Crystalline compositions for controlling blood glucose

• US 20050054818A1
• Filed: 06/30/2004
• Published: 03/10/2005
• Est. Priority Date: 07/02/2003
• Status: Abandoned Application

• Current Assignee: Mark Laurence Brader, Mupalla Sukumar
• Original Assignee: Mark Laurence Brader, Mupalla Sukumar
• Inventors: Brader, Mark Laurence, Sukumar, Mupalla
• Application Number:
  US10/880,884
• Publication Number:
  US 20050054818A1
• Time in Patent Office: Days
• US Class Current: 530/303
• CPC Class Codes: A61K 38/28 Insulins

Abstract

The present invention relates to a process for forming non-adsorbed insulin crystals from zinc, protamine, a hexamer-stabilizing compound, and a polypeptide selected from the group consisting of insulin, an insulin analog, a derivatized insulin, and a derivatized insulin analog. The crystals are suitable for administering to a patient for control of blood glucose levels. The crystals are formed in a process utilizing precisely determined protamine concentrations.

Claims

1. A method of preparing non-adsorbed insulin crystals comprising admixing ingredients comprising

a) a polypeptide selected from the group consisting of insulin, an insulin analog, a derivatized insulin, and a derivatized insulin analog, present at about 0.57 micromoles/mL to about 0.64 micromoles/mL,

b) zinc, present at about 0.3 mole to about 1 mole per mole of polypeptide,

c) protamine, present at a concentration between 0.28 mg/mL to 0.48 mg/mL, and

d) a hexamer-stabilizing compound to form said non-adsorbed insulin crystals,

wherein said non-absorbed insulin crystals are formed,

wherein less than about 2% of said polypeptide is present on said non-adsorbed insulin crystals as adsorbed polypeptide, and

wherein said non-adsorbed crystals have a longest dimension that is between about 0.5 to 10 microns.

2. The method of claim 1, wherein less than about 1% of said polypeptide is present on said non-adsorbed insulin crystals as adsorbed polypeptide.

3. The method of claim 1, wherein less than about 0.2% of said polypeptide is present on said non-adsorbed insulin crystals as adsorbed polypeptide.

4. The method according to claim 1, wherein said polypeptide is human insulin.

5. The method according to claim 1, wherein said polypeptide is a derivatized insulin.

6. The method according to claim 5, wherein said derivatized insulin is an acylated insulin.

7. The method according to claim 6, wherein said acylated insulin is B29-Nε

-octanoyl-human insulin.

8. The method of claim 1, wherein said acylated insulin analog is B29-Nε

-Tetradecanoyl-des(B30)-human insulin.

9. The method according to claim 1, wherein said ingredients further comprise a buffer selected from the group consisting of citrate, phosphate, acetate, TRIS, and glycine.

10. The method according to claim 9, wherein said buffer is citrate.

11. The method according to claim 1, wherein said non-adsorbed crystals have a longest dimension that is between about 0.5 to about 5 microns.

12. The method according to claim 11, wherein said non-adsorbed crystals have a longest dimension that is between about 0.5 to about 3 microns.