Biointerface membranes incorporating bioactive agents

• US 20060204536A1
• Filed: 05/03/2006
• Published: 09/14/2006
• Est. Priority Date: 05/21/2003
• Status: Abandoned Application

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Brauker, James H., Tapsak, Mark, Carr-Brendel, Victoria, Markovic, Dubravka, Shults, Mark
• Application Number:
  US11/416,734
• Publication Number:
  US 20060204536A1
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2400/08 Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: G01N 33/48707 by electrical means G01N33/49, G01N33/493 take precedence

Abstract

A biointerface membrane for an implantable device including a nonresorbable solid portion with a plurality of interconnected cavities therein adapted to support tissue ingrowth in vivo, and a bioactive agent incorporated into the biointerface membrane and adapted to modify the tissue response is provided. The bioactive agents can be chosen to induce vascularization and/or prevent barrier cell layer formation in vivo, and are advantageous when used with implantable devices wherein solutes are transported across the device-tissue interface.

Claims

1. An implantable device, the device comprising a sensing region for sensing an analyte and a biointerface membrane adjacent to the sensing region, wherein the membrane is configured to modify an in vivo tissue response by a porous architecture and by incorporation of a bioactive agent in the membrane.

2. The implantable device of claim 1, wherein the biointerface membrane supports tissue ingrowth and interferes with barrier-cell layer formation, and wherein the biointerface membrane comprises cavities of from about 90 μ

m to about 370 μ

m in at least one dimension.

3. The implantable device of claim 1, wherein the biointerface membrane supports tissue ingrowth and interferes with barrier-cell layer formation, and wherein the biointerface membrane comprises cavities of from about 0.6 μ

m to about 20 μ

m in at least one dimension.

4. The implantable device of claim 1, wherein the biointerface membrane supports tissue ingrowth and interferes with barrier-cell layer formation, and wherein the biointerface membrane comprises cavities, wherein the biointerface membrane comprises a micro-architecture situated within at least some of the cavities of a macro-architecture, wherein the macro-architecture comprises a frame comprising a plurality of elongated strands of a material, wherein the strands are less than about 6 μ

m in all but the longest dimension.

5. The implantable device of claim 1, wherein the biointerface membrane comprises a material selected from the group consisting of silicone, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene, polyvinyl alcohol, polyvinylchloride, polyvinylidene fluoride, polybutylene terephthalate, polymethylmethacrylate, polyether ether ketone, polyurethanes, cellulosic polymers, polysulfones, block copolymers thereof, and mixtures thereof.

6. The implantable device of claim 1, wherein the biointerface membrane comprises silicone.

7. The implantable device of claim 1, wherein the bioactive agent is selected from the group consisting of anti-inflammatory agents, anti-infective agents, anesthetics, inflammatory agents, growth factors, angiogenic factors, growth factors, immunosuppressive agents, antiplatelet agents, anticoagulants, ACE inhibitors, cytotoxic agents, anti-sense molecules, and mixtures thereof.

8. The implantable device of claim 1, wherein the bioactive agent is selected from the group consisting of Sphingosine-1-phosphate, monobutyrin, Cyclosporin A, Anti-thrombospondin-2, Rapamycin, Dexamethasone, and mixtures thereof.

9. The implantable device of claim 1, wherein the bioactive agent comprises an anti-barrier cell agent that employs a mechanism configured to speed up a host infiltration of the porous architecture by inhibiting at least one of foreign body giant cells and occlusive cell layers.

10. The implantable device of claim 9, wherein the anti-barrier cell agent comprises Super Oxide Dismutase Mimetic.

11. The implantable device of claim 9, wherein the anti-barrier cell agent employs an anti-inflammatory mechanism or an immunosuppressive mechanism configured to modify a wound healing of a host tissue.

12. The implantable device of claim 9, wherein the anti-barrier cell agent is selected from the group consisting of cyclosporine, Dexamethasone, and Rapamycin.

13. The implantable device of claim 1, wherein the bioactive agent comprises a non-heparin based synthetic coating configured to improve a performance of a blood-contacting surface.

14. The implantable device of claim 1, wherein the bioactive agent comprises a vascularization agent.

15. The implantable device of claim 14, wherein the vascularization agent is selected from the group consisting of an angiogenic agent configured for stimulating a neovascularization, Sphingosine-1-Phosphate, Monobutyrin, an anti-sense molecule, Basic Fibroblast Growth Factor, Acidic Fibroblast Growth Factor, Vascular Endothelial Growth Factor, Platelet Derived Endothelial Cell Growth Factor BB, Angiopoietin-1, Transforming Growth Factor Beta, Transforming Growth Factor Alpha, Hepatocyte Growth Factor, Tumor Necrosis Factor-Alpha, Angiogenin, Interleukin-8, Hypoxia Inducible Factor-I, Angiotensin-Converting Enzyme Inhibitor Quinaprilat, Angiotropin, Thrombospondin, Peptide KGHK, Low Oxygen Tension, Lactic Acid, Insulin, Growth Hormone, and mixtures thereof.

16. The implantable device of claim 14, wherein the vascularization agent comprises a pro-inflammatory agent configured for promoting an inflammation response or an immune response.

17. The implantable device of claim 16, wherein the pro-inflammatory agent is selected from the group consisting of a xenogenic carrier, a Lipopolysaccharide, and a protein.

18. The implantable device of claim 1, wherein the bioactive agent is incorporated into the biointerface membrane via a carrier matrix.

19. The implantable device of claim 18, wherein the carrier matrix is selected from the group consisting of collagen, a particulate matrix, a non-resorbable matrix, resorbable matrix, a controlled-release matrix, a gel, and mixtures thereof.

20. The implantable device of claim 1, wherein the bioactive agent is cross-linked with a material that forms the biointerface membrane.

21. The implantable device of claim 1, wherein the bioactive agent is configured to be released for a time period of from about one day to about one year.

22. The implantable device of claim 1, wherein the bioactive agent is configured to be released for a time period of from about one week to about four weeks.

23. An implantable glucose device, the device comprising a nonresorbable biointerface membrane adapted to modify an in vivo tissue response, the membrane comprising a porous membrane architecture and having a bioactive agent incorporated therein.

24. The implantable device of claim 23, wherein the biointerface membrane supports tissue ingrowth and interferes with barrier-cell layer formation, and wherein the biointerface membrane comprises cavities of from about 90 μ

m to about 370 μ

m in at least one dimension.

25. The implantable device of claim 23, wherein the biointerface membrane supports tissue ingrowth and interferes with barrier-cell layer formation, and wherein the biointerface membrane comprises cavities of from about 0.6 μ

m to about 20 μ

m in at least one dimension.

26. The implantable device of claim 23, wherein the biointerface membrane supports tissue ingrowth and interferes with barrier-cell layer formation, and wherein the biointerface membrane comprises cavities, wherein the biointerface membrane comprises a micro-architecture situated within at least some of the cavities of a macro-architecture, wherein the macro-architecture comprises a frame comprising a plurality of elongated strands of a material, wherein the strands are less than about 6 μ

m in all but the longest dimension.

27. The implantable device of claim 23, wherein the biointerface membrane comprises a material selected from the group consisting of silicone, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene, polyvinyl alcohol, polyvinylchloride, polyvinylidene fluoride, polybutylene terephthalate, polymethylmethacrylate, polyether ether ketone, polyurethanes, cellulosic polymers, polysulfones, block copolymers thereof, and mixtures thereof.

28. The implantable device of claim 23, wherein the biointerface membrane comprises silicone.

29. The implantable device of claim 23, wherein the bioactive agent is selected from the group consisting of anti-inflammatory agents, anti-infective agents, anesthetics, inflammatory agents, growth factors, angiogenic factors, growth factors, immunosuppressive agents, antiplatelet agents, anticoagulants, ACE inhibitors, cytotoxic agents, anti-sense molecules, and mixtures thereof.

30. The implantable device of claim 23, wherein the bioactive agent is selected from the group consisting of Sphingosine-1-phosphate, monobutyrin, Cyclosporin A, Anti-thrombospondin-2, Rapamycin, Dexamethasone, and mixtures thereof.

31. The implantable device of claim 23, wherein the bioactive agent comprises an anti-barrier cell agent that employs a mechanism configured to speed up a host infiltration of the porous architecture by inhibiting at least one of foreign body giant cells and occlusive cell layers.

32. The implantable device of claim 31, wherein the anti-barrier cell agent comprises Super Oxide Dismutase Mimetic.

33. The implantable device of claim 31, wherein the anti-barrier cell agent employs an anti-inflammatory mechanism or an immunosuppressive mechanism configured to modify a wound healing of a host tissue.

34. The implantable device of claim 31, wherein the anti-barrier cell agent is selected from the group consisting of cyclosporine, Dexamethasone, and Rapamycin.

35. The implantable device of claim 23, wherein the bioactive agent comprises a non-heparin based synthetic coating configured to improve a performance of a blood-contacting surface.

36. The implantable device of claim 23, wherein the bioactive agent comprises a vascularization agent.

37. The implantable device of claim 36, wherein the vascularization agent is selected from the group consisting of an angiogenic agent configured for stimulating a neovascularization, Sphingosine-1-Phosphate, Monobutyrin, an anti-sense molecule, Basic Fibroblast Growth Factor, Acidic Fibroblast Growth Factor, Vascular Endothelial Growth Factor, Platelet Derived Endothelial Cell Growth Factor BB, Angiopoietin-1, Transforming Growth Factor Beta, Transforming Growth Factor Alpha, Hepatocyte Growth Factor, Tumor Necrosis Factor-Alpha, Angiogenin, Interleukin-8, Hypoxia Inducible Factor-I, Angiotensin-Converting Enzyme Inhibitor Quinaprilat, Angiotropin, Thrombospondin, Peptide KGHK, Low Oxygen Tension, Lactic Acid, Insulin, Growth Hormone, and mixtures thereof.

38. The implantable device of claim 36, wherein the vascularization agent comprises a pro-inflammatory agent configured for promoting an inflammation response or an immune response.

39. The implantable device of claim 38, wherein the pro-inflammatory agent is selected from the group consisting of a xenogenic carrier, a Lipopolysaccharide, and a protein.

40. The implantable device of claim 23, wherein the bioactive agent is incorporated into the biointerface membrane via a carrier matrix.

41. The implantable device of claim 40, wherein the carrier matrix is selected from the group consisting of collagen, a particulate matrix, a non-resorbable matrix, resorbable matrix, a controlled-release matrix, a gel, and mixtures thereof.

42. The implantable device of claim 23, wherein the bioactive agent is cross-linked with a material that forms the biointerface membrane.

43. The implantable device of claim 23, wherein the bioactive agent is configured to be released for a time period of from about one day to about one year.

44. The implantable device of claim 23, wherein the bioactive agent is configured to be released for a time period of from about one week to about four weeks.