Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives

• US 9,839,675 B2
• Filed: 02/04/2014
• Issued: 12/12/2017
• Est. Priority Date: 02/04/2013
• 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:
  US14/172,151
• Publication Number:
  US 20140221285A1
• Time in Patent Office: 1,407 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 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• 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 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• 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
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

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) 0.04087 mg/mL zinc chloride;

(e) 6.8 mg/mL sodium chloride;

(f) 0.02 mg/mL polysorbate 20;

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

(h) water.

2. The pharmaceutical formulation according to claim 1, wherein the pharmaceutical formulation is an aqueous pharmaceutical formulation.

3. The pharmaceutical formulation as claimed in claim 1, wherein the pharmaceutical formulation is formulated for injection.

4. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation as claimed in claim 1;

and

(b) a medical device.

5. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation as claimed in claim 1;

and

(b) at least one further active pharmaceutical ingredient;

(c) and optionally a medical device.

6. The kit according to claim 5, wherein the further active pharmaceutical ingredient is an antidiabetic agent.

7. The kit as claimed in claim 5, wherein the further active pharmaceutical ingredient is an antidiabetic agent 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) an FGF-21 analogue;

(e) an FGF-21 derivative;

(f) insulin;

(g) human insulin;

(h) an analogue of insulin; and

(i) a derivative of insulin.

8. A method of treating diabetes mellitus in a subject in need thereof comprising administering to said subject a therapeutically effective amount of the pharmaceutical formulation of claim 1.

9. A method of treating hyperglycemia in a subject in need thereof comprising administering to said subject a therapeutically effective amount of the pharmaceutical formulation of claim 1.

10. A method of lowering glucose levels in a subject in need thereof comprising administering to said subject a therapeutically effective amount of the pharmaceutical formulation of claim 1.

11. A medical device comprising the pharmaceutical formulation as claimed in claim 1, for administering the pharmaceutical formulation to an animal and/or human.

12. A process for preparing the pharmaceutical formulation according to claim 1, wherein the components are mixed together in the form of a solution or suspension, the pH is adjusted to reach pH 7.4, and water is added to reach the final volume.