Super-slippery anti-corrosion and anti-coagulation hydrogel composite coating on medical device surface and preparation method and application thereof

Abstract

The application discloses a kind of medical instrument surface super slippery anticorrosive anticoagulant hydrogel composite coating and its preparation method and application, with N-(3,4-dihydroxyphenethyl)-2-benzoyl benzamide (BPDA) as primer, and the surface hydrogel composite coating formed by grafting hydrophilic polymer on it.Hydrophilic monomer surface grafting polymerization is initiated by light after BPDA is deposited on the surface of substrate, and a layer of hydrogel coating is constructed on the surface of BPDA primer.The primer BPDA provides excellent corrosion resistance, effectively reduces the corrosion rate of metal substrate, and the benzophenone derivative with photo-reactivity on BPDA molecule can mediate the firm combination of hydrogel layer;After meeting water, stable and dense hydration layer is formed, with super lubrication characteristics, which can significantly inhibit the adhesion of protein and cell, and effectively prevent the formation of thrombus.Its excellent anticorrosion and anticoagulant properties are widely applicable to the anticoagulant anticorrosion surface modification of medical instruments and other fields.

Description

TECHNICAL FIELD

[0001] The present application relates to a medical device, in particular a super-slippery anticoagulant and anti-fouling hydrogel composite coating on the surface of a medical device and a preparation method and application thereof. BACKGROUND

[0002] With the continuous progress of medical technology and material science, various medical devices are increasingly widely used in disease diagnosis and treatment and life support, especially medical devices that come into contact with blood and natural cavities of the human body, which are increasingly diverse and have a growing clinical demand.

[0003] Among them, metal materials are widely used in the manufacture of blood-contacting implantable devices such as cardiovascular stents, pacemaker electrodes, artificial heart valves, and left ventricular assist devices due to their excellent mechanical strength, fatigue resistance, and processing performance. At the same time, high polymer materials such as polyurethane, polytetrafluoroethylene, and silicone rubber are also widely used in the manufacture of blood-contacting devices such as artificial blood vessels, hemodialysis circuits, central venous catheters, and ECMO system components, and play an important role in clinical practice due to their excellent flexibility and processing performance.

[0004] On the other hand, more and more medical devices that come into contact with natural cavities of the human body also face problems such as insufficient lubricity and surface biological contamination, typical representatives including urinary catheters, tracheal tubes, gastric tubes, bronchial mirror sheaths, biliary drainage tubes, and reproductive tract intervention devices such as embryo transfer catheters, uterine cavity operation devices, and transurethral endoscopic devices. These devices often need to be inserted or indwelled through narrow and sensitive physiological channels during operation, and the friction coefficient between the surface of the device and the tissue is high, which can easily cause mechanical damage and further cause local tissue inflammation, bleeding, and even significantly increase the patient's pain and discomfort. In addition, long-term contact of the device with body fluids or tissues can also exacerbate bacterial adhesion and biofilm formation, significantly increasing the risk of iatrogenic infection.

[0005] Therefore, such devices require higher requirements for their surface materials, which need to have excellent lubricity, biocompatibility, and anti-fouling ability to improve the safety of clinical use and patient comfort. However, whether it is a metal or a polymer substrate, these medical devices generally have the following problems during use.

[0006] Blood-contacting devices are prone to thrombosis: the surface of the device can easily activate the endogenous or exogenous coagulation cascade, leading to protein adsorption, platelet adhesion and aggregation, and ultimately forming a thrombus. To prevent such complications, anticoagulant drugs are usually used in clinical practice, but long-term use can cause bleeding risks, thrombocytopenia, and other side effects.

[0007] Metallic devices are prone to electrochemical corrosion in vivo: the corrosion process not only damages the structural integrity and functional durability of the device, but also releases metal ions that can cause inflammation, toxicity accumulation, or infection.

[0008] The poor lubricity during the operation of the cavity device can cause mechanical trauma, significantly increasing the risk of tissue damage, pain, and iatrogenic infection.

[0009] To solve the above problems, surface modification of materials is considered as a key strategy to improve the performance of medical devices. By constructing a surface functional layer with superlubricity, corrosion resistance and antithrombosis properties, the blood compatibility and cavity passability of the device can be significantly improved, and the service life of the device can be prolonged and the risk of postoperative complications can be reduced. CN116003692B A surface grafting and crosslinking zwitterionic polymer coating and its preparation method and application, this technology simulates the microenvironment of the blood vessel intima, constructs a zwitterionic polymer coating with micro-nano structure, ultra-low friction coefficient, soft elasticity and superhydrophilicity on the surface of the polymer substrate, which can realize "zero activation" and "zero adhesion" of platelets, thereby effectively improving the anticoagulant properties and anti-biocontamination ability of the device surface. However, the coating construction of this technology relies on the swelling and embedding of benzophenone initiator in organic solvents on the surface of the polymer substrate and the free radical generation mechanism induced by ultraviolet light. This mechanism is mainly suitable for surface modification of polymers, and it is difficult to achieve stable free radical initiation and coating grafting on the surface of metal substrates with dense and chemically inert surfaces, limiting its application in surface modification of metal medical devices such as vascular stents, mechanical valves, pacemaker electrodes, etc. Therefore, it is urgent to develop a universal surface coating that can modify the surface of metal and polymer substrates and has multiple functions such as superlubricity, corrosion resistance and antithrombosis after modification. SUMMARY

[0010] To solve the problems existing in the prior art, the present application provides a medical device surface super-smooth corrosion-resistant and anticoagulant hydrogel composite coating and its preparation method and application. The composite coating prepared based on the surface modification method of dopamine deposition activation and photo-induced polymerization has multiple functions such as corrosion resistance, anticoagulation, superlubricity, etc., and is especially suitable for surface modification of various metal or polymer medical devices, having broad clinical application prospects and industrial promotion value.

[0011] The present application is implemented as follows: a medical device surface super-smooth corrosion-resistant and anticoagulant hydrogel composite coating, the composite coating is composed of N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide primer and hydrophilic polymer hydrogel grafted thereon, and the total thickness of the coating is 10-220 μm.

[0012] Further, the thickness of the N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide primer layer is 5-20 μm, and the thickness of the hydrophilic polymer hydrogel layer is 5-200 μm.

[0013] Further, the preparation method of the N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide comprises the following steps: dissolving 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, and N-hydroxysuccinimide in a solution, stirring at room temperature for 2-5 h to activate the carboxyl group; after the activation is completed, adding triethylamine and dopamine hydrochloride into the solution, and reacting for 20-28 h; after the reaction is completed, adding deionized water to precipitate the product, centrifuging, removing the supernatant, washing twice, centrifuging, and collecting the product; and the molar ratio of 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, N-hydroxysuccinimide, triethylamine, and dopamine hydrochloride is 1:1.1:1.1:1:1.2.

[0014] Further, the hydrophilic polymer hydrogel is a copolymer of a hydrophilic monomer and a chemical crosslinking agent and a physical crosslinking agent, the mass percentage of the chemical crosslinking agent in the hydrophilic monomer is 3%-13%, and the mass percentage of the physical crosslinking agent in the hydrophilic monomer is 3%-30%.

[0015] Further, the hydrophilic monomer is at least one of a zwitterionic monomer, N-vinyl pyrrolidone, and acrylamide; the chemical crosslinking agent is at least one of N,N-methylene bisacrylamide, N,N-bis(acryloyl)cystamine, ethylene glycol dimethacrylate, and carboxybetaine dimethacrylate; the physical crosslinking agent is N-acryloylglycine amide; and the zwitterionic monomer is at least one of methacryloyl ethyl sulfobetaine, 2-methacryloyloxyethyl phosphocholine, and carboxybetaine methacrylate.

[0016] The preparation method of the above-mentioned medical device surface super-smooth corrosion-resistant and anticoagulant hydrogel composite coating comprises the following two steps: first, depositing N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide on the surface of a substrate to introduce a primer containing a benzophenone group on the surface of the substrate; and second, grafting a hydrophilic polymer hydrogel to the surface of the primer by a light-initiated polymerization method.

[0017] Further, the first step of the deposition method of the primer: the substrate is immersed in an organic solvent solution of N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide, and after 5-40 hours, the surface is rinsed with deionized water, and then dried with nitrogen, and the surface is deposited with N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide primer; the organic solvent is at least one of dimethyl sulfoxide, dimethylformamide and dichloromethane; the mass percentage concentration of the organic solvent solution of N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide is 0.1%-1%;

[0018] The second step is to immerse the surface deposited with the primer into a hydrophilic polymer hydrogel pre-polymer solution, and initiate polymerization under 365nm ultraviolet light for 5-40 minutes; the hydrophilic polymer hydrogel pre-polymer solution is a mixed aqueous solution of hydrophilic monomer, chemical crosslinking agent, physical crosslinking agent and photoinitiator.

[0019] Further, in the hydrogel pre-polymer solution, the mass concentration of the hydrophilic monomer in water is 10%-60%, the mass percentage of the chemical crosslinking agent in the hydrophilic monomer is 3%-13%, the mass percentage of the physical crosslinking agent in the hydrophilic monomer is 3%-30%, and the mass percentage of the photoinitiator in the hydrophilic monomer is 0.5%-20%; the hydrophilic monomer is at least one of methacryloyl ethyl sulfobetaine, 2-methacryloyloxyethyl phosphocholine, carboxybetaine methacrylate, N-vinyl pyrrolidone and acrylamide; the chemical crosslinking agent is at least one of N,N-methylene bisacrylamide, N,N-bis(acryloyl)cystamine, ethylene glycol dimethacrylate and carboxybetaine dimethacrylate; the physical crosslinking agent is N-acryloyl glycine amide; and the photoinitiator is at least one of Irgacure 2959 and α-ketoglutaric acid.

[0020] The medical device surface super-smooth anti-corrosion and anti-coagulation hydrogel composite coating prepared by the above method or the medical device surface super-smooth anti-corrosion and anti-coagulation hydrogel composite coating is applied to the preparation of medical devices that contact blood and natural cavities of the human body.

[0021] Further, the substrate surface material of the medical device is metal, polymer or inorganic material.

[0022] The application provides a coating technology capable of forming an anti-corrosion and anti-coagulation coating on different substrate surfaces, which comprises the following steps: depositing N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide primer on the substrate surface through a two-step method, and then grafting and polymerizing hydrophilic polymer hydrogel on the primer to form a composite coating. The prepared composite coating has a dense primer layer, which can effectively prevent corrosion, and the benzophenone unit contained in the primer layer has photo-initiation activity, so that surface radicals can be formed under ultraviolet light irradiation to initiate the graft polymerization of hydrophilic monomers and realize the stable construction of the outer hydrogel coating. The outer hydrogel layer has a nanometer and micrometer topological structure similar to the inner membrane of a blood vessel, a low surface Young's modulus, and super-hydrophilic and super-lubricating properties. When the coating is applied to the surface of a device in contact with blood (such as a contrast guide wire or a central venous catheter), the coating has good anti-coagulation performance; when the coating is applied to the surface of a device in contact with a natural cavity of the human body (such as a urinary catheter or a tracheal tube), the coating can significantly improve the lubricity and reduce the interfacial friction.

[0023] The application has the advantages and technical effects that:

[0024] 1. The high-hydrophilic hydrogel coating preparation technology of the application is simple, the raw materials used are convenient to prepare and low in cost, the coating preparation conditions are mild, the structure, size, shape and bulk properties of the product are not affected, and the coating modification is suitable for irregularly-shaped substrate surfaces.

[0025] 2. The surface grafting and crosslinking technology scheme is creative, and well combines the functions of the dopamine layer (adhesion and anti-corrosion properties for any surface) and the photo-initiation properties of the benzophenone structure in generating surface radicals and initiating polymerization under ultraviolet light irradiation, so that the functional polymer hydrogel can be stably grafted to the surfaces of various medical devices including metals and polymers. Meanwhile, the high-hydrophilic hydrogel layer has excellent blood compatibility, shows extremely low protein adsorption and platelet adhesion tendency, and has the characteristics of super-lubricity and flexibility similar to the inner membrane.

[0026] 3. The coating can realize “zero activation” and “zero adhesion” of platelets in a blood contact environment, and significantly improves the anti-coagulation performance. In addition, in the process of contacting with the natural cavity of the human body, the coating can significantly reduce the frictional resistance in the process of inserting or indwelling the device, reduce mechanical trauma, reduce tissue damage and patient discomfort, and further expand the application value in multiple clinical fields.

[0027] 4. The appropriate crosslinking structure in the coating also provides strong mechanical stability and is conducive to maintaining the surface nanometer and micrometer topological structure, and the technology provides a relatively simple and effective method for the surface functionalization of different materials and different shapes, and is thus suitable for large-scale modification of various surfaces. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the present application, the following briefly introduces the drawings. Obviously, the following described drawings only relate to some embodiments of the present application, and are not a limitation on the present application.

[0029] Figure 1 NMR and IR spectra of BPDA synthesized in Example 1.

[0030] Figure 2 SEM images of the surface of the Mg alloy (AZ31 magnesium alloy) modified by the composite coating prepared in Example 1 at different modification stages.

[0031] Figure 3 SEM images of the cross section of the Mg alloy modified by the composite coating prepared in Example 1 at different modification stages.

[0032] Figure 4 Surface friction coefficient and water contact angle of the Mg alloy before and after modification by the composite coating prepared in Example 1.

[0033] Figure 5 Surface morphology images of the Mg alloy modified by the super-slippery corrosion-resistant anti-coagulation hydrogel coating prepared in Example 1 at different modification stages after immersion in 0.9 wt% sodium chloride solution for 10 h.

[0034] Figure 6 Electrochemical impedance spectroscopy (EIS) (left: Nyquist plot, right: potentiodynamic polarization curve) of the Mg alloy modified by the super-slippery corrosion-resistant anti-coagulation hydrogel coating prepared in Example 1 at different modification stages in 0.9 wt% sodium chloride solution.

[0035] Figure 7 Hemolysis rate of the samples at different modification stages in Example 1.

[0036] Figure 8 Anti-BSA protein adhesion performance of the samples before and after modification in Example 1.

[0037] Figure 9 Anti-platelet activation performance of the samples before and after modification in Example 1.

[0038] Figure 10 In-vitro arteriovenous shunt model of the magnesium alloy pipeline modified by the coating in Example 17.

[0039] Figure 11 Surface SEM images of the magnesium alloy pipeline after in-vitro circulation for 8 h in Example 17.

[0040] Figure 12Water contact angle of PU tubing surface before and after coating modification prepared in Example 18.

[0041] Figure 13 Young's modulus of PU tubing surface before and after coating modification prepared in Example 18. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application is further described in detail below with reference to the drawings. It should be understood that the specific embodiments described herein are only used to explain the present application and not to limit the present application.

[0043] The medical device surface super-smooth anticoagulant hydrogel composite coating of the present application is composed of N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide (hereinafter referred to as BPDA) primer and hydrophilic polymer hydrogel grafted thereon, and the total thickness of the coating is 10-220 μm. The thickness of the N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide primer layer is 5-20 μm, and the thickness of the hydrophilic polymer hydrogel layer is 5-200 μm.

[0044] Further, the preparation method of the N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide is as follows: 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethyl carbimide, and N-hydroxysuccinimide are dissolved in a solution, and the carboxyl group is activated by stirring at room temperature for 2-5 h; after activation, triethylamine and dopamine hydrochloride are added to the solution, and the reaction is carried out for 20-28 h; after the reaction is completed, deionized water is added to precipitate the product, which is centrifuged, the supernatant is removed, and the product is collected after washing twice and centrifugation; the molar ratio of 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethyl carbimide, N-hydroxysuccinimide, triethylamine, and dopamine hydrochloride is 1:1.1:1.1:1:1.2.

[0045] Further, the hydrophilic polymer hydrogel is a copolymer of a hydrophilic monomer and a chemical crosslinking agent and a physical crosslinking agent, the mass percentage of the chemical crosslinking agent in the hydrophilic monomer is 3%-13%, and the mass percentage of the physical crosslinking agent in the hydrophilic monomer is 3%-30%.

[0046] Further, the hydrophilic monomer is selected from one or more of zwitterionic monomer, N-vinyl pyrrolidone (NVP), acrylamide (AAm); the chemical crosslinking agent is selected from one or more of N,N-methylene bisacrylamide (MBA), N,N-bis(acryloyl)cystamine (MSBA), ethylene glycol dimethacrylate (EBA), carboxybetaine dimethacrylate (CBBA); the physical crosslinking agent is N-acryloylglycineamide (NAGA). The zwitterionic monomer is selected from one or more of methacryloyl ethyl sulfobetaine (SBMA), 2-methacryloyloxyethyl phosphocholine (PBMA), carboxybetaine methacrylate (CBMA).

[0047] The method for preparing the above-mentioned super-slippery, anti-corrosion and anti-coagulation hydrogel composite coating on the surface of medical devices comprises the following two steps: first, depositing N-(3,4-dihydroxyphenethyl)-2-benzoylbenzamide on the surface of the substrate to introduce a primer containing a benzophenone group on the surface of the substrate; and second, grafting a hydrophilic polymer hydrogel to the surface of the primer by a photoinitiator-induced polymerization method.

[0048] Further, the method for depositing the BPDA primer is immersing the substrate in an organic solvent solution of BPDA, washing the surface with deionized water after 5-40 hours, and then blowing dry with nitrogen, so that the BPDA primer is deposited on the surface; the organic solvent is selected from one or more of dimethyl sulfoxide (DMSO), dimethylformamide (DMF) and dichloromethane (DCM); and the concentration of the organic solvent solution of BPDA is 0.1wt%-1wt%.

[0049] The hydrophilic polymer hydrogel is grafted to the surface of the BPDA primer by immersing the surface on which the BPDA primer is deposited into a hydrogel prepolymer solution and initiating polymerization under 365 nm ultraviolet light for 5-40 min; the hydrophilic polymer hydrogel prepolymer solution is a mixed aqueous solution of hydrophilic monomer, chemical crosslinking agent, physical crosslinking agent and photoinitiator.

[0050] The hydrogel prepolymer solution has a concentration of 10wt%-60wt% of the hydrophilic monomer in water, 3wt%-13wt% of the chemical crosslinking agent based on the mass percentage of the hydrophilic monomer, 3wt%-30wt% of the physical crosslinking agent based on the mass percentage of the hydrophilic monomer, and 0.5wt%-20wt% of the photoinitiator based on the mass percentage of the hydrophilic monomer.

[0051] The hydrogel prepolymer liquid, wherein the hydrophilic monomer is selected from one or more of methacryloyl ethyl sulfobetaine (SBMA), 2-methacryloyloxyethyl phosphocholine (PBMA), carboxybetaine methacrylate (CBMA), N-vinyl pyrrolidone (NVP), and acrylamide (AAm); the chemical crosslinking agent is selected from one or more of N,N-methylene bisacrylamide (MBA), N,N-bis(acryloyl)cystamine (MSBA), ethylene glycol dimethacrylate (EBA), and carboxybetaine dimethacrylate (CBBA); the physical crosslinking agent is N-acryloylglycineamide (NAGA); and the photoinitiator is selected from one or more of Irgacure 2959 and α-ketoglutaric acid.

[0052] The medical device surface super-smooth antiseptic and anticoagulant hydrogel composite coating prepared by the method or the medical device surface super-smooth antiseptic and anticoagulant hydrogel composite coating is applied to the preparation of a medical device in contact with blood and a natural cavity of a human body.

[0053] Further, the base surface material of the medical device is metal, polymer or inorganic material.

[0054] The specific steps are as follows:

[0055] (1) A certain amount of 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (EDC) and N-hydroxysuccinimide (NHS) are dissolved in a solution, and the carboxyl group is activated by stirring at room temperature for 2-5 h. After activation, triethylamine and dopamine hydrochloride are added to the solution, and the reaction is carried out for 20-28 h. After the reaction is completed, deionized water is added to precipitate the product, which is centrifuged, and the supernatant is removed and washed twice. The collected product is BPDA.

[0056] (2) The base is immersed in the BPDA solution at 60°C and stirred for a certain period of time. After washing with deionized water and drying with nitrogen, a BPDA coating is obtained.

[0057] (3) The BPDA-activated base is immersed in a hydrophilic gel prepolymer liquid composed of a hydrophilic monomer, a chemical crosslinking agent, a physical crosslinking agent and an initiator, and surface grafting crosslinking polymerization is initiated by ultraviolet light or heat. After the reaction is completed, the unreacted precursor solution is washed away with a large amount of deionized water, and a composite coating is formed on the surface of the base.

[0058] The application will be described in detail below with specific examples. Although the preferred embodiments of the application are described below, it should be understood that the application can be implemented in various forms and should not be limited by the embodiments described herein. Those skilled in the art can make several modifications and improvements without departing from the concept of the application. These are within the scope of the application. The reagents or instruments used in the application are not specified by the manufacturer, and are conventional products that can be purchased on the market. All animal experiments were conducted in strict accordance with the protocols approved by the Animal Experiment Ethics Committee of the Chinese Academy of Medical Sciences.

[0059] Example 1 Preparation of super-smooth corrosion-resistant anti-condensation hydrogel composite coating on magnesium alloy surface, the preparation steps are as follows:

[0060] First step: Dissolve 0.716 g of 2-benzoylbenzoic acid, 0.54 g of EDC, and 0.40 g of NHS in 30 mL of DMSO solution, and stir at room temperature for 3 h to activate the carboxyl group. After activation, add 0.32 g of triethylamine, 0.72 g of dopamine hydrochloride to the solution, and react for 24 h. After the reaction is completed, add 100 mL of deionized water, and the product is precipitated. Centrifuge, remove the supernatant, wash twice with deionized water, and centrifuge to obtain the product BPDA.

[0061] Second step: Polishing AZ31 magnesium alloy (1 cm x 1 cm) with 3000# SiC sandpaper, and ultrasonic cleaning with acetone and ethanol for 15 min each time, and blowing dry with nitrogen. Weigh the prepared BPDA dissolved in DMSO solution (BPDA concentration 0.4 wt%), adjust the pH to weak alkaline (pH≈8.5) with triethylamine, immerse the magnesium alloy sheet in it, and stir at 60 ℃ for 24 h. After washing with deionized water, dry with nitrogen to obtain Mg@BPDA coating.

[0062] Third step: Preparation of magnesium alloy surface composite coating (Mg@BPDA / P PN ): First, dissolve the zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine (20 wt%), the chemical crosslinking agent MBA accounting for 7 wt% of the mass fraction of the zwitterionic monomer, the physical crosslinking agent NAGA accounting for 20 wt% of the mass fraction of the zwitterionic monomer, and the photoinitiator Irgacure 2959 accounting for 10 wt% of the mass fraction of the zwitterionic monomer in distilled water to prepare a hydrogel pre-polymer solution. Next, evenly drop the prepared pre-polymer solution onto the magnesium alloy surface previously treated with BPDA. Then, use ultraviolet light with a wavelength of 365 nm to uniformly irradiate the surface for 10 minutes. Finally, remove the unreacted monomers and impurities by washing with a large amount of deionized water, thereby successfully preparing the Mg@BPDA / P PN coating.

[0063] The structure and performance of the prepared Mg alloy surface coating are as follows Figures 1-9 , and shown in Table 1.

[0064] Table 1 Performance analysis of the coating prepared in Example 1

[0065]

[0066] T BPDA : thickness of the BPDA primer layer; T tot : total thickness of the coating; E: surface Young's modulus; CF0: initial friction coefficient of the coating; CF1: friction coefficient after shearing in PBS solution for 10 days; WCA0: initial water contact angle of the coating; WCA1: surface water contact angle after shearing in PBS solution for 10 days; Ad pro : initial protein adsorption amount; Ad pla : platelet adhesion amount; Wlr0: mass loss rate of the bare Mg alloy after immersion for 90 days; Wlr: mass loss rate of the sample after immersion for 90 days after coating modification.

[0067] It can be seen from Figure 1 that the BPDA is successfully synthesized.

[0068] It can be seen from Figure 2 that after the coating is modified, uniform micron-scale groove structures and "paving stone"-like protrusions appear on the surface.

[0069] It can be seen from Figure 3 that after the coating is modified, uniform micron-scale groove structures and "paving stone"-like protrusions appear on the surface, the thickness of the BPDA coating prepared in Example 1 is 11 μm, the thickness of the zwitterionic hydrogel coating is 44 μm, and the overall thickness of the coating is 55 μm.

[0070] Figure 4 The friction coefficient and water contact angle of the Mg alloy surface before and after the preparation of the composite coating can be seen, and it can be seen that the surface after the coating modification exhibits superhydrophilic and superlubrication properties.

[0071] It can be seen from Figure 5 that after 10 h of immersion, the alloy surface without coating modification suffers from obvious corrosion, and the surface is covered with a large amount of corrosion products, showing serious corrosion. The Mg@BPDA sample and the Mg@BPDA / P PN sample maintain relatively flat surfaces, indicating that the coating effectively inhibits the corrosion process of the magnesium alloy.

[0072] Figure 6It can be seen that the corrosion resistance of Mg@BPDA is significantly improved compared with Mg alloy, and the corrosion resistance slightly decreases after further modification of the zwitterionic hydrogel coating, but the influence is not big, and it is still significantly better than magnesium alloy, which is because the hydrophilicity of the zwitterionic polymer coating accelerates the hydration degree of the interface.

[0073] From Figure 7 It can be seen that the hemolysis rate of the modified Mg alloy is less than 5%, which meets the hemolysis rate requirement of medical devices.

[0074] From Figure 8 It can be seen that the surface protein adhesion amount of the composite coating after modification is significantly reduced, so the coating has excellent anti-protein adhesion performance.

[0075] From Figure 9 It can be seen that almost all the platelets on the surface of the unmodified Mg alloy are activated, the shape of the platelets changes from flat to irregular shape, and the tentacles are stretched out, while no activated platelets are observed on the modified coating substrate.

[0076] From Figures 1-9 It can be seen from Table 1 that the coating prepared on the surface of the Mg alloy in the method of Example 1 has excellent superhydrophilic, superlubricating performance and anti-bioadhesion function, and can effectively inhibit the corrosion of the metal. And the friction coefficient and surface water contact angle of the coating after shearing in PBS solution for 10 days are basically unchanged, indicating that the coating has high stability.

[0077] Example 2-3

[0078] According to the method of Example 1, the operation method is the same as that of Example 1, except that the organic solvent for dissolving BPDA is changed. The thickness, surface Young's modulus, protein adsorption amount, platelet adhesion amount, friction coefficient, water contact angle of the composite coating prepared by different organic solvents are measured, and the mass loss rate of the magnesium alloy after immersion for 90 days is measured. As shown in Table 2.

[0079] Table 2 Performance analysis of coatings prepared by different BPDA solvents

[0080]

[0081] It can be seen from Table 2 that different organic solvents can dissolve BPDA and form BPDA coating on the surface of the magnesium alloy substrate, and the formed BPDA primer layer can effectively inhibit the corrosion of the magnesium alloy. And the performance of the super-smooth anti-coagulation coating further formed on its surface is not related to the organic solvent for dissolving BPDA, and the coating still has excellent superhydrophilic, soft elastic, superlubricating performance and anti-bioadhesion function, and the coating has high stability, which is because the physicochemical properties of the BPDA layer are not related to the organic solvent.

[0082] Example 4-11

[0083] The method of Example 1 was followed, except that the immersion time of the magnesium alloy in the BPDA solution was changed, and the thickness, surface Young's modulus, protein adsorption amount, platelet adhesion amount, friction coefficient, water contact angle of the prepared composite coating, and the mass loss rate of the magnesium alloy after immersion for 90 days were measured. The results are shown in Table 3.

[0084] Table 3 Performance analysis of hydrogel coatings prepared by magnesium alloy with different immersion times in BPDA solution

[0085]

[0086] As shown in Table 3, as the immersion time of the magnesium alloy in the BPDA solution increased, the thickness of the BPDA layer increased, resulting in an overall increase in the thickness of the coating, and the corrosion resistance of the coating also improved. However, when the immersion time reached 24 hours, the improvement in corrosion resistance tended to be flat, and the change was no longer significant. The overall coating still maintained excellent superhydrophilicity, soft elasticity, and superlubricity, and had good anti-bioadhesion function, and also showed high stability.

[0087] Examples 12-16

[0088] The method of Example 1 was followed, except that the concentration of the BPDA solution was changed, and the thickness, surface Young's modulus, protein adsorption amount, platelet adhesion amount, friction coefficient, water contact angle of the prepared composite coating, and the mass loss rate of the magnesium alloy after immersion for 90 days were measured. The results are shown in Table 4.

[0089] Table 4 Performance analysis of hydrogel coatings prepared by different concentrations of BPDA

[0090]

[0091] As shown in Table 3, as the concentration of BPDA increased, the thickness of the BPDA layer also increased, resulting in an overall increase in the thickness of the coating, and the corrosion resistance of the coating also improved, but when the thickness of the BPDA layer increased to a certain extent, the improvement in corrosion resistance tended to be flat, and the change was no longer significant. The overall coating maintained excellent superhydrophilicity, soft elasticity, and superlubricity, and had good anti-bioadhesion function, and also showed high stability.

[0092] Example 17

[0093] The method of Example 1 was followed, except that the coating modification was performed on the inner surface of the magnesium alloy pipeline to obtain a magnesium alloy pipeline with a composite coating on the inner surface, and a rabbit arteriovenous shunt model experiment under in vitro circulation was performed, and the results are shown in Figure 10 、 Figure 11 , from Figure 10It can be seen that a large number of red blood cells and platelets adhere to the surface of the unmodified magnesium alloy, while no thrombus forms in the coated magnesium alloy. After 8 hours of extracorporeal circulation, no thrombus forms on the inner surface of the coated magnesium alloy, and the platelet "zero adhesion" can be achieved after long-term blood circulation. Figure 11 It can be seen that a large number of red blood cells and platelets adhere to the surface of the unmodified magnesium alloy, while no thrombus forms in the coated magnesium alloy. After 8 hours of extracorporeal circulation, no thrombus forms on the inner surface of the coated magnesium alloy, and the platelet "zero adhesion" can be achieved after long-term blood circulation.

[0094] Example 18

[0095] According to the method of Example 1, the amount of other components is not changed, except that the hydrophilic monomer is a 30wt% N-vinyl pyrrolidone (NVP) solution, which is used for surface grafting of polymer on the inner and outer surfaces of the polyurethane (PU) tube. The PU tube with a polyethylene pyrrolidone (PVP) coating on the surface is obtained. Figure 12 、 13 The water contact angle and surface Young's modulus of the tube before and after modification can be seen, and the hydrophilicity and soft elasticity of the modified tube are significantly improved.

[0096] The applicant has previously authorized the invention patent CN116003692B "Surface Grafting and Cross-linking of Zwitterionic Polymer Coating and Its Preparation Method and Application", which has discussed the raw material ratio of the zwitterionic polymer coating in the patent, which will not be repeated here.

[0097] Example 19

[0098] According to the method of Example 18, the operation is the same as Example 18, except that the hydrophilic monomer is changed to 30wt% acrylamide (AAm), and other components remain unchanged, to obtain the coating. The protein adsorption amount, platelet adhesion amount, friction coefficient, water contact angle, surface Young's modulus and coating thickness are measured. As shown in Table 5.

[0099] Table 5 Performance analysis of coatings prepared by different monomers

[0100]

[0101] Table 5 data shows that the coating prepared by different monomers has soft elasticity characteristics, low friction coefficient and high hydrophilicity, and exhibits very excellent anti-bioadhesion performance and stability.

[0102] Examples 20-26

[0103] The method of Example 18 was followed, with the exception that the concentration of N-vinylpyrrolidone (NVP) in the precursor solution and the amount of initiator were changed, to obtain surface coatings, and the protein adsorption, platelet adhesion, friction coefficient, water contact angle, surface Young's modulus, and coating thickness of different coatings were measured. The results are shown in Table 6.

[0104] Table 6 Performance analysis of hydrogel coatings prepared with different concentrations of NVP monomer and different amounts of initiator

[0105]

[0106] CF0 / CF1 = initial friction coefficient / PBS solution shear for 10 days friction coefficient.

[0107] From the data in Table 6, it can be seen that as the concentration of NVP monomer increases, the thickness, hydrophilicity, and anti-bioadhesion performance of the coating also increase. In addition, the increase in NVP content also promotes the internal network structure of the coating to be more flexible, reducing the overall stiffness, which is manifested as a decrease in the surface Young's modulus. However, when the NVP content is too high, the mechanical strength of the coating decreases, and the structural stability weakens, resulting in significant changes in the hydrophilicity and lubricity of the coating after PBS shear for 10 days. With changes in the amount of initiator, the lubricity and anti-bioadhesion performance of the coating remain almost unchanged, indicating that the performance of the hydrogel coating is almost independent of the amount of initiator.

[0108] Examples 27-29

[0109] The method of Example 18 was followed, with the exception that the type of crosslinking agent was changed, to obtain surface coatings, and the thickness, elastic modulus, protein adsorption, platelet adhesion, friction coefficient, and water contact angle of coatings with different types of crosslinking agent were measured. The results are shown in Table 7.

[0110] Table 7 Performance analysis of hydrogel coatings prepared with different types of crosslinking agent

[0111]

[0112] From the data in Table 7, it can be seen that compared with the crosslinking agent MBA, the hydrogel coatings formed by the other three crosslinking agents (MSBA, EBA, and CBBA) also exhibit excellent superlubricity, soft elasticity, anti-bioadhesion, high hydrophilicity, and stable mechanical properties, and the thickness of the coating does not change significantly.

[0113] Examples 30-34

[0114] The method of Example 18 was followed, with the exception that the amount of crosslinking agent was changed, to investigate the effect of different amounts of crosslinking agent on the performance of the coating, and the results are shown in Table 8.

[0115] Table 8 Performance analysis of hydrogel coatings prepared with different amounts of chemical crosslinker MBA

[0116]

[0117] With the increase of the content of the chemical crosslinker MBA, the thickness of the coating slightly increased, and the mechanical properties and mechanical stability of the coating were improved within a certain range. However, when the content of MBA was too high, the mechanical stability of the coating decreased, mainly because the excessive chemical crosslinking led to an increase in the brittleness of the coating, which was prone to cracking or falling off. In addition, too high a content of the crosslinker also significantly reduced the hydrophilicity and lubricity of the coating, the anti-bioadhesion performance decreased, thereby affecting the anticoagulant properties of the coating.

[0118] Examples 35-40

[0119] According to the method of Example 18, the operation was the same as that of Example 18, except that the amount of the physical crosslinker N-acryloyl glycine amide (NAGA) in the precursor solution was changed, and the surface coating was obtained. The protein adsorption amount, platelet adhesion amount, friction coefficient, water contact angle, and coating thickness of different coatings were measured. As shown in Table 9.

[0120] Table 9 Performance analysis of hydrogel coatings prepared with different amounts of physical crosslinker NAGA

[0121]

[0122] As can be seen from Table 9, with the increase of the content of the physical crosslinker NAGA, the thickness of the coating increased, the surface Young's modulus increased, and the mechanical properties and mechanical stability of the prepared coating were significantly enhanced. This phenomenon was mainly due to the introduction of physical crosslinking points mainly based on multiple hydrogen bonds in the coating network by NAGA, which improved the compactness and mechanical strength of the coating structure. On the other hand, with the continuous increase of the content of NAGA, the hydrophilicity and lubricity of the coating decreased, and the anti-bioadhesion performance showed a downward trend. This was because the amide groups and amino acid-like structures in the NAGA molecule had certain bioactivity, which was easy to interact with proteins and bacterial surface molecules through hydrogen bonds or electrostatic interactions, thereby promoting their adsorption on the surface of the coating.

[0123] Examples 41-44

[0124] According to the method of Example 18, the operation was the same as that of Example 18, except that the type of the substrate was changed, and the surface coating was obtained on the surface of different substrates. The protein adsorption amount, platelet adhesion amount, friction coefficient, water contact angle, and coating thickness of different coatings were measured. As shown in Table 10.

[0125] Table 10 Performance analysis of hydrogel coatings prepared on different substrate surfaces

[0126]

[0127] As shown in Table 10, according to the technical solution of the present invention, an ultra-slippery, anti-corrosion and anti-condensation hydrogel coating can be formed on the surface of metal materials such as magnesium alloy, stainless steel, and titanium alloy, as well as polymer materials such as polyvinyl chloride (PVC), polyurethane (PU), polydimethylsiloxane (PDMS), and polyethylene terephthalate (PET).

[0128] Characterization methods for the above-mentioned super-slippery, anti-corrosion, and anti-coating hydrogel composite coating:

[0129] 1. Nuclear magnetic resonance hydrogen spectroscopy test

[0130] Prepare 20 mg / mL solution using deuterated dimethyl sulfoxide (C2D6SO) as solvent. -1 The NMR spectrum of BPDA in the BPDA solution was determined using a nuclear magnetic resonance spectrometer (400 Hz).

[0131] 2. Fourier Transform Infrared Spectroscopy (FTIR)

[0132] The functional group composition of BPDA was analyzed using Fourier transform infrared spectroscopy with attenuated total reflectance technique and crystal total reflectance assembly (ATR). The scanning range was set to 400-4000 cm⁻¹. -1 The functional group information of BPDA was determined by relying on ATR-FTIR.

[0133] 3. Analysis of coating surface morphology and thickness under scanning electron microscopy:

[0134] The surface morphology and thickness of the coating were observed using a field emission scanning electron microscope (SEM) (HITACHI S-4800, Hitachi). Before SEM characterization, all samples were subjected to a 60-second gold plating treatment under argon protection to enhance their conductivity. The surface morphology and cross-sectional thickness of the samples were observed under conditions of a fast voltage of 3 kV and a working distance of 10-15 mm.

[0135] 4. Protein adhesion test:

[0136] Protein adsorption was determined using the BCA protein quantification method, employing the BCA protein assay kit. Samples were incubated in PBS at 37°C for 6 h. 2.0 mg / mL BSA protein solution was added to the wells, and the samples were incubated with the BSA protein solution at 37°C for 2 h. The samples were then washed three times with PBS and transferred to a 1.0 w% sodium dodecyl sulfate (SDS) aqueous solution. After sonication for 20 min at room temperature, protein concentration was determined according to the BCA protein assay kit instructions.

[0137] 5. Testing of coating corrosion resistance

[0138] (1) In vitro immersion test

[0139] In vitro immersion test was performed in PBS buffer solution (PH=7.4) at 37±0.5 °C. The same size of samples at different modification stages were taken out after 10 h immersion, and the coating and corrosion products on the surface of the samples were removed, then cleaned with ultrapure water. After drying the samples, the surface morphology of the cleaned substrate was observed by SEM to intuitively evaluate the corrosion degree of the substrate.

[0140] (2) Electrochemical test

[0141] The corrosion condition of magnesium alloy at different modification stages in 0.9 wt% sodium chloride solution was evaluated by electrochemical test.

[0142] Potentiodynamic polarization scan: electrochemical test was performed by electrochemical workstation using a classic three-electrode system, in which the magnesium alloy sample at different modification stages was used as the working electrode, platinum electrode as the counter electrode, and mercury-mercury electrode as the reference electrode, and potentiodynamic polarization scan was performed.

[0143] Electrochemical impedance spectroscopy (EIS): the corrosion rate of magnesium alloy at different modification stages was evaluated by electrochemical impedance spectroscopy (EIS). A conventional three-electrode test system was used, in which the magnesium alloy sample at different modification stages was used as the working electrode, saturated mercury-mercury electrode as the reference electrode, and platinum wire electrode as the counter electrode. The frequency range was 100 kHz to 0.01 Hz, and the alternating current amplitude was 10 mV.

[0144] (3) Long-term immersion test

[0145] In vitro immersion test was performed in SBF solution at 37±0.5 °C for 90 days. According to ASTM-G31-72 standard, the ratio of SBF solution volume to sample surface area was controlled to be 25:1. After immersion, the coating and corrosion products on the surface of the sample were removed, then cleaned with ultrapure water. After drying the sample, the remaining mass of the magnesium alloy substrate was weighed by analytical balance, and the mass loss rate of different samples was calculated combined with the previously recorded initial mass of the substrate.

[0146] 6. Water contact angle test

[0147] The water contact angle (WCA) of samples at different modification stages was measured at room temperature using a contact angle measurement system, and video recording was performed throughout. First, the sample was thoroughly dried, then according to the experimental requirements, the sample was cut into an appropriate size and fixed on a glass slide. A microsyringe was used to drop 3 μL of water onto the sample surface, and after the water droplet and the surface angle stabilized, the imaging system was started to capture the real-time state of the liquid droplet and the sample contact interface. A digital image analyzer was installed on the measurement device, and five independent repeated experiments were performed at different positions of each sample to reduce the error caused by single measurement. The average value of these measurement values was calculated and taken as the final WCA value of each sample.

[0148] 7. Surface friction coefficient test:

[0149] The friction coefficient of the coating was determined using a CSM-friction and wear tester. The sample was pre-equilibrated in 25 °C deionized water. Test conditions: counter abrasive was a 3 mm diameter glass ball, sliding speed was 30 mm / min, sliding distance was 20 mm, and normal load was 800 μN. The friction coefficient was calculated by dividing the friction force by the normal load

[0150] 8. Surface Young's modulus test:

[0151] The Young's modulus of the sample in PBS solution was determined using a desktop PIUMA nanoindenter. A spherical indenter with a radius of 48.5 μm was used to perform a 5 × 5 point array scan in a 100 × 100 μm area with a point spacing of 20 μm.

[0152] 9. Biocompatibility test:

[0153] (1) Platelet adhesion experiment

[0154] Firstly, fresh whole blood was collected from New Zealand white rabbits in vivo, and platelets were isolated from peripheral blood using a special whole blood platelet separation kit. Then, the samples were placed in platelet-rich plasma (PRP) and incubated together at 37°C for two hours to simulate the platelet adhesion process under physiological conditions in vivo. After incubation, the samples were rinsed with PBS solution at 37°C to remove the platelets that did not successfully adhere. Then, the adhered platelets were fixed using a 2.5 wt% glutaraldehyde solution for two hours to ensure that the morphology of the platelets remained stable during subsequent observation. After fixation, the samples were further dehydrated by a series of increasing concentration ethanol solutions (50%, 60%, 70%, 80%, 90%, and 100%) for 30 minutes at each concentration gradient. Finally, after natural drying of the samples at room temperature, the samples were observed using a scanning electron microscope (SEM) to determine the number and morphology of the adhered platelets on the surface of the samples.

[0155] (2) Hemolysis rate test

[0156] The hemolysis rate test was used to evaluate the degree of damage to the blood cells (mainly red blood cells) in the coating. The sample to be tested was placed in a test tube with 10 mL of 0.9% NaCl solution; the positive control used distilled water, and the negative control was 0.9% NaCl solution. Fresh ACD anticoagulated rabbit blood (blood: 3.8% sodium citrate = 4:1) was used, and all test tubes were pre-warmed in a 37°C water bath for 30 minutes. Each test tube was then added with 0.2 mL of diluted fresh anticoagulated rabbit blood (rabbit blood: physiological saline = 4:5), and the test tubes were further incubated in a 37°C water bath for 1 hour. The test tubes were then centrifuged at 2500 r / min for 5 minutes, and the supernatant was collected. The absorbance values of each test tube were measured at 545 nm using a spectrophotometer. The hemolysis rate was calculated as follows: (sample absorbance - positive control absorbance) / (negative control absorbance - positive control absorbance). If the hemolysis rate is less than 5%, the coating meets the hemolysis rate requirements for medical materials.

[0157] (3) Rabbit extracorporeal circulation experiment

[0158] The rabbit arteriovenous shunt model was used for the extracorporeal circulation experiment. Before anesthesia, 0.2 mg of scopolamine was injected intramuscularly. Anesthesia was induced by intramuscular injection of droperidol 5 mg and ketamine 20 mg / kg. Propofol, fentanyl, and scoline were injected into the ear vein to maintain anesthesia. After successful anesthesia, tracheal intubation was performed. After anesthesia, the right femoral artery and left femoral vein were exposed, and then the blood was introduced into the extracorporeal circulation pipeline to establish an arteriovenous shunt model. After 12 hours of circulation, the extracorporeal circulation pipeline was removed, and the incision was sutured. The adhesion of whole blood on the inner surface of the pipeline was observed under SEM.

[0159] 10. Coating wash-off resistance test

[0160] The mechanical stability of the hydrogel coating is verified by an in-vitro circulation experiment by peristaltic pump. Under the action of the peristaltic pump, the inner surface of the pipeline is flushed by PBS solution at a flow rate of 3 mL / s. At different time points, the sample is taken, and the change of the friction coefficient of the sample surface is measured to determine the flushing resistance of the coating.

[0161] The composite coating of the present application has super-lubricating and anti-thrombosis and anti-corrosion properties, and is suitable for surface modification of various medical devices in contact with blood and natural cavities of human body, including but not limited to: metal materials in contact with blood, such as vascular stents, pacemaker electrodes, mechanical valves, etc.; polymer materials in contact with blood, such as artificial blood vessels, hemodialysis pipelines, central venous catheters, etc.; devices in contact with natural cavities of human body, such as urinary catheters, tracheal intubation tubes, bronchoscopes, gastric tubes, intestinal stents, biliary drainage tubes, reproductive tract intervention devices, etc.

[0162] The above describes the preferred embodiments of the present application in detail, but the present application is not limited to the specific details in the above embodiments, and various simple modifications can be made to the technical solutions of the present application within the technical concept of the present application, and these simple modifications all belong to the protection scope of the present application.

Claims

1. A super-slippery, anti-corrosion, and anti-coating hydrogel composite coating for the surface of medical devices, characterized in that, The composite coating consists of N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide primer and hydrophilic polymer hydrogel grafted onto it, with a total coating thickness of 10-220 μm. The hydrophilic polymer hydrogel is a copolymer of hydrophilic monomers with chemical crosslinking agents and physical crosslinking agents, wherein the chemical crosslinking agent accounts for 3%-13% of the mass percentage of the hydrophilic monomers; and the physical crosslinking agent accounts for 3%-30% of the mass percentage of the hydrophilic monomers. The hydrophilic monomer is at least one of zwitterionic monomers, N-vinylpyrrolidone, and acrylamide; the chemical crosslinking agent is at least one of N,N-methylenebisacrylamide, N,N-bis(acryloyl)cysteine, ethylene glycol dimethacrylate, and carboxylate betaine dimethacrylate; the physical crosslinking agent is N-acryloylglycine; and the zwitterionic monomer is at least one of methacryloylethyl sulfobetaine, 2-methacryloyloxyethyl phosphoric acid choline, and carboxylate betaine methacrylate.

2. The super-slippery, anti-corrosion, and anticoagulant hydrogel composite coating for medical device surfaces according to claim 1, characterized in that, The thickness of the N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide primer layer is 5-20 μm, and the thickness of the hydrophilic polymer hydrogel layer is 5-200 μm.

3. The super-slippery, anti-corrosion, and anti-coating hydrogel composite coating for medical device surfaces according to claim 1, characterized in that, The preparation method of N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide is as follows: 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethylcarboimide, and N-hydroxysuccinimide are dissolved in a solution and stirred at room temperature for 2-5 h to activate the carboxyl group; after activation, triethylamine and dopamine hydrochloride are added to the solution and reacted for 20-28 h; after the reaction is completed, deionized water is added to precipitate the product, centrifuged, the supernatant is removed, washed twice, centrifuged again, and the collected product is obtained; wherein the molar ratio of 2-benzoylbenzoic acid, 1-(3-dimethylaminopropyl)-3-ethylcarboimide, N-hydroxysuccinimide, triethylamine, and dopamine hydrochloride is 1:1.1:1.1:1:1.

2.

4. The method for preparing the super-slippery, anti-corrosion, and anti-coating hydrogel composite coating on the surface of a medical device as described in any one of claims 1-3, characterized in that, The process includes the following two steps: First, N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide is deposited on the substrate surface to introduce a primer containing benzophenone groups onto the substrate surface; Second, a hydrophilic polymer hydrogel is grafted onto the primer surface using a photoinitiator-initiated polymerization method.

5. The method for preparing the super-slippery, anti-corrosion, and anticoagulant hydrogel composite coating on the surface of a medical device according to claim 4, characterized in that, The method for depositing the primer in the first step is as follows: The substrate is immersed in an organic solvent solution of N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide. After 5-40 hours, the surface is rinsed with deionized water and then dried with nitrogen gas, thus depositing the N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide primer on the surface. The organic solvent is at least one of dimethyl sulfoxide, dimethylformamide, and dichloromethane. The mass percentage concentration of the organic solvent solution of N-(3,4-dihydroxyphenylethyl)-2-benzoylbenzamide is 0.1%-1%. The second step is to immerse the surface with the deposited primer into a hydrophilic polymer hydrogel prepolymer solution and initiate polymerization under 365 nm ultraviolet light for 5-40 minutes; the hydrophilic polymer hydrogel prepolymer solution is a mixed aqueous solution of hydrophilic monomers, chemical crosslinking agents, physical crosslinking agents and photoinitiators.

6. The method for preparing the super-slippery, anti-corrosion, and anti-coating hydrogel composite coating on the surface of a medical device according to claim 5, characterized in that, In the hydrogel prepolymer solution, the mass concentration of the hydrophilic monomer in water is 10%-60%, the chemical crosslinking agent accounts for 3%-13% of the mass percentage of the hydrophilic monomer, the physical crosslinking agent accounts for 3%-30% of the mass percentage of the hydrophilic monomer, and the photoinitiator accounts for 0.5%-20% of the mass percentage of the hydrophilic monomer; the photoinitiator is at least one of Irgacure 2959 and α-ketoglutaric acid.

7. The application of the super-slippery, anti-corrosion, and anticoagulant hydrogel composite coating for medical device surfaces as described in any one of claims 1-3 or the super-slippery, anti-corrosion, and anticoagulant hydrogel composite coating for medical device surfaces prepared by the preparation method described in any one of claims 4-6 in the preparation of medical devices that come into contact with blood and with the natural cavities of the human body.

8. The application of the super-slippery, anti-corrosion, and anticoagulant hydrogel composite coating on the surface of medical devices according to claim 7 in the preparation of medical devices that come into contact with blood and with natural human cavities, characterized in that, The substrate surface material of the medical device is metal, polymer, or inorganic material.

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