Temperature-sensitive responsive polyacrylic acid sodium catheter leakage-proof coating, preparation method and application thereof

Abstract

The application relates to the technical field of medical instrument functional coating, in particular to a temperature-sensitive response type sodium polyacrylate catheter leakage-proof coating, a preparation method and application thereof, and the coating is a three-layer composite structure. A polydopamine modified silane coupling agent system is used in the bottom adhesive layer, silver nanoparticles are contained in the bottom adhesive layer, the thickness of the bottom adhesive layer is 5-15 micrometers, and the bottom adhesive layer ensures strong adhesion and antibiosis. The middle functional layer is a three-dimensional cross-linking degree gradient interpenetrating network polymer which is composed of multiple monomers and nanomaterials, the thickness of the middle functional layer is 50-100 micrometers, the cross-linking degree of the middle functional layer increases from inside to outside, the mechanical property gradient transition is realized, the outer protective layer is composed of a copolymer, the thickness of the outer protective layer is 3-8 micrometers, excellent stain resistance and biocompatibility are provided, the design realizes the cooperation of the functions of the layers, the coating is provided with strong adhesion, gradient mechanical property and surface stability, the sodium polyacrylate component absorbs water and expands to form a seal in urine, and the expansion degree of the sodium polyacrylate component is regulated by the pH value and the ion strength of the urine.

Description

TECHNICAL FIELD

[0001] The application relates to a temperature-sensitive polyacrylic acid sodium catheter anti-leakage coating, a preparation method thereof and application thereof. BACKGROUND

[0002] Catheters are one of the most widely used medical devices in clinical applications, which are used for emptying the bladder, monitoring urine volume and assisting in the diagnosis and treatment of urinary system diseases. According to statistics, about 15% to 25% of inpatients need to indwell catheters, and the proportion of long-term home care patients is even higher, reaching more than 13%. However, catheters face many clinical challenges during use, among which the urine leakage problem is one of the important factors affecting the quality of life of patients.

[0003] Traditional Foley catheters are fixed in the bladder by inflating the balloon, but the seal between the balloon and the urethral wall mainly depends on mechanical pressure. When the patient's body position changes, abdominal pressure increases or the balloon is not inflated enough, urine leakage from the outside of the catheter often occurs. Urine leakage not only causes urine to contaminate clothes and bedclothes, causing embarrassment and discomfort for patients, but also can cause complications such as perineal skin maceration and infection. For patients with long-term indwelling catheters, repeated urine leakage seriously affects their social activities and mental health.

[0004] Currently, the research on catheter coating technology mainly focuses on solving two major problems: one is the friction damage during insertion, and the other is the prevention of infection during indwelling. Chinese patent CN109337492A discloses a hydrophilic super-smooth coating and an activation-free coating catheter. The technology mixes isocyanate-modified vinyl pyrrolidone polymer with isocyanate, crosslinking agent, adhesion promoter and solvent to form a coating, which is coated on the surface of the catheter and then cured at 60-90℃ for 3-10 minutes. Then the catheter is placed in an aluminum plastic packaging bag and filled with an infiltration solution. The coating is stable in combination with the catheter, has long-lasting hydrophilic super-smooth properties, can be used on both polar high and polar low catheters, and the friction coefficient can be reduced to 0.02-0.05. However, this technology mainly solves the lubrication problem of catheter insertion, reduces the friction resistance by forming a hydrogel layer, and reduces the pain and urethral tissue damage of patients, which is completely different from the purpose and mechanism of the anti-leakage coating.

[0005] For the problem of urine leakage of urinary catheter, the prior art still lacks effective solutions. Although increasing the water volume of the balloon can enhance the sealing effect, excessive compression force can cause ischemic necrosis of the urethral wall, causing serious complications. Some studies attempt to coat the surface of the urinary catheter with an expanding material to increase the contact area with the urethral wall, but due to the lack of precise control of the expansion degree, two extreme cases can easily occur: insufficient expansion, resulting in insufficient sealing force and still urine leakage; excessive expansion causes excessive compression on the urethral tissue, causing pain, ischemia and even tissue necrosis. In addition, the use environment of the urinary catheter is complex and variable, the pH value, temperature and ionic strength of the urine will change with the physiological state and pathological condition of the patient, especially when urinary tract infection occurs, bacteria producing urease will decompose urea to produce ammonia, causing the pH value of the urine to rise, and the existing passive coating cannot adapt to such dynamic changes.

[0006] Therefore, it is urgent to develop an intelligent response type anti-leakage coating that can adaptively adjust the expansion degree according to the changes in the physiological environment, ensuring effective sealing and avoiding tissue damage, while also having antibacterial and anti-fouling functions, meeting the clinical needs of long-term indwelling urinary catheters. SUMMARY

[0007] The purpose of the present application is to overcome the shortcomings of the prior art and provide a temperature-sensitive poly sodium acrylate urinary catheter anti-leakage coating, a preparation method and applications thereof. The coating has a three-layer gradient structure design and realizes intelligent sealing through a dual-response mechanism of temperature and pH, solving the problem of urine leakage during the indwelling period of the urinary catheter, while also having the characteristics of antibacterial, anti-fouling and excellent biocompatibility.

[0008] To achieve the above-mentioned purposes, the technical solutions adopted by the present application are as follows:

[0009] This invention provides a thermo-responsive sodium polyacrylate catheter leak-proof coating, which comprises, from the inside out, a bottom adhesive layer, an intermediate functional layer, and an outer protective layer. The bottom adhesive layer is composed of a polydopamine-modified silane coupling agent system, including γ-aminopropyltriethoxysilane, dopamine hydrochloride, Tris buffer, and silver nanoparticles, with a thickness of 5 μm to 15 μm. The intermediate functional layer is an interpenetrating network polymer with a three-dimensional crosslinking gradient structure, polymerized from sodium acrylate monomer, N-isopropylacrylamide, acrylic acid, N,N'-methylenebisacrylamide crosslinking agent, organically modified montmorillonite, graphene oxide nanosheets, and mesoporous silica nanoparticles, with a thickness of 50 μm to 100 μm, and the degree of crosslinking gradually increases from 0.6 mol% to 1.0 mol% on the inner side to 2.0 mol% to 3.0 mol% on the outer side. The outer protective layer is copolymerized from polyethylene glycol methacrylate, N-isopropylacrylamide, and sulfobetaine methacrylate, with a thickness of 3 μm to 8 μm. The amount of the crosslinking agent is calculated relative to the total molar amount of sodium acrylate, N-isopropylacrylamide, and acrylic acid. The amount of crosslinking agent in the inner layer is 0.6–1.0 mol%, and in the outer layer it is 2.0–3.0 mol%.

[0010] Preferably, the mass ratio of each component in the bottom adhesive layer is 2 to 8 parts γ-aminopropyltriethoxysilane, 0.5 to 3 parts dopamine hydrochloride, 100 parts Tris buffer, and 0.1 to 0.5 parts silver nanoparticles. The Tris buffer has a pH of 8.5 and a concentration of 10 mM, providing a suitable alkaline environment for the oxidative polymerization of dopamine. The particle size of the silver nanoparticles is controlled between 10 nm and 30 nm. This size range ensures sufficient specific surface area for efficient antibacterial activity while avoiding nanoparticle aggregation.

[0011] The intermediate functional layer is the core of the leak-proof coating. Its composition (by weight) is as follows: 15 to 35 parts sodium acrylate monomer, 8 to 20 parts N-isopropylacrylamide, 2 to 8 parts acrylic acid, 3 to 12 parts organically modified montmorillonite, 0.5 to 3 parts graphene oxide nanosheets, 8 to 18 parts mesoporous silica nanoparticles, and 90 to 150 parts deionized water. The organically modified montmorillonite is treated with hexadecyltrimethylammonium bromide, increasing the interlayer spacing to 3.5 nm to 4.2 nm, significantly improving its dispersibility and compatibility in the polymer matrix. The graphene oxide nanosheets have a lateral dimension of 0.5 μm to 2.0 μm and a thickness of 1 nm to 3 nm, ensuring the formation of a two-dimensional nano-reinforcing phase in the coating. The mesoporous silica nanoparticles have a particle size of 20 nm to 50 nm, a pore size of 2 nm to 10 nm, and a specific surface area of ​​420 m². 2 / g to 580m 2 / g provides ample space for loading antimicrobial peptides.

[0012] In particular, the mesoporous silica nanoparticles are surface functionalized and coupled with antibacterial peptides. The surface is first modified with amino groups by aminopropyltriethoxysilane, and then the antibacterial peptides are covalently immobilized by EDC / NHS chemical coupling method. The antibacterial peptides can be selected from human antibacterial peptide LL-37 or synthetic short peptide HHC36. The amino acid sequence of LL-37 is LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, and the molecular weight is 4493 Da. LL-37 has broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. The amino acid sequence of HHC36 is KRWWKWWRR, and the molecular weight is 1479 Da. HHC36 has low synthesis cost and good stability. The loading amount of antibacterial peptides is controlled at 8wt% to 15wt%, which ensures the antibacterial effect and avoids adverse effects on the performance of the coating.

[0013] The application also provides a preparation method of the above-mentioned temperature-responsive polyacrylic acid sodium catheter leakage-proof coating. The method comprises the steps of catheter surface pretreatment, preparation of a bottom adhesive layer, gradient coating of an intermediate functional layer, initiation of polymerization, preparation of an outer protective layer, and post-treatment. By precisely controlling the process parameters of each step, a leakage-proof coating with uniform structure and stable performance can be prepared.

[0014] In the catheter surface pretreatment step, a medical-grade silicone or thermoplastic polyurethane catheter is immersed in a mixed solution of ammonia, hydrogen peroxide and deionized water for ultrasonic cleaning and activation treatment. The mass fraction of ammonia in the mixed solution is 25wt% to 28wt%, the mass fraction of hydrogen peroxide is 30wt%, and the volume ratio of the three is 3:3:4. The ultrasonic treatment is carried out at 60℃ to 80℃ for 30 minutes to 60 minutes, and the ultrasonic power is 100W to 200W. This treatment process not only removes oil stains and impurities on the surface of the catheter, but also introduces active groups such as hydroxyl groups on the surface, laying a foundation for the adhesion of the subsequent coating.

[0015] The preparation of the bottom adhesive layer uses in-situ polymerization method. Tris buffer solution, dopamine hydrochloride, gamma-aminopropyltriethoxysilane and silver nanoparticle dispersion are sequentially added to the reaction container, and the pretreated catheter is completely immersed after uniform stirring. Dopamine undergoes self-oxidation polymerization under alkaline conditions to form a polydopamine layer. Polydopamine contains various functional groups such as catechol, quinone and amino groups, which can strongly adhere to the surface of almost all materials. At the same time, the silane coupling agent forms silanol groups by hydrolysis, which further enhances the adhesion strength by condensation reaction with the surface of the catheter and polydopamine. Silver nanoparticles are embedded in the polydopamine layer, which can continuously release silver ions to play an antibacterial role, and are firmly fixed to avoid shedding. The reaction temperature is controlled at 20℃ to 25℃, and the reaction time is 12 hours to 24 hours, to ensure the formation of an adhesive layer with uniform thickness.

[0016] The preparation of the intermediate functional layer is a key step of the present application. First, low-crosslinking precursor solution A, medium-crosslinking precursor solution C and high-crosslinking precursor solution B are prepared respectively. The main components of the three solutions are the same, and the difference lies in the different contents of the crosslinking agent N,N'-methylenebisacrylamide. The molar fraction of the crosslinking agent in the precursor solution A is 0.6 mol% to 1.0 mol%, the precursor solution C is 1.2 mol% to 1.8 mol%, and the precursor solution B is 2.0 mol% to 3.0 mol%. Low crosslinking makes the polymer network have a larger free volume and strong swelling capacity; high crosslinking limits the swelling of the network but improves the mechanical strength. By sequentially coating the three solutions by programmed dip coating method, a continuous crosslinking degree gradient can be formed inside the coating.

[0017] The precise control of the parameters of the programmed dip coating process is crucial for gradient formation. In the first dip coating, the catheter is immersed in the precursor solution A to a depth of 80 mm, the pulling speed is 2 mm / s, and it stays at 30°C for 5 minutes. The slower pulling speed makes the coating thickness larger, and the lower temperature delays the occurrence of the polymerization reaction, giving time for the diffusion of the crosslinking agent. In the second dip coating, the immersion depth is reduced to 60 mm, the pulling speed is increased to 3 mm / s, and the temperature is kept at 30°C. In the third dip coating, the immersion depth is further reduced to 40 mm, and the pulling speed is increased to 4 mm / s. Through this gradient coating method, the inner coating is thick and low-crosslinking, and the outer coating is thin and high-crosslinking, forming a three-dimensional gradient structure with gradually increasing crosslinking degree from the inside to the outside.

[0018] The initiation polymerization step uses a redox initiation system. Potassium persulfate is used as an oxidizing agent, and N,N,N',N'-tetramethyl ethylenediamine is used as a reducing agent, which forms an efficient free radical initiation system. The initiator solution is sprayed on the surface of the coated catheter in an atomized manner to ensure uniform distribution of the initiator. Subsequently, a temperature gradient polymerization program is used: first, keep at 25°C for 30 minutes, which is beneficial to the uniform polymerization of the inner and outer layers; then increase the temperature to 50°C for 2 hours to accelerate the polymerization reaction; finally, increase the temperature to 70°C for 1 hour to ensure complete polymerization. The whole polymerization process is carried out in a nitrogen-filled reaction kettle to avoid the quenching of free radicals by oxygen. After the polymerization is completed, the catheter is immersed in deionized water for 24 hours, and the water is replaced every 8 hours to fully remove the unreacted monomers and low molecular weight polymers, ensuring the biological safety of the coating.

[0019] The outer protective layer is prepared by solution method. Polyethylene glycol methacrylate, N-isopropyl acrylamide, sulfobetaine methacrylate and azobisisobutyronitrile are dissolved in isopropyl alcohol, and pre-polymerization is carried out at 60°C for 2 hours. The purpose of pre-polymerization is to form a low molecular weight prepolymer with a molecular weight controlled between 10,000 and 30,000, which ensures the film-forming property of the coating and makes the coating have sufficient flexibility. After the pre-polymerization solution is cooled to room temperature, it is coated on the surface of the intermediate functional layer by dip coating or spin coating. The pulling speed is 5 mm / s when dip coating, and the coating is repeated 3 times to ensure the uniformity of the coating thickness. When spin coating, the rotation speed is 1000 rpm, and the time is 30 seconds. The coating is uniformly spread by centrifugal force. After coating is completed, it is dried at 50°C for 30 minutes to remove the solvent and further crosslink the coating.

[0020] The post-treatment step is crucial to improve the performance of the coating. First, it is treated in a vacuum oven at 80°C for 4 hours. This heat treatment process promotes the interfacial bonding between the layers, and the further condensation reaction of the silane coupling agent enhances the adhesion of the bottom layer to the substrate, while removing trace amounts of solvent and moisture remaining in the coating. Subsequently, it is crosslinked by γ-ray irradiation with a dose of 15 kGy to 25 kGy. The high-energy rays generated by irradiation cause crosslinking reactions of the polymer chains, introducing physical crosslinking points on the basis of chemical crosslinking, forming a more dense and stable three-dimensional network structure. Irradiation crosslinking can also effectively kill microorganisms, achieving the purpose of sterilization. Finally, the coated urinary catheter is immersed in simulated urine for 24 hours for hydration treatment. The simulated urine has a pH of 6.5 and contains 0.9 wt% sodium chloride and 5 g / L urea, which is close to the composition of real urine. After sufficient hydration, the coating reaches an equilibrium swelling state, preparing for actual use.

[0021] The application also provides the use of the above-mentioned temperature-responsive polyacrylic acid sodium urinary catheter leak-proof coating in the preparation of leak-proof urinary catheters. After the coating is coated on the surface of a medical-grade silicone or thermoplastic polyurethane urinary catheter, it produces controllable swelling to form a seal in a urine environment. The swelling rate of the coating is 150% to 200%, which is optimized to form an effective seal between the urinary catheter and the urethral wall without causing excessive pressure on the urethral tissue. When the patient's body temperature rises above 38°C, the N-isopropyl acrylamide component in the coating undergoes a phase transition from a hydrophilic stretched state to a hydrophobic contracted state, automatically inhibiting further swelling of the coating, with a volume contraction of 20% to 30% and a response time of less than 15 minutes. This temperature response characteristic provides a self-protection mechanism for the coating, avoiding excessive swelling in abnormal conditions such as fever.

[0022] The coating also has pH response characteristics. Under the condition of normal urine pH 6.5 and temperature 37℃, the coating reaches equilibrium swelling within 30 minutes, and the contact pressure with the urethral wall is 5kPa to 15kPa. This pressure range is carefully designed to form an effective seal while being far below the tissue ischemia threshold. When the pH value is increased to 7.5 to 8.5 due to urinary tract infection, the carboxyl groups of the acrylic component in the coating are fully ionized, generating electrostatic repulsion, which makes the coating swell by an additional 20% to 40%, enhancing the sealing effect. At the same time, the increase in pH triggers the release of antibacterial peptides from the mesoporous silica, with a 24-hour cumulative release of 30% to 40% at pH 8.0, which is 5 to 8 times that at normal pH, achieving intelligent response release.

[0023] The coating has excellent antibacterial performance, with an inhibition rate of more than 99% for E. coli, S. aureus and P. aeruginosa. The synergistic effect of silver nanoparticles and antibacterial peptides forms a double antibacterial barrier. After continuous immersion in simulated urine for 30 days, the retention rates of the swelling performance, temperature responsiveness and antibacterial performance of the coating are all greater than 85%, showing good long-term stability and meeting the use requirements of long-term indwelling catheters.

[0024] Compared with the prior art, the present application has the following beneficial effects:

[0025] The present application realizes intelligent control of the swelling degree of the coating through a temperature and pH dual response mechanism. The polyacrylic acid sodium component swells in urine to form a seal, and its swelling degree is regulated by the pH value and ionic strength of the urine; the low critical solution temperature of the N-isopropyl acrylamide component is close to body temperature, and phase transition occurs when the body temperature abnormally rises to inhibit excessive swelling and avoid tissue damage. This multiple response characteristic enables the coating to adapt to complex and variable physiological environments, which is not possessed by existing passive coatings.

[0026] The present application adopts a three-layer gradient structure design, and each layer has a specific function. The bottom adhesive layer realizes firm adhesion on the surfaces of substrates with different polarities such as silica gel and TPU through the biomimetic adhesion of polydopamine and the chemical bonding of silane coupling agents, overcoming the poor adaptability of traditional coatings. The three-dimensional crosslinking degree gradient structure of the middle functional layer is the core innovation of the present application, the low crosslinking in the inner layer provides high swelling ability to generate sealing pressure, the high crosslinking in the outer layer maintains structural integrity, and the gradient transition layer ensures the continuity of mechanical properties, avoiding delamination between layers. The zwitterionic polymer and low-temperature responsive PNIPAM components in the outer protective layer not only provide lubrication performance to facilitate catheter insertion, but also have anti-pollution function to prevent protein and bacterial adhesion.

[0027] The mechanical properties of the coating are significantly improved by the nanocomposite reinforcement strategy. The two-dimensional sheet structure of organically modified montmorillonite forms physical crosslinking points in the polymer matrix, hindering crack propagation, and the tensile strength is increased from 0.05 MPa of pure superabsorbent polymer to 0.15-0.25 MPa. Graphene oxide nanoplatelets provide additional hydrogen bond crosslinking, and their large specific surface area and unique two-dimensional structure effectively bear stress. Mesoporous silica nanoparticles act as rigid fillers, significantly improving the compressive modulus of the coating through the interaction of surface silicon hydroxyl groups with polymer chains. Irradiation crosslinking introduces physical crosslinking on the basis of chemical crosslinking, forming a dual network structure. These synergistic reinforcement mechanisms enable the coating to maintain high water absorption while having excellent mechanical strength and fatigue resistance, with a performance retention rate of over 85% after 100 cycles of compression.

[0028] The invention realizes the multifunctional integration of antibacterial and antifouling. The silver nanoparticles in the bottom layer continuously release silver ions, achieving broad-spectrum antibacterial through destroying bacterial cell membranes, interfering with DNA replication, and inducing oxidative stress. The intermediate layer loaded with antibacterial peptides releases intelligently under the pH response mechanism, accelerating release when pH rises due to infection, precisely attacking pathogenic bacteria. The antibacterial mechanism of antibacterial peptides is different from that of silver ions, and the synergistic effect of the two reduces the risk of drug resistance. The cation exchange capacity of organically modified montmorillonite can capture calcium and magnesium ions in urine, fixing them inside the coating rather than depositing on the surface, effectively delaying stone formation. The outer layer of zwitterionic polymer prevents crystal nucleation and growth through the hydration layer effect, keeping the coating surface clean. This multi-mechanism synergistic antibacterial and antifouling strategy is significantly superior to single-function coatings.

[0029] The preparation method of the invention is mature, parameters are controllable, and is suitable for industrial production. The programmed dip-coating process can reproducibly produce coatings with ideal gradient structures by precisely controlling the immersion depth, pulling speed, and temperature. The temperature gradient polymerization program ensures the consistency of the polymerization degree of the inner and outer layers. Irradiation crosslinking and sterilization can be completed in the same step, simplifying the process. All raw materials are commercial products or can be prepared according to standard methods, and the cost is controllable.

[0030] The coating of the invention has excellent biocompatibility. All components are FDA-approved or have medical device applications, and after sufficient unreacted monomer removal and sterilization, the cytotoxicity rating reaches 0-1, meeting the standards for mucosa-contacting medical devices. The compressive modulus of the coating at physiological temperature and pH is 4-8 kPa, which is well matched with the elastic modulus of the human urethral mucosa, avoiding tissue damage caused by hardness mismatch. DETAILED DESCRIPTION

[0031] In order to make the objects, technical solutions and advantages of the present application clearer, the present application will be further described in detail below with specific examples. It should be understood that these examples are only used to illustrate the present application and not used to limit the scope of the present application. Various modifications and changes can be made by those skilled in the art to the present application without departing from the spirit and scope of the present application, and these modifications and changes shall be included in the protection scope of the present application.

[0032] The raw materials used in the embodiments of the present application are all commercially available goods unless otherwise specified. Sodium acrylate, N-isopropyl acrylamide, acrylic acid, N,N'-methylenebisacrylamide, potassium persulfate and N,N,N',N'-tetramethylethylenediamine are purchased from Aldrich Reagent Company with a purity of more than 99%. γ-aminopropyltriethoxysilane, dopamine hydrochloride and cetyltrimethylammonium bromide are purchased from Sigma-Aldrich Company. The cation exchange capacity of sodium-based montmorillonite is 100 mmol / 100 g. Graphene oxide is an aqueous dispersion with a solid content of 2 mg / mL. Mesoporous silica nanoparticles, model number JM-SiO2-50, have an average particle size of 40 nm and a specific surface area of 500 m 2 / g. Antimicrobial peptide LL-37 is purchased from Jierong Biochemical (Shanghai) Co., Ltd. with a purity of more than 95%. Antimicrobial peptide HHC36 is synthesized by Nanjing Peptide Biological Technology Co., Ltd. with a purity of more than 98%. Silver nanoparticles have a particle size of 20 nm and are dispersed in water at a concentration of 1 mg / mL with polyvinylpyrrolidone as a stabilizer. Polyethylene glycol methacrylate is purchased from Macklin Reagent Company with a molecular weight of 475 Da. Sulfobetaine methacrylate is purchased from Beijing Inokay Technology Co., Ltd. Medical-grade silicone urinary catheters and thermoplastic polyurethane urinary catheters are purchased from Guangzhou Weili Medical Instrument Co., Ltd. with a specification of 14 Fr.

[0033] Example 1: Preparation of a temperature-sensitive poly(sodium acrylate) urinary catheter leak-proof coating

[0034] This example uses end-point values to prepare a leak-proof coating with the lowest crosslinking degree gradient and the smallest amount of addition. This example covers the minimum end-point value of 0.6 mol% on the inside and the minimum end-point value of 2.0 mol% on the outside of the crosslinking degree of the intermediate functional layer, as well as the minimum amount of addition of each nano-filler. This example can verify the basic performance of the coating under the minimum ratio conditions.

[0035] The catheter surface pretreatment was carried out as follows. Five medical-grade silicone catheters were taken, each with a length of 400 mm and an outer diameter of 4.67 mm. A pretreatment solution was prepared in a 1000 mL beaker by sequentially adding 30 mL of ammonia water with a mass fraction of 25 wt%, 30 mL of hydrogen peroxide with a mass fraction of 30 wt%, and 40 mL of deionized water. The mixture was stirred until homogeneous. The catheters were completely immersed in the solution and placed in an ultrasonic cleaner, with the temperature set to 60°C and the ultrasonic power set to 100 W. The treatment time was 30 minutes. During the ultrasonic treatment, the synergistic effect of ammonia and hydrogen peroxide effectively removed the silicone oil and other organic contaminants on the surface of the catheter, while introducing active groups such as hydroxyl groups onto the surface. After the treatment, the catheters were removed and rinsed repeatedly with deionized water for 5 times, each time for 3 minutes, to ensure that the residual chemical reagents on the surface were completely removed. Then the surface moisture was blown dry with high-purity nitrogen and placed in a clean container for use.

[0036] The bottom adhesive layer was prepared using in-situ polymerization. In a 500 mL three-necked flask, 100 g of Tris buffer solution was added, with a pH value of 8.5 and a concentration of 10 mM. The buffer solution was prepared by dissolving Tris base and adjusting the pH value with hydrochloric acid. Under magnetic stirring, 0.5 g of dopamine hydrochloride was added to the buffer solution and stirred for 10 minutes until completely dissolved. Dopamine begins to oxidize slowly under alkaline conditions, and the solution color gradually changes from colorless to light yellow. Then 2 g of γ-aminopropyl triethoxysilane was added and stirred for 10 minutes to hydrolyze and disperse uniformly. Finally, 10 mL of silver nanoparticle dispersion solution with a concentration of 1 mg / mL was added and stirred for 5 minutes to mix uniformly. The pretreated catheter was completely immersed in the mixture to ensure that all the surface was covered with the solution. The reaction was carried out at room temperature of 20-25°C for 12 hours. During the reaction, dopamine undergoes self-oxidation and polymerization, with its catechol groups being oxidized to o-benzoquinone, followed by Michael addition and Schiff base reaction to form polydopamine. The catechol groups in polydopamine form hydrogen bonds and covalent bonds with the silanol groups and silane coupling agents on the surface of the catheter, achieving firm adhesion. Silver nanoparticles are embedded in the polydopamine layer and are fixed by coordination with catechol and amino groups. After the reaction, the catheter was removed and rinsed thoroughly with deionized water, and dried in a 60°C oven for 2 hours to form a bottom adhesive layer with a thickness of about 5 μm.

[0037] The preparation of the intermediate functional layer first requires the preparation of three precursor solutions with different crosslinking densities. The low crosslinking density precursor solution A is prepared as follows. In a 250 mL beaker, 90 g of deionized water is added, which is treated with nitrogen for 30 minutes to remove dissolved oxygen to prevent inhibition of free radical polymerization. To the water, 15 g of sodium acrylate, 8 g of N-isopropyl acrylamide, and 2 g of acrylic acid are sequentially added, and mixed under magnetic stirring for 10 minutes until complete dissolution. Sodium acrylate provides superabsorbent properties, N-isopropyl acrylamide imparts temperature responsiveness, and acrylic acid introduces pH sensitivity. Subsequently, 3 g of organically modified montmorillonite is added. The preparation method of the montmorillonite is as follows: 10 g of sodium-based montmorillonite is dispersed in 200 mL of deionized water, heated to 80°C, and hexadecyltrimethylammonium bromide solution is slowly added dropwise under stirring, with the amount of CTAB being 1.2 times the cation exchange capacity of the montmorillonite. After 2 hours of reaction, the precipitate is collected by centrifugation and washed with ethanol and water alternately for 3 times, and dried at 60°C under vacuum for 24 hours to obtain organically modified montmorillonite. X-ray diffraction tests show that the interlayer spacing is expanded from the original 1.2 nm to 3.8 nm. After adding the organically modified montmorillonite to the precursor solution, a probe-type ultrasonic instrument is used to ultrasonically disperse for 30 minutes at a power of 300 W to ensure uniform dispersion of the nanosheets. Then 25 mL of graphene oxide dispersion solution with a concentration of 2 mg / mL is added, and stirring is continued for 10 minutes. Finally, the crosslinking agent N,N'-methylene bisacrylamide is added, with the amount being calculated according to the mole fraction, and the total number of moles of monomers is the sum of the moles of sodium acrylate, NIPAM, and acrylic acid, and the mole fraction of the crosslinking agent is 0.6 mol%, i.e. the amount of crosslinking agent is 0.04 g. Stirring is continued until complete dissolution to obtain the low crosslinking density precursor solution A.

[0038] The preparation of the medium crosslinking density precursor solution C is similar to that of the precursor solution A, except that the amount of crosslinking agent is adjusted to a mole fraction of 1.2 mol%, i.e. 0.08 g. The preparation of the high crosslinking density precursor solution B is different from A in that 8 g of mesoporous silica nanoparticles is added instead of graphene oxide, and the amount of crosslinking agent is 2.0 mol%, i.e. 0.14 g. The mesoporous silica needs to be treated with antibacterial peptide before use. The specific method is as follows: 10 g of mesoporous silica is added to 100 mL of absolute ethanol, and 5 mL of aminopropyltriethoxysilane is added, and the reaction is carried out at 80°C under reflux for 12 hours to graft amino groups onto the surface of the silica. After the reaction, the precipitate is collected by centrifugation and washed with ethanol for 3 times, and dried at 80°C under vacuum. The surface amino group density is determined by the indantrione colorimetric method to be 3.0 μmol / m 2In 50 mL phosphate buffer, dissolve antibacterial peptide LL-37 at a concentration of 2 mg / mL, and adjust pH to 6.0. Add EDC 150 mg and NHS 75 mg to activate the carboxyl end of the peptide at room temperature for 30 min. Then add amino-functionalized silica 5 g, adjust pH to 7.4, and react for 4 h. Centrifuge to collect the nanoparticles, and wash with PBS buffer 5 times to remove unbound peptides. Measure the peptide concentration in the supernatant by BCA protein quantification method, and calculate the immobilization efficiency as 65% and the peptide loading as 10 wt%.

[0039] The gradient coating process uses programmed dip-coating method. The catheter with prepared adhesive layer is fixed on the automatic lifting device, and first immersed in the precursor solution A, with the immersion depth set to 80 mm, and the lifting speed set to 2 mm / s. During the lifting process, the solution flows back under the action of gravity and surface tension, forming a uniform liquid film on the surface of the catheter. The coated catheter is placed in a constant temperature oven at 30°C for 5 minutes, during which the water in the solution evaporates slightly, the monomer and crosslinking agent concentrations increase slightly, and the crosslinking agent begins to diffuse to the coated layer. In the second dip-coating, the catheter is immersed in the precursor solution C, with the immersion depth set to 60 mm and the lifting speed set to 3 mm / s. Due to the reduced immersion depth, the second layer is only coated on part of the first layer, forming a decreasing thickness. In the third dip-coating, the catheter is immersed in the precursor solution B, with the immersion depth set to 40 mm and the lifting speed set to 4 mm / s. After three coatings, a gradient structure with gradually increasing crosslinking degree from the inside to the outside is formed on the surface of the catheter.

[0040] The initiator solution for the initiation of polymerization is prepared as follows. Dissolve potassium persulfate 0.5 g in 100 mL of deionized water to make a 5 g / L solution. Take another 100 mL of deionized water and add N,N,N',N'-tetramethyl ethylenediamine 0.3 mL to make a 3 mL / L solution. Mix the two solutions and immediately fill the spray device. Spray the initiator solution evenly on the surface of the coated catheter, with the spraying pressure set to 0.2 MPa, and control the spraying amount so that the surface is just wet. Potassium persulfate and tetramethyl ethylenediamine undergo redox reaction at room temperature to generate free radicals, which attack the double bonds of the monomers to initiate polymerization. Immediately place the sprayed catheter in a reaction kettle filled with nitrogen for protection, and follow the temperature program below: maintain at 25°C for 30 min, during which the polymerization proceeds slowly and the monomers are gradually consumed; increase the temperature to 50°C and maintain for 2 h, during which the polymerization rate increases and the crosslinked network forms; increase the temperature to 70°C and maintain for 1 h to ensure complete conversion of the monomers and solidification of the network. After the polymerization is completed, remove the catheter and immerse it in a large amount of deionized water, and soak at room temperature for 24 h, with the water replaced every 8 h. During the soaking process, unreacted monomers, initiators and low molecular weight polymers are dissolved out, and the coating is fully swollen to reach an equilibrium state. Gently absorb the surface water with filter paper to obtain the catheter with prepared intermediate functional layer. The coating thickness is measured to be about 50 μm with a micrometer.

[0041] The preparation method of the outer protective layer is as follows. In a 100 mL round-bottom flask, 80 g of isopropyl alcohol is added, and then 10 g of polyethylene glycol methacrylate, 5 g of N-isopropyl acrylamide, 3 g of sulfobetaine methacrylate, and 0.1 g of azobisisobutyronitrile are sequentially dissolved. AIBN is used as a thermal initiator to generate free radicals to initiate polymerization at 60°C. The mixed solution is stirred in a 60°C oil bath for 2 hours for pre-polymerization. The purpose of pre-polymerization is to partially polymerize the monomers to form a low molecular weight pre-polymer, and the molecular weight is about 15000 determined by gel permeation chromatography. Pre-polymerization not only increases the viscosity of the solution to facilitate film formation, but also maintains the flexibility of the polymer. After 2 hours of reaction, it is cooled to room temperature to obtain a slightly viscous pre-polymer solution. The solution is coated on the surface of the intermediate functional layer by dip coating at a pulling speed of 5 mm / s, and the coating is repeated 3 times to ensure that the coating is dense and pore-free. After each dip coating, the solution is allowed to partially evaporate at room temperature for 2 minutes. After three times of dip coating, the catheter is placed in a 50°C oven for drying for 30 minutes, and the isopropyl alcohol is completely evaporated, and the polymer is further cross-linked and solidified. The coating thickness is about 3 μm.

[0042] The post-processing steps include heat treatment, radiation cross-linking, and hydration treatment. The catheter with a three-layer coating is placed in a vacuum oven at 80°C for 4 hours, with a vacuum degree of -0.08 MPa. Heat treatment promotes the further condensation of silane coupling agents, the adhesion of the bottom layer to the substrate is more firm, and at the same time, trace amounts of residual solvents and moisture in the coating are removed. Subsequently, radiation cross-linking is performed using a cobalt 60 γ-ray irradiation device, with a radiation dose of 15 kGy and a dose rate of 5 kGy / h. γ-rays have strong penetrating ability and can uniformly irradiate the entire coating. High-energy rays cause hydrogen atoms on the polymer chain to detach to form macromolecular radicals, which couple with each other to form carbon-carbon cross-linking bonds, increasing the network density of the coating, and improving the mechanical strength and stability. Irradiation can also kill bacteria, viruses, and other microorganisms, achieving the purpose of sterilization. The irradiated catheter is immersed in simulated urine for hydration treatment. The preparation method of the simulated urine is as follows: in 1000 mL of deionized water, dissolve 9 g of sodium chloride, 5 g of urea, 2 g of potassium dihydrogen phosphate, and 1 g of magnesium sulfate, and adjust the pH to 6.5 with hydrochloric acid and sodium hydroxide. The catheter is completely immersed in the simulated urine and placed in a 37°C constant temperature oven for 24 hours. The coating is fully water-swollen to reach the use state. After taking out, the surface liquid is drained, and it is sealed and stored in a sterile packaging bag.

[0043] The overall thickness of the prepared anti-leakage coating urinary catheter is 58 μm, wherein the thickness of the adhesive layer is 5 μm, the thickness of the functional layer is 50 μm, and the thickness of the protective layer is 3 μm. The surface of the coating is smooth and uniform without cracks and peeling. The scanning electron microscope observation shows that the interface of the three-layer structure is tightly combined. The coating urinary catheter is immersed in simulated urine, and the coating gradually swells within 30 minutes at 37°C, and the swelling rate reaches 150%. The swelled coating is soft and has certain elasticity, and the touch is similar to that of hydrogel. The contact pressure between the coating and the urethral model silicone tube is 5 kPa, which is sufficient to form a seal but will not cause tissue damage.

[0044] Example 2: Preparation of an anti-leakage coating with moderate ratio of temperature-sensitive response

[0045] In this example, an anti-leakage coating with moderate crosslinking degree gradient and moderate additive amount is prepared by using an intermediate value formula. This example covers intermediate values of multiple parameters, such as an intermediate functional layer crosslinking degree of 0.8 mol% on the inside and 2.5 mol% on the outside, and a nano-filler amount of intermediate ratio. The performance balance of the coating under moderate ratio conditions can be verified through this example.

[0046] The surface pretreatment method of the urinary catheter is the same as that of Example 1, but a thermoplastic polyurethane urinary catheter with an outer diameter of 5.33 mm is used. The mass fraction of ammonia in the pretreatment solution is adjusted to 27 wt%, the ultrasonic temperature is 70°C, the ultrasonic power is 150 W, and the treatment time is 45 minutes. Compared with silicone, TPU material has higher polarity and is easier to be cleaned and activated under the same conditions.

[0047] When preparing the adhesive layer, 1.5 g of dopamine hydrochloride, 5 g of γ-aminopropyl triethoxysilane, and 30 mL of silver nanoparticle dispersion liquid are added to 100 g of Tris buffer. The reaction temperature is 22°C, and the reaction time is 18 hours. The increased amount of dopamine and silane makes the formed adhesive layer thicker and denser, with a thickness of about 10 μm.

[0048] The precursor solution A of the intermediate functional layer is prepared as follows: 120 g of deionized water, 25 g of sodium acrylate, 14 g of N-isopropyl acrylamide, 5 g of acrylic acid, 7.5 g of organically modified montmorillonite, 87.5 mL of graphene oxide dispersion liquid, and 0.06 g of crosslinking agent corresponding to 0.8 mol%. The crosslinking agent in the precursor solution C has a mole fraction of 1.5 mol%, i.e., 0.11 g. In the preparation of the precursor solution B, the amounts of sodium acrylate, NIPAM, and acrylic acid are the same as those in A, 13 g of mesoporous silica is added, the mole fraction of the crosslinking agent is 2.5 mol%, i.e., 0.18 g. The mesoporous silica loaded antibacterial peptide is replaced by HHC36, which has a smaller molecular weight and a higher loading efficiency of 70% in mesoporous silica, with a loading amount of 12 wt%.

[0049] The gradient coating process parameters were adjusted as follows: the first dip coating immersion depth was 80 mm, the pulling speed was 2 mm / s, and the residence time at 35 °C was 7 minutes; the second dip coating immersion depth was 60 mm, the pulling speed was 3 mm / s, and the residence time at 35 °C was 7 minutes; the third dip coating immersion depth was 40 mm, the pulling speed was 4 mm / s, and the residence time at 35 °C was 7 minutes. Higher residence temperature accelerated the diffusion rate, and the transition of the crosslinking degree gradient was more gradual.

[0050] The same initiator system was used for the initiation of polymerization, and the temperature program was adjusted to 25 °C for 30 minutes, 55 °C for 2.5 hours, and 75 °C for 1.5 hours. The appropriate extension of the polymerization time ensured complete polymerization under the condition of moderate crosslinking degree. The thickness of the intermediate functional layer was about 75 μm.

[0051] The solution for the outer protective layer contained polyethylene glycol methacrylate 17.5 g, N-isopropyl acrylamide 10 g, sulfobetaine methacrylate 6.5 g, AIBN 0.3 g, and isopropyl alcohol 100 g. The pre-polymerization conditions were the same, and spin coating was used for preparation at a speed of 1000 rpm for 30 seconds, repeated twice. The thickness of the outer layer was about 5.5 μm.

[0052] In the post-processing, the heat treatment temperature and time were unchanged, and the irradiation dose was increased to 20 kGy. Higher irradiation dose further enhanced the network crosslinking on the basis of moderate crosslinking degree, and the mechanical strength and dimensional stability of the coating were better. The conditions for hydration treatment were the same.

[0053] The total thickness of the coating prepared in this example was about 90.5 μm. In the simulated urine at 37 °C and pH 6.5, the swelling rate was 175%, and the contact pressure was 10 kPa, achieving a good balance between sealing performance and tissue safety. When the temperature rose to 39 °C, the volume of the coating shrank by 25%, and the response time was 12 minutes, with excellent temperature sensitivity.

[0054] Example 3: Preparation of a maximum ratio temperature-sensitive anti-leakage coating

[0055] This example used an end point value formula to prepare an anti-leakage coating with the highest crosslinking degree gradient and the largest amount of addition. This example covered the maximum end point value of 1.0 mole% on the inside and 3.0 mole% on the outside of the crosslinking degree of the intermediate functional layer, as well as the maximum amount of addition of each nano-filler. Through this example, the upper limit of the performance of the coating under the extreme ratio condition could be verified.

[0056] The surface of the urinary catheter was pretreated using a silica gel urinary catheter with an outer diameter of 4.67 mm. The ammonia water mass fraction in the pretreatment solution was 28 wt%, the ultrasonic temperature was 80 °C, the ultrasonic power was 200 W, and the treatment time was 60 minutes. Stronger pretreatment conditions introduced more active groups on the surface.

[0057] The bottom adhesive layer was prepared by adding dopamine hydrochloride 3 g, γ-aminopropyl triethoxysilane 8 g, and silver nanoparticle dispersion 50 mL. The reaction temperature was 25 °C, and the reaction time was 24 hours. The thickness of the bottom layer reached 15 μm, which was the upper limit of the designed thickness. A thicker bottom layer provided stronger adhesion but also affected the flexibility of the coating.

[0058] The precursor solution A of the middle functional layer was prepared with deionized water 150 g, sodium acrylate 35 g, N-isopropyl acrylamide 20 g, acrylic acid 8 g, organically modified montmorillonite 12 g, graphene oxide dispersion 150 mL, and crosslinker mole fraction 1.0 mol% (0.08 g). The crosslinker mole fraction of the precursor solution C was 1.8 mol% (0.14 g). In the precursor solution B, mesoporous silica 18 g and organically modified montmorillonite 12 g were added, and the crosslinker mole fraction was 3.0 mol% (0.24 g). The mesoporous silica simultaneously loaded two kinds of antibacterial peptides, LL-37 and HHC36, with LL-37 accounting for 60% and HHC36 accounting for 40%, and the total loading amount was 15 wt%. The synergistic effect of the two peptides can broaden the antibacterial spectrum and reduce the risk of drug resistance.

[0059] The gradient coating process parameters were as follows: the first immersion coating with immersion depth 80 mm, pulling speed 2 mm / s, and 38 °C for 10 minutes; the second immersion coating with immersion depth 60 mm, pulling speed 3 mm / s, and 38 °C for 10 minutes; the third immersion coating with immersion depth 40 mm, pulling speed 4 mm / s, and 38 °C for 10 minutes. Longer residence time allowed for more complete gradient transition.

[0060] The temperature program for initiating polymerization was 25 °C for 30 minutes, 60 °C for 3 hours, and 80 °C for 2 hours. Higher polymerization temperature and extended time ensured complete polymerization under high crosslinking conditions. The thickness of the middle functional layer reached 100 μm.

[0061] In the outer protective layer solution, polyethylene glycol methacrylate 25 g, N-isopropyl acrylamide 15 g, sulfobetaine methacrylate 10 g, AIBN 0.5 g, and isopropyl alcohol 120 g were used. The dense protective layer was formed by repeating the immersion coating 5 times with a pulling speed of 5 mm / s. The thickness of the outer layer was about 8 μm.

[0062] In the post-processing, the upper limit of the irradiation dose was 25 kGy, which maximized the crosslinking density and stability of the coating. The hydration treatment time was extended to 48 hours to ensure that the thick coating was fully balanced and swollen.

[0063] The total thickness of the coating prepared in this example reached 123 pm. Due to high crosslinking degree and large amount of nanofillers, the mechanical strength of the coating reached the maximum, with tensile strength of 0.30 MPa and compression modulus of 8 kPa. The swelling ratio in simulated urine was 200%, reaching the designed upper limit of swelling, and the contact pressure was 15 kPa. Although the swelling ratio and contact pressure both reached the maximum, they were still within the safe range and would not cause tissue ischemia. The temperature response test showed that the volume shrank by 30% at 40°C, and the response time was 10 minutes, which was the fastest response in the series of examples. The pH response test showed that the additional swelling was 40% at pH 8.5, the cumulative release amount of antimicrobial peptide LL-37 reached 40% in 24 hours, and the intelligent response performance was the best.

[0064] Example 4: Preparation of an optimized ratio of temperature-sensitive response type leakage-proof coating

[0065] Based on the performance test results of the previous examples, this example used an optimized formula and process parameters to prepare a leakage-proof coating with the best overall performance. The parameters of this example were selected between the endpoint value and the intermediate value, and were determined after multiple tests.

[0066] The catheter was made of TPU material with an outer diameter of 5.33 mm. The mass fraction of ammonia in the pretreatment solution was 26 wt%, the ultrasonic temperature was 75°C, the ultrasonic power was 180 W, and the treatment time was 50 minutes.

[0067] Dopamine hydrochloride 2 g and g-aminopropyltriethoxysilane 6 g were added when preparing the bottom adhesive layer, and silver nanoparticle dispersion liquid 35 mL was added. The reaction temperature was 23°C, and the reaction time was 20 hours. The thickness of the bottom layer was about 12 pm.

[0068] The precursor solution A of the middle functional layer was prepared as follows: deionized water 135 g, sodium acrylate 28 g, N-isopropyl acrylamide 16 g, acrylic acid 6 g, organically modified montmorillonite 9 g, graphene oxide dispersion liquid 100 mL, and crosslinker mole fraction 0.7 mol%. The crosslinker mole fraction of the precursor solution C was 1.4 mol%. Mesoporous silica 15 g and organically modified montmorillonite 9 g were added to the precursor solution B, and the crosslinker mole fraction was 2.3 mol%. The mesoporous silica was loaded with LL-37, and the loading amount was 13 wt%.

[0069] The gradient coating process parameters were optimized, with the first dip coating at 32°C for 6 minutes, the second at 33°C for 6 minutes, and the third at 34°C for 6 minutes. The small temperature gradient combined with time control made the crosslinking degree gradient more ideal.

[0070] The temperature program for initiating polymerization was 25°C for 30 minutes, 58°C for 2.8 hours, and 78°C for 1.8 hours. The thickness of the middle functional layer was about 85 pm.

[0071] Outer protective layer solution: polyethylene glycol methacrylate 20 g, N-isopropyl acrylamide 12 g, sulfobetaine methacrylate 8 g, AIBN 0.4 g, isopropyl alcohol 110 g. The coating was prepared by a combination of dip coating and spin coating. The coating was first dip coated once to form the bottom layer, and then spin coated once to form the surface layer. The thickness of the outer layer was about 6 μm.

[0072] Post-treatment irradiation dose: 22 kGy. Hydration treatment: 36 hours.

[0073] The total thickness of the coating prepared in this example was about 103 μm, and the performance was the most balanced in the series of examples. The expansion rate was 185%, the contact pressure was 12 kPa, and the temperature response speed and pH response sensitivity reached excellent levels. Subsequent performance tests showed that this example was the best embodiment.

[0074] Comparative Example 1: Leak-proof coating without temperature-sensitive component

[0075] To verify the contribution of the N-isopropyl acrylamide component to temperature responsiveness, a coating without NIPAM was prepared in this comparative example, and the other components and processes were the same as in Example 2. The intermediate functional layer precursor solution only contained sodium acrylate 25 g, acrylic acid 5 g, and other components, without NIPAM. Due to the absence of NIPAM, the amount of sodium acrylate was increased to 30 g to maintain the total monomer amount. The remaining preparation steps were exactly the same.

[0076] Performance tests showed that the coating had an expansion rate of 180% at 37°C, which was close to that of Example 2. However, when the temperature rose to 40°C, the expansion rate only decreased by 5% to 175%, while that of Example 2 decreased by 25% to 150%. This showed that the coating without the NIPAM component could not effectively respond to temperature changes and could not automatically inhibit expansion when the body temperature abnormally increased, posing a risk of excessive expansion.

[0077] Comparative Example 2: Leak-proof coating without pH-responsive component

[0078] To verify the contribution of the acrylic acid component to pH responsiveness, a coating without acrylic acid was prepared in this comparative example. The intermediate functional layer precursor solution only contained sodium acrylate 25 g, NIPAM 14 g, and other components. The remaining process was the same as in Example 2.

[0079] Performance tests showed that the expansion rate was 170% at pH 6.5, and only increased to 178% at pH 8.0, with an increase of only 5%, while that of Example 2 increased by 25%. This showed that the coating without the acrylic acid component had significantly weakened pH responsiveness and could not enhance the sealing effect when the pH increased due to infection. In addition, due to the weakened pH response trigger, the release of the antibacterial peptide was also not effectively accelerated, and the 24-hour release amount at pH 8.0 was only 15%, which was much lower than the 35% of Example 2.

[0080] Comparative Example 3: Non-nanofiller reinforced leakproof coating

[0081] To verify the reinforcement of nanofillers on the mechanical properties of the coating, this comparative example prepared a coating without organic modified montmorillonite, graphene oxide and mesoporous silica. The intermediate functional layer precursor solution only contained monomers and crosslinkers. The rest of the process was the same as Example 2.

[0082] Performance tests showed that the tensile strength of the coating was only 0.08 MPa, less than half of Example 2. The compression modulus was 1.5 kPa, also much lower than the 6 kPa of Example 2. In the cyclic compression test, the compression stress decreased by more than 50% after 50 cycles, and the coating showed obvious plastic deformation and fatigue damage. After immersion in simulated urine for 15 days, fine cracks appeared on the surface of the coating, and some areas peeled off, showing poor long-term stability. This fully demonstrates the key role of nanocomposite reinforcement in improving the mechanical properties and durability of the coating.

[0083] Comparative Example 4: Non-gradient uniform crosslinked leakproof coating

[0084] To verify the advantages of the crosslinking degree gradient design, this comparative example prepared a coating with uniform crosslinking. The intermediate functional layer used a single precursor solution, with a crosslinker molar fraction of 1.5 mol%, and a uniform coating was formed by one-time dip coating. Other components were the same as Example 2.

[0085] Performance tests showed that the coating swelled unevenly in simulated urine, with limited swelling on the inside and insufficient sealing pressure of 6 kPa, while the outside swelled excessively, causing cracks on the surface. The tensile elongation at break was only 200% in the mechanical test, much lower than the 400% of the gradient coating, showing poor flexibility. Tests in the urethral model found that due to insufficient sealing force on the inside, a small amount of urine leakage still occurred. This proves the necessity of the gradient structure design, with low crosslinking on the inside to provide swelling force and high crosslinking on the outside to maintain integrity, both of which work together to achieve optimal performance.

[0086] Comparative Example 5: Leakproof coating without antibacterial components

[0087] To verify the role of antibacterial components, this comparative example prepared a coating without silver nanoparticles and antibacterial peptides. The bottom adhesive layer did not add silver nanoparticles, and the mesoporous silica did not load antibacterial peptides. The rest was the same as Example 2.

[0088] Performance tests showed that the swelling property and temperature-pH responsiveness of the coating were the same as Example 2. However, in the antibacterial test, the inhibition rate against E. coli was only 25%, and against S. aureus was 30%, much lower than 99% in Example 2. After immersion in the bacteria-containing simulated urine for 7 days, obvious biofilm appeared on the surface of the coating, and the color of the coating changed from transparent to turbid, indicating that the bacteria proliferated massively. This proved the importance of the antibacterial component for preventing catheter-related infections.

[0089] To comprehensively evaluate the performance of the coatings of various examples and comparative examples, the following test methods were designed.

[0090] The swelling rate test was performed according to the following steps. A 50 mm long sample of the coated catheter was cut and accurately weighed to obtain the dry mass, denoted as m0. The sample was completely immersed in 37°C simulated urine, and every 5 minutes, it was taken out and the surface liquid was gently absorbed with filter paper, and then weighed to obtain mt. The change of mt with time was plotted, and when the mass no longer increased, the equilibrium swelling was reached, and the equilibrium mass me was recorded. The swelling rate ER was calculated according to the formula: ER = (me - m0) / m0 x 100%. Each group of samples was tested 3 times to obtain the average value.

[0091] The temperature responsiveness test method was as follows: the equilibrium-swelled coating sample was transferred from 37°C simulated urine to simulated urine at different temperatures, and the temperature was set to 25°C, 30°C, 35°C, 37°C, 38°C, 39°C, and 40°C. After 30 minutes at each temperature, the sample was weighed, and a plot of the swelling rate versus temperature was drawn. The volume change in the interval of 38°C to 40°C was particularly focused on, and the volume shrinkage rate was calculated. The response time was defined as the time required to reach 90% of the shrinkage amount after being transferred from 37°C to 40°C.

[0092] The pH responsiveness test method was as follows: simulated urine with pH values of 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, and 8.5 was prepared, and the ionic strength was kept constant. The equilibrium-swelled coating sample was immersed in solutions with different pH values, and the swelling rate was measured after 30 minutes at 37°C. A plot of the swelling rate versus pH was drawn. The antibacterial peptide release test used HPLC method to detect the peptide concentration in the soaking solution, and the cumulative release rate was calculated.

[0093] The sealing performance test used a self-made sealing pressure test device. The device was composed of a silicone simulated urethral tube and a precision pressure sensor. The inner diameter of the silicone tube was selected according to the outer diameter of the catheter to ensure that the coating could contact the tube wall after swelling. The hydrated coated catheter was inserted into the silicone tube, and simulated urine was injected into the silicone tube, and the contact pressure between the coating and the tube wall was monitored in real time by the pressure sensor. The stable pressure value was recorded. At the same time, the urine leakage test was performed, and a liquid pressure of 20 cmH2O was applied at the bladder end for 24 hours, and the liquid leaked from the urethral end was collected and the volume was measured.

[0094] Mechanical properties were tested on an electronic universal testing machine. For tensile test, the coating was made into dumbbell-shaped strips with a length of 50 mm, a width of 5 mm, and a thickness of about the coating thickness. The test speed was 50 mm / min, and the stress-strain curve was recorded to calculate the tensile strength and elongation at break. For compression test, cylindrical samples with a diameter of 10 mm and a height of 5 mm were used, and the compression speed was 10 mm / min. A strain of 50% was applied, and the compression stress was recorded. For cyclic compression test, the compression was repeated 100 times, each time to a strain of 50% and then unloaded, and the stress decay was observed. All mechanical tests were performed in the hydrated state at a temperature of 37°C.

[0095] Antibacterial properties were tested by agar diffusion method and shake flask method. In the agar diffusion method test, the coating sample was cut into a 10-mm-diameter disc and placed on an agar plate inoculated with the test strain. The plate was incubated at 37°C for 24 hours, and the diameter of the inhibition zone was measured. The test strains included Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa ATCC 27853. In the shake flask method test, the coating sample was immersed in a PBS solution containing 105 CFU / mL bacteria and incubated at 37°C for 24 hours with shaking. The sample was then taken for plate counting, and the antibacterial rate was calculated. The antibacterial rate was equal to the number of colonies in the control group minus the number of colonies in the experimental group, divided by the number of colonies in the control group, multiplied by 100%.

[0096] The long-term stability test method was as follows: the coating catheter was completely immersed in simulated urine and placed in a 37°C constant-temperature incubator to simulate long-term indwelling. The sample was taken out every 5 days for expansion rate, temperature responsiveness, pH responsiveness, and antibacterial property tests, and the tests were performed continuously for 30 days. The performance retention rate was defined as the performance value at the test time point divided by the initial value multiplied by 100%. Scanning electron microscopy was used to observe the surface morphology changes of the coating and to evaluate whether there were defects such as cracks and peeling.

[0097] Biocompatibility evaluation was performed according to the GB / T 16886.5-2017 standard for cytotoxicity test. The coating sample was extracted with normal saline at 37°C for 72 hours, with an extraction ratio of 6 cm 2 The surface area corresponds to 1 mL of the extract. The extract was mixed with L929 mouse fibroblast culture medium at different proportions, with concentrations of 100%, 50%, 25%, and 12.5%. The cells were inoculated in a 96-well plate, and 100 μL of culture medium containing the extract was added to each well. Negative and positive controls were set. After incubation at 37°C in a 5% CO2 incubator for 24 hours, MTT solution was added, and the incubation was continued for 4 hours. The culture medium was discarded, DMSO was added to dissolve the formazan crystals, and the absorbance at 570 nm was measured using a microplate reader. The cell survival rate was equal to the absorbance of the experimental group divided by the absorbance of the control group multiplied by 100%. The toxicity grade was determined according to the cell survival rate.

[0098] The main performance indicators of each embodiment and comparative example are shown in the following table:

[0099] Sample Swelling rate (%) Contact pressure (kPa) Shrinkage rate at 40°C (%) Additional swelling at pH 8 (%) Tensile strength (MPa) Bacteriostatic rate (%) Performance retention rate after 30 days (%) Cell survival rate - 100% extract (%) Cell survival rate - 50% extract (%) Toxicity grade Example 1 150 5 20 20 0.15 99.2 88 86 94 Grade 1 Example 2 175 10 25 25 0.21 99.5 92 91 97 Grade 1 Example 3 200 15 30 40 0.3 99.8 95 88 95 Grade 1 Example 4 185 12 27 32 0.26 99.6 94 93 98 Grade 0 Comparative Example 1 180 10 5 28 0.2 99.3 90 90 96 Grade 1 Comparative Example 2 170 9 26 5 0.19 45 85 92 97 Grade 1 Comparative Example 3 165 8 22 23 0.08 98.5 62 82 91 Grade 1 Comparative Example 4 160 6 24 26 0.18 99 80 89 95 Grade 1 Comparative Example 5 172 10 25 25 0.21 28 70 87 94 Grade 1

[0100] As can be seen from the data in the table, the performance of the coating prepared in Examples 1 to 4 meets the design requirements. Example 3 has the highest performance indicators due to the use of the largest proportion, but considering the cost factor, the optimized formulation of Example 4 has the highest cost performance and the best comprehensive performance, and can be used as the best implementation scheme.

[0101] Comparative Example 1 has significantly reduced temperature response performance due to the lack of NIPAM component, with a shrinkage rate of only 5% at 40°C, which cannot effectively prevent excessive swelling. Comparative Example 2 has significantly reduced pH response performance due to the lack of acrylic acid component, and the release of antibacterial peptides is blocked, resulting in a reduction in the inhibition rate to 45%. Comparative Example 3 has a tensile strength of only 0.08 MPa due to the lack of nano-filler enhancement, poor long-term stability, and a performance retention rate of only 62% after 30 days. The uniform cross-linking design of Comparative Example 4 results in insufficient contact pressure and poor sealing effect. Comparative Example 5 lacks an antibacterial component, with an inhibition rate of only 28%, which cannot effectively prevent infection.

[0102] These comparative data fully demonstrate the necessity and synergistic effect of the technical features of the present application. The temperature-sensitive component NIPAM, the pH-sensitive component acrylic acid, the nano-filler enhancement, the gradient cross-linking structure and the antibacterial component are indispensable, and only the organic combination of these features can achieve excellent leakage prevention performance, intelligent responsiveness, mechanical strength and antibacterial effect.

[0103] As can be seen from the biocompatibility test data, the cytotoxicity grade of all examples and comparative examples reaches 0 or 1, meeting the safety requirements of mucosa-contacting medical devices. This result verifies the rationality of the present application in material selection and preparation process.

[0104] Example 4 shows the best biocompatibility, with a cell survival rate of 93% in a 100% concentration extract, reaching the 0 level toxicity standard. This excellent performance is due to the optimized formulation design in this example. The amount of each component is at a moderate level, which ensures functionality and avoids the accumulation of cytotoxicity caused by excessive addition. In particular, the amount of silver nanoparticles is controlled at 35 mL of dispersion, which is equivalent to a silver content of about 0.03 wt% in the total formulation. This concentration can exert an antibacterial effect without causing significant cytotoxicity to cells. The antibacterial peptide LL-37 is a human-derived peptide, which has excellent biocompatibility. The slow-release characteristics of the 13 wt% loading further reduce the local concentration and avoid stimulation to cells.

[0105] The cell survival rates of Example 2 and Example 4 are both over 90%, showing good biological safety. Example 1 has a minimum ratio, and the amount of each component is low, so the concentration of soluble substances in the extract solution is also low, and the cell survival rate is 86%, which is slightly lower than other examples but still meets the first level standard. Example 3 uses the maximum ratio, and the content of nanofillers and functional components is the highest, and there are relatively more free small molecules in the extract solution, resulting in a cell survival rate of 88%, which is slightly lower than Example 2 with an intermediate ratio, but still within the safety range. This result suggests that in actual application, the formulation design should be balanced according to performance requirements and safety requirements, rather than simply pursuing the maximum addition amount.

[0106] It is worth noting that when the extract solution is diluted to a concentration of 50%, the cell survival rate of all samples is significantly improved, and Example 2 and Example 4 both reach more than 97%. This concentration dependence indicates that the coating material itself does not contain strong toxic substances, and its effect on cells is mainly due to the concentration effect of soluble small molecules. In actual use, the coating surface is in contact with tissue fluid and urine, and the local concentration will be diluted by a large amount of body fluid, so the actual biological safety is better than the in vitro test data.

[0107] The biocompatibility data of the comparative examples is also worth analyzing. Comparative Example 3 lacks nanofiller enhancement, resulting in poor mechanical properties and long-term stability, but due to the simplification of components, its cytotoxicity is slightly lower, with a cell survival rate of 82% under 100% extract solution. This phenomenon shows that the introduction of nanofillers indeed needs to be concerned about its biological safety while improving performance. The organic modified montmorillonite, graphene oxide and mesoporous silica selected by the present application are all materials with biomedical applications, and after strict quality control and surface modification treatment, their biocompatibility is ensured. The amount of these nanofillers in the examples is optimized to play a reinforcing role while not introducing significant cytotoxicity.

[0108] Comparative Example 2 lacks the acrylic component, but its pH-responsive release is blocked, resulting in a slightly higher release amount of antibacterial peptide at normal pH, but its cell survival rate still reaches 92%, indicating that the LL-37 antibacterial peptide is still well selective for mammalian cells even at a higher concentration. This verifies the advantage of antibacterial peptides over traditional antibiotics, which have a much stronger impact on bacteria than on human cells.

[0109] Comparative Example 5 lacks the antibacterial component and should theoretically have the lowest cytotoxicity, but its cell survival rate is 87%, which is not significantly better than the examples containing the antibacterial component. This result further demonstrates the safety of silver nanoparticles and antibacterial peptides at the concentrations used in the present application. Silver nanoparticles are embedded by a polydopamine layer, and the release is controlled and will not cause cytotoxicity due to burst release. The antibacterial peptide is fixed on the surface of mesoporous silica by covalent bonding and is only released faster when triggered by pH response, and the free concentration under normal conditions is very low.

[0110] From the perspective of the preparation process, the treatment of sufficient soaking to remove unreacted monomers is crucial in the present application. Residual monomers such as sodium acrylate, N-isopropyl acrylamide, and potassium persulfate initiator used in the polymerization reaction can cause cytotoxicity. In the examples, the catheter after polymerization was soaked in deionized water for 24 hours and the water was replaced every 8 hours, ensuring the sufficient removal of soluble small molecules. The excellent results of the cytotoxicity test verify the effectiveness of this process. In addition, the irradiation cross-linking and sterilization steps not only improve the mechanical strength and sterility of the coating, but the free radical reactions generated by irradiation can also further consume residual monomer molecules, reducing potential cytotoxicity.

[0111] Biocompatibility is closely related to the chemical composition of the coating. Sodium polyacrylate has been widely used as a superabsorbent material in products such as baby diapers for decades, and its safety has been fully verified. Poly-N-isopropyl acrylamide is widely studied in the biomedical field for drug delivery, tissue engineering, and other applications, and numerous literature reports its good biocompatibility. Polydopamine, as a biomimetic material, has a structure similar to mussel adhesive protein and is non-toxic to cells. Zwitterionic polymers such as sulfobetaine methacrylate do not have strong electrostatic interactions with cell membranes due to their charge balance characteristics, so they have very low cytotoxicity. The rational combination of these materials ensures the overall biological safety of the coating system.

[0112] It should be noted that in vitro cytotoxicity testing, although an important means of evaluating biocompatibility, only represents a part of the evaluation of material safety. A complete biological evaluation should also include multiple aspects such as sensitization, irritation, systemic toxicity, and hemocompatibility. For mucosa-contacting devices such as catheters, animal in vivo urethral irritation and long-term implantation tests are also required. The excellent performance of the present application in cytotoxicity lays a good foundation for subsequent complete biological evaluation. According to literature reports and experience with similar products, coatings using the components of the present application are expected to perform well in other biological evaluation projects.

[0113] Based on the comprehensive results of biocompatibility tests and other performance indicators, Example 4 is the best embodiment not only in terms of optimal balance of functional performance, but also in terms of biological safety, which further verifies the rationality of its selection as the preferred solution. The parameter settings of this example reflect the best balance point of performance and safety, and can be used as a standard formula for industrial production. Although Examples 2 and 3 have advantages in some single performances, considering the biocompatibility and cost-effectiveness, Example 4 is still the best choice.

[0114] The excellent performance of the temperature-sensitive responsive leak-proof coating of the present application is due to the synergistic effect of its unique molecular structure design and multiple action mechanisms. From the molecular level, the carboxyl anions of the sodium acrylate unit produce strong electrostatic repulsion in aqueous solution, driving the polymer chain to stretch, while the carboxyl groups form hydrogen bonds with water molecules, and each carboxyl group can bind multiple water molecules, achieving high expansion. When the pH of urine increases, the ionization degree of carboxyl group increases, the electrostatic repulsion increases, and the expansion degree further increases. This pH response mechanism enables the coating to sense infection signals and enhance sealing. The N-isopropyl acrylamide unit contains hydrophobic isopropyl and hydrophilic amide groups. At low temperatures, the amide group forms hydrogen bonds with water molecules, and the polymer assumes an extended conformation. When the temperature exceeds the lower critical solution temperature, the thermal motion destroys the hydrogen bonds, and the hydrophobic interaction dominates, causing the polymer chain to collapse. This temperature response provides a self-protection mechanism for the coating.

[0115] The formation mechanism of the gradient crosslinking structure lies in the concentration difference and diffusion behavior of the crosslinking agent between different layers. The low crosslinking in the inner layer results in large network pore size and high free volume, and the network can expand significantly to generate swelling stress after water absorption. The high crosslinking in the outer layer results in small network pore size, which limits excessive swelling and maintains the structural integrity. This gradient design is similar to the structure of natural tissues, such as the gradual increase in hardness from the surface to the deep layer of cartilage, achieving rigidity and flexibility. In terms of mechanics, the gradient structure avoids stress concentration at the interface, and when the coating is subjected to external force, the stress can gradually transition in the gradient region, without sudden changes at a certain interface that can cause cracking.

[0116] The enhancement mechanism of nanofillers is multi-faceted. The two-dimensional sheet structure of organically modified montmorillonite is dispersed in the polymer matrix in an exfoliated or intercalated state. The hydroxyl groups on the surface of the sheet form hydrogen bonds with the carboxyl and amide groups of the polymer chains, constituting physical crosslinking points. When the coating is under stress, the sheet bears part of the load and transmits it to the matrix through interfacial shear force, hindering the crack propagation path. At the same time, the interlayer cations of montmorillonite can exchange with calcium and magnesium ions in urine, fixing them inside the coating and preventing the deposition of stones on the surface. Graphene oxide nanosheets have a large specific surface area and abundant oxygen-containing functional groups. The carboxyl, hydroxyl, and epoxy groups form multiple hydrogen bonds or even covalent bonds with the polymer chains, forming a three-dimensional network structure. The high modulus of graphene oxide gives the coating better anti-deformation ability. Mesoporous silica, as a rigid inorganic particle, enhances the interfacial bonding through the interaction between its surface silanol groups and the polymer chains, while the mesoporous structure provides space for drug loading, achieving both structural reinforcement and functional loading.

[0117] Radiation crosslinking, a physical crosslinking introduced on the basis of chemical crosslinking, is achieved through free radical reactions induced by high-energy radiation. The energy of γ-rays is sufficient to break the carbon-hydrogen bonds on the polymer chains, generating macromolecular free radicals, which couple with each other to form carbon-carbon bonds. This crosslinking is randomly distributed, complementary to the regular crosslinking points formed by chemical crosslinking agents, forming a double network structure. The synergistic effect of the double network makes the coating have both high strength and high toughness, which is difficult to achieve in a single crosslinking system.

[0118] The synergy of the antibacterial mechanism lies in the different target points of silver ions and antibacterial peptides. Silver ions mainly combine with thiol groups on the bacterial cell membrane to destroy membrane integrity, and after entering the cell, they combine with DNA to interfere with replication, while catalyzing the production of reactive oxygen to cause oxidative damage. Antimicrobial peptides, on the other hand, electrostatically adsorb to the anionic lipids on the bacterial membrane through cationic interactions, and the hydrophobic segments insert into the membrane to form pores, leading to the leakage of cell contents. The simultaneous action of the two mechanisms makes it difficult for bacteria to develop resistance. The pH-responsive release mechanism ensures that the antibacterial peptides are released slowly under normal conditions to maintain basic antibacterial properties, and are released quickly during infection to enhance antibacterial properties, achieving precise drug delivery.

[0119] The anti-fouling mechanism of zwitterionic polymers lies in their unique hydration layer effect. The sulfobetaine unit carries both positive and negative charges, strongly attracting water molecules to form a tight hydration layer in aqueous solution. When proteins, bacteria, or crystals approach the surface of the coating, they must first break through the hydration layer to be adsorbed, and the high binding energy of the hydration layer constitutes a strong energy barrier. In addition, the charge balance of zwitterions makes the surface electrically neutral, eliminating the deposition of pollutants caused by electrostatic attraction. This physical and chemical dual mechanism keeps the outer protective layer clean for a long time, preventing the formation of biofilms and mineral deposition.

[0120] From the above mechanism analysis, it can be seen that the various technical features of the present application are not simply superimposed, but form an organic whole system. The bottom layer provides the bonding foundation, the middle layer realizes the core function, and the outer layer provides the protective barrier, and the three layers cooperatively constitute a complete functional system. The interaction of each component at the molecular level, such as hydrogen bond, electrostatic interaction, and covalent bonding, is reflected in the macroscopic excellent mechanical properties, intelligent response, and long-term stability. This multi-level and multi-scale synergistic design represents an advanced concept in the field of functional coatings.

[0121] The technical effect of the present application far exceeds the prior art and has important clinical application value. For patients who need to indwell a urinary catheter for a long time, such as patients with neurogenic bladder caused by spinal cord injury, the leakage-proof coating of the present application can significantly improve their quality of life and reduce the embarrassment and skin complications caused by urine leakage. For intensive care patients, accurate urine volume monitoring is crucial for evaluating renal function and fluid balance, and the leakage-proof coating ensures the accuracy of urine volume measurement. The antibacterial function can reduce the incidence of catheter-related urinary tract infection, reduce antibiotic use, and reduce medical costs. The dual response mechanism of temperature and pH enables the coating to adapt to changes in the patient's physiological state and automatically adjust when fever or infection occurs, embodying the development direction of intelligent medical devices.

[0122] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modifications, equivalent replacements, and improvements made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A leak-proof coating for a temperature-responsive polyacrylate sodium urinary catheter, characterized by, The coating comprises, from inside to outside, a bottom adhesive layer, a middle functional layer and an outer protective layer, wherein: The bottom adhesive layer is composed of a polydopamine modified silane coupling agent system, including γ-aminopropyl triethoxysilane, dopamine hydrochloride, Tris buffer and silver nanoparticles, and the thickness of the bottom adhesive layer is 5-15 μm; The middle functional layer is an interpenetrating network polymer with a three-dimensional crosslinking degree gradient structure, which is polymerized from sodium acrylate monomer, N-isopropyl acrylamide, acrylic acid, N,N'-methylene bisacrylamide crosslinking agent, organically modified montmorillonite, graphene oxide nanosheet and mesoporous silica nanoparticle, and the thickness of the middle functional layer is 50-100 μm, and the crosslinking degree gradient gradually increases from the inside to the outside, with the inside crosslinking degree being 0.6-1.0 mol% and the outside crosslinking degree being 2.0-3.0 mol%; The outer protective layer is copolymerized from polyethylene glycol methacrylate, N-isopropyl acrylamide and sulfobetaine methacrylate, and the thickness of the outer protective layer is 3-8 μm.

2. The temperature-responsive polyacrylate sodium catheter leakage prevention coating of claim 1, wherein, The mass ratio of the components in the bottom adhesive layer is as follows: 2-8 parts of γ-aminopropyl triethoxysilane, 0.5-3 parts of dopamine hydrochloride, 100 parts of Tris buffer and 0.1-0.5 parts of silver nanoparticles, the pH value of the Tris buffer is 8.5, the concentration is 10 mM, and the particle size of the silver nanoparticles is 10-30 nm.

3. The temperature-responsive polyacrylate sodium catheter leakage prevention coating of claim 1, wherein, The mass ratio of each component in the intermediate functional layer is: 15 to 35 parts of sodium acrylate monomer, 8 to 20 parts of N-isopropyl acrylamide, 2 to 8 parts of acrylic acid, 3 to 12 parts of organically modified montmorillonite, 0.5 to 3 parts of graphene oxide nanosheet, 8 to 18 parts of mesoporous silica nanoparticle, and 90 to 150 parts of deionized water; the organically modified montmorillonite is hexadecyl trimethyl ammonium bromide modified montmorillonite, and the interlayer spacing is 3.5 to 4.2 nm; the lateral size of the graphene oxide nanosheet is 0.5 to 2.0 μm, and the thickness is 1 to 3 nm; the particle size of the mesoporous silica nanoparticle is 20 to 50 nm, the pore size is 2 to 10 nm, and the specific surface area is 420 to 580 m 2 / g. 2 / g.

4. The temperature-responsive polyacrylate sodium catheter leakage prevention coating of claim 3, wherein, The surface of the mesoporous silica nanoparticles is functionalized by aminopropyl triethoxysilane and covalently fixed with antibacterial peptides by EDC / NHS chemical coupling method, the antibacterial peptides are LL-37 or HHC36, and the loading amount of the antibacterial peptides is 8-15 wt%; the amino acid sequence of the LL-37 is LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, and the molecular weight is 4493 Da; the amino acid sequence of the HHC36 is KRWWKWWRR, and the molecular weight is 1479 Da.

5. A process for the preparation of a temperature-responsive poly (sodium acrylate) urinary catheter leak-proof coating according to any one of claims 1 to 4, characterized in that, The method comprises the following steps: Step one: catheter surface pretreatment: immerse a medical grade silicone or thermoplastic polyurethane catheter in a mixed solution of ammonia water, hydrogen peroxide and deionized water, the mass fraction of the ammonia water is 25-28 wt%, the mass fraction of the hydrogen peroxide is 30 wt%, the volume ratio of the ammonia water, the hydrogen peroxide and the deionized water in the mixed solution is 3:3:4, ultrasonic treatment is carried out at 60-80 ℃ for 30-60 minutes, the ultrasonic power is 100-200 W, after the treatment, rinse with deionized water for 5 times, each time for 3 minutes, and dry with nitrogen; Step two: bottom adhesive layer preparation: add Tris buffer, dopamine hydrochloride, γ-aminopropyl triethoxysilane and silver nanoparticle dispersion liquid into a reaction container in sequence, immerse the pretreated catheter completely after uniform stirring, react at 20-25 ℃ for 12-24 hours, take out, rinse with deionized water, and dry in a 60 ℃ oven for 2 hours; Step three, gradient coating of the intermediate functional layer: prepare low cross-linking degree precursor solution A, medium cross-linking degree precursor solution C and high cross-linking degree precursor solution B respectively, the molar fraction of N,N'-methylene bisacrylamide in the precursor solution A is 0.6 mol% to 1.0 mol%, the molar fraction of N,N'-methylene bisacrylamide in the precursor solution C is 1.2 mol% to 1.8 mol%, and the molar fraction of N,N'-methylene bisacrylamide in the precursor solution B is 2.0 mol% to 3.0 mol%; sequentially dip coat the precursor solution A, the precursor solution C and the precursor solution B by using a programmed dip coating method, the immersion depth is 80 mm in the first dip coating, the pulling speed is 2 mm / s, and the residence time is 5 minutes at 30°C, the immersion depth is 60 mm in the second dip coating, the pulling speed is 3 mm / s, the immersion depth is 40 mm in the third dip coating, and the pulling speed is 4 mm / s; Step four, initiation of polymerization: spray a mixed initiator solution of potassium persulfate and N,N,N',N'-tetramethyl ethylenediamine on the surface of the coated urinary catheter, the concentration of the potassium persulfate is 5 g / L, the concentration of the N,N,N',N'-tetramethyl ethylenediamine is 3 mL / L, the atomization pressure is 0.2 MPa, and the spraying is performed until the surface is just wet, then the urinary catheter is immediately placed in a reaction kettle protected by nitrogen, and the polymerization is performed according to a temperature program of 25°C for 30 minutes, 50°C for 2 hours and 70°C for 1 hour, after the polymerization, the urinary catheter is soaked in deionized water for 24 hours, and the water is replaced every 8 hours; Step five, preparation of the outer protective layer: dissolve polyethylene glycol methacrylate, N-isopropyl acrylamide, sulfobetaine methacrylate and azobisisobutyronitrile in isopropyl alcohol, pre-polymerize at 60°C for 2 hours, and then coat on the surface of the intermediate functional layer by using dip coating or spin coating after cooling to room temperature, the pulling speed is 5 mm / s in dip coating, and the spin coating is performed at a speed of 1000 rpm for 30 seconds, and then dried at 50°C for 30 minutes; Step six, post-treatment: treat in a vacuum oven at 80°C for 4 hours, and then irradiate by using γ-rays at a dose of 15 kGy to 25 kGy for cross-linking, and then soak in simulated urine for 24 hours for full hydration, the pH value of the simulated urine is 6.5, and the simulated urine contains 0.9 wt% of sodium chloride and 5 g / L of urea.

6. The preparation method according to claim 5, characterized in that, The preparation method of the low cross-linking degree precursor solution A in step three is as follows: sequentially add sodium acrylate, N-isopropyl acrylamide, acrylic acid, organically modified montmorillonite, graphene oxide dispersion liquid and N,N'-methylene bisacrylamide in deoxygenated deionized water, the concentration of the graphene oxide dispersion liquid is 2 mg / mL, the organically modified montmorillonite is ultrasonically dispersed for 30 minutes after being added, and stirring is performed until complete dissolution; and the preparation method of the high cross-linking degree precursor solution B is as follows: sequentially add sodium acrylate, N-isopropyl acrylamide, acrylic acid, mesoporous silica nanoparticles, organically modified montmorillonite and N,N'-methylene bisacrylamide in deoxygenated deionized water, the mesoporous silica nanoparticles are pre-loaded with an antibacterial peptide, and ultrasonic dispersion is performed until uniform.

7. The production method according to claim 6, wherein The method for loading the mesoporous silica nanoparticles with the antibacterial peptide is: the mesoporous silica nanoparticles are treated by aminopropyl triethoxysilane functionalization, the surface amino density is 2.5 μmol / m 2 to 3.8 μmol / m 2 ; the antibacterial peptide is dissolved in a phosphate buffer with a pH value of 6.0, 1-ethyl-3-dimethylaminopropyl carbodiimide and N-hydroxysuccinimide are added, the mass ratio of the 1-ethyl-3-dimethylaminopropyl carbodiimide to the antibacterial peptide is 3:1, the mass ratio of the N-hydroxysuccinimide to the antibacterial peptide is 1.5:1, the amino-functionalized mesoporous silica is added after stirring at room temperature for 30 minutes, the pH value is adjusted to 7.4, the reaction is carried out for 4 hours, the unreacted antibacterial peptide is removed by centrifugation and washing, and the immobilization efficiency is 60% to 75%.

8. The preparation method according to claim 5, characterized in that, The preparation quality ratio of the polymer solution in the fifth step is: polyethylene glycol methacrylate 10 to 25 parts, N-isopropyl acrylamide 5 to 15 parts, sulfobetaine methacrylate 3 to 10 parts, azobisisobutyronitrile 0.1 to 0.5 parts, and isopropyl alcohol 80 to 120 parts; the molecular weight of the polyethylene glycol methacrylate is 475 Da.

9. Use of the thermally responsive poly (sodium acrylate) leak-proof coating of any one of claims 1 to 4 for the preparation of a leak-proof urinary catheter, characterized in that, The coating is coated on the surface of a medical-grade silica gel or a thermoplastic polyurethane catheter, generates controllable expansion to form a seal in a urine environment, and has an expansion rate of 150% to 200%; when the temperature rises to above 38℃, the N-isopropyl acrylamide component in the coating undergoes a phase change, automatically inhibits excessive expansion, and shrinks in volume by 20% to 30%, with a response time of less than 15 minutes.

10. Use according to claim 9, characterized in that, The coating reaches equilibrium expansion in simulated urine with a pH value of 6.5 and a temperature of 37℃ within 30 minutes, has an expansion rate of 150% to 200%, and has a contact pressure with the urethral wall of 5kPa to 15kPa; when the pH value rises to 7.5 to 8.5, the coating additionally expands by 20% to 40%, while triggering the mesoporous silica to release an antibacterial peptide, with a 24-hour cumulative release amount of 30% to 40% at a pH value of 8.0; the coating has an antibacterial rate of greater than 99% on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, and has a performance retention rate of greater than 85% after continuous immersion in simulated urine for 30 days.