Magnetically modulated polymeric drug release system

• US 5,019,372 A
• Filed: 09/07/1990
• Issued: 05/28/1991
• Est. Priority Date: 06/27/1986
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Hsieh, Dean S. T., Folkman, Judah, Langer, Robert S. Jr.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US07/579,050
• Time in Patent Office: 263 Days
• Field of Search: 128/1.3, 128/804, 424/9, 424/78, 424/, 424/426, 424/450, 424/490, 424/496, 424/497, 424/422, 424/423, 424/424, 424/451, 424/453
• US Class Current: 424/422
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• 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 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting

Abstract

A magnetically responsive composition for the modulated, sustained administration of a biologically active substance, the composition being in the form of a body sized and shaped for placement in the environment of use, the environment including an aqueous fluid, the body comprising, in admixture, a first phase comprising a biocompatible, plastically deformable, polymeric matrix, the polymeric matrix being insoluble in the environment of use, a second phase having a biologically active substance distributed throughout the matrix to be released to the aqueous fluid outside the matrix, and a third phase comprising a magnetically responsive substance encapsulated within the matrix so that, upon exposure of the body to an oscillating magnetic field, the rate of release of the biologically active substance to the aqueous fluid is increased.

Claims

1. A method of administering a biologically active substance to an animal, e.g., a human, said method comprising

preparing an implant for said animal of a medically responsive composition in the form of a body sized and shaped for placement in the environment of use, said environment including an aqueous fluid, said body comprising, in admixture, a first phase comprising a biocompatible, plastically deformable, polymeric matrix, said polymeric matrix being insoluble in the environment of use, a second phase comprising a biologically active substance distributed throughout said matrix to be released to said aqueous fluid outside said matrix, and a third phase comprising a magnetically responsive substance encapsulated within said matrix so that, upon exposure of said body to an oscillating magnetic field, the rate of release of said biologically active substance to said aqueous fluid is increased,

in order to subject said body in said animal to an oscillating magnetic field which creates sufficient disturbance to increase the rate of release of said biologically active substance.

2. The method of claim 1 wherein said magnetically responsive substance is in the form of discrete particles dispersed throughout said matrix.

3. The method of claim 1 wherein said magnetically responsive substance is in the form of a single piece.

4. The method of claim 1 wherein said magnetically responsive substance is a metal.

5. The method of claim 4 wherein said magnetically responsive substance is stainless steel.

6. The method of claim 3 wherein said magnetically responsive substance is a permanent magnet.

7. The method of claim 2 wherein said particles are beads between 0.8 and 1.4 mm in diameter.

8. The method of claim 1 wherein the ratio, by weight, of said biologically active substance to said polymer is between 1:

99 and 90;

10.

9. The method of claim 1 wherein said active substance has a molecular weight of at least 150 daltons.

10. The method of claim 9 wherein said active substance is a protein.

11. The method of claim 1 wherein said active substance is a peptide hormone selected from the group consisting of insulin, glucagon, parathyroid, pituitary, calcitonin, vasopressin, renin, prolactin, growth, thyroid stimulating, corticotrophin, follical stimulating, luteinising and chorionic gonadotrophin hormones.

12. The method of claim 11 wherein said peptide hormone is insulin.

13. The method of claim 1 wherein said active substance is a steroid.

14. The method of claim 1 wherein said polymeric matrix is an ethylene vinyl ester copolymer of the general formula:

##STR3## wherein R is a member selected from the group consisting of hydrogen, lower alkyl of 1 to 7 carbons, and aryl;

m is 10 to 40% by weight, and n is (100-m) % by weight.

15. The method of claim 1, wherein said polymeric matrix is a crosslinked polymeric matrix.