Post-crosslinkable amphiphilic polyurethane, and preparation method therefor and use thereof in glucose sensor

Abstract

The present application belongs to the technical field of glucose detection. Disclosed are a post-crosslinkable amphiphilic polyurethane, a preparation method therefor and the use thereof in a glucose sensor. The preparation method for the post-crosslinkable amphiphilic polyurethane comprises: reacting a hydrophilic chain oligomer, a hydrophobic chain oligomer, a polydimethylsiloxane oligomer and a diisocyanate to obtain a precursor; and reacting the precursor with a chain extender containing a reactive group to obtain a post-crosslinkable amphiphilic polyurethane. The post-crosslinkable amphiphilic polyurethane is crosslinked with a cross-linking agent to obtain a polyurethane glucose limiting membrane, and the mechanical strength and hardness of the membrane can be adjusted and controlled by means of the crosslinking density, which solves the problem of the reduced performance of a CGM product caused by the degradation of a linear polyurethane glucose limiting membrane during the storage period or the use process. In addition, some unreacted active sites still remain on the crossed-linked surface of the post-crosslinkable amphiphilic polyurethane, and an anti-fouling layer can be modified on the surface thereof, thereby improving the biocompatibility of an electrode and prolonging the service life of the CGM product.

Description

A post-crosslinkable amphiphilic polyurethane and its preparation method and application in glucose sensor

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on December 1, 2023, with application number "202311643363.2" and invention name "A post-crosslinkable amphiphilic polyurethane, its preparation method and its application in glucose sensor", the entire content of which is incorporated by reference into this application. Technical Field

[0002] The present application relates to a post-crosslinkable amphiphilic polyurethane, a preparation method thereof, and an application thereof in a glucose sensor, belonging to the technical field of glucose detection. Background Art

[0003] With the development of society, the risk of diabetes is increasing annually. According to the International Diabetes Federation (IDF), the number of adults with diabetes worldwide is expected to increase by 48% by 2045, from 425 million in 2017 to 625 million. Diabetes has become a global public health issue that urgently needs to be addressed and resolved. Currently, the clinical treatment for diabetes involves measuring blood glucose levels through finger pricks several times a day, followed by insulin injections to normalize blood glucose levels. However, this treatment approach struggles to accurately control postprandial hyperglycemia and nocturnal hypoglycemia, as patients rely on real-time blood glucose data to adjust their insulin dosage. These limitations, coupled with the pain associated with repeated finger pricks, make this approach unsuitable for both patients and physicians. Over the past few decades, more sophisticated implantable blood glucose tracking devices, such as continuous glucose monitors (CGMs), have been developed. CGMs continuously capture blood glucose fluctuations, enabling comprehensive tracking of blood glucose trends over time.

[0004] Currently, amperometric glucose sensors based on glucose oxidase-catalyzed redox reactions of glucose are limited by the Michaelis-Menten kinetics of the glucose oxidase enzymatic reaction, so the sensor response current is not proportional to the glucose concentration, resulting in a very limited range of blood glucose concentrations that the sensor can detect. Typically, the maximum linear response of conventional glucose oxidase sensors to glucose concentration is approximately 2 mmol / L, which is lower than the blood glucose level of a normal human (3.9-6.1 mmol / L) and even lower than the blood glucose level of a diabetic patient, making it difficult to accurately detect glucose concentration. To overcome this shortcoming, in the art, a glucose diffusion-limiting membrane layer is typically applied above the sensing layer of the enzyme sensor. This membrane layer is usually made of some biocompatible polymer material and regulates the glucose flow rate based on the pore flow principle or chemical selectivity. This allows the glucose concentration in the enzyme sensing layer to control the linear range, thereby improving the sensor's glucose linear response range. In other words, the role of this membrane layer is to transform the glucose consumption rate from being controlled by the kinetics of the enzymatic reaction of the enzyme sensing layer to being controlled by diffusion in the membrane layer.

[0005] The outer membrane material used in Medtronic's CGM products is a polyurea-polyurethane polymer, formed by copolymerization of diisocyanates, hydrophilic diols or diamines, short-chain aliphatic diols, and siloxane polymers. During film coating, a polymer solution of a certain viscosity is applied to the electrode surface, and a film is formed after the solvent evaporates. During the storage period of CGM products, polyurethane is susceptible to environmental degradation, resulting in reduced stability of CGM products. Furthermore, the backbone of conventional linear polyurethane polymers lacks reactive sites, making further modification impossible to improve electrode biocompatibility and extend the lifespan of CGM products.

[0006] Summary of the Invention

[0007] In order to solve the above problems, a post-crosslinkable amphiphilic polyurethane, a preparation method thereof and its application in a glucose sensor are provided. The post-crosslinkable amphiphilic polyurethane adopts a chain extender containing reactive groups to react with a precursor to obtain a post-crosslinkable amphiphilic polyurethane. The post-crosslinkable amphiphilic polyurethane is a linear polymer. The hard segment of the chain extender contains reactive groups and can form a polyurethane with a crosslinked network structure under the action of the crosslinker. The post-crosslinkable amphiphilic polyurethane coating is then crosslinked by irradiation or in situ crosslinked on the electrode surface with a crosslinker to obtain a polyurethane glucose-limiting membrane with a crosslinked network structure, which further improves its mechanical properties and hardness. In addition, the mechanical strength and hardness of the polyurethane glucose-limiting membrane can be regulated by the crosslinking density. The molecular weight of the cross-linked polyurethane can be considered to be infinite, which solves the problem of degradation of the linear polyurethane glucose limiting membrane during storage or use, resulting in degradation of the phase structure, or transformation of the phase structure, which may lead to decreased performance of the CGM product. In addition, the post-cross-linked amphiphilic polyurethane will still have some unreacted active sites remaining on the surface after cross-linking, which provides a foundation for further modification of the polyurethane membrane surface by modifying an anti-fouling layer on the surface to improve the biocompatibility of the electrode and extend the service life of the CGM product.

[0008] According to one aspect of the present application, a method for preparing a post-crosslinkable amphiphilic polyurethane is provided, comprising the following steps:

[0009] The hydrophilic chain oligomer, the hydrophobic chain oligomer, the polydimethylsiloxane oligomer and the diisocyanate are reacted to obtain a precursor; the precursor is reacted with a chain extender containing a reactive group to further extend the chain to obtain the post-crosslinkable amphiphilic polyurethane.

[0010] Optionally, the chain extender containing reactive groups comprises the following structural formula:

[0011] Wherein R1 is 0 to 5 methylene groups, R2 is a H atom or 0 to 5 alkyl groups, and R3 contains an allyl group, a carboxyl group, a pyridine group, an imidazole group or an epoxy group having a reactive group.

[0012] Optionally, the chain extender is selected from at least one of trimethylolpropane allyl ether, allyl glyceryl ether, trimethylolpropane monoglycidyl ether, glycerol monoglycidyl ether, N,N-bis(2-hydroxyethyl)isonicotinamide, imidazole diol, 2,2-bis(hydroxymethyl)propionic acid and 2,2-bis(hydroxymethyl)butyric acid;

[0013] Furthermore, the chain extender is allyl glyceryl ether, which is cheap.

[0014] Optionally, the polydimethylsiloxane oligomer comprises bisaminopropyl-terminated polydimethylsiloxane and / or bishydroxy-terminated polydimethylsiloxane; and / or

[0015] The hydrophilic chain oligomer comprises at least one of polyethylene glycol, polyetheramine, propylene glycol-ethylene glycol copolymer and zwitterionic compound; and / or

[0016] The hydrophobic chain oligomer comprises at least one of polycarbonate diol, polytetramethylene ether and polypropylene glycol; and / or

[0017] The diisocyanate comprises at least one of diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate and hexamethylene diisocyanate;

[0018] Furthermore, the polydimethylsiloxane oligomer is a bisaminopropyl-terminated polydimethylsiloxane oligomer, the hydrophilic chain oligomer is polyetheramine, the hydrophobic chain oligomer is polycarbonate diol, and the diisocyanate is dicyclohexylmethane diisocyanate.

[0019] Furthermore, the polyetheramine has higher reactivity; the polycarbonate diol can improve the thermal stability and mechanical properties of polyurethane; the bisaminopropyl-terminated polydimethylsiloxane oligomer has high reactivity; the dicyclohexylmethane diisocyanate has appropriate reactivity, and the synthesized polyurethane is not prone to yellowing.

[0020] Optionally, before adding the diisocyanate, the temperature is raised to 50-60° C., the diisocyanate is added, and the reaction is carried out for 6-10 hours; after adding the chain extender containing a reactive group, the reaction is carried out for 8-12 hours;

[0021] Furthermore, before adding diisocyanate, the temperature was raised to 55° C., diisocyanate was added, and the reaction was carried out for 8 hours; after adding the chain extender containing a reactive group, the reaction was carried out for 10 hours.

[0022] According to another aspect of the present application, the present application also provides a post-crosslinkable amphiphilic polyurethane prepared by the above preparation method.

[0023] According to another aspect of the present application, the present application also provides a polyurethane glucose limiting membrane, which is obtained by adding a crosslinking agent to the above-mentioned post-crosslinkable amphiphilic polyurethane for crosslinking or in situ crosslinking by radiation crosslinking.

[0024] Furthermore, the mass ratio of the cross-linking agent to the post-cross-linkable amphiphilic polyurethane is 1:50 to 1:1000.

[0025] Furthermore, the post-crosslinkable amphiphilic polyurethane is coated on the surface of the electrode enzyme layer and crosslinked by a crosslinking agent or radiation, wherein the coating comprises one of spin coating, roll coating, blade coating and dip coating.

[0026] Furthermore, the post-crosslinkable amphiphilic polyurethane is dissolved in tetrahydrofuran solvent, a crosslinking agent is added, mixed evenly and then coated on the surface of the electrode enzyme layer. During the evaporation of the solvent, the crosslinking agent crosslinks with the polyurethane to form the polyurethane glucose restriction membrane.

[0027] Optionally, the cross-linking agent includes at least one of ethylenedithiol, dithiothreitol, trimethylolpropane trimercaptoacetate, polyethylene glycol dimercaptopropionate, polyethylene glycol diacrylate, polyethylene glycol diamine, polyethylene glycol diglycidyl ether, trimethylolpropane triglycidyl ether and trimethylolpropane tris[3-(aziridine-1-yl)propionate]; preferably, the cross-linking agent is polyethylene glycol dimercaptopropionate; and / or

[0028] The radiation source for the radiation cross-linking includes an electron beam.

[0029] Furthermore, the crosslinking agent is polyethylene glycol dimercaptopropionate; polyethylene glycol dimercaptopropionate as a crosslinking agent can crosslink amphiphilic linear polyurethane containing unsaturated double bonds through a "thiol-ene" click reaction under relatively mild conditions to form a network structure.

[0030] According to another aspect of the present application, the present application also provides a working electrode for a glucose sensor, on which the above-mentioned polyurethane glucose limiting membrane is provided.

[0031] Furthermore, an enzyme layer is provided on the electrode, the enzyme layer includes glucose oxidase, and the thickness of the enzyme layer is 1-10 μm, preferably 3 μm.

[0032] Furthermore, the thickness of the polyurethane glucose limiting membrane is 20-60 μm, preferably 30 μm.

[0033] By controlling the thickness of the enzyme layer and the limiting membrane, leakage of the enzyme layer can be avoided, and at the same time, the flux of glucose penetrating into the electrode enzyme layer can be controlled, thereby improving the glucose linear detection range of the sensor.

[0034] According to another aspect of the present application, the present application also provides a glucose sensor, which includes the above-mentioned working electrode.

[0035] The beneficial effects of this application include but are not limited to:

[0036] 1. According to the post-crosslinkable amphiphilic polyurethane and its preparation method of the present application, a chain extender containing a reactive group is reacted with a precursor to obtain a post-crosslinkable amphiphilic polyurethane. The post-crosslinkable amphiphilic polyurethane is a linear polymer, and the hard segment of the chain extender contains a reactive group, which can form a polyurethane with a cross-linked network structure under the action of the cross-linking agent; the molecular weight of the cross-linked polyurethane can be considered to be infinite, which solves the problem of degradation of the linear polyurethane glucose limiting membrane during storage or use or transformation of the phase structure leading to degradation of the CGM product performance. In addition, some unreacted active sites will still remain on the surface of the post-crosslinked amphiphilic polyurethane after cross-linking, laying the foundation for further modification of the polyurethane membrane surface to improve the biocompatibility of the electrode and extend the service life of the CGM product.

[0037] 2. The polyurethane glucose-limiting membrane provided by this application has a simple process, mild reaction conditions, and is easy to industrialize. The post-crosslinkable amphiphilic polyurethane coating is then cross-linked by irradiation or in situ cross-linked on the electrode surface with a cross-linking agent to obtain a cross-linked network structure of the polyurethane glucose-limiting membrane. The mechanical strength and hardness of the polyurethane glucose-limiting membrane can be regulated by the cross-linking density. The molecular weight of the cross-linked polyurethane can be considered infinite, which solves the problem of CGM product performance degradation caused by polyurethane degradation during storage or use.

[0038] 3. The working electrode for the glucose sensor according to the present application has a simple preparation method, and the binding ability between the polyurethane glucose limiting membrane and the enzyme layer, and between the polyurethane glucose limiting membrane and the electrode substrate is strong. As the working electrode of the glucose sensor, it has a strong linear response ability and accurate detection results, meeting the use requirements of the continuous blood glucose monitoring system. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0040] FIG1 is a surface morphology of a polyurethane glucose limiting membrane on a working electrode 1# for a glucose sensor according to Example 1 of the present application under a scanning electron microscope.

[0041] FIG2 is a cross-sectional morphology of the polyurethane glucose limiting membrane on the working electrode 1# for the glucose sensor involved in Example 1 of the present application in a dry state under a stereo microscope.

[0042] FIG3 is a stress-strain curve diagram of the polyurethane involved in Example 1 of the present application after cross-linking with cross-linking agents of different concentrations to form a film.

[0043] FIG4 is a time-current curve diagram of the working electrode 1# coated with the polyurethane glucose limiting membrane involved in Example 1 of the present application in glucose solutions of different concentrations. DETAILED DESCRIPTION

[0044] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0045] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. The reagents and raw materials used in the present invention can be purchased through conventional channels. Unless otherwise specified, the reagents and raw materials used in the present invention are used in accordance with conventional methods in the art or in accordance with the product instructions. In addition, any methods and materials similar to or equivalent to those described herein can be applied to the present invention. The preferred embodiments and materials described in this patent are for illustrative purposes only.

[0046] Example 1: A working electrode for a glucose sensor 1#

[0047] The preparation of a working electrode 1# for a glucose sensor comprises the following steps:

[0048] 1) 40 g of bisaminopropyl-terminated polydimethylsiloxane oligomer (Mn=10k), 30 g of polycarbonate diol (Mn=2k), 30 g of polyetheramine (Mn=500), 0.2 g of dibutyltin dilaurate, and 600 mL of tetrahydrofuran were added to a 1 L reactor and stirred uniformly; the temperature was raised to 55° C., 30 g of dicyclohexylmethane diisocyanate was added dropwise, and the mixture was stirred and reacted for 8 hours; after 8 hours, 4.5 g of chain extender allyl glycerol ether was added dropwise, and the reaction was continued for 10 hours; after the reaction was completed, the reactants were precipitated in deionized water, filtered, and dried to obtain a post-crosslinkable polyurethane;

[0049] 2) adding 5 g of the post-crosslinkable polyurethane obtained in step 1) to 95 g of tetrahydrofuran, and then adding 0.01 g of polyethylene glycol dimercaptopropionate (Mn=600), and mixing well to form a polyurethane glucose restriction membrane solution;

[0050] 3) Glucose oxidase is coated on the electrode surface, and after cross-linking and curing with glutaraldehyde vapor, an enzyme layer with a thickness of 3 μm is formed. The polyurethane glucose restriction membrane solution obtained in step 2) is further coated on the enzyme layer by scraping. During the evaporation of the solvent, the cross-linking agent cross-links with the polyurethane, forming a restriction membrane layer with a thickness of 30 μm on the surface of the enzyme layer, thereby obtaining a working electrode 1#.

[0051] As shown in Figure 1, the surface morphology of the cross-linked polyurethane glucose-limiting membrane on working electrode #1 was observed using a SEM. The figure shows that the surface structure of the cross-linked polyurethane glucose-limiting membrane on the electrode is intact, with no holes or cracks. This indicates that the coating process ensures the physical integrity of the membrane itself, effectively preventing enzyme layer leakage and controlling glucose flux. Furthermore, as shown in Figure 2, the cross-sectional morphology of the dry state of the polyurethane glucose-limiting membrane on working electrode #1 was observed using a stereomicroscope. It can be seen that the coated polyurethane glucose-limiting membrane completely wraps around the electrode, with a thickness of approximately 30 μm.

[0052] Example 2: A working electrode for a glucose sensor 2#

[0053] The preparation steps of a working electrode 2# for a glucose sensor are different from those in Example 1 in that: in step 1), 4.5g of the chain extender allyl glycerol ether is replaced with 6g of trimethylolpropane allyl ether, and the remaining steps are the same as in Example 1.

[0054] Example 3: A working electrode for a glucose sensor 3#

[0055] The preparation steps of a working electrode 3# for a glucose sensor are different from those in Example 1 in that: in step 2), 0.01g of polyethylene glycol dimercaptopropionate (Mn=600) is changed to 0.1g of polyethylene glycol dimercaptopropionate (Mn=600); the remaining steps are the same as in Example 1.

[0056] Example 4: A working electrode 4# for a glucose sensor

[0057] The preparation steps of a working electrode 4# for a glucose sensor are different from those in Example 1 in that: in step 2), 0.01g of polyethylene glycol dimercaptopropionate (Mn=600) is changed to 0.005g of polyethylene glycol dimercaptopropionate (Mn=600); the remaining steps are the same as in Example 1.

[0058] Example 5: A working electrode for a glucose sensor 5#

[0059] The preparation steps of a working electrode 5# for a glucose sensor differ from those in Example 1 in that: in step 1), 4.5 g of the chain extender allyl glycerol ether is replaced with 4.6 g of 2,2-bis(hydroxymethyl)propionic acid; in step 2), 0.01 g of polyethylene glycol dimercaptopropionate (Mn=600) is replaced with 0.01 g of trimethylolpropane tris[3-(aziridine-1-yl)propionate; and the remaining steps are the same as in Example 1.

[0060] Example 6: A working electrode for a glucose sensor

[0061] The preparation steps of a working electrode 6# for a glucose sensor differ from those in Example 1 in that: in step 1), 4.5 g of the chain extender allyl glycerol ether is replaced with 5 g of 2,2-bis(hydroxymethyl)butyric acid; in step 2), 0.01 g of polyethylene glycol dimercaptopropionate (Mn=600) is replaced with 0.01 g of trimethylolpropane tris[3-(aziridine-1-yl)propionate; and the remaining steps are the same as in Example 1.

[0062] Example 7: A working electrode for a glucose sensor 7#

[0063] The preparation steps of a working electrode 7# for a glucose sensor are different from those in Example 1 in that: in step 3), glucose oxidase is coated on the electrode surface, and after curing, an enzyme layer with a thickness of 3 μm is formed. The polyurethane glucose limiting membrane liquid obtained in step 2) is continued to be scraped on the enzyme layer by scraping. During the evaporation of the solvent, the cross-linking agent cross-links with the polyurethane to form a polyurethane glucose limiting membrane with a thickness of 40 μm on the surface of the enzyme layer. The remaining steps are the same as in Example 1 to obtain a working electrode 7#.

[0064] Example 8: A working electrode for a glucose sensor 8#

[0065] The preparation steps of a working electrode 8# for a glucose sensor are different from those in Example 1 in that: in step 3), glucose oxidase is coated on the electrode surface, and after curing, an enzyme layer with a thickness of 3 μm is formed. The polyurethane glucose limiting membrane liquid obtained in step 2) is continued to be scraped on the enzyme layer by scraping. During the evaporation of the solvent, the crosslinker cross-links with the polyurethane to form a polyurethane glucose limiting membrane with a thickness of 20 μm on the surface of the enzyme layer. The remaining steps are the same as in Example 1 to obtain a working electrode 8#.

[0066] Comparative Example 1: A working electrode D1# for a glucose sensor

[0067] The preparation steps of a working electrode D1# for a glucose sensor are different from those in Example 1 in that: in step 1), 4.5g of chain extender allyl glycerol ether is replaced with 3.1g of 1,4-butanediol, and the remaining steps are the same as in Example 1.

[0068] Comparative Example 2: A working electrode D2# for a glucose sensor

[0069] The preparation steps of a working electrode D2# for a glucose sensor are different from those in Example 1 in that: in step 1), 4.5g of the chain extender allyl glycerol ether is replaced with 4g of 1,6-hexanediamine, and the remaining steps are the same as those in Example 1.

[0070] Comparative Example 3: A working electrode D3# for a glucose sensor

[0071] The preparation steps of a working electrode D3# for a glucose sensor are different from those in Example 1 in that: in step 2), 0.5 g of polyethylene glycol dimercaptopropionate (Mn=600) is added, and the remaining steps are the same as in Example 1.

[0072] Comparative Example 4: A working electrode D4# for a glucose sensor

[0073] The preparation steps of a working electrode D4# for a glucose sensor are different from those in Example 1 in that: in step 2), 0.001 g of polyethylene glycol dimercaptopropionate (Mn=600) is added, and the remaining steps are the same as in Example 1.

[0074] Experimental example

[0075] In addition, the working electrodes 1#-8# and D1#-D4# obtained in Examples 1-8 and Comparative Examples 1-4 were tested to determine the hydration time, water absorption rate, glucose diffusion coefficient, glucose diffusion coefficient after aging for 7 days, and glucose diffusion coefficient after aging for 50 days of their glucose polyurethane limiting membranes. The test results are shown in Table 1. The test method is as follows:

[0076] Hydration time: Soak the prepared polyurethane glucose limiting membrane in purified water, and measure the mass of the polyurethane glucose limiting membrane at regular intervals until the membrane mass does not change. The time when the membrane mass does not change is recorded as the hydration time.

[0077] Water absorption rate: Water absorption rate = (membrane wet mass - membrane dry mass) / membrane dry mass * 100%

[0078] Diffusion coefficient: Given that the permeability area is a fixed value A, let the diffusion flux of glucose molecules be J (unit: mol·cm -2 ·s -1 ), the diffusion coefficient is calculated according to the following formula:

[0079] Where D is the diffusion coefficient, cm 2 / s;

[0080] A is the diffusion and permeability area, cm 2 ;

[0081] V is the volume of the solution in the donor chamber and the receiving chamber, mL;

[0082] l is the thickness of the polyurethane glucose restriction membrane, cm;

[0083] △t is the sampling interval, s;

[0084] C10 is the concentration of the supply solution after the previous sampling, mmol / L;

[0085] C20 is the concentration of the receiving fluid after the previous sampling, mmol / L;

[0086] C2t is the concentration of the receiving solution after △t time, mmol / L;

[0087] Table 1

[0088] It can be seen from Table 1 that the smaller the water absorption rate of the polyurethane membrane and the smaller the diffusion coefficient, the more it can limit the flux of glucose. Generally speaking, a water absorption rate between 15% and 25% is more appropriate. The difference between the working electrode D1# and the working electrode D2# and the working electrode 1# of Example 1 is that the chain extenders are different. The chain extender 1,4-butanediol of the working electrode D1# and the chain extender 1,6-hexanediamine of the working electrode D2# cannot be cross-linked subsequently and cannot form a cross-linked structure. Therefore, as time goes by, degradation occurs, resulting in a decrease in the diffusion coefficient and a decrease in product performance; the difference between the working electrode D3# and the working electrode 1# of Example 1 is that the amount of the cross-linking agent polyethylene glycol dimercaptopropionate (Mn=600) is increased, and the cross-linking The density is higher, and the mechanical strength and hardness of the polyurethane glucose limiting membrane are also higher. However, since the added cross-linking agent is hydrophilic, its hydration time is shortened, its water absorption rate and diffusion coefficient are increased, resulting in excessive sensitivity of the working electrode, which has a negative impact on its glucose detection. The difference between working electrode D4# and working electrode 1# of Example 1 is that the amount of cross-linking agent polyethylene glycol dimercaptopropionate (Mn=600) is reduced, resulting in a lower cross-linking density. After aging, the diffusion coefficient decreases significantly, resulting in a significant decrease in sensitivity and failing to meet the requirements of use. In addition, the cross-linking density of the polyurethane glucose limiting membrane is low, and its mechanical strength and hardness deteriorate. When the electrode is subjected to force, the polyurethane glucose limiting membrane cannot protect the enzyme layer, causing the enzyme layer to crack, which has a negative impact on its glucose detection.

[0089] The foregoing is merely an embodiment of the present application, and the scope of protection of the present application is not limited by these specific embodiments, but is determined by the claims of the present application. For those skilled in the art, the present application may have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc. made within the technical ideas and principles of the present application should be included in the scope of protection of the present application.

Claims

1. A method for preparing a post-crosslinkable amphiphilic polyurethane, characterized in that: The following steps are involved: The hydrophilic chain oligomer, the hydrophobic chain oligomer, the polydimethylsiloxane oligomer and the diisocyanate are reacted to obtain a precursor; the precursor is reacted with a chain extender containing a reactive group to further extend the chain to obtain the post-crosslinkable amphiphilic polyurethane.

2. The preparation method according to claim 1, characterized in that: The chain extender containing reactive groups includes the following structural formula: Wherein R1 is 0 to 5 methylene groups, R2 is a H atom or 0 to 5 alkyl groups, and R3 contains an allyl group, a carboxyl group, a pyridine group, an imidazole group or an epoxy group having a reactive group.

3. The preparation method according to claim 2, characterized in that: The chain extender is selected from at least one of trimethylolpropane allyl ether, allyl glyceryl ether, trimethylolpropane monoglycidyl ether, glycerol monoglycidyl ether, N,N-bis(2-hydroxyethyl)isonicotinamide, imidazole diol, 2,2-bis(hydroxymethyl)propionic acid and 2,2-bis(hydroxymethyl)butyric acid; Preferably, the chain extender is allyl glyceryl ether.

4. The preparation method according to claim 1, characterized in that: The polydimethylsiloxane oligomer includes bis-aminopropyl terminated polydimethylsiloxane and / or bis-hydroxy terminated polydimethylsiloxane; and / or The hydrophilic chain oligomer comprises at least one of polyethylene glycol, polyetheramine, propylene glycol-ethylene glycol copolymer and zwitterionic compound; and / or The hydrophobic chain oligomer comprises at least one of polycarbonate diol, polytetramethylene glycol and polypropylene glycol; and / or The diisocyanate comprises at least one of diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate and hexamethylene diisocyanate; Preferably, the polydimethylsiloxane oligomer is a bis-aminopropyl terminated polydimethylsiloxane oligomer. The hydrophilic chain oligomer is polyetheramine, the hydrophobic chain oligomer is polycarbonate diol, and the diisocyanate is dicyclohexylmethane diisocyanate.

5. The preparation method according to claim 1, characterized in that: Before adding diisocyanate, heat to 50-60°C, add diisocyanate, and react for 6-10 hours; after adding chain extender containing reactive groups, react for 8-12 hours; Preferably, before adding the diisocyanate, the temperature is raised to 55° C., the diisocyanate is added, and the reaction is carried out for 8 hours; after adding the chain extender containing a reactive group, the reaction is carried out for 10 hours.

6. Post-crosslinkable amphiphilic polyurethane prepared by the preparation method according to any one of claims 1 to 5.

7. A polyurethane glucose limiting membrane, characterized in that The polyurethane glucose limiting membrane is obtained by crosslinking the post-crosslinkable amphiphilic polyurethane described in claim 6 by adding a crosslinking agent or crosslinking in situ by radiation crosslinking.

8. The polyurethane glucose limiting membrane according to claim 7, characterized in that The cross-linking agent includes at least one of ethylenedithiol, dithiothreitol, trimethylolpropane trimercaptoacetate, polyethylene glycol dimercaptopropionate, polyethylene glycol diacrylate, polyethylene glycol diamine, polyethylene glycol diglycidyl ether, trimethylolpropane triglycidyl ether and trimethylolpropane tris[3-(aziridine-1-yl)propionate]; preferably, the cross-linking agent is polyethylene glycol dimercaptopropionate; and / or The radiation source for the radiation crosslinking includes electron beams.

9. A working electrode for a glucose sensor, characterized in that: The working electrode is provided with the polyurethane glucose limiting membrane according to any one of claims 7 to 8.

10. A glucose sensor, characterized in that: The glucose sensor comprises the working electrode according to claim 9.

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