Hydrophilic, swellable coatings for biosensors

• US 6,784,274 B2
• Filed: 08/06/2002
• Issued: 08/31/2004
• Est. Priority Date: 03/27/1995
• Status: Expired due to Term

• Current Assignee: Minimed, Inc. (Medtronic Plc)
• Original Assignee: Minimed, Inc. (Medtronic Plc)
• Inventors: Mastrototoro, John J., Decker, Christian C., Van Antwerp, William Peter
• Primary Examiner(s): COONEY, JOHN M
• Application Number:
  US10/213,265
• Publication Number:
  US 20030069383A1
• Time in Patent Office: 756 Days
• Field of Search: 427/2.12, 427/58, 428/423.1, 428/426, 528/77, 528/85
• US Class Current: 528/77
• 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 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: C08G 18/4833 Polyethers containing oxyethylene units
• CPC Class Codes: C08G 18/61 Polysiloxanes
• CPC Class Codes: C08G 18/6674 with compounds of group C08G18/3203
• CPC Class Codes: C08G 77/458 containing polyurethane sequences
• CPC Class Codes: C08J 2323/06 Polyethene
• CPC Class Codes: C08J 5/2287 After-treatment
• 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

Methods for reducing the electrode impedance of implantable biosensors by coating the surface of the biosensor with a uniform hydrogel which allows unimpeded water movement around the sensor are provided. The surface coatings are compositions which are biocompatible and are capable of water uptake of at least 120% of their weight, more preferably at least 200% of their weight. Upon the uptake of water, the hydrogels used in the present invention will also swell and provide a layer of water around the electrodes to which the hydrogels are attached. The hydrogels can be prepared from (a) a diisocyanate, (b) a hydrophilic polymer which is a hydrophilic diol, a hydrophilic diamine, or a combination thereof, and optionally, (c) a chain extender.

Claims

1. A method for forming an implantable biosensor having a biocompatible coating, the method comprising coating the implantable biosensor with a hydrogel composition formed by admixing (a) a diisocyante, the diisocyanate comprising about 50 mol % of the reactants in the admixture;

(b) a hydrophilic polymer selected from, the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof; and

, optionally, (c) a chain extender, thereby forming the implantable biosensor having the hydrogel coating, wherein the hydrogel composition has a water pickup of at least about 120% by weight.

2. The method in accordance with claim 1, wherein the coating is by spin coating, dipping or spraying.

3. The method in accordance with claim 1, wherein the hydrogel composition has a water pickup of from about 120% to about 400% by weight.

4. The method in accordance with claim 1, wherein the diisocyanate is a member selected from the group consisting of isophorone diisocyanate, 1,6-hexamethylene diisocyanate and 4,4′

-methylenebis(cyclohexyl isocyanate).

5. The method in accordance with claim 1, wherein the hydrophilic polymer diol is a member selected from the group consisting of a poly(alkylene)-glycol, a polyester-based diol and a polycarbonate polyol.

6. The method in accordance with claim 1, wherein the hydrophilic polymer diamine is a diamino poly(oxyalkylene).

7. The method in accordance with claim 4, wherein the diamino poly(oxyalkylene) is poly(propylene glycol) bis(2-aminopropyl ether).

8. The method in accordance with claim 4, wherein the diamino poly(oxyalkylene) is a member selected from the group consisting of a polyoxypropylenediamine having an average molecular weight of about 230, a polyoxyethylenediamine having an average molecular weight of about 600, a polyoxyethylenediamine having an average molecular weight of about 900 and a polyoxypropylenediamine having an average molecular weight of about 2000.

9. The method in accordance with claim 1, wherein the chain extender is selected from the group consisting of an alkylene diol, an alkylene diamine, aminoalkanol and combinations thereof.

10. The method in accordance with claim 1, wherein the chain extender is selected from the group consisting of butanediol, ethylenediamine;

hexamethylenediamine, 1,2-diaminocyclohexane and isophoronediamine.

11. The method in accordance with claim 1, wherein the diisocyanate is 1,6-hexamethylene diisocyanate and the hydrophilic polymer is selected from the group consisting of a polyoxyethylenediamine having an average molecular weight of about 600, a polyoxypropylenediamine having an average molecular weight of about 2000 and a poly(ethylene glycol) having in average molecular weight of about 2000 and is present in an amount of about 40 to about 50 mol %.

12. The method in accordance with claim 1, wherein the diisocyanate is 1,6-hexamethylene diisocynate, the hydrophilic polymer is selected from the group consisting of a polyoxyethylenediamine having an average molecular weight of about 600, a polyoxypropylenediamine having an average molecular weight of about 2000 and a poly(ethylene glycol) having at avenge molecular weight of about 2000 and is present in amount of about 40 to about 50 mol %, and the chain extender is butanediol and is present in an amount of about 2.5 to about 10 mol %.

13. A method for forming an implantable biosensor having a biocompatible coating, the method comprising coating the implantable biosensor with biocompatible composition formed by admiring (a) a diisocyanate, the diisocyanate comprising about 50 mol % of the reactants in the mixture;

(b) a hydrophilic polymer which is a member selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof;

(c) a siloxane polymer having a glucose groups at the chain termini, the biocompatible composition having a glucose diffusion coefficient of from about 1×

10<sup>−

9</sup> cm²/sec to about 200×

10<sup>−

9</sup> cm²/sec, a water pickup of at least 25% and a ratio of D_{oxygen/glucose} of from about 5 to about 200.

14. The method in accordance with claim 13, wherein the functional groups are members selected from the group consisting of amino, hydroxyl and carboxylic acid.

15. The method in accordance with claim 13, wherein the hydrophilic polymer is a poly(ethylene)glycol selected from the group consisting of PEG 200, PEG 400 and PEG 600.

16. The method in accordance with claim 13, wherein the diisocynate is a member selected horn the group consisting of isophorone diisocyanate, 1,6-hexamethylene diisocyanate and 4,4′

-methylenebis(cyclohexyl isocyanate).

17. The method in accordance with claim 13, wherein the reaction mixture further comprises (d) a chain extender.

18. The method in accordance with claim 17, wherein the chain extender is selected from the group consisting of an alkylene diol, an alkylene diamine, an aminoalkanol and combinations thereof.

19. The method in accordance with claim 13, wherein the diisocyanate is 1,6-hexamethylene diisocyanate, the hydrophilic polymer is selected from the group consisting of PEG 400 and PEG 600 and is present in an amount of about 17 to about 32 mol %, and the siloxane polymer is aminopropyl polysiloxane having a molecular weight of about 2000 to about 4000 and is present in an amount of about 17 to about 32 mol %.