Stabilized Polypeptide Formulations

• US 20080267907A1
• Filed: 05/22/2006
• Published: 10/30/2008
• Est. Priority Date: 05/25/2005
• Status: Active Grant

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Poulsen, Christian
• Granted Patent: US 8,097,584 B2
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids

Abstract

The present invention relates to a pharmaceutical formulation comprising a polypeptide and ethylenediamine or salts thereof and an antimicrobial preservative agent.

Claims

1. A pharmaceutical formulation comprising a polypeptide, ethylenediamine or salts thereof and an antimicrobial preservative agent.

2. A pharmaceutical formulation according to claim 1, wherein the concentration of ethylenediamine is in the range from 1-100 mM.

3. A pharmaceutical formulation according to claim 2, wherein the concentration of ethylenediamine is in the range from 1-50 mM.

4. A pharmaceutical formulation according to claim 3, wherein the concentration of ethylenediamine is in the range from 3-25 mM.

5. A pharmaceutical formulation according to claim 4, wherein the concentration of ethylenediamine is in the range from 5-16 mM.

6. A pharmaceutical formulation according to claim 1, wherein the polypeptide is selected from the group consisting of insulin, human growth hormone, glucagon, GLP-1, exendin-4, FVII, FXIII, a mixture of FVII and FXIII, IL-20, IL-21, IL-28a, IL-29, IL-31 and/or analogues and/or derivates thereof.

7. A pharmaceutical formulation according to claim 6, wherein the polypeptide is insulin or an analogue or derivatives thereof.

8. A pharmaceutical formulation according to claim 1, wherein the antimicrobial preservative agent is selected from the group consisting of phenol, o-cresol, m-cresol, p-cresol, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, 2-phenoxyethanol, butyl p-hydroxybenzoate, 2-phenylethanol, benzyl alcohol, chlorobutanol, thimerosal, bronopol, benzoic acid, imidurea, chlorohexidine, sodium dehydroacetate, chlorocresol, ethyl p-hydroxybenzoate, benzethonium chloride, chlorphenesine (3p-chlorphenoxypropane-1,2-diol) or mixtures thereof.

9. A pharmaceutical formulation according to claim 8, wherein the antimicrobial preservative agent is selected from the group consisting of phenol, m-cresol or mixtures thereof.

10. A pharmaceutical formulation according to claim 9, wherein the antimicrobial preservative agent is present in a concentration from 0.1 mg/ml to 20 mg/ml.