Sustained release intraocular implants and related methods

• US 20050244468A1
• Filed: 04/30/2004
• Published: 11/03/2005
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Nivaggioli, Thierry, Huang, Glenn T.
• Granted Patent: US 8,119,154 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics

Abstract

Biocompatible intraocular implants include a steroid and a polymer associated with each other to facilitate release of the steroid into an eye for a period of time greater than about two months. The steroid may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the steroid may be associated with a polymeric coating having one or more openings effective to permit the steroid to be released into an external environment. The implants may be placed in an eye to treat one or more ocular conditions. The steroid is released from the implant for more than about two months, and may be release for more than several years.

Claims

1. A biodegradable intraocular implant comprising:

a steroid associated with a biodegradable polymer matrix that releases drug at a rate effective to sustain release of a therapeutically effective amount of the steroid from the implant for a time greater than about two months from a time in which the implant is placed in an ocular site or region of an eye.

2. The implant of claim 1, wherein the steroid is a corticosteroid.

3. The implant of claim 1, wherein the steroid is selected from the group consisting of a fluocinolone, a triamcinolone, and a mixture thereof.

4. The implant of claim 1, further comprising an ophthalmically acceptable therapeutic agent in addition to the steroid.

5. The implant of claim 1, wherein the steroid is dispersed within the biodegradable polymer matrix.

6. The implant of claim 1, wherein the matrix comprises a mixture of a first biodegradable polymer having terminal acid groups, and a second biodegradable polymer having terminal acid groups.

7. The implant of claim 6, wherein the first biodegradable polymer is a poly (D,L-lactide-co-glycolide).

8. The implant of claim 7, wherein the second biodegradable polymer is a poly (D,L-lactide).

9. The implant of claim 1, wherein the matrix releases drug at a rate effective to sustain release of a therapeutically effective amount of the steroid from the implant for more than three months from the time the implant is placed in the vitreous of the eye.

10. The implant of claim 1, wherein the matrix releases drug at a rate effective to sustain release of a therapeutically effective amount of the steroid from the implant for more than four months from the time the implant is placed in the vitreous of the eye.

11. The implant of claim 1, wherein the steroid is fluocinolone, and the matrix releases drug at a rate effective to sustain release of a therapeutically effective amount of fluocinolone for about three months.

12. The implant of claim 1, wherein the steroid is triamcinolone, and the matrix releases drug at a rate effective to sustain release of a therapeutically effective amount of triamcinolone for more than three months.

13. The implant of claim 12, wherein the matrix releases drug at a rate effective to sustain release of triamcinolone for a about three months to about six months.

14. The implant of claim 1, wherein the matrix comprises a mixture of biodegradable polymers, at least one of the biodegradable polymers is a polylactide having a molecular weight less than 40 kD.

15. The implant of claim 14, wherein the polylactide has a molecular weight less than 20 kD.

16. The implant of claim 14, wherein the polylactide has a molecular weight of about 10 kD.

17. The implant of claim 14, wherein the polylactide is a poly (D,L-lactide).

18. The implant of claim 14, wherein the polylactide has terminal free acid groups.

19. The implant of claim 14, wherein the matrix comprises a mixture of poly(lactide-co-glycolide) and polylactide.

20. The implant of claim 19, wherein the poly(lactide-co-glycolide) and the polylactide each have terminal free acid groups.

21. The implant of claim 1, wherein the matrix comprises a first biodegradable polymer having terminal free acid groups, and a different second biodegradable polymer having terminal free acid groups.

22. The implant of claim 21, wherein the first biodegradable polymer is a poly(lactide-co-glycolide).

23. The implant of claim 22, wherein the second biodegradable polymer is a polylactic acid.

24. The implant of claim 1, wherein the matrix comprises a mixture of different biodegradable polymers, each biodegradable polymer having an inherent viscosity of in a range of about 0.16 dl/g to about 0.24 dl/g.

25. The implant of claim 24, wherein each of the biodegradable polymers has an inherent viscosity of about 0.2 dl/g.

26. The implant of claim 1 which is formed by an extrusion process.

35. A method of treating an ocular condition of a patient, comprising the step of placing the implant of claim 1 in an eye of the patient to provide a therapeutically effective amount of the steroid to the patient for at least about two months.

36. The method of claim 35, wherein the ocular condition is an inflammation of the eye.

37. The method of claim 35, wherein the implant is placed in the posterior of the eye.

38. The method of claim 35, wherein the implant is placed in the eye with a trocar.

39. The method of claim 35, wherein the implant is placed in the eye with a syringe.

40. The method of claim 35, further comprising a step of administering a therapeutic agent in addition to the steroid to the patient.

27. A method of making a biodegradable intraocular implant, comprising the step of:

extruding a mixture of a steroid and a biodegradable polymer to form a biodegradable material that releases drug at a rate effective to sustain release of a therapeutically effective amount of the steroid from the implant for a time greater than about two months from a time in which the implant is placed in an ocular site or region of an eye.

28. The method of claim 27, wherein the steroid is a corticosteroid.

29. The method of claim 27, wherein the steroid is a fluocinolone or a triamcinolone.

30. The method of claim 27, further comprising a step of mixing the steroid with the polymer before the extrusion step.

31. The method of claim 27, wherein the steroid and the polymer are in a powder form.

32. The method of claim 27, wherein the polymer comprises a mixture of biodegradable polymers, at least one of the biodegradable polymers is a polylactide having a molecular weight less than 40 kD.

33. The method of claim 27, wherein the polymer comprises a first biodegradable polymer having terminal free acid groups, and a different second biodegradable polymer having terminal free acid groups.

34. The method of claim 27, wherein the polymer comprises a mixture of different biodegradable polymers, each biodegradable polymer having an inherent viscosity of in a range of about 0.16 dl/g to about 0.24 dl/g.

41. An intraocular implant, comprising:

a polymeric layer covering a core containing a steroid, the polymeric layer including a plurality of holes sized to permit a liquid to pass therethrough, and to permit the steroid to pass from the implant to an external environment at a rate of less than 2 μ

g/day for a period of time at least about 2 months after the implant is placed in an eye of a patient.

42. The implant of claim 41, wherein the polymeric outer layer comprises polytetrafluoroethylene, polyfluorinated ethylenepropylene, polylactic acid, polyglycolic acid, silicone, or a mixture thereof.

43. The implant of claim 41, wherein the polymeric outer layer is biodegradable.

44. The implant of claim 41, wherein the implant has less than four holes.

45. The implant of claim 41, wherein each of the holes has a diameter from about 250 μ

m to about 500 μ

m.

46. The implant of claim 41, wherein the steroid is a corticosteroid.

47. The implant of claim 41, wherein the steroid is a fluocinolone, a triamcinolone, or a mixture thereof.

48. The implant of claim 41, wherein the holes are configured to release about 0.5 μ

g/day of the steroid from the implant.

49. The implant of claim 41, wherein the holes are configured to release the steroid from the implant for about one year.

50. The implant of claim 41, further comprising another therapeutic agent in addition to the steroid.

51. A method of treating an ocular condition of a patient, comprising the step of placing the implant of claim 41 in an eye of the patient to provide a therapeutically effective amount of the steroid to the patient for at least about two months.

52. The method of claim 51, wherein the ocular condition is an inflammation of the eye.

53. The method of claim 51, wherein the implant is placed in the posterior of the eye.

54. The method of claim 51, wherein the implant is placed in the eye with a trocar.

55. The method of claim 51, wherein the implant is placed in the eye with a syringe.

56. The method of claim 51, further comprising a step of administering a therapeutic agent in addition to the steroid to the patient.

57. A method of making an intraocular implant, comprising the steps of:

forming a polymeric coating over a core comprising a steroid; and

forming a plurality of holes in the coating, the holes being sized to permit a liquid to pass therethrough, and to permit the steroid to pass from the implant to an external environment at a rate of less than 2 μ

g/day for a period of time at least about 2 months after the implant is placed in an eye of a patient.

58. The method of claim 57, wherein the holes are formed to permit the steroid to pass from the implant at a rate of about 0.5 μ

g/day.