Antibacterial and anti-sticking latex catheter and preparation method thereof

Abstract

The invention provides an antibacterial and anti-sticking latex catheter and a preparation method thereof, and relates to the technical field of medical implant materials.The preparation method comprises the following steps that S1, vinyl pyrrolidone, unsaturated carboxylic acid monomers and an initiator are placed in a first solvent, and polyvinylpyrrolidone with carboxyl side chains is obtained; s2, putting the polyvinylpyrrolidone with the carboxyl side chain, an activating agent and a catalyst into a second solvent to obtain activated polyvinylpyrrolidone; s3, putting the antibacterial agent and the activated polyvinylpyrrolidone into a third solvent to obtain quaternary ammonium salt group grafted polyvinylpyrrolidone; s4, activating the latex particles to obtain activated latex particles; s5, putting the quaternary ammonium salt group grafted polyvinylpyrrolidone and the activated latex particles into a fourth solvent to obtain antibacterial and anti-sticking latex particles; s6, the antibacterial and anti-sticking latex particles are melted and extruded into the antibacterial and anti-sticking latex catheter. The hydrophilicity and the antibacterial property 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] As an auxiliary tool widely used in the medical field, latex catheters play an indispensable role in clinical practice due to their excellent softness and durability. However, despite the many advantages of latex catheters, their surface may gradually become sticky due to the residue of urine, urethral secretions and other body fluids during long-term use. This problem cannot be ignored.

[0003] During the use of latex catheters, their inner wall will constantly contact the patient's urine. Urine contains not only water, but also various mineral salts, urea, uric acid and other metabolic wastes. The long-term deposition of these components on the inner wall of the catheter will gradually form a thick shell. This shell not only affects the drainage effect of the catheter, making urine discharge difficult, but also may cause catheter blockage, increasing the difficulty of catheter removal. For patients who need to have a long-term indwelling catheter, this blockage phenomenon will undoubtedly bring them great inconvenience and pain.

[0004] In addition to the precipitation of mineral salts and the accumulation of urine scale, the surface of latex catheters may also become more viscous due to the residue of urethral secretions and other body fluids. Urethral secretions are the products of urethral mucosal cell metabolism, which may contain proteins, mucus and other biological macromolecules. The attachment of these substances to the surface of the catheter will further increase its viscosity, making the catheter more susceptible to contamination during use.

[0005] What’s more serious is that the antibacterial properties of latex itself are relatively weak. Although latex has a certain natural antibacterial ability, the antibacterial substances on its surface may be gradually consumed during long-term use, making it difficult to effectively inhibit the growth of bacteria on the surface of the catheter. Especially when the patient’s urethra is inflamed or infected, bacteria are more likely to find a suitable living environment on the surface of the catheter and multiply in large numbers. These bacteria may not only cause or aggravate urinary tract infections, but may also retrogradely infect the bladder, kidneys and other organs through the catheter, causing more serious consequences.

[0006] Urinary tract infection is one of the common complications of patients with indwelling urinary catheters. According to statistics, the incidence of urinary tract infection in patients with indwelling urinary catheters is as high as tens of percentage points. This high infection rate not only increases the pain and medical expenses of patients, but may also affect the patient's recovery process and quality of life. Therefore, how to reduce the problem of increased viscosity and poor antibacterial properties of latex urinary catheters during use has become an important issue that needs to be solved in the medical field. Summary of the invention

[0007] The purpose of the present invention is 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 a stable chemical bond, which can not only improve the hydrophilicity and antibacterial property of the latex particles, but also enable the prepared antibacterial and anti-sticking latex tube 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 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 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] Further, 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 12-24h;

[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 includes one or more of dibenzoyl peroxide or azobisisobutyronitrile;

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

[0022] And / or, the mass 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] Further, on the basis of 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 having a carboxyl side chain is 30,000-200,000.

[0025] Further, on the basis of 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 2-4h;

[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 dodecyldimethylbenzylammonium chloride, hexadecyltrimethylammonium bromide, benzyltrimethylammonium chloride, and hexadecylpyridinium chloride;

[0032] And / or, the third solvent includes 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 polyvinyl pyrrolidone is (1-3):1;

[0035] And / or, the mass 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] Further, on the basis of the above technical solution, in step S4, 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, etching time 30-60s;

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

[0038] Further, on the basis of 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] Further, based on the above technical solution, in step S6, the process of melting and extruding 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 catheter prepared by the method for preparing the antibacterial and anti-stick latex catheter.

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

[0047] The present invention grafts polyvinyl pyrrolidone (PVP) and a quaternary ammonium salt antibacterial agent with high antibacterial performance through chemical bonds, and activates and treats the surface of latex particles, effectively promoting the interaction between polyvinyl pyrrolidone and latex particles after the grafting of quaternary ammonium salt groups, and realizing the close combination between the two by forming a stable and firm chemical bond. The introduction of polyvinyl pyrrolidone greatly enhances the hydrophilicity of latex particles, so that the latex material shows better wettability and dispersibility under a wet environment. In addition, the successful grafting of the quaternary ammonium salt antibacterial agent gives the latex particles excellent antibacterial properties, can effectively inhibit or kill a variety of bacteria and microorganisms, thereby significantly improving the hygienic safety of the product, and fundamentally solving the problem that the traditional latex tube is easy to cause the wall viscosity to increase and is difficult to clean due to attached substances (such as protein, grease, etc.) during use. These attached 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 service life of the product, and also bring users a more convenient and hygienic use experience. DETAILED DESCRIPTION

[0048] In order to make the purpose, technical scheme and advantages of the present invention clearer, the technical scheme in the embodiment 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 only 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 ordinary technicians in the field without making creative work are within the scope of protection of the present invention. The process parameters of the following embodiments that do not specify specific conditions are usually based on conventional conditions.

[0049] The endpoints and any values ​​of the ranges disclosed in the present invention 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 endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be regarded as 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 catheter, comprising the following steps:

[0051] S1: placing vinyl pyrrolidone, unsaturated carboxylic acid monomers 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 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) PVP is a non-toxic, non-irritating macromolecular compound with good biocompatibility and lubricity. When added into a latex catheter and in contact with an aqueous liquid, the PVP molecule rapidly absorbs water to form a hydrophilic gel layer, thereby significantly reducing the viscosity of the catheter. The present invention grafts polyvinyl pyrrolidone (PVP) with a quaternary ammonium salt antibacterial agent with high-efficiency antibacterial performance through chemical bonds, and then activates and treats the surface of latex particles, effectively promoting the interaction between the polyvinyl pyrrolidone and the latex particles after the quaternary ammonium salt group is grafted, and by forming a stable and firm chemical bond, a close combination between the two is achieved. The introduction of polyvinyl pyrrolidone greatly enhances the hydrophilicity of the latex particles, so that the latex material shows better wettability and dispersibility in a humid environment. And the successful grafting of the quaternary ammonium salt antibacterial agent gives the latex particles excellent antibacterial properties, which can effectively inhibit or kill 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 existence of the above-mentioned unique structure, fundamentally solves the problem that the traditional latex tube is easy to cause the viscosity of the tube wall to increase and is difficult to clean due to the attachment of substances (such as protein, grease, etc.) during use. These attached 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 service life of the product, and also bring users a more convenient and hygienic use 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 12-24h;

[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 includes one or more of dibenzoyl peroxide or azobisisobutyronitrile;

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

[0064] And / or, the mass 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, too much initiator may cause premature termination of the polymer chain, thereby affecting the molecular weight and molecular weight distribution of the polymer. Too little initiator may cause incomplete polymerization. The type and concentration of the initiator have a great influence 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 higher proportion of carboxyl functional groups in the polymer molecules. The high carboxyl content not only provides abundant reaction sites for the subsequent activation reaction, enhances the interaction between the polymer and the antibacterial agent, but also gives the polymer itself better water solubility, ion exchange capacity and potential biocompatibility, which is crucial to improving the performance of the final product.

[0069] Furthermore, during the polymerization process, the choice of initiator and its dosage have a profound impact on the structure and properties of the polymer. If the amount of initiator is too much, it will lead to too many free radicals generated in the chain initiation stage, thereby accelerating the polymerization rate, but it may also cause premature chain termination reaction, resulting in insufficient polymer chain length, reduced molecular weight, narrow molecular weight distribution, and even the production of a large number of oligomers. This will not only reduce the physical and mechanical properties of the polymer, such as tensile strength and toughness, but may also affect its performance in subsequent processing and applications.

[0070] On the contrary, if the amount of initiator is too small, the chain initiation rate will slow down. Although the polymerization time can be extended, it may lead to incomplete polymerization reaction and some monomers cannot be effectively converted into polymers, resulting in waste of raw materials and unstable product quality. In addition, too low initiator concentration may also lead to increased differences in polymer chain length and wider 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 having a carboxyl side chain is 30,000-200,000.

[0073] Specifically, the present invention limits the number average molecular weight of polyvinyl pyrrolidone with carboxyl side chains to 30000-200000 because it has good hydrophilicity. PVP within this range has 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. The present invention limits its number average molecular weight to within the range of 30000-200000 when designing and synthesizing polyvinyl pyrrolidone with carboxyl side chains, because the strength of hydrophilicity is not only related to the type and quantity 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 interaction between molecular chains during the dissolution process, which may cause the dissolution rate to slow down, and even cannot be completely dissolved in some solvents, forming gel or precipitation. 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 to form an active acyl intermediate (-CO-NH-C≡N) by promoting the removal of protons from the carboxyl group. This acyl intermediate has a higher reactivity and can more easily react with amine compounds such as quaternary ammonium salt organic antibacterial 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 antibacterial 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 2-4h;

[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 dodecyldimethylbenzylammonium chloride, hexadecyltrimethylammonium bromide, benzyltrimethylammonium chloride, and hexadecylpyridinium chloride;

[0083] Specifically, the positively charged nitrogen atom in the quaternary ammonium salt can undergo an effective nucleophilic addition reaction with the acyl intermediate in the activated polyvinyl pyrrolidone. During this reaction, the nitrogen atom attacks the acyl carbon atom, resulting in the rupture of the carbon-oxygen double bond and the formation of a new carbon-nitrogen single bond. At the same time, the oxygen atom in the original acyl group combines with the hydrogen atom to generate a water molecule as a byproduct of the reaction. Thus, a stable amide bond is formed, firmly connecting the quaternary ammonium salt to the molecular chain of the activated polyvinyl pyrrolidone.

[0084] And / or, the third solvent includes 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 polyvinyl pyrrolidone is (1-3):1;

[0087] And / or, the mass 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 70-90W, air flow rate 90-110mL / min, air pressure 50-70Pa, etching time 30-60s;

[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 to add a large number of active hydroxyl groups on their surfaces, which can react with the carbonyl groups on the pyridine ring in polyvinyl pyrrolidone to generate 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 exist on both the pyridine ring and the amide bond, but 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 weak. In order to make full use of the different properties of the two carbonyl groups and prevent the hydrolysis of the amide bond, the present invention limits the reaction to be carried out in a slightly acidic environment. The acidic condition helps to prevent the hydrolysis of the amide bond, thereby avoiding unnecessary reactions between the carbonyl group in the amide bond and the hydroxyl group, resulting in the separation of the quaternary ammonium salt positive ion. More importantly, under acidic conditions, the carbonyl group on the pyridine ring is protonated, 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 process of melt extrusion 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 embodiments 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: In a nitrogen atmosphere, vinyl pyrrolidone, acrylic acid and dibenzoyl peroxide are placed in ethanol, heated and stirred at 70°C for 20 hours 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 volume ratio of the total mass of vinyl pyrrolidone 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 for 4 hours at a pH of 5 and a temperature of 30° C. 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 volume ratio of the total mass of polyvinyl pyrrolidone 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, 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 volume ratio of the total mass of dodecyldimethylbenzylammonium chloride and activated polyvinylpyrrolidone to ethanol is 1 g:5 mL.

[0112] S4: treating the latex particles (particle size of 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, freeze-drying, and drying at -40°C for 3 days to obtain antibacterial and anti-sticking latex particles;

[0115] Among them, the mass ratio of quaternary ammonium salt group-grafted polyvinyl pyrrolidone and 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 the mass volume ratio of 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; the temperature of the die section is controlled at 230°C.

[0119] Example 2

[0120] S1: In an argon atmosphere, vinyl pyrrolidone, methacrylic acid and azobisisobutyronitrile are placed in isopropanol, and heated and stirred at 80°C for 14 hours 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 volume ratio of the total mass of vinyl pyrrolidone, methacrylic acid and azobisisobutyronitrile to isopropanol is 1 g:5 mL.

[0123] S2: placing polyvinyl pyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and triethylamine in isopropanol, stirring for 3 hours at a pH of 4 and a temperature of 30°C 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 volume ratio of the total mass of polyvinylpyrrolidone with a carboxyl side chain, N,N'-dicyclohexylcarbodiimide and triethylamine to isopropanol is 1 g:5 mL.

[0126] S3: placing cetylpyridinium chloride and activated polyvinyl pyrrolidone in isopropanol 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 volume ratio of the total mass of cetylpyridinium chloride and activated polyvinylpyrrolidone to isopropanol is 1 g:5 mL.

[0129] S4: treating the latex particles (particle size of 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 isopropanol at a pH of 5, stirring at 40°C for 12 hours, freeze-drying, and drying at -50°C for 2 days to obtain antibacterial and anti-sticking latex particles;

[0132] Among them, the mass ratio of quaternary ammonium salt group-grafted polyvinyl pyrrolidone and 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; the temperature of the die section is controlled at 240°C.

[0136] Example 3

[0137] S1: In a helium atmosphere, vinyl pyrrolidone, maleic acid and azobisisobutyronitrile are placed in 1,4-dioxane, and heated and stirred at 60°C for 24 hours 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 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 for 2 hours at a pH of 6 and a temperature of 50°C to obtain activated polyvinyl pyrrolidone;

[0141] The mass ratio of polyvinyl pyrrolidone with 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: placing benzyltrimethylammonium chloride and activated polyvinyl pyrrolidone in water, stirring 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 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 of 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, freeze-drying, and drying at -40°C for 4 days to obtain antibacterial and anti-sticking latex particles;

[0149] Among them, the mass ratio of quaternary ammonium salt group-grafted polyvinyl pyrrolidone and 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 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; the temperature of the die section is controlled at 220°C.

[0153] Comparative Example 1

[0154] The difference between this comparative example and Example 1 is 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] The difference between this comparative example and Example 1 is 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 of 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] The difference between this comparative example and Example 1 is that in step S5, the reaction is carried out under weak 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 standard ISO22196-2011;

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

[0164] Cut a 2cm long antibacterial and anti-stick latex catheter, place it on a balance and weigh it, record it as m1, place the catheter in a container filled with distilled water, keep it for 1 minute and then take it out. Place the catheter straight, absorb the surface water droplets with filter paper and quickly weigh it, record it as m2. Weigh each catheter 3 times. Water absorption rate = (m2-m1) / m1×100%.

[0165] Performance data

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

[0167]

[0168] Table 2: Water absorption of the antibacterial and anti-adhesive 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 Table 1 and Table 2, compared with Example 1, since the molar ratio of vinyl pyrrolidone and unsaturated carboxylic acid monomer in Comparative Example 1 is reduced, the carboxyl content in the prepared polyvinyl pyrrolidone with a carboxyl side chain is reduced, which further affects the grafting of activated polyvinyl pyrrolidone with the quaternary ammonium salt organic antibacterial agent, resulting in decreased hydrophilicity and antibacterial properties.

[0171] As shown in Table 1 and Table 2, compared with Example 1, in Comparative Example 2, due to the excessive addition of initiator in Comparative Example 2, too many free radicals are generated in the chain initiation stage, thereby accelerating the polymerization reaction rate and causing premature chain termination reaction, so that the number average molecular weight of the prepared polyvinyl pyrrolidone with carboxyl side chains is 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, in Comparative Example 3, since amino groups are introduced on the surface of the latex particles in Comparative Example 3, the amino groups are alkaline, which promotes the hydrolysis of the amide bond connecting the activated polyvinyl pyrrolidone and the quaternary ammonium salt cations, thereby reacting with the amino groups to separate the quaternary ammonium salt cations and reduce the antibacterial property of the catheter.

[0173] As shown in Table 1 and Table 2, compared with Example 1, in Comparative Example 4, since the reaction is carried out under weak alkaline conditions, the hydrolysis of the amide bond connecting the activated polyvinyl pyrrolidone and the quaternary ammonium salt cation is promoted, the quaternary ammonium salt cation is separated, and the antibacterial property of the catheter is reduced.

[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 aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned 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 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; S3: placing the antibacterial agent and activated polyvinyl pyrrolidone in a third solvent and stirring to obtain quaternary ammonium salt group-grafted polyvinyl pyrrolidone; S4: activating the latex particles to obtain activated latex particles; S5: placing the quaternary ammonium salt group-grafted polyvinyl pyrrolidone and 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-sticking latex 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 12-24h; 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 includes one or more of dibenzoyl peroxide or azobisisobutyronitrile; And / or, the first solvent includes one or more of ethanol, isopropanol, and 1,4-dioxane; And / or, the mass 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-adhesive latex 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 having a carboxyl side chain is 30,000-200,000.

4. The method for preparing the antibacterial and anti-sticking latex 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, the activator is a carbodiimide coupling agent, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or N,N'-dicyclohexylcarbodiimide; And / or, the catalyst includes one or more of N-hydroxybenzenesulfonimide, triethylamine, and 1-hydroxybenzotriazole; And / or, in step S2, the pH is 4-6, the stirring temperature is 20-50°C, and the stirring time is 2-4h; 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.

5. The method for preparing the antibacterial and anti-adhesive 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-adhesive latex urinary catheter according to claim 1, characterized in that: In step S3, the antibacterial agent is a quaternary ammonium salt organic antibacterial agent, including one or more of dodecyldimethylbenzylammonium chloride, hexadecyltrimethylammonium bromide, benzyltrimethylammonium chloride, and hexadecylpyridinium chloride; And / or, 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 polyvinyl pyrrolidone is (1-3):1; And / or, the mass 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-adhesive latex urinary catheter according to claim 1, characterized in that: In step S4, 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, etching time 30-60s; And / or, 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 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-sticking 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 made by the method for making an antibacterial and anti-stick latex catheter as claimed in any one of claims 1 to 9.

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