A multifunctional medical device coating and methods of making and using the same

Abstract

The application discloses a kind of composite function medical instrument coating and its preparation method and application, it is related to medical instrument coating preparation technical field.The method includes the following steps: acrylamide is subjected to radical polymerization, and linear quaternary polyacrylamide copolymer is prepared;Glycidyl methacrylate is added, and modified polyacrylamide copolymer is prepared;Polyvinylpyrrolidone is added, and coating composition is prepared;Coating is applied on the surface of pretreated substrate, and heating is cured, and composite function medical instrument coating is prepared.The application endows coating with superlubricity, long-acting antibacterial, high-efficiency anticoagulation, high adhesion, body fluid immersion stability and other comprehensive performance.It fundamentally solves the technical problems of weak adhesion, easy swelling and falling off, fast functional attenuation and insufficient biocompatibility of existing coating.

Description

Technical Field

[0001] This invention relates to the field of medical device coating preparation technology, specifically to a composite functional medical device coating, its preparation method, and its application. Background Technology

[0002] Interventional and implantable medical devices come into long-term contact with human blood and tissue fluid during clinical use. The surface lubricity, antibacterial properties, anticoagulant properties, biocompatibility, coating adhesion, and long-term stability directly determine their clinical safety and service life.

[0003] Existing hydrophilic antibacterial and anticoagulant coatings for medical devices mostly use single polyacrylamide, single PVP, or a simple physical blend of the two, which has significant drawbacks. Pure polyacrylamide has excellent hydrophilicity but weak antibacterial and anticoagulant properties, and its molecular chain rigidity is insufficient, leading to swelling, peeling, and detachment after prolonged immersion in body fluids. Pure PVP has better antibacterial properties but low mechanical strength and poor interfacial adhesion to the substrate. Physical mixing of the two easily leads to phase separation, resulting in uneven coating performance, rapid functional decay, and an inability to simultaneously achieve lubrication, antibacterial, and anticoagulant functions. Existing modification technologies often involve direct copolymerization with functional monomers containing double bonds, which involves adding functional monomers before polymerization. This results in poor molecular structure tunability, uncontrollable grafting sites, and a single cross-linking method. Furthermore, conventional coatings rely solely on single cross-linking of double bonds, lacking an epoxy interfacial anchoring structure, leading to weak chemical bonding between the coating and the substrate. This results in easy delamination after prolonged immersion, easy loss of functional additives, and insufficient antibacterial and anticoagulant effectiveness. Therefore, a new technology is urgently needed to fundamentally solve the industry's technical challenges of weak coating adhesion, easy swelling and detachment, rapid functional decay, and insufficient biocompatibility. Summary of the Invention

[0004] To address the aforementioned technical problems, the present invention aims to provide a composite functional medical device coating, its preparation method, and its application, thereby solving the problem of poor performance of existing thermosetting coatings for medical devices.

[0005] The technical solution of this invention to solve the above-mentioned technical problems is as follows: A method for preparing a coating for a composite functional medical device is provided, comprising the following steps: (1) Acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, and β-hydroxyethyl acrylate-heparin ester were dissolved in deionized water and subjected to free radical polymerization. The mixture was cooled to room temperature, purified, and dried to obtain a linear quaternary polyacrylamide copolymer. (2) The linear quaternary polyacrylamide copolymer obtained in step (1) is dispersed in a solution to obtain a dispersion, glycidyl methacrylate is added, and the reaction is carried out at a constant temperature. After purification and drying, the modified polyacrylamide copolymer is obtained. (3) Dissolve the modified polyacrylamide copolymer obtained in step (2) in a mixed solvent, then add polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer, stir evenly to obtain a coating composition; (4) Pre-treat the substrate to obtain a pre-treated substrate, then coat the surface of the pre-treated substrate with the coating composition obtained in step (3), then heat and cure, and finally clean and dry to obtain a composite functional medical device coating.

[0006] Based on the above technical solution, the present invention can be further improved as follows: Further, in step (1), the mass ratio of acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, β-hydroxyethyl acrylate-heparin ester and deionized water is 60-70:15-20:8-12:3-5:100-120.

[0007] Furthermore, in step (1), when carrying out the free radical polymerization reaction, the pH value is adjusted to 6.5-7.5, the temperature is raised to 60-70℃, an initiator is added, and a constant temperature free radical polymerization reaction is carried out for 4-6 hours.

[0008] Furthermore, the initiator is a mixture of ammonium persulfate and sodium bisulfite.

[0009] Furthermore, the mass ratio of acrylamide to initiator is 60-70:0.5-1.

[0010] Furthermore, in step (1), a dialysis bag with a molecular weight cutoff of 10,000 is used for dialysis purification for 72 hours to complete the purification process.

[0011] Furthermore, in step (1), the product is vacuum dried at 60 °C.

[0012] Furthermore, in step (2), the concentration of the linear quaternary polyacrylamide copolymer in the dispersion is 10-15 wt%.

[0013] Furthermore, in step (2), the solution is an ethanol solution with a concentration of 30 wt%.

[0014] Furthermore, in step (2), the mass of glycidyl methacrylate is 5-12% of the mass of the linear quaternary polyacrylamide copolymer.

[0015] Furthermore, in step (2), when carrying out the constant temperature reaction, the pH value is adjusted to 7.5-8.5, the temperature is raised to 55-65℃, and the reaction is carried out at a constant temperature with stirring for 3-5 hours.

[0016] Furthermore, in step (2), dialysis is used to complete the purification process.

[0017] Furthermore, in step (2), the product is vacuum dried at 60 °C.

[0018] Furthermore, in step (3), the mass ratio of the modified polyacrylamide copolymer, mixed solvent, polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer is 24-40:15-25:25-40:8-15:2-4:0.4-0.6:0.1-0.3. Furthermore, the mixed solvent is a mixture of ethanol and deionized water in a volume ratio of 2:1.

[0019] Furthermore, the crosslinking agent is polyethylene glycol diacrylate.

[0020] Furthermore, the thermal initiator is benzoyl peroxide.

[0021] Furthermore, the accelerator is dimethylaniline.

[0022] Furthermore, the defoamer is silicone.

[0023] Furthermore, in step (3), the coating composition is prepared under conditions of 5-30℃ and 400-600 r / min.

[0024] Furthermore, in step (3), stir for 60-90 minutes.

[0025] Furthermore, in step (4), the pretreatment includes: ultrasonically cleaning the substrate with acetone and anhydrous ethanol in sequence, then rinsing with deionized water and drying; or the pretreatment is: plasma surface activation treatment, ozone activation or silane coupling agent base treatment.

[0026] Furthermore, in step (4), coating is performed by dip coating or spray coating.

[0027] Furthermore, in step (4), the coating thickness of the dry film is controlled to be 8-22 μm.

[0028] Furthermore, in step (4), after coating, the mixture is left to stand at room temperature for 10-15 minutes to allow it to naturally defoam.

[0029] Furthermore, in step (4), the temperature is first kept at 80-90℃ for 30-40 min, and then the temperature is raised to 110-130℃ and kept for 60-90 min to complete the heating and curing process.

[0030] Furthermore, in step (4), the product is vacuum dried at 60-70℃ for 15-20 min.

[0031] The present invention also provides a composite functional medical device coating prepared by the above-mentioned method for preparing the composite functional medical device coating.

[0032] The present invention also provides the application of the above-mentioned composite functional medical device coating in the preparation of medical devices.

[0033] The present invention has the following beneficial effects: 1. The molecular structure is characterized by the polyacrylamide main chain maintaining its original structure. After the side chain amide group undergoes ring-opening addition with GMA, the three-membered epoxy ring completely disappears and is transformed into a flexible hydroxyl spacer segment. The molecular side chain only retains carbon-carbon double bonds that can participate in thermosetting crosslinking. There is no residual epoxy structure, and subsequent thermosetting crosslinking is achieved solely by dangling double bonds.

[0034] 2. This invention maintains a fixed type and amount of acrylamide monomer without any substitutions or adjustments. It first prepares a linear backbone by free radical copolymerization with hydrophilic, antibacterial, and anticoagulant functional monomers. After polymerization, polymerizable carbon-carbon double-bond dual-functional groups are introduced into the polyacrylamide side chains via chemical grafting. These side-chain double bonds participate in thermosetting free radical crosslinking, endowing the coating with comprehensive properties such as super-lubricity, long-lasting antibacterial effect, high-efficiency anticoagulation, high adhesion, and stability against immersion in body fluids. This makes it suitable for surface modification of implantable and interventional medical devices that come into direct contact with human blood and tissue fluid, such as vascular interventional catheters, cardiac stents, and artificial valves. It fundamentally solves the industry's technical problems of weak coating adhesion, easy swelling and peeling, rapid functional decline, and insufficient biocompatibility.

[0035] 3. Core Innovation Points: Molecular design innovation: polymerization first, grafting later; first copolymerize to form a macromolecular backbone, and then graft functional groups to the sides in the post-modification stage, without destroying the original copolymer composition and hydrophilic, antibacterial and anticoagulant functional structure, and the grafting sites are controllable and the structure is regular.

[0036] Innovation in side-chain functional structure: Carbon-carbon double bonds are introduced, and glycidyl methacrylate (GMA) is selected as the post-grafting agent. After copolymerization, polymerizable carbon-carbon double bonds are introduced into the PAM side chain. Innovative curing mechanism: After copolymerization modification, each polymer chain uniformly carries suspended active double bonds. During the thermosetting stage, it can undergo free radical multi-point cross-linking with bifunctional cross-linking agents and PVP molecules to form a high-density three-dimensional interpenetrating network, which significantly improves the coating's density, wear resistance, swelling resistance, and interfacial adhesion.

[0037] The formulation and process are compatible and innovative: the original comonomer ratio, polymerization conditions, coating composition formulation, coating and step-by-step curing parameters are all retained, and only the post-polymerization side-linking double bond process is added. The process changes are small, easy to scale up, and suitable for industrial production.

[0038] Long-lasting performance innovation: The double-bond cross-linked network is highly dense, which can firmly lock the hydrophilic, antibacterial, and anticoagulant functional groups on the molecular chain, inhibit the dissolution and loss of small molecule additives, and make the coating resistant to body fluid immersion, swelling, and peeling off. The antibacterial and anticoagulant properties are long-lasting and stable. Detailed Implementation

[0039] The principles and features of this invention are described below. The examples given are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer should be followed. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0040] The raw materials used in the following examples are: Acrylamide (AM), 2-acrylamide-2-methylpropanesulfonic acid (AMPS), methacryloyloxyethyltrimethylammonium chloride (DMC), β-hydroxyethyl acrylate-heparin ester (HEA-Hep), glycidyl methacrylate (GMA), polyvinylpyrrolidone (PVP-K90, molecular weight 60,000-120,000), polyethylene glycol diacrylate (PEGDA), benzoyl peroxide (BPO).

[0041] Example 1: A composite functional medical device coating, the preparation method of which includes the following steps: (1) Add deionized water to the reactor, purge with nitrogen to remove oxygen for 30 min, then add acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride and β-hydroxyethyl acrylate-heparin ester in sequence, and stir until completely dissolved; then adjust the pH to 7, raise the temperature to 65℃, add the initiator (a mixture of ammonium persulfate and sodium bisulfite), and carry out a constant temperature free radical polymerization reaction for 5 h, cool to room temperature, dialyze and purify using a dialysis bag with a molecular weight cutoff of 10000 for 72 h, and vacuum dry at 60 ℃ to obtain a linear quaternary polyacrylamide copolymer; The mass ratio of acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, β-hydroxyethyl acrylate-heparin ester and deionized water is 65:18:10:4:110. (2) The linear quaternary polyacrylamide copolymer obtained in step (1) was dispersed in a solution (ethanol solution with a concentration of 30 wt%) to obtain a dispersion (the concentration of the linear quaternary polyacrylamide copolymer was 12 wt%). Glycidyl methacrylate (mass of 8% of the mass of the linear quaternary polyacrylamide copolymer) was added, the pH value was adjusted to 8, the temperature was raised to 60℃, and the reaction was stirred at a constant temperature for 4 h. After the reaction was completed, unreacted GMA and by-product small molecules were removed by dialysis, and the modified polyacrylamide copolymer was obtained by vacuum drying at 60 ℃. (3) At 25°C and 500 r / min, the modified polyacrylamide copolymer obtained in step (2) was dissolved in a mixed solvent (a mixture of ethanol and deionized water in a volume ratio of 2:1), and then polyvinylpyrrolidone, crosslinking agent (polyethylene glycol diacrylate), thermal initiator (benzoyl peroxide), accelerator (dimethylaniline) and defoamer (silicone) were added and stirred for 80 min to obtain the coating composition; The mass ratio of the modified polyacrylamide copolymer, mixed solvent, polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer is 32:20:35:12:3:0.5:0.2. (4) Pre-treatment of the substrate, including ultrasonic cleaning of the substrate with acetone and anhydrous ethanol in sequence, followed by rinsing with deionized water and drying to obtain a pre-treated substrate. Then, the coating composition obtained in step (3) is applied to the surface of the pre-treated substrate by dip coating, and the dry film thickness is controlled to be 8-22 μm. After coating, the substrate is left to stand at room temperature for 10 min to naturally defoam, and then heated and cured. Specifically, the first step is low temperature pre-curing: 85℃ for 30 min to form a preliminary entanglement and weak cross-linking network; the second step is high temperature final curing: the temperature is raised to 120℃ for 60 min, and the side chain carbon-carbon double bonds undergo free radical cross-linking with the cross-linking agent and PVP to construct a dense three-dimensional interpenetrating network. Finally, the substrate is ultrasonically cleaned with deionized water for 8 min to remove uncured small molecules and residual additives on the surface, and then placed in a vacuum drying oven at 65℃ for 18 min to dry and cool to room temperature to obtain a composite functional medical device coating.

[0042] Example 2: A composite functional medical device coating, the preparation method of which includes the following steps: (1) Add deionized water to the reactor, purge with nitrogen to remove oxygen for 30 min, then add acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride and β-hydroxyethyl acrylate-heparin ester in sequence, and stir until completely dissolved; then adjust the pH to 6.5, raise the temperature to 60℃, add the initiator (a mixture of ammonium persulfate and sodium bisulfite), and carry out a constant temperature free radical polymerization reaction for 6 h, cool to room temperature, dialyze and purify using a dialysis bag with a molecular weight cutoff of 10000 for 72 h, and vacuum dry at 60 ℃ to obtain a linear quaternary polyacrylamide copolymer; The mass ratio of acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, β-hydroxyethyl acrylate-heparin ester and deionized water is 60:15:8:3:100. (2) The linear quaternary polyacrylamide copolymer obtained in step (1) was dispersed in a solution (ethanol solution with a concentration of 30 wt%) to obtain a dispersion (the concentration of the linear quaternary polyacrylamide copolymer was 10 wt%). Glycidyl methacrylate (mass of 5% of the mass of the linear quaternary polyacrylamide copolymer) was added, the pH value was adjusted to 7.5, the temperature was raised to 55℃, and the reaction was stirred at a constant temperature for 5 h. After the reaction was completed, unreacted GMA and by-product small molecules were removed by dialysis, and the modified polyacrylamide copolymer was obtained by vacuum drying at 60 ℃. (3) At 5℃ and 400 r / min, the modified polyacrylamide copolymer obtained in step (2) was dissolved in a mixed solvent (a mixture of ethanol and deionized water in a volume ratio of 2:1), and then polyvinylpyrrolidone, crosslinking agent (polyethylene glycol diacrylate), thermal initiator (benzoyl peroxide), accelerator (dimethylaniline) and defoamer (silicone) were added and stirred for 60 min to obtain the coating composition; The mass ratio of the modified polyacrylamide copolymer, mixed solvent, polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer is 24:15:25:8:2:0.4:0.1. (4) Pre-treatment of the substrate includes: ultrasonic cleaning of the substrate with acetone and anhydrous ethanol in sequence, followed by rinsing with deionized water and drying to obtain a pre-treated substrate. Then, the coating composition obtained in step (3) is applied to the surface of the pre-treated substrate by dip coating, and the dry film thickness is controlled to be 8-22 μm. After coating, the substrate is left to stand at room temperature for 10 min to naturally defoam, and then heated and cured. Specifically, the first step is low temperature pre-curing: 80℃ for 30 min to form a preliminary entanglement and weak cross-linking network; the second step is high temperature final curing: the temperature is raised to 110℃ for 60 min, and the side chain carbon-carbon double bonds and cross-linking agents and PVP undergo free radical cross-linking to construct a dense three-dimensional interpenetrating network. Finally, the substrate is ultrasonically cleaned with deionized water for 5 min to remove uncured small molecules and residual additives on the surface. The substrate is then placed in a vacuum drying oven at 60℃ for 20 min to dry and cooled to room temperature to obtain a composite functional medical device coating.

[0043] Example 3: A composite functional medical device coating, the preparation method of which includes the following steps: (1) Add deionized water to the reactor, purge with nitrogen for 30 min to remove oxygen, then add acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride and β-hydroxyethyl acrylate-heparin ester in sequence, and stir until completely dissolved; then adjust the pH to 7.5, raise the temperature to 70℃, add the initiator (a mixture of ammonium persulfate and sodium bisulfite), and carry out a constant temperature free radical polymerization reaction for 4 h, cool to room temperature, dialyze and purify using a dialysis bag with a molecular weight cutoff of 10000 for 72 h, and vacuum dry at 60 ℃ to obtain a linear quaternary polyacrylamide copolymer; The mass ratio of acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, β-hydroxyethyl acrylate-heparin ester and deionized water is 70:20:12:5:120. (2) The linear quaternary polyacrylamide copolymer obtained in step (1) was dispersed in a solution (ethanol solution with a concentration of 30 wt%) to obtain a dispersion (the concentration of the linear quaternary polyacrylamide copolymer was 15 wt%). Glycidyl methacrylate (mass of 12% of the mass of the linear quaternary polyacrylamide copolymer) was added, the pH value was adjusted to 8.5, the temperature was raised to 65℃, and the reaction was stirred at a constant temperature for 3 h. After the reaction was completed, unreacted GMA and by-product small molecules were removed by dialysis, and the modified polyacrylamide copolymer was obtained by vacuum drying at 60 ℃. (3) At 30°C and 600 r / min, the modified polyacrylamide copolymer obtained in step (2) was dissolved in a mixed solvent (a mixture of ethanol and deionized water in a volume ratio of 2:1), and then polyvinylpyrrolidone, crosslinking agent (polyethylene glycol diacrylate), thermal initiator (benzoyl peroxide), accelerator (dimethylaniline) and defoamer (silicone) were added and stirred for 90 min to obtain the coating composition; The mass ratio of the modified polyacrylamide copolymer, mixed solvent, polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer is 40:25:40:15:4:0.6:0.3. (4) Pre-treatment of the substrate, including ultrasonic cleaning of the substrate with acetone and anhydrous ethanol in sequence, followed by rinsing with deionized water and drying to obtain a pre-treated substrate. Then, the coating composition obtained in step (3) is applied to the surface of the pre-treated substrate by spraying, and the dry film thickness is controlled to be 8-22 μm. After coating, the substrate is left to stand at room temperature for 15 min to naturally defoam, and then heated and cured. Specifically, the first step is low temperature pre-curing: 90℃ for 40 min to form a preliminary entanglement and weak cross-linking network; the second step is high temperature final curing: the temperature is raised to 130℃ for 90 min, and the side chain carbon-carbon double bonds and cross-linking agents and PVP undergo free radical cross-linking to construct a dense three-dimensional interpenetrating network. Finally, the substrate is ultrasonically cleaned with deionized water for 10 min to remove uncured small molecules and residual additives on the surface, and then placed in a vacuum drying oven at 70℃ for 15 min to dry and cool to room temperature to obtain a composite functional medical device coating.

[0044] Comparative Example 1: A medical device coating, the preparation method of which includes the following steps: In step (3), the modified polyacrylamide copolymer was replaced with PAM (polyacrylamide), that is, PAM and PVP were physically blended to obtain a coating composition. The rest was the same as in Example 1 to obtain a medical device coating.

[0045] Comparative Example 2: A medical device coating, the preparation method of which includes the following steps: Excluding step (2), the rest is the same as in Example 1, and a medical device coating is obtained.

[0046] Test case I. The experimental method is as follows: 1. Surface lubricity (coefficient of sliding friction) Test standard: Refer to YYT1898-2024 Test method for adhesion of hydrophilic coating on intravascular catheters and guidewires; Testing instrument: Medical coating friction coefficient tester; Test method: Fix each group of coating samples on the test platform, use a stainless steel simulated conduit probe, load 5g, sliding speed 5mm / s, test in room temperature dry state and simulated wet state (physiological saline wetting) respectively, and perform 5 parallel tests for each group and take the average value.

[0047] 2. Antibacterial properties and long-lasting antibacterial stability Test standard: Refer to GB / T 31402-2023 Determination of antibacterial activity of plastics and other non-porous materials surfaces; Tested bacterial strains: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa; Test method: The film-applied method was used to test the immediate antibacterial rate in the first 24 hours; the samples were then immersed in simulated body fluid at 37℃ for 72 hours, 7 days, and 30 days, and the antibacterial rate was retested after removal.

[0048] 3. Anticoagulant and antiplatelet adsorption properties Prothrombin time (PT): Using a fully automated coagulation analyzer, the coated sample was co-incubated with fresh rabbit plasma to determine the prothrombin time, and the extension rate was calculated by comparing it with the blank substrate. Platelet adsorption: The sample was incubated with platelet-rich plasma using an enzyme-linked immunosorbent assay (ELISA). After washing, the number of residual platelets on the surface was measured, and the platelet adsorption reduction rate was calculated.

[0049] 4. Stability and performance degradation under immersion in body fluids Simulated body fluid: physiological saline, prepared to simulate human tissue fluid, pH=7.35-7.45, and soaked at a constant temperature of 37℃ for 30 days; Test indicators: Observe whether the coating swells, peels, or flakes off; test the changes in friction coefficient and antibacterial rate before and after immersion, and calculate the performance degradation rate.

[0050] 2. The coatings prepared in Example 1 and Comparative Examples 1-2 were subjected to performance testing, and the results are shown in Tables 1-4.

[0051] Table 1. Friction coefficient and macroscopic state after 30 days of immersion

[0052] Table 2 Antibacterial performance test data (antibacterial rate %)

[0053] Table 3 Anticoagulant and antiplatelet properties

[0054] Table 4. Overall performance degradation rate after 30 days of immersion

[0055] As can be seen from Tables 1-4: 1. Lubrication performance analysis The friction coefficient of Example 1 of this invention is only 0.028, which is much lower than that of Comparative Example 1 (0.085) and Comparative Example 2 (0.052). The reason is that a high-density three-dimensional interpenetrating network is constructed by first copolymerizing and then grafting double bonds, the PAM and PVP molecular chains are tightly entangled, and the hydrophilic groups on the surface are uniformly enriched to form a stable hydrated layer; while in physical blending Comparative Example 1, there is phase separation and the surface hydrophilic structure is uneven; the conventional copolymerization Comparative Example 2 has a loose crosslinking network, poor stability of the hydrated layer, and its lubricity is not as good as that of this invention.

[0056] 2. Analysis of long-lasting antibacterial effect In Example 1, the initial antibacterial rate was close to 99.7% or higher, and remained above 99.4% after 72 hours of immersion, showing almost no attenuation. In Comparative Example 1, the small antibacterial molecules from the physical blend were easily precipitated and lost, and the antibacterial rate dropped significantly to 60%-65% after 72 hours. In Comparative Example 2, the conventional copolymer crosslinking sites were disordered, and functional groups were easily migrated and lost, resulting in significant attenuation of antibacterial properties. The thermosetting crosslinking of the side chain double bonds in this invention can lock the antibacterial functional groups, inhibit the dissolution of small molecules, and achieve long-lasting antibacterial effect.

[0057] 3. Analysis of anticoagulant and antiplatelet properties Example 1 showed that coagulation time was prolonged by 48% and platelet adsorption was reduced by 82%, which was far superior to the two control groups. The HEA-Hep heparin anticoagulant units were fixed by a dense cross-linked network and were not easily detached or lost; the heparin in the physical blending group was easy to precipitate and had weak interfacial binding; the conventional copolymerization group had poor molecular structure regularity, uneven distribution of anticoagulant groups, and limited anticoagulant effect.

[0058] 4. Analysis of Immersion Stability and Adhesion After 30 days of immersion in simulated body fluids, Example 1 showed no swelling or peeling, with a performance degradation of only 3.2%. Comparative Example 1 exhibited severe phase separation, with molecular chains easily swelling, resulting in a degradation of up to 28.6% and peeling. Comparative Example 2 showed insufficient cross-linking network density, still exhibiting slight swelling and performance degradation. This verifies that the molecular design of this invention, involving polymerization followed by grafting and thermosetting multi-point cross-linking, can significantly improve coating density, interfacial anchoring force, and long-term stability.

[0059] 5. Overall validation conclusions of the control group Comparative Example 1: Pure PAM / PVP physical blend: phase separation exists, weak lubrication / antibacterial / anticoagulation properties, and extremely poor long-term stability; Comparative Example 2: Conventional double bond direct copolymerization: The performance is better than that of the physical blend group, but the grafting sites are uncontrollable, the crosslinking network is loose, and the functional groups are easily lost. The overall performance and long-term effect are significantly lower than those of Example 1 of the present invention. This fully verifies the innovation and technical superiority of the molecular design, side linking modification, and thermosetting crosslinking mechanism of the present invention, which can meet the long-term use requirements of high-end medical devices such as vascular intervention and cardiac stents.

[0060] Example 1 Performance Test: Sliding friction coefficient 0.028; antibacterial rates against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa were 99.9%, 99.8%, and 99.7%, respectively, and the antibacterial rate remained at 99.6% after 72 h of immersion; prothrombin time was prolonged by 48%, and platelet adsorption decreased by 82%; after immersion in simulated body fluid for 30 days, there was no swelling or detachment, and the performance degradation was only 3.2%.

[0061] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a coating for a composite functional medical device, characterized in that, Includes the following steps: (1) Acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, and β-hydroxyethyl acrylate-heparin ester were dissolved in deionized water and subjected to free radical polymerization. The mixture was cooled to room temperature, purified, and dried to obtain a linear quaternary polyacrylamide copolymer. (2) The linear quaternary polyacrylamide copolymer obtained in step (1) is dispersed in a solution to obtain a dispersion, glycidyl methacrylate is added, and the reaction is carried out at a constant temperature. After purification and drying, the modified polyacrylamide copolymer is obtained. (3) Dissolve the modified polyacrylamide copolymer obtained in step (2) in a mixed solvent, then add polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer, stir evenly to obtain a coating composition; (4) Pre-treat the substrate to obtain a pre-treated substrate, then coat the surface of the pre-treated substrate with the coating composition obtained in step (3), then heat and cure, and finally clean and dry to obtain a composite functional medical device coating.

2. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (1), the mass ratio of acrylamide, 2-acrylamide-2-methylpropanesulfonic acid, methacryloyloxyethyltrimethylammonium chloride, β-hydroxyethyl acrylate-heparin ester and deionized water is 60-70:15-20:8-12:3-5:100-120.

3. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (1), when carrying out the free radical polymerization reaction, the pH value is adjusted to 6.5-7.5, the temperature is raised to 60-70℃, an initiator is added, and the free radical polymerization reaction is carried out at a constant temperature for 4-6 hours.

4. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (2), the concentration of the linear quaternary polyacrylamide copolymer in the dispersion is 10-15 wt%.

5. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (2), when carrying out the constant temperature reaction, adjust the pH value to 7.5-8.5, raise the temperature to 55-65℃, and stir the reaction at a constant temperature for 3-5 hours.

6. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (3), the mass ratio of modified polyacrylamide copolymer, mixed solvent, polyvinylpyrrolidone, crosslinking agent, thermal initiator, accelerator and defoamer is 24-40:15-25:25-40:8-15:2-4:0.4-0.6:0.1-0.

3.

7. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (4), the pretreatment includes: ultrasonically cleaning the substrate with acetone and anhydrous ethanol in sequence, then rinsing with deionized water and drying.

8. The method for preparing the composite functional medical device coating according to claim 1, characterized in that, In step (4), first keep the temperature at 80-90℃ for 30-40 min, then raise the temperature to 110-130℃ and keep it at 60-90 min to complete the heating and curing process.

9. The composite functional medical device coating prepared by the method of preparing the composite functional medical device coating according to any one of claims 1-8.

10. The application of the composite functional medical device coating according to claim 9 in the preparation of medical devices.

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