Hydrophilic polymeric material for coating biosensors

• US 20020123087A1
• Filed: 12/29/2000
• Published: 09/05/2002
• Est. Priority Date: 12/29/2000
• Status: Active Grant

• Current Assignee: Minimed, Inc. (Medtronic Plc)
• Original Assignee: Minimed, Inc. (Medtronic Plc)
• Inventors: Cochran, Brooks B., Ponder, Bill C., Vachon, David J.
• Granted Patent: US 6,642,015 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: C08G 18/5024 containing primary and/or secondary amino groups
• CPC Class Codes: C08G 18/61 Polysiloxanes
• CPC Class Codes: C08G 18/6685 with compounds of group C08G18/3225 or polyamines of C08G18/38
• CPC Class Codes: C09D 175/02 Polyureas
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31663 As siloxane, silicone or silane

Abstract

Disclosed is a biocompatible membrane comprising a hydrophilic polyurea composition. The hydrophilic polyutea composition comprises the product of a reaction mixture comprising (a) an amino terminated polysiloxane, (b) a hydrophilic polymer selected from the group consisting of a diamino terminated copolymer of polypropylene glycol and polyethylene glycol, polyethylene glycol, polypropylene glycol and diamino polyethylene glycol having an average molecular weight of from about 400 to about 2000, and (c) a diisocyanate selected from the group consisting of hexamethylene-1,6-diisocyanate, dicyclohexylmethane 4,4′-diisocyanate, and isophorone diisocyanate, and constituting about 50 mole % of the reaction mixture. In this mixture, (a) and (b) constitute a polymeric portion of the reaction mixture, and the hydrophilic polyurea composition has a ratio of its diffusion coefficient for oxygen to its diffusion coefficient for glucose of from about 2,000 to about 10,000. Also provided are biosensors coated with a membrane of the invention, and methods of using such biosensors to measure an analyte in a tissue of a subject.

Claims

1. A biocompatible membrane comprising a hydrophilic polyurea composition comprising the product of a first reaction mixture comprising:

(a) an amino terminated polysiloxane;

(b) a hydrophilic polymer selected from the group consisting of a diamino terminated copolymer of polypropylene glycol and polyethylene glycol, polyethylene glycol, polypropylene glycol and diamino polyethylene glycol having an average molecular weight of from about 400 to about 2000; and

(c) a diisocyanate selected from the group consisting of hexamethylene-1,6-diisocyanate, dicyclohexylmethane 4,4′

-diisocyanate, and isophorone diisocyanate, and constituting about 50 mole % of the reaction mixture;

wherein (a) and (b) constitute a polymeric portion of the first reaction mixture, and

wherein the hydrophilic polyurea composition has a ratio of its diffusion coefficient for oxygen to its diffusion coefficient for glucose of from greater than 2,000 to about 10,000.

2. The biocompatible membrane of claim 1, wherein the hydrophilic polyurea composition further comprises the product of blend of the first reaction mixture and

a second reaction mixture, wherein the second reaction mixture comprises (a), (b) and (c).

3. The biocompatible membrane of claim 1, wherein the hydrophilic polyurea composition has a ratio of its diffusion coefficient for oxygen to its diffusion coefficient for glucose of from about 3,000 to about 7,000.

4. The biocompatible membrane of claim 1, wherein the hydrophilic polyurea composition has a ratio of its diffusion coefficient for oxygen to its diffusion coefficient for glucose of from about 5,000 to about 7,000.

5. The biocompatible membrane of claim 1, wherein the hydrophilic polymer comprises a polypropylene glycol)-block-poly(ethylene glycol) bis(2-aminopropyl ether).

6. The biocompatible membrane of claim 1, wherein the polysiloxane has a molecular weight of from about 500 to about 3,500.

7. The biocompatible membrane of claim 6, wherein the polysiloxane has a molecular weight of about 2,500.

8. The biocompatible membrane of claim 1, wherein the mixture further comprises a chain extender.

9. The biocompatible membrane of claim 8, wherein the chain extender is selected from the group consisting of N-methyl diethanolamine, ethylene diamine, butane diol, diethylene glycol, propane diol and water.

10. The biocompatible membrane of claim 1, wherein the mixture has a glucose diffusion coefficient of from about 1×

10<sup>−

9</sup> cm²/s to about 200×

10<sup>−

9</sup> cm²/s at 37°

C.

11. The biocompatible membrane of claim 1, wherein the mixture has a glucose diffusion coefficient of from about 2.5 ×

10<sup>−

9</sup> cm²/s to about 10×

10<sup>−

9</sup> cm²/s at 37°

C.

12. The biocompatible membrane of claim 1, wherein the polysiloxane content is from about 15 mole percent to about 75 mole percent of the polymeric portion of the mixture.

13. The biocompatible membrane of claim 1, wherein the polysiloxane content is about 50 mole percent of the polymeric portion of the mixture.

14. The biocompatible membrane of claim 1, wherein the hydrophilic polymer comprises a combination of a diamino terminated copolymer of polypropylene glycol and polyethylene glycol having an average molecular weight of about 600;

and

a diamino terminated copolymer of polypropylene glycol and polyethylene glycol having an average molecular weight of about 900.

15. The biocompatible membrane of claim 14, wherein the diamino terminated copolymer of polypropylene glycol and polyethylene glycol comprises a polypropylene glycol)-block-poly(ethylene glycol) bis(2-aminopropyl ether).

16. The biocompatible membrane of claim 1, wherein the polymeric portion of the mixture comprises about 50 mole percent polysiloxane, about 25 mole percent hydrophilic polymer having an average molecular weight of about 600, and about 25 mole percent hydrophilic polymer having an average molecular weight of about 900.

17. The biocompatible membrane of claim 16, wherein the hydrophilic polymer comprises a diamino terminated copolymer of polypropylene glycol and polyethylene glycol.

18. The biocompatible membrane of claim 17, wherein the diamino terminated copolymer of polypropylene glycol and polyethylene glycol comprises a polypropylene glycol)-block-poly(ethylene glycol) bis(2-aminopropyl ether).

19. An implantable biosensor for measuring an analyte in biological tissue, the biosensor having a coating adhered thereto, the coating comprising a biocompatible membrane of claim 1.

20. The implantable biosensor of claim 19, further comprising a transducer that generates a signal upon contact with the analyte.

21. The implantable biosensor of claim 20, wherein the analyte is glucose and the transducer is glucose oxidase.

22. A method of measuring an analyte in a tissue of a subject, the method comprising introducing an implantable biosensor of claim 20 into the tissue of the subject and detecting the signal generated by the transducer, wherein the amount of signal corresponds to the amount of analyte.

23. The method of claim 22, wherein the analyte is glucose and the transducer is glucose oxidase.