Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives

• US 10,610,595 B2
• Filed: 10/13/2017
• Issued: 04/07/2020
• 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:
  US15/783,712
• Publication Number:
  US 20180125981A1
• Time in Patent Office: 907 Days
• Field of Search: None
• 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 47/26 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 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

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

Claims

1. A pharmaceutical formulation consisting of:

(a) 3.5 mg/mL insulin aspart;

(b) 31.62 mg/mL sorbitol;

(c) 1.72 mg/mL metacresol;

(d) 1.50 mg/mL phenol;

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

(f) 0.58 mg/mL sodium chloride;

(g) 1.88 mg/mL Na₂HPO₄×

7 H₂O;

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

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

(j) and water.

2. A process 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 reach pH 7.4 and adding water to reach a final volume.

3. A kit comprising one or more separate packages of

(a) the pharmaceutical formulation according to claim 1;

and

(b) a medical device.

4. 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.

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

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

(a) a GLP-1 receptor agonist;

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

(c) a 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.

7. The kit according to claim 3, wherein the kit comprises more than one analogue and/or derivative of insulin, wherein one analogue and/or derivative of insulin is a fast acting insulin and one analogue and/or derivative of insulin is a long acting insulin.

8. The kit according to claim 7, wherein the fast acting insulin is selected from the group consisting of insulin aspart, insulin lispro and insulin glulisine and wherein the long acting insulin is selected from the group consisting of insulin glargin, insulin detemir and/or insulin degludec.

9. A method of treating diabetes mellitus in a subject in need thereof comprising using the kit of claim 3 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

10. A method of treating hyperglycemia in a subject in need thereof comprising using the kit of claim 3 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

11. A method of lowering blood glucose level in a subject in need thereof comprising using the kit of claim 3 to administer to the subject the pharmaceutical formulation of the kit employing the medical device of the kit.

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

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

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

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