Insulin formulation

• US 5,534,488 A
• Filed: 08/13/1993
• Issued: 07/09/1996
• Est. Priority Date: 08/13/1993
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Hoffmann, James A.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Lukton, David
• Application Number:
  US08/106,106
• Time in Patent Office: 1,061 Days
• Field of Search: 514/3, 514/4, 530/304
• US Class Current: 514/6.4
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• 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

Abstract

The present invention is directed to an insulin formulation comprising a suspension of Ultralente crystals and a total formulation zinc concentration of between about 0.5 milligrams to about 20 milligrams per 100 units of insulin. Greater than fifty percent of the total zinc in the formulation resides in the soluble fraction, rather than in complex with the insulin. This insulin formulation generally has a pH from between about 6.0 to about 7.4. In addition, the insulin formulation of the present invention does not contain other proteins like protamine. This zinc-modified formulation displays characteristics of a very long lasting human insulin product.

Claims

1. A formulation of human insulin comprising a suspension of human Ultralente insulin crystals in a total formulation zinc concentration of between about 0.5 milligrams to about 20 milligrams per 100 units of insulin wherein the formulation does not contain proteins other than insulin.

2. The insulin formulation of claim 1 wherein the pH is between about 6.0 and 7.4.

3. The insulin formulation of claim 2 wherein the formulation further comprises preservatives.

4. The insulin formulation of claim 3 wherein the formulation further comprises isotonicity agents.

5. The insulin formulation of claim 4 wherein the formulation further comprises a buffer.

6. The insulin formulation of claim 5 wherein the formulation comprises a total formulation zinc concentration of between about 0.5 milligrams to about 7 milligrams per 100 units of insulin.

7. The insulin formulation of claim 6 wherein the formulation pH is between about 6.2 to about 7.2.

8. The insulin formulation of claim 7 wherein the preservative is methyl paraben.

9. The insulin formulation of claim 8 wherein the isotonicity agent is sodium chloride.

10. The insulin formulation of claim 5 wherein the buffer is acetate.

11. A method for making the insulin formulation of claim 1, said method comprising combining zinc with Ultralente insulin crystals.

12. The method of claim 11 wherein the Ultralente insulin is in the form of an aqueous suspension.

13. The method of claim 11 wherein the zinc used is a zinc salt selected form the group consisting of zinc acetate, zinc bromide, zinc chloride, zinc iodide, zinc fluoride and zinc sulfate.

14. The method of claim 11 wherein the zinc used is a solid form selected from the group consisting of zinc chloride and zinc acetate.

15. The method of claim 11 wherein the zinc used is a solution selected from the group consisting of zinc chloride and zinc acetate.

16. The method of claim 11 wherein pH adjustments are made to the formulation after the zinc and Ultralente insulin are combined.

17. The insulin formulation produced by the method of claim 11.

18. A method of treating diabetes mellitus in human patients, said method comprising administering to said human patient a therapeutically acceptable amount of the insulin formulation of claim 1 via subcutaneous injection.

19. The method of claim 18 wherein said subcutaneous injection is administered one time per day.