Controlled release bioactive agent delivery device

• US 8,021,680 B2
• Filed: 04/29/2004
• Issued: 09/20/2011
• Est. Priority Date: 05/02/2003
• Status: Expired due to Fees

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Shen, Byron C., de Juan, Eugene, Chappa, Ralph A., Varner, Signe E., Anderson, Aron B., Lawin, Laurie R.
• Primary Examiner(s): Desai; Anand
• Assistant Examiner(s): Mercier; Melissa S
• Application Number:
  US10/835,530
• Publication Number:
  US 20050019371A1
• Time in Patent Office: 2,700 Days
• Field of Search: None
• US Class Current: 424/428
• CPC Class Codes: A61F 2310/00353 Bone cement, e.g. polymethylmethacrylate or PMMA
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

The invention provides a controlled release bioactive agent delivery device that includes a body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension, and a polymeric coated composition in contact with the body member, the polymeric coated composition including a first polymer, a second polymer, and a bioactive agent, wherein the first polymer comprises polyalkyl(meth)acrylate, aromatic poly(meth)acrylate, or a combination of polyalkyl(meth)acrylate and aromatic poly(meth)acrylate, and wherein the second polymer comprises poly(ethylene-co-vinyl acetate). The invention also provides methods of delivering a bioactive agent to a patient in a controlled release manner, as well as methods of making a controlled release bioactive agent delivery device.

Claims

1. An ocular controlled release bioactive agent delivery device comprising:

a. a coil-shaped body member formed of a material that has a cross-section of 1 mm or less and does not include a lumen, the body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension;

b. a polymeric coated composition in contact with at least a portion of the body member, the polymeric coated composition comprising a first polymer, a second polymer, and a bioactive agent,

wherein the first polymer comprises polyalkyl(meth)acrylate, and

wherein the second polymer comprises poly(ethylene-co-vinyl acetate); and

c. a cap positioned at the proximal end of the body member,

wherein the body member has a length from its proximal end to its distal end of 1 cm or less, and the cap has a thickness that is 10% or less of the length of the body member, and

wherein the bioactive agent is present in an amount in the range of 1 μ

g to 10 mg of bioactive agent per cm² of the coated surface of the device.

2. The device according to claim 1 wherein the polymeric coated composition is in contact with a portion of the body member that does not include the distal end.

3. The device according to claim 1 wherein the polymeric coated composition has a thickness, and wherein the thickness decreases towards the distal end of the body member.

4. The device according to claim 1 wherein the body member is spiral.

5. The device according to claim 1 wherein the body member includes surface configurations.

6. The device according to claim 1 wherein the cap has a thickness of 0.5 mm or less.

7. The device according to claim 1 wherein the first polymer comprises polyalkyl(meth)acrylate selected from the group consisting of polyalkyl(meth)acrylates having alkyl chain lengths in the range of 2 to 8 carbons.

8. The device according to claim 7 wherein the first polymer comprises poly(n-butyl)methacrylate.

9. The device according to claim 1 wherein the poly(ethylene-co-vinyl acetate) has a vinyl acetate concentration in the range of 10% to 90% by weight.

10. The device according to claim 1 further comprising a surface pretreatment.

11. The device according to claim 10 wherein the surface pretreatment is a compound selected from the group consisting of silane, polyurethane, parylene, or a combination thereof.

12. The device according to claim 1 wherein the polymeric coated composition is formulated to release bioactive agent in a therapeutically effective amount for a period of 6 months or more when the device is implanted in a patient'"'"'s eye.

13. The device according to claim 1 wherein the distal end of the body member is spaced from the longitudinal axis.

82. The device according to claim 1 wherein the bioactive agent is present within the polymeric coated composition in an amount in the range of 100 μ

g to 1500 μ

g.

14. An ocular controlled release bioactive agent delivery device comprising:

a. a coil-shaped body member formed of a material that has a cross-section of 1 mm or less, the body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension;

b. a polymeric coated composition in contact with an external surface of the body member, the polymeric coated composition comprising a first polymer, a second polymer, and a bioactive agent,

wherein the first polymer comprises polyalkyl(meth)acrylate, and

wherein the second polymer comprises poly(ethylene-co-vinyl acetate); and

c. a cap positioned at the proximal end of the body member,

wherein the body member has a length from its proximal end to its distal end of 1 cm or less, and the cap has a thickness that is 10% or less of the length of the body member, and

wherein the bioactive agent is present in an amount in the range of 1 μ

g to 10 mg of bioactive agent per cm² of the coated surface of the device.

15. The device according to claim 14 wherein the external surface of the body member in contact with the polymeric coated composition does not include the distal end of the body member.

16. The device according to claim 14 wherein the polymeric coated composition has a thickness, and wherein the thickness decreases towards the distal end of the body member.

17. The device according to claim 14 wherein the body member is spiral.

18. The device according to claim 14 wherein the body member includes surface configurations.

19. The device according to claim 14 wherein at least a portion of the body member includes a lumen configured to serve as a delivery mechanism for delivery of a bioactive agent to an implantation site upon implantation of the device in a patient'"'"'s eye.

20. The device according to claim 19 wherein the body member includes one or more apertures.

21. The device according to claim 19 wherein the bioactive agent to be delivered by the lumen is different from the bioactive agent included in the coating composition.

22. The device according to claim 19 wherein the body member is formed of a material that is permeable or semi-permeable to the bioactive agent to be delivered to a patient'"'"'s eye from the lumen.

23. The device according to claim 14 wherein the cap has a thickness of 0.5 mm or less.

24. The device according to claim 14 wherein the first polymer comprises polyalkyl(meth)acrylate selected from the group consisting of polyalkyl(meth)acrylates having alkyl chain lengths in the range of 2 to 8 carbons.

25. The device according to claim 24 wherein the first polymer comprises poly(n-butyl)methacrylate.

26. The device according to claim 14 wherein the poly(ethylene-co-vinyl acetate) has a vinyl acetate concentration in the range of 10% to 90% by weight.

27. The device according to claim 14 further comprising a surface pretreatment.

28. The device according to claim 27 wherein the surface pretreatment is a compound selected from the group consisting of silane, polyurethane, parylene, or a combination thereof.

29. The device according to claim 14 wherein the polymeric coated composition is formulated to release bioactive agent in a therapeutically effective amount for a period of 6 months or more when the device is implanted in a patient'"'"'s eye.

30. The device according to claim 14 wherein the distal end of the body member is spaced from the longitudinal axis.

83. The device according to claim 14 wherein the bioactive agent is present within the polymeric coated composition in an amount in the range of 100 μ

g to 1500 μ

g.

31. An ocular controlled release bioactive agent delivery device comprising:

a. a coil-shaped body member formed of a material having a cross-section of 1 mm or less, the body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension;

b. a polymeric coated composition in contact with the body member, the polymeric coated composition comprising;

(i) a first polymer selected from polyalkyl(meth)acrylate,

(ii) a second polymer comprising poly(ethylene-co-vinyl acetate), and

(iii) a bioactive agent selected from triamcinolone acetonide, 13-cis retinoic acid, 5-fluorouridine, and combinations thereof; and

c. a cap positioned at the proximal end of the body member,

wherein the body member has a length from its proximal end to its distal end of 1 cm or less, and the cap has a thickness that is 10% or less of the length of the body member,

wherein the polymeric coated composition is formulated to release bioactive agent in a therapeutically effective amount for a period of 6 months or more when the device is implanted in a patient'"'"'s eye, and

wherein the bioactive agent is present in an amount in the range of 1 μ

g to 10 mg of bioactive agent per cm² of the coated surface of the device.

32. The device according to claim 31 wherein the polymeric coated composition is in contact with a portion of the body member that does not include the distal end.

33. The device according to claim 31 wherein the polymeric coated composition has a thickness, and wherein the thickness decreases towards the distal end of the body member.

34. The device according to claim 31 wherein the body member is spiral.

35. The device according to claim 31 wherein the body member includes surface configurations.

36. The device according to claim 31 wherein at least a portion of the body member includes a lumen configured to serve as a delivery mechanism for delivery of a bioactive agent to an implantation site upon implantation of the device in a patient'"'"'s eye.

37. The device according to claim 36 wherein the body member includes one or more apertures.

38. The device according to claim 36 wherein the bioactive agent to be delivered by the lumen is different from the bioactive agent included in the coating composition.

39. The device according to claim 36 wherein the body member is formed of a material that is permeable or semi-permeable to the bioactive agent to be delivered to a patient'"'"'s eye from the lumen.

40. The device according to claim 31 wherein the cap has a thickness of 0.5 mm or less.

41. The device according to claim 31 wherein the first polymer comprises polyalkyl(meth)acrylate selected from the group consisting of polyalkyl(meth)acrylates having alkyl chain lengths in the range of 2 to 8 carbons.

42. The device according to claim 41 wherein the first polymer comprises poly(n-butyl)methacrylate.

43. The device according to claim 31 wherein the poly(ethylene-co-vinyl acetate) has a vinyl acetate concentration in the range of 10% to 90% by weight.

44. The device according to claim 31 wherein the distal end of the body member is spaced from the longitudinal axis.

45. The device according to claim 31 further comprising a surface pretreatment.

46. The device according to claim 45 wherein the surface pretreatment is a compound selected from the group consisting of silane, polyurethane, parylene, or a combination thereof.

84. The device according to claim 31 wherein the bioactive agent is present within the polymeric coated composition in an amount in the range of 100 μ

g to 1500 μ

g.

47. An ocular controlled release bioactive agent delivery device comprising:

a. a coil-shaped body member formed of a material having a cross-section of 1 mm or less, the body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension;

b. a polymeric coated composition in contact with the body member, the polymeric coated composition comprising a first polymer, a second polymer, and a bioactive agent; and

c. a cap positioned at the proximal end of the body member,

wherein the body member has a length from its proximal end to its distal end of 1 cm or less, and the cap has a thickness that is 10% or less of the length of the body member,

wherein the first polymer comprises polyalkyl(meth)acrylate,

wherein the second polymer comprises poly(ethylene-co-vinyl acetate),

wherein the bioactive agent is present in an amount in the range of 1 μ

g to 10 mg of bioactive agent per cm² of the coated surface of the device, and

wherein the polymeric coated composition is formulated to release bioactive agent in a therapeutically effective amount for a period of 6 months or more when the device is implanted in a patient'"'"'s eye.

48. The device according to claim 47 wherein the polymeric coated composition is in contact with a portion of the body member that does not include the distal end.

49. The device according to claim 47 wherein the polymeric coated composition has a thickness, and wherein the thickness decreases towards the distal end of the body member.

50. The device according to claim 47 wherein the body member is spiral.

51. The device according to claim 47 wherein the body member includes surface configurations.

52. The device according to claim 47 wherein at least a portion of the body member includes a lumen configured to serve as a delivery mechanism for delivery of a bioactive agent to an implantation site upon implantation of the device in a patient'"'"'s eye.

53. The device according to claim 47 wherein the body member includes one or more apertures.

54. The device according to claim 52 wherein the bioactive agent to be delivered by the lumen is different from the bioactive agent included in the coating composition.

55. The device according to claim 47 wherein the body member is formed of a material that is permeable or semi-permeable to the bioactive agent to be delivered to a patient'"'"'s eye from the lumen.

56. The device according to claim 47 wherein the cap has a thickness of 0.5 mm or less.

57. The device according to claim 47 wherein the first polymer comprises polyalkyl(meth)acrylate selected from the group consisting of polyalkyl(meth)acrylates having alkyl chain lengths in the range of 2 to 8 carbons.

58. The device according to claim 57 wherein the first polymer comprises poly(n-butyl)methacrylate.

59. The device according to claim 47 wherein the poly(ethylene-co-vinyl acetate) has a vinyl acetate concentration in the range of 10% to 90% by weight.

60. The device according to claim 47 further comprising a surface pretreatment.

61. The device according to claim 60 wherein the surface pretreatment is selected from the group consisting of silane, polyurethane, parylene, or combinations of any one or more of these.

62. The device according to claim 47 wherein the distal end of the body member is spaced from the longitudinal axis.

85. The device according to claim 47 wherein the bioactive agent is present within the polymeric coated composition in an amount in the range of 100 μ

g to 1500 μ

g.

63. An ocular controlled release bioactive agent delivery device comprising:

a. a coil-shaped body member formed of a material having a cross-section of 1 mm or less, the body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end, wherein at least a portion of the body member deviates from the direction of extension;

b. a polymeric coated composition in contact with the body member, the polymeric coated composition comprising a first polymer, a second polymer, and triamcinolone acetonide; and

c. a cap positioned at the proximal end of the body member,

wherein the body member has a length from its proximal end to its distal end of 1 cm or less, and the cap has a thickness that is 10% or less of the length of the body member,

wherein the first polymer comprises polyalkyl(meth)acrylate,

wherein the second polymer comprises poly(ethylene-co-vinyl acetate),

wherein the polymeric coated composition is formulated to release a therapeutically effective amount of the triamcinolone acetonide when the device is implanted in a patient'"'"'s eye for a period of 6 months or more, and

wherein the bioactive agent is present in an amount in the range of 1 μ

g to 10 mg of bioactive agent per cm² of the coated surface of the device.

64. The device according to claim 63 wherein the polymeric coated composition is in contact with a portion of the body member that does not include the distal end.

65. The device according to claim 63 wherein the polymeric coated composition has a thickness, and wherein the thickness decreases towards the distal end of the body member.

66. The device according to claim 63 wherein the body member is spiral.

67. The device according to claim 63 wherein the body member includes surface configurations.

68. The device according to claim 63 wherein at least a portion of the body member includes a lumen configured to serve as a delivery mechanism for delivery of a bioactive agent to an implantation site upon implantation of the device in a patient'"'"'s eye.

69. The device according to claim 68 wherein the body member includes one or more apertures.

70. The device according to claim 68 wherein the bioactive agent to be delivered by the lumen is different from the bioactive agent included in the coating composition.

71. The device according to claim 68 wherein the body member is formed of a material that is permeable or semi-permeable to the bioactive agent to be delivered to a patient'"'"'s eye from the lumen.

72. The device according to claim 63 wherein the cap has a thickness of 0.5 mm or less.

73. The device according to claim 63 wherein the first polymer comprises polyalkyl(meth)acrylate selected from the group consisting of polyalkyl(meth)acrylates having alkyl chain lengths in the range of 2 to 8 carbons.

74. The device according to claim 73 wherein the first polymer comprises poly(n-butyl)methacrylate.

75. The device according to claim 63 wherein the poly(ethylene-co-vinyl acetate) has a vinyl acetate concentration in the range of 10% to 90% by weight.

76. The device according to claim 63 further comprising a surface pretreatment.

77. The device according to claim 76 wherein the surface pretreatment is a compound selected from the group consisting of silane, polyurethane, parylene, or a combination thereof.

78. The device according to claim 63 wherein the distal end of the body member is spaced from the longitudinal axis.

79. The device according to claim 63 wherein the polymeric coated composition is formulated to release the triamcinolone acetonide at an average release rate in the range of 0.5 μ

g/day to 2 μ

g per day.

80. The device according to claim 63 wherein the polymeric coated composition is formulated to release the triamcinolone acetonide at an average release rate in the range of 0.5 μ

g/day to 4.2 μ

g/day in vitro.

81. The device according to claim 63 wherein the polymeric coated composition is formulated to release triamcinolone acetonide in an amount in the range of 12.4% to 28.7% of total triamcinolone acetonide present in the composition, within 29 days after implantation in the patient'"'"'s eye.

86. The device according to claim 63 wherein the triamcinolone acetonide is present within the polymeric coated composition in an amount in the range of 100 μ

g to 1500 μ

g.