Device for Interstitial Fluid Extraction, Production Process Thereof and Analyzing Process of Interstitial Fluid Using the Device

Abstract

A device for interstitial fluid extraction, having a base material formed from a synthetic resin film, a pressure sensitive adhesive layer, a hydrogel layer formed from at least one hydrophilic polymer selected from the group consisting of polyvinyl alcohol and polyvinyl pyrrolidone, and a release layer, wherein the hydrogel layer has an area of a size that the pressure sensitive adhesive layer is exposed from around the hydrogel layer, does substantially not contain a sodium ion and causes no water separation.

1 . A device for interstitial fluid extraction, comprising
 a base material formed from a synthetic resin film;   a pressure sensitive adhesive layer arranged on one surface of the base material;   a hydrogel layer arranged on the surface of the pressure sensitive adhesive layer and formed from at least one hydrophilic polymer selected from the group consisting of polyvinyl alcohol and polyvinyl pyrrolidone; and   a release layer covering exposed surfaces of both pressure sensitive adhesive layer and hydrogel layer, wherein   the hydrogel layer has an area of a size that the pressure sensitive adhesive layer is exposed from around the hydrogel layer, does substantially not contain a sodium ion and causes no water separation when measured according to the measuring method described in the present description.   
     
     
         2 . The device for interstitial fluid extraction according to  claim 1 , wherein the hydrogel layer further contains an osmotic pressure control agent composed of at least one compound selected from the group consisting of potassium chloride, potassium phosphate, magnesium chloride, magnesium phosphate, calcium chloride, calcium phosphate, amino acids, urea, acetic acid, ammonia, tricine, thiamine, riboflavin, nicotinic acid amide, pyridoxine, cyanocobalamine and ascorbic acid in a proportion that an osmolarity falls within a range of from 0.05 to 0.94 osmoles. 
     
     
         3 . The device for interstitial fluid extraction according to  claim 1 , wherein the hydrogel layer is formed by irradiating a coating film of an aqueous solution of the hydrophilic polymer with radiation to crosslink the hydrophilic polymer. 
     
     
         4 . The device for interstitial fluid extraction according to  claim 1 , wherein the hydrogel layer is obtained by irradiating a coating film of an aqueous solution of the hydrophilic polymer, said aqueous solution having a hydrophilic polymer concentration within a range of from 7 to 30% by weight, containing an osmotic pressure control agent composed of at least one compound selected from the group consisting of potassium chloride, potassium phosphate, magnesium chloride, magnesium phosphate, calcium chloride, calcium phosphate, amino acids, urea, acetic acid, ammonia, tricine, thiamine, riboflavin, nicotinic acid amide, pyridoxine, cyanocobalamine and ascorbic acid in a proportion that an osmolarity falls within a range of from 0.05 to 0.94 osmoles, substantially containing no sodium ion, and satisfying, assuming that the concentration of the hydrophilic polymer is b % by weight, and the osmolarity of the osmotic pressure control agent is a osmole(s), the relationship represented by the following expression (A):
     a≦ 0.1 b− 0.6  (A)
   with radiation selected from the group consisting of α-ray, electron beam and γ-ray to crosslink the hydrophilic polymer.   
     
     
         5 . The device for interstitial fluid extraction according to  claim 4 , wherein the hydrogel layer is obtained by irradiating the coating film of the aqueous solution of the hydrophilic polymer with electron beam, whose accelerating voltage is within a range of from 200 kV to 10 MV and whose irradiation dose is within a range of from 5 to 20,000 kGy, to crosslink the hydrophilic polymer. 
     
     
         6 . The device for interstitial fluid extraction according to  claim 1 , wherein the hydrophilic polymer is polyvinyl alcohol having a saponification degree within a range of from 78 to 100 mol % and an average polymerization degree within a range of from 500 to 4,000. 
     
     
         7 . The device for interstitial fluid extraction according to  claim 1 , wherein the water content in the hydrogel layer is within a range of from 70 to 95% by weight. 
     
     
         8 . The device for interstitial fluid extraction according to  claim 1 , wherein the swelling rate of the hydrogel layer, which is obtained by multiplying a value obtained by dividing a weight after immersing the hydrogel layer in physiological saline for 24 hours by a weight before the immersion in the physiological saline by 100, is within a range of from 100 to 300%. 
     
     
         9 . The device for interstitial fluid extraction according to  claim 1 , which is used in an analyzing process of an interstitial fluid, comprising extracting the interstitial fluid in the hydrogel layer through the skin of a vertebrate subjected to a permeability-improving treatment, analyzing the interstitial fluid collected in the hydrogel layer after a predetermined period of time has elapsed to measure the concentrations of a sodium ion and glucose contained therein and calculating out a value corresponding to a glucose concentration in the blood of the vertebrate on the basis of these measured values. 
     
     
         10 . The device for interstitial fluid extraction according to  claim 1 , wherein the hydrogel layer is arranged directly or through an intermediate layer composed of a nonwoven fabric or synthetic resin film on the surface of the pressure sensitive adhesive layer. 
     
     
         11 . A production process of a device for interstitial fluid extraction, comprising providing a base material formed from a synthetic resin film;
 arranging a pressure sensitive adhesive layer on one surface of the base material;   arranging a hydrogel layer formed by irradiating a coating film of an aqueous solution of at least one hydrophilic polymer selected from the group consisting of polyvinyl alcohol and polyvinyl pyrrolidone with radiation to crosslink the hydrophilic polymer on the surface of the pressure sensitive adhesive layer; and   covering exposed surfaces of both pressure sensitive adhesive layer and hydrogel layer with a release layer, wherein   the hydrogel layer has an area of a size that the pressure sensitive adhesive layer is exposed from around the hydrogel layer, does substantially not contain a sodium ion and causes no water separation when measured according to the measuring method described in the present description.   
     
     
         12 . The production process according to  claim 11 , wherein in the step of arranging the hydrogel layer, the hydrogel layer is formed by irradiating a coating film of an aqueous solution of the hydrophilic polymer, said aqueous solution having a hydrophilic polymer concentration within a range of from 7 to 30% by weight, containing an osmotic pressure control agent composed of at least one compound selected from the group consisting of potassium chloride, potassium phosphate, magnesium chloride, magnesium phosphate, calcium chloride, calcium phosphate, amino acids, urea, acetic acid, ammonia, tricine, thiamine, riboflavin, nicotinic acid amide, pyridoxine, cyanocobalamine and ascorbic acid in a proportion that an osmolarity falls within a range of from 0.05 to 0.94 osmoles, substantially containing no sodium ion, and satisfying, assuming that the concentration of the hydrophilic polymer is b % by weight, and the osmolarity of the osmotic pressure control agent is a osmole(s), the relationship represented by the following expression (A):
     a≦ 0.1 b− 0.6  (A)
   with radiation selected from the group consisting of α-ray, electron beam and γ-ray to crosslink the hydrophilic polymer, and the hydrogel layer is then arranged o the surface of the pressure sensitive adhesive layer.   
     
     
         13 . The production process according to  claim 12 , wherein in the step of arranging the hydrogel layer, the hydrogel layer is formed by irradiating the coating film of the aqueous solution of the hydrophilic polymer with electron beam, whose accelerating voltage is within a range of from 200 kV to 10 MV and whose irradiation dose is within a range of from 5 to 20,000 kGy, to crosslink the hydrophilic polymer, and the hydrogel layer is then arranged o the surface of the pressure sensitive adhesive layer. 
     
     
         14 . An analyzing process of an interstitial fluid, comprising extracting a interstitial fluid in a hydrogel layer through the skin of a vertebrate subjected to a permeability-improving treatment analyzing the interstitial fluid collected in the hydrogel layer after a predetermined period of time has elapsed to measure the concentrations of a sodium ion and glucose contained therein and calculating out a value corresponding to a glucose concentration in the blood of the vertebrate on the basis of these measured values, wherein the device for interstitial fluid extraction according to  claim 1  is used. 
     
     
         15 . A device for interstitial fluid extraction, by which an interstitial fluid is extracted in a hydrogel layer through the skin of a vertebrate subjected to a permeability-improving treatment on the basis of a difference in osmotic pressure, and which comprises
 a base material formed from a synthetic resin film;   a pressure sensitive adhesive layer arranged on one surface of the base material;   a hydrogel layer arranged on the surface of the pressure sensitive adhesive layer and formed from at least one hydrophilic polymer selected from the group consisting of polyvinyl alcohol and polyvinyl pyrrolidone; and   a release layer covering exposed surfaces of both pressure sensitive adhesive layer and hydrogel layer, wherein   the hydrogel layer contains an osmotic pressure control agent, does substantially not contain a sodium ion, and satisfies, assuming that the concentration of the hydrophilic polymer is b % by weight, and the osmolarity of the osmotic pressure control agent is a osmole(s), the relationship represented by the following expression (A):
     a≦ 0.1 b− 0.6  (A)
 
   (however, 0.05≦a≦0.94, and 7≦b≦30).   
     
     
         16 . The device for interstitial fluid extraction according to  claim 15 , wherein the osmotic pressure control agent is at least one compound selected from the group consisting of potassium chloride, potassium phosphate, magnesium chloride, magnesium phosphate, calcium chloride, calcium phosphate, amino acids, urea, acetic acid, ammonia, tricine, thiamine, riboflavin, nicotinic acid amide, pyridoxine, cyanocobalamine and ascorbic acid. 
     
     
         17 . The device for interstitial fluid extraction according to  claim 15 , wherein the device for interstitial fluid extraction can extract the interstitial fluid in the hydrogel layer without applying any electric energy. 
     
     
         18 . The device for interstitial fluid extraction according to  claim 15 , wherein the hydrogel layer does substantially not contain an enzyme metabolizing an interstitial fluid component.