Methods for treating inflammation-mediated conditions of the eye

• US 6,726,918 B1
• Filed: 10/20/2000
• Issued: 04/27/2004
• Est. Priority Date: 07/05/2000
• Status: Expired due to Term

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Oculex Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Hu, Mae W. L., Wong, Vernon G.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): EVANS, CHARESSE L
• Application Number:
  US09/693,008
• Time in Patent Office: 1,285 Days
• Field of Search: 424/400, 424/422, 424/423, 424/426, 424/427, 424/428, 424/489
• US Class Current: 424/422
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 5/38 of the suprarenal hormones

Abstract

Methods for treating inflammation-mediated conditions of the eye are described, comprising: implanting into the vitreous of the eye of an individual a bioerodible implant comprising a steroidal anti-inflammatory agent and a bioerodible polymer, wherein the implant delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.05 μg/ml dexamethasone within about 48 hours and maintains a concentration equivalent to at least about 0.03 μg/ml dexamethasone for at least about three weeks.

Claims

1. A method for treating an inflammation-mediated condition of the eye in an individual, comprising:

implanting into the vitreous of the eye a bioerodible implant comprising a steroidal anti-inflammatory agent and a bioerodible polymer, wherein the implant delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.05 μ

g/ml dexamethasone within about 48 hours and maintains a concentration equivalent to at least about 0.03 μ

g/ml dexamethasone for at least about three weeks.

2. The method according to claim 1, wherein the steroidal anti-inflammatory agent is selected from the group consisting of cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone.

3. The method according to claim 1, wherein the steroidal anti-inflammatory agent is dexamethasone.

4. The method according to claim 1, wherein the implant delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.1 μ

g/ml dexamethasone within about 48 hours and maintains a concentration equivalent to at least about 0.03 μ

g/ml dexamethasone for at least about three weeks.

5. The method according to claim 1, wherein said concentration is maintained for least about four weeks.

6. The method according to claim 1, wherein the steroidal anti-inflammatory agent comprises about 50 to about 80 weight percent of the implant.

7. The method according to claim 6, wherein the steroidal anti-inflammatory agent comprises about 70% by weight of the implant.

8. The method according to claim 1, wherein the bioerodible polymer is a polyester.

9. The method according to claim 8, wherein the bioerodible polymer is polylactic acid polyglycolic acid (PLGA) copolymer.

10. The method according to claim 1, wherein the inflammation-mediated condition of the eye is selected from the group consisting of uveitis, macular edema, acute macular degeneration, retinal detachment, ocular tumors, fungal infections, viral infections, multifocal choroiditis, diabetic uveitis, proliferative vitreoretinopathy (PVR), sympathetic opthalmia, Vogt Koyanagi-Harada (VKH) syndrome, histoplasmosis, and uveal diffusion.

11. The method according to claim 10, wherein the inflammation-mediated condition of the eye is uveitis.

12. The method according to claim 10, wherein the inflammation-mediated condition of the eye is proliferative vitreoretinopathy (PVR).

13. The method according to claim 1, wherein the individual is a human.

39. The method according to claim 10, wherein the inflammation-mediated condition of the eye is macular edema.

41. The method according to claim 1, wherein the steroidal anti-inflammatory agent is fluocinolone acetonide.

14. A method for treating an inflammation-mediated condition of the eye in an individual, comprising:

implanting a solid body into the vitreous of the eye, said body comprising particles of a steroidal anti-inflammatory agent entrapped within a bioerodible polymer, whereby said agent is delivered to the vitreous at a rate and for a time sufficient to reach a concentration equivalent to at least about 0.05 μ

g/ml dexamethasone within about 48 hours, and maintains a concentration equivalent to at least about 0.03 μ

g/ml dexamethasone for at least about three weeks.

15. A method for treating an inflammation-mediated condition of the eye in an individual, comprising:

implanting into the vitreous of the eye a bioerodible implant comprising a steroidal anti-inflammatory agent and a bioerodible polymer, wherein the implant delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.2 μ

g/ml dexamethasone within about 6 hours and maintains a concentration equivalent to at least about 0.01 μ

g/ml dexamethasone for at least about three weeks.

16. The method according to claim 15, wherein the steroidal anti-inflammatory agent is selected from the group consisting of cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone.

17. The method according to claim 15, wherein the steroidal anti-inflammatory agent is dexamethasone.

18. The method according to claim 15, wherein the implant delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.4 μ

g/ml dexamethasone within about 6 hours and maintains a concentration equivalent to at least about 0.01 μ

g/ml dexamethasone for at least about three weeks.

19. The method according to claim 15, wherein the implant delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.2 μ

g/ml dexamethasone within about 6 hours and maintains a concentration equivalent to at least about 0.1 μ

g/ml dexamethasone for at least about three weeks.

20. The method according to claim 15, wherein said concentration is maintained for least about four weeks.

21. The method according to claim 15, wherein said concentration is maintained for least about six weeks.

22. The method according to claim 15, wherein the steroidal anti-inflammatory agent comprises about 50 to about 80 weight percent of the implant.

23. The method according to claim 22, wherein the steroidal anti-inflammatory agent comprises about 70% by weight of the implant.

24. The method according to claim 22, wherein the steroidal anti-inflammatory agent comprises about 50% by weight of the implant.

25. The method according to claim 15, wherein the bioerodible polymer is a polyester.

26. The method according to claim 25, wherein the bioerodible polymer is polylactic acid polyglycolic acid (PLGA) copolymer.

27. The method according to claim 15, wherein the inflammation-mediated condition of the eye is selected from the group consisting of uveitis, macular edema, acute macular degeneration, retinal detachment, ocular tumors, fungal infections, viral infections, multifocal choroiditis, diabetic uveitis, proliferative vitreoretinopathy (PVR), sympathetic opthalmia, Vogt Koyanagi-Harada (VKH) syndrome, histoplasmosis, and uveal diffusion.

28. The method according to claim 27, wherein the inflammation-mediated condition of the eye is uveitis.

29. The method according to claim 27, wherein the inflammation-mediated condition of the eye is proliferative vitreoretinopathy (PVR).

30. The method according to claim 15, wherein the individual is a human.

40. The method according to claim 27, wherein the inflammation-mediated condition of the eye is macular edema.

42. The method according to claim 15, wherein the steroidal anti-inflammatory agent is fluocinolone acetonide.

31. A method for treating an inflammation-mediated condition of the eye in an individual, comprising:

implanting a bioerodible solid body into the vitreous of the eye, said body comprising particles of a steroidal anti-inflammatory agent entrapped within a bioerodible polymer, whereby said agent is delivered to the vitreous at a rate and for a time sufficient to reach a concentration equivalent to at least about 0.2 μ

g/ml dexamethasone within about 6 hours, and maintains a concentration equivalent to at least about 0.01 μ

g/ml dexamethasone for at least about three weeks.

32. A solid bioerodible implant for treating an inflammation-mediated condition of the eye, consisting essentially of:

dexamethasone particles entrapped within a polylactic acid polyglycolic acid (PLGA) copolymer, wherein the dexamethasone makes up between about 50 percent by weight and about 80 percent by weight of the implant, and wherein the implant releases at least about 10% of the drug load within 1 week when measured under infinite sink conditions in vitro.

33. A solid bioerodible implant for treating an inflammation-mediated condition of the eye, the implant consisting essentially of:

dexamethasone particles entrapped within a polyactic acid polyglycolic acid (PLGA) copolymer matrix, wherein the dexamethasone makes up between about 50 percent by weight and about 80 percent by weight of the implant, and wherein the implant releases at least about 15% of the dexamethasone within 2 weeks when measured under infinite sink conditions in vitro.

34. The solid bioerodible implant of claim 33, wherein the implant releases at least about 20% of the dexamethasone within 2 weeks when measured under infinite sink conditions in vitro.

35. The solid bioerodible implant of claim 34, wherein the implant releases at least about 40% of the dexamethasone within 2 weeks when measured under infinite sink conditions in vitro.

36. A method for treating an inflammation-mediated condition of the eye in an individual, comprising:

implanting into the vitreous of the eye a bioerodible implant comprising a steroidal anti-inflammatory agent and a bioerodible polymer, wherein the implant releases at least about 15% of the steroidal anti-inflammatory agent within 2 weeks when measured under infinite sink conditions in vitro.

37. The method according to claim 36, wherein the implant releases at least about 20% of the steroidal anti-inflammatory agent within 2 weeks when measured under infinite sink conditions in vitro.

38. The method according to claim 37, wherein the implant releases at least about 40% of the steroidal anti-inflammatory agent within 2 weeks when measured under infinite sink conditions in vitro.