Biodegradable medical implant with encapsulated buffering agent

• US 7,785,615 B2
• Filed: 05/28/2004
• Issued: 08/31/2010
• Est. Priority Date: 05/28/2004
• Status: Active Grant

• Current Assignee: Cardinal Health Switzerland 515 GmbH (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Landau, George, Patel, Premal, Dave, Vipul Bhupendra
• Primary Examiner(s): Silverman; Eric E.
• Application Number:
  US10/856,462
• Publication Number:
  US 20050267565A1
• Time in Patent Office: 2,286 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61L 27/446 with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 31/128 containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
• CPC Class Codes: A61L 31/129 containing macromolecular fillers

Abstract

A medical device for placement at a site in a patient'"'"'s body and for controlling pH levels at the site in the patient'"'"'s body includes one or more structural components made of a first biodegradable and/or bioabsorbable material or, alternatively, one or more structural components having a coating thereon made of a first biodegradable and/or bioabsorbable material. The device also includes a buffering agent and at least one second biodegradable and/or bioabsorbable material on or in the one or more structural components, or alternatively, on or in the coating on the one or more structural components. The at least one second biodegradable and/or bioabsorbable material encapsulates the buffering agent and the buffering agent is dispersed from the at least one second biodegradable and/or bioabsorbable material in response to hydrolysis of the first biodegradable and/or bioabsorbable material. Additionally, the device can include a drug that is either also encapsulated by the at least one second biodegradable and/or bioabsorbable material or is included with the first biodegradable and/or bioabsorbable material.

Claims

1. A medical device for placement at a site in a patient'"'"'s body and for maintaining pH levels at the site in the patient'"'"'s body at neutral pH, the device comprising:

one or more structural components made of a first biodegradable and/or bioabsorbable material which is a polymer of poly (alpha-hydroxy acid);

a buffering agent; and

at least one second biodegradable and/or bioabsorbable material encapsulating the buffering agent on or in the one or more structural components, said buffering agent being encapsulated by the second biodegradable and/or bioabsorbable material, the buffering agent being released from the second biodegradable and/or bioabsorbable material as the second biodegradable and/or bioabsorbable material degrades, in response to a reduction in the pH level at the site in the patient'"'"'s body resulting from the hydrolysis of the first biodegradable and/or bioabsorbable material,

wherein the device is configured so that upon exposure to an acidic environment, an amount of the second biodegradable and/or bioabsorbable material degrades and releases the encapsulated buffering agent in an amount that provides a stoichiometric balance between the amount of buffering agent released and the total amount of acid released from the device, such that the pH level is raised to a neutral pH level.

2. The medical device according to claim 1, wherein the at least one second biodegradable and/or bioabsorbable material is a surface erodible polymer.

3. The medical device according to claim 1, wherein the at least one second biodegradable and/or bioabsorbable material is a bulk erodible polymer.

4. The medical device according to claim 1, wherein the polymer of poly (alpha hydroxy acid) is aliphatic.

5. The medical device according to claim 4, wherein the aliphatic polymer is selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly (caprolactone), poly (p-dioxanone) and poly (trimethylene carbonate).

6. The medical device according to claim 1, wherein the at least one second biodegradable and/or bioabsorbable material is a either a homo polymer, a copolymer or a blend of polymers.

7. The medical device according to claim 6, wherein the at least one second biodegradable and/or bioabsorbable material is a polymer selected from the group consisting of polysaccharides, poly(orthoesters), proteins, water soluble polymers and PEG based copolymers.

8. The medical device according to claim 7, wherein the at least one second absorbable material is in the form of a microparticle.

9. The medical device according to claim 7, wherein the at least one second biodegradable and/or bioabsorbable material is in the form of a nanoparticle.

10. The medical device according to claim 1, further comprising a drug encapsulated by the at least one second biodegradable and/or bioabsorbable material.

11. The medical device according to claim 1, further comprising a drug with the first biodegradable and/or bioabsorbable material.

12. The medical device according to claim 1, wherein the buffering agent is selected from the group consisting of calcium hydroxyapatite, carbonated apatite, tricalcium phosphate, calcium carbonate, sodium bicarbonate, calcium phosphate;

carbonated calcium phosphates, magnesium hydroxide, amine monomers, and lactate dehydrogenase.

13. The medical device according to claim 1, wherein the buffering agent is released from the at least one second biodegradable and/or bioabsorbable material at pH <

7.4.

14. The medical device according to claim 13, wherein the buffering agent is released from the at least one second biodegradable and/or bioabsorbable material at pH ranging from about 3 to about 6.

15. The medical device according to claim 14, wherein the buffering agent is released from the at least one second biodegradable and/or bioabsorbable material at pH of about 5.

16. The medical device according to claim 13, wherein the buffering agent raises pH at the site after being released from the at least one second biodegradable and/or bioabsorbable material.

17. The medical device according to claim 16, wherein the buffering agent raises pH to about 7.4 at the site after being released from the at least one second biodegradable and/or bioabsorbable material.

18. The medical device according to claim 1, wherein the device is a stent.

19. The medical device according to claim 1, wherein the device is a valve.

20. The medical device according to claim 1, wherein the device is selected from the group consisting of clamps, screws, plates, clips, staples, hooks, buttons, snaps, prosthetics, grafts, injectable polymers, vertebrae discs, anchoring devices, suture anchors, septal occlusion devices, injectable defect fillers, preformed defect fillers, bone waxes, cartilage replacements, spinal fixation devices, drug delivery devices and foams.

41. The medical device according to claim 1, wherein a spray drying process is used to encapsulate the buffering agent within the at least one second biodegradable and/or bioabsorbable material.

42. The medical device according to claim 1, wherein a coacervation process is used to encapsulate the buffering agent within the at least one second biodegradable and/or bioabsorbable material.

21. A medical device for placement at a site in a patient'"'"'s body and for maintaining pH levels at the site in the patient'"'"'s body at neutral pH, the device comprising;

one or more structural components having a coating thereon, the coating made of a first biodegradable and/or bioabsorbable material which is a polymer of poly (alpha-hydroxy acid);

a buffering agent; and

at least one second biodegradable and/or bioabsorbable material encapsulating the buffering agent on or in the one or more structural components, said buffering agent being encapsulated by the second biodegradable and/or bioabsorbable material, the buffering agent being released from the second biodegradable and/or bioabsorbable material as the second biodegradable and/or bioabsorbable material degrades, in response to a reduction in the pH level at the site in the patient'"'"'s body resulting from the hydrolysis of the first biodegradable and/or bioabsorbable material,

wherein the device is configured so that upon exposure to an acidic medium an amount of the second biodegradable and/or bioabsorbable material degrades and releases the encapsulated buffering agent in an amount that provides a stoichiometric balance between the amount of buffering agent released and the total amount of acid released from the device, such that the pH level is raised to a neutral pH level.

22. The medical device according to claim 21, wherein the at least one second biodegradable and/or bioabsorbable material is a surface erodible polymer.

23. The medical device according to claim 21, wherein the at least one second biodegradable and/or bioabsorbable material is a bulk erodible polymer.

24. The medical device according to claim 21, wherein the polymer of a poly (alpha hydroxy acid) is aliphatic.

25. The medical device according to claim 24, wherein the aliphatic polymer is selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly(caprolactone), poly(p-dioxanone) and poly(trimethylene carbonate).

26. The medical device according to claim 21, wherein the at least one second biodegradable and/or bioabsorbable material is a either a homopolymer, a copolymer or a blend of polymers.

27. The medical device according to claim 26, wherein the at least one second biodegradable and/or bioabsorbable material is a polymer selected from the group consisting of polysaccharides, poly(orthoesters), proteins, water soluble polymers and PEG based copolymers.

28. The medical device according to claim 27, wherein the at least one second biodegradable and/or bioabsorbable material is in the form of a microparticle.

29. The medical device according to claim 27, wherein the at least one second biodegradable and/or bioabsorbable material is in the form of a nanoparticle.

30. The medical device according to claim 21, further comprising a drug encapsulated by the at least one second biodegradable and/or bioabsorbable material.

31. The medical device according to claim 21, further comprising a drug with the first biodegradable and/or bioabsorbable material.

32. The medical device according to claim 21, wherein the buffering agent is selected from the group consisting of calcium hydroxyapatite, carbonated apatite, tricalcium phosphate, calcium carbonate, sodium bicarbonate, calcium phosphates, carbonated calcium phosphates, magnesium hydroxide, amine monomers, and lactate dehydrogenase.

33. The medical device according to claim 21, wherein the buffering agent is released from the at least one second biodegradable and/or bioabsorbable material at pH <

7.4.

34. The medical device according to claim 33, wherein the buffering agent is released from the at least one second biodegradable and/or bioabsorbable material at pH ranging from about 3 to about 6.

35. The medical device according to claim 34, wherein the buffering agent is released from the at least one second biodegradable and/or bioabsorbable material at pH of about 5.

36. The medical device according to claim 33, wherein the buffering agent raises pH at the site after being released from the at least one second biodegradable and/or bioabsorbable material.

37. The medical device according to claim 36, wherein the buffering agent raises pH to about 7.4 at the site after being released from the at least one second biodegradable and/or bioabsorbable material.

38. The medical device according to claim 21, wherein the device is a stent.

39. The medical device according to claim 21, wherein the device is a valve.

40. The medical device according to claim 21, wherein the device is selected from the group consisting of clamps, screws, plates, clips, staples, hooks, buttons, snaps, prosthetics, grafts, injectable polymers, vertebrae discs, anchoring devices, suture anchors, septal occlusion devices, injectable defect fillers, preformed defect fillers, bone waxes, cartilage replacements, spinal fixation devices, drug delivery devices and foams.

43. The medical device according to claim 21, wherein a spray drying process is used to encapsulate the buffering agent within the at least one second biodegradable and/or bioabsorbable material.

44. The medical device according to claim 21, wherein a coacervation process is used to encapsulate the buffering agent within the at least one second biodegradable and/or bioabsorbable material.