Preparation Comprising Insulin, Nicotinamide and an Amino Acid

• US 20130281364A1
• Filed: 11/07/2012
• Published: 10/24/2013
• Est. Priority Date: 06/26/2009
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Havelund, Svend, Ribel-Madsen, Ulla, Sturis, Jeppe, Naver, Helle, Schlein, Morten, Ludvigsen, Svend, Olsen, Helle Birk
• Application Number:
  US13/671,034
• Publication Number:
  US 20130281364A1
• Time in Patent Office: Days
• US Class Current: 514/6.3
• 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 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• 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 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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: 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 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.

Claims

1. An insulin preparation comprising:

an insulin compound;

a nicotinic compound;

arginine; and

a buffer.

2. The insulin preparation of claim 1, wherein the buffer is a phosphate buffer.

3. The insulin preparation of claim 2, wherein the insulin compound comprises B28Asp human insulin.

4. The insulin preparation of claim 1, wherein the insulin compound is selected from the group consisting of B28Asp human insulin, B28LysB29Pro human insulin, and B3LysB29Glu human insulin.

5. The insulin preparation of claim 4, wherein the buffer is a phosphate buffer.

6. An insulin preparation comprising:

B28Asp human insulin;

nicotinamide;

zinc;

arginine; and

a phosphate buffer.

7. The insulin preparation of claim 6, wherein the nicotinamide is present at a concentration ranging from about 1 mM to about 300 mM.

8. The insulin preparation of claim 7, wherein less than about 4 zinc ions are present per six B28Asp human insulin molecules.

9. The insulin preparation of claim 8, wherein the arginine is present in a concentration from about 10 mM to about 60 mM.

10. The insulin preparation of claim 9, wherein the arginine is present in a concentration ranging from about 10 mM to about 40 mM.

11. The insulin preparation of claim 10, wherein the preparation has a pH of about 7.4 or less.

12. The insulin preparation of claim 11, wherein the preparation has a pH of about 7.1.

13. The insulin preparation of claim 6 wherein the nicotinamide is present at a concentration ranging from about 80 mM to about 260 mM.

14. The insulin preparation of claim 13, wherein the arginine is present in a concentration ranging from about 10 mM to about 40 mM.

15. The insulin preparation of claim 14, wherein the preparation has a pH of about 7.4 or less.

16. The insulin preparation of claim 15, wherein less than about 4 zinc ions are present per six B28Asp human insulin molecules.

17. The insulin preparation of claim 14, wherein the preparation has a pH of about 7.1.

18. The insulin preparation of claim 17, wherein less than about 4 zinc ions are present per six B28Asp human insulin molecules.

19. An aqueous insulin preparation consisting essentially of:

an insulin analog;

a nicotinic compound;

arginine;

a buffer;

zinc;

a preservative; and

an isotonicity agent.

20. The aqueous insulin preparation of claim 19, wherein the buffer is a phosphate buffer.

21. The aqueous insulin preparation of claim 20, wherein the insulin analog is selected from the group consisting of B28Asp human insulin, B28LysB29Pro human insulin, and B3LysB29Glu human insulin.

22. The aqueous insulin preparation of claim 20, wherein the insulin analog is B28Asp human insulin.

23. The insulin preparation of claim 22, wherein the nicotinic compound is nicotinamide.

24. The insulin preparation of claim 23 wherein the nicotinamide is present at a concentration ranging from about 80 mM to about 260 mM.

25. The insulin preparation of claim 24, wherein the arginine is present in a concentration ranging from about 10 mM to about 40 mM.

26. The insulin preparation of claim 25, wherein the preservative is selected from the group consisting of phenol, cresol, and combinations thereof, and wherein the preparation has a pH of about 7.4 or less.

27. The insulin preparation of claim 26, wherein less than about 4 zinc ions are present per six insulin analog molecules.

28. The insulin preparation of claim 26, wherein the preparation has a pH of about 7.1.