Process for making systems for the controlled release of macromolecules

• US 4,591,496 A
• Filed: 01/16/1984
• Issued: 05/27/1986
• Est. Priority Date: 01/16/1984
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert, Siegel, Ronald, Cohen, Jonathan M.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/571,007
• Time in Patent Office: 862 Days
• Field of Search: 424/14, 424/16, 424/19, 424/22, 424/78, 424/15, 264/109, 264/123, 264/125
• US Class Current: 424/467
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

A new method for making polymeric systems for the sustained release of macromolecular drugs is described. The method consists of mixing drug and polymer, e.g. ethylene-vinyl acetate copolymer powders below the glass transition temperature of the polymer, and compressing the mixture at a temperature above the glass transition point. The macromolecule is not exposed to organic solvent during the fabrication process. The sustained release and bioactivity of macromolecules is unchanged throughout the pressure casting and release processes.

Claims

1. A method for making a glass-like matrix useful as a delivery system for the controlled release of biologically active substances comprising the steps of:

preparing a polymeric material in powder form at a temperature below its glass transition temperature, said polymeric material having limited water sorptivity;

preparing a swellable biologically active substance in powder form at a temperature less than the minimal temperature at which substantial degradation of the substance occurs;

combining said polymeric material powder and said biologically active substance powder as a mixture in ratios ranging from 97-10 parts polymeric material powder by weight to 3-90 parts biologically active substance powder by weight; and

compressing said mixture to form a solid, glass-like matrix, said compression occurring at a temperature greater than the glass transition temperature of said polymeric material but less than the minimal temperature for substantial degradation of said biologically active substance.

2. In the method of claim 1, the improvement wherein said polymer is an ethylene-vinyl ester copolymer of the general formula ##STR3## wherein R is hydrogen, lower alkyl of 1 to 7 carbons, or aryl, m is (10 to 40) % by weight and n is (100-m) % by weight.

3. In the method of claim 1, the improvement wherein said biologically active substance is an enzyme.

4. In the method of claim 1, the improvement wherein said biologically active substance is a hormone.

5. In the method of claim 1, the improvement wherein said biologically active substance is an enzyme inhibitor.

6. In the method of claim 1, the improvement wherein said biologically active substance is an antigen.

7. In the method of claim 1, the improvement wherein said biologically active substance is a drug.