A super-stable antibiofouling coating and its preparation method and application

Abstract

The application discloses an ultrastable antibioadhesion coating and a preparation method and application thereof, and belongs to the technical field of functional materials. The coating provided by the application comprises an A component and a B component; the A component comprises nanoparticles, carboxyl silicone oil, a silane coupling agent and a solvent; the B component comprises a base material and a solvent; the nanoparticles comprise at least one of silicon nanoparticles, iron nanoparticles or zinc nanoparticles; and the base material comprises an epoxy resin. The carboxyl silicone oil and the functionalized nanoparticles are combined through cooperation of the A component and the B component and are embedded in the base material, so that the prepared coating can be used for preparing the ultrastable antibioadhesion coating, the stability and durability of the coating are good, and the coating can effectively reduce adhesion of blood components, proteins, bacteria and cells and the like, and the coating and the prepared coating have good application prospects in implantable medical devices.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of functional materials, and particularly relates to an ultra-stable anti-bioadhesion coating and a preparation method and application thereof. BACKGROUND

[0002] Although certain progress has been made in the field of implantable medical devices, such as cardiac pacemakers, venous filters and hemodialysis devices, there are still significant limitations and shortcomings. These devices often encounter problems such as thrombosis, biological contamination and infection when in direct contact with blood or biological tissues, leading to functional failure and increased clinical risk. Existing technologies attempt to reduce these adverse reactions through methods such as anticoagulant coatings, antibacterial coatings, superhydrophobic / superoleophobic coatings and lubricant-infused porous surfaces (SLIPS), but their effectiveness and stability are limited. Among them, anticoagulant coatings, such as heparin coatings, can reduce the direct contact of blood with the device surface and reduce the risk of thrombosis, but they may lose effectiveness over time and need to be replaced or supplemented regularly to maintain their effectiveness. Antibacterial coatings reduce bacterial adhesion and biofilm formation by adding antibacterial substances to the device surface, but they also need to be replaced or supplemented regularly, and their long-term accumulation can cause inflammatory reactions. Superhydrophobic / superoleophobic coatings can reduce protein and cell adhesion, but the effect is limited, and complex preparation processes may be required, and their stability in dynamic fluid environments is poor. SLIPS technology reduces the adhesion of biological substances by infusing lubricating liquid into porous surfaces, thus exhibiting certain anti-adhesion properties, however, this structure is relatively complex to prepare, and the lubricating liquid may be lost in a fluid environment, resulting in the failure of the coating function.

[0003] The limitations of the above-mentioned coatings are mainly due to the instability, lack of durability, biocompatibility problems and complexity of the preparation process of the coatings. The coatings may fall off or lose effectiveness after long-term implantation or frequent use, leading to a decrease in antithrombotic and anti-contamination properties. Certain coating materials may cause inflammatory reactions or long-term accumulation in the body, leading to adverse consequences. In addition, the preparation process of some high-performance coatings is complex and costly, limiting their widespread application in medical devices. Therefore, it is of great significance to develop a surface modification method that can provide a more stable, durable and biocompatible surface to reduce thrombosis and biological contamination of implantable medical devices. Such a coating technology needs to be able to maintain the functionality and safety of the device without causing inflammation or tissue damage, thereby prolonging the service life of the device and improving its clinical effectiveness. SUMMARY

[0004] In order to overcome at least one of the problems existing in the prior art, one of the purposes of the present application is to provide a coating material with which a coating layer with good stability, durability and anti-adhesion can be prepared.

[0005] The second object of the present application is to provide a coating.

[0006] The third object of the present application is to provide a method for preparing the coating.

[0007] The fourth object of the present application is to provide a catheter.

[0008] The fifth object of the present application is to provide an implantable medical device.

[0009] To achieve the above objects, the present application adopts the following technical solutions:

[0010] The first aspect of the present application provides a coating, comprising A component and B component; the A component comprises nanoparticles, carboxyl silicone oil, silane coupling agent and solvent; the B component comprises matrix material and solvent; the nanoparticles comprise at least one of silicon nanoparticles, iron nanoparticles or zinc nanoparticles; the matrix material comprises epoxy resin; the solvent in the A component is the same as or different from the solvent in the B component.

[0011] In some embodiments of the present application, the matrix material is selected from epoxy resin.

[0012] In some embodiments of the present application, the nanoparticles are selected from silicon nanoparticles.

[0013] In the embodiments of the present application, epoxy resin is used as the matrix material, which can cooperate with the silicon nanoparticles to achieve good composite effect. However, the matrix material of the present application is not limited to epoxy resin, and other resins with smooth properties can also be used as the matrix material of the present application; the nanoparticles can also be iron nanoparticles or zinc nanoparticles.

[0014] Preferably, the mass ratio of the nanoparticles to the matrix material is 1:(10-25); further preferably 1:(12-20); more preferably 1:(14-18); for example, it can be any one of 1:14, 1:15, 1:16, 1:17, 1:18 or a range value formed by any two, such as 1:(15-17).

[0015] Preferably, the mass ratio of the nanoparticles to the carboxyl silicone oil is 1:(10-25); further preferably 1:(12-20); more preferably 1:(14-18); for example, it can be any one of 1:14, 1:15, 1:16, 1:17, 1:18 or a range value formed by any two, such as 1:(15-17).

[0016] Preferably, the mass ratio of the nanoparticles to the silane coupling agent is 1:(10-25); further preferably 1:(12-20); more preferably 1:(14-18); for example, it can be any one of 1:14, 1:15, 1:16, 1:17, 1:18 or a range value formed by any two of them, such as 1:(15-17).

[0017] Preferably, the A component comprises components in the following mass fractions: 0.1-1 parts of nanoparticles, 1-10 parts of carboxyl silicone oil, 1-10 parts of silane coupling agent and 3-20 parts of solvent; the B component comprises components in the following mass fractions: 1-10 parts of matrix material and 1-10 parts of solvent; the mass ratio of the A component to the B component is 1:(0.1-1).

[0018] Further preferably, the A component comprises components in the following mass fractions: 0.2-0.7 parts of nanoparticles, 2-8 parts of carboxyl silicone oil, 2-8 parts of silane coupling agent and 5-15 parts of solvent; the B component comprises components in the following mass fractions: 2-8 parts of matrix material and 2-8 parts of solvent; the mass ratio of the A component to the B component is 1:(0.2-0.8).

[0019] More preferably, the A component comprises components in the following mass fractions: 0.2-0.5 parts of nanoparticles, 4-6 parts of carboxyl silicone oil, 4-6 parts of silane coupling agent and 8-12 parts of solvent; the B component comprises components in the following mass fractions: 4-6 parts of matrix material and 4-6 parts of solvent; the mass ratio of the A component to the B component is 1:(0.4-0.6).

[0020] Preferably, the solvent in the A component and the solvent in the B component are each independently selected from ester solvents.

[0021] Preferably, the ester solvent is selected from C1-C10 ester solvents; further preferably, the ester solvent comprises at least one of methyl formate, ethyl formate, isopropyl formate, methyl acetate, ethyl acetate or isopropyl acetate; more preferably, the ester solvent is selected from ethyl acetate.

[0022] Preferably, the solvent in the A component and the solvent in the B component are the same and are both selected from ethyl acetate.

[0023] Preferably, the average particle size of the nanoparticles is 10-1000 nm; further preferably 15-300 nm; for example, it can be any one of 15 nm, 30 nm, 50 nm, 100 nm, 200 nm, 300 nm or a range value formed by any two of them, such as 30-100 nm.

[0024] Preferably, the A component further comprises an active drug.

[0025] In some embodiments of the present application, the active drug comprises an antibacterial drug, an anti-inflammatory drug, or a combination thereof.

[0026] The introduction of the active drug such as antibacterial drug, anti-inflammatory drug, and the like in the system of the present application is advantageous to provide a sustained drug release effect, thereby endowing the coating with more abundant functions.

[0027] The second aspect of the present application provides a coating prepared from the coating material according to the first aspect of the present application.

[0028] The third aspect of the present application provides a preparation method of the coating according to the second aspect of the present application, comprising the following steps: curing the coating material to obtain the coating; and the curing condition is: curing at 10-30°C for 12-36h; or curing at 35-100°C for 1-5h.

[0029] Preferably, the curing condition is: curing at 20-30°C for 12-36h; or curing at 35-95°C for 1-5h; further preferably, the curing condition is: curing at 23-27°C for 12-36h; or curing at 40-90°C for 1-5h; still further preferably, the curing condition is: curing at 23-27°C for 18-30h; or curing at 40-90°C for 2-4h.

[0030] The fourth aspect of the present application provides a catheter comprising a catheter substrate and a coating arranged on the surface of the catheter substrate; the coating is the coating according to the second aspect of the present application, or is prepared by the preparation method according to the third aspect of the present application.

[0031] Preferably, the material of the catheter substrate comprises at least one of metal, rubber, or plastic.

[0032] In some embodiments of the present application, the catheter substrate comprises at least one of polytetrafluoroethylene (PTFE), polyurethane (PU), or polycarbonate (PC); in some specific embodiments of the present application, the catheter substrate is selected from polycarbonate (PC).

[0033] The fifth aspect of the present application provides an implantable medical device comprising the coating according to the second aspect of the present application, or the catheter according to the fourth aspect of the present application.

[0034] In some embodiments of the present application, the implantable medical device comprises at least one of a cardiac pacemaker, a central venous catheter, a venous filter, or a hemodialysis device.

[0035] The beneficial effects of the present application are: in the A component of the present application, the nanoparticles capture and store silicone oil, thereby providing lubricity of the coating material; the silane coupling agent is used to functionalize the nanoparticles, enhancing their bonding force with the matrix material; the carboxyl silicone oil acts as a lubricant, reducing the friction coefficient of the coating surface, thereby improving its lubricity and anti-adhesion. The matrix material (such as epoxy resin) in the B component serves as a matrix, ensuring the stability and durability of the coating. Through the cooperation of the A component and the B component, the carboxyl silicone oil and the functionalized nanoparticles are combined and embedded in the matrix material, forming a coating that can be used to prepare an ultra-stable anti-bioadhesion coating. The coating has good stability, good durability, and can effectively reduce the adhesion of blood components, proteins, bacteria and cells, etc. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 Structural comparison chart of the solid-like smooth coating modified catheter and the conventional catheter prepared in Example 2.

[0037] Figure 2 Quantitative analysis chart of the amount of FITC-BSA and Fg adhered to the surface of the solid-like smooth coating modified catheter and the conventional catheter of Example 2.

[0038] Figure 3 Blood cell adhesion chart of the inner cavity of the solid-like smooth coating modified catheter and the conventional catheter of Example 2 after 2 hours of in-vitro blood circulation.

[0039] Figure 4 SEM chart of the blood cells adhered to the inner cavity surface of the solid-like smooth coating modified catheter and the conventional catheter of Example 2.

[0040] Figure 5 Thrombus weight, lumen blockage rate and blood flow rate of the solid-like smooth coating modified catheter and the conventional catheter of Example 2.

[0041] Figure 6 Blood compatibility test data of the solid-like smooth coating modified catheter and the conventional catheter of Example 2.

[0042] Figure 7 Fluorescence image of the anti-pollution performance test of the solid-like smooth coating modified catheter and the conventional catheter of Example 2 after long-term immersion.

[0043] Figure 8 Quantitative analysis chart of the anti-pollution performance test of the solid-like smooth coating modified catheter and the conventional catheter of Example 2 after long-term immersion.

[0044] Figure 9 Physical chart of the solid-like smooth coating modified catheter and the conventional catheter of Example 2 after different dynamic fluid treatment and 2 hours of in-vitro blood circulation.

[0045] Figure 10 Quantitative analysis of the modified solid-like smooth coated catheter of Example 2 and the conventional catheter after being subjected to different dynamic fluid treatments and in-vitro blood circulation for 2 hours. DETAILED DESCRIPTION

[0046] The application will be further described in the following with specific examples. It should be understood that the following examples are only used to further illustrate the application, and should not be construed as limiting the scope of the application. Some non-essential improvements and adjustments made by those skilled in the art according to the principles set forth in the application are within the scope of the application. The following examples specifically show that the process parameters are only one example in the appropriate range, that is, those skilled in the art can make appropriate choices within the scope of the present application according to the description herein, and are not limited to the specific data of the following examples. The raw materials, reagents or devices used in the following examples and comparative examples, unless otherwise specified, can be obtained from conventional commercial channels, or can be obtained by existing known methods.

[0047] Example 1

[0048] A solid-like smooth (SSC-COOH) coating solution was prepared by the following steps:

[0049] First, 0.3 grams of silicon nanoparticles (average particle size 50 nm), 5.0 grams of carboxyl silicone oil, 10.0 grams of ethyl acetate, and 5.0 grams of silane coupling agent were stirred at 500 rpm for 12 hours at 25°C to obtain solution A; 5.0 grams of epoxy resin was completely dissolved in 5.0 grams of ethyl acetate and stirred for 4 hours to obtain solution B. Solution A was mixed with solution B and stirred at 500 rpm for 1.0 hour to form a uniform SSC-COOH coating solution, which prepared for the subsequent coating and curing steps. This process carefully controlled the ratio of materials and reaction conditions to ensure the uniformity and stability of the coating, thereby improving the performance of medical devices.

[0050] Example 2

[0051] A solid-like smooth coating modified catheter (SSCMC) modified with a solid-like smooth (SSC-COOH) coating was prepared by the following steps:

[0052] First, the surface of the medical catheter (material: polycarbonate PC) is thoroughly cleaned to remove grease and impurities, and then the surface energy of the catheter surface is improved by using plasma treatment technology to enhance the adhesion of the coating. Next, the SSC-COOH coating solution prepared in Example 1 is uniformly coated on the surface of the catheter, and a film coating machine or spraying technology is used to ensure uniform distribution of the coating. Finally, the coating is naturally cured at room temperature for 24 hours, or baked at 40°C for 2 hours to accelerate the curing process, and finally a uniform and stable solid-like smooth (SSC-COOH) coating is formed, obtaining a solid-like smooth coating modified catheter (SSCMC) which provides excellent anti-thrombosis and anti-biofouling performance for medical catheters.

[0053] The unmodified conventional medical catheter (material: polycarbonate PC) is compared with the solid-like smooth coating modified catheter prepared in Example 2 in terms of structure and performance. Figure 1 The structure comparison chart of the solid-like smooth coating modified catheter prepared in Example 2 and the conventional catheter is shown in FIG. 1, wherein (a) is a structure comparison chart of the solid-like smooth coating modified catheter and the conventional catheter; and (b) is an enlarged structure chart of the solid-like smooth coating modified catheter. Figure 1 In (a) of FIG. 1, the solid-like smooth coating modified catheter is a catheter modified by SSC-COOH (solid-like smooth) coating, which has the property of "Slippery" (smooth), meaning it has the ability to reduce adhesion; while the conventional catheter is a traditional catheter without SSC-COOH coating modification, and the surface is easy to adhere to platelets, proteins, bacteria and cells. Figure 1 In (b) of FIG. 1, the solid substrate refers to the solid substrate of the catheter surface, on which the SSC-COOH coating is attached; the van der Waals force refers to the SSC-COOH coating reducing adhesion by reducing the van der Waals force; the electrostatic force interaction refers to the SSC-COOH coating reducing adhesion by reducing the electrostatic force interaction; the hydrogen bond refers to the SSC-COOH coating reducing adhesion by reducing the hydrogen bond; and the carboxyl silicone oil is a key ingredient in the SSC-COOH coating, which is a functional group for forming chemical bonds with nanoparticles or other coating components, providing lubrication and anti-adhesion properties.

[0054] Performance test

[0055] The unmodified conventional medical catheter (material: polycarbonate PC) and the solid-like smooth coating modified catheter prepared in Example 2 are subjected to the following performance tests:

[0056] (1) Evaluation of the comprehensive physical and chemical properties of the SSC-COOH coating

[0057] First, an oil paper test is used to evaluate the oiliness of the coating surface to ensure that the silicone oil is effectively immobilized in the coating. Subsequently, a transparency test is conducted to evaluate the transparency of the SSC-COOH coating, which is crucial to ensure that the coating does not affect the optical performance of medical devices. Furthermore, the surface morphology of the SSC-COOH coating is observed using a scanning electron microscope (SEM) to confirm the uniformity and smoothness of the coating, which is critical for the anti-adhesion properties and durability of the coating. Finally, the elemental composition of the SSC-COOH coating is analyzed by X-ray photoelectron spectroscopy (XPS) to confirm the successful combination of silicon nanoparticles and epoxy resin, ensuring the chemical stability and long-term effectiveness of the coating. These tests comprehensively evaluate the physical and chemical properties of the SSC-COOH coating, ensuring that it meets the requirements of high-performance medical coatings.

[0058] (2) Evaluation of the anti-adhesion properties of SSC-COOH coating

[0059] In the experiment to evaluate the anti-protein adhesion properties of the SSC-COOH coating, the solid-like smooth coating modified catheter treated with the SSC-COOH coating and the conventional catheter without modification are incubated with fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) solution and fluorescent fibrinogen (Fg) solution for 24 hours, respectively. Subsequently, the protein adhesion on the surface of each group of catheters is observed using a fluorescence microscope, and the fluorescence images are quantitatively analyzed using Image J software to measure the fluorescence intensity, thereby evaluating the effect of the SSC-COOH coating in reducing protein adhesion compared to the unmodified catheter. This process allows for a direct comparison of the anti-protein adhesion properties of the SSC-COOH coating and verifies the effectiveness of the coating in reducing biomolecule adhesion.

[0060] (3) Evaluation of the anti-thrombogenic properties of SSC-COOH coating

[0061] First, the SSC-COOH coated catheter and the unmodified control catheter are respectively inserted into an in vitro blood circulation model to simulate the real blood flow environment. The circulation system runs for 2 hours without adding anticoagulants to observe and compare the thrombus formation inside the two catheters. After the experiment, the catheter samples are collected and the morphology of the thrombus is observed in detail using a scanning electron microscope (SEM), and the weight of the thrombus is measured to evaluate the effect of the SSC-COOH coating in inhibiting thrombus formation and verify its anti-thrombogenic properties. This experimental step provides important information about the potential effect of the SSC-COOH coating in the actual blood environment.

[0062] (4) Evaluation of the durability of SSC-COOH coating

[0063] To evaluate the long-term anti-fouling performance and durability of SSC-COOH coating, the catheter samples with SSC-COOH coating were treated in dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 7, 14 and 30 days, and in water flow environment at 100 r / min (about 2.6 m / s) for 7 days, respectively. Then, the protein, bacteria and cell adhesion experiments were performed on these catheter samples to evaluate the change of anti-fouling performance of the coating after long-term immersion by observing and quantifying the adhesion, and the tested proteins, bacteria and cells included fluorescein isothiocyanate bovine serum albumin, fluorescent fibrinogen, Escherichia coli, Staphylococcus aureus, NIH 3T3 cells and Raw 264.7 cells. In addition, in-vitro blood circulation experiments were also performed on these SSC-COOH coated catheters treated under different conditions to verify the stability and durability of the coating in long-term use by comparing the anti-thrombosis performance before and after the experiment, so as to ensure that the coating can still maintain excellent anti-thrombosis properties in dynamic fluid environment. The experimental results will provide important data support for the practical application of SSC-COOH coating.

[0064] The test results are shown in Table 1. Figures 2-10

[0065] Figure 2 The figure for the quantitative analysis of the adhesion amount of FITC-BSA and Fg on the surface of the solid-like smooth coating modified catheter of Example 2 and the conventional catheter. The column chart in the figure shows that the solid-like smooth coating modified catheter (SSCMC) of Example 2 exhibits significantly lower fluorescence intensity in the adsorption of FITC-BSA and Fg than the PC conventional catheter, and the difference is statistically significant, which indicates that the SSCMC effectively reduces the adsorption of proteins on the surface of the catheter, thereby reducing biological fouling and related clinical complications.

[0066] Figure 3 The figure for the adhesion of blood cells on the inner cavity of the solid-like smooth coating modified catheter of Example 2 and the conventional catheter after in-vitro blood circulation for 2 hours, wherein (a1) is the top view of the conventional catheter; (a2) is the side view of the conventional catheter; (b1) is the top view of the solid-like smooth coating modified catheter of Example 2; (b2) is the side view of the solid-like smooth coating modified catheter of Example 2. The picture shows that the untreated PC conventional catheter has obvious thrombus formation inside, while the solid-like smooth coating modified catheter (SSCMC) of Example 2 is almost transparent without thrombus formation, which shows that the SSCMC has significant advantages in preventing thrombus formation, which helps to reduce the thrombus complications related to implantable medical devices, and reflects the potential clinical value of SSCMC in blood contact applications.

[0067] Figure 4 ​SEM images of blood cells adhered to the inner lumen surface of a conventional catheter and a solid-like smooth coating modified catheter of Example 2, wherein (al) is a low magnification SEM image of a conventional catheter; (a2) is a high magnification SEM image of a conventional catheter; (bl) is a low magnification SEM image of a solid-like smooth coating modified catheter of Example 2; (b2) is a high magnification SEM image of a solid-like smooth coating modified catheter of Example 2. The SEM images show that the untreated PC conventional catheter surface has a large number of blood cells and platelets adhered, forming a fibrin-like thrombus structure; in contrast, the surface of the solid-like smooth coating modified catheter (SSCMC) of Example 2 is relatively smooth, with significantly reduced blood cell adhesion and almost no thrombus formation, indicating that the SSCMC has a significant effect on reducing blood cell adhesion and preventing thrombus formation, which is of great significance for improving the safety and effectiveness of blood-contacting medical devices.

[0068] Figure 5 Thrombus weight, lumen occlusion rate and blood flow rate in the tube of a conventional catheter and a solid-like smooth coating modified catheter of Example 2, wherein (a) is thrombus weight, (b) is lumen occlusion, (c) is blood flow rate in the tube. As can be seen from the figure, compared with the PC conventional catheter, the thrombus weight of the solid-like smooth coating modified catheter (SSCMC) of Example 2 is significantly reduced, the lumen occlusion rate is also significantly reduced, and the blood flow rate in the tube is significantly increased, indicating that the SSCMC significantly improves the antithrombotic performance of the catheter, reduces thrombus formation, reduces lumen occlusion, and maintains a high blood flow rate, which is crucial for the clinical application of blood-contacting medical devices.

[0069] Figure 6 Blood compatibility test data for a conventional catheter and a solid-like smooth coating modified catheter of Example 2, wherein (a) is thrombin-anti-thrombin III enzyme complex (TAT) (an early marker of coagulation activation), (b) is tissue-type fibrinogen activation inhibitor 1 complex (PIC) (a risk indicator for venous thromboembolism), (c) is thrombomodulin (TM), (d) is platelet (PLT), (e) is white blood cell (WBC), (f) is serum albumin (ALB), (g) is acute inflammation indicator C-reactive protein (CRP), (h) is tumor necrosis factor (TNF-α), (i) is interleukin 6 (il-6), (j) is interleukin 10 (il-10), (k) is liver function indicator alanine 552 transaminase (ALT), (l) is kidney function indicator serum creatinine (Scr). From the figure, it can be seen that compared with the PC conventional catheter, the solid-like smooth coating modified catheter (SSCMC) of Example 2 has significantly reduced thrombin-anti-thrombin III enzyme complex (TAT), tissue-type fibrinogen activation inhibitor 1 complex (PIC), C-reactive protein (CRP), interleukin 6 (il-6), interleukin 10 (il-10), tumor necrosis factor (TNF-α), and serum albumin (ALB), and significantly increased thrombomodulin (TM), platelet (PLT), and white blood cell (WBC), indicating that the SSCMC has a significant effect on improving the blood compatibility of the catheter, which is of great significance for improving the safety and effectiveness of blood-contacting medical devices. Figure 6It can be seen that compared with the PC regular catheter, the solid-like smooth coating modified catheter (SSCMC) of Example 2 has smaller changes in blood compatibility parameters at each time point, indicating that the SSCMC has less impact on blood components and organ function; in particular, in terms of coagulation parameters (TAT, PIC, TM), platelet count (PLT), inflammation indicators (CRP, TNF-a, IL-6, IL-10), and liver and kidney function indicators (ALT, Scr), the parameter levels of the SSCMC group are closer to the normal range, and there is no significant difference compared with the PC group; these results show that the SSCMC has good blood compatibility, does not cause excessive coagulation or inflammation, and does not cause damage to liver and kidney function, which is crucial for the safety of blood contact medical devices.

[0070] Figure 7 The fluorescence images of the anti-fouling performance test of the solid-like smooth coating modified catheter of Example 2 and the regular catheter after long-term immersion. The images show that after 7 days, 14 days and 30 days of dynamic fluid environment treatment, and 7 days of high-speed water flow impact treatment, the fluorescence intensity of the surface of the solid-like smooth coating modified catheter (SSCMC) of Example 2 is significantly lower than that of the PC regular catheter, indicating that the SSCMC effectively reduces the adhesion of proteins, bacteria and cells over a long period of time; in particular, after 30 days of blood flow environment treatment, the SSCMC still maintains high anti-biofouling ability, which proves that the SSCMC has excellent durability and stability, and can continuously provide protection against thrombosis and biofouling during long-term implantation; these results show the potential of the SSCMC in improving the biocompatibility of medical devices and reducing long-term implantation complications.

[0071] Figure 8 The quantitative analysis chart of the anti-fouling performance test of the solid-like smooth coating modified catheter of Example 2 and the regular catheter after long-term immersion. The chart shows that there are significant differences between the groups, and under all test conditions, the fluorescence intensity and cell count of the solid-like smooth coating modified catheter (SSCMC) of Example 2 are generally lower than those of the PC regular catheter, indicating that the SSCMC has a significant effect in reducing protein, bacterial and cell adhesion; in particular, after long-term dynamic fluid environment and high-speed water flow impact, the SSCMC catheter can still maintain a low adhesion level, proving its excellent anti-biofouling durability; these results further confirm the potential of the SSCMC in reducing biofouling and related complications in long-term implantation applications.

[0072] Figure 9Figure 1 shows the photographs of samples of the conventional catheter and the solid- like smooth coating modified catheter of Example 2 after being subjected to different dynamic fluid treatments and in-vitro blood circulation for 2 hours, wherein (al) is the top view of the blood circulation sample of the conventional catheter after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 30 days, (a2) is the side view of the blood circulation sample of the conventional catheter after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 30 days, (bl) is the top view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 7 days, (b2) is the side view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 7 days, (cl) is the top view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 14 days, (c2) is the side view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 14 days, (dl) is the top view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 30 days, (d2) is the side view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a dynamic fluid environment at 0.2 m / s (arterial blood flow rate) for 30 days, (el) is the top view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a water flow environment at 100 r / min (about 2.6 m / s) for 7 days, (e2) is the side view of the blood circulation sample of the solid-like smooth coating modified catheter of Example 2 after being treated in a water flow environment at 100 r / min (about 2.6 m / s) for 7 days. It is shown in the figure that the PC conventional catheter surface has obvious turbidity and color change after in-vitro blood circulation for 2 hours, especially after 30 days of dynamic fluid treatment, the turbidity and color change of the sample is most obvious, which indicates that the PC conventional catheter may have material degradation or biological contamination under long-term fluid environment; in contrast, the solid-like smooth coating modified catheter (SSCMC) of Example 2 maintains high transparency and surface integrity under the same conditions, with less color and appearance change; these results indicate that the SSCMC has good stability and anti-biological contamination ability under long-term dynamic fluid environment, which helps to maintain the performance of the catheter and prolong its service life. The coating technology provided by the present application is of great significance for improving the reliability and safety of implanted medical devices.

[0073] Figure 10The quantitative analysis chart of the solid-like smooth coating modified catheter of Example 2 and the conventional catheter after different dynamic fluid treatment and 2 hours of in vitro blood circulation, the quantitative data including thrombus weight, lumen blockage rate and blood flow rate in the tube. It is shown in the chart that the thrombus weight of the solid-like smooth coating modified catheter (SSCMC) of Example 2 is significantly lower than that of PC, the lumen blockage rate is also significantly reduced, and the blood flow rate is significantly increased under all the tested flow rate conditions; these results show that the SSCMC has significant advantages in reducing thrombosis, reducing lumen blockage and maintaining blood flow rate. The coating technology provided by the present application can significantly improve the safety and effectiveness of blood contact medical devices and reduce the risk of thrombus-related complications.

[0074] From the above data, it can be seen that the SSC-COOH modified catheter shows significantly reduced thrombosis in the in vitro blood circulation experiment, with a reduction in thrombus weight of at least 12 times compared with the unmodified catheter, and a reduction in lumen blockage rate from nearly 60% to 3.3%. In addition, the adhesion of proteins, bacteria and cells to the surface of the SSC-COOH modified catheter is reduced by 94.9% to 97.1%, the adhesion of bacteria is reduced by at least 86.7%, and the adhesion of cells is reduced by more than 5.8 times. In terms of durability and stability, it still maintains at least 70% and 80% reduction in adhesion effect of proteins, bacteria and cells after long-term static immersion and dynamic fluid impact. These results show that the SSC-COOH coating technology has significant effect in improving the antithrombotic and antibiofouling performance of medical devices, while having good biocompatibility and long-term stability. It can be seen that the new solid-like lubricating coating provided in Example 1 of the present application effectively solves the problems of thrombosis, biofouling and infection encountered by existing implantable medical devices during long-term use, and improves the functionality and safety of the device. The SSC-COOH coating forms a stable lubricating layer on the surface of the medical device, effectively inhibiting the adhesion of proteins, bacteria, cells and platelets, thereby prolonging the service life of the device and improving its clinical effect.

[0075] In addition, in the in vitro blood circulation experiment, the blood flow flux of SSC-COOH remained at 91%, while that of the unmodified catheter decreased to 48%. These data further confirm the effectiveness of the SSC-COOH coating technology. The present application reduces the risk of device-related complications in patients by reducing thrombosis and biofouling, improves the safety of treatment; and prolongs the service life of the medical device, reduces the frequency of replacing the device, thereby reducing the medical cost; and improves the stability and durability of the device, ensures the persistence and reliability of the treatment effect, and enhances the treatment effect.

[0076] Moreover, the SSC-COOH coating of the present application can improve the safety of patient treatment by reducing the risk of medical device-related complications, and reduce the medical costs caused by device replacement and complication treatment, thereby bringing substantial benefits to patients and society. In addition, the SSC-COOH coating technology of the present application also has wide application potential and can be applied to various medical devices and implants that require anti-pollution and anti-thrombus properties, thereby providing new possibilities for the design and application of medical devices. In summary, the SSC-COOH coating technology of the present application has significant advantages in improving the functionality, safety and economy of medical devices, and has good application prospects in implantable medical devices.

[0077] The SSC-COOH in embodiments 1-2 of the present application forms a stable and durable coating on the surface of implantable medical devices such as catheters by combining carboxyl silicone oil with functional nanoparticles and embedding them in epoxy resin, effectively reducing the adhesion of blood components, proteins, bacteria and cells, thereby prolonging the service life of the device and improving its clinical effect. The preparation of this coating involves chemical treatment and physical coating, first preparing a solid-like lubricating solution through hydrolysis, condensation and cross-linking reaction, then uniformly coating on the surface of medical devices and solidifying. The design of SSC-COOH coating takes into account the challenges of long-term implantation and dynamic fluid environment, by optimizing the ratio of nanoparticles and lubricant (i.e. carboxyl silicone oil) and the thickness of the coating, to ensure that the coating maintains its anti-pollution performance during long-term use. In addition, the SSC-COOH coating is designed with full consideration of biocompatibility to ensure that it does not cause inflammation, tissue damage or other adverse reactions when in contact with the human body, and maintains the functionality and safety of the device while maintaining biocompatibility. The SSC-COOH coating technology of the present application not only improves the anti-thrombus and anti-biological pollution performance of existing medical devices, but also has wide application potential, bringing good development prospects for the design and application of medical implants and long-term blood contact devices.

[0078] On the basis of embodiments 1-2, the adhesion of the coating can also be enhanced by adjusting the size and surface functionalization of the nanoparticles; loading antibacterial and anti-inflammatory drugs to provide sustained drug release; and using atomic layer deposition technology to precisely control the thickness of the coating. In addition, replacing the epoxy resin in embodiments 1-2 with other resins with smooth properties can further optimize performance, for example, the preparation of environmentally responsive coatings can be achieved. The above improvements and alternatives aim to improve the stability, durability of the coating and ensure its effectiveness under different physiological conditions, thereby providing more reliable protection for medical devices.

[0079] To sum up, in the A component of the present application, nanoparticles capture and store silicone oil, thereby providing lubricity of the coating material; silane coupling agent is used to functionalize nanoparticles, enhancing the binding force of the nanoparticles with the epoxy resin; carboxyl silicone oil serves as a lubricant, reducing the friction coefficient of the coating surface, thereby improving the lubricity and anti-adhesion of the coating. The epoxy resin in the B component serves as a matrix, ensuring the stability and durability of the coating. Through the cooperation of the A component and the B component, the carboxyl silicone oil and the functionalized nanoparticles are combined and embedded in the matrix material such as epoxy resin, forming a coating that can be used to prepare an ultra-stable anti-bioadhesion coating. The coating has good stability and durability, and can effectively reduce the adhesion of blood components, proteins, bacteria and cells, etc. The coating and the coating prepared therefrom have good application prospects in implantable medical devices.

Claims

1. An implantable medical device, comprising: The implantable medical device comprises a coating or a catheter; the catheter comprises a catheter substrate and a coating arranged on the surface of the catheter substrate; the coating is prepared by a coating material; The coating material comprises an A component and a B component; the A component comprises nanoparticles, carboxyl silicone oil, silane coupling agent and solvent; the B component comprises matrix material and solvent; the nanoparticles comprise at least one of silicon nanoparticles, iron nanoparticles or zinc nanoparticles; the matrix material comprises epoxy resin; the solvent in the A component is the same as or different from the solvent in the B component.

2. The implantable medical device of claim 1, wherein, The mass ratio of the nanoparticles to the matrix material is 1: (10-25); And / or, the mass ratio of the nanoparticles to the carboxyl silicone oil is 1: (10-25); And / or, the mass ratio of the nanoparticles to the silane coupling agent is 1: (10-25).

3. The implantable medical device of claim 1, wherein, The A component comprises components in the following mass fractions: 0.1-1 part of nanoparticles, 1-10 parts of carboxyl silicone oil, 1-10 parts of silane coupling agent and 3-20 parts of solvent; the B component comprises components in the following mass fractions: 1-10 parts of matrix material and 1-10 parts of solvent; the mass ratio of the A component to the B component is 1: (0.1-1).

4. The implantable medical device of claim 1, wherein, The solvent in the A component and the solvent in the B component are each independently selected from ester solvents; And / or, the average particle size of the nanoparticles is 10-1000 nm.

5. The implantable medical device of claim 1, wherein, The A component further comprises an active drug.

6. The implantable medical device of claim 1, wherein, The preparation method of the coating comprises the following steps: curing the coating material to obtain the coating; the curing condition is: curing at 10-30℃ for 12-36h; or, curing at 35-100℃ for 1-5h.

7. The implantable medical device of claim 1, wherein, The material of the catheter substrate comprises at least one of metal, rubber or plastic.

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