COMPOSITIONS AND METHODS FOR THE PREVENTION AND CONTROL OF INSULIN-INDUCED HYPOGLYCEMIA

• US 20080160073A1
• Filed: 10/29/2007
• Published: 07/03/2008
• Est. Priority Date: 12/27/2002
• Status: Active Grant

• Current Assignee: Diobex, Inc.
• Original Assignee: Diobex, Inc.
• Inventors: Green, Daniel T., Henry, Robert R.
• Granted Patent: US 7,678,763 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• 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 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• 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

Pharmaceutical compositions comprising both insulin and glucagon can be administered to control and treat diabetes while reducing or eliminating the risk of insulin-induced hypoglycemia.

Claims

1. A pharmaceutical formulation comprising:

insulin in an amount effective for the control of diabetes; and

glucagon in an amount effective for the prevention of hypoglycemia in a human or other mammal, wherein said pharmaceutical formulation is configured to be administered subcutaneously, and wherein a ratio of insulin to glucagon is about 1 unit of insulin to between more than 40 milliunits to 200 milliunits of glucagon.

2. The pharmaceutical composition of claim 1, wherein the amount of glucagon is between about 50 and 100 milliunits.

3. The pharmaceutical composition of claim 1, wherein the glucagon is a longer-acting form of glucagon.

4. The pharmaceutical composition of claim 3, wherein the longer-acting form of glucagon contains iodine.

5. The pharmaceutical composition of claim 3, wherein the longer-acting form of glucagon contains zinc.

6. The pharmaceutical composition of claim 5, wherein the longer-acting form of glucagon further comprises protamine.

7. A method of treating diabetes in a human or other mammal without inducing hypoglycemia, said method comprising:

administering insulin in an amount therapeutically effective for the control of diabetes, wherein said insulin is in an amount between 0.5 and 20 Units of insulin; and

administering glucagon in time and an amount therapeutically effective for the prevention of hypoglycemia, wherein said glucagon is administered subcutaneously, and wherein the amount of glucagon administered is between more than 5 and less than or equal to 100 ng per kg of patient per minute of desired glucagon effectiveness.

8. The method of claim 7, wherein the amount of glucagon administered is between 6 and less than 18 ng per kg of patient per minute of desired glucagon effectiveness.

9. The method of claim 7, wherein said glucagon is a glucagon with a prolonged duration of action.

10. The method of claim 7, wherein said glucagon is contained in a liposomal formulation.

11. The method of claim 7, wherein said glucagon is contained in a microsphere.

12. The method of claim 7, comprising administering a formulation comprising both insulin and glucagon.

13. The method of claim 7, wherein said insulin and glucagon are contained in a pump that controls administration of a drug to a patient.

14. The method of claim 13, wherein said glucagon is administered simultaneously with insulin.

15. The method of claim 14, wherein a ratio of glucagon to insulin is about more than 40 to 200 milliunits of glucagon to 1 unit of insulin.

16. The method of claim 15, wherein 2 units of insulin are administered.

17. The method of claim 7, wherein 10 units of insulin are administered and between 30 and 90 ng per kg of patient per minute of glucagon are administered subcutaneously.

18. A kit for the administration of glucagon and insulin in amounts to prevent hypoglycemia, said kit comprising:

glucagon;

insulin, wherein said glucagon and insulin are in a ratio of 1-20 units of insulin to 32-480 milliunits of glucagon;

a means for administering glucagon subcutaneously; and

instructions for the administration of insulin and glucagon so that the glucagon prevents a hypoglycemic event.

19. The kit of claim 18, wherein the concentration of glucagon when completely dissolved in the glycerine solution is more than 500 micrograms per milliliter but less than 2000 micrograms per milliliter.

20. The kit of claim 18, wherein said glucagon and insulin are in a ratio of 1-3 units of insulin to 32-96 milliunits of glucagon.

21. The kit of claim 18, wherein the means for administering the glucagon subcutaneously is a pump and said pump is configured to deliver between about 6 to 20 ng/kg/minute of glucagon.