Pharmaceutical compositions comprising dextran with a molecular weight of 1.0-100 KDA and processes for their preparation

• US 7,781,400 B2
• Filed: 07/28/2009
• Issued: 08/24/2010
• Est. Priority Date: 01/18/2006
• Status: Expired due to Fees

• Current Assignee: Bows Pharmaceuticals AG
• Original Assignee: Bows Pharmaceuticals AG
• Inventors: Sabetsky, Vladimir A.
• Primary Examiner(s): Ha; Julie
• Application Number:
  US12/510,533
• Publication Number:
  US 20090281020A1
• Time in Patent Office: 392 Days
• Field of Search: None
• US Class Current: 514/1.1
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 3/10 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: C08L 5/02 Dextran; Derivatives thereof

Abstract

A solid or semisolid implant obtainable by providing a liquid composition comprising an aqueous solution of dextran with molecular weight of 1.0-100 kDa and introducing the liquid composition into the body of a mammal, whereby the implant is formed in situ in the body of the mammal. A process for preparing a composition useful for biomedical application, comprising the steps of providing a liquid composition comprising an aqueous solution of dextran having a molecular weight of 1-100 kDa; and bringing the liquid composition to solidify; whereby water is gradually eliminated from the liquid composition during the solidification. A biomedical article prepared from the composition.

Claims

1. A process for preparing a composition, said composition being suitable for the controlled release of a biologically active protein in the body of a mammal, said process comprising:

(a) providing an aqueous solution of dextran having a molecular weight of 1-100 kDa at a concentration within the range of 25-75% by weight;

(b) introducing a biologically active protein into the aqueous solution of (a) to form a liquid composition; and

(c) forming a solid matrix from said dextran in said liquid composition by bringing said dextran in said liquid composition to a solid form by gradually eliminating water from said liquid composition by evaporation or extraction, thereby providing a composition in which said biologically active protein is contained within said solid matrix.

2. The process of claim 1, wherein the molecular weight of dextran is 1-70 kDa.

3. The process of claim 1, wherein dextran is present in said aqueous solution of (a) at a concentration within the range of 50-75% by weight.

4. The process of claim 1, wherein water is eliminated from said liquid composition by evaporation.

5. The process of claim 4, wherein said evaporation is performed at temperature of from 0°

C. to 500°

C.

6. The process of claim 5, wherein said evaporation is performed at temperature of from 20°

C. to 370°

C.

7. The process of claim 4, wherein the rate of evaporation is 0.1-75% by weight of said liquid composition per hour.

8. The process of claim 1, wherein water is eliminated from said liquid composition by extraction.

9. The process of claim 8, wherein said extraction is performed by adding 1-10 parts by weight of ethanol, liquid polyethylene glycol (PEG), or liquid polypropylene glycol (PPG), to 1 part by weight of said liquid composition.

10. The process of claim 1, wherein said biologically active protein is dissolved or suspended in said aqueous solution.

11. The process of claim 1, wherein said biologically active protein is introduced in an amount so as to be present at a concentration of 0.01 to 25% by weight in said liquid composition.

12. The process of claim 1, wherein said protein is insulin.

13. An article for biomedical applications comprising a composition prepared by the process of claim 1.

14. The article of claim 13, wherein said article is in the form of a hard pharmaceutical capsule.

15. The article of claim 13, wherein said protein is insulin.

16. The article of claim 13, wherein said protein is insulin and said article is in the form of a hard pharmaceutical capsule.