Crystallized carbohydrate matrix for biologically active substances, a process of preparing said matrix, and the use thereof

• US 4,713,249 A
• Filed: 10/22/1985
• Issued: 12/15/1987
• Est. Priority Date: 11/12/1981
• Status: Expired due to Fees

• Current Assignee: Ulf Schroder
• Original Assignee: Ulf Schroder
• Inventors: Schroder, Ulf
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US06/789,933
• Time in Patent Office: 784 Days
• Field of Search: 427/213.3, 428/402.24, 424/22, 424/35, 424/484, 424/488
• US Class Current: 424/1.37
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

The invention shows that it is possible to produce a depot matrix for biologically active substances, consisting of carbohydrate microspheres, such that the carbohydrate polymers included in the microsphere are stabilized to a microsphere by crystallization, which implies using non-covalent bonds, the substance enclosed retaining its biological activity.

Claims

1. A composition useful for the prolonged release of a biologically-active substance comprising a sphere or particle comprising a non-covalently cross-linked crystalline polymeric carbohydrate matrix, said matrix incorporating 0.001-50% by weight of an absorbed or covalently bonded biologically-active substance.

2. The composition of claim 1 wherein said sphere or particle has an average diameter within the range of 0.01-1,000 μ

m.

3. The composition of claim 1 wherein said sphere or particle has an average diameter within the range of 0.01-1.0 μ

m.

4. The composition of claim 1 wherein said carbohydrate is selected from the group consisting of dextran, starch and the derivatives thereof.

5. The composition of claim 1 wherein the carbohydrate is selected from the group consisting of alginate, chitosan, agarose, carrageenan, cellulose, glycogen, pullullan and the derivatives thereof.

6. The composition of claim 1 wherein said biologically-active substance is an antigen.

7. The composition of claim 1 wherein the biologically-active substance is insulin.

8. The composition of claim 1 wherein the biologically-active substance is an allergen.

9. The composition of claim 1 wherein the biologically-active substance is a growth hormone.

10. A process for producing a composition useful for the prolonged release of a biologically-active substance, comprising,

(a) forming a solution of a polymeric carbohydrate and a biologically-active substance in one or more hydrophillic solvents;

(b) emulsifying the mixture of the carbohydrate and the biologically active substance in a liquid hydrophobic medium to form spherical droplets; and

(c) introducing the emulsion into a crystallizing medium to form spheres having a non-covalently cross-linked crystalline polymeric carbohydrate matrix, said matrix incorporating 0.001-50% by weight of the biologically-active substance.

11. The process of claim 10 wherein the droplets are crystallized by introducing them into a crystallizing medium comprising acetone, ethanol or methanol.

12. The process of claim 10 wherein the emulsification is conducted at 4°

-40°

C. so that the activity of the biologically-active substance is preserved.