Hydrophilic coating as well as preparation method and application thereof

Abstract

The invention discloses a hydrophilic coating as well as a preparation method and application thereof, and belongs to the technical field of coating materials. The hydrophilic coating comprises a base coating and a lubricating coating attached to the base coating, the thickness of the base coating is 0.1-120 [mu] m, and the thickness of the lubricating coating is 0.1-100 [mu] m. The lubricating coating is prepared from the following components in percentage by mass: 10 to 20 percent of thiolated hyaluronic acid, 40 to 50 percent of sodium hyaluronate, 10 to 20 percent of sulfobetaine, 5 to 10 percent of ethanol and the balance of water. 100 parts by mass of the substrate coating comprise the following components: 25-35 parts of polyimide, 5-15 parts of polyvinylpyrrolidone, 5-8 parts of modified chitosan, 1-3 parts of a cross-linking agent and the balance of a solvent. According to the hydrophilic coating provided by the invention, the defects in the prior art are successfully overcome through a specific multi-layer structural design and a specific material ratio, and the prepared hydrophilic coating has excellent hydrophilicity, lubricity and adhesive force.

Description

Technical Field

[0001] The present invention belongs to the technical field of coating materials, and in particular relates to a hydrophilic coating and a preparation method and application thereof. Background Art

[0002] With the continuous development of medical technology, the importance of medical devices such as various vascular catheters, guidewires, stents, intraocular lenses, heart valves, artificial pacemakers, and orthopedic implants in clinical applications has become increasingly prominent. For medical devices that must be inserted and moved through body tissue, one of the key properties that requires attention is their lubricity. Since most devices are made of metal and plastic, these materials have poor lubricity to body tissue, causing mechanical wear and discomfort when medical devices pass through human tissue. Therefore, hydrophilic lubricating coatings on the surface of medical devices have become a research hotspot as a key technology to improve the performance of medical devices.

[0003] Currently, many prior art reports have reported on hydrophilic lubricating coatings on medical devices. For example, Chinese patent CN108117830B discloses a water-based hydrophilic lubricating coating, whose components include acrylamide-modified vinyl pyrrolidone polymer, water-based polyurethane, a water-based crosslinking agent, a leveling agent, and a solvent. The coating has a long-lasting hydrophilic lubricating effect and is non-corrosive to the substrate. Another example is Chinese patent CN112574460A, which proposes a polymer medical device with a hydrophilic lubricating coating and a preparation method thereof. The method treats the surface of the polymer medical device with oxygen plasma, then immerses it in a pretreatment solution containing a photoinitiator, and finally coats the treated surface with a precursor solution of the hydrophilic lubricating coating and performs photocuring to obtain a coating with lubricating and hydrophilic properties. Although the above patents can all demonstrate a certain degree of stability and lubrication effects, they still have the same problems as other existing technologies: first, most coatings cannot form a good bond with the substrate, the coating adhesion is insufficient, and it is easy to fall off during long-term use, affecting the service life of the medical device; second, the lubrication performance of the coating needs to be improved and cannot meet the needs of long-term use; third, it is difficult to achieve an ideal balance between the hydrophilicity and lubricity of the existing coatings. Coatings with good hydrophilicity often have insufficient lubricity, while coatings with good lubricity have relatively poor hydrophilicity; in addition, the coating component design in the existing technology is relatively simple, and it is difficult to simultaneously meet multiple requirements such as hydrophilicity, lubricity and biocompatibility.

[0004] Therefore, there is an urgent need to develop a medical device surface coating with excellent hydrophilicity, long-lasting lubricity and good adhesion to meet the needs of clinical applications. Summary of the Invention

[0005] In order to solve the technical problems of improving the hydrophilicity, adhesion and lubricity of medical coatings and achieve the technical effects of high hydrophilicity, lasting low friction and high adhesion strength, the present invention provides a hydrophilic coating and its preparation method and application.

[0006] The technical solution adopted by the present invention to solve its technical problem is: A hydrophilic coating comprises a base coating and a lubricating coating attached to the base coating, wherein the base coating has a thickness of 0.1-120 μm and the lubricating coating has a thickness of 0.1-100 μm.

[0007] Based on 100 parts by mass, the components of the base coating include: 25-35 parts of polyimide, 5-15 parts of polyvinyl pyrrolidone, 5-8 parts of modified chitosan, 1-3 parts of a crosslinking agent, and the remainder of solvent.

[0008] Furthermore, the mass ratio of polyimide to polyvinylpyrrolidone is 1.8-3:1, and can be selected from any of 1.8:1, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, and 3:1. Polyimide is a commonly used component in medical coatings and exhibits excellent chemical stability and mechanical properties. However, its molecular structure is too regular and lacks hydrophilic groups. Therefore, when used alone, the coating has poor hydrophilicity. Furthermore, its high curing temperature can easily generate curing stress, resulting in poor elastic modulus and adhesion of the coating. Polyvinylpyrrolidone contains a large number of polar lactam groups in its structure, which exhibits good hydrophilicity and wettability, but its inherent heat resistance and mechanical strength are low. The present application compounds the two and optimizes the relative dosage. After the two are mixed, the interaction between them can not only improve the adhesion and hydrophilicity of the coating, but also reduce the curing temperature.

[0009] Furthermore, the K value of polyvinyl pyrrolidone is 22-33, preferably 22-28. Polyvinyl pyrrolidone in this K value range has an appropriate molecular chain length, which can better interact with polyimide to enhance the flexibility of the coating; when the K value is too large, the polyvinyl pyrrolidone molecular chain is longer, forming a closer intermolecular interaction with the polyimide, which is not conducive to the flexibility and adhesion strength of the coating.

[0010] Further, described modified chitosan is selected from least one in phthaloylated chitosan, carboxylated chitosan, chitosan quaternary ammonium salt, is preferably chitosan quaternary ammonium salt.Modified chitosan especially chitosan quaternary ammonium salt can improve the adhesive force and the lubricity of coating, one, because chitosan quaternary ammonium salt can and the functional group generation chemical action or physical adsorption of substrate surface, and can also improve the crosslinking degree between polyvinyl pyrrolidone and the polyimide, and the latter two act together to stabilize coating structure, improve the adhesive force of coating, guarantee that basal coating is in the use process of medical device, particularly under the physiological environment of human body complexity and external mechanical action (as bending, friction etc.), can firmly adhere to substrate surface, can not come off easily.The two, because chitosan quaternary ammonium salt can and the composition in lubricating coating produce interaction force, serve as the effect of interfacial bonding agent and lubricating coating is better attached to on the basal layer, helps hydrophilic and lubricating component in the lubricating layer to play a role better.

[0011] Furthermore, the degree of substitution of the chitosan quaternary ammonium salt is ≥92%, preferably ≥95%. The degree of substitution of the chitosan quaternary ammonium salt refers to the degree of replacement of amino groups in the chitosan with quaternary ammonium groups. When the degree of substitution is too low, the binding interaction between the chitosan molecules and the substrate is relatively simple, and the binding force with the substrate is weak. In addition, the hydrophilicity and lubricity of the coating are changed by affecting the adsorption of the active ingredients in the lubricating coating, thereby reducing the lubrication performance of the coating.

[0012] Furthermore, the cross-linking agent is trimethylolpropane trimethacrylate and / or trimethylolpropane triacrylate.

[0013] Furthermore, the base coating composition also includes 7-9 parts of a coupling agent, which is an organosilicon coupling agent, preferably KH560.

[0014] Furthermore, the base coating may further comprise 1-5 parts of a nano-functional filler, including but not limited to at least one of silver, titanium dioxide, and zinc dioxide. A suitable amount of the above nano-functional filler can impart antibacterial properties to the coating and improve its toughness and structural stability, but excessive amounts can impair the coating's adhesion.

[0015] Furthermore, the particle diameter of the nano-functional filler is 10-100 nm, preferably 10-50 nm.

[0016] Furthermore, the components of the base coating also include 0-2 parts of auxiliary agents, which include but are not limited to at least one of a leveling agent, a defoaming agent, and a surfactant, and can be selected according to actual needs. The present invention does not strictly limit this.

[0017] Furthermore, the solvent includes but is not limited to at least one of acetone, methanol, ethanol, isopropanol, dimethylformamide, dimethyl sulfoxide, dichloromethane, cyclohexanone, tetrahydrofuran, glycerol and deionized water.

[0018] Furthermore, the lubricating coating comprises the following components in mass fractions: 10-20% thiolated hyaluronic acid, 40-50% sodium hyaluronate, 10-20% sulfobetaine, 5-10% ethanol, and the balance made up of water.

[0019] Sodium hyaluronate has excellent hydrophilicity. Its molecular structure contains multiple hydroxyl groups, which can form hydrogen bonds with water molecules, thereby absorbing and binding large amounts of water, keeping the coating surface moist and improving the coating's wetting properties. While retaining the basic structure of hyaluronic acid, thiol groups are introduced. These highly reactive groups can better lock in water molecules, further enhancing the coating's hydrophilicity and hydration capacity, maintaining good hydrophilicity and reducing the coefficient of friction. Furthermore, the thiol groups in thiolated hyaluronic acid possess certain antioxidant properties, which can improve the coating's resistance to environmental factors (such as UV rays, oxygen, and moisture), extending the coating's stability and service life.

[0020] Further, the number-average molecular weight of the thiolated hyaluronic acid is 8000-100000, and the degree of thiolation is 30-50%. The thiolated hyaluronic acid with moderate number-average molecular weight can form a denser structure with the effect of sodium hyaluronate, absorbs and combines more water molecules, and the coating hydrophilicity and lubricity are better, but when the number-average molecular weight is too large, the excessive entanglement between the molecular chains can reduce the coating hydrophilicity and the bonding force with the base coating. The higher the degree of thiolation, the more thiol groups there are in the coating, and the crosslinking with sodium hyaluronate and sulfobetaine is more sufficient, but after exceeding the specified range, the excessive crosslinking in the coating will cause the coating to become brittle, and hydrophilicity is reduced.

[0021] Furthermore, the number average molecular weight of the thiolated hyaluronic acid is 50,000, and the degree of thiolation is 40%.

[0022] Furthermore, the number average molecular weight of the sodium hyaluronate is 200,000-500,000.

[0023] Secondly, the present application also provides a method for preparing a hydrophilic coating, comprising the following steps: S1. Clean the substrate surface, mix the components of the base coating evenly, and then spray them on the substrate surface. Keep the temperature at 60-80°C for 0.5-2 hours, 100-110°C for 1-2 hours, and 150-160°C for 2-3 hours to obtain the base coating on the substrate surface. S2. Evenly mix the components of the lubricating coating, soak the substrate in S1 in the mixed components of the lubricating coating for a period of time, then take it out and perform thermal curing.

[0024] The staged thermal curing in S1 can effectively alleviate the problem of thermal stress in the coating. At a relatively low temperature (60-80°C), the coating begins to slowly solidify, and the molecular chains gradually lose their mobility, resulting in less internal stress. As the temperature rises, the mobility of the molecular chains increases, which can partially release the internal stress. This significantly reduces the internal stress of the final cured coating, improves adhesion to the substrate, and reduces the possibility of cracking and shedding during use.

[0025] Furthermore, the soaking time d in S2 is ≥ 2s, preferably 2-10s.

[0026] Furthermore, the temperature of thermal curing in S2 is 50-66° C., and the curing time is 2-4 hours.

[0027] Furthermore, the present application does not impose strict restrictions on the material of the substrate, and may be selected from but is not limited to at least one of polyetheretherketone resin, silicone resin, polyurethane resin, polyacrylate resin, polyamide resin, polyethylene resin, polypropylene resin, epoxy resin, nylon elastomer, polyethylene terephthalate, polybutylene terephthalate, polycarbonate resin, polyvinyl chloride resin, phenolic resin, etc.

[0028] Finally, the present application also provides the application of the hydrophilic coating on medical devices, including but not limited to catheters (such as intravascular angiography catheters, balloon dilatation catheters, central venous catheters, over-the-needle peripheral catheters, micro-floating catheters, arteriovenous pressure measurement catheters, angiography catheters, balloon catheters, PTCA catheters, PTA catheters, microcatheters, thrombolytic catheters, guide catheters, tracking balloons, etc.), guidewires (such as hard guidewires, soft-head guidewires, renal artery guidewires, micro guidewires, push guidewires, super-smooth guidewires, etc.), stents (such as vascular stents, prostate stents, biliary stents, esophageal stents, etc.), embolic devices (such as filters, spring emboli, embolic microspheres, platinum microemboli, occluders, etc.).

[0029] Beneficial effects of the present invention: (1) The hydrophilic coating of the present invention utilizes the dual properties of the base coating and the lubricating coating. The contact angle test verifies that it has good hydrophilic properties, which helps to reduce the friction between medical devices and human tissues and reduce damage to tissues.

[0030] (2) The use of the compound polyimide and polyvinyl pyrrolidone of the present invention can significantly improve the adhesion of the coating, and further cooperate with the force of the chitosan quaternary ammonium salt on the lubricating coating, thereby increasing the bonding of the lubricating coating on the base layer. Ultimately, the combined effect improves the adhesion strength of the hydrophilic coating on the substrate (level 0-1), which can meet the use requirements of medical devices.

[0031] (3) The present invention optimizes the material ratio in the lubricating layer and utilizes thiolated hyaluronic acid and sodium hyaluronate to further improve the hydrophilicity and lubricity of the coating, effectively reducing the friction coefficient. DETAILED DESCRIPTION

[0032] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0033] Unless otherwise specified, the following raw materials were used in the Examples and Comparative Examples: Polyimide (CAS: 62929-02-6): Matrimid 5218. Polyvinylpyrrolidone (CAS: 9003-39-8), K value 25. Chitosan quaternary ammonium salt (CAS: 70694-72-3): 95% substitution, specifically hydroxypropyltrimethylammonium chloride chitosan, purchased from Wuhan Narabai. The coupling agent was silicone coupling agent KH560. The diameter of the nano-zinc dioxide particles was 18 nm. The diameter of the nano-silver particles was 35 nm. Thiolated hyaluronic acid: number average molecular weight 50,000 Da, degree of thiolation 40%. Sodium hyaluronate (CAS: 9067-32-7): number average molecular weight 300,000 Da. The sulfobetaine (CAS: 3637-26-1) was methacryloylethyl sulfobetaine. Example 1

[0034] This embodiment provides a hydrophilic coating, including a base coating and a lubricating coating attached to the base coating. The base coating has a thickness of 5 μm, and the lubricating coating has a thickness of 7.5 μm.

[0035] The components of the base coating include, based on 100 parts by mass: 30 parts of polyimide, 13.6 parts of polyvinyl pyrrolidone, 5 parts of chitosan quaternary ammonium salt, 2 parts of trimethylolpropane trimethacrylate, 8 parts of coupling agent, 2 parts of nano zinc dioxide particles, 7 parts of dimethylformamide, and ethanol as the balance.

[0036] The lubricating coating comprises the following components by mass fraction: 15% thiolated hyaluronic acid, 45% sodium hyaluronate, 12% sulfobetaine, 5% ethanol, and the balance made up of water.

[0037] The preparation method of the hydrophilic coating comprises the following steps: S1. Clean the substrate surface, mix the components of the base coating evenly, and then spray them on the substrate surface. Keep the temperature at 70°C for 1 hour, 100°C for 1 hour, and 150°C for 3 hours in sequence to obtain a base coating on the substrate surface. S2. Mix the components of the lubricating coating evenly, soak the substrate of S1 in the mixed components of the lubricating coating for 5 seconds, then take it out and heat cure it at 55°C for 3 hours. Example 2

[0038] This embodiment provides a hydrophilic coating, including a base coating and a lubricating coating attached to the base coating. The base coating has a thickness of 10.2 μm, and the lubricating coating has a thickness of 5.0 μm.

[0039] The components of the base coating include, based on 100 parts by mass: 35 parts of polyimide, 12 parts of polyvinyl pyrrolidone, 5 parts of chitosan quaternary ammonium salt, 3 parts of trimethylolpropane trimethacrylate, 7 parts of coupling agent, 4 parts of nano zinc dioxide particles, 8 parts of dimethylformamide, and ethanol as the balance.

[0040] The lubricating coating comprises the following components by mass fraction: 10% thiolated hyaluronic acid, 50% sodium hyaluronate, 10% sulfobetaine, 10% ethanol, and the balance made up of water.

[0041] The preparation method of the hydrophilic coating comprises the following steps: S1. Clean the substrate surface, mix the components of the base coating evenly, and then spray them on the substrate surface. Keep the temperature at 60° C. for 2 h, 100° C. for 2 h, and 150° C. for 3 h in sequence to obtain a base coating on the substrate surface. S2. Mix the components of the lubricating coating evenly, soak the substrate of S1 in the mixed components of the lubricating coating for 2 seconds, then take it out and heat cure it at 50°C for 4 hours. Example 3

[0042] This embodiment provides a hydrophilic coating, including a base coating and a lubricating coating attached to the base coating. The base coating has a thickness of 10.0 μm, and the lubricating coating has a thickness of 9.7 μm.

[0043] The components of the base coating include, based on 100 parts by mass, 25 parts of polyimide, 13 parts of polyvinyl pyrrolidone, 8 parts of chitosan quaternary ammonium salt, 1 part of trimethylolpropane triacrylate, 9 parts of coupling agent, 1 part of nano zinc dioxide particles, 5 parts of dimethylformamide, and the balance is supplemented by ethanol.

[0044] The lubricating coating comprises the following components by mass fraction: 20% of thiolated hyaluronic acid, 40% of sodium hyaluronate, 15% of sulfobetaine, 5% of ethanol, and the balance of water.

[0045] The preparation method of the hydrophilic coating comprises the following steps: S1. Clean the substrate surface, mix the components of the base coating evenly, and then spray them on the substrate surface. Keep the temperature at 80°C for 0.5 h, 110°C for 1 h, and 160°C for 2 h in sequence to obtain a base coating on the substrate surface. S2. Mix the components of the lubricating coating evenly, soak the substrate of S1 in the mixed components of the lubricating coating for 10 seconds, then take it out and heat cure it at 66°C for 3 hours.

[0046] Comparative Example 1 This comparative example provides a hydrophilic coating. The method is substantially the same as that of Example 1, except that, based on 100 parts by mass, the base coating comprises: 35 parts polyacrylamide, 5 parts chitosan quaternary ammonium salt, 2 parts trimethylolpropane trimethacrylate, 8 parts coupling agent, 2 parts nano-zinc dioxide particles, 7 parts dimethylformamide, with ethanol providing the balance; and the polyacrylamide has a number average molecular weight of 9,000,000.

[0047] Comparative Example 2 This comparative example provides a hydrophilic coating. The method is substantially the same as that of Example 1, except that, based on 100 parts by mass, the base coating comprises: 30 parts polyimide, 3 parts polyvinyl pyrrolidone, 5 parts chitosan quaternary ammonium salt, 2 parts trimethylolpropane trimethacrylate, 8 parts coupling agent, 2 parts nano zinc dioxide particles, and 7 parts dimethylformamide, with the balance being made up of ethanol.

[0048] Comparative Example 3 This comparative example provides a hydrophilic coating, which is basically the same as Example 1, except that chitosan quaternary ammonium salt is not added to the base coating.

[0049] Comparative Example 4 This comparative example provides a hydrophilic coating, which is basically the same as Example 1, except that: polyvinyl pyrrolidone (CAS: 9003-39-8) has a K value of 30.

[0050] Comparative Example 5 This comparative example provides a hydrophilic coating, which is basically the same as Example 1, except that the lubricating coating comprises the following components by weight: 45% thiolated hyaluronic acid, 15% sodium hyaluronate, 12% sulfobetaine, 5% ethanol, and the balance water.

[0051] Comparative Example 6 This comparative example provides a hydrophilic coating, which is basically the same as Example 1, except that: chitosan quaternary ammonium salt (CAS: 70694-72-3): the degree of substitution is 40%.

[0052] Comparative Example 7 This comparative example provides a hydrophilic coating and a preparation method thereof. The method is substantially the same as that of Example 1, except that step S1 of the preparation method comprises: cleaning the substrate surface, uniformly mixing the components of the base coating, and spraying the mixture onto the substrate surface; maintaining the mixture at 100°C for 7 hours to obtain the base coating on the substrate surface.

[0053] Performance testing method: 1. Contact angle: The water contact angles of the hydrophilic coatings prepared in the examples and comparative examples were measured using a JC2000D2W contact angle meter and a static drop-three-point method. The smaller the test data, the better the hydrophilicity of the coating.

[0054] 2. Coefficient of Friction (COF): The hydrophilic coatings of the Examples and Comparative Examples were applied to the surface of a nickel-titanium alloy medical guidewire (sample specifications: diameter * length / 0.3 * 400 mm). The friction of the medical guidewires was tested and the coefficient of friction was calculated using a tribometer according to ASTM D3359. The guidewires were soaked in saline before testing. The test conditions were: a holding force of 4 N, 25 friction cycles, a test sample length of 20 cm, a pulling speed of 5 mm / s, and a test temperature of 25 ± 3°C. The test data was graded as follows: COF < 0.01, designated A; 0.01 ≤ COF < 0.015, designated B; 0.015 ≤ COF < 0.02, designated C; 0.02 ≤ COF < 0.03, designated D; and COF ≥ 0.03, designated E. A lower coefficient of friction indicates better lubricity of the coating.

[0055] 3. Adhesion: Coatings from the above examples and comparative examples were applied to stainless steel substrates according to the preparation methods. After the coatings were inspected for visible defects, adhesion was tested according to GB / T9286-1998 (cross-hatch method). The adhesion results were graded from 0 to 5, with 0 being the best and 5 being the worst.

[0056] The above test results are shown in Table 1.

[0057] Table 1 Serial number contact angle Friction coefficient Adhesion Example 1 2.8° A Level 0 Example 2 3.5° A Level 0 Example 3 5.9° A Level 1 Comparative Example 1 34.0° D Level 2 Comparative Example 2 22.6° C Level 2 Comparative Example 3 23.5° C Level 3 Comparative Example 4 18.0° B Level 3 Comparative Example 5 16.2° B Level 2 Comparative Example 6 20.7° B Level 3 Comparative Example 7 25.3° C Level 4 Analysis: As can be seen from the above table, the hydrophilic coatings described in Examples 1-3 have a low contact angle (2.8-5.9°) and friction coefficient (<0.01), and a high adhesion (level 0). This proves that the hydrophilic coating provided in this application can successfully solve the technical problems of insufficient hydrophilicity, adhesion and lubricity of medical coatings through a specific multi-layer structure design and material ratio, and provides a surface modification solution with excellent performance for medical devices.

[0058] 4. In vitro cytotoxicity test: carried out in accordance with the national standard GB / T 16886.5-2017.

[0059] (1) Sample preparation: Under sterile conditions, 1.5 g of the hydrophilic coating sample of Example 1 was extracted according to the ratio in Table 2 below. After the extraction, the sample was checked for changes in the extraction and stored at 20-30°C. It was used in the experiment within 24 h. A blank control, a negative control (high-density polyethylene, manufactured by Alfa Aesar), and a positive control sample (zinc diethyldithiocarbamate, used at a concentration of 0.1%) were prepared under the same conditions.

[0060] Table 2

[0061] (2) Aseptic operation during the experiment: L-929 cells (American Type Culture Collection CCL1, NCTC clone 929) were cultured in MEM medium containing 10% fetal bovine serum and antibiotics (penicillin 100 U / ml, streptomycin 100 μg / ml) in a 37°C, 5% CO2 incubator. The cells were digested with trypsin to prepare a cell suspension, centrifuged (200g, 3min), and then redispersed in fresh culture medium to adjust the cell density to 1x105cells / ml. The above cell suspension was inoculated into a 96-well culture plate, 100μL per well, and cultured in a carbon dioxide incubator for 24h (5% CO2, 37℃, humidity>90%). After the cells grew into a monolayer, the original culture medium was aspirated and 100μL of different concentrations of test sample extracts (100%, 75%, 50%, 25%), blank control solution, positive control solution (100%) and negative control solution (100%) were added respectively. The plates were incubated at 37℃, 5% CO2 for 24h. Six parallel samples were made for each group.

[0062] After 24 hours of incubation, remove the 96-well plate and observe cell morphology under a microscope. Then, remove the liquid and add 50 μL of MTT (1 mg / mL) to each well. Incubate in a CO2 incubator for 2 hours. Discard the MTT solution and add 100 μL of isopropanol solution to each well. Shake the plate and measure absorbance at 570 nm (reference wavelength 650 nm) on a microplate reader.

[0063] (3) Statistical methods Survival rate (%) = (100 × OD 570e ) / OD 570b In the formula OD 570e ——Average optical density of test sample / negative control / positive control; OD 570b ——Average value of blank optical density.

[0064] Evaluation criteria: If the survival rate drops to less than 70% of the blank, it is considered potentially cytotoxic. The survival rate of the 50% test sample extract should be at least the same as or higher than the survival rate of the 100% test sample extract. Otherwise, the test should be repeated; the survival rate of the 100% test sample extract is the final result. Statistical results are shown in Table 3 Table 3 Group Survival rate% Blank control 100.0 Negative control 96.3 Positive control 5.7 100% sample extract 91.6 75% sample extract 94.0 50% sample extract 93.7 25% sample extract 95.1 According to the results, the extract of the hydrophilic coating has no potential toxic effect on L-929 cells.

[0065] 5. In vitro hemolysis test: carried out in accordance with the national standard GB / T 16886.4-2022.

[0066] (1) Prepare samples using direct contact method Take three portions of the test sample from Example 1, 5 g of each, and place them in 10.0 mL of the contact solution. Store at 20-30°C and use within 24 hours. Prepare a negative control (0.9% sodium chloride injection) and a positive control sample (purified water) under the same conditions.

[0067] (2) Experimental method: Place all test tubes in a constant temperature water bath at 37°C for 30 min, then add 0.2 mL of diluted rabbit blood to each test tube of the experimental group and 0.2 mL of diluted rabbit blood to each test tube of the control group. Mix gently and continue to keep warm in a 37°C water bath for 60 min. Pour out the solution in the tube and centrifuge for 5 min (800 g). Aspirate the supernatant and pour it into a cuvette. Measure the absorbance of each group at a wavelength of 545 nm using a spectrophotometer.

[0068] (3) Statistical methods Hemolysis rate (%) = (AB) / (CB) × 100%; Where A is the mean of sample readings, B is the mean of negative control readings, and C is the mean of positive control readings.

[0069] Evaluation criteria: The absorbance of the negative control tube should be no greater than 0.03, and the absorbance of the positive control tube should be 0.8±0.3. Otherwise, the test should be repeated; if the hemolysis rate is less than 5%, the sample is considered qualified. The results are shown in the table below.

[0070] Table 4

[0071] According to the above results, the hemolysis rate of the hydrophilic coating of the present application in direct contact with the sample is 1.2%, and the hemolysis rate is less than 5%. It is believed that the hydrophilic coating has no effect on the hemolysis performance.

[0072] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0073] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A hydrophilic coating, characterized in that: The invention comprises a base coating and a lubricating coating attached to the base coating, wherein the base coating has a thickness of 0.1-120 μm and the lubricating coating has a thickness of 0.1-100 μm; The lubricating coating comprises the following components by mass fraction: 10-20% of thiolated hyaluronic acid, 40-50% of sodium hyaluronate, 10-20% of sulfobetaine, 5-10% of ethanol, and the balance of water.

2. The hydrophilic coating according to claim 1, characterized in that The number average molecular weight of the thiolated hyaluronic acid is 8,000-100,000, and the thiolation degree is 30-50%.

3. The hydrophilic coating according to claim 1, characterized in that Based on 100 parts by mass, the components of the base coating include: 25-35 parts of polyimide, 5-15 parts of polyvinyl pyrrolidone, 5-8 parts of modified chitosan, 1-3 parts of a crosslinking agent, and the remainder of solvent.

4. The hydrophilic coating according to claim 3, characterized in that The mass ratio of the polyimide to polyvinyl pyrrolidone is 1.8-3:

1.

5. The hydrophilic coating according to claim 3, characterized in that The modified chitosan is selected from at least one of phthalated chitosan, carboxylated chitosan, and chitosan quaternary ammonium salt.

6. The hydrophilic coating according to claim 3, characterized in that The modified chitosan is chitosan quaternary ammonium salt, and the substitution degree of the chitosan quaternary ammonium salt is greater than or equal to 92%.

7. The hydrophilic coating according to claim 3, characterized in that The base coating composition also includes 7-9 parts of a coupling agent.

8. The hydrophilic coating according to claim 3, characterized in that The crosslinking agent is trimethylolpropane trimethacrylate and / or trimethylolpropane triacrylate.

9. The method for preparing a hydrophilic coating according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1. Clean the substrate surface, mix the components of the base coating evenly, and then spray them on the substrate surface. Keep the temperature at 60-80°C for 0.5-2 hours, 100-110°C for 1-2 hours, and 150-160°C for 2-3 hours to obtain the base coating on the substrate surface. S2. Evenly mix the components of the lubricating coating, soak the substrate in S1 in the mixed components of the lubricating coating for a period of time, then take it out and perform thermal curing.

10. Use of the hydrophilic coating according to any one of claims 1 to 8 in medical devices, characterized in that: The medical device includes any one of a catheter, a guide wire, a stent, and an embolization device.

Images