Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor

• US 6,699,493 B2
• Filed: 11/28/2001
• Issued: 03/02/2004
• Est. Priority Date: 11/29/2000
• Status: Expired due to Term

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Oculex Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Wong, Vernon G.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/997,094
• Publication Number:
  US 20020182185A1
• Time in Patent Office: 825 Days
• Field of Search: 424/428, 514/772.3, 514/772.6, 514/781
• US Class Current: 424/428
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 9/0008 Introducing ophthalmic products into the ocular cavity or retaining products therein putting in contact lenses A61F9/0061; introducing or retaining media in cavities of the body in general A61M31/00
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

Claims

1. A method for preventing transplant rejection in an eye of an individual, comprising:

a) performing an ocular transplant procedure on an eye of an individual; and

b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

2. The method of claim 1, wherein the ocular transplant procedure is selected from the group consisting of retinal pigment epithelium (RPE) transplant and cornea transplant.

3. The method of claim 2, wherein the ocular transplant procedure is an RPE transplant.

4. The method of claim 2, wherein the ocular transplant procedure is a cornea transplant.

5. The method of claim 1, wherein the bioerodible drug delivery system is placed in the anterior chamber of the eye.

6. The method of claim 1, wherein the bioerodible drug delivery system is placed in the vitreous cavity of the eye.

7. The method of claim 1, wherein the immunosuppressive agent is selected from the group consisting of dexamethasone, cyclosporin A, azathioprine, brequinar, gusperimus, 6-mercaptopurine, mizoribine, rapamycin, tacrolimus (FK-506), denopterin, edatrexate, methotrexate, piritrexim, pteropterin, raltitrexed, trimetrexate, cladribine, fludarabine, 6-mercaptopurine, thiamiprine, thiaguanine, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, doxifluridine, emitefur, enocitabine, floxuridine, fluorouracil, gemcitabine, egafur, fluocinolone, triaminolone, anecortave acetate, fluorometholone, medrysone, and prednislone.

8. The method of claim 7, wherein the immunosuppressive agent is dexamethasone.

9. The method of claim 8, wherein the bioerodible drug delivery system comprises about 50% by weight of dexamethasone, about 15% by weight of hydroxypropyl methylcellulose and about 35% by weight of polylactic polyglycolic acid.

10. The method of claim 8, wherein the bioerodible drug delivery system comprises about 60% by weight of dexamethasone and about 40% by weight of polylactic polyglycolic acid.

11. The method of claim 8, wherein the bioerodible drug delivery system comprises about 50% by weight of dexamethasone and about 50% by weight of polylactic polyglycolic acid.

12. The method of claim 7, wherein the immunosuppressive agent is cyclosporin A.

13. The method of claim 1, wherein the bioerodible polymer is a polyester.

14. The method of claim 1, wherein the bioerodible polymer is a polylactic acid polyglycolic acid copolymer.

15. The method of claim 14, wherein the bioerodible drug delivery system further comprises hydroxy propyl methyl cellulose.

16. The method of claim 1, wherein the individual is a human.

17. A method for preventing transplant rejection in the eye of an individual, comprising:

a) performing an ocular transplant procedure on an eye of an individual; and

b) implanting a solid body into the eye, wherein the body comprises particles of an immunosuppressive agent entrapped within a bioerodible polymer, and whereby the agent is released from the body by erosion of the polymer.

18. A kit for preventing transplant rejection in an eye, comprising:

a) a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer, wherein the drug delivery system is designed to be implanted in an eye of an individual who has undergone or is undergoing an ocular transplant procedure; and

b) instructions for use.

19. The kit of claim 18, wherein the immunosuppressive agent is dexamethasone.

20. A method comprising

a) performing a retinal pigment epithelium transplant or a cornea transplant on an eye of an individual;

and

b) placing in the eye a bioerodible drug delivery system comprising dexamethasone or cyclosporin A and a bioerodible polymer.

21. The method of claim 20, wherein the bioerodible drug delivery system is placed in an anterior chamber of the eye.

22. The method of claim 20, wherein the bioerodible drug delivery system is placed in a vitreous cavity of the eye.

23. The method of claim 20, wherein the bioerodible drug delivery system comprises about 50% by weight of dexamethasone or cyclosporin A, about 15% by weight of hydroxypropyl methylcellulose, and about 35% by weight of polylactic polyglycolic acid.

24. The method of claim 20, wherein the bioerodible drug delivery system comprises about 60% by weight of dexamethasone or cyclosporin A and about 40% by weight of polylactic polyglycolic acid.

25. The method of claim 20, wherein the bioerodible drug delivery system comprises about 50% by weight of dexamethasone or cyclosporin A and about 50% by weight of polylactic polyglycolic acid.

26. The method of claim 20, wherein the bioerodible polymer is a polyester.

27. The method of claim 20, wherein the bioerodible polymer is a polylactic acid polyglycolic acid copolymer.

28. The method of claim 20, wherein the bioerodible drug delivery system further comprises hydroxy propyl methyl cellulose.

29. The method of claim 20, wherein the individual is a human.

30. A method comprising placing in an eye of an individual a bioerodible drug delivery system;

wherein the bioerodible drug delivery system includes an immunosuppressive agent and a bioerodible polymer; and

wherein the eye of the individual has undergone or is undergoing an ocular transplant procedure.

31. The method of claim 30, wherein the ocular transplant procedure is selected from the group consisting of retinal pigment epithelium (RPE) transplant and cornea transplant.

32. The method of claim 31, wherein the ocular transplant procedure is an RPE transplant.

33. The method of claim 31, wherein the ocular transplant procedure is a cornea transplant.

34. The method of claim 30, wherein the bioerodible drug delivery system is placed in the anterior chamber of the eye.

35. The method of claim 30, wherein the bioerodible drug delivery system is placed in the vitreous cavity of the eye.

36. The method of claim 30, wherein the immunosuppressive agent is selected from the group consisting of dexamethasone, cyclosporin A, azathioprine, brequinar, gusperimus, 6-mercaptopurine, mizoribine, rapamycin, tacrolimus (FK-506), denopterin, edatrexate, methotrexate, piritrexim, pteropterin, raltitrexed, trimetrexate, cladribine, fludarabine, 6-mercaptopurine, thiamiprine, thiaguanine, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, doxifluridine, emitefur, enocitabine, floxuridine, fluorouracil, gemcitabine, egafur, fluocinolone, triaminolone, anecortave acetate, fluorometholone, medrysone, and prednislone.

37. The method of claim 36, wherein the immunosuppressive agent is dexamethasone.

38. The method of claim 30, wherein the bioerodible drug delivery system comprises about 50% by weight of dexamethasone, about 15% by weight of hydroxypropyl methylcellulose and about 35% by weight of polylactic polyglycolic acid.

39. The method of claim 30, wherein the bioerodible drug delivery system comprises about 60% by weight of dexamethasone and about 40% by weight of polylactic polyglycolic acid.

40. The method of claim 30, wherein the bioerodible drug delivery system comprises about 50% by weight of dexamethasone and about 50% by weight of polylactic polyglycolic acid.

41. The method of claim 36, wherein the immunosuppressive agent is cyclosporin A.

42. The method of claim 30, wherein the bioerodible polymer is a polyester.

43. The method of claim 30, wherein the bioerodible polymer is a polylactic acid polyglycolic acid copolymer.

44. The method of claim 30, wherein the bioerodible drug delivery system further comprises hydroxy propyl methyl cellulose.

45. The method of claim 30, wherein the individual is a human.