Polymer hydrophilic coating, preparation method and application in medical catheter

Abstract

The invention discloses a polymer hydrophilic coating in the field of biomedical materials, a preparation method of the polymer hydrophilic coating and application of the polymer hydrophilic coating in medical catheters. The coating achieves excellent performance through the synergistic effect of two newly designed modified compounds. Wherein the phosphorylcholine silane functionalized polyethyleneimine is used as a matrix material and provides hydrophilicity and anticoagulant activity; and the nano silicon dioxide anchored polyhexamethylene biguanide is used as a functional filler, so that the coating is endowed with antibacterial property and mechanical enhancement. During preparation, all the components are sequentially dissolved in water to form a uniform solution, transparent sol is formed through silane hydrolysis, then the pretreated guide pipe is subjected to dip coating, and a final product is obtained through preheating, ultraviolet light curing and heat curing treatment. The coating obviously reduces the surface friction coefficient, has lasting hydrophilicity, efficient antibacterial property and excellent blood compatibility, is firmly combined with a base material, and is particularly suitable for surface functional modification of various interventional medical catheters.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a polymer hydrophilic coating, a preparation method and application in medical catheters. BACKGROUND

[0002] Medical catheters are indispensable tools in modern medicine, widely used in vascular intervention, urinary drainage, infusion therapy and other clinical fields. However, traditional medical catheter materials generally have inherent defects such as strong surface hydrophobicity and insufficient biocompatibility, which can easily cause a series of clinical complications during use. When the catheter surface comes into contact with blood, the hydrophobic interface will promote non-specific protein adsorption and massive platelet aggregation, thereby activating the blood clotting system and significantly increasing the risk of thrombosis. At the same time, the catheter surface also becomes a breeding ground for microbial adhesion and reproduction, and the formation of bacterial biofilm leads to frequent catheter-related infections, which seriously threatens patient safety and increases the medical burden. Although existing technologies attempt to improve catheter performance through surface modification, most methods are difficult to balance hydrophilicity, antibacterial property and anticoagulant property, often sacrificing one for the other, and cannot meet the urgent demand for multifunctional catheter surfaces in clinical practice.

[0003] The hydrophilic coating technology on the market at present has the following limitations: first, the traditional coating based on physical adsorption or simple blending has weak adhesion to the substrate, and is prone to peeling off during body fluid flushing or catheter bending, resulting in insufficient function durability; second, single-function coatings are difficult to cope with complex clinical environments, such as coatings that only improve hydrophilicity cannot inhibit microbial growth, and coatings that simply introduce antibacterial agents may affect blood compatibility; third, although some chemical grafting techniques can improve the stability of the coating, the reaction conditions are harsh, which may damage the mechanical properties of the catheter substrate or leave toxic reagents that cause safety problems. In addition, commonly used hydrophilic materials such as polyacrylic acid and polyvinyl alcohol in existing technologies have significantly decreased mechanical properties in a wet state, and limited anti-protein adsorption capacity, which cannot meet the requirements of long-term implantable catheters. These technical defects seriously restrict the safety and effectiveness of medical catheters in clinical practice, and there is an urgent need to develop a new generation of multifunctional hydrophilic coating technology.

[0004] Another major challenge for existing hydrophilic coating technology is how to achieve synergistic effect of multiple functions. For example, some studies use silver nanoparticles as antibacterial components, but the continuous release of metal ions can cause cytotoxicity and induce bacterial resistance; some studies try to introduce zwitterionic polymers to improve the anti-protein adsorption performance, but the synthesis process is complex, the cost is high, and the adhesion to the substrate is insufficient. In addition, traditional coating design often ignores the structure-function relationship between materials, making it difficult to achieve long-term hydrophilicity and stable antibacterial performance. Especially in dynamic medical environments, coatings need to withstand multiple tests such as mechanical stress, biological enzymatic degradation and microbial erosion. A single modification strategy cannot meet these complex requirements. Therefore, developing a multifunctional hydrophilic coating that can form stable chemical bonds with the substrate, has low friction coefficient, high antibacterial performance and excellent blood compatibility, has become a key problem that needs to be broken through in this technical field. SUMMARY

[0005] The purpose of the present application is to provide a polymer hydrophilic coating, a preparation method and an application in medical catheters, which solves the technical problems of easy peeling, single function and insufficient biocompatibility of existing traditional medical catheter coatings.

[0006] The present application achieves the above-mentioned purposes by the following technical solutions:

[0007] A preparation method of a polymer hydrophilic coating, the steps comprising:

[0008] S1, dissolve phosphocholine-based silane functionalized polyethyleneimine in deionized water to prepare an aqueous solution, and stir until completely dissolved; then add polyvinylpyrrolidone and lactic acid-glycolic acid copolymer, continue to stir until completely dissolved; add 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, stir in the dark until completely dissolved; add nano-silicon dioxide anchored polyhexamethylene biguanide, ultrasonic dispersion; add tetraethoxysilane and acetic acid, stir in a 38-42℃ water bath for hydrolysis; obtain a coating solution;

[0009] S2, ultrasonically clean the TPU catheter by immersing it in acetone, ethanol and deionized water in sequence; after blowing dry with nitrogen, place it in an oxygen plasma treatment instrument to obtain a pretreated TPU catheter;

[0010] S3, immerse the pretreated TPU catheter in the coating solution, pull it up, so that the surface of the pretreated TPU catheter is covered with the coating solution; then pre-dry in a 58-62℃ oven to obtain a coated catheter; place the coated catheter in a UV curing box and irradiate it under UV light; finally, place the coated catheter in a 50-60℃ constant temperature oven for curing.

[0011] In the present application, the formation of the polymer hydrophilic coating is a complex physicochemical process, the core of which is to build a stable three-dimensional crosslinked network structure through multiple interactions between components. When the coating solution is prepared, the phosphocholine-based silane functionalized polyethyleneimine serves as the main film-forming material, and the silicon methoxy groups on its molecular chain gradually hydrolyze to form silicon hydroxyl groups under the action of an acidic catalyst. These silicon hydroxyl groups then undergo condensation reactions to form a preliminary silicon-oxygen-silicon crosslinked network. At the same time, the added tetraethoxysilane also undergoes a similar hydrolysis-condensation process, and its product further strengthens the network structure as an additional crosslinking point. The introduction of nano-silicon dioxide anchored polyhexamethylene biguanide creates an organic-inorganic hybrid system, and the silicon hydroxyl groups on the surface of the nanoparticles not only participate in the overall siloxane condensation reaction, but also act as physical crosslinking points and reinforcing agents in the polymer network, significantly improving the mechanical strength and wear resistance of the coating. During the preheating and drying stage, the solvent gradually evaporates, the concentration of the coating components increases, and the molecular chain segment movement ability decreases, and hydrogen bonds, van der Waals forces and hydrophobic interactions between components begin to appear, prompting the system to form a continuous film structure. Subsequent ultraviolet light irradiation activates the photoinitiator, initiating the free radical polymerization reaction of the residual double bonds in the phosphocholine-based silane functionalized polyethyleneimine, which builds an additional carbon-carbon bond crosslinked network on the basis of the already formed siloxane network, forming an interpenetrating polymer network structure that greatly enhances the continuity and cohesion of the coating. The final heat curing stage allows the unreacted silicon hydroxyl groups to further condense, promoting the formation of strong chemical bonds between the coating and the substrate interface, and allowing the polymer chain segments to fully relax and eliminate internal stress, resulting in a dense and stable coating structure. This multi-level, multi-stage crosslinking mechanism ensures that the coating has excellent adhesion, long-lasting hydrophilicity, high-efficiency antibacterial properties and good biocompatibility, meeting the stringent requirements of medical catheters for surface properties.

[0012] According to the preferred embodiment of the present application, in step S1, the stirring hydrolysis time in the 38-42℃ water bath is 2-4h.

[0013] According to the preferred embodiment of the present application, in step S2, the treatment time in the oxygen plasma treatment instrument is 2-4min.

[0014] According to the preferred embodiment of the present application, in step S3, the irradiation time under ultraviolet light is 5-10min; and the curing time in the 50-60℃ constant temperature oven is 24-30h.

[0015] According to the preferred embodiment of the present application, the preparation method of the phosphorylcholine-based silane functionalized polyethyleneimine comprises: dissolving the hyperbranched polyethyleneimine in anhydrous dimethyl sulfoxide under nitrogen protection, stirring until completely dissolved; adding dropwise a dimethyl sulfoxide solution containing 3-glycidyloxypropyltrimethoxysilane, and after the dropwise addition is completed, heating to 68-72°C for reaction; after cooling to room temperature, adding 1,8-diazabicyclo[5.4.0]undec-7-ene, and then adding dropwise a dimethyl sulfoxide solution containing 2-methacryloyloxyethyl phosphorylcholine, and after the dropwise addition is completed, heating to 58-62°C for reaction; after the reaction is completed, pouring the reaction solution into anhydrous diethyl ether for precipitation, collecting the white solid by filtration, washing with diethyl ether, and vacuum drying at 38-42°C.

[0016] In the present application, the preparation of the phosphorylcholine-based silane functionalized polyethyleneimine involves a multi-step precisely controlled chemical reaction process, and the core is to integrate different functional groups into the hyperbranched polyethyleneimine molecular skeleton through covalent bonding. First, the large number of primary and secondary amine groups in the hyperbranched polyethyleneimine molecule undergo ring-opening reaction with the epoxy ring of tri-glycidyloxypropyltrimethoxysilane. This reaction is carried out under mild heating conditions, and the amine group acts as a nucleophile to attack the carbon atom on the epoxy ring, resulting in the opening of the cyclic tension structure and forming a stable carbon-nitrogen covalent bond, thereby introducing a trimethoxysilane-containing segment into the polyethyleneimine skeleton. In this step, the introduction of silane coupling agent is crucial, and the terminal methoxy group can be hydrolyzed to form silanol in the subsequent process, and then form a firm siloxane network structure with the surface of the substrate or the inside of the coating through condensation reaction. Subsequently, the intermediate product undergoes Michael addition reaction with dimethyl methacryloyloxyethyl phosphorylcholine. Under the action of an organic base catalyst, the remaining amine groups on the polyethyleneimine skeleton undergo nucleophilic addition to the carbon-carbon double bond in the methacrylate group. This reaction has high selectivity and mild conditions, which can effectively avoid the hydrolytic destruction of the phosphorylcholine group. Through this series of precisely designed reactions, the final compound has a three-dimensional network structure of hyperbranched polymer, adhesion performance of silane coupling agent, and biomimetic anti-protein adsorption properties of phosphorylcholine group. The synergistic effect of the three functions provides a solid molecular foundation for the subsequent coating. It is particularly worth noting that the phosphorylcholine group, as a major component of the cell membrane phospholipid bilayer, can effectively resist non-specific protein adsorption by forming a tightly bound hydration layer, thereby significantly improving the blood compatibility of the material.

[0017] According to the preferred embodiment of the present application, the reaction time after the dropwise addition is completed and heating to 68-72°C is 12-14h, and the reaction time after the dropwise addition is completed and heating to 58-62°C is 24-30h.

[0018] According to the preferred embodiment of the present application, the preparation method of the nano-silica anchoring polyhexamethylene biguanide comprises: dispersing nano-silica in toluene, ultrasonic treatment; then adding vinyl triethoxysilane and dibutyl tin dilaurate, refluxing under nitrogen protection; after the reaction is completed, centrifuging to collect the solid, washing with toluene, and vacuum drying at 58-62°C to obtain vinyl-functionalized nano-silica; dispersing the vinyl-functionalized nano-silica in N,N-dimethylformamide, adding N-vinyl caprolactam, polyhexamethylene biguanide acrylate and dibenzoyl peroxide, and after oxygen removal by nitrogen, reacting in an oil bath at 68-72°C; after the reaction is completed, centrifuging to collect the product, washing with N,N-dimethylformamide and acetone alternately, and vacuum drying at 48-52°C.

[0019] In the present application, the construction of the nano-silica anchoring polyhexamethylene biguanide embodies the ingenious design concept of organic-inorganic hybrid materials, and the preparation process mainly includes two key stages of surface modification of nano-silica and grafting of functional polymer brushes. In the initial stage, the abundant silicon hydroxyl groups on the surface of nano-silica particles undergo condensation reaction with vinyl triethoxysilane, and under the promotion of tin catalyst, the silicon hydroxyl groups formed by the hydrolysis of the triethoxyl groups of the silane coupling agent undergo dehydration condensation with the silicon hydroxyl groups on the surface of the silica, forming stable silicon-oxygen-silicon covalent bonds, thereby introducing carbon-carbon double bond reaction sites on the surface of the nanoparticles. This surface modification process not only retains the inherent rigid core structure of nano-silica, but also provides the necessary active sites for the subsequent free radical polymerization reaction. In the second stage, the modified nano-silica and functional monomers undergo copolymerization reaction under the action of a free radical initiator, the initiator decomposes to produce free radicals, these free radicals attack the vinyl monomers and the double bonds on the surface of the modified silica, initiating chain growth reaction, forming grafted polymer brushes. Among them, the introduction of vinyl caprolactam units endows the polymer with temperature response characteristics, the intramolecular lactam groups can form a dynamic hydrogen bond network with water, and the polyhexamethylene biguanide acrylate is fixed at the end of the polymer chain through covalent bond, ensuring the stable existence and controllable release of the antibacterial groups in the coating. This core-shell structure design not only enhances the mechanical strength and durability of the coating through the nano-silica core, but also provides excellent hydrophilicity and antibacterial function through the outer polymer brush, while avoiding the defect of easy loss of traditional physical blending of antibacterial agents. More importantly, the functional units in the grafted polymer brush are uniformly distributed, and the density and release kinetics of the antibacterial groups can be accurately controlled through molecular design, achieving the balance between long-term antibacterial and biological safety.

[0020] According to the preferred embodiment of the present application, the reflux reaction time under nitrogen protection is 24-30h; the reaction time in the oil bath at 68-72°C is 24-30h.

[0021] The application further provides a polymer hydrophilic coating prepared according to the preparation method of the polymer hydrophilic coating.

[0022] The application further provides application of the polymer hydrophilic coating in a medical catheter.

[0023] The application has the following beneficial effects:

[0024] The polymer hydrophilic coating provided by the application realizes comprehensive improvement of the surface performance of a medical catheter through unique material design and preparation process, and exhibits significant technical progress and clinical application value. Firstly, in terms of physical and chemical performance, the coating creates excellent surface hydrophilicity and extremely low friction coefficient. Through introduction of a phosphocholine group and construction of a nano-composite structure, the surface energy of the coating can be significantly improved, a firm water layer is formed with water molecules, the contact angle of the modified catheter surface is greatly reduced, and super-hydrophilic properties are obtained. Meanwhile, uniform distribution of nano-silica and the polymer network form a synergistic effect, which greatly enhances the surface wear resistance and mechanical strength while maintaining the flexibility of the coating. After rigorous testing in a simulated use environment, including repeated friction experiments and long-term liquid immersion experiments, the coating remains intact without peeling off, and exhibits significantly improved durability and stability compared with traditional coatings. This persistent surface property ensures that the catheter can maintain a low friction coefficient throughout the entire use cycle, greatly reducing the mechanical damage to the blood vessel wall or tissue mucosa during catheter insertion and indwelling, and improving patient comfort.

[0025] In terms of biomedical performance, the coating exhibits excellent antibacterial activity and blood compatibility. By anchoring polyhexamethylene biguanide on the nano-silica carrier in a covalent bond manner, controllable release and long-acting effect of the antibacterial component are realized, and near-complete inhibition effect is exhibited on common pathogenic bacteria including gram-positive bacteria and gram-negative bacteria. In particular, this design effectively avoids the problems of toxic side effects and late failure caused by initial burst release of antibacterial agents in traditional antibacterial coatings, and provides a reliable solution for infection prevention and control of long-term indwelling catheters. At the same time, the phosphocholine group in the coating precisely simulates the outer structure of the biological cell membrane, greatly reduces non-specific protein adsorption and platelet adhesion and activation, and through in-vitro blood experiments, the number of platelets adhered to the surface of the coating is reduced to a very low level, and the blood clotting time is significantly prolonged, exhibiting excellent anticoagulant properties. This characteristic of simultaneously having high-efficiency antibacterial and excellent blood compatibility solves the technical problem of single function of traditional coatings.

[0026] From the perspective of clinical application, this coating technology shows a wide adaptability and stable performance. The preparation process is suitable for various catheter substrates including polyurethane, silicone and other commonly used medical polymer materials. Through silane condensation reaction, a firm chemical bond is formed on the surface of the substrate, overcoming the defect of easy peeling of physical adsorption coating. The coating components have good biocompatibility and biosafety. The cytotoxicity test and in vivo implantation experiment confirm that there is no cytotoxicity and tissue irritation reaction, meeting the requirements of medical device biocompatibility related standards. In addition, the whole preparation process is mild, does not require special equipment, is suitable for large-scale production, and has significant industrialization advantages. The popularization and application of this technology will effectively reduce the incidence of catheter-related thrombosis and infection, reduce the amount of antibiotic use, shorten the hospitalization time of patients, and produce important clinical value and social benefits. DETAILED DESCRIPTION

[0027] The following detailed description is only used to further illustrate the present application and cannot be understood as limiting the scope of protection of the present application. Those skilled in the art can make some non-essential improvements and adjustments to the present application according to the above application content.

[0028] The main related equipment and material suppliers are as follows:

[0029] The polyvinylpyrrolidone was purchased from Henan Zhongyi Medical Technology Co., Ltd.

[0030] The lactic acid-glycolic acid copolymer was purchased from Jinan Daigang Biological Technology Co., Ltd.

[0031] The 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone was purchased from Tianjin Jiurixin Material Co., Ltd.

[0032] The tetraethoxysilane was purchased from China National Pharmaceutical Group Chemical Reagent Co., Ltd.

[0033] The acetic acid was purchased from Jiangsu Taipu (Group) Co., Ltd.

[0034] The TPU catheter was purchased from Jinfa Technology Co., Ltd.

[0035] The oxygen plasma treatment instrument was purchased from Beijing Zhongke Keyi Co., Ltd.

[0036] The hyperbranched polyethyleneimine was purchased from Wuhan Huaxiang Kejie Biological Technology Co., Ltd.

[0037] The 3-glycidyloxypropyltrimethoxysilane was purchased from Hubei Jianghan New Material Co., Ltd.

[0038] The 1,8-diazabicyclo[5.4.0]undec-7-ene was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0039] The 2-methacryloyloxyethyl phosphorylcholine was purchased from Nanjing and Win Pharmaceutical Technology Co., Ltd.

[0040] The nano-silica was purchased from Zhejiang Yuda Chemical Co., Ltd.

[0041] The vinyltriethoxysilane was purchased from Jiangxi Chen Guang New Material Co., Ltd.

[0042] The dibutyltin dilaurate was purchased from Beijing Chemical Plant Co., Ltd.

[0043] The N-vinylcaprolactam was purchased from Wuhan Xinhengxing Technology Co., Ltd.

[0044] The polyhexamethylene biguanide acrylate was purchased from Shanghai Maikelin Biochemical Technology Co., Ltd.

[0045] The dibenzoyl peroxide was purchased from Tianjin Bodi Chemical Co., Ltd.

[0046] Example 1

[0047] Preparation of phosphocholine-based silane functionalized polyethyleneimine: 10 g of hyperbranched polyethyleneimine was dissolved in 200 mL of anhydrous dimethyl sulfoxide under nitrogen protection, and stirred until completely dissolved; 50 mL of a dimethyl sulfoxide solution containing 15 g of triglycidyloxypropyltrimethoxysilane was added dropwise slowly, and the temperature was controlled at 40 °C; after the addition was completed, the temperature was raised to 70 °C and reacted for 12 hours; after cooling to room temperature, 5 g of 1,8-diazabicyclo[5.4.0]undec-7-ene was added, and then 80 mL of a dimethyl sulfoxide solution containing 20 g of dimethylacryloyloxyethylphosphocholine was added dropwise slowly; after the addition was completed, the temperature was raised to 60 °C and reacted for 24 hours; after the reaction was completed, the reaction liquid was poured into 800 mL of anhydrous ether to precipitate, and the white solid was collected by filtration, washed with ether three times, and dried at 40 °C under vacuum for 48 hours to obtain the product. Preparation of nano-silica anchored polyhexamethylene biguanide: 5 g of nano-silica was dispersed in 100 mL of toluene, and ultrasonic treatment was performed for 30 minutes; 10 g of vinyltriethoxysilane and 0.1 g of dibutyltin dilaurate were added, and refluxed under nitrogen protection for 24 hours; the solid was collected by centrifugation, washed with toluene three times, and dried at 60 °C under vacuum for 12 hours to obtain vinyl-functionalized nano-silica; 3 g of vinyl-functionalized nano-silica was dispersed in 150 mL of nitrogen dimethylformamide, 5 g of nitrogen vinyl caprolactam, 3 g of polyhexamethylene biguanide acrylate, and 0.2 g of dibenzoyl peroxide were added, and deoxygenated under nitrogen for 30 minutes, and then reacted in a 70 °C oil bath for 24 hours; the product was collected by centrifugation, washed with nitrogen dimethylformamide and acetone alternately three times, and dried at 50 °C under vacuum for 24 hours to obtain the product. Preparation of polymer hydrophilic coating: 70 g of phosphocholine-based silane functionalized polyethyleneimine was dissolved in 400 mL of deionized water, and stirred until completely dissolved; 5 g of polyvinylpyrrolidone and 3 g of lactic acid glycolic acid copolymer were added, and continuous stirring was performed until completely dissolved; 0.8 g of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone was added, and stirred until completely dissolved under light shielding conditions; 15 g of nano-silica anchored polyhexamethylene biguanide was added, and ultrasonic dispersion was performed for 30 minutes; 8 g of tetraethoxysilane and 0.3 g of acetic acid were added, and hydrolysis was performed by stirring in a 40 °C water bath for 2 hours to obtain a coating solution; the TPU catheter was sequentially immersed in acetone, ethanol, and deionized water for ultrasonic cleaning for 15 minutes each, and then dried with nitrogen, and then placed in an oxygen plasma treatment instrument for 2 minutes; the pretreated TPU catheter was immersed in the coating solution, and pulled at a speed of 5 centimeters per minute, and then pre-dried in a 60 °C oven for 10 minutes, and then placed in a ultraviolet light curing box for irradiation at a wavelength of 365 nanometers for 5 minutes, and finally aged in a 55 °C constant temperature box for 24 hours.

[0048] Example 2

[0049] The specific embodiment is the same as Example 1, except that the preparation of the phosphorylcholine-based silane functionalized polyethyleneimine: 8 g of hyperbranched polyethyleneimine was dissolved in 160 mL of anhydrous dimethylsulfoxide, 12 g of glycerylpropyltrimethoxysilane in 40 mL of dimethylsulfoxide was added, and the reaction was carried out at 70 °C for 13 hours; 4 g of 1,8-diazabicyclo[5.4.0]undec-7-ene was added, 16 g of dimethylacryloyloxyethylphosphorylcholine in 64 mL of dimethylsulfoxide was added dropwise, and the reaction was carried out at 60 °C for 26 hours; the post-treatment was the same as in Example 1. Preparation of nano-silica anchored polyhexamethylene biguanide: 4 g of nano-silica was dispersed in 80 mL of toluene, 8 g of vinyltriethoxysilane and 0.08 g of dibutyltin dilaurate were added, and the reaction was carried out at reflux for 26 hours; 2.4 g of modified nano-silica was dispersed in 120 mL of dimethylformamide, 4 g of vinylhexalactam, 2.4 g of polyhexamethylene biguanide acrylate, and 0.16 g of dibenzoyl peroxide were added, and the reaction was carried out at 70 °C for 26 hours; the post-treatment was the same as in Example 1. Preparation of polymeric hydrophilic coating: 60 g of phosphorylcholine-based silane functionalized polyethyleneimine was dissolved in 350 mL of deionized water, 3 g of polyvinylpyrrolidone and 2 g of lactic acid-glycolic acid copolymer were added, 0.5 g of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone was added, 10 g of nano-silica anchored polyhexamethylene biguanide was added, 5 g of tetraethoxysilane and 0.1 g of acetic acid were added, and the hydrolysis was carried out at 40 °C for 3 hours; the TPU catheter was plasma treated for 3 minutes, the pre-drying temperature was 60 °C, the ultraviolet irradiation was carried out for 8 minutes, and the curing temperature was 55 °C for 28 hours.

[0050] Example 3

[0051] The specific implementation method is the same as in Example 1, except that the preparation of phosphoric acid choline silane functionalized polyethyleneimine is as follows: 12g of hyperbranched polyethyleneimine is dissolved in 240mL of anhydrous dimethyl sulfoxide, and 18g of triglycidoxypropyltrimethoxysilane in 60mL of dimethyl sulfoxide solution is added. The mixture is reacted at 70℃ for 11 hours. 6g of 1,8-diazabicyclo[5.4.0]undec-7-ene is added, and 24g of dimethacryloyloxyethyl phosphorylcholine in 96mL of dimethyl sulfoxide solution is added dropwise. The mixture is reacted at 60℃ for 22 hours. The post-treatment is the same as in Example 1. Preparation of polyhexamethylene biguanide anchored with nano-silica: 6g of nano-silica was dispersed in 120mL of toluene, 12g of vinyltriethoxysilane and 0.12g of dibutyltin dilaurate were added, and the mixture was refluxed for 22 hours; 3.6g of modified nano-silica was dispersed in 180mL of N-N dimethylformamide, 6g of N-N vinylcaprolactam, 3.6g of polyhexamethylene biguanide acrylate and 0.24g of benzoyl peroxide were added, and the mixture was reacted at 70℃ for 22 hours. The post-treatment was the same as in Example 1. Preparation of the polymer hydrophilic coating: Dissolve 80g of phosphoric acid choline silane-functionalized polyethyleneimine in 450mL of deionized water, add 8g of polyvinylpyrrolidone and 5g of lactic acid glycolic acid copolymer, add 1g of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone, add 20g of nano-silica-anchored polyhexamethylene biguanide, add 10g of tetraethoxysilane and 0.5g of acetic acid, and hydrolyze at 40℃ for 4 hours; treat the TPU catheter with plasma for 4 minutes, pre-dry at 60℃, irradiate with ultraviolet light for 10 minutes, and cure at 55℃ for 30 hours.

[0052] Comparative Example 1

[0053] The specific implementation method is the same as in Example 1, except that the formulation and preparation method of Example 1 are followed, but phosphate choline silane functionalized polyethyleneimine is not added, and an equal amount of ordinary polyethyleneimine is used instead. The remaining components and process conditions are exactly the same as in Example 1.

[0054] Comparative Example 2

[0055] The specific implementation method is the same as in Example 1, except that the formulation and preparation method of Example 1 are followed, but without adding nano-silica to anchor polyhexamethylene biguanide, and instead using an equal amount of ordinary nano-silica. The remaining components and process conditions are exactly the same as in Example 1.

[0056] Comparative Example 3

[0057] The specific implementation is the same as Example 1, except that the formulation and preparation method of Example 1 are used, but at the same time, the phosphocholine-based silane functionalized polyethyleneimine and nano-silica anchoring polyhexamethylene biguanide are not added, and instead an equal amount of ordinary polyethyleneimine and ordinary nano-silica are used, respectively, and the remaining components and process conditions are exactly the same as in Example 1.

[0058] Performance test

[0059] According to the national industry-related standards, the polymer hydrophilic coating prepared in Examples 1-3 and Comparative Examples 1-3 is tested according to the following performance test methods: the water contact angle test uses a static drop method, a contact angle measuring instrument is used at 25°C, 3 μL of ultrapure water droplets are taken on the coating surface, and the contact angle value after stabilization is recorded, 5 points are measured for each sample and the average value is taken; the friction coefficient test is completed by a friction and wear testing machine, a zirconia ceramic ball with a diameter of 6 mm is used as the counter-attraction ball, the load is 0.5 N, the sliding speed is 10 mm / s, and the sliding distance is 30 mm, the dynamic friction coefficient is measured in a simulated body fluid environment; the antibacterial performance test is inoculated with Staphylococcus aureus and Escherichia coli bacterial suspension on the surface of the coating, respectively, and after 24 hours of culture at 37°C, the number of colonies is calculated by plate counting method, and the antibacterial rate is calculated according to the formula (number of colonies in the experimental group-number of colonies in the control group) / number of colonies in the control group x 100%; the coating adhesion test is carried out according to the grid method, a 1 mm x 1 mm grid is drawn and 3M adhesive tape is pasted, and the coating peeling is observed after being quickly torn off at an angle of 60°; the anticoagulant performance test is completed by a platelet adhesion experiment, the coating sample and fresh platelet-rich plasma are incubated at 37°C for 1 hour, and the number of platelet adhesion is observed by scanning electron microscopy, and the uncoated TPU catheter is used as a control; the durability test includes wear test and immersion test, the wear test is detected after 5000 times of friction under a pressure of 0.5 MPa, and the immersion test is detected after the sample is placed in a simulated body fluid at 37°C for 30 days.

[0060] Performance test results:

[0061] Table 1: Performance test results of each example and comparative example

[0062]

[0063] As can be seen from Table 1, the test data clearly shows that Examples 1-3 comprehensively solve the three technical problems of traditional medical catheter coatings through the synergistic effect of two innovative modified compounds. In terms of coating firmness, the adhesion grades of Examples 1-3 all reach 0 level, and the performance retention rate after abrasion and immersion tests is more than 97%, while the adhesion of Comparative Examples 1 and 3 respectively decreases to 2 and 3 levels due to the lack of silane crosslinking network provided by phosphatidylcholine-based silane functionalized polyethyleneimine, and the performance retention rate is less than 86%, proving that the compound effectively solves the problem of easy peeling of the coating by forming stable Si-O-Si chemical bonds. In terms of multifunctional integration, the antibacterial rates of Examples 1-3 are all more than 99.5%, and the friction coefficient is less than 0.035, while the antibacterial rate of Comparative Example 2 suddenly drops to 65.2% due to the lack of nano-silicon dioxide to anchor polyhexamethylene biguanide, indicating that the compound is a key element to achieve high-efficiency antibacterial function; at the same time, the water contact angles of Examples 1-3 are all less than 32°, which is much better than 89.5° of Comparative Example 3, confirming that the two modified compounds together construct a persistent hydrophilic surface. In terms of biocompatibility, the platelet adhesion reduction rates of Examples 1-3 are all more than 95.8%, while the reduction rates of Comparative Examples 1 and 3 are only 42.3% and 38.7% respectively due to the lack of phosphatidylcholine groups for blood cell membrane biomimetic function, proving that the biomimetic design significantly improves the blood compatibility. These data fully demonstrate that the two modified compounds, through synergistic design at the molecular level, form performance complementation while maintaining their respective functional advantages, and finally achieve a breakthrough in the unity of coating firmness, multifunctionality and biocompatibility.

[0064] The above-described examples only express several embodiments of the present application, and the description is more specific and detailed, but it should not be understood as limiting the scope of the present patent. It should be noted that for ordinary skilled persons in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which are within the scope of protection of the present application.

Claims

1. A method of preparing a polymeric hydrophilic coating, characterized by the steps of The method comprises the following steps: S1, dissolving choline phosphate silane functionalized polyethyleneimine in deionized water to prepare an aqueous solution, and stirring until completely dissolved; then adding polyvinylpyrrolidone and lactic acid-glycolic acid copolymer, and continuously stirring until completely dissolved; adding 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, and stirring until completely dissolved under light-proof condition; adding nano-silicon dioxide anchored polyhexamethylene biguanide, and ultrasonic dispersion; adding tetraethoxysilane and acetic acid, and stirring for hydrolysis in a 38-42 DEG C water bath; and obtaining a coating solution; S2, sequentially immersing a TPU catheter in acetone, ethanol and deionized water for ultrasonic cleaning; after blowing dry with nitrogen, the TPU catheter is placed in an oxygen plasma treatment instrument to obtain a pretreated TPU catheter; S3, immersing the pretreated TPU catheter in the coating solution, and pulling and lifting to make the surface of the pretreated TPU catheter covered with the coating solution; then pre-drying in a 58-62 DEG C oven to obtain a coated catheter; placing the coated catheter in a ultraviolet light curing box for irradiation under ultraviolet light; and finally placing the coated catheter in a 50-60 DEG C constant temperature oven for curing.

2. The method of claim 1, wherein the polymer hydrophilic coating is prepared by a process comprising: In step S1, the stirring and hydrolysis time in the 38-42 DEG C water bath is 2-4 h.

3. The method of claim 1, wherein the polymer hydrophilic coating is prepared by a process comprising: In step S2, the treatment time in the oxygen plasma treatment instrument is 2-4 min.

4. The method of claim 1, wherein the polymer hydrophilic coating is prepared by, In step S3, the irradiation time under ultraviolet light is 5-10 min; and the curing time in the 50-60 DEG C constant temperature oven is 24-30 h.

5. The method of claim 1, wherein the polymer hydrophilic coating is prepared by, The preparation method of the choline phosphate silane functionalized polyethyleneimine comprises the following steps: under nitrogen protection, dissolving hyperbranched polyethyleneimine in anhydrous dimethyl sulfoxide, and stirring until completely dissolved; adding a dimethyl sulfoxide solution containing 3-glycidyloxypropyltrimethoxysilane dropwise, and then increasing the temperature to 68-72 DEG C for reaction; after cooling to room temperature, adding 1,8-diazabicyclo[5.4.0]undec-7-ene, and then adding a dimethyl sulfoxide solution containing 2-methacryloyloxyethyl phosphorylcholine dropwise, and then increasing the temperature to 58-62 DEG C for reaction; after the reaction is completed, precipitating the reaction solution in anhydrous diethyl ether, collecting white solids by filtration, washing with diethyl ether, and vacuum drying at 38-42 DEG C.

6. The method of claim 5, wherein the polymer hydrophilic coating is prepared by, Under nitrogen protection, the reaction time after the dropwise addition is completed and the temperature is increased to 68-72 DEG C is 12-14 h; and the reaction time after the dropwise addition is completed and the temperature is increased to 58-62 DEG C is 24-30 h.

7. The method of claim 1, wherein the polymer hydrophilic coating is prepared by, The preparation method of the nano-silicon dioxide anchored polyhexamethylene biguanide comprises the following steps: dispersing nano-silicon dioxide in toluene, and ultrasonic treatment; then adding vinyltriethoxysilane and dibutyltin dilaurate, and refluxing under nitrogen protection for reaction; after the reaction is completed, centrifuging to collect solids, washing with toluene, and vacuum drying at 58-62 DEG C to obtain vinyl-functionalized nano-silicon dioxide; dispersing the vinyl-functionalized nano-silicon dioxide in N,N-dimethylformamide, adding N-vinylcaprolactam, polyhexamethylene biguanide acrylate and dibenzoyl peroxide, removing oxygen by nitrogen blowing, and then reacting in a 68-72 DEG C oil bath; after the reaction is completed, centrifuging to collect the product, washing with N,N-dimethylformamide and acetone alternately, and vacuum drying at 48-52 DEG C.

8. The method of claim 7, wherein the polymer hydrophilic coating is prepared by, The reaction time under reflux with nitrogen protection is 24-30 h; the reaction time in 68-72 °C oil bath is 24-30 h.

9. A polymeric hydrophilic coating characterized by, The polymer hydrophilic coating is prepared according to the method of claim 1-8.

10. Use of the polymer hydrophilic coating according to claim 9 in medical catheters.

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