Silicone based membranes for use in implantable glucose sensors

• US 20070244379A1
• Filed: 04/14/2006
• Published: 10/18/2007
• Est. Priority Date: 05/22/2002
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Boock, Robert, Rixman, Monica
• Granted Patent: US 7,613,491 B2
• Time in Patent Office: Days
• US Class Current: 600/345
• 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: A61B 5/6848 Needles
• CPC Class Codes: C08G 77/12 containing silicon bound to hydrogen C08G77/045 takes precedence
• CPC Class Codes: C08G 77/20 containing silicon bound to unsaturated aliphatic groups C08G77/045 takes precedence
• CPC Class Codes: C08G 77/46 containing polyether sequences
• CPC Class Codes: C08L 2666/14 Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C08L 83/04 Polysiloxanes

Abstract

Membrane systems incorporating silicone polymers are described for use in implantable analyte sensors. Some layers of the membrane system may comprise a blend of a silicone polymer with a hydrophilic polymer, for example, a triblock poly(ethylene oxide) -poly(propylene oxide)-poly(ethylene oxide) polymer. Such polymeric blends provide for both high oxygen solubility and aqueous analyte solubility.

Claims

1. A membrane for use in an analyte sensor, comprising:

a silicone elastomer; and

a poly(ethylene oxide) and poly(propylene oxide) co-polymer, wherein the membrane is adapted to permit diffusion of both the analyte and oxygen therethrough.

2. The membrane of claim 1, wherein the silicone elastomer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

3. The membrane of claim 2, wherein the silicone elastomer comprises vinyl substituents.

4. The membrane of claim 1, wherein the silicone elastomer is an elastomer produced by curing a MED-4840 mixture.

5. The membrane of claim 1, wherein the copolymer comprises hydroxy substituents.

6. The membrane of claim 1, wherein the co-polymer is a triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) polymer.

7. The membrane of claim 1, wherein the co-polymer is a triblock poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) polymer.

8. The membrane of claim 1, wherein the co-polymer is a PLURONIC®

polymer.

9. The membrane of claim 1, wherein the co-polymer is PLURONIC®

F-127.

10. The membrane of claim 1, wherein the analyte is glucose.

11. The membrane of claim 1, wherein at least a portion of the co-polymer is cross-linked.

12. The membrane of claim 1, wherein from about 5% w/w to about 30% w/w of the membrane is the co-polymer.

13. An implantable analyte sensor, comprising:

an enzyme layer comprising an enzyme for which the analyte is a substrate; and

a bioprotective layer positioned between the enzyme layer and tissue adjacent to the sensor when implanted, wherein the bioprotective layer comprises a silicone elastomer and a poly(ethylene oxide) and poly(propylene oxide) co-polymer.

14. The sensor of claim 13, further comprising a diffusion resistance layer positioned between the enzyme layer and the bioprotective layer.

15. The sensor of claim 14, wherein the diffusion resistance layer also comprises the silicone elastomer and the poly(ethylene oxide) and poly(propylene oxide) co-polymer.

16. The sensor of claim 15, wherein a ratio of the silicone elastomer to the co-polymer is different in the diffusion resistance layer than in the bioprotective layer.

17. The sensor of claim 13, further comprising a cell disruptive layer positioned between the bioprotective layer and tissue adjacent to the sensor when implanted.

18. The sensor of claim 13, wherein the silicone elastomer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

19. The sensor of claim 18, wherein the silicone elastomer comprises vinyl substituents.

20. The sensor of claim 13, wherein the silicone elastomer is an elastomer produced by curing a MED-4840 mixture.

21. The sensor of claim 13, wherein the copolymer comprises hydroxy substituents.

22. The sensor of claim 13, wherein the co-polymer is a triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) polymer.

23. The sensor of claim 13, wherein the co-polymer is a triblock poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) polymer.

24. The sensor of claim 13, wherein the co-polymer is a PLURONIC®

polymer.

25. The sensor of claim 13, wherein the co-polymer is PLURONIC®

F-127.

26. The sensor of claim 13, wherein the analyte is glucose.

27. The sensor of claim 13, wherein at least a portion of the co-polymer is cross-linked.

28. The sensor of claim 13, wherein from about 5% w/w to about 30% w/w of the bioprotective layer is the co-polymer.

29. The sensor of claim 13, wherein the enzyme layer also comprises the silicone elastomer and the co-polymer.

30. The sensor of claim 29, wherein a ratio of the silicone elastomer to the co-polymer is different in the enzyme layer than in the bioprotective layer.

31. The sensor of claim 13, wherein the sensor is configured to be wholly implanted.

32. The sensor of claim 13, wherein the sensor is configured to be transcutaneously implanted.

33. The sensor of claim 13, wherein at least a portion of the bioprotective layer is porous and adjacent to tissue when implanted.

34. An implantable analyte sensor, comprising:

an enzyme layer comprising an enzyme for which the analyte is a substrate; and

a diffusion resistance layer comprising a silicone elastomer and a poly(ethylene oxide) and poly(propylene oxide) co-polymer, wherein the diffusion resistance layer is positioned between the enzyme layer and tissue adjacent to the sensor when implanted.

35. The sensor of claim 34, further comprising a bioprotective layer positioned between the diffusion resistance layer and tissue adjacent to the sensor when implanted.

36. The sensor of claim 34, wherein the silicone elastomer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

37. The sensor layer of claim 36, wherein the silicone elastomer comprises vinyl substituents.

38. The sensor of claim 34, wherein the silicone elastomer is an elastomer produced by curing a MED-4840 mixture.

39. The sensor of claim 34, wherein the copolymer comprises hydroxy substituents.

40. The sensor of claim 34, wherein the co-polymer is a PLURONIC®

polymer.

41. The sensor of claim 34, wherein the co-polymer is PLURONIC®

F-127.

42. The sensor of claim 34, wherein the analyte is glucose.

43. The sensor of claim 34, wherein at least a portion of the co-polymer is cross-linked.

44. The sensor of claim 34, wherein from about 5% w/w to about 30% w/w of the diffusion resistance layer is the co-polymer.

45. The sensor of claim 34, wherein the ratio of the silicone elastomer to co-polymer varies within the diffusion resistance layer.

46. The sensor of claim 34, wherein the sensor is configured to be wholly implanted.

47. The sensor of claim 34, wherein the sensor is configured to be transcutaneously implanted.

48. An implantable analyte sensor, comprising at least one polymer membrane, wherein every polymer membrane in said sensor comprises a silicone elastomer and a poly(ethylene oxide) and poly(propylene oxide) co-polymer.

49. The sensor of claim 48, wherein the silicone elastomer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

50. The sensor of claim 49, wherein the silicone elastomer comprises vinyl substituents.

51. The sensor of claim 48, wherein the silicone elastomer is an elastomer produced by curing a MED-4840 mixture.

52. The sensor of claim 48, wherein the copolymer comprises hydroxy substituents.

53. The sensor of claim 48, wherein the co-polymer is a PLURONIC®

polymer.

54. The sensor of claim 48, wherein the co-polymer is PLURONIC®

F-127.

55. The sensor of claim 48, wherein at least a portion of the co-polymer is cross-linked.

56. The sensor of claim 48, wherein from about 5% w/w to about 30% w/w of each polymer membrane is the co-polymer.

57. The sensor of claim 48, wherein the sensor comprises at least two polymer membranes having a ratio of the silicone elastomer to the co-polymer that is different.

58. The sensor of claim 48, wherein the sensor is configured to be wholly implanted.

59. The sensor of claim 48, wherein the sensor is configured to be transcutaneously implanted.

60. A method of manufacturing a membrane for use in an analyte sensor, the method comprising:

mixing a precursor of a silicone elastomer with a poly(ethylene oxide) and poly(propylene oxide) co-polymer; and

heating the mixture.

61. The method of claim 60, wherein a ratio of co-polymer to silicone elastomer that is mixed is from about 1:

20 w/w to about 1;

4 w/w.

62. The method of claim 60, further comprising mixing the co-polymer with a cross-linking agent.

63. The method of claim 62, wherein the cross-linking agent is mixed with the co-polymer prior to mixing the co-polymer with the silicone elastomer precursor.

64. The method of claim 62, wherein the cross-linking agent is selected from the group consisting of one or more of ethylene glycol diglycidyl ether and poly(ethylene glycol) diglycidyl ether.

65. The method of claim 62, wherein the cross-linking agent comprises dicumyl peroxide.

66. The method of claim 62, wherein the ratio of cross-linking agent to co-polymer is from about 10 cross-linking agent molecules per co-polymer molecule to about 30 cross-linking agent molecules per co-polymer molecule.

67. The method of claim 62, wherein the amount of cross-linking agent added relative to the silicone elastomer and co-polymer is from about 0.5% to about 15% w/w.

68. The method of claim 60, further comprising, after the mixing step but before the heating step, drawing the mixture into a thin film.

69. The method of claim 68, further comprising, after the drawing step but before the heating step, placing a piece of porous silicon on the thin film.