Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives

• US 9,895,424 B2
• Filed: 01/08/2015
• Issued: 02/20/2018
• Est. Priority Date: 01/09/2014
• Status: Active Grant

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Bley, Oliver, Loos, Petra, Bidlingmaier, Bernd, Kamm, Walter, Berchtold, Harald
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US14/592,750
• Publication Number:
  US 20150216941A1
• Time in Patent Office: 1,139 Days
• Field of Search: None
• 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 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Stabilized pharmaceutical formulations of insulin analogs and/or insulin derivatives are disclosed.

Claims

1. A pharmaceutical formulation consisting of:

(a) 3.5 mg/mL insulin aspart;

(b) 1.72 mg/mL metacresol;

(c) 1.50 mg/mL phenol;

(d) 0.0196 mg/mL Zn(II);

(e) 6.2 mg/mL sodium chloride;

(f) 1.88 mg/mL Na₂HPO₄×

7H₂O;

(g) from 0.1 mg/mL to 0.5 mg/mL protamine;

(h) sodium hydroxide and/or hydrochloric acid to adjust the pH to a pH in the range from 7.1 to 7.6; and

(i) water.

2. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation according to claim 1;

and

(b) a medical device.

3. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation according to claim 1;

(b) at least one further active pharmaceutical ingredient; and

(c) optionally a medical device.

4. The kit according to claim 3, wherein the further active pharmaceutical ingredient is an antidiabetic agent.

5. The kit according to claim 4, wherein the antidiabetic agent is selected from the group consisting of:

(a) a GLP-1 receptor agonist;

(b) a dual GLP-1 receptor/glucagon receptor agonist;

(c) human FGF-21;

(d) a FGF-21 analogue;

(e) a FGF-21 derivative;

(f) insulin;

(g) human insulin;

(h) an analogue of insulin; and

(i) a derivative of insulin.

6. A method of treating diabetes mellitus in a subject in need thereof comprising using the kit of claim 2 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

7. A method of treating hyperglycemia in a subject in need thereof comprising using the kit of claim 2 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

8. A method of lowering blood glucose level in a subject in need thereof comprising using the kit of claim 2 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

9. A method of treating diabetes mellitus in a subject in need thereof comprising administering the pharmaceutical formulation of claim 1 to the subject.

10. A method of treating hyperglycemia in a subject in need thereof comprising administering the pharmaceutical formulation of claim 1 to the subject.

11. A method of lowering blood glucose levels in a subject in need thereof comprising administering the pharmaceutical formulation of claim 1 to the subject.

12. A medical device comprising the pharmaceutical formulation of claim 1 for administering the pharmaceutical formulation to an animal and/or human.

13. A method for preparing the pharmaceutical formulation according to claim 1, comprising the steps of:

mixing together the components in the form of a solution or suspension, adjusting the pH to a pH in the range from 7.1 to 7.6, and adding water to reach a final volume.

14. A pharmaceutical formulation consisting of:

(a) 3.5 mg/mL insulin aspart;

(b) 1.72 mg/mL metacresol;

(c) 1.50 mg/mL phenol;

(d) 0.0196 mg/mL Zn(II);

(e) 6.2 mg/mL sodium chloride;

(f) 1.88 mg/mL Na₂HPO₄×

7H₂O;

(g) sodium hydroxide and/or hydrochloric acid to adjust the pH to 7.4; and

(h) water.

15. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation according to claim 14;

and

(b) a medical device.

16. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation according to claim 14;

(b) at least one further active pharmaceutical ingredient; and

(c) optionally a medical device.

17. The kit according to claim 16, wherein the further active pharmaceutical ingredient is an antidiabetic agent.

18. The kit according to claim 17, wherein the antidiabetic agent is selected from the group consisting of:

(a) a GLP-1 receptor agonist;

(b) a dual GLP-1 receptor/glucagon receptor agonist;

(c) human FGF-21;

(d) a FGF-21 analogue;

(e) a FGF-21 derivative;

(f) insulin;

(g) human insulin;

(h) an analogue of insulin; and

(i) a derivative of insulin.

19. A method of treating diabetes mellitus in a subject in need thereof comprising using the kit of claim 15 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

20. A method of treating hyperglycemia in a subject in need thereof comprising using the kit of claim 15 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

21. A method of lowering blood glucose level in a subject in need thereof comprising using the kit of claim 15 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

22. A method of treating diabetes mellitus in a subject in need thereof comprising administering the pharmaceutical formulation of claim 14 to the subject.

23. A method of treating hyperglycemia in a subject in need thereof comprising administering the pharmaceutical formulation of claim 14 to the subject.

24. A method of lowering blood glucose levels in a subject in need thereof comprising administering the pharmaceutical formulation of claim 14 to the subject.

25. A medical device comprising the pharmaceutical formulation of claim 14 for administering the pharmaceutical formulation to an animal and/or human.

26. A method for preparing the pharmaceutical formulation according to claim 14, comprising the steps of:

mixing together the components in the form of a solution or suspension, adjusting the pH to 7.4, and adding water to reach a final volume.