ENZYME MATRICES FOR USE WITH ETHYLENE OXIDE STERILIZATION

• US 20150122647A1
• Filed: 11/04/2014
• Published: 05/07/2015
• Est. Priority Date: 11/07/2013
• Status: Abandoned Application

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Shah, Rajiv, Yang, Qingling, Mucic, Robert C., Wang, Jenn-Hann Larry
• Application Number:
  US14/532,364
• Publication Number:
  US 20150122647A1
• Time in Patent Office: Days
• US Class Current: 204/403.14
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001

Abstract

The invention pertains to analyte sensors designed to include layered compositions that provide these sensors with enhanced functional and/or material properties including, for example, resistance to damage caused by ethylene oxide during sterilization processes. Embodiments of the invention include polyvinyl alcohol N-methyl-4(4′-formylstyryl)pyridinium (SbQ) polymer materials and methods for employing such materials during the ethylene oxide sterilization of glucose sensors.

Claims

1. A method of making an analyte sensor apparatus comprising:

disposing a working electrode, a reference electrode, and a counter electrode on a base layer;

disposing an analyte sensing layer over the working electrode, wherein;

the analyte sensing layer comprises glucose oxidase disposed within a polyvinyl alcohol polymer comprising N-methyl-4(4′

-formylstyryl)pyridinium (PVA-SbQ);

the PVA-SbQ polymer is selected for an ability to inhibit damage to glucose oxidase by ethylene oxide; and

disposing an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of analyte therethrough;

so that an analyte sensor apparatus is made.

2. The method of claim 1, wherein the analyte sensing layer:

(a) comprises PVA-SbQ in an amount from 5% to 15% by weight;

(b) comprises glucose oxidase in an amount from 10 KU/mL to 20 KU/mL;

(c) comprises polyvinyl alcohol having a molecular weight from 25 kilodaltons to 125 kilodaltons;

(d) comprises 1.0% to 4.0% N-methyl-4(4′

-formylstyryl)pyridinium; and

/or

(e) is between 4 and 12 microns in thickness.

3. The method of claim 1, wherein the analyte sensor apparatus comprises a further layer disposed over the analyte sensing layer, wherein the further layer:

(a) comprises PVA-SbQ;

(b) comprises a hydrophilic polyurethane;

(c) does not include an albumin; and

/or

(d) is between 1 and 3 microns in thickness.

4. The method of claim 1, wherein the analyte modulating layer comprises:

(1) a polyurethane/polyurea polymer formed from a mixture comprising;

(a) a diisocyanate;

(b) a hydrophilic polymer comprising a hydrophilic diol or hydrophilic diamine; and

(c) a siloxane having an amino, hydroxyl or carboxylic acid functional group at a terminus; and

/or

(2) a branched acrylate polymer formed from a mixture comprising;

(a) a butyl, propyl, ethyl or methyl-acrylate;

(b) an amino-acrylate;

(c) a siloxane-acrylate; and

(d) a poly(ethylene oxide)-acrylate.

5. The method of claim 1, wherein the analyte modulating layer is formed from a composition comprising a diisocyanate having a phenyl moiety.

6. A method of inhibiting damage to glucose oxidase caused by ethylene oxide vapor during a sterilization process, the method comprising disposing the glucose oxidase within a matrix comprising a polyvinyl alcohol polymer comprising N-methyl-4(4′

-formylstyryl)pyridinium (PVA-SbQ), so that damage to glucose oxidase is inhibited.

7. The method of claim 6, wherein the glucose oxidase is disposed within an analyte sensor apparatus, wherein the analyte sensor apparatus comprises:

a base layer;

a working electrode, a reference electrode, and a counter electrode disposed on the base layer;

an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer comprises the glucose oxidase disposed within the PVA-SbQ; and

an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of analyte therethrough.

8. The method of claim 7, wherein the analyte sensing layer:

(a) comprises PVA-SbQ in an amount from 5% to 15% by weight;

(b) comprises glucose oxidase in an amount from 10 KU/mL to 20 KU/mL;

(c) comprises polyvinyl alcohol having a molecular weight from 25 kilodaltons to 125 kilodaltons;

(d) comprises 1.0% to 4.0% N-methyl-4(4′

-formylstyryl)pyridinium; and

/or

(e) is between 4 and 12 microns in thickness.

9. The method of claim 6, wherein the analyte sensor apparatus comprises a further layer disposed over the analyte sensing layer, wherein the further layer:

(a) comprises PVA-SbQ;

(b) comprises a hydrophilic polyurethane;

(c) does not include an albumin; and

/or

(d) is between 1 and 3 microns in thickness.

10. A method of inhibiting microbial growth on an analyte sensor apparatus, the method comprising:

exposing the analyte sensor apparatus to an ethylene oxide vapor so as to contact a microorganism present on the analyte sensor apparatus or a container in which the analyte sensor apparatus is disposed; and

allowing the ethylene oxide to alkylate DNA of the microorganism, thereby inhibiting microbial growth,

wherein the analyte sensor apparatus comprises;

a base layer;

a working electrode, a reference electrode, and a counter electrode disposed on the base layer;

an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer comprises glucose oxidase disposed within a polyvinyl alcohol polymer comprising N-methyl-4(4′

-formylstyryl)pyridinium (PVA-SbQ); and

an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of analyte therethrough.

11. The method of claim 10, wherein the analyte sensing layer:

(a) comprises PVA-SbQ in an amount from 5% to 15% by weight;

(b) comprises glucose oxidase in an amount from 10 KU/mL to 20 KU/mL;

(c) comprises polyvinyl alcohol having a molecular weight from 25 kilodaltons to 125 kilodaltons;

(d) comprises 1.0% to 4.0% N-methyl-4(4′

-formylstyryl)pyridinium; and

/or

(e) is between 4 and 12 microns in thickness.

12. The method of claim 10, wherein the analyte sensor apparatus comprises a further layer disposed over the analyte sensing layer, wherein the further layer:

(a) comprises PVA-SbQ;

(b) comprises a hydrophilic polyurethane;

(c) does not include an albumin; and

/or

(d) is between 1 and 3 microns in thickness.

13. The method of claim 10, wherein:

the method uses ethylene oxide vapor in a concentration range from 50 to 1,500 mg/L;

the method uses humidity in a range from 30% to 90%;

the methods is performed at a temperature from 25-55°

C.;

or

the method is performed for at least 2 hours.

14. The method of claim 10, wherein the analyte modulating layer is formed from a diisocyanate comprising a phenyl moiety.

15. A composition of matter comprising:

(1) analyte sensor apparatus having;

a base layer;

a working electrode, a reference electrode, and a counter electrode disposed on the base layer;

an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer comprises glucose oxidase entrapped within;

(a) a polyvinyl alcohol polymer comprising N-methyl-4(4′

-formylstyryl)pyridinium (SbQ);

or (b) a hydrophilic polyurethane;

an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of analyte therethrough; and

(2)ethylene oxide vapor.

16. The composition of claim 15, wherein the analyte sensing layer:

(a) comprises PVA-SbQ in an amount from 5% to 15% by weight;

(b) comprises glucose oxidase in an amount from 10 KU/mL to 20 KU/mL;

(c) comprises polyvinyl alcohol having a molecular weight from 25 kilodaltons to 125 kilodaltons;

(d) comprises 1.0% to 4.0% N-methyl-4(4′

-formylstyryl)pyridinium; and

/or

(e) is between 4 and 12 microns in thickness.

17. The composition of claim 15, wherein the composition does not comprise an albumin.

18. The composition of claim 15, wherein the analyte modulating layer comprises:

polyurethane/polyurea polymer formed from a mixture comprising;

(a) a diisocyanate;

(b) a hydrophilic polymer comprising a hydrophilic diol or hydrophilic diamine; and

(c) a siloxane having an amino, hydroxyl or carboxylic acid functional group at a terminus; and

/or

a branched acrylate polymer formed from a mixture comprising;

(a) a butyl, propyl, ethyl or methyl-acrylate;

(b) an amino-acrylate;

(c) a siloxane-acrylate; and

19. The composition of claim 15, wherein the analyte sensor apparatus comprises a further layer disposed over the analyte sensing layer, wherein the further layer:

(a) comprises PVA-SbQ;

(b) comprises a hydrophilic polyurethane;

(c) does not include an albumin; and

/or

(d) is between 1 and 3 microns in thickness.

20. The composition of claim 15, wherein the analyte sensing layer comprises glucose oxidase trapped within a hydrophilic polyurethane.