceutical formulation of claim 1 comprising an analogue of exendin-4.

3. The aqueous pharmaceutical formulation of claim 2, wherein the analogue of exedin-4 is selected from a group comprising lixisentatide, exenatide and liraglutide.

4. The aqueous pharmaceutical formulation of claim 3 comprising 0.1 μ

g to 10 μ

g lixisenatide per U insulin glargine.

5. The aqueous pharmaceutical formulation of claim 4 comprising 0.2 to 1 μ

g lixisenatide per U insulin glargine.

6. The aqueous pharmaceutical formulation of claim 5 comprising 0.25 μ

g to 0.7 μ

g lixisenatide per U insulin glargine.

7. The aqueous pharmaceutical formulation of claim 1 comprising at least one excipient selected from the group comprising zinc, m-cresol, glycerol, polysorbate 20 and sodium.

8. The aqueous pharmaceutical formulation of claim 7 comprising 90 μ

g/mL zinc, 2.7 mg/mL m-cresol and 20 mg/ml glycerol 85%.

9. The aqueous pharmaceutical formulation of claim 7 comprising 90 μ

g/mL zinc, 2.7 mg/mL m-cresol, 20 μ

g/mL polysorbate 20 and 20 mg/mL glycerol 85%.

10. The aqueous pharmaceutical formulation of claim 1, wherein the pH is between 3.4 and 4.6.

11. The aqueous pharmaceutical formulation of claim 10, wherein the pH is 4.

12. The aqueous pharmaceutical formulation of claim 10, wherein the pH is 4.5.

13. A method of treating Type I and Type II Diabetes Mellitus in a patient comprising administering to said patient an aqueous pharmaceutical formulation comprising 300 U/mL of insulin glargine [equimolar to 300 IU human insulin].

14. The method of claim 13 wherein said aqueous pharmaceutical formulation further comprises an analogue of exendin-4.

15. The method of claim 14 wherein the analogue of exendin-4 is selected from a group comprising lixisentatide, exenatide and liraglutide.

16. The method of claim 15 comprising 0.1 μ

g to 10 μ

g lixisenatide per U insulin glargine.

17. The method of claim 16 comprising 0.2 to 1 μ

g lixisenatide per U insulin glargine.

18. The method of claim 17 comprising 0.25 μ

g to 0.7 μ

g lixisenatide per U insulin glargine.

19. The method of claim 13 further comprising at least one excipient selected from the group comprising zinc, m-cresol, glycerol, polysorbate 20 and sodium.

20. The method of claim 19 comprising 90 μ

g/mL zinc, 2.7 mg/mL m-cresol and 20 mg/mL glycerol 85%.

21. The method of claim 19 comprising 90 μ

g/mL zinc, 2.7 mg/mL m-cresol, 20 μ

g/mL polysorbate 20 and 20 mg/mL glycerol 85%.

22. The method of claim 13 wherein the pH is between 3.4 and 4.6.

23. The method of claim 22 wherein the pH is 4.

24. The method of claim 22 wherein the pH is 4.5.

25. An aqueous pharmaceutical formulation comprising 300 U/mL of insulin glargine [equimolar to 300 IU human insulin], 90 μ

g zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, HCL and NaOH ad and having a pH of 4.0.