Techniques to improve polyurethane membranes for implantable glucose sensors

• US 20030217966A1
• Filed: 05/22/2002
• Published: 11/27/2003
• Est. Priority Date: 05/22/2002
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Shults, Mark C., Tapsak, Mark A., Rhodes, Rathbun K., McClure, Jason D.
• Granted Patent: US 7,226,978 B2
• Time in Patent Office: Days
• US Class Current: 210/500.21
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• 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 31/12 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: B01D 69/1411 containing dispersed material in a continuous matrix
• CPC Class Codes: B01D 71/54 Polyureas; Polyurethanes
• CPC Class Codes: B01D 71/80 Block polymers
• CPC Class Codes: B05D 3/007 After-treatment
• CPC Class Codes: B05D 5/00 Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Abstract

The invention provides an implantable membrane for regulating the transport of analytes therethrough that includes a matrix including a first polymer; and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less. In one aspect, the homogeneous membrane of the present invention has hydrophilic domains dispersed substantially throughout a hydrophobic matrix to provide an optimum balance between oxygen and glucose transport to an electrochemical glucose sensor.

Claims

1. A membrane that regulates the transport of analytes comprising:

(a) a matrix comprising a first polymer; and

(b) a second polymer dispersed throughout said matrix, wherein said second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400×

magnification or less.

2. The membrane of claim 1, wherein said membrane is substantially free of observable domains.

3. The membrane of claim 1, wherein said first polymer comprises homopolymer A and said second polymer comprises copolymer AB.

4. The membrane of claim 3, wherein copolymer AB comprises a random or ordered block copolymer.

5. The membrane of claim 4, wherein said random or ordered block copolymer is selected from the group consisting of ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.

6. The membrane of claim 1, wherein said first polymer comprises copolymer AB and wherein said second polymer comprises copolymer AB.

7. The membrane of claim 6, wherein copolymer AB comprises a random or ordered block copolymer.

8. The membrane of claim 7, wherein said random or ordered block copolymer is selected from the group consisting of ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.

9. The membrane of claim 6, wherein the amount of B in copolymer AB of said first polymer is different than the amount of B in copolymer AB of said second polymer.

10. The membrane of claim 1, wherein said first polymer comprises homopolymer A and said second polymer comprises homopolymer B.

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

12. The membrane of claim 1, further including an enzyme reactive with said analyte.

13. The membrane of claim 12, wherein said enzyme is glucose oxidase.

14. The membrane of claim 1, in combination with a proximal layer of enzyme reactive with said analyte.

15. The membrane of claim 14, wherein said enzyme is glucose oxidase.

16. The membrane of claim 1, wherein said second polymer is a hydrophobic-hydrophilic copolymer component comprising the reaction products of a hydrophobic A polymer and a hydrophilic B polymer.

17. The membrane of claim 16, wherein the hydrophilic B polymer is polyethylene oxide.

18. The membrane of claim 1, wherein the hydrophobic A polymer is a polyurethane.

19. The membrane of claim 18, wherein the polyurethane is polyetherurethaneurea.

20. A polymeric membrane for regulation of glucose and oxygen in a subcutaneous glucose measuring device comprising:

(a) a matrix comprising a first polymer; and

(b) a second polymer dispersed throughout said matrix, wherein said second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400×

magnification or less.

21. A polymeric membrane for regulating the transport of analytes comprising at least one block copolymer AB, wherein B forms a network of microdomains which are not photomicroscopically observable when hydrated at 400×

magnification or less.

22. The membrane of claim 21, wherein the ratio of A to B in said copolymer is 70:

30 to 90;

10.

23. A membrane and sensor combination, said sensor being adapted for evaluating an analyte within a body fluid, said membrane comprising:

(a) a matrix comprising a first polymer; and

(b) a second polymer dispersed throughout said matrix, wherein said second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400×

magnification or less.

24. The combination of claim 23, wherein the sensor comprises an electrochemical sensor.

25. The combination of claim 23, wherein the analyte diffuses through the membrane to the sensor for evaluation thereof.

26. An implantable device for measuring an analyte in a hydrophilic body fluid, comprising:

(a) a polymeric membrane comprising (i) a matrix comprising a first polymer; and

(ii) a second polymer dispersed throughout said matrix, wherein said second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400×

magnification or less; and

(b) a proximal layer of enzyme reactive with said analyte.

27. The device of claim 26, further including a sensor for evaluating the analyte.

28. The device of claim 26, wherein the sensor comprises an electrochemical sensor.

29. The device of claim 26, wherein the analyte is glucose.

30. The device of claim 26, wherein the enzyme is glucose oxidase.

31. A method of monitoring glucose levels, comprising:

(a) providing (i) a host, and (ii) an implantable device according to claim 26;

and

(b) implanting said device in said host.

32. The method according to claim 31, wherein said implanting is subcutaneous.

33. A method of measuring glucose in a biological fluid, comprising:

(a) providing (i) a host, and (ii) an implantable device according to claim 26, said device being capable of accurate continuous glucose sensing; and

(b) implanting said device in said host.

34. The method according to claim 33, wherein said implanting is subcutaneous.

35. A method for preparing an implantable membrane comprising the steps of:

(a) forming a composition comprising a dispersion of a second polymer within a matrix of a first polymer, said dispersion forming a network of microdomains which are not photomicroscopically observable when hydrated at 400×

magnification or less;

(b) maintaining said composition at a temperature sufficient to maintain said first polymer and said second polymer substantially soluble;

(c) applying said composition at said temperature to a substrate to form a film thereon; and

(d) permitting said resultant film to dry to form said membrane.

36. The method of claim 35, wherein said forming step comprises forming a mixture or a blend.

37. The method of claim 35, wherein said maintaining step comprises heating the combination to a temperature of about 70°

C.

38. The method of claim 35, wherein said permitting step comprises drying at a temperature from about 120°

C. to about 150°

C.

39. The method of claim 35, wherein said second polymer is polyethylene oxide.

40. The method of claim 35, wherein said first polymer is a polyurethane.

41. The method of claim 35, wherein the second polymer is a random or ordered block copolymer selected from the group consisting of ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.

42. An implantable membrane formed in accordance with the method of claim 35.