WO2021184843A1 - Copolymère triséquencé pour biocapteur implantable, application associée et procédé de préparation associé - Google Patents
Copolymère triséquencé pour biocapteur implantable, application associée et procédé de préparation associé Download PDFInfo
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- WO2021184843A1 WO2021184843A1 PCT/CN2020/135162 CN2020135162W WO2021184843A1 WO 2021184843 A1 WO2021184843 A1 WO 2021184843A1 CN 2020135162 W CN2020135162 W CN 2020135162W WO 2021184843 A1 WO2021184843 A1 WO 2021184843A1
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- triblock copolymer
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Definitions
- the invention relates to the technical field of block copolymers, in particular to a triblock copolymer for implantable biosensors, and also to the application and preparation method of the triblock copolymer.
- Implantable biosensor refers to a sensor device that can be partially or completely implanted into the human body, which can measure the content of target analyte molecules without the need for additional reagents and pre-separation and treatment of body fluids or blood.
- the advantage of the implantable biosensor is that it can continuously measure some important physiological and pathological parameters in the body that change over time, such as blood oxygen, blood sugar, virus antibodies, etc., so as to more directly reflect the physical signs of the tested object due to environmental changes, Changes caused by physical activity, diet, and medications.
- the sensing part of the implanted sensor needs to interact with the analyte in the tissue to detect the presence of the analyte.
- the biocompatibility permeable membrane has very high technical requirements for its components, such as extremely low cytotoxicity, good hydrophilicity and biocompatibility, appropriate permeability and diffusion performance for the target analyte, and barrier to potential interferences Performance, as well as heat resistance, hydrolysis resistance and resistance to other degradation mechanisms within a given time of use.
- the material is also required to have a stable chemical molecular structure, so that it can maintain stable properties for a long time before being used. Therefore, the current options for biocompatible permeable membranes are very limited.
- permeable membranes are mostly made of polyethylene glycol, poly(2-hydroxyethyl methacrylate) and other generally recognized highly biocompatible hydrophilic polymers or their mixtures, and are made by adding polyester Or hydrophobic materials such as polysiloxane are copolymerized with hydrophilic materials or directly mixed to control the overall permeability of the permeable membrane.
- This type of permeable membrane material has a common problem, that is, the glass transition temperature of the hydrophobic part is lower than room temperature, the mobility is very high, it is easy to migrate to the surface and repel the hydrophilic part, causing the microphase separation of the material.
- the prior art CN201610792708.4 discloses a high biocompatibility triblock copolymer.
- the copolymer material in this patent application can also be used in implantable biosensors, it has a permeation and diffusion performance for target analytes.
- the controllability of the sensor, and the demand for oxygen permeability of the sensor involving the oxidase reaction need to be improved.
- the material of the present invention has great improvements in these properties.
- the block copolymer of the present invention is particularly suitable for use as an implantable biosensor biocompatible permeable membrane.
- the copolymer has extremely low cytotoxicity, good hydrophilicity and biocompatibility, and is suitable for target analytes. Permeation and diffusion properties and barrier properties to potential interferences, as well as heat resistance, hydrolysis resistance and resistance to other degradation mechanisms within a given time of use.
- a triblock copolymer for implantable biosensors of the present invention is polymerized by adding a block polymerization reagent and a small molecule chain extender to a mixture of the following block materials:
- Block A a highly hydrophilic soft segment material, selected from dihydroxy, dicarboxyl or diamine-terminated polyethylene glycol, polypropylene glycol and polybutylene glycol, and amine-terminated poly(ethylene glycol)/ One or more of poly(propylene glycol) copolymers with a number average molecular weight of 500-3000;
- Block B a rigid and highly hydrophobic hard segment material, selected from one or more of dihydroxy or diamine-terminated polycarbonate, bisphenol A polycarbonate and polymethyl methacrylate, the number is average The molecular weight is 1000-3000;
- Block C flexible polymer, selected from one or more of poly double-end epoxy polysiloxane, dihydroxy polydimethylsiloxane and poly(-2-hydroxyethyl methacrylate) Species with a number average molecular weight of 500-3000;
- the general formula of the copolymer is (-AbBbC-) n , where A, B, and C are block structures, and b is a block polymerization reagent,
- a block is 5-40 parts
- B block is 5-20 parts
- C block is 20-70 parts
- block polymerization reactant b is 10-40 parts.
- the permeable membrane synthesized from the raw materials in the ratio range has a stable and controllable low permeability of water-soluble small molecules, and is suitable for detecting water-soluble small molecules through enzyme reaction (for example: detecting the content of glucose in solution or blood by glucose oxidase) )
- the biosensor is used to control the rate of penetration of the detected substance to the surface of the sensor.
- b is an isocyanate-based polymerization reagent.
- the isocyanate polymerization reactant is selected from one or more of the following substances: 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, cyclohexane dimethylene diisocyanate, 4, 4'-diphenylmethane diisocyanate, xylylene diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, 4,4'-dicycloethylmethane diisocyanate.
- the structural formulas of these substances are:
- the small molecule chain extender is selected from one or more of the following substances: ethylene glycol, water, butanediol, ethylenediamine, hydroquinone dihydroxyethyl ether, benzidine, 3,3'-Dichlorobenzidine, 3,3'-Dichloro-4,4'-Diaminodiphenylmethane.
- ethylene glycol water, butanediol, ethylenediamine, hydroquinone dihydroxyethyl ether, benzidine, 3,3'-Dichlorobenzidine, 3,3'-Dichloro-4,4'-Diaminodiphenylmethane.
- the use of the small molecule chain extender as described above allows the block copolymer of the present invention to be further polymerized, and the molecular weight of the final material is increased to make it have the desired performance.
- a block is 15-30 parts, B block is 5-10 parts, C block is 40-50 parts, and block polymerization reactant b is 20-25 parts. Parts, small molecule chain extender is 0-5 parts.
- A-b, B-b, and C-b are covalently connected by a urea or carbamate group.
- the invention also relates to the application of the triblock copolymer in implantable biosensors.
- the present invention also relates to a method for preparing the triblock copolymer, which includes the following steps:
- Step 1 Add the highly hydrophilic soft segment material, the rigid and highly hydrophobic hard segment material, and the flexible polymer into an organic solvent and mix them uniformly at 30-45°C; organic solvents include tetrahydrofuran and cyclohexanone Or isobutanol; the total mass ratio of the volume of the organic solvent and the soft segment material with high hydrophilicity, the rigid segment material with high rigidity and hydrophobicity, and the flexible polymer is 2-10ml:1g;
- Step 2 Add a catalyst to the mixed solution of Step 1, and add a block polymerization reagent dropwise, heat up to 55-70°C, and react for 12-20 hours;
- the catalyst includes triethylenediamine or tin dibutyl diisooctoate;
- Step 3 Add a small molecule chain extender to the reaction solution of Step 2, and react for 12h-18h; the quality of the small molecule chain extender and the soft segment material with high hydrophilicity, the hard segment material with rigidity and high hydrophobicity, and the flexibility are more.
- the total mass ratio of the polymer is 0.1-0.3g:1g;
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- the block copolymer and preparation method of the present invention have the following advantages:
- the present invention combines the advantages of three types of single polymer molecules so that its block copolymer has the characteristics of adjustable permeability, adjustable physical properties, better hydrolytic stability and heat resistance stability, and Comparing the simple mixing of the three types of polymer molecules, the use of isocyanate chain extenders such as diisocyanates to combine them through the chain extension reaction can prevent the phenomenon of micro-phase separation during the film formation process.
- the triblock copolymer of the present invention has more stable physical and chemical properties, and has better hydrolysis and heat resistance than simple hydrophilic/hydrophobic copolymers or blends such as polyether and polyester polyurethane.
- the hydrophilicity, permeability and physical strength of the multi-block copolymer can be continuously adjusted by adjusting the percentage of each block in the material.
- this material has a significantly improved ratio of oxygen to glucose permeability and the stability of the ratio, which can better avoid oxygen Problems such as decreased sensor measurement accuracy caused by insufficient supply.
- Fig. 1 is a comparison of the permeability of small molecule analytes (such as glucose) measured when the ratio of hydrophilic material to hydrophobic material is different between the present invention material and the hydrophilic/hydrophobic copolymer or blend material of the prior art.
- small molecule analytes such as glucose
- Figure 2 is a comparison between the water and heat resistance of the material of the present invention and the hydrophilic/hydrophobic copolymer or blend material of the prior art.
- Figure 3 is a comparison of the storage stability of the hydrophilic contact angle on the surface of the film prepared from the material of the present invention and the hydrophilic/hydrophobic copolymer or blend material of the prior art.
- Figure 4 is a comparison of the ratio of oxygen permeability to glucose permeability of the present invention material and the hydrophilic/hydrophobic copolymer or blended material of the prior art when the glucose permeability is similar.
- the general formula of the block copolymer of the present invention is AbBbC, where A, B, and C are block structures, b is a block polymerization reagent, and Ab, Bb, and Cb are covalently bonded through urea or urethane groups. connect.
- A represents a highly hydrophilic soft segment material, which is a block composed of at least one of polyethylene glycol, polypropylene glycol, and polyetheramine.
- A is preferably selected from dihydroxy, dicarboxyl or diamine-terminated polyethylene
- B represents a rigid and highly hydrophobic hard segment material, which is a block composed of at least one of polycarbonate and polymethyl methacrylate, and B is preferably selected from dihydroxy or diamine-terminated polycarbonate and bisphenol A
- C represents a flexible polymer, which is a block composed of at least one of polydimethylsiloxane and poly(2-hydroxyethyl methacrylate), and C is preferably selected from the group consisting of poly-two-terminated epoxy polysiloxane One or more of alkane, dihydroxy polydimethylsiloxane and poly(-2-hydroxyethyl methacrylate), with a number average molecular weight of 500-3000; this type of block plays a certain transitional role Makes the type A block and the type B block less prone to microphase separation during mixing and film formation.
- b represents a block polymerization reaction agent, specifically an isocyanate block polymerization reaction agent, including one or more of diphenylmethane diisocyanate, hexamethylene diisocyanate, and dicyclohexylmethane diisocyanate.
- Block and block are connected by isocyanate block polymerization reaction agent through polycondensation mechanism to generate stable polyurethane or polyurea multi-block copolymer.
- the reaction mechanism is as follows:
- Q is a small molecule chain extender with bifunctionality, selected from water, ethylene glycol, 1,4-butanediol, benzidine, diethylene glycol, 1,2-propylene glycol, dipropylene glycol, 1 ,6-Hexanediol, neopentyl glycol, diethyltoluenediamine, 3,5-dimethylthiotoluenediamine.
- the mass parts of the three kinds of blocks and the block polymerization reagent are as follows: A block is 5-40 parts, B block is 5-20 parts, and C block is 20-70 parts.
- the weight ratio of the block polymerization reactant b is 10-40 parts, and the small molecule chain extender is 0-10 parts.
- the total number of parts by mass is 100 parts: 15-30 parts for A block, 5-10 parts for B block, 40-50 parts for C block, 20-25 parts for block polymerization reactant b, 0-5 parts of small molecule chain extender.
- the permeable membrane made of the block copolymer material synthesized according to this raw material ratio has a stable and controllable low permeability of water-soluble small molecules, which is suitable for the detection of water-soluble small molecules by enzyme reaction (for example: detection by glucose oxidase)
- the biosensor based on the glucose content in the solution or blood is used to control the rate of penetration of the test substance to the surface of the sensor.
- the triblock copolymer of the present invention is a linear polymer.
- the preparation method of the above-mentioned high biocompatibility triblock copolymer includes the following steps:
- Step 1 Add the highly hydrophilic soft segment material, the rigid and highly hydrophobic hard segment material, and the flexible polymer into an organic solvent, and mix them uniformly at 30-45°C; the organic solvent includes tetrahydrofuran or isobutanol , The total mass ratio of the volume of the organic solvent and the soft segment material with high hydrophilicity, the hard segment material with rigidity and high hydrophobicity, and the flexible polymer is 2-10ml:1g.
- Step 2 Add a catalyst to the mixed solution of Step 1, and add a block polymerization reagent dropwise. The temperature is raised to 55-70° C., and the reaction is carried out for 12-20 hours; the catalyst includes triethylene diamine or dibutyl tin diisooctoate.
- Step 3 Add a small molecule chain extender to the reaction solution of Step 2, and react for 12h-18h; the volume of deionized water and the soft segment material with high hydrophilicity, the hard segment material with rigidity and high hydrophobicity, and the flexible polymer
- the total mass ratio is 0.1-0.3g:1g.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- the triblock copolymer of the present invention in the preparation of biocompatible permeable membranes for implantable biosensors.
- the prepared permeable membrane has a highly controllable permeability of small molecules, good water resistance and heat resistance, adjustable hydrophilicity and biocompatibility, which is mainly realized by multi-block copolyurea or polyurethane containing amphiphilic molecules of.
- Raw materials polyetheramine, number average molecular weight 1500; polycarbonate diol, number average molecular weight 3000; diamino-terminated polydimethylsiloxane, number average molecular weight 3000; diphenylmethane diisocyanate; the above raw materials are in accordance with The total mass is 50g, and the ratio of mass parts is 5:10:70:15; 10:9:63:18; 15:9:55:21; 20:8:48:24; 25:8:40:27; 30:7:33:30; 35:7:26:32; 40:6:20:34 to make 8 kinds of polymer materials.
- the reaction solvent is 100ml of tetrahydrofuran and 50ml of deionized water.
- the synthesis method is as follows:
- Step 1 Add polyetheramine, polycarbonate diol, and diamino-terminated polydimethylsiloxane to tetrahydrofuran, and mix uniformly at 40°C.
- Step 2 Add triethylene diamine to the mixed solution of step 1, and add diphenylmethane diisocyanate dropwise, heat up to 65° C., and react for 12 hours.
- Step 3 Add deionized water to the reaction solution of Step 2, and react for 12 hours.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- Raw materials polyethylene glycol, number average molecular weight 1500; diamino-terminated polydimethylsiloxane, number average molecular weight 3000; diphenylmethane diisocyanate; the above raw materials are 50g in total mass, and the ratio of mass parts is 5 :75:20; 10:68:22; 15:60:25; 20:52:28; 25:45:30; 30:37:33; 35:30:35; 40:22:38 for matching production 8 kinds of polymer materials.
- the reaction solvent is 100ml of tetrahydrofuran and 50ml of deionized water.
- the corresponding comparative polymer materials were synthesized according to the above-mentioned synthesis method.
- Raw materials polyethylene glycol, with a number average molecular weight of 12000; polydimethylsiloxane, with a number average molecular weight of 9000; the above-mentioned raw materials have a total mass of 50g, and the ratio of mass parts is 5:95; 10:90; 15:85; 20:80; 25:75; 30:70; 35:65; 40:60 were mixed in a solvent to make 8 kinds of comparative mixed polymer materials.
- the reaction solvent is 100 ml of tetrahydrofuran.
- the corresponding comparative polymer materials were synthesized according to the above-mentioned synthesis method.
- Raw materials polyetheramine, number average molecular weight 1000, mass 25g; polycarbonate diol, number average molecular weight 5000, mass 10g; diamino-terminated polydimethylsiloxane, number average molecular weight 5000, mass 15g; Tetrahydrofuran, 100ml; Diphenylmethane diisocyanate, mass 12g; Deionized water 50ml.
- the synthesis method is as follows:
- Step 1 Add polyetheramine, polycarbonate diol, and diamino-terminated polydimethylsiloxane to tetrahydrofuran, and mix uniformly at 40°C.
- Step 2 Add triethylene diamine to the mixed solution of step 1, and add diphenylmethane diisocyanate dropwise, heat up to 65° C., and react for 12 hours.
- Step 3 Add deionized water to the reaction solution of Step 2, and react for 12 hours.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- Raw materials amino terminated polypropylene glycol, molecular weight 500, mass 15g; polyetheramine, molecular weight 600, mass 10g; poly(bisphenol A carbonate), molecular weight 5000, mass 25g; diamino terminated polydimethylsiloxane Alkane, molecular weight is 20000, mass 10g; poly(2-hydroxyethyl methacrylate), molecular weight is 5000, mass 5g; isobutanol 150ml; hexamethylene diisocyanate, mass 15g; deionized water 150ml.
- the synthesis method is as follows:
- Step 1 Add amino-terminated polypropylene glycol, polyetheramine, poly(bisphenol A carbonate), diamino-terminated polydimethylsiloxane, and poly(-2-hydroxyethyl methacrylate) to In isobutanol, mix well at 35°C.
- Step 2 Add tin dibutyl diisooctoate to the mixed solution of step 1, and add hexamethylene diisocyanate dropwise, increase the temperature to 60° C., and react for 16 hours.
- Step 3 Add deionized water to the reaction solution of Step 2, and react for 14 hours.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- Raw materials amino terminated polypropylene glycol, molecular weight 500, mass 8g; polyetheramine, molecular weight 600, mass 10g; poly(bisphenol A carbonate), molecular weight 3000, mass 15g; diamino terminated polydimethylsiloxane Alkane, with a molecular weight of 2400 and a mass of 10 g; poly(2-hydroxyethyl methacrylate) with a molecular weight of 800 and a mass of 10 g; 300 ml of isobutanol; hexamethylene diisocyanate with a mass of 10 g; and 15 ml of ethylene diamine.
- the synthesis method is as follows:
- Step 1 Add amino-terminated polypropylene glycol, polyetheramine, poly(bisphenol A carbonate), diamino-terminated polydimethylsiloxane, and poly(-2-hydroxyethyl methacrylate) to In isobutanol, mix well at 35°C.
- Step 2 Add tin dibutyl diisooctoate to the mixed solution of step 1, and add hexamethylene diisocyanate dropwise, increase the temperature to 60° C., and react for 16 hours.
- Step 3 Add ethylenediamine to the reaction solution of Step 2, and react for 14 hours.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- Raw materials amino terminated polyethylene glycol, number average molecular weight 2000, mass 16g; polymethyl methacrylate, number average molecular weight 2000, mass 10g; dicarboxyl terminated polydimethylsiloxane, number average molecular weight 1200, the mass is 20g; tetrahydrofuran, 500ml; 3g isophorone diisocyanate and 6g dicyclohexylmethane diisocyanate; ethylene glycol 10ml.
- the synthesis method is as follows:
- Step 1 Add amino-terminated polyethylene glycol, polymethyl methacrylate, and diamino-terminated polydimethylsiloxane to tetrahydrofuran, and mix uniformly at 30°C.
- Step 2 Add triethylene diamine to the mixed solution of step 1, and add the mixed solution of diphenylmethane diisocyanate and dicyclohexylmethane diisocyanate dropwise, heat up to 55° C., and react for 14 hours.
- Step 3 Add deethylene glycol to the reaction solution of Step 2, and react for 18 hours.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- Raw materials amino-terminated polyethylene glycol, number average molecular weight 3000, mass 35g; polycarbonate diol, number average molecular weight 1,200, mass 8g; polymethyl methacrylate, number average molecular weight 1,200, mass 16g; poly( 2-hydroxyethyl methacrylate), number average molecular weight 2500, mass 35g; isobutanol 600ml; trimethylhexamethylene diisocyanate 10g; hydroquinone dihydroxyethyl ether 10ml.
- the synthesis method is as follows:
- Step 1 Add amino-terminated polyethylene glycol, polycarbonate diol, polymethyl methacrylate, and poly(-2-hydroxyethyl methacrylate) to isobutanol, at 45°C well mixed.
- Step 2 Add tin dibutyl diisooctoate to the mixed solution of step 1, and add dicyclohexylmethane diisocyanate dropwise, increase the temperature to 70° C., and react for 20 hours.
- Step 3 Add hydroquinone dihydroxyethyl ether to the reaction solution of Step 2, and react for 16 hours.
- Step 4 After cooling, the reaction product is washed, filtered, and dried to obtain the triblock copolymer.
- the 8 kinds of triblock copolymers prepared in Example 1 and the 8 kinds of polymer materials and 8 kinds of mixed materials prepared in Comparative Examples 1 and 2 were respectively dissolved in an organic solvent such as tetrahydrofuran, and then spin-coated on aluminum Dry the surface of the pan until the solvent has evaporated to prepare a film, and then carefully remove the film from the aluminum pan.
- an organic solvent such as tetrahydrofuran
- test method Perform glucose permeability performance test on the prepared film, the test method is as follows:
- the prepared film is sandwiched between the two solution chambers of the transdermal tester.
- the solution chamber on one side is filled with high-concentration glucose solution, the other side is added with the same volume of phosphate buffer solution, and then the solutions on both sides are regularly taken out for glucose concentration Test and measure the thickness of the film, and then calculate the glucose permeability of the film through a formula.
- the higher the proportion of hydrophilic components (such as polypropylene glycol, polyethylene glycol, polyetheramine, etc.) in the material the higher the glucose permeability.
- the glucose permeability of the material prepared by the present invention has a more ideal linear relationship with its hydrophilic component ratio. This allows the material of the present invention to better control the permeability by changing the ratio of different raw materials to meet the requirements for use in implantable biosensors.
- the triblock copolymer prepared in Example 2 and the materials prepared in Comparative Example 1 and Comparative Example 2 by using polyethylene glycol of similar mass ratio were respectively prepared into thin films, and the heat resistance and hydrolysis resistance properties were compared.
- the film preparation process is as follows: the tested material is dissolved in an organic solvent such as tetrahydrofuran, then spin-coated on the surface of the glass sheet and heated to 40°C until the solvent is completely evaporated, so that the tested material forms a thin film on the glass surface.
- each sample film (about 0.1g per sample) in a constant temperature and humidity oven at 60°C and 100% relative humidity. Take out the sample at 0, 5, 10, 15, 20, and dissolve the sample in an organic solvent such as For tetrahydrofuran, use size exclusion chromatography (SEC) or gel permeation chromatography (GPC) to measure its molecular weight distribution and calculate the number average molecular weight. Compare the calculated number average molecular weight with the unsoaked sample to get the ratio of "average molecular weight/initial molecular weight", expressed as a percentage. As shown in Figure 2, the average molecular weight of the comparative material was significantly reduced after storage at high temperature and high humidity, indicating that its molecules had been partially decomposed, and its resistance to heat and hydrolysis was poor.
- the triblock copolymer material and polyether polyurethane of the present invention prepared in Example 2 have good hydrolysis resistance and thermal decomposition resistance.
- the triblock copolymer prepared in Example 3 and the materials prepared in Comparative Example 1 and Comparative Example 2 using similar mass ratios of polyethylene glycol were compared for the hydrophilic contact angle of the film surface.
- the hydrophilic contact angle test method is to dissolve the tested material in an organic solvent such as tetrahydrofuran, then spin-coat on the surface of the glass sheet and heat it to 40°C until the solvent is completely evaporated, so that the tested material forms a thin film on the glass surface, and then sample the thin film Store at room temperature (about 25°C) and indoor relative humidity (about 20%-40%). Take out the sample regularly (e.g.
- the surface hydrophilicity of homopolymer blends and diblock copolymers is reduced after being placed for a period of time, while the surface hydrophilicity of the new material prepared in Example 1 is relatively stable. , It will not change much after 6 months of storage at room temperature.
- the triblock copolymer material prepared in Example 4 and the materials prepared in Comparative Example 3 and Comparative Example 4 were respectively dissolved in an organic solvent such as tetrahydrofuran, and then spin-coated on the surface of an aluminum plate and dried until the solvent was completely evaporated. After forming a film, carefully remove the film from the aluminum pan. Perform oxygen permeability performance test on the prepared film.
- the test method is as follows:
- the prepared film is sandwiched between the two solution chambers of the transdermal tester, and the same volume of deoxygenated phosphate buffer solution is added to the solution chambers on both sides and put into the oxygen sensor and then sealed. After that, oxygen is supplied to the solution chamber on one side and the dissolved oxygen test is performed on the solution chambers on both sides regularly. After the dissolved oxygen concentration on both sides is close to equilibrium, the film is taken out for thickness measurement, and then the oxygen permeability of the film is calculated by the formula and the oxygen permeation is calculated The ratio of the rate to the glucose permeability. As shown in FIG. 4, the oxygen/glucose permeability ratio of the material made by the present invention is significantly higher than that of Comparative Example 1 and Comparative Example 2.
- the synthesized material of the present invention is more suitable for implantable biosensors based on oxidase reaction, especially for the use requirements of implantable glucose sensors based on glucose oxidase.
- concentration of glucose in the solution or tissue fluid on the outer side of the membrane is higher and the dissolved oxygen concentration is lower, the material membrane made by the present invention can more effectively ensure that the oxygen supply on the inner side of the membrane is higher than the permeated glucose, and ensure that the glucose oxidase reaction is based on The normal operating mechanism of the sensor is not affected by fluctuations in dissolved oxygen concentration.
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Abstract
La présente invention concerne un copolymère triséquencé pour un biocapteur implantable. Le copolymère triséquencé est formé par polymérisation par addition d'un réactif de polymérisation séquencée et d'un allongeur de chaîne micromoléculaire dans une solution mixte des substances de séquence suivantes : une séquence A qui est un matériau de segment mou ayant une hydrophilie élevée et a un poids moléculaire moyen en nombre de 500 à 3000 ; une séquence B qui est un matériau de segment dur rigide ayant une hydrophobicité élevée et a un poids moléculaire moyen en nombre de 1000 à 3000 ; et une séquence C qui est un polymère flexible et a un poids moléculaire moyen en nombre de 500 à 3000 ; la formule générale du copolymère séquencé est A-b-B-b-C ; A, B et C étant des structures de séquence, b étant un réactif de polymérisation séquencée, la somme des parties en masse des substances étant 100 : 5 à 40 parties de la séquence A, 5 à 20 parties de la séquence B, 20 à 70 parties de la séquence C, 10 à 40 parties du réactif de polymérisation séquencée, et 0 à 10 parties de l'allongeur de chaîne micromoléculaire. La présente invention concerne en outre une application du copolymère triséquencé et un procédé de préparation du copolymère triséquencé.
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WO2024060897A1 (fr) * | 2022-09-19 | 2024-03-28 | 苏州百孝医疗科技有限公司 | Polycarbonate polyuréthane biocompatible, son procédé de préparation et son utilisation |
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