Methods for preparing and using implantable substance delivery devices

• US 6,692,759 B1
• Filed: 06/28/2001
• Issued: 02/17/2004
• Est. Priority Date: 06/28/2000
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Wong, Corinne Gail, Hsu, Hung Tao, Pontes de-Carvalho, Ricardo Azevedo
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/894,914
• Time in Patent Office: 964 Days
• Field of Search: 424/423, 424/424, 424/426, 424/427, 424/428, 424/433, 428/402
• US Class Current: 424/423
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

Method for preparing an implantable device for a sustained delivery of a substance within a body of a human or an animal subject, the method including; dissolving a biocompatible polymer in a suitable solvent solution to produce a polymer-solvent solution; adding the substance to the polymer-solvent solution to produce a polymer-solvent solution-substance admixture; drying the polymer-solvent solution-substance admixture to form a substantially dry mass; and one or more of the following three steps:

(1) adding a second polymer-solvent solution-substance admixture to the dry mass and this second polymer-solvent solution-substance admixture is then allowed to dry; and/or,

(2) refrigerating the mass; and/or,

(3) adding a liquid to the mass to cause the mass to soften and thereafter manipulating the softened mass to a desired shape.

Claims

1. A method for preparing an implantable device for a sustained delivery of a chemical substance within a body of a human or an animal subject, said method comprising the steps of:

(A) dissolving a biocompatible polymer in a suitable solvent solution to produce a polymer-solvent solution;

(B) adding said chemical substance to said polymer-solvent solution to produce a polymer-solvent solution-substance admixture;

(C) drying said polymer-solvent solution-substance admixture to form a substantially dry mass; and

(D) refrigerating said mass.

2. A method according to claim 1 wherein, between steps C and D, said method further comprises:

adding a liquid to said mass to cause said mass to soften;

manipulating said softened mass to a desired shape.

3. A method according to claim 1 wherein a second polymer-solvent solution-substance admixture made by steps (A) and (B) is added to said substantially dry mass of said step (C) and said second polymer-solvent solution-substance admixture is allowed to dry.

4. A method according to claim 1 wherein said polymer is non-biodegradable.

5. A method according to claim 4 wherein said non-biodegradable polymer is selected from the group consisting of Hydron, polyester, polycarbonate, polysulfone, polyvinyl chloride, polyethylene, polypropylene, poly(N-vinyl pyrrolidone), poly(methyl methacrylate), poly(vinyl alcohol), poly(acrylic acid), polyacrylamide, poly(ethylene-co-vinyl acetate), poly(ethylene glycol), poly(methacrylic acid), mixtures thereof and combinations thereof.

6. A method according to claim 4 wherein said non-biodegradable, polymer is Hydron.

7. A method according to claim 1 wherein said polymer is biodegradable.

8. A method according to claim 7 wherein said , biodegradable polymer is selected from the group consisting of poly (ethylene glycol), polyvinylpyrrolidine, polylactides (PLA), polyglycolides (PGA), poly(lactide-co-glycolides) (PLGA), polyanhydrides, polyorthoesters, mixtures thereof and combinations thereof.

9. A method according to claim 1 wherein said solvent solution comprises an organic solvent.

10. A method according to claim 1 wherein said solvent solution comprises ethanol.

11. A method according to claim 1 wherein said solvent solution comprises about 70% ethanol.

12. A method according to claim 1 wherein said substance is a therapeutic agent.

13. A method according to claim 1 wherein said substance is a biomolecule.

14. A method according to claim 1 wherein said substance is a therapeutic biomolecule.

15. A method according to claim 1 wherein said substance is an anti-inflammatory agent.

16. A method according to claim 1 wherein said substance is an antineoplastic agent.

17. A method according to claim 1 wherein said substance is a protein.

18. A method according to claim 1 wherein said substance is a steroid.

19. A method according to claim 1 wherein said substance is a hormone.

20. A method according to claim 1 wherein said substance is an RNA, DNA or combination thereof.

21. A method according to claim 1 wherein said substance is an anti-sense oligoribonucleotide sequence, antisense oligonucleotide sequence or a combination thereof.

22. A method according to claim 1 wherein said substance is an anti-sense oligonucleotide, anti-sense oligoribonucleotide or combination thereof to a focal adhesion kinase RNA.

23. A method according to claim 1 wherein said substance is an anti-sense oligonucleotide anti-sense oligoribonucleotide or combination thereof to a focal adhesion kinase gene.

24. A method according to claim 1 wherein said substance comprises VEGF, bFGF or a combination thereof.

25. A method for using an implantable device comprising a step of introducing a device produced according to claim 1 into a body of a human or animal subject such that said substance will be released from said device.

26. A method according to claim 25 wherein said introducing step comprises a step of implanting said device into an eye.

27. A method according to claim 25 wherein said introducing step comprises a step of implanting into a vitreous of an eye by surgical means.

28. A method according to claim 25 wherein said introducing step comprises a step of implanting said device into a subchoroidal space, where a sclera is cut to expose a choroidea.

29. A method according to claim 25 wherein said substance causes a therapeutic benefit to occur in said body of said subject into which said device is implanted.

30. A method according to claim 25 wherein said introducing step causes a desired disease or disorder in said animal so as to provide an animal model for said disease or disorder.

31. A method according to claim 30 wherein said disorder is neovascularization.

32. A method according to claim 30 wherein said disease is age-related macular degeneration.

33. An implantable substance delivery device for a sustained delivery of a substance within a body of a human or an animal subject made by a method according to claim 1.

34. A method according to claim 1 wherein said substance is a chemical.