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

• US 7,678,763 B2
• Filed: 10/29/2007
• Issued: 03/16/2010
• Est. Priority Date: 12/27/2002
• Status: Expired due to Fees

• Current Assignee: Diobex, Inc.
• Original Assignee: Diobex, Inc.
• Inventors: Green, Daniel T., Henry, Robert R.
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US11/927,621
• Publication Number:
  US 20080160073A1
• Time in Patent Office: 869 Days
• Field of Search: None
• US Class Current: 514/6.5
• 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 provided are methods of administering glucagon so as to reduce the risk of inducing hypoglycemia.

Claims

1. A system for reducing the risk of hypoglycemia, said system comprising:

a syringe for administration of glucagon to a subject; and

a slow release dosage of glucagon that provides 2 to 16 ng of glucagon per kilogram of subject weight per minute to a subject, for a period of at least 1 hour, wherein said glucagon is administered subcutaneously.

2. The system of claim 1, wherein the syringe is a pen-like syringe.

3. The system of claim 1, wherein the system further comprises instructions, wherein the instructions direct the subject to administer the glucagon prior to bedtime.

4. The system of claim 1, wherein the slow release dosage of glucagon is present in an amount sufficient to provide 1 to 20 ng of glucagon per kilogram of subject weight per minute to a subject for at least 4 hours.

5. The system of claim 1, wherein the slow release dosage of glucagon is in a suspension comprising a pharmaceutically acceptable carrier, and wherein the glucagon is present in the suspension at a concentration of 600 to 800 micrograms per milliliter.

6. The system of claim 1, wherein the slow release dosage of glucagon provides glucagon at a rate of 6 to 20 ng per kg of subject weight per minute for a 50 to 100 kg subject.

7. The system of claim 1, wherein the slow release dosage of glucagon is a depot formulation.

8. The system of claim 1, wherein the slow release dosage of glucagon provides glucagon to the subject at a rate of 6 and 20 ng per kg of subject weight per minute for a 50 to 100 kg subject.

9. The system of claim 1, wherein the slow release dosage of glucagon comprises a polymer.

10. The system of claim 1, wherein the slow release dosage of glucagon provides a basal replacement dose of glucagon.

11. The system of claim 1, wherein the slow release dosage of glucagon comprises glycerine.

12. The system of claim 11, wherein the slow release dosage of glucagon is present in an amount sufficient to supply glucagon at a rate of 4 to 20 ng per kg of subject weight per minute overnight.

13. The system of claim 1, wherein the slow release dosage of glucagon is present in an amount sufficient to supply glucagon at a rate of 4 to 16 ng per kg of subject weight per minute for at least 1 hour.

14. The system of claim 1, wherein the slow release dosage of glucagon is present in an amount sufficient to supply glucagon at a rate of 4 to 16 ng per kg of subject weight per minute for 5 to 8 hours.

15. A depot glucagon formulation comprising glucagon, wherein the depot glucagon formulation provides glucagon to a subject at a rate between 2 to 16 ng per kg of subject weight per minute when administered subcutaneously to the subject, wherein the subject weighs 50 to 100 kg.

16. The depot glucagon formulation of claim 15, wherein the formulation is in a unit dose sufficient to supply glucagon at a rate of 4 to 16 ng per kg of subject weight per minute for 5 to 8 hours.

17. A pharmaceutical composition comprising:

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

glucagon in an amount effective for reducing the risk of hypoglycemia in a human or other mammal, wherein said insulin is present in said composition at a ratio of insulin to glucagon of about 1 unit of insulin to between more than 0.02 milliunits up to 200 milliunits of glucagon, and wherein the glucagon is part of a slow release dosage that provides 2 to 16 ng of glucagon per kilogram of subject weight per minute to the subject wherein said glucagon is administered subcutaneously.

18. The pharmaceutical composition of claim 17, wherein said pharmaceutical composition is configured to be administered subcutaneously, and wherein the ratio of insulin to glucagon is about 1 unit of insulin to between more than 40 milliunits to 200 milliunits of glucagon.

19. 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 reducing the risk of hypoglycemia, wherein said glucagon is administered subcutaneously, and wherein the amount of glucagon administered is 2 to 16 ng per kilogram of subject weight per minute to the subject.

20. A kit for the administration of glucagon and insulin in amounts to reduce the risk of 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 reduces the risk of a hypoglycemic event by providing 2 to 16 ng of glucagon per kilogram of subject weight per minute to the subject.