Hydrogel formulations for use in electroosmotic extraction and detection of glucose

• US 20040062759A1
• Filed: 09/17/2003
• Published: 04/01/2004
• Est. Priority Date: 07/12/1995
• Status: Abandoned Application

• Current Assignee: Animas Technologies LLC (Johnson & Johnson)
• Original Assignee: Cygnus, Inc. (Johnson & Johnson)
• Inventors: Abraham, William, Plante, Phillip J., Joshi, Priti S., Berner, Bret, Vijayakumar, Prema
• Application Number:
  US10/664,467
• Publication Number:
  US 20040062759A1
• Time in Patent Office: Days
• US Class Current: 424/94.1
• CPC Class Codes: A61K 49/0006 Skin tests, e.g. intradermal testing, test strips, delayed hypersensitivity
• CPC Class Codes: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/0496 characterised by using specific chemical compositions, e.g. hydrogel compositions, adhesives
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions

Abstract

A hydrogel patch is disclosed which is comprised of a polymeric material which forms a gel with water with the material being present in an amount of about 0.5% to 40% by weight based on the weight of the patch. Electrical conductively of the water is increased by the addition of an electrolyte. The patch comprises an enzyme which is capable of catalyzing a reaction with a biomedically important molecule such as glucose. Glucose drawn into the patch undergoes a reaction with the aid of the enzyme and the hydrogen peroxide released flows through the electrically conductivity of the water and may react at an electrode surface to generate a signal related to the amount of glucose entering the patch. The patch is also preferably comprised of a buffer which maintains the pH of the patch in the range of from about 3 to 9, and may be further comprised of a cross-linking agent, a biocide, a humectant, and a surfactant. The patch is preferably in the form of a thin (5 μm-50 mils), flat circular disc (0.5 to 10 cm² of area) which will conform to the contours of human skin and may have a non-woven fabric embedded therein and removable release liners on each surface.

Claims

1. A hydrogel patch, comprising:

(a) a hydrophilic compound which forms a gel in the presence of water, which compound is present in an amount of about 4% or more by weight based on the weight of the hydrogel;

(b) water in an amount of about 95% or less based on the weight of the hydrogel;

(c) an enzyme capable of catalyzing a reaction; and

(d) an electrolyte.

2. The hydrogel patch of claim 1, wherein background signal in the gel is less than approximately 200 nA.

3. The hydrogel patch of claim 1, wherein background signal in the gel is less than approximately 50 nA.

4. The hydrogel patch of claim 1, wherein a product of the reaction in step (c) is not degraded more than 20% in 30 minutes.

5. The hydrogel patch of claim 1, wherein diffusion of an analyte that reacts in the reaction of step (c) is rate limiting, and wherein diffusion of the analyte is more rapid than the measurement time.

6. The hydrogel patch of claim 1, wherein the hydrogel further comprises components for maintaining a selected hydrogel environment, and wherein the environment enhances the conversion of analyte to product of the reaction in step (c).

7. The hydrogel patch of claim 1, wherein the enzyme catalyzes a reaction between glucose and oxygen resulting in the generation of electrons.

8. The hydrogel patch of claim 7, further comprising:

(e) a buffering agent present in an amount sufficient to maintain a pH in the hydrogel in a range of from about 3 to about 9.

9. The hydrogel patch of claim 8, further comprising:

(f) mutarotase.

10. The hydrogel patch of claim 1, wherein the hydrophilic compound is selected from the group consisting of polyethylene oxide, polyacrylic acid, polyvinyl alcohol, Carbopol®

, and polyacrylamidomethylpropanesulfonate and copolymers thereof;

the electrolyte is selected from the group consisting of NaCl and KCl and the enzyme is glucose oxidase, wherein glucose oxidase is present in an amount in a range of 10 Units to 5,000 Units per gram of the sum of the absorbant material in step (a) and the aqueous solution in step (b).

11. The hydrogel patch of claim 1, wherein the hydrophilic compound is present in an amount of less than about 40% by weight and the water is present in an amount of more than 60% by weight based on the weight of the hydrogel.

12. The hydrogel patch as claimed in claim 1, wherein the hydrophilic compound is present in an amount in the range of from about 8% to about 12% based on total weight of the hydrogel when a humectant is present in the hydrogel.

13. The hydrogel patch as claimed in claim 1, wherein the hydrophilic compound is present in an amount in the range of from about 15% to about 20% based on total weight of the hydrogel when a humectant is omitted from the hydrogel.

14. The hydrogel patch of claim 1, characterized by a flat configuration having a thickness in a range of about 5 μ

m to about 60 mils.

15. The hydrogel patch of claim 14, characterized by a first and a second surface area wherein each surface area is in a range of about 0.5 cm² to about 10 cm² and wherein the patch has a thickness of from about 5 μ

m to 10 mils.

16. The hydrogel patch as claimed in claim 1, further comprising a structural support material embedded in the hydrogel, wherein the structural support material is a non-woven fabric having an outer parameter configuration and size substantially equal to that of the hydrogel patch.

17. An absorbent material patch, characterized by:

(a) an absorbent material having embedded therein a dry enzyme;

(b) a package attached to a first surface of the absorbent material, the package containing an aqueous solution of water having dissolved therein an electrolyte, the package being separated from the absorbent material by a seal which is breakable on the application of force and further wherein the package is readily detachable from the absorbent material after the seal is broken.

18. The absorbent patch as claimed in claim 17, wherein the enzyme is lyophilized glucose oxidase present in an amount in the range of 10 Units to 5,000 Units per gram of the sum of the absorbent material in step (a) and the aqueous solution in step (b).

19. The absorbent patch as claimed in claim 18, wherein the enzyme is present in an amount of 100 to 3,000 units per gram of the sum of the absorbent material in step (a) and the aqueous solution in step (b), the aqueous solution further comprises a buffering agent dissolved in the water which buffering agent is present in an amount sufficient to maintain the pH of the absorbent patch in the range of from about 3 to about 9.

20. The absorbent patch as claimed in claim 17, wherein the absorbent material is a sponge and the enzyme catalyzes a reaction with glucose.

21. The absorbent patch as claimed in claim 17, wherein the absorbent material has a first and a second surface area wherein each surface area is in a range of from about 0.5 cm² to about 10 cm² and a thickness in the range of about 5 μ

m to about 50 mils.

22. A patch having a thickness in a range of about 5 μ

m to 50 mils and a first and a second surface each having an area in a range of about 0.5 cm² to about 10 cm², comprising;

a material which holds water in place;

an enzyme which catalyzes a reaction with glucose.

23. The patch of claim 22, further comprising;

water in an amount of about one to twenty times by weight the amount of the material which holds water in place;

a chloride containing salt, and

a buffering agent present in an amount sufficient to maintain the pH of the patch in a range of from about 3 to 9.

24. The patch as claimed in claim 23, wherein the enzyme is glucose oxidase, the material which holds water in place is a polymeric compound which forms a gel in the presence of water and the salt is selected from the group consisting of NaCl and KCl.

25. The patch as claimed in claim 24, further comprising:

a release liner on the first surface and the second surface; and

a non-woven material embedded in the material which holds water in place.

26. The patch as claimed in claim 24, characterized by sufficient flexibility so as to conform to human skin, adhesive on human skin without leaving tactile gel residue on the skin when the gel is removed.

27. A dry gel patch on a solid support, prepared by the method comprising:

(a) mixing dry gel components and an amount of water to form a gel mixture;

(b) cross-linking the gel mixture to form a hydrated gel;

(c) attaching the hydrated gel to a solid support; and

(d) drying the gel on the solid support,

wherein said dry gel components comprise a hydrophilic compound which forms a gel in the presence of water, which compound is present in an amount of about 4% or more by weight based on the weight of the hydrated gel, an enzyme capable of catalyzing a reaction, an electrolyte, and

wherein the amount of water is about 95% or less based on the weight of the hydrated gel.