Antibacterial and anti-stick latex catheter and preparation method thereof

Abstract

The present invention provides an antibacterial and anti-sticking latex catheter and a preparation method thereof, which relates to the technical field of medical implant materials. The method comprises the following steps: S1: placing vinyl pyrrolidone, an unsaturated carboxylic acid monomer, and an initiator in a first solvent to obtain polyvinyl pyrrolidone with a carboxyl side chain; S2: placing the polyvinyl pyrrolidone with a carboxyl side chain, an activator, and a catalyst in a second solvent to obtain activated polyvinyl pyrrolidone; S3: placing the antibacterial agent and the activated polyvinyl pyrrolidone in a third solvent to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone; S4: performing an activation treatment on latex particles to obtain activated latex particles; S5: placing the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles in a fourth solvent to obtain antibacterial and anti-sticking latex particles; and S6: melting and extruding the antibacterial and anti-sticking latex particles to form an antibacterial and anti-sticking latex catheter. The hydrophilicity and antibacterial properties of the latex catheter are effectively improved.

Description

Technical Field

[0001] The invention relates to the technical field of medical implant materials, in particular to an antibacterial and anti-sticking latex catheter and a preparation method thereof. Background Art

[0002] Latex urinary catheters, widely used as auxiliary tools in the medical field, play an indispensable role in clinical practice due to their excellent softness and certain durability. However, despite their many advantages, latex urinary catheters can gradually become sticky due to residual urine, urethral secretions, and other body fluids during long-term use. This problem cannot be ignored.

[0003] During use, the inner wall of a latex urinary catheter is constantly exposed to the patient's urine. Urine contains not only water but also various mineral salts, urea, uric acid, and other metabolic waste products. The long-term deposition of these components on the inner wall of the catheter gradually forms a thick coating. This coating not only affects the drainage efficiency of the catheter, preventing urine from flowing smoothly, but can also cause catheter blockage, making removal more difficult. For patients who require long-term indwelling catheters, this blockage undoubtedly causes great inconvenience and pain.

[0004] In addition to the precipitation of mineral salts and the accumulation of urine scale, the surface of latex catheters can also become more viscous due to the accumulation of urethral secretions and other body fluids. Urethral secretions are the metabolic products of urethral mucosal cells and may contain proteins, mucus, and other biomacromolecules. The adhesion of these substances to the catheter surface further increases its viscosity, making it more susceptible to contamination during use.

[0005] More seriously, latex itself has relatively weak antibacterial properties. While latex has some natural antibacterial properties, the antibacterial substances on its surface may gradually be depleted over long-term use, making it difficult to effectively inhibit bacterial growth on the catheter surface. Especially in cases of inflammation or infection in the patient's urethra, bacteria are more likely to find a suitable living environment on the catheter surface and multiply in large numbers. These bacteria may not only cause or aggravate urinary tract infections, but may also retrogradely infect organs such as the bladder and kidneys through the catheter, resulting in even more serious consequences.

[0006] Urinary tract infections (UTIs) are a common complication among patients with indwelling urinary catheters. Statistics show that the incidence of UTIs among these patients is as high as several tens of percentage points. This high infection rate not only increases patient suffering and medical costs, but can also impact recovery and quality of life. Therefore, mitigating the increased viscosity and poor antibacterial properties of latex urinary catheters during use has become a critical and pressing issue in the medical field. Summary of the Invention

[0007] The present invention aims to provide an antibacterial and anti-sticking latex catheter and a preparation method thereof. The present invention grafts polyvinyl pyrrolidone with a quaternary ammonium salt antibacterial agent, and then activates latex particles so that the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the latex particles are connected together by forming stable chemical bonds. This not only improves the hydrophilicity and antibacterial properties of the latex particles, but also enables the prepared antibacterial and anti-sticking latex catheter to solve the problem of increased viscosity caused by substances attached to the tube wall.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] The present invention provides a method for preparing an antibacterial and anti-stick latex urinary catheter, comprising the following steps:

[0010] S1: placing vinyl pyrrolidone, an unsaturated carboxylic acid monomer, and an initiator in a first solvent and stirring to obtain polyvinyl pyrrolidone with a carboxyl side chain;

[0011] S2: placing polyvinyl pyrrolidone with a carboxyl side chain, an activator, and a catalyst in a second solvent and stirring to obtain activated polyvinyl pyrrolidone;

[0012] S3: placing the antibacterial agent and activated polyvinyl pyrrolidone in a third solvent and stirring to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone;

[0013] S4: activating the latex particles to obtain activated latex particles;

[0014] S5: placing the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles in a fourth solvent, stirring, and freeze-drying to obtain antibacterial and anti-sticking latex particles;

[0015] S6: The antibacterial and anti-sticking latex particles are melted and extruded to form an antibacterial and anti-sticking latex catheter.

[0016] Furthermore, based on the above technical solution, the reaction conditions in step S1 include:

[0017] Under a protective gas atmosphere, heat and stir at a temperature of 60-80°C for 12-24 hours;

[0018] Wherein, the protective gas includes nitrogen, argon or helium;

[0019] And / or, the unsaturated carboxylic acid monomer includes one or more of acrylic acid, methacrylic acid, and maleic acid;

[0020] and / or, the initiator comprises one or more of dibenzoyl peroxide or azobisisobutyronitrile;

[0021] and / or, the first solvent comprises one or more of ethanol, isopropanol, and 1,4-dioxane;

[0022] And / or, the mass-to-volume ratio of the total mass of vinyl pyrrolidone, the unsaturated carboxylic acid monomer and the initiator to the first solvent is 1 g:(5-10) mL.

[0023] Furthermore, based on the above technical solution, in step S1, the molar ratio of vinyl pyrrolidone to the unsaturated carboxylic acid monomer is 1:(8-10), and the molar amount of the initiator accounts for 0.1-3% of the total molar amount of vinyl pyrrolidone and the unsaturated carboxylic acid monomer;

[0024] And / or, the number average molecular weight of the polyvinyl pyrrolidone with a carboxyl side chain is 30,000-200,000.

[0025] Furthermore, based on the above technical solution, in step S2, the second solvent includes one or more of water, ethanol, isopropanol, tetrahydrofuran or N,N-dimethylformamide;

[0026] and / or, the activator is a carbodiimide coupling agent, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or N,N'-dicyclohexylcarbodiimide;

[0027] And / or, the catalyst includes one or more of N-hydroxybenzenesulfonimide, triethylamine, and 1-hydroxybenzotriazole;

[0028] And / or, in step S2, the pH is 4-6, the stirring temperature is 20-50° C., and the stirring time is 2-4 h;

[0029] And / or, the mass volume ratio of the total mass of the polyvinyl pyrrolidone with a carboxyl side chain, the activator and the catalyst to the second solvent is 1 g: (5-10) mL.

[0030] Furthermore, based on the above technical solution, in step S2, the mass ratio of polyvinyl pyrrolidone with a carboxyl side chain, the activator and the catalyst is 1:(3-4):(0.01-0.1).

[0031] Further, on the basis of the above technical solution, in step S3, the antibacterial agent is a quaternary ammonium salt organic antibacterial agent, including one or more of dodecyldimethylbenzyl ammonium chloride, hexadecyltrimethylammonium bromide, benzyltrimethylammonium chloride, and hexadecylpyridinium chloride;

[0032] and / or, the third solvent comprises one or more of water, isopropanol, ethanol, and dichloromethane;

[0033] And / or, the reaction conditions in step S3 include: stirring at 20-40° C. for 4-12 h;

[0034] and / or, the mass ratio of the antimicrobial agent to the activated polyvinylpyrrolidone is (1-3):1;

[0035] And / or, the mass-to-volume ratio of the total mass of the antimicrobial agent and the activated polyvinyl pyrrolidone to the third solvent is 1 g:(5-10) mL.

[0036] Furthermore, based on the above technical solution, in step S4, the activation treatment is oxygen plasma treatment, and the oxygen plasma treatment conditions are: power 70-90 W, air flow rate 90-110 mL / min, air pressure 50-70 Pa, and etching time 30-60 s;

[0037] And / or, in step S2, the particle size of the latex particles is 1-100 μm.

[0038] Furthermore, based on the above technical solution, in step S5, the fourth solvent includes one or more of water, isopropanol, ethanol, and dichloromethane;

[0039] And / or, the freeze drying comprises: a temperature of -40 to -50°C and a drying time of 2 to 4 days;

[0040] And / or, the reaction conditions in step S5 include: pH 4-6, stirring at 20-40° C. for 4-12 h;

[0041] and / or, the mass ratio of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone to the activated latex particles is 1:(2-3);

[0042] And / or, the mass volume ratio of the total mass of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles to the fourth solvent is 1 g: (10-15) mL.

[0043] Furthermore, based on the above technical solution, in step S6, the melt extrusion process includes:

[0044] The temperature of the feeding section is controlled at 100-150℃; the temperature of the barrel section is controlled at 200-220℃; the temperature of the die section is controlled at 200-220℃; the temperature of the die section is controlled at 220-240℃.

[0045] The present invention also provides an antibacterial and anti-stick latex urinary catheter prepared by the above-mentioned preparation method of the antibacterial and anti-stick latex urinary catheter.

[0046] The present invention provides an antibacterial and anti-stick latex urinary catheter and a preparation method thereof, which has the following beneficial effects:

[0047] The present invention grafts polyvinyl pyrrolidone (PVP) and a quaternary ammonium salt antimicrobial agent with high-efficiency antimicrobial performance together through a chemical bond, and then activates the surface of the latex particles, effectively promoting the interaction between the polyvinyl pyrrolidone and the latex particles after the quaternary ammonium salt group grafting, and achieving close combination between the two by forming a stable and firm chemical bond. The introduction of polyvinyl pyrrolidone greatly enhances the hydrophilicity of the latex particles, making the latex material show better wettability and dispersibility under a wet environment. In addition, the successful grafting of the quaternary ammonium salt antimicrobial agent gives the latex particles excellent antimicrobial performance, can effectively inhibit or kill various bacteria and microorganisms, thereby significantly improving the hygienic safety of the product, and fundamentally solving the problem that traditional latex pipes are prone to increase in pipe wall viscosity and are difficult to clean due to adherent substances (such as protein, grease, etc.) in use. These adherent substances tend to reduce the circulation efficiency of the pipeline and even affect the service life of the product. The latex tube of the present invention, with its excellent antibacterial and anti-stick properties, can effectively prevent the accumulation of such substances, keep the pipeline clean and unobstructed, extend the product's service life, and also bring users a more convenient and hygienic use experience. DETAILED DESCRIPTION

[0048] In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention. The process parameters for which specific conditions are not specified in the following examples are generally in accordance with conventional conditions.

[0049] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to form one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed in the present invention.

[0050] According to a first aspect of the present invention, there is provided a method for preparing an antibacterial and anti-stick latex urinary catheter, comprising the following steps:

[0051] S1: placing vinyl pyrrolidone, an unsaturated carboxylic acid monomer, and an initiator in a first solvent and stirring to obtain polyvinyl pyrrolidone with a carboxyl side chain;

[0052] S2: placing polyvinyl pyrrolidone with a carboxyl side chain, an activator, and a catalyst in a second solvent and stirring to obtain activated polyvinyl pyrrolidone;

[0053] S3: placing the antibacterial agent and activated polyvinyl pyrrolidone in a third solvent and stirring to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone;

[0054] S4: activating the latex particles to obtain activated latex particles;

[0055] S5: placing the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles in a fourth solvent, stirring, and freeze-drying to obtain antibacterial and anti-sticking latex particles;

[0056] S6: The antibacterial and anti-sticking latex particles are melted and extruded to form an antibacterial and anti-sticking latex catheter.

[0057] Specifically, polyvinyl pyrrolidone (PVP) is a nontoxic, non-irritating macromolecular compound with good biocompatibility and lubricity. When added to a latex catheter and in contact with an aqueous liquid, the PVP molecules rapidly absorb moisture to form a hydrophilic gel layer, significantly reducing the viscosity of the catheter. The present invention grafts polyvinyl pyrrolidone (PVP) with a quaternary ammonium salt antimicrobial agent having high-efficiency antimicrobial properties through a chemical bond, and then activates the surface of the latex particles, effectively promoting the interaction between the polyvinyl pyrrolidone and the latex particles after the quaternary ammonium salt group grafting, and achieving a close bond between the two by forming a stable and firm chemical bond. The introduction of polyvinyl pyrrolidone greatly enhances the hydrophilicity of the latex particles, allowing the latex material to exhibit better wettability and dispersibility under a humid environment. Furthermore, the successful grafting of the quaternary ammonium salt antimicrobial agent imparts excellent antimicrobial properties to the latex particles, effectively inhibiting or killing a variety of bacteria and microorganisms, thereby significantly improving the hygienic safety of the product. The antibacterial and anti-sticking latex tube prepared by the present invention, due to the presence of the above-mentioned unique structure, fundamentally solves the problem that traditional latex tubes are prone to increased viscosity of the tube wall and difficulty in cleaning due to attached substances (such as proteins, grease, etc.) during use. These attached substances often reduce the circulation efficiency of the pipeline and even affect the service life of the product. However, the latex tube of the present invention, with its excellent antibacterial and anti-stick properties, can effectively prevent the accumulation of such substances, keep the pipeline clean and unobstructed, extend the service life of the product, and also provide users with a more convenient and hygienic user experience.

[0058] As an optional embodiment of the present invention, the reaction conditions in step S1 include:

[0059] Under a protective gas atmosphere, heat and stir at a temperature of 60-80°C for 12-24 hours;

[0060] Wherein, the protective gas includes nitrogen, argon or helium;

[0061] And / or, the unsaturated carboxylic acid monomer includes one or more of acrylic acid, methacrylic acid, and maleic acid;

[0062] and / or, the initiator comprises one or more of dibenzoyl peroxide or azobisisobutyronitrile;

[0063] and / or, the first solvent comprises one or more of ethanol, isopropanol, and 1,4-dioxane;

[0064] And / or, the mass-to-volume ratio of the total mass of vinyl pyrrolidone, the unsaturated carboxylic acid monomer and the initiator to the first solvent is 1 g:(5-10) mL.

[0065] As an optional embodiment of the present invention, the molar ratio of vinyl pyrrolidone to the unsaturated carboxylic acid monomer is 1:(8-10), such as 1:8.5, 1:9, 1:9.5, etc., and the molar amount of the initiator accounts for 0.1-3% of the total molar amount of vinyl pyrrolidone and the unsaturated carboxylic acid monomer, such as 0.5%, 1%, 1.5%, 2%, 2.5%, etc.;

[0066] Specifically, the present invention limits the molar ratio of vinyl pyrrolidone to unsaturated carboxylic acid monomer to 1:(8-10) in order to make the polymer have a high carboxyl content, thereby performing an activation reaction.

[0067] Furthermore, excessive amounts of initiator may lead to premature termination of the polymer chain, thereby affecting the molecular weight and molecular weight distribution of the polymer. Too little initiator may result in incomplete polymerization. The type and concentration of the initiator have a significant impact on the molecular weight distribution of the polymer. Selecting the appropriate initiator and initiator concentration can effectively control the molecular weight distribution of the polymer.

[0068] The present invention limits the molar ratio of vinyl pyrrolidone to unsaturated carboxylic acid monomers to 1:(8-10), aiming to promote a high proportion of carboxyl functional groups in the polymer molecule. This high carboxyl content not only provides abundant reactive sites for subsequent activation reactions, enhancing the interaction between the polymer and the antimicrobial agent, but also imparts improved water solubility, ion exchange capacity, and potential biocompatibility to the polymer itself, which is crucial for enhancing the performance of the final product.

[0069] Furthermore, during the polymerization process, the choice and dosage of initiator have a profound impact on the structure and properties of the polymer. Excessive initiator levels can lead to excessive free radical generation during the chain initiation phase, accelerating the polymerization rate. However, this can also cause premature chain termination, resulting in insufficient polymer chain length, reduced molecular weight, a narrower molecular weight distribution, and even the production of a large number of oligomers. This can not only reduce the polymer's physical and mechanical properties, such as tensile strength and toughness, but can also affect its performance in subsequent processing and applications.

[0070] Conversely, if the amount of initiator is too low, the chain initiation rate slows down. While this can extend the polymerization time, it may lead to incomplete polymerization, with some monomers not effectively converted into polymers, resulting in raw material waste and unstable product quality. Furthermore, too low an initiator concentration may also increase the variation in polymer chain length and broaden the molecular weight distribution, affecting product uniformity and processing performance.

[0071] Therefore, the present invention can precisely control the kinetics of the polymerization reaction by precisely adjusting the molar amount of the initiator to 0.1-3% of the total molar amount of vinyl pyrrolidone and unsaturated carboxylic acid monomers, thereby obtaining a polymer with a specific molecular weight distribution, uniform structure and excellent performance.

[0072] And / or, the number average molecular weight of the polyvinyl pyrrolidone with a carboxyl side chain is 30,000-200,000.

[0073] Specifically, the present invention limits the number average molecular weight of polyvinylpyrrolidone with carboxyl side chains to 30,000-200,000 because it has good hydrophilicity. PVP within this range has a sufficient molecular weight to ensure hydrophilicity, but does not affect solubility due to excessive molecular weight.

[0074] For PVP, the pyrrolidone ring structure on its molecular chain itself has a certain hydrophilicity, and the introduction of carboxyl side chains further enhances the hydrophilic properties. When designing and synthesizing polyvinyl pyrrolidone with carboxyl side chains, the present invention limits its number average molecular weight to within the range of 30,000-200,000. This is because the strength of hydrophilicity is not only related to the type and number of functional groups, but also closely related to the molecular weight of the polymer. When the number average molecular weight of PVP is too low, although its solubility is good, due to the short molecular chain, it may not be able to form a sufficiently tight and stable network structure, thereby affecting its physical stability and mechanical properties in aqueous solution. In addition, low-molecular-weight PVP may be more easily metabolized and excreted by organisms. On the contrary, when the number average molecular weight of PVP is too high, although its molecular chain is longer and may form a more complex structure, the excessively high molecular weight is often accompanied by a decrease in solubility. High-molecular-weight PVP requires more energy to destroy the interactions between molecular chains during the dissolution process, which may lead to a slower dissolution rate and even incomplete dissolution in certain solvents, forming a gel or precipitate. Therefore, the present invention limits the number average molecular weight of PVP with carboxyl side chains to the range of 30,000-200,000. PVP has a sufficient molecular weight to ensure good hydrophilicity and certain physical stability, but does not significantly reduce solubility due to excessive molecular weight.

[0075] As an optional embodiment of the present invention, in step S2, the second solvent includes one or more of water, ethanol, isopropanol, tetrahydrofuran or N,N-dimethylformamide;

[0076] and / or, the activator is a carbodiimide coupling agent, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or N,N'-dicyclohexylcarbodiimide;

[0077] Specifically, carbodiimide coupling agents can react with polyvinyl pyrrolidone with a carboxyl side chain, promoting the deprotonation of the carboxyl group to form an active acyl intermediate (-CO-NH-C≡N). This acyl intermediate has higher reactivity and can more easily react with amine compounds such as quaternary ammonium salt organic antimicrobial agents to form a stable amide bond. The formation of the amide bond not only enhances the connection strength between the activated polyvinyl pyrrolidone and the quaternary ammonium salt organic antimicrobial agent, but also ensures the stability and reliability of the grafting reaction. In addition, during the activation process of the carbodiimide coupling agent, the carbon-nitrogen triple bond (C≡N) in its molecular structure can also avoid interference from other functional groups, ensuring the selectivity and efficiency of the reaction.

[0078] And / or, the catalyst includes one or more of N-hydroxybenzenesulfonimide, triethylamine, and 1-hydroxybenzotriazole;

[0079] And / or, in step S2, the pH is 4-6, the stirring temperature is 20-50° C., and the stirring time is 2-4 h;

[0080] The mass volume ratio of the total mass of the polyvinyl pyrrolidone with a carboxyl side chain, the activator and the catalyst to the second solvent is 1 g: (5-10) mL.

[0081] As an optional embodiment of the present invention, the mass ratio of polyvinyl pyrrolidone with a carboxyl side chain, the activator and the catalyst is 1: (3-4): (0.01-0.1);

[0082] As an optional embodiment of the present invention, in step S3, the antibacterial agent is a quaternary ammonium salt organic antibacterial agent, including one or more of dodecyldimethylbenzyl ammonium chloride, hexadecyltrimethylammonium bromide, benzyltrimethylammonium chloride, and hexadecylpyridinium chloride;

[0083] Specifically, the positively charged nitrogen atom in the quaternary ammonium salt is able to undergo an efficient nucleophilic addition reaction with the acyl intermediate in the activated polyvinylpyrrolidone. During this reaction, the nitrogen atom attacks the acyl carbon atom, breaking the carbon-oxygen double bond and forming a new carbon-nitrogen single bond. Simultaneously, the oxygen atom in the original acyl group combines with the hydrogen atom to produce a water molecule as a byproduct of the reaction. This forms a stable amide bond, firmly connecting the quaternary ammonium salt to the molecular chain of the activated polyvinylpyrrolidone.

[0084] and / or, the third solvent comprises one or more of water, isopropanol, ethanol, and dichloromethane;

[0085] And / or, the reaction conditions in step S3 include: stirring at 20-40° C. for 4-12 h;

[0086] and / or, the mass ratio of the antimicrobial agent to the activated polyvinylpyrrolidone is (1-3):1;

[0087] And / or, the mass-to-volume ratio of the total mass of the antimicrobial agent and the activated polyvinyl pyrrolidone to the third solvent is 1 g:(5-10) mL.

[0088] As an optional embodiment of the present invention, in step S4, the activation treatment is oxygen plasma treatment, and the oxygen plasma treatment conditions are: power 70-90 W, air flow rate 90-110 mL / min, air pressure 50-70 Pa, and etching time 30-60 s;

[0089] And / or, in step S2, the particle size of the latex particles is 1-100 μm.

[0090] Specifically, the present invention activates latex particles through oxygen plasma, thereby adding a large number of active hydroxyl groups to their surfaces, which can react with the carbonyl groups on the pyridine ring in polyvinyl pyrrolidone to form ester bonds, thereby forming a tight and stable connection between the latex particles, polyvinyl pyrrolidone and the quaternary ammonium salt organic antibacterial agent, effectively improving the antibacterial and hydrophilic properties of the latex particles.

[0091] As an optional embodiment of the present invention, in step S5, the fourth solvent includes one or more of water, isopropanol, ethanol, and dichloromethane;

[0092] And / or, the freeze drying comprises: a temperature of -40 to -50°C and a drying time of 2 to 4 days;

[0093] And / or, the reaction conditions in step S5 include: pH 4-6 (such as 4.5, 5, 5.5, etc.), stirring at 20-40° C. for 4-12 hours;

[0094] Specifically, in polyvinyl pyrrolidone, carbonyl groups are present on both the pyridine ring and the amide bond. However, the pyridine ring is an electron-deficient aromatic ring, and the carbonyl group thereon has a low electron cloud density and a strong electrophilicity due to the conjugation effect. The carbonyl group in the amide bond is connected to the nitrogen atom, and the nitrogen atom has a certain electron-donating effect, so that the electron cloud density of the carbonyl group is relatively high and the electrophilicity is relatively weak. In order to fully utilize the different properties of the two carbonyl groups and prevent the hydrolysis of the amide bond, the present invention limits the reaction to a slightly acidic environment. Acidic conditions help prevent the hydrolysis of the amide bond, thereby avoiding unnecessary reactions between the carbonyl group in the amide bond and the hydroxyl group, which leads to the separation of the quaternary ammonium salt positive ion. More importantly, under acidic conditions, the carbonyl group on the pyridine ring undergoes protonation, and the protonated carbonyl oxygen atom carries a positive charge, which enhances the positive charge of the carbonyl carbon atom and increases the electrophilicity. The enhanced electrophilicity means that the carbonyl group is more susceptible to attack by the hydroxyl group, thereby promoting the reaction between the carbonyl group on the pyridine ring and the hydroxyl group on the emulsified particles.

[0095] and / or, the mass ratio of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone to the activated latex particles is 1:(2-3);

[0096] And / or, the mass volume ratio of the total mass of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles to the fourth solvent is 1 g: (10-15) mL.

[0097] As an optional embodiment of the present invention, in step S6, the melt extrusion process includes:

[0098] The temperature of the feeding section is controlled at 100-150℃; the temperature of the barrel section is controlled at 200-220℃; the temperature of the die section is controlled at 200-220℃; the temperature of the die section is controlled at 220-240℃.

[0099] According to a second aspect of the present invention, there is provided an antibacterial and anti-stick latex catheter produced by the method for producing the antibacterial and anti-stick latex catheter as described above.

[0100] The present invention will be further described in detail below with reference to specific examples and comparative examples.

[0101] The chemical reagents and latex particles used in the present invention are all commercially available products.

[0102] Example 1

[0103] S1: Vinyl pyrrolidone, acrylic acid, and dibenzoyl peroxide were placed in ethanol under a nitrogen atmosphere, and heated and stirred at 70°C for 20 h to obtain polyvinyl pyrrolidone with a carboxyl side chain;

[0104] The molar ratio of vinyl pyrrolidone to acrylic acid is 1:9, and the molar amount of dibenzoyl peroxide accounts for 0.5% of the total molar amount of vinyl pyrrolidone and acrylic acid;

[0105] The mass-to-volume ratio of the total mass of vinylpyrrolidone acrylic acid and dibenzoyl peroxide to ethanol is 1 g: (5-10) mL.

[0106] S2: Polyvinyl pyrrolidone with a carboxyl side chain, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and N-hydroxybenzenesulfonimide are placed in ethanol and stirred at pH 5 and 30°C for 4 hours to obtain activated polyvinyl pyrrolidone;

[0107] The mass ratio of polyvinyl pyrrolidone with a carboxyl side chain, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxybenzenesulfonimide is 1:3:0.05;

[0108] The mass-to-volume ratio of the total mass of polyvinylpyrrolidone with a carboxyl side chain, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxybenzenesulfonimide to ethanol is 1 g:5 mL.

[0109] S3: placing dodecyldimethylbenzyl ammonium chloride and activated polyvinyl pyrrolidone in ethanol and stirring at 40°C for 10 hours to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone;

[0110] The mass ratio of dodecyldimethylbenzyl ammonium chloride and activated polyvinyl pyrrolidone is 2:1;

[0111] The mass-to-volume ratio of the total mass of dodecyldimethylbenzyl ammonium chloride and activated polyvinyl pyrrolidone to ethanol is 1 g:5 mL.

[0112] S4: treating the latex particles (particle size 80 μm) with oxygen plasma to obtain activated latex particles;

[0113] Among them, the power is 80W, the air flow rate is 100mL / min, the air pressure is 60Pa, and the etching time is 60s;

[0114] S5: placing the quaternary ammonium group-grafted polyvinyl pyrrolidone and activated latex particles in ethanol at a pH of 4, stirring at 30°C for 10 hours, and then freeze-drying and drying at -40°C for 3 days to obtain antibacterial and anti-sticking latex particles;

[0115] The mass ratio of quaternary ammonium salt group-grafted polyvinyl pyrrolidone to activated latex particles is 1:2;

[0116] The mass volume ratio of the total mass of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles to ethanol is 1 g:10 mL.

[0117] S6: Melting and extruding the antibacterial and anti-sticking latex particles to form an antibacterial and anti-sticking latex catheter;

[0118] The melt extrusion process includes: the temperature of the feeding section is controlled at 130°C; the temperature of the barrel section is controlled at 210°C; the temperature of the head section is controlled at 220°C; and the temperature of the die section is controlled at 230°C.

[0119] Example 2

[0120] S1: Vinyl pyrrolidone, methacrylic acid, and azobisisobutyronitrile were placed in isopropanol under an argon atmosphere and heated with stirring at 80°C for 14 h to obtain polyvinyl pyrrolidone with a carboxyl side chain;

[0121] The molar ratio of vinyl pyrrolidone to methacrylic acid is 1:8, and the molar amount of azobisisobutyronitrile accounts for 2% of the total molar amount of vinyl pyrrolidone and methacrylic acid;

[0122] The mass-to-volume ratio of the total mass of vinyl pyrrolidone, methacrylic acid and azobisisobutyronitrile to isopropyl alcohol is 1 g:5 mL.

[0123] S2: polyvinyl pyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and triethylamine are placed in isopropanol, stirred at pH 4 and 30°C for 3 h to obtain activated polyvinyl pyrrolidone;

[0124] The mass ratio of polyvinyl pyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and triethylamine is 1:4:0.06;

[0125] The mass-to-volume ratio of the total mass of polyvinylpyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and triethylamine to isopropyl alcohol is 1 g:5 mL.

[0126] S3: placing cetylpyridinium chloride and activated polyvinyl pyrrolidone in isopropyl alcohol and stirring at 40°C for 10 hours to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone;

[0127] The mass ratio of cetylpyridinium chloride and activated polyvinylpyrrolidone is 3:1;

[0128] The mass-to-volume ratio of the total mass of cetylpyridinium chloride and activated polyvinylpyrrolidone to isopropyl alcohol is 1 g:5 mL.

[0129] S4: treating the latex particles (particle size 80 μm) with oxygen plasma to obtain activated latex particles;

[0130] Among them, the power is 80W, the air flow rate is 100mL / min, the air pressure is 60Pa, and the etching time is 60s;

[0131] S5: placing the quaternary ammonium group-grafted polyvinyl pyrrolidone and activated latex particles in isopropyl alcohol at a pH of 5, stirring at 40°C for 12 hours, and then freeze-drying and drying at -50°C for 2 days to obtain antibacterial and anti-sticking latex particles;

[0132] The mass ratio of quaternary ammonium salt group-grafted polyvinyl pyrrolidone to activated latex particles is 1:2.5;

[0133] The mass volume ratio of the total mass of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles to the fourth solvent is 1 g:10 mL.

[0134] S6: Melting and extruding the antibacterial and anti-sticking latex particles to form an antibacterial and anti-sticking latex catheter;

[0135] The melt extrusion process includes: the temperature of the feeding section is controlled at 150°C; the temperature of the barrel section is controlled at 200°C; the temperature of the head section is controlled at 220°C; and the temperature of the die section is controlled at 240°C.

[0136] Example 3

[0137] S1: Vinyl pyrrolidone, maleic acid, and azobisisobutyronitrile were placed in 1,4-dioxane under a helium atmosphere and heated and stirred at 60°C for 24 h to obtain polyvinyl pyrrolidone with a carboxyl side chain;

[0138] The molar ratio of vinyl pyrrolidone to maleic acid is 1:10, and the molar amount of azobisisobutyronitrile accounts for 1% of the total molar amount of vinyl pyrrolidone and maleic acid;

[0139] The mass-to-volume ratio of the total mass of vinyl pyrrolidone, maleic acid, and azobisisobutyronitrile to 1,4-dioxane is 1 g:5 mL.

[0140] S2: placing polyvinyl pyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide, and 1-hydroxybenzotriazole in water, stirring at pH 6 and 50°C for 2 h to obtain activated polyvinyl pyrrolidone;

[0141] The mass ratio of polyvinylpyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole is 1:4:0.1;

[0142] The mass volume ratio of the total mass of polyvinylpyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole to water is 1 g:5 mL.

[0143] S3: Benzyltrimethylammonium chloride and activated polyvinyl pyrrolidone were placed in water and stirred at 40°C for 12 hours to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone;

[0144] The mass ratio of benzyltrimethylammonium chloride and activated polyvinylpyrrolidone is 3:1;

[0145] The mass-to-volume ratio of the total mass of benzyltrimethylammonium chloride and activated polyvinylpyrrolidone to water is 1 g:5 mL.

[0146] S4: treating the latex particles (particle size 80 μm) with oxygen plasma to obtain activated latex particles;

[0147] Among them, the power is 80W, the air flow rate is 100mL / min, the air pressure is 60Pa, and the etching time is 60s;

[0148] S5: placing the quaternary ammonium group-grafted polyvinyl pyrrolidone and activated latex particles in water at a pH of 4, stirring at 40°C for 12 hours, and then freeze-drying and drying at -40°C for 4 days to obtain antibacterial and anti-sticking latex particles;

[0149] The mass ratio of quaternary ammonium salt group-grafted polyvinyl pyrrolidone to activated latex particles is 1:3;

[0150] The mass volume ratio of the total mass of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles to water is 1 g:10 mL.

[0151] S6: Melting and extruding the antibacterial and anti-sticking latex particles to form an antibacterial and anti-sticking latex catheter;

[0152] The melt extrusion process includes: the temperature of the feeding section is controlled at 100°C; the temperature of the barrel section is controlled at 200°C; the temperature of the head section is controlled at 210°C; and the temperature of the die section is controlled at 220°C.

[0153] Comparative Example 1

[0154] This comparative example differs from Example 1 in that, in step S1, the molar ratio of vinyl pyrrolidone to acrylic acid is 1:6, and the remaining steps and technical parameters are the same as those in Example 1.

[0155] Comparative Example 2

[0156] This comparative example differs from Example 1 in that, in step S1, the molar amount of dibenzoyl peroxide accounts for 5% of the total molar amount of vinyl pyrrolidone and acrylic acid, and the remaining steps and technical parameters are the same as those in Example 1.

[0157] Comparative Example 3

[0158] The difference between this comparative example and Example 1 is that in step S4, the activation treatment for the latex particles is nitrogen plasma treatment, and the remaining steps and technical parameters are the same as those in Example 1.

[0159] Comparative Example 4

[0160] This comparative example differs from Example 1 in that, in step S5, the reaction is carried out under weakly alkaline conditions of pH 8, and the remaining steps and technical parameters are the same as those in Example 1.

[0161] Performance Testing

[0162] The antibacterial and anti-stick latex catheter prepared above was tested for its antibacterial properties against Escherichia coli, Enterobacter faecalis and Candida albicans according to the standard ISO22196-2011;

[0163] Test method for water absorption of antibacterial and anti-stick latex catheters:

[0164] Cut a 2 cm length of antibacterial, non-stick latex urinary catheter and weigh it on a scale (m1). Place the catheter in a container filled with distilled water for 1 minute before removing it. Place the catheter upright and absorb any water droplets on the surface with filter paper. Quickly weigh the catheter and record its weight (m2). Weigh each catheter three times. Water absorption = (m2 - m1) / m1 × 100%.

[0165] Performance data

[0166] Table 1: Comparative table of antibacterial properties of the antibacterial and anti-sticking latex catheters prepared in Examples 1-3 and Comparative Examples 1-4

[0167]

[0168] Table 2: Water absorption of the antibacterial and anti-sticking latex catheters prepared in Examples 1-3 and Comparative Examples 1-4

[0169] m1 / g m2 / g (m2-m1) / mg Water absorption / % Example 1 0.3324 0.3438 11.4 3.43 Example 2 0.3245 0.3421 17.6 5.42 Example 3 0.3545 0.36078 13.3 3.75 Comparative Example 1 0.3312 0.3364 5.2 1.57 Comparative Example 2 0.3342 0.3383 4.1 1.23 Comparative Example 3 0.3297 0.3390 9.3 2.82 Comparative Example 4 0.3402 0.3484 8.2 2.41

[0170] As shown in Tables 1 and 2, compared with Example 1, in Comparative Example 1, the molar ratio of vinyl pyrrolidone and unsaturated carboxylic acid monomers is reduced, resulting in a decrease in the carboxyl content in the prepared polyvinyl pyrrolidone with a carboxyl side chain, further affecting the grafting of activated polyvinyl pyrrolidone with the quaternary ammonium salt organic antibacterial agent, resulting in a decrease in hydrophilicity and antibacterial properties.

[0171] As shown in Tables 1 and 2, compared with Example 1, in Comparative Example 2, due to the excessive addition of initiator in Comparative Example 2, excessive free radicals are generated in the chain initiation stage, thereby accelerating the polymerization reaction rate and causing premature chain termination reaction, resulting in the number average molecular weight of the prepared polyvinyl pyrrolidone with carboxyl side chains being less than 30,000, affecting the hydrophilicity and antibacterial properties of the catheter.

[0172] As shown in Table 1 and Table 2, compared with Example 1, Comparative Example 3 has an amino group introduced on the surface of the latex particles. The amino group is alkaline, which promotes the hydrolysis of the amide bond connecting the activated polyvinyl pyrrolidone and the quaternary ammonium salt cation, thereby reacting with the amino group to separate the quaternary ammonium salt cation and reduce the antibacterial property of the catheter.

[0173] As shown in Tables 1 and 2, compared with Example 1, in Comparative Example 4, since the reaction was carried out under weak alkaline conditions, the hydrolysis of the amide bond connecting the activated polyvinylpyrrolidone and the quaternary ammonium salt positive ion was promoted, causing the quaternary ammonium salt positive ion to be separated, thereby reducing the antibacterial property of the catheter.

[0174] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing an antibacterial and anti-stick latex urinary catheter, characterized in that: The steps include: S1: placing vinyl pyrrolidone, an unsaturated carboxylic acid monomer, and an initiator in a first solvent and stirring to obtain polyvinyl pyrrolidone with a carboxyl side chain; S2: placing polyvinyl pyrrolidone with a carboxyl side chain, an activator, and a catalyst in a second solvent and stirring to obtain activated polyvinyl pyrrolidone; Wherein, the activator is a carbodiimide coupling agent, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or N,N'-dicyclohexylcarbodiimide; The catalyst includes one or more of N-hydroxybenzenesulfonimide, triethylamine, and 1-hydroxybenzotriazole; S3: placing the antibacterial agent and activated polyvinyl pyrrolidone in a third solvent and stirring to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone; Wherein, the antibacterial agent is a quaternary ammonium salt organic antibacterial agent, including one or more of dodecyldimethylbenzyl ammonium chloride, hexadecyltrimethylammonium bromide, benzyltrimethylammonium chloride, and hexadecylpyridinium chloride; S4: activating the latex particles to obtain activated latex particles; The activation treatment is oxygen plasma treatment, and the oxygen plasma treatment conditions are: power 70-90W, air flow rate 90-110mL / min, air pressure 50-70Pa, and etching time 30-60s; S5: placing the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles in a fourth solvent, stirring, and freeze-drying to obtain antibacterial and anti-sticking latex particles; S6: The antibacterial and anti-sticking latex particles are melted and extruded to form an antibacterial and anti-sticking latex catheter.

2. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: The reaction conditions in step S1 include: Under a protective gas atmosphere, heat and stir at a temperature of 60-80°C for 12-24 hours; Wherein, the protective gas includes nitrogen, argon or helium; And / or, the unsaturated carboxylic acid monomer includes one or more of acrylic acid, methacrylic acid, and maleic acid; and / or, the initiator comprises one or more of dibenzoyl peroxide or azobisisobutyronitrile; and / or, the first solvent comprises one or more of ethanol, isopropanol, and 1,4-dioxane; And / or, the mass-to-volume ratio of the total mass of vinyl pyrrolidone, the unsaturated carboxylic acid monomer and the initiator to the first solvent is 1 g: (5-10) mL.

3. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S1, the molar ratio of vinyl pyrrolidone to the unsaturated carboxylic acid monomer is 1:(8-10), and the molar amount of the initiator accounts for 0.1-3% of the total molar amount of vinyl pyrrolidone and the unsaturated carboxylic acid monomer; And / or, the number average molecular weight of the polyvinyl pyrrolidone with a carboxyl side chain is 30,000-200,000.

4. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S2, the second solvent includes one or more of water, ethanol, isopropanol, tetrahydrofuran or N,N-dimethylformamide; And / or, in step S2, the pH is 4-6, the stirring temperature is 20-50° C., and the stirring time is 2-4 h; And / or, the mass-to-volume ratio of the total mass of the polyvinyl pyrrolidone with a carboxyl side chain, the activator and the catalyst to the second solvent is 1 g: (5-10) mL.

5. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S2, the mass ratio of polyvinyl pyrrolidone with a carboxyl side chain, the activator and the catalyst is 1:(3-4):(0.01-0.1).

6. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S3, the third solvent includes one or more of water, isopropanol, ethanol, and dichloromethane; And / or, the reaction conditions in step S3 include: stirring at 20-40° C. for 4-12 h; and / or, the mass ratio of the antimicrobial agent to the activated polyvinylpyrrolidone is (1-3):1; And / or, the mass-to-volume ratio of the total mass of the antimicrobial agent and the activated polyvinyl pyrrolidone to the third solvent is 1 g: (5-10) mL.

7. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S2, the particle size of the latex particles is 1-100 μm.

8. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S5, the fourth solvent includes one or more of water, isopropanol, ethanol, and dichloromethane; And / or, the freeze drying comprises: a temperature of -40 to -50°C and a drying time of 2 to 4 days; And / or, the reaction conditions in step S5 include: pH 4-6, stirring at 20-40° C. for 4-12 h; and / or, the mass ratio of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone to the activated latex particles is 1:(2-3); And / or, the mass-to-volume ratio of the total mass of the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and the activated latex particles to the fourth solvent is 1 g: (10-15) mL.

9. The method for preparing the antibacterial and anti-stick latex urinary catheter according to claim 1, characterized in that: In step S6, the process of melt extrusion includes: The temperature of the feeding section is controlled at 100-150℃; the temperature of the barrel section is controlled at 200-220℃; the temperature of the die section is controlled at 200-220℃; the temperature of the die section is controlled at 220-240℃.

10. An antibacterial and anti-stick latex catheter produced by the method for producing an antibacterial and anti-stick latex catheter according to any one of claims 1 to 9.

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