Method of increasing the bioavailability of recombinant human insulin isophane in a patient

• US 8,257,735 B2
• Filed: 11/23/2010
• Issued: 09/04/2012
• Est. Priority Date: 05/19/1998
• Status: Expired due to Fees

• Current Assignee: SDG, Inc.
• Original Assignee: SDG, Inc.
• Inventors: Lau, John R., Geho, W. Blair
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US12/953,013
• Publication Number:
  US 20110135727A1
• Time in Patent Office: 651 Days
• Field of Search: None
• US Class Current: 424/450
• CPC Class Codes: A61K 49/1812 liposomes, polymersomes, e.g. immunoliposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• 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

The instant invention is drawn to a hepatocyte targeted composition comprising a mixture of free recombinant human insulin isophane and free Recombinant human regular insulin insulin and a mixture of recombinant human insulin isophane and Recombinant human regular insulin insulin associated with a water insoluble target molecule complex, wherein the complex comprises multiple linked individual units and a supra-molecular lipid construct matrix. Recombinant human insulin isophane and Recombinant human regular insulin insulin are present within the complex in at least one form wherein the recombinant human insulin isophane and Recombinant human regular insulin insulin have regions of positive charge which interacts with a negative charge on the complex. The invention also includes methods for the manufacture of the composition and methods of managing blood glucose levels in individuals with Type I and Type II diabetes.

Claims

1. A method of increasing the bioavailability of recombinant human insulin isophane in a patient, said method comprising:

administering recombinant human insulin isophane in a hepatocyte-targeting composition, said composition comprising free recombinant human insulin isophane and recombinant human insulin isophane associated with a water insoluble target molecule complex,

wherein said target molecule complex comprises multiple linked individual units and a supra-molecular lipid construct matrix containing a negative charge, each of said individual units comprising;

(a) a bridging component selected from the group consisting of a transition element, an inner transition element, a neighbor element of said transition element and a mixture of any of the foregoing elements, (b) a complexing component, provided that when said transition element is chromium, a chromium target molecule complex is created,

wherein said multiple linked individual units are combined with said supra-molecular lipid construct matrix, wherein said insulins are associated with said target molecule complex that contains a negative charge;

thereby the association between recombinant human insulin isophane and said water insoluble target molecule complex is altered within said patient to form new structures associated with said recombinant human insulin isophane, wherein said new structures are present in soluble and insoluble forms and are delivered to sites of insulin activity in a hepatocyte in the liver of the patient.

2. The method of claim 1, wherein delivery of recombinant human insulin isophane to sites of insulin activity in a hepatocyte in the liver of the patient occurs over a plurality of meals.

3. The method of claim 1, wherein delivery of recombinant human insulin isophane to sites of insulin activity in a hepatocyte in the liver of the patient comprises a hepatic component delivered at mealtime.