An antibacterial catheter and a method for manufacturing the same

Abstract

The application discloses an antibacterial catheter and a preparation method thereof, and belongs to the technical field of catheters, and aims to solve the problem of poor antibacterial effect and short duration caused by the poor combination of an antibacterial agent and a thermoplastic polyurethane elastomer after antibacterial treatment of the existing catheter. The antibacterial catheter comprises a pipe body and n antibacterial layers formed on the outer wall of the pipe body in sequence, wherein n is a positive integer; the material of the pipe body is a polyurethane elastomer; the material of the antibacterial layer comprises 100 parts of the polyurethane elastomer and 1-10 parts of an antibacterial agent in terms of mass fraction, and the antibacterial agent is a pyrithione compound. The application can achieve long-term antibacterial effect based on the multilayer antibacterial layer and the hydrogen bond between the antibacterial agent and the polyurethane elastomer.

Description

Technical Field

[0001] This invention belongs to the field of catheter technology, and particularly relates to an antibacterial catheter and its preparation method. Background Technology

[0002] Catheters are medical devices used in clinical surgery to drain pus, blood, and fluid accumulated between body tissues or in body cavities, preventing postoperative infection and promoting wound healing. Polyurethane elastomer (PUE) is a commonly used material for catheters, possessing good wear resistance, toughness, and processability.

[0003] Because thermoplastic polyurethane elastomers have low antibacterial activity, they are prone to bacterial growth when the external environment is suitable. Therefore, it is necessary to incorporate antibacterial agents to improve the antibacterial activity of thermoplastic polyurethane elastomers.

[0004] However, adding antibacterial agents directly to thermoplastic polyurethane elastomers results in large amounts of antibacterial agents, high costs, and poor bonding between the antibacterial agents and thermoplastic polyurethane elastomers, leading to poor antibacterial effects and short durations of action. Summary of the Invention

[0005] Based on the above analysis, the present invention aims to provide an antibacterial catheter and its preparation method, in order to solve the problem in the prior art that the antibacterial agent and the thermoplastic polyurethane elastomer are not tightly bonded after antibacterial treatment of existing catheters, resulting in poor antibacterial effect and short duration.

[0006] The objective of this invention is mainly achieved through the following technical solutions.

[0007] This invention provides an antibacterial catheter, comprising a tube body and n antibacterial layers sequentially formed on the outer wall of the tube body, where n is a positive integer;

[0008] The tube body is made of polyurethane elastomer;

[0009] The antibacterial layer consists of 100 parts by weight of polyurethane elastomer and 1 to 10 parts by weight of antibacterial agent, which is a pyridinethione compound.

[0010] Furthermore, in the antibacterial layer, the antibacterial agent molecules are bonded to the molecular chains of the polyurethane elastomer by hydrogen bonds.

[0011] Furthermore, the content of antibacterial agents in the first to the nth antibacterial layers gradually increases.

[0012] Furthermore, the number of antibacterial layers is 2 to 4.

[0013] Furthermore, the antibacterial layer consists of three layers, which are the first antibacterial layer, the second antibacterial layer, and the third antibacterial layer, respectively, in a direction that gradually moves away from the tube body.

[0014] Furthermore, the mass fraction of polyurethane elastomer in the first antibacterial layer is 100 parts, and the mass fraction of antibacterial agent in the first antibacterial layer is 1 to 3 parts.

[0015] Furthermore, the second antibacterial layer contains 100 parts by mass of polyurethane elastomer and 4 to 6 parts by mass of antibacterial agent.

[0016] Furthermore, the third antibacterial layer contains 100 parts by mass of polyurethane elastomer and 7 to 10 parts by mass of antibacterial agent.

[0017] Furthermore, the pyridinethione compounds are one or more of N-oxy-2-thiopyridine, N-oxy-2-thiopyridine sodium salt, N-oxy-2-thiopyridine zinc salt, and N-oxy-2-thiopyridine copper salt in any proportion.

[0018] The present invention also provides a method for preparing an antibacterial catheter, which is used in the preparation of the above-mentioned antibacterial catheter. The preparation method includes the following steps:

[0019] Provide a tube;

[0020] Multiple antibacterial layers are formed sequentially on the outer wall of the tube.

[0021] Compared with the prior art, the present invention can achieve at least one of the following beneficial effects:

[0022] A) The antibacterial catheter provided by this invention forms a multi-layered antibacterial layer on the outer wall of the catheter body. Antibacterial agent molecules are effectively bonded to polyurethane elastomer molecular chains through supramolecular forces (hydrogen bonds), resulting in excellent compatibility and adhesion between the antibacterial agent and the polyurethane elastomer. This not only enhances the overall performance of the antibacterial layer but also achieves a long-lasting antibacterial effect, inhibiting bacterial adhesion and growth, and reducing the risk of infection. Simultaneously, through the effective bonding between the antibacterial agent molecules and the polyurethane elastomer molecular chains, the antibacterial agent in the antibacterial layer will not be released into the external environment, thereby reducing the risk of environmental contamination.

[0023] B) The antibacterial layer in the antibacterial catheter provided by the present invention has a multi-layer structure, and the content of antibacterial agent in the multi-layer antibacterial layer gradually increases along the direction gradually away from the tube body. This can realize the transition between the tube body and the antibacterial layer, improve the connection performance between the antibacterial layer and the tube body, and prevent the antibacterial layer from falling off the tube body. At the same time, the content of antibacterial agent is the highest in the outermost antibacterial layer, thereby effectively reducing the amount of antibacterial agent added while ensuring the antibacterial effect.

[0024] C) The antibacterial catheter provided by the present invention uses pyridine thionone compounds as antibacterial agents in the antibacterial layer. It is a low-toxicity and effective antibacterial agent that can form hydrogen bonds with polyurethane elastomers, has a high antibacterial effect, and can broadly inhibit the growth of a variety of bacteria.

[0025] D) The method for preparing the antibacterial catheter provided by the present invention uses an automated coating component to replace the existing manual coating. In the reservoir tube, since the density of the first antibacterial layer material is greater than that of the nth antibacterial layer material, the organic solvent solution of the antibacterial agent material from the first to the nth layers can be arranged sequentially from bottom to top. Then, the organic solvent solution of the antibacterial agent material in the reservoir tube is sequentially coated onto the tube body by a coating ring brush, realizing one-time feeding and multi-layer antibacterial coating.

[0026] In this invention, the above-described technical solutions can be combined with each other to achieve more preferred combinations. Other features and advantages of this invention will be set forth in the following description, and some advantages may become apparent from the description or be learned by practicing the invention. The objects and other advantages of this invention can be realized and obtained through the embodiments described and the accompanying drawings, which are particularly pointed out. Attached Figure Description

[0027] The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. Throughout the drawings, the same reference numerals denote the same parts.

[0028] Figure 1 This is a schematic diagram of the structure of the antibacterial catheter provided by the present invention;

[0029] Figure 2 This is a comparison of the infrared spectra of the antibacterial catheter prepared in Example 1 of the present invention and the initial catheter for comparison.

[0030] Figure 3 This is a comparison chart of the antibacterial rates of the antibacterial catheters prepared in Examples 1-3 and Comparative Example 1 after 12 hours.

[0031] Figure 4 This is a comparison chart of the antibacterial rates of the antibacterial catheters prepared in Examples 1-3 and Comparative Example 1 after 15 days.

[0032] Figure label:

[0033] 1-Tube body; 2-First antibacterial layer; 3-Second antibacterial layer; 4-Third antibacterial layer. Detailed Implementation

[0034] The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings, which constitute a part of the present invention and are used together with the embodiments of the present invention to illustrate the principles of the present invention, but are not intended to limit the scope of the present invention.

[0035] This invention provides an antibacterial catheter, see [link to documentation]. Figure 1 It includes a tube body 1 and n antibacterial layers formed sequentially on the outer wall of the tube body 1, where n is a positive integer. The material of the tube body 1 is polyurethane elastomer. The material of the antibacterial layer, calculated by mass parts, includes 100 parts of polyurethane elastomer and 1 to 10 parts of antibacterial agent. The antibacterial agent is a pyridine thione compound. The antibacterial agent molecule is hydrogen bonded to the molecular chain of the polyurethane elastomer. The content of antibacterial agent in the first antibacterial layer to the nth antibacterial layer gradually increases.

[0036] Compared with existing technologies, the antibacterial catheter provided by this invention forms a multi-layered antibacterial layer on the outer wall of the tube body 1. Antibacterial agent molecules are effectively bonded to polyurethane elastomer molecular chains through supramolecular forces (hydrogen bonds), resulting in excellent compatibility and adhesion between the antibacterial agent and the polyurethane elastomer. This not only enhances the overall performance of the antibacterial layer but also achieves a long-lasting antibacterial effect, inhibiting bacterial adhesion and growth, and reducing the risk of infection. Simultaneously, through the effective bonding between the antibacterial agent molecules and the polyurethane elastomer molecular chains, the antibacterial agent in the antibacterial layer will not be released into the external environment, thereby reducing the risk of environmental contamination.

[0037] On the other hand, the antibacterial layer in the above-mentioned antibacterial catheter has a multi-layer structure, and the content of antibacterial agent in the multi-layer antibacterial layer gradually increases along the direction gradually away from the tube body 1. This can realize the transition between the tube body 1 and the antibacterial layer, improve the connection performance between the antibacterial layer and the tube body 1, and prevent the antibacterial layer from falling off the tube body 1. At the same time, the content of antibacterial agent is the highest in the outermost antibacterial layer, so as to effectively reduce the amount of antibacterial agent added while ensuring the antibacterial effect.

[0038] On the other hand, pyridine thione compounds are used as antibacterial agents for the antibacterial layer. These are low-toxicity and effective antibacterial agents that can form hydrogen bonds with polyurethane elastomers, exhibiting high antibacterial effects and broadly inhibiting the growth of various bacteria.

[0039] For example, the number of antibacterial layers is 2 to 4 (e.g., 3 layers).

[0040] For example, see the 3-story building. Figure 1Along the direction gradually away from the tube body 1, there are three antibacterial layers: a first antibacterial layer 2, a second antibacterial layer 3, and a third antibacterial layer 4. The mass fraction of polyurethane elastomer in the first antibacterial layer 2, the second antibacterial layer 3, and the third antibacterial layer 4 is 100 parts. The mass fraction of antibacterial agent in the first antibacterial layer 2 is 1 to 3 parts, the mass fraction of antibacterial agent in the second antibacterial layer 3 is 4 to 6 parts, and the mass fraction of antibacterial agent in the third antibacterial layer 4 is 7 to 10 parts.

[0041] This invention also provides a method for preparing an antibacterial catheter, comprising the following steps:

[0042] Step 1: Provide a coating assembly, which includes a coating ring brush, a liquid delivery ring, a liquid delivery pipe and a liquid storage pipe. The outlet end of the liquid storage pipe is connected to the inlet of the liquid delivery ring through the liquid delivery pipe. The coating ring brush is located on the inner wall of the liquid delivery ring.

[0043] Step 2: Place the coating ring brush on the outer wall of the tube body 1;

[0044] Step 3: Add the organic solvent solution of the first to nth antibacterial layer materials sequentially into the storage tube;

[0045] Step 4: Drive the coating ring brush to slide back and forth relative to the tube body 1. The organic solvent solution of the first antibacterial layer material in the storage tank is sequentially delivered to the coating ring brush through the liquid delivery pipe and the liquid delivery circulation to coat the tube body 1 with all the organic solvent solution of the first antibacterial layer material. The coating ring brush then stops sliding.

[0046] Step 5: Curing the first antibacterial layer;

[0047] Step 6: Drive the coating ring brush to slide back and forth relative to the tube body 1. The organic solvent solution of the next layer of antibacterial material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the next layer of antibacterial material onto the tube body 1. The coating ring brush stops sliding.

[0048] Step 7: Curing the next antibacterial layer;

[0049] Step 8: Repeat steps 6 to 7 until the nth antibacterial layer is prepared, and an antibacterial catheter is obtained.

[0050] It should be noted that the density of the organic solvent solution for the antibacterial layer material can be controlled in the following ways:

[0051] The density can be controlled by introducing branches of different densities into the polyurethane elastomer molecular chain, or by using organic solvents of different densities; these methods will not be detailed here.

[0052] Compared with the prior art, the method for preparing antibacterial catheters provided by the present invention uses an automated coating component to replace the existing manual coating. In the reservoir tube, since the density of the first antibacterial layer material is greater than that of the nth antibacterial layer material, the organic solvent solution of the antibacterial agent material from the first to the nth layers can be arranged sequentially from bottom to top. Then, the organic solvent solution of the antibacterial agent material in the reservoir tube is sequentially coated onto the tube body 1 by a coating ring brush, realizing one-time feeding and multi-layer antibacterial coating.

[0053] In order to effectively solidify the antibacterial layer, the solidification process in steps 5 and 7 above includes the following steps:

[0054] The tube body 1 coated with antibacterial agent is naturally dried at a temperature of 20-30℃ for 0.5-1.5 hours to complete the first curing.

[0055] After the first curing, the tube body 1 is vacuum dried at 70-80℃ for 2-4 hours to remove organic solvents and complete the second curing.

[0056] For example, the method for preparing the organic solvent solution of the above-mentioned antibacterial layer material includes the following steps:

[0057] Step a: The hydroxyl-terminated polymer and the polyisocyanate are stirred and reacted to obtain a polyurethane prepolymer;

[0058] Step b: Add the organic solvent solution of the chain extender to the polyurethane prepolymer to react, mix and stir to react, and obtain the organic solvent solution of the polyurethane elastomer.

[0059] Step c: Add the organic solvent solution of the antibacterial agent to the organic solvent solution of the polyurethane elastomer to react and obtain the organic solvent solution of the antibacterial layer material.

[0060] For example, in the above steps, the hydroxyl-terminated polymer is 63-87% by mass percentage of the polyurethane elastomer organic solvent solution, the polyisocyanate is 11-31%, the chain extender is 2-6%, and the organic solvent is 0.02-0.06%, wherein the molar ratio of isocyanate groups (-NCO) in the polyisocyanate to active hydrogen (-OH) in the chain extender is 1:1-1.1:1 (e.g., 1:1, 1.05:1, or 1.1:1); the antibacterial agent is 1-10% by mass percentage of the antibacterial agent organic solvent solution, and the organic solvent is 90-99%.

[0061] It should be noted that, unlike existing methods that involve adding reactive antibacterial agents during the synthesis of polyurethane elastomers or melt-blending polyurethane elastomers with antibacterial agents, the above-mentioned method for preparing an organic solvent solution for antibacterial layer materials involves adding antibacterial agents to polyurethane elastomers through solution blending. This allows the antibacterial agent molecules to form hydrogen bonds with the polyurethane elastomer molecular chains, thereby achieving a long-term antibacterial effect.

[0062] In order to ensure the yield of polyurethane prepolymer, in step a above, the reaction temperature is 70-80℃, the reaction time is 1-2h, and the reaction is carried out in a protective atmosphere.

[0063] Similarly, in order to ensure the yield of the organic solvent solution of polyurethane elastomer, the reaction temperature in step b above is 70-80°C and the reaction time is 5-6 hours.

[0064] In order to ensure the yield of the organic solvent solution for the antibacterial layer material, the reaction temperature in step c above is 70-80℃ and the reaction time is 2-12h.

[0065] To reduce the adverse effects of moisture in the terminal hydroxyl polymer on the reaction, the following steps are included before step a above:

[0066] The hydroxyl-terminated polymer raw material is subjected to dehydration and drying under reduced pressure of 0.8–1 bar, temperature of 98–102 °C (e.g., 100 °C), and time of 1.5–2.5 h (e.g., 2 h).

[0067] The hydroxyl-terminated polymer raw material after dehydration and drying under reduced pressure is cooled to 75–85°C (e.g., 80°C) to obtain a dried hydroxyl-terminated polymer.

[0068] Accordingly, in order to reduce the adverse effects of moisture in the chain extender on the reaction, the following steps are included between steps a and b:

[0069] The chain extender raw material is subjected to vacuum dehydration and drying at a pressure of 0.8–1 bar, a temperature of 98–102 °C (e.g., 100 °C), and a time of 1.5–2.5 h (e.g., 2 h).

[0070] The chain extender raw material after dehydration and drying under reduced pressure is cooled to 20-30°C (e.g., 25°C) to obtain the dried chain extender.

[0071] For example, in step a above, the molecular weight of the hydroxyl-terminated polymer is 1000–4000 g / mol, and the dispersion is 1.5–2. The hydroxyl-terminated polymer is one or more of polyether polyols and polyester polyols mixed in any proportion, wherein the polyether polyol is one or more of polymethyl dimethylsiloxane oxide (PDMS), polytetrahydrofuran ether diol (PTMEG), polyethylene glycol (PEG), and polypropylene glycol (PPG) mixed in any proportion, and the polyester polyol is one or more of polycaprolactone diol (PCL) and polyethylene terephthalate diol mixed in any proportion.

[0072] The polyisocyanate is a difunctional isocyanate, for example, one or more of toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), diphenylmethane diisocyanate (MDI), dicyclohexylmethane diisocyanate (HMDI), and hexamethylene diisocyanate (HDI) in any proportion.

[0073] In step b above, the chain extender is one or more of the following: a glycol chain extender and a diamine chain extender, mixed in any proportion. The glycol chain extender is one or more of the following: a mixture of 1,4-butanediol, ethylene glycol, 1,3-propanediol, and neopentyl glycol, mixed in any proportion. The diamine chain extender is one or more of the following: a mixture of diaminopyridine (DAP), diethyltoluenediamine (DETDA), and bis(sec-butylaminodiphenylmethane) (MDBA), mixed in any proportion.

[0074] In order to ensure that the chain extender is fully dissolved, in step b above, the organic solvent in the organic solvent solution of the chain extender is one or more of tetrahydrofuran (THF), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and dimethyl sulfoxide (DMSO) in any proportion.

[0075] Accordingly, for antibacterial agents, pyridinethiones are one or more of the following compounds in any proportion: N-oxy-2-thiopyridine (pyridinethion, abbreviated as PT), sodium N-oxy-2-thiopyridine (sodium pyridinethion, abbreviated as SPT), zinc N-oxy-2-thiopyridine (zinc pyridinethion, abbreviated as ZPT), and copper N-oxy-2-thiopyridine (copper pyridinethion, abbreviated as CPT).

[0076] In order to ensure that the antibacterial agent is fully dissolved, in step c above, the organic solvent in the organic solvent solution of the antibacterial agent is one or more of carbon tetrachloride (TCC), tetrahydrofuran (THF), acetone (ACE), toluene (TOL), and dioxane (DIOX) in any proportion.

[0077] It should be noted that, unless otherwise specified, all components used in this invention are commercially available.

[0078] Example 1

[0079] The method for preparing the antibacterial catheter provided in this embodiment includes the following steps:

[0080] Step A: Prepare organic solvent solutions for the first layer of antibacterial agent material, the second layer of antibacterial agent material, and the third layer of antibacterial agent material, respectively;

[0081] Cut the TPU tube into 20mm long segments as the tube body, and ultrasonically clean the surface of the tube with deionized water 3 times, 5 seconds each time. After taking it out, wipe the surface of the tube body dry with a paper towel.

[0082] Step B: Place the coating ring brush onto the outer wall of the pipe;

[0083] Step C: Add the organic solvent solutions of the first layer of antibacterial agent material, the second layer of antibacterial agent material, and the third layer of antibacterial agent material sequentially into the storage tube;

[0084] Step D: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the first antibacterial layer material in the storage tank is sequentially delivered to the coating ring brush through the liquid delivery pipe and the liquid delivery circulation, so that the organic solvent solution of the first antibacterial layer material is completely coated on the tube body, and the coating ring brush stops sliding.

[0085] Step E: Dry the tube coated with the first antibacterial layer at 25°C for 1 hour, and then vacuum dry it at 80°C for 3 hours.

[0086] Step F: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the second antibacterial layer material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the second antibacterial layer material onto the tube body. The coating ring brush then stops sliding.

[0087] Step G: Dry the tube coated with the second antibacterial layer at 25°C for 1 hour, and then vacuum dry it at 80°C for 3 hours.

[0088] Step H: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the third antibacterial layer material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the third antibacterial layer material onto the tube body. The coating ring brush then stops sliding.

[0089] Step 1: Dry the tube coated with the third antibacterial layer at 25°C for 1 hour, and then vacuum dry it at 80°C for 3 hours to obtain the antibacterial catheter.

[0090] The preparation methods and process parameters of the organic solvent solutions for the first, second, and third layers of antibacterial agents are basically the same, as detailed below:

[0091] PTMEG (hydroxyl-terminated polymer) was dehydrated and dried under reduced pressure at 100°C and 0.8 bar for 2 hours. After cooling to 80°C, 4,4'-diphenylmethane diisocyanate (polyisocyanate) that had been preheated and melted was added. The mixture was stirred and reacted at 80°C for 1 hour. The content of 4,4'-diphenylmethane diisocyanate was determined by titration using the di-n-butylamine acetone method. Once the predetermined value was reached, the reaction was stopped to obtain the polyurethane prepolymer.

[0092] 1,4-Butanediol (chain extender) was dehydrated and dried under reduced pressure at 100°C and 0.8 bar for 2 hours. After cooling to 25°C, it was completely dissolved in N,N-dimethylformamide (organic solvent).

[0093] A solution of 1,4-butanediol in N,N-dimethylformamide was added to the polyurethane prepolymer, and the mixture was stirred at 80°C for 6 hours to obtain an organic solvent solution of the polyurethane elastomer.

[0094] A tetrahydrofuran solution of zinc pyrithione (an antibacterial agent) was added to an organic solvent solution of polyurethane elastomer, and the mixture was stirred at 80°C for 8 hours to obtain an antibacterial layer material.

[0095] The organic solvent solution of the polyurethane elastomer, calculated by mass percentage, consists of 63% hydroxyl-terminated polymer, 31% polyisocyanate, 5.98% chain extender, and 0.02% organic solvent. The organic solvent solution of the antibacterial agent, calculated by mass percentage, consists of 10% antibacterial agent and 90% organic solvent.

[0096] In the first antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:1; in the second antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:5; and in the third antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:10.

[0097] Example 2

[0098] The method for preparing the antibacterial catheter provided in this embodiment includes the following steps:

[0099] Step A: Prepare organic solvent solutions for the first layer of antibacterial agent material, the second layer of antibacterial agent material, and the third layer of antibacterial agent material, respectively;

[0100] Cut the TPU tube into 20mm long segments to serve as the tube body. Clean the surface of the tube with deionized water using ultrasonic cleaning twice, 10 seconds each time. After removing the tube, wipe the surface of the tube body dry with a paper towel.

[0101] Step B: Place the coating ring brush onto the outer wall of the pipe;

[0102] Step C: Add the organic solvent solutions of the first layer of antibacterial agent material, the second layer of antibacterial agent material, and the third layer of antibacterial agent material sequentially into the storage tube;

[0103] Step D: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the first antibacterial layer material in the storage tank is sequentially delivered to the coating ring brush through the liquid delivery pipe and the liquid delivery circulation, so that the organic solvent solution of the first antibacterial layer material is completely coated on the tube body, and the coating ring brush stops sliding.

[0104] Step E: Dry the tube coated with the first antibacterial layer at 30°C for 0.5 hours, and then vacuum dry it at 80°C for 2 hours.

[0105] Step F: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the second antibacterial layer material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the second antibacterial layer material onto the tube body. The coating ring brush then stops sliding.

[0106] Step G: Dry the tube coated with the second antibacterial layer at 30°C for 0.5 hours, and then vacuum dry it at 80°C for 2 hours.

[0107] Step H: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the third antibacterial layer material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the third antibacterial layer material onto the tube body. The coating ring brush then stops sliding.

[0108] Step 1: Dry the tube coated with the third antibacterial layer at 30°C for 0.5 hours, and then vacuum dry it at 80°C for 2 hours to obtain the antibacterial catheter.

[0109] The preparation methods and process parameters of the organic solvent solutions for the first, second, and third layers of antibacterial agents are basically the same, as detailed below:

[0110] PDMS (hydroxyl-terminated polymer) was dehydrated and dried under reduced pressure at 98°C and 0.8 bar for 2.5 h. After cooling to 75°C, toluene diisocyanate (polyisocyanate) that had been preheated and melted was added. The mixture was stirred and reacted at 75°C for 1.5 h. The content of toluene diisocyanate was determined by the di-n-butylamine acetone method. Once the predetermined value was reached, the reaction was stopped to obtain the polyurethane prepolymer.

[0111] Ethylene glycol (chain extender) was dehydrated and dried under reduced pressure at 98°C and 0.8 bar for 2.5 h. After cooling to 20°C, it was completely dissolved in tetrahydrofuran (organic solvent).

[0112] Ethylene glycol tetrahydrofuran solution was added to polyurethane prepolymer, and the mixture was stirred at 75°C for 5 hours to obtain an organic solvent solution of polyurethane elastomer.

[0113] A dioxane solution of sodium pyrithione (antibacterial agent) was added to an organic solvent solution of polyurethane elastomer, and the mixture was stirred at 75°C for 12 hours to obtain an antibacterial layer material.

[0114] The organic solvent solution of the polyurethane elastomer, calculated by mass percentage, consists of 77% hydroxyl-terminated polymer, 18% polyisocyanate, 4.95% chain extender, and 0.05% organic solvent; the organic solvent solution of the antibacterial agent, calculated by mass percentage, consists of 5% antibacterial agent and 95% organic solvent.

[0115] In the first antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:3; in the second antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:4; and in the third antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:8.

[0116] Example 3

[0117] The method for preparing the antibacterial catheter provided in this embodiment includes the following steps:

[0118] Step A: Prepare organic solvent solutions for the first layer of antibacterial agent material, the second layer of antibacterial agent material, and the third layer of antibacterial agent material, respectively;

[0119] Cut the TPU tube into 20mm long segments as the tube body, and ultrasonically clean the surface of the tube with deionized water 4 times, 3 seconds each time. After taking it out, wipe the surface of the tube body dry with a paper towel.

[0120] Step B: Place the coating ring brush onto the outer wall of the pipe;

[0121] Step C: Add the organic solvent solutions of the first layer of antibacterial agent material, the second layer of antibacterial agent material, and the third layer of antibacterial agent material sequentially into the storage tube;

[0122] Step D: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the first antibacterial layer material in the storage tank is sequentially delivered to the coating ring brush through the liquid delivery pipe and the liquid delivery circulation, so that the organic solvent solution of the first antibacterial layer material is completely coated on the tube body, and the coating ring brush stops sliding.

[0123] Step E: Dry the tube coated with the first antibacterial layer at 20°C for 1.5 hours, and then vacuum dry it at 70°C for 4 hours.

[0124] Step F: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the second antibacterial layer material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the second antibacterial layer material onto the tube body. The coating ring brush then stops sliding.

[0125] Step G: Dry the tube coated with the second antibacterial layer at 20°C for 1.5 hours, and then vacuum dry it at 70°C for 4 hours.

[0126] Step H: Drive the coating ring brush to slide back and forth relative to the tube body. The organic solvent solution of the third antibacterial layer material in the storage tube flows to the coating ring brush in sequence through the liquid delivery tube and the liquid delivery circulation tube, coating all the organic solvent solution of the third antibacterial layer material onto the tube body. The coating ring brush then stops sliding.

[0127] Step 1: Dry the tube coated with the third antibacterial layer at 20°C for 1.5 hours, and then vacuum dry it at 70°C for 4 hours to obtain the antibacterial catheter.

[0128] The preparation methods and process parameters of the organic solvent solutions for the first, second, and third layers of antibacterial agents are basically the same, as detailed below:

[0129] PTMEG (hydroxyl-terminated polymer) was dehydrated and dried under reduced pressure at 102°C and 1.0 bar for 1.5 h. After cooling to 75°C, preheated and melted dicyclohexylmethane diisocyanate (polyisocyanate) was added. The mixture was stirred and reacted at 70°C for 2.5 h. The content of dicyclohexylmethane diisocyanate was determined by the di-n-butylamine acetone method. Once the predetermined value was reached, the reaction was stopped to obtain the polyurethane prepolymer.

[0130] 1,4-Butanediol (chain extender) was dehydrated and dried under reduced pressure at 102°C and 1.0 bar for 1.5 h. After cooling to 30°C, it was completely dissolved in carbon tetrachloride (organic solvent).

[0131] A carbon tetrachloride solution of 1,4-butanediol was added to the polyurethane prepolymer, and the mixture was stirred at 70°C for 6 hours to obtain an organic solvent solution of the polyurethane elastomer.

[0132] An N,N-dimethylformamide solution of copper pyridinethione (antibacterial agent) was added to an organic solvent solution of polyurethane elastomer, and the mixture was stirred at 70°C for 5 hours to obtain an antibacterial layer material.

[0133] The organic solvent solution of the polyurethane elastomer, calculated by mass percentage, consists of 87% hydroxyl-terminated polymer, 11% polyisocyanate, 2.97% chain extender, and 0.03% organic solvent; the organic solvent solution of the antibacterial agent, calculated by mass percentage, consists of 1% antibacterial agent and 99% organic solvent.

[0134] In the first antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:2; in the second antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:6; and in the third antibacterial layer material, the mass ratio of polyurethane elastomer to zinc pyridinethione is 100:7.

[0135] Comparative Example 1

[0136] The method for preparing the antibacterial catheter provided in this comparative example includes the following steps:

[0137] Step A: The antibacterial catheter is prepared by using the existing melt blending method with a mass ratio of polyurethane elastomer to zinc pyridine thione of 100:5.

[0138] Infrared characterization was performed on the initial tubing and the antibacterial catheter prepared in Example 1, respectively. Figure 2 As shown, 2200cm -1 The absorption peaks of isocyanates completely disappeared, at 1650–1750 cm⁻¹. -1 There is a distinct C=O vibration peak between them, at 1540 cm⁻¹. -1 The presence of NH bending vibration peaks on both sides indicates that the isocyanate has reacted with the hydroxyl groups to form urethane bonds, proving the formation of a polyurethane structure. Compared to the tube body, the infrared characteristic peaks of the antibacterial catheter show changes, proving that the antibacterial layer has been successfully coated onto the tube body surface, conforming to the designed structural characteristics.

[0139] The antibacterial catheters prepared in Examples 1-3 and Comparative Example 1 were tested for antibacterial activity using the surface contact method: Bacterial suspensions (Escherichia coli or Staphylococcus aureus) were cultured in Mueller-Hinton Broth (MHB) medium at 37°C until the optical density at 600 nm reached 0.8, indicating the entry into the logarithmic growth phase. Bacterial cells were collected at 4°C, washed with sterile PBS (pH 7.4), and resuspended in PBS to a final concentration of 6 × 10⁻⁶. 6 cells / mL. Examples 1-3 and Comparative Example 1 (area 0.01-0.04 cm²) were compared. 2 Add 50 μL of bacterial suspension and shake at 37 °C for 4 h. Then, take 25 μL of the suspension and inoculate it onto sterile LB culture dishes at a series of gradient concentrations (×1, ×10, ×100, ×1000).

[0140] After incubation at 37°C for 12 hours, bacterial colony counts were performed, and Examples 1-3 were compared with Comparative Example 1. (See attached text) Figure 3 .from Figure 3 It can be seen that the inhibition rates of Examples 1-3 and Comparative Example 1 against Escherichia coli and Staphylococcus aureus can all reach 100%.

[0141] Examples 1-3 and Comparative Example 1 were each added to 50 μL of bacterial suspension and shaken for 15 days. After shaking, the suspensions were removed, rinsed with water, and then added back to 50 μL of freshly prepared bacterial suspension (the bacterial suspension preparation method is as described above). The suspensions were shaken at 37°C for 4 hours. Then, 25 μL of the suspension was inoculated onto sterile LB trombone plates at a series of gradient concentrations (×1, ×10, ×100, ×1000). After incubation at 37°C for 12 hours, bacterial colony counts were performed, and Examples 1-3 were compared with Comparative Example 1 (see [reference]). Figure 4 .from Figure 4 It can be seen that the inhibition rate of Escherichia coli and Staphylococcus aureus in Examples 1-3 can still be maintained above 76%, while the inhibition rate of Escherichia coli and Staphylococcus aureus in Comparative Example 1 is significantly reduced to below 20%.

[0142] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for producing an antibacterial catheter, characterized by, The antibacterial catheter comprises a tube body and n antibacterial layers formed on the outer wall of the tube body in sequence, wherein n is a positive integer greater than or equal to 2; the material of the tube body is polyurethane elastomer; the antibacterial layer comprises 100 parts of polyurethane elastomer and 1-10 parts of antibacterial agent by mass fraction, the antibacterial agent is a pyrithione compound, and the preparation method comprises the following steps: providing a tube body; and forming multiple antibacterial layers on the outer wall of the tube body in sequence. The preparation method comprises the following steps: step 1: providing a coating assembly, wherein the coating assembly comprises a coating ring brush, a liquid delivery ring, a liquid delivery pipe and a liquid storage pipe, the liquid outlet end of the liquid storage pipe is connected with the liquid inlet of the liquid delivery ring through the liquid delivery pipe, and the coating ring brush is arranged on the inner wall of the liquid delivery ring; step 2: sleeving the coating ring brush on the outer wall of the tube body; step 3: sequentially adding organic solvent solutions of first layer to nth antibacterial layer materials into the liquid storage pipe; step 4: driving the coating ring brush to reciprocally slide relative to the tube body, the organic solvent solution of the first layer antibacterial layer material in the liquid storage pipe flows to the coating ring brush through the liquid delivery pipe and the liquid delivery ring in sequence, the organic solvent solution of the first layer antibacterial layer material is completely coated on the tube body, and the coating ring brush stops sliding; step 5: curing the first layer antibacterial layer; step 6: driving the coating ring brush to reciprocally slide relative to the tube body, the organic solvent solution of the next layer antibacterial layer material in the liquid storage pipe flows to the coating ring brush through the liquid delivery pipe and the liquid delivery ring in sequence, the organic solvent solution of the next layer antibacterial layer material is completely coated on the tube body, and the coating ring brush stops sliding; step 7: curing the next layer antibacterial layer; and step 8: repeating steps 6 to 7 until the nth antibacterial layer is prepared, thereby obtaining the antibacterial catheter. In step 3, different density branched chains are introduced into the molecular chain of the polyurethane elastomer, or the density of the organic solvent solution of the antibacterial layer material is controlled by using organic solvents with different densities. The content of the antibacterial agent in the first layer antibacterial layer to the nth antibacterial layer gradually increases.

2. The method for preparing the antibacterial catheter according to claim 1, characterized in that, In the antibacterial layer, the antibacterial agent molecules and the molecular chains of the polyurethane elastomer are bonded by hydrogen bonds.

3. The method for preparing the antibacterial catheter according to claim 1, characterized in that, The number of the antibacterial layers is 2-4.

4. The method of claim 3, wherein the antimicrobial catheter is prepared by the steps of: The number of the antibacterial layers is 3, which are a first antibacterial layer, a second antibacterial layer and a third antibacterial layer in sequence and gradually away from the tube body.

5. The method of claim 4, wherein the antimicrobial catheter is prepared by the steps of: The mass fraction of the polyurethane elastomer in the first antibacterial layer is 100 parts, and the mass fraction of the antibacterial agent in the first antibacterial layer is 1-3 parts.

6. The method of claim 4, wherein the antimicrobial catheter is prepared by the steps of: The mass fraction of the polyurethane elastomer in the second antibacterial layer is 100 parts, and the mass fraction of the antibacterial agent in the second antibacterial layer is 4-6 parts.

7. The method for preparing the antibacterial catheter according to claim 4, characterized in that, The mass fraction of the polyurethane elastomer in the third antibacterial layer is 100 parts, and the mass fraction of the antibacterial agent in the third antibacterial layer is 7-10 parts.

8. The method of producing an antibacterial catheter according to any one of claims 1 to 7, characterized by, The pyrithione compound is one or more of N-oxide-2-sulfenyl pyridine, N-oxide-2-sulfenyl pyridine sodium salt, N-oxide-2-sulfenyl pyridine zinc salt and N-oxide-2-sulfenyl pyridine copper salt in any proportion.

Images