TWI387605B - Hydrogel composition - Google Patents
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- TWI387605B TWI387605B TW94138007A TW94138007A TWI387605B TW I387605 B TWI387605 B TW I387605B TW 94138007 A TW94138007 A TW 94138007A TW 94138007 A TW94138007 A TW 94138007A TW I387605 B TWI387605 B TW I387605B
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本發明大體而言係關於水膠體組合物。將一申請案中之水膠體組合物調試以用於經皮方法測定分析物(例如,葡萄糖)之濃度。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).
在對某些生理學異常性之診斷及維持中,體液中分析物之定量測定係十分重要的。舉例而言,在某些個體中應監控乳酸鹽、膽固醇及膽紅素。詳言之,糖尿病患者個體經常檢查其體液中之葡萄糖含量以控制其飲食中之葡萄糖攝入係重要的。該等測試之結果可用於決定需要投予(若有,則)何種胰島素或其它藥物。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.
在一些現有技術中,可使用刺血針以自使用者提取流體(例如,血液)。接著將該流體用器具或量計來測定分析物之濃度。應需要消除使用刺血針之需要,而仍然準確地測定分析物之濃度。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.
一種用於得到樣品而不使用刺血針之非侵入性方法係使用在間質流體(ISF)中發現之分析物之經皮樣品。在該方法中,將組合物置於皮膚上且幫助促進自使用者之皮膚提取ISF至感應器具或量計。該組合物需要具有足夠機械及熱穩定性以在皮膚取樣位點與感應器具之間提供相對靜態的、反應性的且水性的導體。應需要找到含有該等屬性之組合物且將其調試以用於經皮取樣。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.
根據一實施例,一種水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自式I:
該第二單體係選自由式II及式III組成之群,其中式II為
式III為
根據一實施例,一電化學感應器系統包含一電化學感應器及一水膠體組合物。該電化學感應器具有至少一相對電極及一工作電極。該水膠體組合物接觸該工作電極。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自甲基丙烯酸羥基烷基酯、丙烯醯胺、N,N-二烷基丙烯醯胺、甲基丙烯酸、丙烯酸、甲基丙烯酸金屬鹽、丙烯酸金屬鹽、衣康酸、馬來酸、甲基丙烯醯胺、N,N-二烷基丙烯醯胺、苯乙烯磺酸、苯乙烯磺酸金屬鹽、苯乙烯羧酸、苯乙烯羧酸金屬鹽、丙烯醯胺-2-甲基丙烷磺酸、丙烯醯胺-2-甲基丙烷磺酸金屬鹽、鹵化2-乙烯基N-烷基吡錠、鹵化4-乙烯基N-烷基吡錠或上文所討論之式I。該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、式II、式III及式IV,其中式II及式III係如上文所討論。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.
式IV為
根據一實施例,一電化學感應器系統包含一電化學感應器及一水膠體組合物。該電化學感應器具有至少一相對電極及一工作電極。該水膠體組合物接觸該工作電極。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自上文所討論之式I。該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、式II、式III及式IV組成之群,該等式係如上文所討論。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.
根據一另外實施例,一電化學感應器系統包含一電化學感應器及一水膠體組合物。該電化學感應器具有至少一相對電極及一工作電極。該水膠體組合物接觸該工作電極。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自由下列各物組成之群:N-乙烯基吡咯啶酮、甲基丙烯酸羥基烷基酯、丙烯醯胺及N,N-二烷基丙烯醯胺。該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、N-乙烯基丙烯醯胺、乙烯基酯及乙烯基醚。該第一單體與該第二單體之比率為約0.1:99.9至約99.9:0.1。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.
根據另一實施例,一電化學感應器系統包含一電化學感應器及一水膠體組合物。該電化學感應器具有至少一相對電極及一工作電極。該水膠體組合物接觸該工作電極。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體具有親水特徵。該第二單體具有疏水特徵。第一單體與第二單體之比率為約0.1:99.9至約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.
根據一方法,分析物之濃度藉由將水膠體組合物置於皮膚上來測定。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自甲基丙烯酸羥基烷基酯、丙烯醯胺、N,N-二烷基丙烯醯胺、甲基丙烯酸、丙烯酸、甲基丙烯酸金屬鹽、丙烯酸金屬鹽、衣康酸、馬來酸、甲基丙烯醯胺、N,N-二烷基丙烯醯胺、苯乙烯磺酸、苯乙烯磺酸金屬鹽、苯乙烯羧酸、苯乙烯羧酸金屬鹽、丙烯醯胺-2-甲基丙烷磺酸、丙烯醯胺-2-甲基丙烷磺酸金屬鹽、鹵化2-乙烯基N-烷基吡錠、鹵化4-乙烯基N-烷基吡錠或上文所討論之式I。該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、式II、式III及式IV,該等式係如上文所討論。提供一感應器且將該水膠體組合物一般定位於皮膚與感應器之間且偶合皮膚與感應器。取樣間質流體以使用該感應器測定該分析物之濃度。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.
根據另一方法,測定分析物之濃度。該方法包含將水膠體組合物置於皮膚上。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自上文所討論之式I。該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、式II、式III及式IV,該等式係如上文所討論。提供一感應器且將該水膠體組合物一般定位於皮膚與感應器之間且偶合皮膚與感應器。取樣間質流體以使用該感應器測定該分析物之濃度。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.
根據一另外方法,測定分析物之濃度。該方法包含將水膠體組合物置於皮膚上。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體係選自由下列各物組成之群:N-乙烯基吡咯啶酮、甲基丙烯酸羥基烷基酯、丙烯醯胺及N,N-二烷基丙烯醯胺。該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、N-乙烯基醯胺、乙烯基酯及乙烯基醚。第一單體與第二單體之比率為約0.1:99.9至約99.9:0.1。提供一感應器且將該水膠體組合物一般定位於皮膚與感應器之間且偶合皮膚與感應器。取樣間質流體以使用該感應器測定該分析物之濃度。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.
根據另一方法,測定分析物之濃度。該方法包含將水膠體組合物置於皮膚上。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑。該第一單體具有親水特徵。該第二單體具有疏水特徵。第一單體與第二單體之比率為約0.1:99.9至約99.9:0.1。提供一感應器且將該水膠體組合物一般位於皮膚及感應器之間且偶合皮膚與感應器。取樣間質流體以使用該感應器測定該分析物之濃度。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.
本發明係關於新穎水膠體組合物。該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑(例如,水)。該水膠體組合物係無規共聚網路,其以聚合鏈形式組合至少該第一單體與該第二單體。該共聚網路藉由第一單體及第二單體之體積百分數至少在一定程度上加以控制。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.
下文所識別之術語始終具有下列意義:術語"烷基"意謂線性或支鏈之飽和碳基團。術語"(C1 -C3 )烷基"、"(C1 -C1 8 )烷基"及"(C3 -C1 8 )烷基"意謂分別具有1至約3個碳原子、1至約18個碳原子或約3至約18個碳原子之線性或支鏈飽和碳基團。該等基團包括(但不限於)甲基、乙基、正丙基、異丙基、正丁基、異丁基、第二丁基、第三丁基及其類似基團。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.
術語"視情況經取代"意謂(除非另外指示,否則)經如此改質之部分可具有所指示之一或多個取代基。每一取代基可置換經如此改質之部分上之任何氫原子,限制條件為該置換在化學上係可行且穩定的。舉例而言,化學上不穩定之化合物應係其中兩個取代基之每一個經由每一取代基之雜原子與一單一C原子鍵結之化合物。化學上不穩定之化合物之另一實例應係其中一烷氧基鍵結至一烯烴之不飽和碳上而形成烯醇醚之化合物。當在任何部分上存在兩個取代基時,每一取代基係獨立於另一取代基選擇以致該等取代基相應地可相同或不同。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.
術語"環烷基"意謂飽和單環烷基。術語"(C3 -C7 )環烷基"意謂約3至約7個碳原子之飽和單環烷基。該等基團包括(但不限於)環丙基、環丁基、環戊基、環己基及環庚基。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.
術語"(C3 -C6 )二羥基烷基"意謂包括鍵結至飽和碳之兩個羥基(-OH)組份之如上文所描述的烷基。該等(C3 -C6 )二羥基烷基可為直鏈或支鏈的。(C3 -C6 )二羥基烷基之羥基組份通常係彼此毗鄰的。然而(C3 -C6 )二羥基組份可添加於任何可用之碳處。(C3 -C6 )二羥基烷基包括(但不限於)2,3-二羥基丙基、3,4-二羥基丁基、5,6-二羥基己基及其類似基團。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.
術語"(C2 -C6 )羥基烷基"意謂包括鍵結至一飽和碳之一羥基(-OH)組份之如上文所描述的烷基。該等(C2 -C6 )羥基烷基可為直鏈或支鏈的。(C2 -C6 )羥基烷基之羥基組份可位於任何可用之碳處。(C2 -C6 )羥基烷基包括(但不限於)2-羥基乙基、3-羥基丙基及其類似基團。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.
術語"鹵基"意謂選自Cl、Br及F之原子。The term "halo" means an atom selected from the group consisting of Cl, Br and F.
術語"鹵烷基"意謂包括鍵結至一飽和碳之一或多個鹵基組份之如上文所描述的烷基。該等鹵烷基可為直鏈或支鏈的。鹵烷基之鹵基組份可位於任何可用之碳處。該等鹵烷基包括(但不限於)2-氯乙基、3-溴丙基、2,2,3,3,3-五氟丙基及其類似基團。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.
術語"硝基"意謂選自-NO2 、氰基(-CN)、-NHCH3 及-NHC2 H5 之原子。The term "nitro" means an atom selected from the group consisting of -NO 2 , cyano (-CN), -NHCH 3 and -NHC 2 H 5 .
術語"雜環部分"係含有一環狀結構之物質,其中除碳之外(例如,硫、氧或氮)原子形成該環之部分。舉例而言,3-7員雜環部分包括至少一個形成3-7員環結構之環或骨架之部分之除碳之外的其它原子。4-8員雜環部分包括至少一個形成4-8員環結構之環或骨架之部分之除碳之外的其它原子。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.
術語"親水特徵"意謂具有對水或其它極性溶劑之親合力;容易吸收或溶解於水或其它極性溶劑中。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.
術語"疏水特徵"意謂不具有對水或其它極性溶劑之親合力;不容易吸收或溶解於水或其它極性溶劑中。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.
術語"芳族部分"意謂含有一或多個苯環之物質。芳族取代基可為單環、二環或三環的。芳族取代基之非限制性實例包括苯基、苄基、萘基、蒽基及其類似基團。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.
諸如"(甲基)丙烯酸"之表示法本文中用來表示視情況之甲基取代基。因此,舉例而言,"(甲基)丙烯酸"包括甲基丙烯酸及丙烯酸。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.
如上文所討論,該等水膠體組合物包括第一單體及第二單體。第一單體之一實施例係關於式I之化合物,其係N-乙烯基醯胺。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.
其中R為CH3 且R1為H之式I之一非限制性實例係N-乙烯基乙醯胺。式I之其它實例包括R為CH2 CH3 且R1為H,其係N-乙烯基丙醯胺。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.
式I之環狀結構之非限制性實例包括N-乙烯基吡咯啶酮,其係在其骨幹中包括4個碳及1個氮之5員雜環化合物。N-乙烯基吡咯啶酮如下文化合物A所示:
需要式I具有親水特徵。需要獨立選擇R及R1使得式I具有親水特徵。亦需要選擇R與R1之組合以形成具有親水特徵之式I之環狀結構。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.
在一實施例中,式I之第一單體及式II之第二單體(其係如下文所討論)、交聯劑及溶劑形成水膠體組合物。第一單體與第二單體之比率為約0.1:99.9至約99.9:0.1。更特定言之,第一單體與第二單體之比率為約20:80至約80:20且,甚至更具體言之為約40:60至約60:40。第二單體之一實施例係關於式II之化合物,其係N-乙烯基醯胺。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.
其中R3或R4為(C3 -C1 8 )烷基且其中該烷基視情況經一或多個取代基取代之式II的實例包括(但不限於)N-乙烯基丁醯胺、N-乙烯基戊醯胺、N-乙烯基十二醯胺、N-乙烯基4-氯丁醯胺及其類似物。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.
其中R3或R4為(C3 -C7 )環烷基且其中該環烷基視情況經一或多個取代基取代之式II的實例包括(但不限於)N-乙烯基環己基羧醯胺、N-乙烯基環戊基羧醯胺、N-乙烯基4-溴環己基羧醯胺及其類似物。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.
其中R3或R4為芳族部分且其中該芳族部分視情況經一或多個取代基取代之式II的實例包括(但不限於)N-乙烯基苯甲醯胺、N-乙烯基4-硝基苯甲醯胺、N-乙烯基萘醯胺及其類似物。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.
需要式II具有疏水特徵。需要獨立選擇R3及R4使得式II具有疏水特徵。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.
在另一實施例中,式I之第一單體及式III之第二單體(其係如下文所討論)、交聯劑及溶劑形成水膠體組合物。第二單體之另一實施例係關於式III之化合物,其係乙烯基醚。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.
其中R5為(C3 -C1 8 )烷基且其中該烷基視情況經一或多個取代基取代之式III的實例包括(但不限於)乙烯基丙基醚、乙烯基己基醚、乙烯基十二烷基醚、乙烯基4-氯丁基醚及其類似物。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.
其中R5為(C3 -C7 )環烷基且其中該環烷基視情況經一或多個取代基取代之式III的實例包括(但不限於)乙烯基環己基醚、乙烯基環戊基醚、乙烯基4-溴環己基醚及其類似物。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.
其中R5為芳族部分且其中該芳族部分視情況經一或多個取代基取代之式III的實例包括(但不限於)乙烯基苯基醚、乙烯基4-硝基苯基醚、乙烯基2-萘基醚及其類似物。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.
當將第一單體及第二單體與溶劑(例如,水)相混合時,該等物質之結構完整性可能不如所需強烈。若將第一單體及第二單體與大量溶劑混合,則尤其可能為該情況。為進一步增加機械強度,將交聯劑添加至該第一單體及該第二單體中。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.
可使用之交聯劑之非限制性實例包括(但不限於)下列:多官能乙烯基醚、二乙烯基苯、多官能丙烯酸酯及多官能丙烯醯胺。為成為合意之第一及第二單體之交聯劑,該交聯劑必須具有能連接兩聚合鏈之幾何形狀。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.
根據一實施例,可使用式V之交聯化合物(多官能乙烯基醚)。According to an embodiment, a crosslinking compound of formula V (polyfunctional vinyl ether) can be used.
可用作交聯劑之多官能乙烯基醚之一實例係二乙二醇二乙烯基醚,其如下文化合物B所示:
預期可使用其它多官能乙烯基醚作為交聯劑,諸如三乙二醇二乙烯基醚及四(乙二醇)二乙烯基醚。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.
根據另一實施例,可使用式VI之交聯化合物(二乙烯基苯):
用作交聯劑之多官能丙烯酸酯之一實例為乙二醇二甲基丙烯酸酯(EGDMA),其如下文化合物C所示。An example of a polyfunctional acrylate useful as a crosslinking agent is ethylene glycol dimethacrylate (EGDMA), which is shown below as Compound C.
可用作交聯劑之多官能丙烯醯胺之一實例為N,N'-亞甲基二丙烯醯胺,其如下文化合物D所示。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.
該共聚網路組合物一般包含約0.01至約10體積%之交聯劑。固化前,共聚網路組合物在本文中定義為包括第一單體、第二單體、交聯劑及以下將討論之其它組份。所定義之共聚網路組合物不包括溶劑(例如,水)。更具體言之,聚合網路組合物包含約0.1至約1體積%之交聯劑。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.
為幫助聚合,可將光引發劑添加至第一單體、第二單體及交聯劑中。光引發劑之一實例為Ciba專業化學製品有限公司(Ciba Specialty Chemicals Pty,Ltd.)以Irgacure2959所銷售之2-羥基-4'-(2-羥基乙氧基)-2-甲基苯丙酮。預期可添加其它光引發劑。該聚合網路組合物一般包含0.0001至約5重量%之光引發劑。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.
將第一單體及第二單體與溶劑混合。通常所用之溶劑之一實例係水。溶劑之其它實例為水混合物。預期在本發明中可使用其它溶劑。水量可進行變化且主要視存在於水膠體組合物中之第一單體及第二單體之量而定。預期可將其它物質添加至第一單體、第二單體、交聯劑及溶劑之水膠體組合物中。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.
在添加交聯劑之後,第一單體與第二單體形成交聯之共聚網路。為用交聯劑達成第一單體與第二單體之聚合,可藉由諸如紫外(以添加UV引發劑達成之UV輻射)、熱引發(以添加熱引發劑達成)、γ-射線及電子束之方法引發聚合。為幫助聚合,可將光引發劑添加至第一單體、第二單體及交聯劑中。在一方法中,將共聚網路浸泡於溶劑(例如,水)中以形成水膠體組合物。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.
在一實施例中,可將水膠體組合物調試以充當皮膚與感應器(例如,電化學感應器)之間之界面。在一方法中,該感應器使用該水膠體組合物測定ISF(間質流體)中所要分析物之濃度。可量測之分析物包括葡萄糖、脂質概況(例如,膽固醇、甘油三酯、LDL及HDL)、微量白蛋白、血色素A1 C 、果糖、乳酸鹽或膽紅素。預期可測定其它分析物之濃度。如在本申請案內所用,術語"濃度"係指分析物之濃度、活性(例如,酶及電解質)、力價(例如,抗體)或用來量測所要分析物之任何其它量測濃度。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.
水膠體組合物(其在該實施例中將用作皮膚與感應器之間之界面)包含第一單體、第二單體、交聯劑及溶劑(例如,水)。該水膠體組合物係以聚合鏈形式組合至少第一單體與第二單體之無規共聚網路。該共聚網路藉由該第一單體及該第二單體之體積百分數至少在一定程度上加以控制。在本申請案中,有利的係該水膠體組合物具有凝膠強度與可撓性之間之平衡。亦需要該水膠體組合物具有合意之信號強度。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.
調試第一單體以對水膠體組合物提供親水特徵。第一單體包括式I之化合物(N-乙烯基醯胺),其於上文更詳細地討論。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.
預期可使用其它第一單體,包括甲基丙烯酸羥基烷基酯、丙烯醯胺、N,N-二烷基丙烯醯胺、甲基丙烯酸、丙烯酸、甲基丙烯酸金屬鹽、丙烯酸金屬鹽、衣康酸、馬來酸、甲基丙烯醯胺、N,N-二烷基丙烯醯胺、苯乙烯磺酸、苯乙烯磺酸金屬鹽、苯乙烯羧酸、苯乙烯羧酸金屬鹽、丙烯醯胺-2-甲基丙烷磺酸、丙烯醯胺-2-甲基丙烷磺酸金屬鹽、鹵化2-乙烯基N-烷基吡錠或鹵化4-乙烯基N-烷基吡錠。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.
可用作第一單體之甲基丙烯酸羥基烷基酯之一實例係甲基丙烯酸羥基乙酯,其如下文化合物E所示。An example of a hydroxyalkyl methacrylate which can be used as the first monomer is hydroxyethyl methacrylate, which is shown below as compound E.
可用作第一單體之丙烯醯胺如下文化合物F所示。The acrylamide which can be used as the first monomer is shown in the following compound F.
可用作第一單體之N,N-二烷基丙烯醯胺之一實例係N,N-二甲其丙烯醯胺,其如文化合物G所示。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.
根據另一實施例,第一單體可為甲基丙烯酸,其如下文化合物H所示:
調試第二單體以對水膠體組合物提供機械強度。調試第二單體亦對水膠體組合物提供疏水特徵。藉由對水膠體組合物提供疏水特徵,較佳地控制溶劑(例如,水)之量。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.
在一實施例中,第二單體係關於於式II之化合物(N-乙烯基醯胺),其係更詳細地討論於上文中。In one embodiment, the second single system is related to the compound of formula II (N-vinylguanamine), which is discussed in more detail above.
在另一實施例中,第二單體係關於式III之化合物(乙烯基醚),其係更詳細地討論於上文中。In another embodiment, the second single system is related to the compound of formula III (vinyl ether), which is discussed in more detail above.
第二單體之一另外實施例係關於式IV之化合物,其係乙烯酯。An additional embodiment of one of the second monomers is a compound of formula IV which is a vinyl ester.
其中R2為(C1 -C1 8 )烷基且其中該烷基視情況經一或多個取代基取代之式IV之實例包括(但不限於)2-氯乙基、3-溴丙基、2,2,3,3,3-五氟丙基及其類似基團。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.
其中R2為(C3 -C7 )環烷基且其中該環烷基視情況經一或多個取代基取代之式IV之實例包括(但不限於)環戊基、環己基、2-氯環己基、4-溴環己基及其類似基團。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.
其中R2為芳族部分且其中該芳族部分視情況經一或多個取代基取代之式IV之實例包括(但不限於)苯甲酸乙烯酯、苯基乙酸乙烯酯、4-溴苯甲酸乙烯酯、4-硝基苯甲酸乙烯酯、1-萘二甲酸乙烯酯、2-萘二甲酸乙烯酯及其類似物。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.
諸如乙酸乙烯酯或十二酸乙烯酯之乙烯酯可用作第二單體。乙酸乙烯酯如下文化合物J所示,而十二酸乙烯酯如化合物K所示。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.
除由式II-IV形成之第二單體外,預期第二單體可另外包括(但不限於)(甲基)丙烯酸烷基酯,其包括甲基丙烯酸烷基酯及丙烯酸烷基酯。可用作第二單體之甲基丙烯酸烷基酯之一實例係甲基丙烯酸甲酯,其如下文化合物L所示。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.
第一單體與第二單體之比率為約0.1:99.9至約99.9:0.1。更具體言之,第一單體與第二單體之比率為約80:20至約20:80,且甚至更具體言之為約60:40至約40:60。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.
使用第一單體及第二單體之共聚物網路之一實例係下文式M所示。An example of a copolymer network using the first monomer and the second monomer is shown by the following formula M.
該共聚網路組合物一般包含約0.01至約10體積%之交聯劑。如上文所討論,固化前該共聚網路組合物在本文中定義為包括第一單體、第二單體、交聯劑及以下所討論之其它組份。所定義之共聚網路組合物不包括溶劑(例如,水)。更具體言之,該聚合網路組合物包含約0.1至約1體積%之交聯劑。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.
如上文所討論,為幫助聚合,可將光引發劑添加至第一單體、第二單體及交聯劑中。光引發劑之一實例係Ciba專業化學製品有限公司以Irgacure2959所銷售之2-羥基-4'-(2-羥基乙氧基)-2-甲基苯丙酮。預期可添加其它光引發劑。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.
將第一單體及第二單體與溶劑混合。通常所用之溶劑之一實例為水。溶劑之另一實例為水混合物。預期在本發明中可使用其它溶劑。然而,在測定分析物濃度之應用中,需要溶劑大體上與皮膚有生物可相容性。水量可進行變化且主要視存在於水膠體組合物中之第一聚合物及第二聚合物之量而定。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.
預期可添加其它物質至第一單體、第二單體、交聯劑及溶劑之水膠體組合物中。舉例而言,可將電解質添加至水膠體組合物中。視水膠體組合物之應用而定,該電解質可起多重作用。首先,電解質係當溶解時離子化以產生導電介質之化學化合物。其次,合意之電解質含有高鹽濃度,當用於接觸皮膚之應用時其幫助在皮膚上施加滲透壓。藉由在皮膚上施加滲透壓,電解質幫助將含有分析物之間質流體(ISF)驅出。可使用之電解質之非限制性實例包括氯化物之鈉鹽及鉀鹽、磷酸鹽、檸檬酸鹽、乙酸鹽及乳酸鹽。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.
溶液可另外包括酶以幫助測定分析物濃度。視分析物而定,酶可幫助將分析物轉化成可經諸如電化學偵測之偵測的物種。可用於測定葡萄糖之酶之一實例係葡萄糖氧化酶。預期可使用其它酶,諸如葡萄糖脫氫酶。若其它分析物具有重要性,則經適當選擇之酶可幫助測定該分析物之濃度。通常(若使用酶,則)在第一單體及第二單體固化之後添加。第一單體及第二單體之固化通常涉及使用熱應力或應用電磁輻射,其可負面影響酶之活性。然而,預期可在固化之前將酶與第一單體及第二單體混合。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.
溶液可另外包括滲透增強劑。滲透增強劑在將水膠體組合物應用於皮膚上之應用中係合意的。滲透增強劑幫助打開皮膚之毛孔。可使用之滲透增強劑之非限制性實例包括(但不限於)角鯊烯、不飽和脂肪酸、脂肪醇之甘油衍生物、二甲亞碸及脂肪酸之烷基酯。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.
可添加至水膠體組合物中之其它物質包括殺生物劑、保濕劑、界面活性劑及其組合。殺生物劑幫助抑制細菌生長。可使用之殺生物劑之非限制性實例包括對氧苯甲酸酯系列之防腐劑、苯甲酸鈉、氯苄烷銨及三烷基胺。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.
保濕劑在需要保持皮膚濕潤之應用中起幫助作用。可使用之保濕劑之非限制性實例包括甘油、己二醇及山梨糖醇、麥芽糖醇、聚右旋糖、丙二醇、乳酸及乳酸金屬鹽。界面活性劑幫助偶合水膠體組合物與皮膚以獲得其之間經改良之接觸。可使用之界面活性劑之非限制性實例包括諸如TRITONX-100(具有分子式C1 4 H2 2 O(C2 H4 O)n 之乙氧基化辛基苯酚,其中"n"之平均值為9或10)及山梨糖醇及諸如TWEENT M 系列之山梨糖醇衍生物。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.
若用於電化學應用中,則該水膠體組合物可在其使用前在電極表面上乾燥及重新構成。若重新構成,則所添加之溶劑可包括電解質。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.
在電化學應用中,該水膠體組合物一般具有約0.1密耳至約100密耳之厚度,更具體言之,具有約1密耳至約30密耳之厚度。在一實施例中藉由水膠體組合物覆蓋之電化學感應器之表面積為約0.1 cm2 至約100 cm2 。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 .
該水膠體組合物具有足夠之機械及熱穩定性以提供皮膚取樣位點與感應器之間之相對穩定、反應性及水性之管道,更具體言之,需要水膠體組合物具有實體均一性及可撓性及反抗剪切力之機械穩定性。在經選擇之應用中,可需要水膠體組合物在所要之持續時間內(例如,約24至約72或更多小時)保持水含量為約50至約90重量%。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).
此外,該水膠體組合物具有高親水性以抵抗長期使用期間之脫水。藉由減少或大體上消除脫水,未改變水膠體組合物之傳輸特性。亦需要水膠體組合物保持皮膚之多孔性。該水膠體組合物亦需要顯示相對高之可壓縮性以幫助保證良好之皮膚/感應器連接性或皮膚黏接性。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.
亦需要水膠體組合物具有足夠大之多孔性用於酶捕集。舉例而言,在某些涉及葡萄糖濃度測定之應用中,需要該水膠體組合物提供用於葡萄糖氧化酶(GO)之基質及用於葡萄糖及過氧化氫之擴散通道。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.
在添加交聯劑之後,第一單體與第二單體形成交聯之共聚物網路。為以交聯劑達成第一單體與第二單體之聚合,可藉由諸如紫外(UV)輻射(例如,高強度UV輻射)、熱引發(例如,冷凍-解凍循環)、γ-射線及電子束之方法引發聚合。為幫助聚合,可將光引發劑添加至第一單體、第二單體及交聯劑中。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.
在一方法中,將共聚網路浸泡於溶劑(例如,水)中以製得水膠體組合物。該溶劑可包括上文所討論之組份,諸如電解質、酶、滲透增強劑、殺生物劑、保濕劑、界面活性劑及其組合。預期可將電解質、酶、滲透增強劑、殺生物劑、保濕劑、界面活性劑及其組合單獨自溶劑添加至共聚網路中。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.
在一方法中,將水膠體組合物乾燥以除去溶劑且形成經乾燥之共聚網路或經乾燥之水膠體組合物。該經乾燥之水膠體組合物可為薄膜形式。經乾燥之水膠體組合物可另外包括機械支撐物。該機械支撐物幫助對經乾燥之水膠體組合物薄膜提供機械強度。機械支撐物之實例包括聚合物網、編織品、非編織品、纖維素(例如,紙)或其組合。纖維素材料之實例包括市售之紙(例如,紙抹布、紙巾或濾紙)或纖維素織物。預期其它機械支撐物可與經乾燥之水膠體組合物薄膜一起使用。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.
通常,存在約10至約90重量%之纖維素基質而剩餘物為共聚網路。因此,在一實施例中,存在10重量%之纖維素基質及90重量%之共聚網路。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.
在一實施例中,將共聚網路吸收至多孔纖維素基質中。舉例而言,第一單體與第二單體之間的接枝共聚反應可發生至多孔纖維素基質上。該反應可藉由使用高能量輻射、化學引發及在光引發劑存在下之紫外(UV)輻射引發。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.
水膠體組合物之一實例展示於圖1中,該水膠體組合物具有一包括一經乾燥之水膠體組合物薄膜12及一機械支撐物14之經乾燥之水膠體薄膜系統10。預期該機械支撐物可多於一層。根據另一實施例,該機械支撐物可嵌入水膠體組合物內。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.
在一方法中,該經乾燥之水膠體組合物薄膜可用溶劑(例如,水)來重新構造。包括共聚網路及溶劑之水膠體組合物可包含約1至約99體積%之水。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.
在一方法中,該水膠體組合物用以幫助用感應器測定間質流體(ISF)之分析物濃度。更具體言之,調試水膠體組合物以充當一般在皮膚與感應器之間且偶合皮膚與感應器之界面。在該方法中,感應器測定來自ISF樣品中之所要分析物的濃度。在一實施例中,該感應器為一電化學感應器。電化學感應器之一實例包括一使用一接觸、含鉑工作電極之標準三電極穩壓器。預期可使用其它電化學感應器,包括彼等具有較少電極之感應器,諸如二電極電化學感應器,其包括一相對電極及一工作電極。亦預期可使用其它感應器,諸如光學感應器。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.
參見圖2,根據一實施例展示一電化學感應器。電化學感應器30包括一相對電極32、一工作電極34及一參考電極36。該電化學感應器之一詳細實例包括一碳相對電極、一鉑工作電極及一銀/氯化銀參考電極。預期相對電極、工作電極及參考電極可用其它材料製得。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.
如圖3中所示,電化學感應器系統50包括圖2之電化學感應器30、一經乾燥之水膠體薄膜52及一黏接環54。經乾燥之水膠體薄膜52包括諸如上文所描述之無溶劑之彼等的水膠體組合物。在該實施例中,黏接環54具有兩個作用:(a)覆蓋一部分經乾燥之水膠體薄膜52且緊固其與電化學感應器30;及(b)緊固包括經乾燥之水膠體薄膜52之電化學感應器系統50與皮膚。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.
在一方法中,將水膠體組合物添加至皮膚上。該水膠體組合物可位於諸如腕部與肘部之間之手前臂之皮膚位點處。預期水膠體組合物可位於諸如腹部之其它皮膚位點處。在該方法中接著將皮膚進行預處理以增加皮膚滲透性。預處理之一實例係使用超音波能量以破壞角質層之脂質雙層以便增加皮膚之滲透性。藉由增加皮膚滲透性,增加經皮取樣中所用之間質流體(ISF)之量。此引起重要分析物(例如,葡萄糖)之經改良取樣於ISF中找到。感應器在接觸水膠體組合物及ISF之後測定所要分析物之濃度。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.
超音波能量系統之一非限制性來源係由Sontra醫藥公司(Sontra Medical Corporation)所銷售之Sontra SonoPrep超音皮膚滲透系統。該SonoPrep系統在有限之持續時間(約10至20秒)內對皮膚施用相對低頻率超音波能量。該裝置中所含之超音喇叭每秒振動約55,000次(55 KHz)且經由液體偶合介質對皮膚施用能量以製得在偶合介質中擴張及收縮之空蝕氣泡。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.
在另一方法中,自電化學感應器系統(例如,電化學感應器系統50)將水膠體組合物添加至皮膚。接著對皮膚進行預處理以增加皮膚滲透性。預處理之一實例係使用上文所討論之超音波能量,使用例如Sontra醫藥公司(Sontra Medical Corporation)所銷售之Sontra's SonoPrep超音皮膚滲透系統。該電化學感應器在接觸水膠體組合物及ISF之後測定所要分析物之濃度。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.
使用非侵入性測試方法測定葡萄糖濃度。生成如圖4a、圖4b所示之曲線的方法如下。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.
共聚混合物包括第一單體(N-乙烯基吡咯啶酮)、第二單體(乙酸乙烯酯)、Ciba專業化學製品有限公司以Irgacure2959所銷售之光引發劑(2-羥基-4'-(2-羥基乙氧基)-2-甲基苯丙酮)及交聯劑(二乙二醇二乙烯基醚)。該共聚混合物包括50份N-乙烯基吡咯啶酮、50份乙酸乙烯酯、0.5份Irgacure2959及0.5份二乙二醇二乙烯基醚。將第一單體、第二單體、光引發劑及交聯劑混合。將共聚混合物用氮氣(N2 )鼓泡約5分鐘。接著將該共聚混合物置於紫外燈下約2.25小時。接著將該共聚混合物移開且貯存於冰箱中。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.
將該共聚混合物固化以形成經乾燥之共聚薄膜。該經乾燥之共聚薄膜藉由在80℃下以熱去離子水漂洗兩次歷經2小時來純化。將該共聚薄膜用空氣冷卻以重新形成經乾燥之共聚薄膜。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.
在4℃下將經乾燥之共聚薄膜與溶液混合16小時以上以形成水膠體薄膜。預先製備之溶液係經磷酸鹽緩衝之生理食鹽水溶液,其含有5重量%之葡萄糖氧化酶。在該溶液中所包括之唯一其它添加劑係界面活性劑(0.05重量%之TritonX-100)。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).
將該水膠體薄膜切割成所要尺寸且在電化學感應器系統之工作區域上乾燥。將電化學感應器上之經乾燥之水膠體薄膜用經緩衝之溶劑(經磷酸鹽緩衝之生理食鹽水)重新構成以形成水膠體組合物。將該水膠體組合物施用於腕部與肘部之間之手前臂之三個不同位置處。前臂位點1靠近腕部,前臂位點3靠近肘部,且前臂位點2位於前臂位點1與3之間。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.
將前臂位點1-3處之手前臂皮膚藉由於此處施用超音波能量進行預處理。水膠體組合物中之葡萄糖氧化酶接觸皮膚及含有葡萄糖之間質流體(ISF)。葡萄糖氧化酶幫助將ISF中之葡萄糖轉化成過氧化物。響應過氧化物之偵測,自電化學感應器產生電流。該電流對應於ISF中之葡萄糖濃度。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.
經一段時間對於每一前臂位點1-3量測電流。亦經相同時間使用Analis所銷售之ANALOX-葡萄糖分析器GM 10(Glucose Analyser GM 10)量測真實葡萄糖濃度,其係比較方法。此於圖4a、圖4b中標記為"血漿葡萄糖"參見圖4a,將藉由使用前臂位點1-3之以上方法及比較方法(圖4a中標記為血漿葡萄糖)而測定之電流(奈安培)相對於時間(秒)繪製曲線。此外,圖4a之曲線包括以mg/dL為表示之葡萄糖,其與所量測之電流相關。為更好地比較相同點,將前臂位點2及3之續數相對於所觀察到之最高感應器信號電流正規化。前臂2及3之經正視化之讀數在圖4b與前臂位點1及血漿葡萄糖一起展示。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.
展示使用本發明之方法(前臂位點1-3)所測定之葡萄糖值之測試之結果與在比較方法(血漿葡萄糖)中目標之平行葡萄糖值有關。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).
在實例2中,製得兩種不同之本發明之組合物。在本發明之水膠體墊1中,將共聚網路及纖維素基質接枝在一起,在本發明之水膠體墊2中,形成共聚網路且接著將其置於耐綸網上。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.
具體言之,在本發明之水膠體墊1中,將共聚網路及纖維素基質接枝在一起。該共聚網路包含60份N-乙烯基吡咯啶酮(第一單體)、40份乙酸乙烯酯(第二單體)、1份二乙二醇二乙烯基醚及1份係紫外(UV)引發劑之(2-羥基-4'-(2-羥基乙氧基)-2-甲基苯丙酮。共聚網路與纖維素基質之重量比率為2:1。所用之纖維素基質係獲自Kimberly-Clark之Kimwipes吸收抹布(absorbent wiper)EX-L。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.
將單體混合物吸收至多孔Kimwipes吸收抹布EX-L中且接著曝露於UV中輻射2小時以完成聚合反應。反應之後,將經凝膠之共聚網路及纖維素基質浸入水中以除去未反應之單體。纖維素與交聯之共聚網路相互滲透且,因此,經化學方式鍵結在一起。第一單體與第二單體亦以化學方式彼此鍵結。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.
將經化學方式鍵結之共聚物/纖維素網路與水完全合以形成水膠體薄片。在完全水合之後,將具有酶(葡萄糖氧化酶)之緩衝液添加至該水膠體薄片中。接著將該水膠體薄片乾燥且儲存。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.
將該水膠體薄片切割成所要尺寸以形成水膠體墊。將該水膠體墊連接至電化學感應器之表面。接著將經連接之水膠體墊用包括緩衝液之水再水合。本發明之水膠體墊1具有約60至約90重量%之水且一般係均一且機械穩定的。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.
將皮膚使用Sontra SonoPrep超音皮膚滲透系統之超音波能量處理。在皮膚之兩個不同區域-腕部及肘部執行測試。將本發明之水膠體墊1黏附於每一該等位置之皮膚上。藉由電化學感應器量測電流且在每一位置處測定葡萄糖濃度。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.
本發明之水膠體墊2包含共聚物網路。該共聚網路包含60份N-乙烯基吡咯啶酮(第一單體)、40份乙酸乙烯酯(第二單體)、1份二乙二醇二乙烯基醚及1份(2-羥基-4'-(2-羥基乙氧基)-2-甲基苯丙酮。將該共聚網路曝露於UV中輻射2小時以完成聚合反應。在反應之後,將經凝膠之共聚網路浸入水中以除去未反應之單體。第一單體與第二單體以化學方式彼此鍵結。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.
將共聚網路用水完全水合以形成水膠體薄片。在完全水合之後,將具有酶(葡萄糖氧化酶)之緩衝液添加至水膠體薄片中。接著將該水膠體薄片乾燥且儲存。為改良水膠體薄片之處理,使用耐綸網支撐水膠體薄片。將帶有耐綸網之水膠體薄片切割成所要尺寸以形成本發明之水膠體墊2。將本發明之水膠體墊2連接至電化學感應器之表面。接著將經連接之水膠體墊2用包括緩衝液之水再水合。經水合之本發明之水膠體墊2包含約60至約90重量%之水且一般係均一且機械穩定的。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.
將皮膚(前臂)使用Sontra SonoPrep超音皮膚滲透系統處理。將經水合之本發明之水膠體墊2黏附於皮膚(前臂)上。藉由電化學感應器量測電流且測定葡萄糖濃度。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.
使用本發明之水膠體墊1及2之測試結果展示於圖5中。圖5以電流(奈安培)及葡萄糖濃度(mg/dL)相對於時間繪製曲線。具體言之,圖5描繪使用電化學感應器測試血液且量測葡萄糖濃度之比較方法(圖5中標記為血漿葡萄糖)。圖5之比較方法未使用水膠體組合物。在該比較方法中,每30分鐘取血液樣品且用Lunenberg,Massachusetts之Analox Instruments U.S.A.,Inc.所銷售之Analox GM9D分析器加以分析。使用本發明之水膠體墊1(在腕部與肘部處)及水膠體墊2(前臂)之方法的結果亦繪製曲線。如圖5中所示,來自本發明之方法(使用本發明之水膠體墊1及2)之葡萄糖濃度一般與來自比較方法1之目標之血漿葡萄糖濃度有關。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.
水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體係選自式I:
替代實施例A之水膠體組合物,其中該交聯劑係多官能乙烯基醚、二乙烯基苯、多官能丙烯酸酯或多官能丙烯醯胺。Aqueous colloidal composition of Alternate Embodiment A wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide.
替代實施例B之水膠體組合物,其中該交聯劑係多官能乙烯基醚,該多官能乙烯基醚係二乙二醇二乙烯基醚、三乙二醇二乙烯基醚及四(乙二醇)二乙烯基醚。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.
替代實施例B之水膠體組合物,其中該交聯劑係二乙烯基苯。A hydrocolloid composition of the alternative embodiment B, wherein the crosslinking agent is divinylbenzene.
替代實施例B之水膠體組合物,其中該交聯劑係多官能丙烯酸酯,該多官能丙烯酸酯係乙二醇二甲基丙烯酸酯(EGDMA)、聚乙二醇二丙烯酸酯、二乙二醇二甲基丙烯酸酯、二乙二醇二丙烯酸酯、乙二醇二丙烯酸酯或二甲基丙烯酸1,3-二羥基丙酯。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.
替代實施例B之水膠體組合物,其中該交聯劑係多官能丙烯醯胺。Alternately the hydrocolloid composition of embodiment B, wherein the crosslinker is a polyfunctional acrylamide.
替代實施例A之水膠體組合物,其中該溶劑係水。A hydrocolloid composition of Alternate Embodiment A wherein the solvent is water.
替代實施例A之水膠體組合物另外包括光引發劑。The hydrocolloid composition of Alternative Example A additionally includes a photoinitiator.
替代實施例A之水膠體組合物,其中該第一單體與該第二單體之比率係約20:80至約80:20。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.
替代實施例A之水膠體組合物,其中該第二單體係選自式II。A hydrocolloid composition of the alternative embodiment A, wherein the second single system is selected from Formula II.
替代實施例A之水膠體組合物,其中該第二單體係選自式III。The hydrocolloid composition of Alternate Embodiment A wherein the second single system is selected from Formula III.
替代實施例A之水膠體組合物,其中該第一單體係N-乙烯基乙醯胺、N-乙烯基丙醯胺、N-乙烯基吡咯啶酮或N-乙烯基己內醯胺,該第二單體係選自R3或R4係視情況經取代之(C3 -C1 8 )烷基之式II。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.
替代實施例A之水膠體組合物,其中該第一單體係N-乙烯基乙醯胺、N-乙烯基丙醯胺、N-乙烯基吡咯啶酮或N-乙烯基己內醯胺,該第二單體係選自R3或R4係視情況經取代之(C3 -C7 )環烷基之式II。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.
替代實施例A之水膠體組合物,其中該第一單體係N-乙烯基乙醯胺、N-乙烯基丙醯胺、N-乙烯基吡咯啶酮或N-乙烯基己內醯胺,該第二單體係選自R3或R4係視情況經取代之芳族部分之式II。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.
替代實施例A之水膠體組合物,其中該第一單體係N-乙烯基乙醯胺、N-乙烯基丙醯胺、N-乙烯基吡咯啶酮或N-乙烯基己內醯胺,該第二單體係選自R3或R4係視情況經取代之(C3 -C1 8 )烷基之式II。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.
替代實施例A之水膠體組合物,其中該第一單體係N-乙烯基乙醯胺、N-乙烯基丙醯胺、N-乙烯基吡咯啶酮或N-乙烯基己內醯胺,該第二單體係選自R3或R4係視情況經取代之(C3 -C7 )環烷基之式II。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.
替代實施例A之水膠體組合物,其中該第一單體係N-乙烯基乙醯胺、N-乙烯基丙醯胺、N-乙烯基吡咯啶酮或N-乙烯基己內醯胺,該第二單體係選自R3或R4係視情況經取代之芳族部分之式II。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.
一電化學感應器系統包含:一電化學感應器,其具有至少一相對電極及一工作電極;及一水膠體組合物,其接觸該工作電極,該水膠體組合物包含第一罩體、第二單體、交聯劑及溶劑,該第一單體係選自甲基丙烯酸羥基烷基酯、丙烯醯胺、N,N-二烷基丙烯醯胺、甲基丙烯酸、丙烯酸、甲基丙烯酸金屬鹽、丙烯酸金屬鹽、衣康酸、馬來酸、甲基丙烯醯胺、N,N-二烷基丙烯醯胺、苯乙烯磺酸、苯乙烯磺酸金屬鹽、苯乙烯羧酸、苯乙烯羧酸金屬鹽、丙烯醯胺-2-甲基丙烷磺酸、丙烯醯胺-2-甲基丙烷磺酸金屬鹽、鹵化2-乙烯基N-烷基吡錠、鹵化4-乙烯基N-烷基吡錠或式I,其中式I為
其中式IV為
其中該第一單體與該第二單體之比率為約0.1:99.9至約99.9:0.1。Wherein the ratio of the first monomer to the second monomer is from about 0.1:99.9 to about 99.9:0.1.
替代實施例R之電化學感應器系統另外包括一緊固該水膠體組合物與該電化學感應器之黏接結構。The electrochemical sensor system of Alternate Embodiment R additionally includes a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor.
替代實施例R之電化學感應器系統,其中該電化學感應器另外包括一參考電極。An electrochemical sensor system of alternative embodiment R, wherein the electrochemical sensor additionally comprises a reference electrode.
替代實施例R之電化學感應器系統,其中該水膠體組合物係經乾燥之水膠體組合物。An electrochemical sensor system of alternative embodiment R wherein the hydrocolloid composition is a dried hydrocolloid composition.
替代實施例U之電化學感應器系統,其中該經乾燥之水膠體組合物係薄膜。An electrochemical sensor system of alternative embodiment U, wherein the dried hydrocolloid composition is a film.
替代實施例R之電化學感應器系統另外包括一機械支撐物以幫助對該水膠體組合物提供機械強度。The electrochemical sensor system of Alternate Embodiment R additionally includes a mechanical support to help provide mechanical strength to the hydrocolloid composition.
替代實施例W之電化學感應器系統,其中該機械支撐物係聚合物網、編織品、非編織品、纖維素或其組合。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.
替代實施例R之電化學感應器系統,其中該水膠體組合物具有約0.1密耳至約100密耳之厚度。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.
替代實施例Y之電化學感應器系統,其中該水膠體組合物具有約1密耳至約30密耳之厚度。An electrochemical sensor system of alternative embodiment Y wherein the hydrocolloid composition has a thickness of from about 1 mil to about 30 mils.
替代實施例R之電化學感應器系統,其中該第一單體與該第二單體之比率為約20:80至約80:20。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.
一電化學感應器系統,包含:一電化學感應器,其具有至少一相對電極及一工作電極;及一水膠體組合物,其接觸該工作電極,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體係選自式I
替代實施例BB之電化學感應器系統另外包括一緊固該水膠體組合物與該電化學感應器之黏接結構。The electrochemical sensor system of the alternative embodiment BB additionally includes a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor.
替代實施例BB之電化學感應器系統,其中該電化學感應器另外包括一參考電極。An electrochemical sensor system of the alternative embodiment BB, wherein the electrochemical sensor additionally comprises a reference electrode.
替代實施例BB之電化學感應器系統,其中該水膠體組合物係經乾燥之水膠體組合物。An electrochemical sensor system of the alternative embodiment BB, wherein the hydrocolloid composition is a dried hydrocolloid composition.
替代實施例EE之電化學感應器系統,其中該經乾燥之水膠體組合物係薄膜。An electrochemical sensor system of the alternative embodiment EE, wherein the dried hydrocolloid composition is a film.
替代實施例BB之電化學感應器系統另外包括一機械支撐物以幫助對該水膠體組合物提供機械強度。The electrochemical sensor system of Alternative Embodiment BB additionally includes a mechanical support to help provide mechanical strength to the hydrocolloid composition.
替代實施例GG之電化學感應器系統,其中該機械支撐物係聚合物網、編織品、非編織品、紙或其組合。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.
替代實施例BB之電化學感應器系統,其中該交聯劑係多官能乙烯基醚、二乙烯基苯、多官能丙烯酸酯或多官能丙烯醯胺。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.
替代實施例BB之電化學感應器系統,其中該第一單體與該第二單體之比率為約20:80至約80:20。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.
一電化學感應器系統,包含:一電化學感應器,其具有至少一相對電極及一工作電極;及一水膠體組合物,其接觸該工作電極,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體係選自由下列各物組成之群:N-乙烯基吡咯啶酮、甲基丙烯酸羥基烷基酯、丙烯醯胺及N,N-二烷基丙烯醯胺,該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、N-乙烯基丙烯醯胺、乙烯基酯及乙烯基醚,且其中該第一單體與該第二單體之比率為約0.1:99.9至約99.9:0.1。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.
替代實施例KK之電化學感應器系統另外包括一緊固該水膠體組合物與該電化學感應器之黏接結構。The electrochemical sensor system of Alternate Embodiment KK additionally includes a bonding structure for fastening the hydrocolloid composition to the electrochemical sensor.
替代實施例KK之電化學感應器系統,其中該電化學感應器另外包括一參考電極。An electrochemical sensor system of alternative embodiment KK, wherein the electrochemical sensor additionally comprises a reference electrode.
替代實施例KK之電化學感應器系統,其中該水膠體組合物係經乾燥之水膠體組合物。An electrochemical sensor system of alternative embodiment KK, wherein the hydrocolloid composition is a dried hydrocolloid composition.
替代實施例NN之電化學感應器系統,其中該經乾燥之水膠體組合物係薄膜。An electrochemical sensor system of an alternative embodiment NN, wherein the dried hydrocolloid composition is a film.
替代實施例KK之電化學感應器系統另外包括一機械支撐物以幫助對該水膠體組合物提供機械強度。The electrochemical sensor system of Alternate Embodiment KK additionally includes a mechanical support to help provide mechanical strength to the hydrocolloid composition.
替代實施例PP之電化學感應器系統,其中該機械支撐物係聚合物網、編織品、非編織品、紙或其組合。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.
替代實施例KK之電化學感應器系統,其中該第一單體係N-乙烯基吡咯啶酮且該第二單體係乙烯酯。An electrochemical sensor system of alternative embodiment KK, wherein the first single system N-vinyl pyrrolidone and the second single system vinyl ester.
替代實施例KK之電化學感應器系統,其中該交聯劑係多官能乙烯基醚、二乙烯基苯、多官能丙烯酸酯或多官能丙烯醯胺。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.
替代實施例KK之電化學感應器系統,其中該第一單體與該第二單體之比率係約20:80至約80:20。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.
一電化學感應器系統,包含:一電化學感應器,其具有至少一相對電極及一工作電極;及一水膠體組合物,其接觸該工作電極,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體具有親水特徵,該第二單體具有疏水特徵,且其中該第一單體與該第二單體之比率為約0.1:99.9至約99.9:0.1。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.
一種測定一分析物濃度之方法,該方法包含以下行為:將水膠體組合物置於皮膚上,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體係選自甲基丙烯酸羥基烷基酯、丙烯醯胺、N,N-二烷基丙烯醯胺、甲基丙烯酸、丙烯酸、甲基丙烯酸金屬鹽、丙烯酸金屬鹽、衣康酸、馬來酸、甲基丙烯醯胺、N,N-二烷基丙烯醯胺、苯乙烯磺酸、苯乙烯磺酸金屬鹽、苯乙烯羧酸、苯乙烯羧酸金屬鹽、丙烯醯胺-2-甲基丙烷磺酸、丙烯醯胺-2-甲基丙烷磺酸金屬鹽、鹵化2-乙烯基N-烷基吡錠、鹵化4-乙烯基N-烷基吡錠或式I,其中式I為
替代方法A之方法另外包括預處理皮膚以改良皮膚之滲透性。The method of Alternative Method A additionally includes pretreating the skin to improve the permeability of the skin.
替代方法B之方法,其中該預處理包括對皮膚施用超音波能量。The method of alternative method B, wherein the pretreating comprises applying ultrasonic energy to the skin.
替代方法A之方法,其中該皮膚係手前臂。The method of alternative A, wherein the skin is a forearm.
替代方法A之方法,其中該分析物係葡萄糖。The method of alternative method A, wherein the analyte is glucose.
替代方法A之方法,其中該感應器係一電化學感應器。The method of alternative method A, wherein the inductor is an electrochemical sensor.
替代方法A之方法,其中該第一單體與該第二單體之比率係約20:80至約80:20。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.
一種測定一分析物濃度之方法,該方法包含以下行為:將水膠體組合物置於皮膚上,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體係選自式I
替代方法H之方法另外包括預處理皮膚以改良皮膚之滲透性。The method of Alternative Method H additionally includes pretreating the skin to improve the permeability of the skin.
替代方法I之方法,其中該預處理包括對皮膚施用超音波能量。The method of alternative method I, wherein the pretreating comprises applying ultrasonic energy to the skin.
替代方法H之方法,其中皮膚係手前臂。Alternative method H, wherein the skin is attached to the forearm.
替代方法H之方法,其中該分析物係葡萄糖。The method of alternative method H, wherein the analyte is glucose.
替代方法H之方法,其中該感應器係一電化學感應器。The method of alternative method H, wherein the inductor is an electrochemical sensor.
替代方法H之方法,其中該第一單體與該第二單體之比率係約20:80至約80:20。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.
一種測定一分析物濃度之方法,該方法包含以下行為:將水膠體組合物置於皮膚上,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體係選自由下列各物組成之群:N-乙烯基吡咯啶酮、甲基丙烯酸羥基烷基酯、丙烯醯胺及N,N-二烷基丙烯醯胺,該第二單體係選自由下列各物組成之群:(甲基)丙烯酸烷基酯、N-乙烯基醯胺、乙烯基酯及乙烯基醚,且其中該第一單體與該第二單體之比率為約0.1:99.9至約99.9:0.1;提供一感應器,該水膠體組合物一般位於皮膚與該感應器之間且偶合該皮膚與該感應器;及取樣間質流體以使用該感應器測定該分析物濃度。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 .
替代方法O之方法另外包括預處理皮膚以改良皮膚之滲透性。The method of Alternative Method O additionally includes pretreating the skin to improve the permeability of the skin.
替代方法P之方法,其中該預處理包括對皮膚施用超音波能量。A method of alternative P, wherein the pretreating comprises applying ultrasonic energy to the skin.
替代方法O之方法,其中皮膚係手前臂。Alternative method O, wherein the skin is attached to the forearm.
替代方法O之方法,其中該分析物係葡萄糖。A method of Alternative O, wherein the analyte is glucose.
替代方法O之方法,其中該感應器係一電化學感應器。The method of alternative method O, wherein the inductor is an electrochemical sensor.
替代方法O之方法,其中該第一單體係N-乙烯基吡咯啶酮且該第二單體係乙烯酯。The method of alternative method O, wherein the first single system N-vinylpyrrolidone and the second single system vinyl ester.
替代方法U之方法,其中該交聯劑係多官能乙烯基醚、二乙烯基苯、多官能丙烯酸酯或多官能丙烯醯胺。The method of alternative method U, wherein the crosslinking agent is a polyfunctional vinyl ether, divinylbenzene, a polyfunctional acrylate or a polyfunctional acrylamide.
替代方法O之方法,其中該第一單體與該第二單體之比率係約20:80至約80:20。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.
一種測定一分析物濃度之方法,該方法包含以下行為:將水膠體組合物置於皮膚上,該水膠體組合物包含第一單體、第二單體、交聯劑及溶劑,該第一單體具有親水特徵,該第二單體具有疏水特徵,其中該第一單體與該第二單體之比率係約0.1:99.9至約99.9:0.1;提供一感應器,該水膠體組合物一般定位於皮膚與該感應器之間且偶合該皮膚與該感應器;及取樣間質流體以使用該感應器測定該分析物濃度。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.
儘管本發明已參考一或多個特定實施例加以描述,但是熟習此項技術者應認識到在不背離本發明之精神及範疇下可對其進行許多變化。預期每一該等實施例及其顯著變化屬於本發明之精神及範疇。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...經乾燥之水膠體薄膜系統10. . . Dried water colloidal film system
12...經乾燥之水膠體組合物薄膜12. . . Dried water colloidal composition film
14...機械載體14. . . Mechanical carrier
30...電化學感應器30. . . Electrochemical sensor
32...相對電極32. . . Relative electrode
34...工作電極34. . . Working electrode
36...參考電極36. . . Reference electrode
50...電化學感應器系統50. . . Electrochemical sensor system
52...經乾燥之水膠體薄膜52. . . Dried water colloid film
54...黏接環54. . . Adhesive ring
圖1為根據一實施例之一經乾燥之水膠體及一機械支撐物。1 is a dried hydrocolloid and a mechanical support in accordance with an embodiment.
圖2為根據一實施例之一電化學感應器。2 is an electrochemical inductor in accordance with an embodiment.
圖3為包括圖2之電化學感應器之一電化學感應器系統。3 is an electrochemical sensor system including one of the electrochemical inductors of FIG. 2.
圖4a為繪製電流、葡萄糖濃度相對於時間之曲線圖。Figure 4a is a plot of current, glucose concentration versus time.
圖4b為圖4a繪製電流、葡萄糖濃度相對於時間之經正規化之曲線圖。Figure 4b is a graph plotting the normalization of current and glucose concentration versus time in Figure 4a.
圖5為繪製電流、葡萄糖濃度相對於時間之曲線圖。Figure 5 is a graph plotting current, glucose concentration versus time.
10...經乾燥之水膠體薄膜系統10. . . Dried water colloidal film system
12...經乾燥之水膠體組合物薄膜12. . . Dried water colloidal composition film
14...機械支撐物14. . . Mechanical support
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