Potentiation of glucose elimination

• US 9,801,925 B2
• Filed: 03/05/2015
• Issued: 10/31/2017
• 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:
  US14/639,860
• Publication Number:
  US 20150174210A1
• Time in Patent Office: 971 Days
• Field of Search: None
• 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 restoring normal insulin kinetics in a patient in need thereof comprising administering to a patient having an insulin-related disorder an inhaled insulin composition comprising a diketopiperazine such that said inhaled insulin composition produces in the patient a rapid increase in serum insulin concentration of between about 75 mU/L and about 375 mU/L within 20 minutes of administration, wherein said patient'"'"'s glucose elimination rate returns to baseline by about 6 hours after administration.

2. The method of claim 1, wherein said rapid increase in serum insulin concentration is between about 100 mU/L and about 375 mU/L.

3. The method of claim 2, wherein said rapid increase in serum insulin concentration is between about 125 mU/L and about 375 mU/L.

4. The method of claim 1, wherein said rapid increase in serum insulin concentration is achieved within about 15 minutes after administration.

5. The method of claim 1, wherein said rapid increase in serum insulin concentration descends through half maximal within about 80 minutes after administration.

6. The method of claim 1, wherein said rapid increase in serum insulin concentration descends through half maximal within about 50 minutes after administration.

7. The method of claim 1, wherein said rapid increase in serum insulin concentration descends through half maximal within about 35 minutes after administration.

8. The method of claim 1, wherein said patient'"'"'s glucose elimination rate reaches its maximum between about 30 and about 90 minutes after administration.

9. The method of claim 8, wherein said patient'"'"'s glucose elimination rate reaches its maximum between about 45 and about 60 minutes after administration.

10. The method of claim 1, wherein said diketopiperazine is fumaryl diketopiperazine.

11. The method of claim 1, wherein said inhaled insulin composition is administered from approximately 10 minutes prior to a meal to approximately 30 minutes after a meal.

12. The method of claim 11 wherein about 74% of the glucose lowering activity of said inhaled insulin composition has been expended within about 180 minutes after administration.

13. The method of claim 12 wherein said patient'"'"'s glucose elimination rate returns to baseline within about 270 minutes after administration.

14. A method of restoring normal insulin kinetics in a patient in need thereof wherein said comprising

administering to a patient having an insulin-related disorder from approximately 10 minutes prior to a meal to approximately 30 minutes after a meal an inhaled insulin composition comprising fumaryl diketopiperazine;

wherein said composition produces in the patient a a rapid increase in serum insulin levels of at least between about 75 mU/L and about 375 mU/L achieved within about 20 minutes after administration; and

wherein about 74% of the glucose lowering activity of said inhaled insulin composition has been expended within about 180 minutes after administration, and said patient'"'"'s glucose elimination rate returns to baseline within about 270 minutes after administration.