Methods for preparing and using implantable substance delivery devices

• US 7,592,016 B2
• Filed: 02/05/2004
• Issued: 09/22/2009
• Est. Priority Date: 06/28/2001
• Status: Active Grant

• 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, de-Carvalho, Ricardo Azevedo Pontes
• Primary Examiner(s): Azpuru; Carlos A.
• Application Number:
  US10/773,835
• Publication Number:
  US 20040247645A1
• Time in Patent Office: 2,056 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 428/31544 Addition polymer is perhalogenated

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 substance within a body of a human or an animal subject, said method comprising the steps of:

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

(B) adding said 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;

(D) adding a liquid to said mass to cause said mass to soften and;

(E) manipulating said softened mass to a desired shape.

2. A method according to claim 1 which further comprises a step F, said step F comprising refrigerating said mass.

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 polymethylmethacrylate, 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-blodegradable, polymer is polymethylmethacrylate.

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 to about 95% ethanol.

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

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

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

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

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

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

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

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

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

21. 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.

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 gene.

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

24. 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.

25. A method according to claim 24 wherein said introducing step comprises a step of implanting said device into an eye.

26. A method according to claim 24 wherein said introducing step comprises a step of implanting into a vitreous of an eye by surgical means.

27. A method according to claim 24 wherein said introducing step comprises a step of implanting said device into a subchoroldal space, where a sclera is cut to expose a choroidea.

28. A device according to claim 24 wherein said substance causes a therapeutic benefit to occur in said body of said subject into which said device is implanted.

29. A method according to claim 24 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.

30. A method according to claim 29 wherein said disorder is neovascularization.

31. A method according to claim 29 wherein said disease is age-related macular degeneration.

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

33. A method for preparing an implantable device for a sustained delivery of a 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 substance to said polymer-solvent solution to produce a polymer-solvent solution-substance admixture;

(C) drying said polymer-solvent solution-substance admixture

(D) adding a second polymer-solvent solution-substance admixture to said air-dried polymer-solvent solution-substance admixture of said step (C) and said second polymer-solvent solution-substance admixture is allowed to dry;

wherein said biocompatible polymer is selected from the group consisting of biodegradable-polymers and non-biodegradable polymers.

34. A method according to claim 33 comprising a step after D, wherein said step comprises:

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

manipulating said softened mass to a desired shape.

35. A method according to claim 33 comprising a step after D wherein said step comprises refrigerating said mass.

36. A method according to claim 33 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.

37. A method according to claim 33 wherein said non-biodegradable, polymer is Hydron.

38. A method according to claim 33 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.

39. A method according to claim 33 wherein said solvent solution comprises an organic solvent.

40. A method according to claim 33 wherein said solvent solution comprises ethanol.

41. A method according to claim 33 wherein said solvent solution comprises about 70% ethanol.

42. A method according to claim 33 wherein said substance is a chemical.

43. A method according to claim 33 wherein said substance is a therapeutic agent.

44. A method according to claim 33 wherein said substance is a biomolecule.

45. A method according to claim 33 wherein said substance is a therapeutic biomolecule.

46. A method according to claim 33 wherein said substance is a protein.

47. A method according to claim 33 wherein said substance is a steroid.

48. A method according to claim 33 wherein said substance is a hormone.

49. A method according to claim 33 wherein said substance is an RNA, DNA or combination thereof.

50. A method according to claim 33 wherein said substance is an anti-sense oligoribonucleotide sequence, antisense oligonucleotide sequence or a combination thereof.

51. A method according to claim 33 wherein said substance is an anti-sense oligonucleotide, anti-sense oligoribonucleotide or combination thereof to a focal adhesion kinase RNA.

52. A method according to claim 33 wherein said substance is an anti-sense oligonucleotide anti-sense oligoribonucleotide or combination thereof to a focal adhesion kinase gene.

53. A method according to claim 33 wherein said substance comprises VEGF, bFGF or a combination thereof.

54. A method for using an implantable device comprising a step of introducing a device produced according to claim 33 into a body of a human or animal subject such that said substance will be released from said device.

55. A method according to claim 54 wherein said introducing step comprises a step of implanting said device into an eye.

56. A method according to claim 54 wherein said introducing step comprises a step of implanting into a vitreous of an eye by surgical means.

57. A method according to claim 54 wherein said introducing step comprises a step of implanting said device into a subchoroidal space, where a sclera is cut to expose a choroidea.

58. A method according to claim 54 wherein said substance causes a therapeutic benefit to occur in said body of said subject into which said device is implanted.

59. A method according to claim 54 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.

60. A method according to claim 59 wherein said disorder is neovascularization.

61. A method according to claim 59 wherein said disease is age-related macular degeneration.

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