Silicone based membranes for use in implantable glucose sensors

• US 7,613,491 B2
• Filed: 04/14/2006
• Issued: 11/03/2009
• Est. Priority Date: 05/22/2002
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Boock, Robert, Rixman, Monica
• Primary Examiner(s): Nasser; Robert L
• Application Number:
  US11/404,417
• Publication Number:
  US 20070244379A1
• Time in Patent Office: 1,299 Days
• Field of Search: None
• US Class Current: 600/347
• 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 device for use in an implantable analyte sensor, comprising:

an enzyme layer comprising an enzyme; 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.

2. The device of claim 1, further comprising a bioprotective layer positioned between the diffusion resistance layer and tissue adjacent to the sensor when implanted.

3. The device of claim 1, wherein the silicone elastomer is a dimethyl-siloxane and methyihydrogen-siloxane copolymer.

4. The device layer of claim 3, wherein the silicone elastomer comprises vinyl substituents.

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

6. The device of claim 1, wherein the copolymer comprises hydroxy substituents.

7. The device of claim 1, wherein the co-polymer is a PLURONIC®

polymer.

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

F-127.

9. The device of claim 1, wherein the analyte is glucose.

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

11. The sensor device of claim 1, wherein from about 5% w/w to about 30% w/w of the diffusion resistance layer is the co-polymer.

12. The device of claim 1, wherein the ratio of the silicone elastomer to co-polymer varies within the diffusion resistance layer.

13. The device of claim 1, wherein the sensor is configured to be wholly implanted.

14. The device of claim 1, wherein the sensor is configured to be transcutaneously implanted.

15. A device for use in an implantable analyte sensor, comprising at least one polymer membrane comprising an enzyme, wherein every polymer membrane in said sensor comprises a silicone elastomer and a poly(ethylene oxide) and poly(propylene oxide) co-polymer.

16. The device of claim 15, wherein the silicone elastomer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

17. The device of claim 16, wherein the silicone elastomer comprises vinyl substituents.

18. The device of claim 15, wherein the silicone elastomer is an elastomer produced by curing a MED-4840 mixture.

19. The device of claim 15, wherein the copolymer comprises hydroxy substituents.

20. The device of claim 15, wherein the co-polymer is a PLURONIC®

polymer.

21. The device of claim 15, wherein the co-polymer is PLURONIC®

F-127.

22. The device of claim 15, wherein at least a portion of the co-polymer is cross-linked.

23. The device of claim 15, wherein from about 5% w/w to about 30% w/w of each polymer membrane is the co-polymer.

24. The device of claim 15, wherein the sensor comprises at least two polymer membranes having a ratio of the silicone elastomer to the co-polymer that is different.

25. The device of claim 15, wherein the sensor is configured to be wholly implanted.

26. The device of claim 15, wherein the sensor is configured to be transcutaneously implanted.

27. An analyte sensor, comprising:

a working electrode; and

a membrane disposed over the working electrode, the membrane comprising;

an enzyme layer comprising an enzyme, and

an additional layer disposed over the enzyme layer comprising a silicone elastomer and a poly(ethylene oxide) and poly(propylene oxide) co-polymer.

28. The sensor of claim 27, wherein the analyte is glucose.

29. The sensor of claim 27, wherein the enzyme is glucose oxidase.

30. The sensor of claim 27, wherein the additional layer is adapted to resist diffusion of the analyte therethrough.

31. The sensor of claim 27, wherein the additional layer is adapted to resist cellular attachment.

32. The sensor of claim 27, wherein the additional layer is impermeable to cells.

33. The sensor of claim 27, wherein the additional layer is resistant to the effects of one or more oxidative species.

34. The sensor of claim 27, wherein at least a portion of the additional layer is porous.

35. The sensor of claim 27, wherein the ratio of the silicone elastomer to co-polymer varies within the additional layer.

36. The sensor of claim 27, wherein the porosity of the additional layer varies from one side of the layer to the other.

37. The sensor of claim 27, wherein the silicone elastomer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

38. The sensor of claim 27, wherein the silicone elastomer comprises vinyl substituents.

39. The sensor of claim 27, wherein the silicone elastomer is an elastomer produced by curing a MED-4840 mixture.

40. The sensor of claim 27, wherein the copolymer comprises hydroxy substituents.

41. The sensor of claim 27, wherein the co-polymer is a PLURONIC®

polymer.

42. The sensor of claim 27, wherein the co-polymer is PLURONIC®

F-127.

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

44. The sensor of claim 27, wherein from about 5% w/w to about 30% w/w of the additional layer is the co-polymer.

45. An analyte sensor, comprising:

a working electrode;

an enzyme layer disposed over the working electrode and comprising an enzyme; and

an additional layer, wherein the additional layer comprises a blend of a silicone polymer and a hydrophilic polymer, wherein the additional layer is adapted to substantially prevent penetration of one or more interferants into an electrolyte phase adjacent to the working electrode.

46. The sensor of claim 45, wherein the one or more interferants comprise acetaminophen.

47. The sensor of claim 45, wherein the additional layer is positioned between the working electrode and the enzyme layer.

48. The sensor of claim 45, wherein the additional layer is disposed over the enzyme layer.

49. The sensor of claim 45, wherein the analyte is glucose.

50. The sensor of claim 45, wherein the enzyme is glucose oxidase.

51. The sensor of claim 45, wherein the silicone polymer is a dimethyl-siloxane and methylhydrogen-siloxane copolymer.

52. The sensor of claim 45, wherein the silicone polymer comprises vinyl substituents.

53. The sensor of claim 45, wherein the silicone polymer is an elastomer produced by curing a MED-4840 mixture.

54. The sensor of claim 45, wherein the hydrophilic polymer is a poly(ethylene oxide) and poly(propylene oxide) co-polymer.

55. The sensor of claim 54, wherein the copolymer comprises hydroxy substituents.

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

polymer.

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

F-127.

58. The sensor of claim 54, wherein at least a portion of the co-polymer is cross-linked.

59. The sensor of claim 45, wherein from about 5% w/w to about 30% w/w of the additional layer is the hydrophilic polymer.