TWI387605B - Hydrogel composition - Google Patents

Description

Hydrocolloid composition

The present invention is generally directed to hydrocolloid compositions. The hydrocolloid composition of one application is debugged for use in a percutaneous method to determine the concentration of an analyte (eg, glucose).

Quantitative determination of analytes in body fluids is important in the diagnosis and maintenance of certain physiological abnormalities. For example, lactate, cholesterol, and bilirubin should be monitored in certain individuals. In particular, individuals with diabetes often check the amount of glucose in their body fluids to control the glucose uptake in their diet. The results of these tests can be used to determine which insulin or other drug to be administered, if any.

In some prior art, a lancet can be used to extract fluid (eg, blood) from a user. The fluid is then used to determine the concentration of the analyte using an instrument or meter. It is desirable to eliminate the need to use a lancet while still accurately determining the concentration of the analyte.

One non-invasive method for obtaining a sample without the use of a lancet is to use a transdermal sample of the analyte found in the interstitial fluid (ISF). In this method, the composition is placed on the skin and helps promote the extraction of the ISF from the skin of the user to the sensing device or gauge. The composition needs to have sufficient mechanical and thermal stability to provide a relatively static, reactive, and aqueous conductor between the skin sampling site and the sensing device. Compositions containing these attributes should be found and debugged for transdermal sampling.

According to an embodiment, a hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from the formula I: Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 It is selected from 1 carbon to 5 carbon atoms to form a 3-7 membered heterocyclic moiety.

The second single system is selected from the group consisting of Formula II and Formula III, wherein Formula II is Wherein R 3 and R 4 are independently selected from the group consisting of H, CH ₃ , (C ₃ -C _{1 8} )alkyl, (C ₃ -C ₇ )cycloalkyl or an aromatic moiety. The alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moieties. The heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The aromatic moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. If R3 is H or CH _3, then R4 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety. The alkyl, cycloalkyl or aromatic moiety is optionally substituted with one or more substituents. If R4 is H or CH _3, then R ₃ is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety. The alkyl, cycloalkyl or aromatic moiety is optionally substituted with one or more substituents.

Formula III is Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety. The alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moieties. The heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The aromatic moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

According to an embodiment, an electrochemical sensor system includes an electrochemical sensor and a hydrocolloid composition. The electrochemical sensor has at least one opposing electrode and a working electrode. The hydrocolloid composition contacts the working electrode. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from the group consisting of hydroxyalkyl methacrylate, acrylamide, N,N-dialkyl acrylamide, methacrylic acid, acrylic acid, metal methacrylate, metal acrylate, itaconic acid , maleic acid, methacrylamide, N,N-dialkyl acrylamide, styrene sulfonic acid, metal styrene sulfonate, styrene carboxylic acid, metal styrene carboxylic acid, acrylamide - 2-methylpropanesulfonic acid, acrylamide-2-methylpropanesulfonic acid metal salt, halogenated 2-vinyl N-alkylpyrazole, halogenated 4-vinyl N-alkylpyridinium or discussed above Formula I. The second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV, wherein Formulas II and III are as discussed above.

Formula IV is Wherein R2 is selected from (C ₁ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl, and aromatic moiety. The alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moieties. The heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The aromatic moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

According to an embodiment, an electrochemical sensor system includes an electrochemical sensor and a hydrocolloid composition. The electrochemical sensor has at least one opposing electrode and a working electrode. The hydrocolloid composition contacts the working electrode. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from Formula I discussed above. The second single system is selected from the group consisting of alkyl (meth)acrylates, formula II, formula III, and formula IV, which are as discussed above.

According to an additional embodiment, an electrochemical sensor system includes an electrochemical sensor and a hydrocolloid composition. The electrochemical sensor has at least one opposing electrode and a working electrode. The hydrocolloid composition contacts the working electrode. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from the group consisting of N-vinylpyrrolidone, hydroxyalkyl methacrylate, acrylamide, and N,N-dialkyl acrylamide. The second single system is selected from the group consisting of alkyl (meth)acrylates, N-vinyl acrylamides, vinyl esters, and vinyl ethers. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

In accordance with another embodiment, an electrochemical sensor system includes an electrochemical sensor and a hydrocolloid composition. The electrochemical sensor has at least one opposing electrode and a working electrode. The hydrocolloid composition contacts the working electrode. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first monomer has a hydrophilic character. The second monomer has a hydrophobic character. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

According to one method, the concentration of the analyte is determined by placing the hydrocolloid composition on the skin. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from the group consisting of hydroxyalkyl methacrylate, acrylamide, N,N-dialkyl acrylamide, methacrylic acid, acrylic acid, metal methacrylate, metal acrylate, itaconic acid , maleic acid, methacrylamide, N,N-dialkyl acrylamide, styrene sulfonic acid, metal styrene sulfonate, styrene carboxylic acid, metal styrene carboxylic acid, acrylamide - 2-methylpropanesulfonic acid, acrylamide-2-methylpropanesulfonic acid metal salt, halogenated 2-vinyl N-alkylpyrazole, halogenated 4-vinyl N-alkylpyridinium or discussed above Formula I. The second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV, as discussed above. A sensor is provided and the hydrocolloid composition is generally positioned between the skin and the sensor and couples the skin and the sensor. The interstitial fluid is sampled to determine the concentration of the analyte using the sensor.

According to another method, the concentration of the analyte is determined. The method comprises placing a hydrocolloid composition on the skin. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from Formula I discussed above. The second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV, as discussed above. A sensor is provided and the hydrocolloid composition is generally positioned between the skin and the sensor and couples the skin and the sensor. The interstitial fluid is sampled to determine the concentration of the analyte using the sensor.

The concentration of the analyte is determined according to an additional method. The method comprises placing a hydrocolloid composition on the skin. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first single system is selected from the group consisting of N-vinylpyrrolidone, hydroxyalkyl methacrylate, acrylamide, and N,N-dialkyl acrylamide. The second single system is selected from the group consisting of alkyl (meth)acrylates, N-vinylguanamines, vinyl esters, and vinyl ethers. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. A sensor is provided and the hydrocolloid composition is generally positioned between the skin and the sensor and couples the skin and the sensor. The interstitial fluid is sampled to determine the concentration of the analyte using the sensor.

According to another method, the concentration of the analyte is determined. The method comprises placing a hydrocolloid composition on the skin. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent. The first monomer has a hydrophilic character. The second monomer has a hydrophobic character. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. A sensor is provided and the hydrocolloid composition is typically positioned between the skin and the sensor and couples the skin to the sensor. The interstitial fluid is sampled to determine the concentration of the analyte using the sensor.

This invention relates to novel hydrocolloid compositions. The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent, and a solvent (eg, water). The hydrocolloid composition is a random copolymer network that combines at least the first monomer and the second monomer in the form of a polymeric chain. The copolymer network is controlled, at least to some extent, by the volume percentage of the first monomer and the second monomer.

The terms identified below always have the following meaning: The term "alkyl" means a linear or branched saturated carbon group. The terms "(C ₁ -C ₃ )alkyl", "(C ₁ -C _{1 8} )alkyl" and "(C ₃ -C _{1 8} )alkyl" mean 1 to about 3 carbon atoms, respectively. A linear or branched saturated carbon group of from 1 to about 18 carbon atoms or from about 3 to about 18 carbon atoms. Such groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, t-butyl, and the like.

The term "optionally substituted" means (unless otherwise indicated) that the portion so modified may have one or more of the indicated substituents. Each substituent may replace any hydrogen atom on the thus modified moiety, with the proviso that the substitution is chemically feasible and stable. For example, a chemically labile compound should be a compound in which each of the two substituents is bonded to a single C atom via a hetero atom of each substituent. Another example of a chemically labile compound is a compound in which an alkoxy group is bonded to an unsaturated carbon of an olefin to form an enol ether. When two substituents are present on any moiety, each substituent is selected independently of the other substituent such that the substituents may be the same or different, respectively.

The term "cycloalkyl" means a saturated monocyclic alkyl group. The term "(C ₃ -C ₇ )cycloalkyl" means a saturated monocyclic alkyl group of from about 3 to about 7 carbon atoms. Such groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.

The term "(C ₃ -C ₆ )dihydroxyalkyl" means an alkyl group as described above comprising two hydroxyl (-OH) groups bonded to a saturated carbon. The (C ₃ -C ₆ )dihydroxyalkyl groups may be straight or branched. The hydroxyl component of the (C ₃ -C ₆ ) dihydroxyalkyl group is usually adjacent to each other. However, the (C ₃ -C ₆ ) dihydroxy component can be added to any available carbon. (C ₃ -C ₆ )Dihydroxyalkyl includes, but is not limited to, 2,3-dihydroxypropyl, 3,4-dihydroxybutyl, 5,6-dihydroxyhexyl, and the like.

The term "(C ₂ -C ₆ )hydroxyalkyl" is intended to include an alkyl group as described above bonded to a hydroxyl (-OH) component of a saturated carbon. The (C ₂ -C ₆ )hydroxyalkyl groups can be straight or branched. The hydroxyl component of the (C ₂ -C ₆ ) hydroxyalkyl group can be located at any available carbon. (C ₂ -C ₆ )hydroxyalkyl groups include, but are not limited to, 2-hydroxyethyl, 3-hydroxypropyl, and the like.

The term "halo" means an atom selected from the group consisting of Cl, Br and F.

The term "haloalkyl" is intended to include an alkyl group as described above bonded to one or more halo groups of a saturated carbon. The haloalkyl groups can be straight or branched. The haloalkyl halide component can be located at any available carbon. Such haloalkyl groups include, but are not limited to, 2-chloroethyl, 3-bromopropyl, 2,2,3,3,3-pentafluoropropyl and the like.

The term "nitro" means an atom selected from the group consisting of -NO ₂ , cyano (-CN), -NHCH ₃ and -NHC ₂ H ₅ .

The term "heterocyclic moiety" is a material containing a cyclic structure in which an atom other than carbon (for example, sulfur, oxygen or nitrogen) forms part of the ring. For example, the 3-7 membered heterocyclic moiety includes at least one atom other than carbon that forms part of the ring or backbone of the 3-7 membered ring structure. The 4-8 membered heterocyclic moiety includes at least one atom other than carbon which forms part of the ring or backbone of the 4-8 membered ring structure.

The term "hydrophilic feature" means having an affinity for water or other polar solvent; it is readily absorbed or dissolved in water or other polar solvent.

The term "hydrophobic feature" means having no affinity for water or other polar solvents; it is not readily absorbed or dissolved in water or other polar solvents.

The term "aromatic moiety" means a substance containing one or more benzene rings. The aromatic substituent can be monocyclic, bicyclic or tricyclic. Non-limiting examples of aromatic substituents include phenyl, benzyl, naphthyl, anthryl and the like.

A notation such as "(meth)acrylic acid" is used herein to denote a methyl substituent as appropriate. Thus, for example, "(meth)acrylic" includes methacrylic acid and acrylic acid.

As discussed above, the hydrocolloid compositions include a first monomer and a second monomer. An example of a first monomer is a compound of formula I which is N-vinyl decylamine.

Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 It is selected from 1 carbon to 5 carbon atoms to form a 3-7 membered heterocyclic moiety.

CH ₃ wherein R is H and R1 is one of formula I, N- vinyl-based non-limiting examples as acetamide. Other examples of Formula I include R being CH ₂ CH ₃ and R1 being H, which is N-vinyl acrylamide.

Non-limiting examples of the cyclic structure of Formula I include N-vinylpyrrolidone, which is a 5-membered heterocyclic compound comprising 4 carbons and 1 nitrogen in its backbone. N-vinylpyrrolidone is shown below as Compound A: Another example of a cyclic structure of formula I is N-vinyl caprolactam.

It is desirable for Formula I to have a hydrophilic character. It is necessary to independently select R and R1 such that Formula I has a hydrophilic character. It is also desirable to select a combination of R and R1 to form a cyclic structure of formula I having a hydrophilic character.

In one embodiment, the first monomer of Formula I and the second monomer of Formula II (which are discussed below), a crosslinking agent, and a solvent form a hydrocolloid composition. The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. More specifically, the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20 and, even more specifically, from about 40:60 to about 60:40. An example of a second monomer is a compound of formula II which is N-vinylguanamine.

Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cyclo alkyl, nitro and cyano, with the proviso that: when R3 is H or CH _3, then R4 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, Group or an aromatic moiety optionally substituted with one or more substituents.

Wherein R3 or R4 is (C ₃ -C _{1 8)} alkyl and wherein the alkyl group optionally substituted examples of formula II include (but are not limited to) N- vinylbutyrolactam acyl substituted by one or more amine, N - vinyl pentamidine, N-vinyl dodecylamine, N-vinyl 4-chlorobutylimamine and the like.

Wherein R3 or R4 is (C ₃ -C ₇₎ cycloalkyl wherein the cycloalkyl and optionally substituted with one or more substituents of formula II include (but are not limited to) N- vinylcyclohexyl 2carboxamide Amine, N-vinylcyclopentylcarboxamide, N-vinyl 4-bromocyclohexylcarboxamide and the like.

Examples of Formula II wherein R3 or R4 is an aromatic moiety and wherein the aromatic moiety is optionally substituted with one or more substituents include, but are not limited to, N-vinylbenzamide, N-vinyl 4- Nitrobenzamide, N-vinylnaphthylamine and the like.

Formula II is required to have hydrophobic character. It is necessary to independently select R3 and R4 such that Formula II has a hydrophobic character.

In another embodiment, the first monomer of Formula I and the second monomer of Formula III, which are discussed below, a crosslinking agent, and a solvent form a hydrocolloid composition. Another embodiment of the second monomer is a compound of formula III which is a vinyl ether.

Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano .

Examples of Formula III wherein R5 is (C ₃ -C _{1 8} )alkyl and wherein the alkyl group is optionally substituted with one or more substituents include, but are not limited to, vinyl propyl ether, vinyl hexyl ether, Vinyl lauryl ether, vinyl 4-chlorobutyl ether and the like.

Examples of Formula III wherein R5 is (C ₃ -C ₇ )cycloalkyl and wherein the cycloalkyl is optionally substituted with one or more substituents include, but are not limited to, vinylcyclohexyl ether, vinylcyclopentane Ether, vinyl 4-bromocyclohexyl ether and the like.

Examples of Formula III wherein R5 is an aromatic moiety and wherein the aromatic moiety is optionally substituted with one or more substituents include, but are not limited to, vinyl phenyl ether, vinyl 4-nitrophenyl ether, ethylene 2-naphthyl ether and its analogs.

When the first monomer and the second monomer are mixed with a solvent (e.g., water), the structural integrity of the materials may not be as strong as desired. This is especially the case if the first monomer and the second monomer are mixed with a large amount of solvent. To further increase the mechanical strength, a crosslinking agent is added to the first monomer and the second monomer.

Non-limiting examples of crosslinking agents that can be used include, but are not limited to, the following: polyfunctional vinyl ethers, divinyl benzene, polyfunctional acrylates, and multifunctional decylamines. In order to be a desirable crosslinker for the first and second monomers, the crosslinker must have a geometry that links the two polymeric chains.

According to an embodiment, a crosslinking compound of formula V (polyfunctional vinyl ether) can be used.

Where "x" is from 0 to about 4. In Formula V, "x" helps determine the identity of the crosslinked compound. In particular, the greater the "x" component of the compound of Formula V, the better the flexibility and tear strength of Formula V. By improving the flexibility and tear strength, the amount of solvent added to form the hydrocolloid can be greater.

An example of a polyfunctional vinyl ether useful as a crosslinking agent is diethylene glycol divinyl ether, which is shown below as Compound B:

It is contemplated that other polyfunctional vinyl ethers can be used as crosslinking agents such as triethylene glycol divinyl ether and tetra (ethylene glycol) divinyl ether.

According to another embodiment, a crosslinking compound of formula VI (divinylbenzene) can be used: Wherein R6 is selected from CH _2, O or CH ₂ -CH _2.

An example of a polyfunctional acrylate useful as a crosslinking agent is ethylene glycol dimethacrylate (EGDMA), which is shown below as Compound C.

Other multifunctional acrylates are contemplated as crosslinkers, such as polyethylene glycol diacrylate, diethylene glycol dimethacrylate, diethylene glycol diacrylate, ethylene glycol diacrylate, and dimethyl. 1,3-dihydroxypropyl acrylate.

An example of a polyfunctional acrylamide which can be used as a crosslinking agent is N,N'-methylenebispropenylamine, which is shown below as Compound D.

It is contemplated that other polyfunctional acrylamides can be used as the crosslinking agent.

The copolymer network composition typically comprises from about 0.01 to about 10% by volume of a crosslinking agent. Prior to curing, the copolymer network composition is defined herein to include a first monomer, a second monomer, a crosslinking agent, and other components as discussed below. The copolymer network composition as defined does not include a solvent (e.g., water). More specifically, the polymeric network composition comprises from about 0.1 to about 1% by volume of a crosslinking agent.

To aid in polymerization, a photoinitiator can be added to the first monomer, the second monomer, and the crosslinking agent. An example of a photoinitiator is Ciba Specialty Chemicals Pty, Ltd. with Irgacure. 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone sold in 2959. Other photoinitiators are expected to be added. The polymeric network composition typically comprises from 0.0001 to about 5% by weight of a photoinitiator.

The first monomer and the second monomer are mixed with a solvent. An example of one of the solvents commonly used is water. Other examples of solvents are water mixtures. Other solvents are contemplated for use in the present invention. The amount of water can vary and depends primarily on the amount of the first monomer and the second monomer present in the hydrocolloid composition. It is contemplated that other materials may be added to the hydrocolloid composition of the first monomer, the second monomer, the crosslinking agent, and the solvent.

After the addition of the crosslinking agent, the first monomer forms a crosslinked copolymer network with the second monomer. In order to achieve polymerization of the first monomer and the second monomer with a crosslinking agent, such as ultraviolet (UV radiation by adding a UV initiator), thermal initiation (by adding a thermal initiator), γ-ray and The electron beam method initiates polymerization. To aid in polymerization, a photoinitiator can be added to the first monomer, the second monomer, and the crosslinking agent. In one method, the copolymer network is soaked in a solvent (eg, water) to form a hydrocolloid composition.

In an embodiment, the hydrocolloid composition can be tuned to act as an interface between the skin and an inductor (eg, an electrochemical sensor). In one method, the sensor uses the hydrocolloid composition to determine the concentration of an analyte in an ISF (interstitial fluid). Analyzable analytes include glucose, lipid profiles (eg, cholesterol, triglycerides, LDL, and HDL), microalbumin, hemoglobin A _{1 C} , fructose, lactate, or bilirubin. It is expected that the concentration of other analytes can be determined. As used in this application, the term "concentration" refers to the concentration of an analyte, activity (eg, enzyme and electrolyte), force (eg, antibody), or any other concentration used to measure the desired analyte.

The hydrocolloid composition, which in this embodiment will serve as the interface between the skin and the sensor, comprises a first monomer, a second monomer, a crosslinking agent, and a solvent (eg, water). The hydrocolloid composition combines a random copolymer network of at least a first monomer and a second monomer in the form of a polymeric chain. The copolymer network is controlled, at least to some extent, by the volume percentage of the first monomer and the second monomer. In the present application, it is advantageous for the hydrocolloid composition to have a balance between gel strength and flexibility. It is also desirable for the hydrocolloid composition to have a desirable signal strength.

The first monomer is tuned to provide a hydrophilic character to the hydrocolloid composition. The first monomer comprises a compound of formula I (N-vinylguanamine), which is discussed in more detail above.

Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 It is selected from 1 carbon to 5 carbon atoms to form a 3-7 membered heterocyclic moiety.

It is contemplated that other first monomers may be used, including hydroxyalkyl methacrylate, acrylamide, N,N-dialkyl acrylamide, methacrylic acid, acrylic acid, metal methacrylate, metal acrylate, clothing Kang acid, maleic acid, methacrylamide, N,N-dialkyl acrylamide, styrene sulfonic acid, styrene sulfonate metal salt, styrene carboxylic acid, styrene carboxylic acid metal salt, acrylonitrile Amine-2-methylpropanesulfonic acid, acrylamide-2-methylpropanesulfonic acid metal salt, halogenated 2-vinyl N-alkylpyrazole or halogenated 4-vinyl N-alkylpyridinium.

An example of a hydroxyalkyl methacrylate which can be used as the first monomer is hydroxyethyl methacrylate, which is shown below as compound E.

Other hydroxyalkyl methacrylates are contemplated for use as the first monomer, such as hydroxypropyl methacrylate, hydroxyethyl acrylate, 2,3-dihydroxypropyl methacrylate, and 2,3-dihydroxypropyl acrylate. ester.

The acrylamide which can be used as the first monomer is shown in the following compound F.

An example of an N,N-dialkyl acrylamide which can be used as the first monomer is N,N-dimethyl decylamine, which is shown as Compound G.

Other N,N-dimethyl acrylamides are contemplated for use as the first monomer, such as N,N-di-n-propyl acrylamide, N-isopropyl acrylamide, and N,N-dimethyl Acrylamide.

According to another embodiment, the first monomer may be methacrylic acid as shown below for compound H:

The second monomer is commissioned to provide mechanical strength to the hydrocolloid composition. Commissioning the second monomer also provides hydrophobic characteristics to the hydrocolloid composition. The amount of solvent (e.g., water) is preferably controlled by providing a hydrophobic character to the hydrocolloid composition.

In one embodiment, the second single system is related to the compound of formula II (N-vinylguanamine), which is discussed in more detail above.

Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cyclo alkyl, nitro and cyano, with the proviso that: when R3 is H or CH _3, then R4 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, Group or an aromatic moiety optionally substituted with one or more substituents.

In another embodiment, the second single system is related to the compound of formula III (vinyl ether), which is discussed in more detail above.

Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group optionally substituted with a substituent or more substituents selected from the group consisting of live of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro And a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide base.

An additional embodiment of one of the second monomers is a compound of formula IV which is a vinyl ester.

Wherein R 2 is selected from (C ₁ -C _{1 8} )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano .

Examples of Formula IV wherein R2 is (C ₁ -C _{1 8)} alkyl and wherein the alkyl group optionally substituted with one or more substituents to include (but not limited to) 2-chloroethyl, 3-bromopropyl 2,2,3,3,3-pentafluoropropyl group and the like.

Examples of Formula IV wherein R 2 is (C ₃ -C ₇ )cycloalkyl and wherein the cycloalkyl is optionally substituted with one or more substituents include, but are not limited to, cyclopentyl, cyclohexyl, 2-chloro Cyclohexyl, 4-bromocyclohexyl and the like.

Examples of Formula IV wherein R2 is an aromatic moiety and wherein the aromatic moiety is optionally substituted with one or more substituents include, but are not limited to, vinyl benzoate, vinyl phenyl acetate, ethylene 4-bromobenzoate Ester, vinyl 4-nitrobenzoate, vinyl 1-naphthalene dicarboxylate, vinyl 2-naphthalene dicarboxylate and the like.

A vinyl ester such as vinyl acetate or vinyl dodecate can be used as the second monomer. Vinyl acetate is shown below as compound J, and vinyl dodecanoate is shown as compound K.

It is contemplated that other vinyl esters can be used as the second monomer, such as vinyl propionate and vinyl butyrate. Formula IV is required to have hydrophobic character. It is desirable to select R2 such that Formula IV has hydrophobic character.

In addition to the second monomer formed from Formula II-IV, it is contemplated that the second monomer may additionally include, but is not limited to, an alkyl (meth)acrylate comprising an alkyl methacrylate and an alkyl acrylate. An example of one of the alkyl methacrylates that can be used as the second monomer is methyl methacrylate, which is shown below as compound L.

Other alkyl methacrylates are contemplated for use as the second monomer, such as ethyl methacrylate, propyl methacrylate, butyl methacrylate, amyl methacrylate, hexyl methacrylate, methacrylic acid. Heptyl ester, octyl methacrylate, 2-ethylhexyl methacrylate, decyl methacrylate, decyl methacrylate, undecyl methacrylate and dodecyl methacrylate.

The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. More specifically, the ratio of the first monomer to the second monomer is from about 80:20 to about 20:80, and even more specifically from about 60:40 to about 40:60.

An example of a copolymer network using the first monomer and the second monomer is shown by the following formula M.

The first monomer used in formula M is N-vinylpyrrolidone and the second monomer used in formula M is vinyl acetate. "n" and "m" in the formula M represent possible repeating monomer units, wherein "n" and "m" are greater than or equal to 1. The "n" and "m" of the formula M depend on the ratio of the first monomer to the second monomer present. It is contemplated that other combinations of the first monomer and the second monomer disclosed above can be used to form the hydrocolloid composition.

The copolymer network composition typically comprises from about 0.01 to about 10% by volume of a crosslinking agent. As discussed above, the copolymerized network composition is defined herein to include a first monomer, a second monomer, a crosslinker, and other components discussed below prior to curing. The copolymer network composition as defined does not include a solvent (e.g., water). More specifically, the polymeric network composition comprises from about 0.1 to about 1% by volume of a crosslinking agent.

As discussed above, to aid polymerization, a photoinitiator can be added to the first monomer, the second monomer, and the crosslinker. An example of a photoinitiator is Ciba Specialty Chemicals Ltd. with Irgacure 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone sold in 2959. Other photoinitiators are expected to be added.

The first monomer and the second monomer are mixed with a solvent. An example of one of the solvents commonly used is water. Another example of a solvent is a water mixture. Other solvents are contemplated for use in the present invention. However, in applications where analyte concentrations are determined, it is desirable that the solvent be substantially biocompatible with the skin. The amount of water can vary and depends primarily on the amount of first polymer and second polymer present in the hydrocolloid composition.

It is contemplated that other materials may be added to the hydrocolloid composition of the first monomer, the second monomer, the crosslinking agent, and the solvent. For example, an electrolyte can be added to the hydrocolloid composition. Depending on the application of the hydrocolloid composition, the electrolyte can act multiple times. First, the electrolyte is a chemical compound that ionizes when dissolved to produce a conductive medium. Second, the desirable electrolytes contain high salt concentrations which help to exert osmotic pressure on the skin when used in contact with the skin. By applying an osmotic pressure to the skin, the electrolyte helps drive out the interstitial fluid (ISF) containing the analyte. Non-limiting examples of electrolytes that can be used include the sodium and potassium chlorides, phosphates, citrates, acetates, and lactates.

The solution may additionally include an enzyme to aid in determining the analyte concentration. Depending on the analyte, the enzyme can help convert the analyte into a species that can be detected by, for example, electrochemical detection. An example of an enzyme that can be used to determine glucose is glucose oxidase. Other enzymes such as glucose dehydrogenase are contemplated. If other analytes are of importance, an appropriately selected enzyme can help determine the concentration of the analyte. Usually (if an enzyme is used) it is added after the first monomer and the second monomer have solidified. The curing of the first monomer and the second monomer generally involves the use of thermal stress or the application of electromagnetic radiation, which can negatively affect the activity of the enzyme. However, it is contemplated that the enzyme can be mixed with the first monomer and the second monomer prior to curing.

The solution may additionally include a penetration enhancer. Permeation enhancers are desirable in applications where a hydrocolloid composition is applied to the skin. Penetration enhancers help open the pores of the skin. Non-limiting examples of penetration enhancers that can be used include, but are not limited to, squalene, unsaturated fatty acids, glycerol derivatives of fatty alcohols, dimethyl hydrazine, and alkyl esters of fatty acids.

Other materials that may be added to the hydrocolloid composition include biocides, humectants, surfactants, and combinations thereof. Biocides help inhibit bacterial growth. Non-limiting examples of biocides that can be used include the para-oxybenzoate series of preservatives, sodium benzoate, benzalkonium chloride, and trialkylamines.

Humectants help in applications where skin moisturization is required. Non-limiting examples of humectants that can be used include glycerin, hexylene glycol, and sorbitol, maltitol, polydextrose, propylene glycol, lactic acid, and metal lactate. The surfactant assists in coupling the hydrocolloid composition to the skin to achieve improved contact therebetween. Non-limiting examples of surfactants that can be used include, for example, TRITON X-100 (ethoxylated octylphenol of the formula C _{1 4} H _{2 2} O(C ₂ H ₄ O) _n wherein the average of "n" is 9 or 10) and sorbitol and such as TWEEN ^{T M} series of sorbitol derivatives.

If used in electrochemical applications, the hydrocolloid composition can be dried and reconstituted on the electrode surface prior to its use. If reconstituted, the solvent added may include an electrolyte.

In electrochemical applications, the hydrocolloid compositions typically have a thickness of from about 0.1 mils to about 100 mils, and more specifically from about 1 mil to about 30 mils. In one embodiment, the electrochemical sensor covered by the hydrocolloid composition has a surface area of from about 0.1 cm ² to about 100 cm ² .

The hydrocolloid composition has sufficient mechanical and thermal stability to provide a relatively stable, reactive, and aqueous conduit between the skin sampling site and the sensor, and more particularly, the hydrocolloid composition is required to have physical homogeneity and Flexibility and mechanical stability against shear forces. In selected applications, the hydrocolloid composition may be required to maintain a water content of from about 50 to about 90 weight percent for the desired duration (e.g., from about 24 to about 72 or more hours).

In addition, the hydrocolloid composition is highly hydrophilic to resist dehydration during long term use. The transport characteristics of the hydrocolloid composition are not altered by reducing or substantially eliminating dehydration. Hydrocolloid compositions are also required to maintain the porosity of the skin. The hydrocolloid composition also needs to exhibit relatively high compressibility to help ensure good skin/sensor connectivity or skin adhesion.

It is also desirable for the hydrocolloid composition to have a sufficiently large porosity for enzyme capture. For example, in certain applications involving glucose concentration determination, the hydrocolloid composition is required to provide a substrate for glucose oxidase (GO) and a diffusion channel for glucose and hydrogen peroxide.

After the addition of the crosslinking agent, the first monomer forms a crosslinked copolymer network with the second monomer. To achieve polymerization of the first monomer and the second monomer with a crosslinking agent, such as by ultraviolet (UV) radiation (eg, high intensity UV radiation), thermal initiation (eg, freeze-thaw cycle), gamma-ray And the method of electron beam initiates polymerization. To aid in polymerization, a photoinitiator can be added to the first monomer, the second monomer, and the crosslinking agent.

In one method, the copolymer network is soaked in a solvent (eg, water) to produce a hydrocolloid composition. The solvent can include the components discussed above, such as electrolytes, enzymes, penetration enhancers, biocides, humectants, surfactants, and combinations thereof. It is contemplated that electrolytes, enzymes, penetration enhancers, biocides, humectants, surfactants, and combinations thereof, can be added separately from the solvent to the copolymer network.

In one method, the hydrocolloid composition is dried to remove solvent and form a dried copolymer network or dried hydrocolloid composition. The dried hydrocolloid composition can be in the form of a film. The dried hydrocolloid composition can additionally include a mechanical support. The mechanical support aids in providing mechanical strength to the dried water colloidal composition film. Examples of mechanical supports include polymeric meshes, wovens, nonwovens, cellulose (eg, paper), or combinations thereof. Examples of cellulosic materials include commercially available paper (e.g., paper rags, paper towels, or filter paper) or cellulosic fabrics. Other mechanical supports are contemplated for use with the dried water colloidal composition film.

Typically, from about 10 to about 90% by weight of the cellulosic substrate is present and the remainder is a copolymeric network. Thus, in one embodiment, there is 10% by weight of the cellulosic substrate and 90% by weight of the copolymeric network.

In one embodiment, the copolymer network is absorbed into the porous cellulosic matrix. For example, a graft copolymerization reaction between the first monomer and the second monomer can occur onto the porous cellulose substrate. The reaction can be initiated by the use of high energy radiation, chemical initiation, and ultraviolet (UV) radiation in the presence of a photoinitiator.

An example of a hydrocolloid composition is shown in Figure 1, which has a dried hydrocolloid film system 10 comprising a dried hydrocolloid composition film 12 and a mechanical support 14. It is contemplated that the mechanical support can be more than one layer. According to another embodiment, the mechanical support can be embedded within the hydrocolloid composition.

In one method, the dried water colloidal composition film can be reconstituted with a solvent (eg, water). The hydrocolloid composition comprising a copolymer network and a solvent may comprise from about 1 to about 99 volume percent water.

In one method, the hydrocolloid composition is used to aid in determining the analyte concentration of interstitial fluid (ISF) with an inductor. More specifically, the hydrocolloid composition is tuned to act as an interface between the skin and the sensor and to couple the skin to the sensor. In this method, the sensor measures the concentration of the desired analyte from the ISF sample. In one embodiment, the inductor is an electrochemical sensor. An example of an electrochemical sensor includes a standard three-electrode regulator using a contact, platinum-containing working electrode. Other electrochemical sensors are contemplated, including those having fewer electrodes, such as a two-electrode electrochemical sensor, including an opposing electrode and a working electrode. It is also contemplated that other sensors, such as optical sensors, can be used.

Referring to Figure 2, an electrochemical inductor is shown in accordance with an embodiment. The electrochemical sensor 30 includes an opposite electrode 32, a working electrode 34, and a reference electrode 36. A detailed example of the electrochemical inductor includes a carbon counter electrode, a platinum working electrode, and a silver/silver chloride reference electrode. It is contemplated that the opposing, working and reference electrodes can be made from other materials.

As shown in FIG. 3, the electrochemical sensor system 50 includes the electrochemical sensor 30 of FIG. 2, a dried hydrocolloid film 52, and a bonding ring 54. The dried hydrocolloid film 52 comprises a hydrocolloid composition such as the solvent-free ones described above. In this embodiment, the adhesive ring 54 has two functions: (a) covering a portion of the dried hydrocolloid film 52 and fastening it to the electrochemical sensor 30; and (b) fastening including the dried water colloid The electrochemical sensor system 50 of the membrane 52 is attached to the skin.

In one method, the hydrocolloid composition is added to the skin. The hydrocolloid composition can be located at a skin site such as the forearm of the hand between the wrist and the elbow. It is contemplated that the hydrocolloid composition can be located at other skin sites such as the abdomen. The skin is then pretreated in the method to increase skin permeability. One example of pretreatment is the use of ultrasonic energy to disrupt the lipid bilayer of the stratum corneum to increase skin permeability. By increasing skin permeability, the amount of interstitial fluid (ISF) used in percutaneous sampling is increased. This resulted in improved sampling of important analytes (eg, glucose) found in the ISF. The sensor measures the concentration of the desired analyte after contacting the hydrocolloid composition and the ISF.

One of the non-limiting sources of ultrasonic energy systems is the Sontra SonoPrep sold by Sontra Medical Corporation. Ultrasonic skin penetration system. The SonoPrep The system applies relatively low frequency ultrasound energy to the skin for a limited duration (about 10 to 20 seconds). The supersonic horn contained in the device vibrates about 55,000 times per minute (55 KHz) and applies energy to the skin via the liquid coupling medium to produce cavitation bubbles that expand and contract in the coupling medium.

In another method, a hydrocolloid composition is added to the skin from an electrochemical sensor system (eg, electrochemical sensor system 50). The skin is then pretreated to increase skin permeability. One example of pretreatment is the use of the ultrasonic energy discussed above, using, for example, Sontra's SonoPrep sold by Sontra Medical Corporation. Ultrasonic skin penetration system. The electrochemical sensor measures the concentration of the desired analyte after contacting the hydrocolloid composition and the ISF.

Instance Example 1

Glucose concentrations were determined using a non-invasive test method. The method of generating the curves as shown in Figs. 4a and 4b is as follows.

The copolymer mixture comprises a first monomer (N-vinylpyrrolidone), a second monomer (vinyl acetate), and Ciba Specialty Chemicals Co., Ltd. as Irgacure Photoinitiator (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone) and crosslinker (diethylene glycol divinyl ether) sold in 2959. The copolymer mixture comprises 50 parts of N-vinylpyrrolidone, 50 parts of vinyl acetate, and 0.5 part of Irgacure. 2959 and 0.5 parts of diethylene glycol divinyl ether. The first monomer, the second monomer, the photoinitiator, and the crosslinking agent are mixed. The copolymerization mixture was bubbled with nitrogen (N ₂ ) for about 5 minutes. The copolymer mixture was then placed under an ultraviolet lamp for about 2.25 hours. The copolymer mixture was then removed and stored in a freezer.

The copolymerization mixture is cured to form a dried copolymer film. The dried copolymer film was purified by rinsing twice with hot deionized water at 80 ° C for 2 hours. The copolymer film was cooled with air to reform the dried copolymer film.

The dried copolymer film was mixed with the solution at 4 ° C for more than 16 hours to form a hydrocolloid film. The previously prepared solution was a phosphate buffered physiological saline solution containing 5% by weight of glucose oxidase. The only other additive included in the solution is the surfactant (0.05% by weight of Triton) X-100).

The hydrocolloid film is cut to the desired size and dried on the working area of the electrochemical sensor system. The dried hydrocolloid film on the electrochemical sensor is reconstituted with a buffered solvent (phosphate buffered physiological saline) to form a hydrocolloid composition. The hydrocolloid composition is applied to three different positions of the forearm of the hand between the wrist and the elbow. The forearm site 1 is close to the wrist, the forearm site 3 is close to the elbow, and the forearm site 2 is located between the forearm sites 1 and 3.

The forearm skin at the forearm sites 1-3 is pretreated by applying ultrasonic energy here. Glucose oxidase in the hydrocolloid composition contacts the skin and contains interstitial fluid (ISF) between glucose. Glucose oxidase helps convert glucose in the ISF to a peroxide. In response to the detection of peroxide, a current is generated from the electrochemical sensor. This current corresponds to the glucose concentration in the ISF.

The current is measured for each of the forearm sites 1-3 over a period of time. The true glucose concentration was also measured at the same time using the ANAlOX-Glucose Analyzer GM 10 (Glucose Analyser GM 10) sold by Analis, which is a comparison method. This is labeled as "plasma glucose" in Figures 4a and 4b. See Figure 4a, the current measured by the above method using the forearm sites 1-3 and the comparison method (labeled plasma glucose in Figure 4a). ) Draw a curve relative to time (seconds). In addition, the graph of Figure 4a includes glucose in mg/dL, which correlates with the measured current. To better compare the same points, the number of forearm sites 2 and 3 is normalized relative to the highest observed sensor signal current. The forward-looking readings of the forearms 2 and 3 are shown in Figure 4b along with the forearm site 1 and plasma glucose.

The results of the tests demonstrating the glucose values determined using the methods of the invention (forearm sites 1-3) are related to the target parallel glucose values in the comparison method (plasma glucose).

Example 2

In Example 2, two different compositions of the present invention were prepared. In the hydrocolloid pad 1 of the present invention, a copolymer network and a cellulose substrate are grafted together, and in the hydrocolloid pad 2 of the present invention, a copolymer network is formed and then placed on a nylon web.

Specifically, in the hydrocolloid pad 1 of the present invention, the copolymer network and the cellulose substrate are grafted together. The copolymer network comprises 60 parts of N-vinylpyrrolidone (first monomer), 40 parts of vinyl acetate (second monomer), 1 part of diethylene glycol divinyl ether and 1 part of ultraviolet (UV) The initiator (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone. The weight ratio of the copolymer network to the cellulose matrix is 2: 1. The cellulose matrix used is obtained. Kimwipes from Kimberly-Clark Absorbent wiper EX-L.

Absorb the monomer mixture into the porous Kimwipes The polymerization was carried out by absorbing the rag EX-L and then exposing it to UV for 2 hours. After the reaction, the gelled copolymer network and the cellulose substrate are immersed in water to remove unreacted monomers. The cellulose and crosslinked copolymer network interpenetrate and, therefore, are chemically bonded together. The first monomer and the second monomer are also chemically bonded to each other.

The chemically bonded copolymer/cellulose network is fully combined with water to form a hydrocolloid sheet. After complete hydration, a buffer with an enzyme (glucose oxidase) is added to the hydrocolloid sheet. The hydrocolloid sheet is then dried and stored.

The hydrocolloid sheet is cut to the desired size to form a hydrocolloid pad. The hydrocolloid pad is attached to the surface of the electrochemical sensor. The attached hydrocolloid pad is then rehydrated with water including buffer. The hydrocolloid pad 1 of the present invention has from about 60 to about 90% by weight water and is generally uniform and mechanically stable.

Use Sontra SonoPrep for skin Ultrasonic energy processing of the supersonic skin infiltration system. Tests were performed on two different areas of the skin - the wrist and the elbow. The hydrocolloid pad 1 of the present invention is adhered to the skin of each of these positions. The current is measured by an electrochemical sensor and the glucose concentration is determined at each position.

The hydrocolloid pad 2 of the present invention comprises a copolymer network. The copolymer network comprises 60 parts of N-vinylpyrrolidone (first monomer), 40 parts of vinyl acetate (second monomer), 1 part of diethylene glycol divinyl ether and 1 part (2-hydroxyl) -4'-(2-Hydroxyethoxy)-2-methylpropiophenone. The copolymerization network was exposed to UV radiation for 2 hours to complete the polymerization. After the reaction, the gelled copolymer network was immersed. The water is removed to remove unreacted monomers. The first monomer and the second monomer are chemically bonded to each other.

The copolymer network is completely hydrated with water to form a hydrocolloid sheet. After complete hydration, a buffer with an enzyme (glucose oxidase) is added to the hydrocolloid sheet. The hydrocolloid sheet is then dried and stored. In order to improve the treatment of the hydrocolloid sheet, a nylon mesh is used to support the water colloid sheet. The hydrocolloid sheet with the nylon mesh is cut to the desired size to form the hydrocolloid pad 2 of the present invention. The hydrocolloid pad 2 of the present invention is attached to the surface of an electrochemical sensor. The joined hydrocolloid pad 2 is then rehydrated with water including buffer. The hydrocolloid pad 2 of the present invention, which is hydrated, comprises from about 60 to about 90% by weight water and is generally uniform and mechanically stable.

Use Sontra SonoPrep for the skin (forearm) Ultrasonic skin penetration system treatment. The hydrocolloid 2 of the present invention is adhered to the skin (forearm). The current is measured by an electrochemical sensor and the glucose concentration is determined.

The test results using the hydrocolloid pads 1 and 2 of the present invention are shown in FIG. Figure 5 plots current (naiamper) and glucose concentration (mg/dL) versus time. In particular, Figure 5 depicts a comparison method (labeled plasma glucose in Figure 5) for testing blood using an electrochemical sensor and measuring glucose concentration. The comparative method of Figure 5 did not use a hydrocolloid composition. In this comparison method, blood samples were taken every 30 minutes and analyzed using an Analox GM9D analyzer sold by Analox Instruments U.S.A., Inc. of Lunenberg, Massachusetts. The results of the method of using the hydrocolloid pad 1 (at the wrist and elbow) and the hydrocolloid pad 2 (forearm) of the present invention are also plotted. As shown in Figure 5, the glucose concentration from the method of the invention (using the hydrocolloid pads 1 and 2 of the present invention) is generally related to the plasma glucose concentration from the target of Comparative Method 1.

Alternative embodiment A

The hydrocolloid composition comprises a first monomer, a second monomer, a crosslinking agent and a solvent, and the first single system is selected from the group consisting of Formula I: Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 Is selected from the group consisting of 1 carbon to 5 carbon atoms to form a 3-7 member heterocyclic moiety; the second single system is selected from the group consisting of Formula II and Formula III, wherein Formula II is Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cyclo alkyl, nitro and cyano, with the proviso that: when R3 is H or CH _3, then R4 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, Group or an aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

Alternative embodiment B

Aqueous colloidal composition of Alternate Embodiment A wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide.

Alternative embodiment C

The hydrocolloid composition of any of the embodiments B, wherein the crosslinking agent is a polyfunctional vinyl ether, the polyfunctional vinyl ether is diethylene glycol divinyl ether, triethylene glycol divinyl ether, and tetra (B) Glycol) divinyl ether.

Alternative embodiment D

A hydrocolloid composition of the alternative embodiment B, wherein the crosslinking agent is divinylbenzene.

Alternative embodiment E

The hydrocolloid composition of Embodiment B, wherein the crosslinking agent is a polyfunctional acrylate, the multifunctional acrylate ethylene glycol dimethacrylate (EGDMA), polyethylene glycol diacrylate, and diethyl phthalate. Alcohol dimethacrylate, diethylene glycol diacrylate, ethylene glycol diacrylate or 1,3-dihydroxypropyl dimethacrylate.

Alternative Embodiment F

Alternately the hydrocolloid composition of embodiment B, wherein the crosslinker is a polyfunctional acrylamide.

Alternative embodiment G

A hydrocolloid composition of Alternate Embodiment A wherein the solvent is water.

Alternative embodiment H

The hydrocolloid composition of Alternative Example A additionally includes a photoinitiator.

Alternative embodiment I

A further alternative embodiment A hydrocolloid composition wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative embodiment J

A hydrocolloid composition of the alternative embodiment A, wherein the second single system is selected from Formula II.

Alternative embodiment K

The hydrocolloid composition of Alternate Embodiment A wherein the second single system is selected from Formula III.

Alternative embodiment L

A hydrocolloid composition of the alternative embodiment A, wherein the first single system is N-vinylacetamide, N-vinylpropionamide, N-vinylpyrrolidone or N-vinylcaprolactam, the second single-based system is selected from R3 or R4 of optionally substituted (C ₃ -C _{1 8)} alkyl group of formula II.

Alternative embodiment M

A hydrocolloid composition of the alternative embodiment A, wherein the first single system is N-vinylacetamide, N-vinylpropionamide, N-vinylpyrrolidone or N-vinylcaprolactam, the second single-based system is selected from R3 or R4 of optionally substituted (C ₃ -C ₇₎ cycloalkyl group of the formula II.

Alternative embodiment N

A hydrocolloid composition of the alternative embodiment A, wherein the first single system is N-vinylacetamide, N-vinylpropionamide, N-vinylpyrrolidone or N-vinylcaprolactam, The second single system is selected from Formula II wherein R3 or R4 is optionally substituted for the aromatic moiety.

Alternative embodiment O

A hydrocolloid composition of the alternative embodiment A, wherein the first single system is N-vinylacetamide, N-vinylpropionamide, N-vinylpyrrolidone or N-vinylcaprolactam, the second single-based system is selected from R3 or R4 of optionally substituted (C ₃ -C _{1 8)} alkyl group of formula II.

Alternative embodiment P

A hydrocolloid composition of the alternative embodiment A, wherein the first single system is N-vinylacetamide, N-vinylpropionamide, N-vinylpyrrolidone or N-vinylcaprolactam, the second single-based system is selected from R3 or R4 of optionally substituted (C ₃ -C ₇₎ cycloalkyl group of the formula II.

Alternative embodiment Q

A hydrocolloid composition of the alternative embodiment A, wherein the first single system is N-vinylacetamide, N-vinylpropionamide, N-vinylpyrrolidone or N-vinylcaprolactam, The second single system is selected from Formula II wherein R3 or R4 is optionally substituted for the aromatic moiety.

Alternative embodiment R

An electrochemical sensor system comprising: an electrochemical sensor having at least one opposite electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising a first cover, a monomer, a crosslinking agent and a solvent, the first single system is selected from the group consisting of hydroxyalkyl methacrylate, acrylamide, N,N-dialkyl acrylamide, methacrylic acid, acrylic acid, methacrylic acid Metal salt, metal acrylate, itaconic acid, maleic acid, methacrylamide, N,N-dialkyl acrylamide, styrene sulfonic acid, metal styrene sulfonate, styrene carboxylic acid, benzene Metal carboxylate, acrylamide-2-methylpropanesulfonic acid, acrylamide-2-methylpropanesulfonic acid metal salt, halogenated 2-vinyl N-alkylpyrazole, halogenated 4-vinyl N - an alkylpyridinium or formula I wherein formula I is Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 Is selected from the group consisting of 1 carbon to 5 carbon atoms to form a 3-7 member heterocyclic moiety; the second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV. Where formula II is Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cyclo alkyl, nitro and cyano, with the proviso that: when R3 is H or CH _3, then R4 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, Group or an aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano.

Wherein formula IV is Wherein R 2 is selected from (C ₁ -C _{1 8} )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano .

Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

Alternative embodiment S

The electrochemical sensor system of Alternate Embodiment R additionally includes a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor.

Alternative embodiment T

An electrochemical sensor system of alternative embodiment R, wherein the electrochemical sensor additionally comprises a reference electrode.

Alternative embodiment U

An electrochemical sensor system of alternative embodiment R wherein the hydrocolloid composition is a dried hydrocolloid composition.

Alternative Embodiment V

An electrochemical sensor system of alternative embodiment U, wherein the dried hydrocolloid composition is a film.

Alternative embodiment W

The electrochemical sensor system of Alternate Embodiment R additionally includes a mechanical support to help provide mechanical strength to the hydrocolloid composition.

Alternative embodiment X

An electrochemical sensor system of alternative embodiment W, wherein the mechanical support is a polymer mesh, a woven fabric, a nonwoven fabric, cellulose, or a combination thereof.

Alternative embodiment Y

An electrochemical sensor system of alternative embodiment R wherein the hydrocolloid composition has a thickness of from about 0.1 mils to about 100 mils.

Alternative embodiment Z

An electrochemical sensor system of alternative embodiment Y wherein the hydrocolloid composition has a thickness of from about 1 mil to about 30 mils.

Alternative embodiment AA

An electrochemical sensor system of alternative embodiment R wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative embodiment BB

An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single system being selected from the group consisting of Formula I Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 Is selected from the group consisting of 1 carbon to 5 carbon atoms to form a 3-7 member heterocyclic moiety; the second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV. Where formula II is Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cyclo alkyl, nitro and cyano, with the proviso that: when R3 is H or CH _3, then R4 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, Group or an aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano Where the formula IV is Wherein R 2 is selected from (C ₁ -C _{1 8} )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

Alternative embodiment CC

The electrochemical sensor system of the alternative embodiment BB additionally includes a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor.

Alternative embodiment DD

An electrochemical sensor system of the alternative embodiment BB, wherein the electrochemical sensor additionally comprises a reference electrode.

Alternative embodiment EE

An electrochemical sensor system of the alternative embodiment BB, wherein the hydrocolloid composition is a dried hydrocolloid composition.

Alternative embodiment FF

An electrochemical sensor system of the alternative embodiment EE, wherein the dried hydrocolloid composition is a film.

Alternative embodiment GG

The electrochemical sensor system of Alternative Embodiment BB additionally includes a mechanical support to help provide mechanical strength to the hydrocolloid composition.

Alternative embodiment HH

An electrochemical sensor system of an alternative embodiment GG, wherein the mechanical support is a polymer mesh, a woven fabric, a non-woven fabric, paper, or a combination thereof.

Alternative Example II

An electrochemical sensor system of the alternative embodiment BB, wherein the crosslinking agent is a polyfunctional vinyl ether, divinyl benzene, a polyfunctional acrylate or a polyfunctional acrylamide.

Alternative embodiment JJ

An electrochemical sensor system of alternative embodiment BB, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative embodiment KK

An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent and a solvent, the first single system being selected from the group consisting of N-vinylpyrrolidone, hydroxyalkyl methacrylate, acrylamide, and N,N- a dialkyl acrylamide, the second single system being selected from the group consisting of alkyl (meth)acrylate, N-vinyl acrylamide, vinyl ester, and vinyl ether, and wherein The ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.

Alternative embodiment LL

The electrochemical sensor system of Alternate Embodiment KK additionally includes a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor.

Alternative embodiment MM

An electrochemical sensor system of alternative embodiment KK, wherein the electrochemical sensor additionally comprises a reference electrode.

Alternative embodiment NN

An electrochemical sensor system of alternative embodiment KK, wherein the hydrocolloid composition is a dried hydrocolloid composition.

Alternative embodiment OO

An electrochemical sensor system of an alternative embodiment NN, wherein the dried hydrocolloid composition is a film.

Alternative embodiment PP

The electrochemical sensor system of Alternate Embodiment KK additionally includes a mechanical support to help provide mechanical strength to the hydrocolloid composition.

Alternative embodiment QQ

An electrochemical sensor system of an alternative embodiment PP, wherein the mechanical support is a polymer mesh, a woven fabric, a nonwoven fabric, paper, or a combination thereof.

Alternative embodiment RR

An electrochemical sensor system of alternative embodiment KK, wherein the first single system N-vinyl pyrrolidone and the second single system vinyl ester.

Alternative embodiment SS

An electrochemical sensor system of the alternative embodiment KK, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide.

Alternative embodiment TT

An electrochemical sensor system of alternative embodiment KK, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative embodiment UU

An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising a first monomer, a second monomer having a hydrophilic character, a second monomer having a hydrophobic character, and wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to About 99.9: 0.1.

Alternative A

A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single The system is selected from the group consisting of hydroxyalkyl methacrylate, acrylamide, N,N-dialkyl acrylamide, methacrylic acid, acrylic acid, metal methacrylate, metal acrylate, itaconic acid, maleic acid. , methacrylamide, N,N-dialkyl acrylamide, styrene sulfonic acid, metal styrene sulfonate, styrene carboxylic acid, metal styrene carboxylic acid, acrylamide-2-methyl Propane sulfonic acid, acrylamide-2-methylpropane sulfonate metal salt, halogenated 2-vinyl N-alkylpyrazole, halogenated 4-vinyl N-alkylpyridinium or formula I, wherein formula I is Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 Is selected from the group consisting of 1 carbon to 5 carbon atoms to form a 3-7 member heterocyclic moiety; the second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV. Where formula II is Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, naphthenic a base, a nitro group and a cyano group, with the proviso that when R ₃ is H or CH ₃ , then R 4 is a (C ₃ -C _{1 8} )alkyl group, a (C ₃ -C ₇ )cycloalkyl group or an aromatic moiety. wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, ( C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl Or an aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano Where the formula IV is Wherein R 2 is selected from (C ₁ -C _{1 8} )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1; providing a sensor, the hydrocolloid composition generally positioned between the skin and the sensor and coupling the skin to The sensor; and sampling the interstitial fluid to determine the analyte concentration using the sensor.

Alternative B

The method of Alternative Method A additionally includes pretreating the skin to improve the permeability of the skin.

Alternative C

The method of alternative method B, wherein the pretreating comprises applying ultrasonic energy to the skin.

Alternative method D

The method of alternative A, wherein the skin is a forearm.

Alternative E

The method of alternative method A, wherein the analyte is glucose.

Alternative method F

The method of alternative method A, wherein the inductor is an electrochemical sensor.

Alternative G

The method of alternative method A, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative method H

A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single System selected from formula I Wherein R and R1 are independently selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )dihydroxyalkyl, and (C ₂ -C ₆ )hydroxyalkyl; or a combination of R and R1 Is selected from the group consisting of 1 carbon to 5 carbon atoms to form a 3-7 member heterocyclic moiety; the second single system is selected from the group consisting of alkyl (meth)acrylates, Formula II, Formula III, and Formula IV. Where formula II is Wherein R3 and R4 are independently selected from the Department of _{H, CH 3, (C 3} -C 1 8) alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group of substituents: halo, haloalkoxy a cycloalkyl group, a nitro group, a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, naphthenic a (C ₃ -C ₇ )cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, naphthenic a base, a nitro group and a cyano group, with the proviso that when R ₃ is H or CH ₃ , then R 4 is a (C ₃ -C _{1 8} )alkyl group, a (C ₃ -C ₇ )cycloalkyl group or an aromatic moiety. wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C _{1 8)} alkyl, ( C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl Or an aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R5 is selected from (C ₃ -C _{1 8)} alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of: halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein formula IV is Wherein R 2 is selected from (C ₁ -C _{1 8} )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro a cyano group, a 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1; providing a sensor, the hydrocolloid composition generally positioned between the skin and the sensor and coupling the skin And the sensor; and sampling the interstitial fluid to determine the analyte concentration using the sensor.

Alternative method I

The method of Alternative Method H additionally includes pretreating the skin to improve the permeability of the skin.

Alternative method J

The method of alternative method I, wherein the pretreating comprises applying ultrasonic energy to the skin.

Alternative method K

Alternative method H, wherein the skin is attached to the forearm.

Alternative method L

The method of alternative method H, wherein the analyte is glucose.

Alternative method M

The method of alternative method H, wherein the inductor is an electrochemical sensor.

Alternative method N

The method of alternative method H, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative method O

A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single The system is selected from the group consisting of N-vinylpyrrolidone, hydroxyalkyl methacrylate, acrylamide and N,N-dialkyl acrylamide, the second single system being selected from A group consisting of alkyl (meth)acrylate, N-vinylguanamine, vinyl ester, and vinyl ether, and wherein the ratio of the first monomer to the second monomer is about 0.1: 99.9 to about 99.9:0.1; providing a sensor, the hydrocolloid composition generally located between the skin and the sensor and coupling the skin to the sensor; and sampling the interstitial fluid to determine the analyte concentration using the sensor .

Alternative method P

The method of Alternative Method O additionally includes pretreating the skin to improve the permeability of the skin.

Alternative method Q

A method of alternative P, wherein the pretreating comprises applying ultrasonic energy to the skin.

Alternative method R

Alternative method O, wherein the skin is attached to the forearm.

Alternative method S

A method of Alternative O, wherein the analyte is glucose.

Alternative method T

The method of alternative method O, wherein the inductor is an electrochemical sensor.

Alternative method U

The method of alternative method O, wherein the first single system N-vinylpyrrolidone and the second single system vinyl ester.

Alternative method V

The method of alternative method U, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide.

Alternative method W

The method of alternative method O, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20.

Alternative method X

A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single The body has a hydrophilic character, the second monomer has a hydrophobic character, wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1; providing an inductor, the hydrocolloid composition is generally Positioning the skin and the sensor and coupling the skin to the sensor; and sampling the interstitial fluid to determine the analyte concentration using the sensor.

While the invention has been described with respect to the specific embodiments of the invention, it will be understood that Each such embodiment and its significant variations are intended to be within the spirit and scope of the invention.

10. . . Dried water colloidal film system

12. . . Dried water colloidal composition film

14. . . Mechanical carrier

30. . . Electrochemical sensor

32. . . Relative electrode

34. . . Working electrode

36. . . Reference electrode

50. . . Electrochemical sensor system

52. . . Dried water colloid film

54. . . Adhesive ring

1 is a dried hydrocolloid and a mechanical support in accordance with an embodiment.

2 is an electrochemical inductor in accordance with an embodiment.

3 is an electrochemical sensor system including one of the electrochemical inductors of FIG. 2.

Figure 4a is a plot of current, glucose concentration versus time.

Figure 4b is a graph plotting the normalization of current and glucose concentration versus time in Figure 4a.

Figure 5 is a graph plotting current, glucose concentration versus time.

10. . . Dried water colloidal film system

12. . . Dried water colloidal composition film

14. . . Mechanical support

Claims (71)

A hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent and a solvent, the first single system being selected from the group consisting of Formula I: Wherein the combination of R and R1 is selected from 1 carbon to 5 carbon atoms such that a 3-7 membered heterocyclic moiety is formed; the second single system is selected from the group consisting of Formula II and Formula III, wherein Formula II is Wherein R 3 and R 4 are independently selected from the group consisting of H, CH ₃ , (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl a cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl , nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, naphthenic a base, a nitro group and a cyano group, with the proviso that when R ₃ is H or CH ₃ , then R 4 is a (C ₃ -C ₁₈ )alkyl group, a (C ₃ -C ₇ )cycloalkyl group or an aromatic moiety, wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C ₁₈₎ -alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, or Aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R 5 is selected from (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. The hydrocolloid composition of claim 1, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide. The hydrocolloid composition of claim 2, wherein the crosslinking agent is a polyfunctional vinyl ether, the polyfunctional vinyl ether is diethylene glycol divinyl ether, triethylene glycol divinyl ether, and tetra (B) Glycol) divinyl ether. The hydrocolloid composition of claim 2, wherein the crosslinking agent is divinylbenzene. The hydrocolloid composition of claim 2, wherein the crosslinking agent is a multifunctional acrylate, the multifunctional acrylate ethylene glycol dimethacrylate (EGDMA), polyethylene glycol diacrylate, and diethyl phthalate. Alcohol dimethacrylate, diethylene glycol diacrylate, ethylene glycol diacrylate or 1,3-dihydroxypropyl dimethacrylate. The hydrocolloid composition of claim 2, wherein the crosslinking agent is a polyfunctional acrylamide. The hydrocolloid composition of claim 1, wherein the solvent is water. The hydrocolloid composition of claim 1 additionally comprising a photoinitiator. The hydrocolloid composition of claim 1, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. The hydrocolloid composition of claim 1, wherein the second single system is selected from Formula II. The hydrocolloid composition of claim 1, wherein the second single system is selected from the group consisting of III. The hydrocolloid composition of claim 1, wherein the first single system N-vinylpyrrolidone or N-vinyl caprolactam, the second single system selected from the group consisting of R3 or R4 is optionally substituted Formula II of (C ₃ -C ₁₈ )alkyl. The hydrocolloid composition of claim 1, wherein the first single system N-vinylpyrrolidone or N-vinyl caprolactam, the second single system selected from the group consisting of R3 or R4 is optionally substituted Formula (II) of (C ₃ -C ₇ )cycloalkyl. The hydrocolloid composition of claim 1, wherein the first single system N-vinylpyrrolidone or N-vinyl caprolactam, the second single system selected from the group consisting of R3 or R4 is optionally substituted Formula II of the aromatic part. The hydrocolloid composition of claim 1, wherein the first single system N-vinylpyrrolidone or N-vinyl caprolactam, the second single system selected from the group consisting of R3 or R4 is optionally substituted Formula II of (C ₃ -C ₁₈ )alkyl. The hydrocolloid composition of claim 1, wherein the first single system N-vinylpyrrolidone or N-vinyl caprolactam, the second single system selected from the group consisting of R3 or R4 is optionally substituted Formula (II) of (C ₃ -C ₇ )cycloalkyl. The hydrocolloid composition of claim 1, wherein the first single system N-vinylpyrrolidone or N-vinyl caprolactam, the second single system selected from the group consisting of R3 or R4 is optionally substituted Formula II of the aromatic part. An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising the first monomer a second monomer, a crosslinking agent, and a solvent, wherein the first single system is selected from the group consisting of Formula I, wherein Formula I is Wherein the combination of R and R1 is selected from 1 carbon to 5 carbon atoms such that a 3-7 membered heterocyclic moiety is formed; the second single system is selected from the group consisting of Formula II, Formula III and Formula IV, wherein II is Wherein R 3 and R 4 are independently selected from the group consisting of H, CH ₃ , (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl a cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl , nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, naphthenic a base, a nitro group and a cyano group, with the proviso that when R ₃ is H or CH ₃ , then R 4 is a (C ₃ -C ₁₈ )alkyl group, a (C ₃ -C ₇ )cycloalkyl group or an aromatic moiety, wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C ₁₈₎ -alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, or Aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R 5 is selected from (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein formula IV is Wherein R 2 is selected from (C ₁ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. The electrochemical sensor system of claim 18, further comprising a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor. The electrochemical sensor system of claim 18, wherein the electrochemical sensor additionally comprises a reference electrode. The electrochemical sensor system of claim 18, wherein the hydrocolloid composition is a dried hydrocolloid composition. The electrochemical sensor system of claim 21, wherein the dried hydrocolloid composition is a film. The electrochemical sensor system of claim 18, additionally comprising a mechanical support to assist in providing mechanical strength to the hydrocolloid composition. The electrochemical sensor system of claim 23, wherein the mechanical support is a polymer mesh, a woven fabric, a non-woven fabric, cellulose, or a combination thereof. The electrochemical sensor system of claim 18, wherein the hydrocolloid composition has a thickness of from about 0.1 mils to about 100 mils. The electrochemical sensor system of claim 25, wherein the hydrocolloid composition has a thickness of from about 1 mil to about 30 mils. The electrochemical sensor system of claim 18, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising the first monomer The second monomer, the crosslinking agent and the solvent, the first single system is selected from the formula I Wherein the combination of R and R1 is selected from the group consisting of 1 carbon to 5 carbon atoms such that a 3-7 membered heterocyclic moiety is formed; the second single system is selected from the group consisting of Formula II, Formula III and Formula IV, Where formula II is Wherein R 3 and R 4 are independently selected from the group consisting of H, CH ₃ , (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl a cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl , nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, a cycloalkyl, a nitro group and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, naphthenic a base, a nitro group and a cyano group, with the proviso that when R ₃ is H or CH ₃ , then R 4 is a (C ₃ -C ₁₈ )alkyl group, a (C ₃ -C ₇ )cycloalkyl group or an aromatic moiety, wherein the alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C ₁₈₎ -alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl, or Aromatic moiety optionally substituted with one or more substituents; and wherein formula III is Wherein R 5 is selected from (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein formula IV is Wherein R 2 is selected from (C ₁ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. The electrochemical sensor system of claim 28, further comprising a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor. The electrochemical sensor system of claim 28, wherein the electrochemical sensor additionally comprises a reference electrode. The electrochemical sensor system of claim 28, wherein the hydrocolloid composition is a dried hydrocolloid composition. The electrochemical sensor system of claim 31, wherein the dried hydrocolloid composition is a film. The electrochemical sensor system of claim 28, additionally comprising a mechanical support to assist in providing mechanical strength to the hydrocolloid composition. The electrochemical sensor system of claim 33, wherein the mechanical support is a polymer mesh, a woven fabric, a non-woven fabric, paper, or a combination thereof. The electrochemical sensor system of claim 28, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide. The electrochemical sensor system of claim 28, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising the first monomer And a second monomer, a crosslinking agent and a solvent, the first single system being selected from the group consisting of N-vinylpyrrolidone, the second single system being selected from the group consisting of: Vinyl esters and vinyl ethers, and wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1. The electrochemical sensor system of claim 37, further comprising a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor. The electrochemical sensor system of claim 37, wherein the electrochemical sensor additionally comprises a reference electrode. The electrochemical sensor system of claim 37, wherein the hydrocolloid composition is a dried hydrocolloid composition. The electrochemical sensor system of claim 40, wherein the dried hydrocolloid composition is a film. The electrochemical sensor system of claim 37, additionally comprising a mechanical support to assist in providing mechanical strength to the hydrocolloid composition. The electrochemical sensor system of claim 42, wherein the mechanical support is a polymer mesh, a woven fabric, a non-woven fabric, paper, or a combination thereof. The electrochemical sensor system of claim 37, wherein the first single system N-vinyl pyrrolidone and the second single system vinyl ester. The electrochemical sensor system of claim 37, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide. The electrochemical sensor system of claim 37, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. An electrochemical sensor system comprising: an electrochemical sensor having at least one opposing electrode and a working electrode; and a hydrocolloid composition contacting the working electrode, the hydrocolloid composition comprising the first monomer a second monomer having a hydrophilic character, a second monomer having a hydrophobic character, and wherein the ratio of the first monomer to the second monomer is about 0.1:99.9 To approximately 99.9:0.1. A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single The system is selected from Formula I, wherein Formula I is Wherein the combination of R and R1 is selected from 1 carbon to 5 carbon atoms such that a 3-7 membered heterocyclic moiety is formed; the second single system is selected from the group consisting of Formula II, Formula III and Formula IV, wherein II is Wherein R 3 and R 4 are independently selected from the group consisting of H, CH ₃ , (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl a cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl , nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, a cycloalkyl, nitro and cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl , a nitro group and a cyano group, with the proviso that: when R3 is H or CH _3, then R4 is (C ₃ -C ₁₈₎ alkyl, (C ₃ -C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl group, a cycloalkyl group or an aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C ₁₈₎ alkyl, (C ₃ - C ₇₎ cycloalkyl or an aromatic moiety, wherein the alkyl, cycloalkyl or aromatic portion Optionally substituted with one or more substituents; and wherein formula III is Wherein R 5 is selected from (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein formula IV is Wherein R 2 is selected from (C ₁ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1; providing a sensor, the hydrocolloid composition generally positioned between the skin and the sensor and coupling the skin to The sensor; and sampling the interstitial fluid to determine the analyte concentration using the sensor. The method of claim 48, additionally comprising pretreating the skin to improve the skin The permeability of the skin. The method of claim 49, wherein the pretreating comprises applying ultrasonic energy to the skin. The method of claim 48, wherein the skin is a forearm. The method of claim 48, wherein the analyte is glucose. The method of claim 48, wherein the sensor is an electrochemical sensor. The method of claim 48, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single System selected from formula I Wherein the combination of R and R1 is selected from 1 carbon to 5 carbon atoms such that a 3-7 membered heterocyclic moiety is formed; the second single system is selected from the group consisting of Formula II, Formula III and Formula IV, wherein II is Wherein R 3 and R 4 are independently selected from the group consisting of H, CH ₃ , (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl a cycloalkyl, nitro, cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl , nitro and cyano; (C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, a cycloalkyl, a nitro group and a cyano group; and an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, naphthenic a base, a nitro group and a cyano group, with the proviso that when R ₃ is H or CH ₃ , then R 4 is a (C ₃ -C ₁₈ )alkyl group, a (C ₃ -C ₇ )cycloalkyl group or an aromatic moiety, wherein alkyl, cycloalkyl or aromatic moiety optionally substituted with one or more substituents, with the proviso that: when R4 is H or CH _3, then R3 is (C ₃ -C ₁₈₎ alkyl, (C ₃ -C ₇ ) a cycloalkyl or aromatic moiety in which an alkyl group, a cycloalkyl group or an aromatic moiety Subdivided by one or more substituents; and wherein Formula III is Wherein R 5 is selected from (C ₃ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein formula IV is Wherein R 2 is selected from (C ₁ -C ₁₈ )alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, cycloalkyl, nitro, a cyano, 4-8 membered heterocyclic moiety, wherein the heterocyclic moiety is optionally substituted with one or more of the following groups: alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; C ₃ -C ₇ )cycloalkyl, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyanide And an aromatic moiety, wherein the aromatic moiety is optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cycloalkyl, nitro and cyano; Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1; providing a sensor, the hydrocolloid composition generally positioned between the skin and the sensor and coupling the skin to The sensor; and sampling the interstitial fluid to determine the analyte concentration using the sensor. The method of claim 55, additionally comprising pretreating the skin to improve the permeability of the skin. The method of claim 56, wherein the pretreating comprises applying ultrasonic energy to the skin. The method of claim 55, wherein the skin is a forearm. The method of claim 55, wherein the analyte is glucose. The method of claim 55, wherein the sensor is an electrochemical sensor. The method of claim 55, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single The system is selected from the group consisting of N-vinylpyrrolidone, the second monomer Is selected from the group consisting of vinyl esters and vinyl ethers, and wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1; providing a sensor, The hydrocolloid composition is typically positioned between the skin and the sensor and couples the skin and sensor; and the interstitial fluid is sampled to determine the analyte concentration using the sensor. The method of claim 62, additionally comprising pretreating the skin to improve the permeability of the skin. The method of claim 63, wherein the pretreating comprises applying ultrasonic energy to the skin. The method of claim 62, wherein the skin is a forearm. The method of claim 62, wherein the analyte is glucose. The method of claim 62, wherein the sensor is an electrochemical sensor. The method of claim 62, wherein the first single system N-vinylpyrrolidone and the second single system vinyl ester. The method of claim 68, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide. The method of claim 62, wherein the ratio of the first monomer to the second monomer is from about 20:80 to about 80:20. A method for determining an analyte concentration, the method comprising the steps of: placing a hydrocolloid composition on a skin, the hydrocolloid composition comprising a first monomer, a second monomer, a crosslinking agent, and a solvent, the first single The second monomer has a hydrophobic character, wherein the ratio of the first monomer to the second monomer is about 0.1:99.9 to about 99.9:0.1; An inductor is provided, the hydrocolloid composition is generally positioned between the skin and the sensor and coupled to the skin and the sensor; and the interstitial fluid is sampled to determine the analyte concentration using the sensor.