Hydrophilic, swellable coatings for biosensors

• US 6,462,162 B2
• Filed: 07/28/1998
• Issued: 10/08/2002
• Est. Priority Date: 03/27/1995
• Status: Expired due to Term

• Current Assignee: Minimed, Inc. (Medtronic Plc)
• Original Assignee: Minimed, Inc. (Medtronic Plc)
• Inventors: Van Antwerp, William Peter, Mastrototoro, John J., Decker, Christian C.
• Primary Examiner(s): COONEY, JOHN M
• Application Number:
  US09/123,930
• Publication Number:
  US 20010008931A1
• Time in Patent Office: 1,533 Days
• Field of Search: 528/77, 528/85, 427/2.12, 427/58, 428/423.1
• 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 making a hydrogel, said method comprising:

admixing (a) a diisocyanate, said diisocyanate comprising about 50 mol% of the reactants in said 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 said hydrogel, wherein said hydrogel has a water pickup of at least about 120% by weight.

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

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

-methylenebis(cyclohexyl isocyanate).

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

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

6. The method in accordance with claim 5, wherein said diamino poly(oxyalkylene) is poly(propylene glycol) bis(2-aminopropyl ether).

7. The method in accordance with claim 5, wherein said 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 weigt of about 2000.

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

9. The method in accordance with claim 1, wherein said chain extender is selected from the group consisting of butanediol, ethylenediamine, hexamethylenediamine, 1,2-diaminocyclohexane and isophoronediamine.

10. The method in accordance with claim 1, wherein said diisocyanate is 1,6-hexamethylene diisocyanate and said 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 an average molecular weight of about 2000 and is present in an amount of about 40 to about 50 mol%.

11. The method in accordance with claim 1, wherein said diisocyanate is 1,6-hexamethylene diisocyanate, said 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 an average molecular weight of about 2000 and is present in amount of about 40 to about 50 mol%, and said chain extender is butanediol and is present in an amount of about 2.5 to about 10 mol%.

12. A hydrogel, said hydrogel formed by admixing

(a) a diisocyanate, said diisocyanate comprising about 50 mol% of the reactants in said 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 said hydrogel, wherein said hydrogel has a water pickup of at least about 120% by weight.

13. A hydrogel in accordance with claim 12, wherein said hydrogel has a water pickup of from about 120% to about 400% by weight.

14. A hydrogel in accordance with claim 12, wherein said diisocyanate is a member selected from the group consisting of isophorone diisocyanate, 1,6-hexamethylene diisocyanate and 4,4′

-methylenebis(cyclohexyl isocyanate).

15. A hydrogel in accordance with claim 12, wherein said hydrophilic diol is a member selected from the group consisting of a poly(alkylene)-glycol, a polyester-based diol and a polycarbonate polyol.

16. A hydrogel in accordance with claim 12, wherein said hydrophilic polymer diamine is a diamino poly(oxyalkylene).

17. A hydrogel in accordance with claim 16, wherein said diamino poly(oxyalkylene) is poly(propylene glycol) bis(2-aminopropyl ether).

18. A hydrogel in accordance with claim 16, wherein said diamino poly(oxyalkylene) is 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 or a polyoxypropylenediamine having an average molecular weight of about 2000.

19. A hydrogel in accordance with claim 12, wherein said chain extender is selected from the group consisting of an alkylene diol, an alkylene diamine, an aminoalkanol and combinations thereof.

20. A hydrogel in accordance with claim 12, wherein said chain extender is selected from the group consisting of butanediol, ethylenediamine, hexamethylenediamine, 1,2-diaminocyclohexane and isophoronediamine.

21. A hydrogel in accordance with claim 12, wherein said diisocyanate is 1,6-hexamethylene diisocyanate and said 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 an average molecular weight of about 2000 and is present in an amount of about 40 to about 50 mol%.

22. A hydrogel in accordance with claim 12, wherein said diisocyanate is 1,6-hexamethylene diisocyanate, said 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 an average molecular weight of about 2000 and is present in an amount of about 40 to about 50 mol%, and said chain extender is butadenediol and is present in an amount of about 2.5 to about 10 mol%.