Long acting injectable insulin composition and methods of making and using thereof

• US 7,544,656 B2
• Filed: 03/04/2004
• Issued: 06/09/2009
• Est. Priority Date: 03/04/2003
• Status: Expired due to Fees

• Current Assignee: TDC Bio S.a.r.l.
• Original Assignee: Cambridge Technology Development Incorporated (Novanta Inc.)
• Inventors: Sabetsky, Vladimir
• Primary Examiner(s): Lukton; David
• Application Number:
  US10/792,383
• Publication Number:
  US 20040234616A1
• Time in Patent Office: 1,923 Days
• Field of Search: 514/3, 514/59, 424/400, 436/529, 524/54
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

A method of lowering blood glucose in a mammal includes injecting a therapeutically effective amount of crystallized dextran microparticles and insulin to the mammal to lower blood glucose of the mammal. The composition may be a one phase or a structured multi-phase composition for controlled release of insulin over an extended period of time.

Claims

1. A method of making a pharmaceutical composition suitable for injection into the body of a mammal, said method comprising:

providing crystallized dextran microparticles that do not include insulin; and

combining the crystallized dextran microparticles with insulin in an amount effective to lower the blood glucose level of said mammal.

2. The method of claim 1, wherein:

the composition comprises a flowable colloidal composition; and

the microparticles comprise crystallized dextran microparticles having an average diameter of 0.5 to 5 microns.

3. The method of claim 2, wherein:

the composition comprises a two phase composition comprising a dextran phase and a PEG phase;

the insulin is selectively partitioned in the PEG phase and the microparticles are selectively partitioned in the dextran phase; and

the composition forms a structured implant comprising a PEG phase core and a dextran phase shell after injection into the body of the mammal.

4. The method of claim 1, wherein the provided crystallized dextran microparticles are porous.

5. The method of claim 4, wherein the provided crystallized dextran microparticles have a porosity of at least 10% by volume.

6. The method of claim 4, wherein the porous crystallized dextran microparticles are combined with the insulin such that at least a portion of the insulin is contained within the pores of the crystallized dextran microparticles.

7. The method of claim 1, wherein the composition is prepared to be in the form of an aqueous suspension.

8. The method of claim 1, wherein the crystallized dextran microparticles are provided in the crystallized microparticle form prior to said combining step.

9. The method of claim 1, wherein the crystallized dextran microparticles are provided in a solution comprising the formed crystallized dextran microparticles and a suitable carrier.

10. The method of claim 9, wherein said combining step comprises adding the insulin to the solution and allowing the insulin to permeate into pores present in the dextran microparticles or become attached to a surface of the dextran microparticles.