Techniques to improve polyurethane membranes for implantable glucose sensors

• US 9,179,869 B2
• Filed: 09/10/2014
• Issued: 11/10/2015
• Est. Priority Date: 05/22/2002
• Status: Expired due to Term

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Tapsak, Mark A., Rhodes, Rathbun K., Shults, Mark C., McClure, Jason D.
• Primary Examiner(s): SELLMAN, CACHET I
• Application Number:
  US14/482,458
• Publication Number:
  US 20140378798A1
• Time in Patent Office: 426 Days
• Field of Search: 427/2.11, 427/2.12, 424/424, 600/347, 204/403.11
• US Class Current: 1/1
• 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 69/141 Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
• 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 method for preparing an implantable membrane for an implantable glucose sensor, the method comprising:

forming a composition comprising a dispersion of a first polymer within a matrix of a second polymer, wherein the first polymer comprises a hydrophilic segment, wherein the second polymer comprises polyurethaneurea;

applying the composition to at least one of a substrate or a layer on the substrate to form a film thereon; and

drying the film to form a membrane configured to cover at least a portion of an electrode of the implantable glucose sensor, whereby the membrane is configured to reduce passage of glucose therethrough, whereby the membrane is configured to change a ratio of oxygen to glucose from a concentration ratio in a body fluid to a new ratio in which there is a stoichiometric excess of oxygen in an enzyme layer of the implantable glucose sensor, whereby the membrane is configured to extend an upper limit of linearity of glucose measurement to a higher value than that which could be achieved without the membrane.

2. The method of claim 1, wherein the substrate comprises the electrode.

3. The method of claim 1, further comprising applying an enzyme on the substrate to form an enzyme layer thereon.

4. The method of claim 1, wherein the composition further comprises a solvent.

5. The method of claim 1, wherein drying the film forms a membrane with a network of microdomains, wherein the microdomains are substantially uniform in size and are substantially distributed throughout the membrane.

6. The method of claim 1, wherein the microdomains are not observable at 400×

magnification or less.

7. A method for preparing a plurality of implantable membranes for a plurality of implantable glucose sensors, the method comprising:

forming a composition comprising a dispersion of a first polymer within a matrix of a second polymer, wherein the first polymer comprises a hydrophilic segment, wherein the second polymer comprises a hydrophobic segment;

applying the composition to at least one of a substrate or a layer on the substrate to form a film thereon; and

drying the film to form a membrane configured to cover at least a portion of an electrode of the implantable glucose sensor and configured to change a ratio of oxygen to glucose from a concentration ratio in a body fluid to a new ratio in which there is a stoichiometric excess of oxygen in an enzyme layer of the implantable glucose sensor;

repeating at least the applying and drying steps under constant conditions to form a plurality of implantable membranes for a plurality of implantable glucose sensors, wherein the plurality of sensors demonstrate under constant conditions a substantially constant percent standard deviation of sensor output of less than 30%.

8. The method of claim 7, wherein the second polymer comprises polyurethane.

9. The method of claim 8, wherein the polyurethane is polyurethaneurea.

10. The method of claim 7, wherein the substrate comprises the electrode.

11. The method of claim 7, further comprising applying an enzyme on the substrate to form an enzyme layer thereon.

12. The method of claim 7, wherein the composition further comprises a solvent.

13. The method of claim 7, wherein drying the film forms a membrane with a network of microdomains, wherein the microdomains are substantially uniform in size and are substantially distributed throughout the membrane.

14. The method of claim 13, wherein the microdomains are not observable at 400×

magnification or less.

15. The method of claim 7, wherein the second polymer comprises polysiloxanes or polycarbosiloxanes.

16. The method of claim 7, wherein the plurality of sensors demonstrate under constant conditions a substantially constant percent standard deviation of sensor output of less than 25%.

17. The method of claim 7, wherein the plurality of sensors demonstrate under constant conditions a substantially constant percent standard deviation of sensor output of less than 20%.