Potentiation of glucose elimination

• US 9,006,175 B2
• Filed: 01/10/2006
• Issued: 04/14/2015
• Est. Priority Date: 06/29/1999
• Status: Expired due to Fees

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Boss, Anders Hasager, Steiner, Solomon S., Woods, Rodney J., Sulner, Joseph W.
• Primary Examiner(s): Vivlemore, Tracy
• Assistant Examiner(s): SHIN, MONICA A
• Application Number:
  US11/329,686
• Publication Number:
  US 20070020191A1
• Time in Patent Office: 3,381 Days
• Field of Search: None
• US Class Current: 514/5.9
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/545 Heterocyclic compounds A61K47/558 takes precedence
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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 5/50 for increasing or potentiating the activity of insulin

Abstract

Methods related to the treatment of diabetes and improving the efficiency of insulin utilization are provided. The method enables effective control of prandial glucose levels while reducing the risk of postprandial hypoglycemia. In particular, methods of potentiating the activity of endogenous insulin in type 2 diabetics and exogenous long-acting insulin in diabetics requiring basal insulin replacement are provided.

Claims

1. A method of potentiating the glucose elimination rate in a human patient with diabetes comprising:

producing a spike in serum insulin concentration with an exogenously-administered inhaled insulin composition, wherein said spike comprises the maximum serum insulin concentration which is obtained by about 20 minutes after administration of said inhaled insulin composition, and wherein said exogenously-administered inhaled insulin composition is administered from approximately 10 minutes prior to a meal to approximately 30 minutes after a meal, wherein said glucose elimination rate returns to baseline by about 6 hours after administration.

2. The method of claim 1 wherein said diabetes is type 2 diabetes.

3. The method of claim 1 wherein said maximum serum insulin concentration is about 75 mU/L or greater than 75 mU/L.

4. The method of claim 3 wherein said maximum serum insulin concentration is about 100 mU/L or greater than 100 mU/L.

5. The method of claim 4 wherein said maximum serum insulin concentration is about 125 mU/L or greater than 125 mU/L.

6. The method of claim 1 wherein said maximum serum insulin concentration is achieved within about 15 minutes.

7. The method of claim 6 wherein said maximum serum insulin concentration is achieved within about 10 minutes.

8. The method of claim 1 wherein said potentiation comprises the glucose elimination rate reaching its maximum within about 30 to 90 minutes after administration of said inhaled insulin composition.

9. The method of claim 8 wherein said potentiation comprises the glucose elimination rate reaching its maximum within about 1 hour.

10. The method of claim 9 wherein said potentiation comprises the glucose elimination rate reaching its maximum within about 45 minutes.

11. The method of claim 1 wherein said serum insulin concentration descends through half-maximal by about 80 minutes after said maximum serum insulin concentration is achieved.

12. The method of claim 11, wherein said serum insulin concentration descends through half-maximal by about 50 minutes after said maximum serum insulin concentration is achieved.

13. The method of claim 1 wherein said glucose elimination rate continues to rise after serum insulin concentration begins to fall.

14. The method of claim 1 wherein said glucose elimination rate begins to fall by about 1 hour after insulin administration.

15. The method of claim 1 wherein said exogenously-administered inhaled insulin composition comprises a complex between a diketopiperazine and human insulin.

16. The method of claim 15 wherein said diketopiperazine is fumaryl diketopiperazine.

17. A method of treating an insulin-related disorder comprising:

administering to a human patient having diabetes an exogenously-administered inhaled insulin composition such that said exogenously-administered inhaled insulin composition produces a spike in serum insulin concentration wherein said spike comprises the maximum serum insulin concentration which is achieved by about 20 minutes after administration of said inhaled insulin composition, and wherein said exogenously-administered inhaled insulin composition is administered from approximately 10 minutes prior to a meal to approximately 30 minutes after a meal, and wherein the glucose elimination rate of the human patient returns to baseline by about 6 hours after administration.

18. The method of claim 17 wherein said exogenously-administered inhaled insulin composition comprises a complex between a diketopiperazine and human insulin.

19. The method of claim 18 wherein said diketopiperazine is fumaryl diketopiperazine.

20. The method of claim 17 wherein said diabetes is type 2 diabetes.

21. The method of claim 17 further comprising administering a long-acting basal insulin.

22. The method of claim 17 wherein said serum insulin concentration descends through half-maximal by about 80 minutes after said maximum serum insulin concentration is achieved.

23. The method of claim 22 wherein said serum insulin concentration descends through half-maximal by about 50 minutes after said maximum serum insulin concentration is achieved.

24. A method of maintaining blood glucose levels in a human patient with diabetes in a normal range comprising:

providing an exogenously-administered inhaled insulin composition, such that said exogenously administered inhaled insulin composition produces a spike in serum insulin concentration comprising maximum serum insulin concentration achieved within about 30 minutes of administration of said inhaled insulin composition, and wherein said exogenously-administered inhaled insulin composition is administered from approximately 10 minutes prior to a meal to approximately 30 minutes after a meal, and wherein the glucose elimination rate of the human patient returns to baseline by about 6 hours after administration.

25. The method of claim 24 wherein said maximum serum insulin concentration is obtained within about 15 minutes of administration.

26. The method of claim 25 wherein said exogenously-administered inhaled insulin composition comprises a complex between a diketopiperazine and human insulin.

27. The method of claim 26 wherein said diketopiperazine is fumaryl diketopiperazine.

28. The method of claim 24 wherein said exogenously-administered inhaled insulin composition is a non-naturally occurring form of insulin.

29. The method of claim 24 wherein said serum insulin concentration descends through half-maximal by about 80 minutes after said maximum serum insulin concentration is achieved.

30. The method of claim 29 wherein said serum insulin concentration descends through half-maximal by about 50 minutes after said maximum serum insulin concentration is achieved.