Compositions and methods for the prevention and control of insulin-induced hypoglycemia

• US 7,655,618 B2
• Filed: 06/28/2005
• Issued: 02/02/2010
• Est. Priority Date: 12/27/2002
• Status: Expired due to Fees

• Current Assignee: HOWL Technologies Incorporated
• Original Assignee: Diobex, Inc.
• Inventors: Green, Daniel T., Henry, Robert R.
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US11/169,825
• Publication Number:
  US 20060014670A1
• Time in Patent Office: 1,680 Days
• Field of Search: 514/12
• US Class Current: 514/1.1
• 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 glucagon can be administered to control and treat diabetes while reducing or eliminating the risk of insulin-induced hypoglycemia. Also provide are methods of administering glucagon so as to reduce the risk of inducing hypoglycemia.

Claims

1. A method of treating diabetes in a human while reducing the risk of inducing hypoglycemia, said method comprising:

administering insulin in an amount therapeutically effective for the control of diabetes, wherein said insulin is administered in an amount of 1-20 Units of insulin per hour; and

subcutaneously administering glucagon in an amount therapeutically effective for reducing the risk of hypoglycemia while administering the glucagon in a fashion to avoid the induction of hyperglycemia, wherein the glucagon is administered while the human has a blood glucose level of at least 70 mg/dl, wherein the glucagon is subcutaneously administered in a dosage that provides 2 to 16 ng of glucagon per kilogram of patient weight each minute for said hour, thereby treating diabetes while reducing the risk of inducing hypoglycemia.

2. The method of claim 1, wherein the amount of glucagon administered is between 6 and 18 ng/kg/min.

3. The method of claim 1, wherein said glucagon is a glucagon with a prolonged duration of action.

4. The method of claim 1, wherein said glucagon is contained in a liposomal formulation.

5. The method of claim 1, wherein said glucagon is contained in a microsphere.

6. The method of claim 1, comprising administering a formulation comprising both insulin and glucagon.

7. The method of claim 1, wherein said insulin and glucagon are contained in a pump that controls administration of a drug to a patient.

8. The method of claim 7, wherein said glucagon is administered simultaneously with insulin.

9. The method of claim 8, wherein said insulin and glucagon are administered simultaneously at a ratio of glucagon to insulin of about more than 40 milliunits of glucagon to 1 unit of insulin.

10. The method of claim 9, wherein 2 units of insulin are administered.

15. The method of claim 1, wherein the glucagon is administered daily.

16. The method of claim 15, wherein the glucagon is administered at bedtime and wherein the human is not suffering from hypoglycemic symptoms.

19. The method of claim 1, wherein said subcutaneous administration provides plasma glucagon levels that are sustained for at least 6 hours in the range of 100 to 200 pg/ml.

11. A kit for the administration of glucagon and insulin in amounts to reduce the risk of hypoglycemia during the treatment of diabetes, said kit comprising:

glucagon;

insulin;

wherein said glucagon and insulin are present in said kit at a ratio of 1-20 Units of insulin to 32 up to 480 milliunits of glucagon;

a means for administering glucagon subcutaneously; and

instructions for the administration of insulin and glucagon so that the glucagon reduces the risk of a hypoglycemic event, wherein said instructions recite that between 1 and 20 Units of insulin is administered per hour and that glucagon is subcutaneously administered in a dosage that provides 2 to 16 ng of glucagon per kilogram of patient weight each minute for said hour, and wherein the glucagon is administered while the human has a blood glucose level of at least 70 mg/dl.

12. The kit of claim 11, said kit further comprising glycerine solution for dissolution of the glucagon, 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.

13. The kit of claim 11, wherein said glucagon and insulin are present in said kit at a ratio of 1-3 Units of insulin to 32 up to 96 milliunits of glucagon.

14. The kit of claim 11, wherein the means for administering the glucagon subcutaneously is a pump and said pump is configured to deliver between about 6 to 20 ng of glucagon per kg of patient weight per minute.

17. A method of treating diabetes in a human while reducing the risk of inducing hypoglycemia, said method comprising:

administering insulin in an amount therapeutically effective for the control of diabetes, wherein 1-20 Units of insulin are released to the subject per hour; and

subcutaneously administering glucagon in an amount therapeutically effective for reducing the risk of hypoglycemia while administering the glucagon in a fashion to avoid the induction of hyperglycemia, wherein the glucagon is administered while the human has a blood glucose level of at least 70 mg/dl, wherein the glucagon is subcutaneously administered in a dosage that provides 2 to 16 ng of glucagon per kilogram of patient weight per minute, thereby treating diabetes while reducing the risk of inducing hypoglycemia, and wherein the delivery of glucagon occurs daily for more than one week.

18. The method of claim 17, wherein the delivery of glucagon is on a chronic basis.

20. A method of treating diabetes in a subject while reducing the risk of insulin-induced hypoglycemia in the subject, which method comprises:

administering insulin in an amount therapeutically effective for the control of diabetes, wherein 1-20 Units of insulin are released to the subject per hour;

administering glucagon subcutaneously;

wherein administration of glucagon occurs daily;

wherein when said glucagon is administered the subject has a blood glucose level of at least 70 mg/dL and is not suffering hypoglycemic symptoms;

wherein said glucagon is administered subcutaneously in a dosage that provides 2 to 16 ng of glucagon per kilogram of subject per minute; and

wherein said subcutaneous administration provides plasma glucagon levels that are sustained for 6 to 8 hours in the range of 100 to 200 pg/ml.

21. The method of claim 20, wherein the administration of insulin comprises administering a single dose of a long acting form of insulin.