Controlled release bioactive agent delivery device

• US 20050019371A1
• Filed: 04/29/2004
• Published: 01/27/2005
• Est. Priority Date: 05/02/2003
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Juan, Eugene de, Varner, Signe E., Anderson, Aron B., Lawin, Laurie R., Shen, Byron C.
• Granted Patent: US 8,021,680 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• 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. A controlled release bioactive agent delivery device comprising:

a. 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

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,

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).

2. The device according to claim 1 wherein the body member is coil-shaped.

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

4. The device according to claim 1 wherein the body member is fabricated from twisted wire.

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

6. The device according to claim 5 wherein the body member has a roughened surface.

7. The device according to claim 1 wherein the body member is a threaded shaft.

8. The device according to claim 1 wherein a cap is positioned at the proximal end of the body member.

9. The device according to claim 1 wherein the body member includes a lumen.

10. The device according to claim 9 wherein the polymeric coated composition is provided entirely within the lumen of the body member.

11. The device according to claim 10 wherein a second polymeric coated composition is provided in contact with an external surface of the body member.

12. The device according to claim 11 wherein the second polymeric coated composition comprises a bioactive agent.

13. The device according to claim 12 wherein the bioactive agent of the second polymeric coated composition is different from the bioactive agent of the polymeric coated composition within the lumen.

14. The device according to claim 12 wherein the bioactive agent of the second polymeric coated composition is the same as the bioactive agent of the polymeric coated composition within the lumen.

15. The device according to claim 9 wherein the lumen includes a substance, and wherein the polymeric coated composition is in contact with an external surface of the body member.

16. The device according to claim 15 wherein the substance is the same as the bioactive agent of the polymeric coated composition.

17. The device according to claim 15 wherein the substance is different from the bioactive agent of the polymeric coated composition.

18. 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.

19. The device according to claim 18 wherein the first polymer comprises poly(n-butyl)methacrylate.

20. The device according to claim 1 wherein the first polymer comprises aromatic poly(meth)acrylate selected from the group consisting of polyaryl(meth)acrylate, polyaralkyl(meth)acrylate, and polyaryloxyalkyl(meth)acrylate.

21. The device according to claim 20 wherein the aromatic poly(meth)acrylate comprises aryl groups having from 6 to 16 carbon atoms.

22. 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.

23. The device according to claim 1 wherein the polymeric coated composition comprises two or more layers on the body member.

24. The device according to claim 1 or claim 23 further comprising a surface pretreatment.

25. The device according to claim 24 wherein the surface pretreatment is selected from the group consisting of silane, polyurethane, parylene, or combinations thereof.

26. The device according to claim 1 wherein the bioactive agent is selected from the group consisting of triamcinolone acetonide, 13-cis retinoic acid, 5-fluorouridine, and combinations thereof.

27. The device according to claim 1 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 effective surface area of the device.

28. The device according to claim 1 wherein the bioactive agent is present in an amount of 75% by weight or less of the polymeric coated composition.

29. The device according to claim 1 wherein the bioactive agent is released in a therapeutically effective amount when implanted in a patient.

30. The device according to claim 1 wherein the bioactive agent is released in a therapeutically effective amount for a period of 6 months or more when implanted in a patient.

31. The device according to claim 26 wherein the bioactive agent is triamcinolone acetonide, and the triamcinolone acetonide has a release rate in the range of 0.5 μ

g/day to 2 μ

g/day when implanted in an eye.

32. The device according to claim 1 wherein the bioactive agent is present in an amount in the range of 1 μ

g to 5 mg in the polymeric coated composition.

33. The device according to claim 1 wherein the polymeric coated composition has a final coating thickness in the range of 0.1 μ

m to 100 μ

m when provided on an external surface of the body member.

34. The device according to claim 1 wherein the distal end of the body member is positioned at the longitudinal axis.

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

36. The device according to claim 1 wherein the proximal end of the body member is positioned at the longitudinal axis.

37. The device according to claim 1 wherein the polymeric coated composition is provided with a stepped configuration towards the distal end of the body member.

38. The device according to claim 37 wherein the stepped configuration comprises a tapered configuration towards the distal end of the body member.

39. A method of delivering a bioactive agent to a patient comprising:

a. providing a controlled release bioactive agent delivery device according to any one of claims 1 through 38,

b. inserting the device into a patient'"'"'s body, and

c. removing the device from the patient'"'"'s body once a therapeutically effective amount of bioactive agent has been delivered to the patient.

40. The method according to claim 39 wherein the step of inserting the device into a patient'"'"'s body comprises inserting the device into an eye of the patient.

41. A method of making a controlled release bioactive agent delivery device comprising:

a. providing 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

b. providing a polymeric coating composition comprising a first polymer, a second polymer, and a bioactive agent in contact with the body member, 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).

42. The method according to claim 41 wherein the step of providing a polymeric coating composition in contact with the body member comprises providing the polymeric coating composition on an external surface of the body member.

43. The method according to claim 41 wherein the body member includes a lumen, and wherein the step of providing a polymeric coating composition in contact with the body member comprises providing the polymeric coating composition in the lumen.

44. The method according to any one of claims 41-43 wherein the step of providing a polymeric coating composition in contact with the body member comprises providing the polymeric coating under controlled humidity conditions.