High-temperature-resistant antibacterial sputum suction catheter and preparation method thereof

Abstract

The invention provides a high-temperature-resistant antibacterial sputum suction catheter and a preparation method thereof, and belongs to the technical field of medical instruments. The preparation method comprises the following steps: quaternary ammonium salt chitosan is treated by chitosanase to obtain modified chitosan, polytetrahydrofuran, polyethylene glycol and diisocyanate react to obtain a prepolymer, the prepolymer, dimethylolpropionic acid and the modified chitosan react to obtain a polyurethane prepolymer, modified silane and the polyurethane prepolymer are mixed to obtain a mixed material, and the mixed material is dried to obtain a finished product. And performing extrusion molding on the mixture to obtain the high-temperature-resistant antibacterial sputum suction catheter. Hydrophilic groups in the modified silane and polyurethane polymer can reduce the friction force on the surface of the sputum suction catheter and reduce vascular endothelial injury; in addition, quaternary ammonium salt structures in the resveratrol and the modified chitosan can jointly destroy metabolism of bacteria to achieve a good antibacterial effect, and the combined non-antibiotic antibacterial strategy can delay generation of drug-resistant bacteria.

Description

Technical Field

[0001] The invention relates to the technical field of medical devices, and in particular to a high-temperature resistant and antibacterial sputum suction catheter and a preparation method thereof. Background Art

[0002] Suction catheters are crucial medical devices in clinical respiratory care. They are mainly used to clear sputum and secretions from the patient's respiratory tract, maintain airway patency, and prevent complications such as lung infection. In various intensive care units, respiratory medicine departments and other departments, suction operations are very frequent, and their effect directly affects the patient's respiratory function recovery and overall recovery process. However, there are many problems with the suction catheters currently used in clinical practice, which seriously restrict their effectiveness and safety.

[0003] At present, the mainstream suction catheters on the market are mostly made of ordinary silicone or PVC materials. These materials are prone to softening, deformation, or even structural damage during high-temperature and high-pressure sterilization, resulting in lumen collapse, surface roughness, or changes in pore size, significantly reducing suction efficiency and increasing the risk of patient injury. At the same time, existing antibacterial technologies, such as silver nanoparticle coatings and hydrophilic polymer layers, have problems such as degradation, agglomeration, or interfacial peeling at high temperatures, and the antibacterial function is uncontrollably attenuated. Although traditional ethylene oxide sterilization can avoid high-temperature damage, its residual toxicity and insufficient penetration make it difficult to meet the sterilization requirements of complex catheter structures, resulting in a high risk of catheter-related infection. It is urgent to develop new catheter materials that have both high temperature resistance and long-term antibacterial properties.

[0004] Chinese patent CN 111423693B discloses a PEEk-based medical tubing material and its preparation method and application. After PEEK, PEI and PPSU are dried to remove moisture, the raw materials are weighed according to the formula, mixed evenly, melt blended, extruded and granulated in a twin-screw extruder, and then extruded in a single-screw extruder to produce PEEK-based medical tubing. The prepared PEEK-based medical tubing has good high temperature resistance, but the invention does not involve its antibacterial effect.

[0005] Therefore, providing a new catheter material that has both high temperature resistance and good antibacterial properties is an important issue that needs to be urgently addressed in this field. Summary of the invention

[0006] In order to solve the problems existing in the prior art, the present invention provides a high temperature resistant antibacterial sputum suction catheter and a preparation method thereof. Specifically, the technical solution of the present invention includes the following contents: A method for preparing a high temperature resistant and antibacterial sputum suction catheter, the method comprising the following steps: Quaternary ammonium salt chitosan is treated with chitosanase to obtain modified chitosan. A prepolymer is obtained by reacting polytetrahydrofuran, polyethylene glycol and diisocyanate. A polyurethane prepolymer is obtained by reacting the prepolymer, dimethylolpropionic acid and modified chitosan. A modified silane and the polyurethane prepolymer are mixed to obtain a mixture, and the mixture is extruded into a high-temperature resistant and antibacterial sputum suction catheter.

[0007] Furthermore, the preparation method of the modified silane includes the following steps: Hydroxypropyl-β-cyclodextrin and resveratrol react to obtain modified resveratrol. 3-mercaptopropyltrimethoxysilane, itaconic acid and an initiator react to obtain carboxylated silane. The modified resveratrol and the carboxylated silane are mixed and then subjected to acid treatment and alkali treatment in sequence to obtain the modified silane.

[0008] Furthermore, the weight ratio of the hydroxypropyl-β-cyclodextrin to the resveratrol is 2-3:1.5-2.5.

[0009] Furthermore, the reaction conditions of the hydroxypropyl-β-cyclodextrin and the resveratrol include a reaction temperature of 55-60 °C and a reaction time of 8-12 h.

[0010] Furthermore, the weight ratio of the 3-mercaptopropyltrimethoxysilane, the itaconic acid and the initiator is 19-22:12-14:0.13-0.15.

[0011] Furthermore, the initiator is benzoin diethyl ether.

[0012] Furthermore, the reaction conditions of the 3-mercaptopropyltrimethoxysilane, the itaconic acid and the initiator are to be irradiated with 365 nm ultraviolet light for 30-60 min.

[0013] Furthermore, the weight ratio of the modified resveratrol to the carboxylated silane is 1-3:9-11.

[0014] Furthermore, the conditions of the acid treatment include a solution pH of 3.5-4.5, a treatment temperature of 45-55 °C and a treatment time of 8-12 h.

[0015] Furthermore, the conditions of the alkali treatment include a solution pH of 8.0-8.3, a treatment temperature of 24-26 °C and a treatment time of 2-3 h.

[0016] Furthermore, the weight ratio of the polytetrahydrofuran, the polyethylene glycol, the diisocyanate, the dimethylolpropionic acid and the modified chitosan is 4.5-5.5:2.5-3.5:0.9-1.5:0.3-0.5:0.15-0.25.

[0017] Furthermore, the diisocyanate includes hexamethylene diisocyanate or isophorone diisocyanate.

[0018] Furthermore, the reaction conditions of the polytetrahydrofuran, polyethylene glycol and diisocyanate include a reaction temperature of 80-90 °C and a reaction time of 3-4 h.

[0019] Furthermore, the reaction conditions of the prepolymer, dimethylolpropionic acid and modified chitosan include a reaction temperature of 55-65 °C and a reaction time of 4-6 h.

[0020] Furthermore, the weight ratio of the modified silane to the polyurethane prepolymer is 30-40:70-90.

[0021] Furthermore, the mixing conditions of the modified silane and the polyurethane prepolymer include a mixing temperature of 180-190 °C and a mixing time of 15-25 min.

[0022] Furthermore, the conditions for extrusion molding include a temperature of 175 °C in zone 1, 185 °C in zone 2, 190 °C in zone 3, 190 °C in zone 4, and 185 °C for the die head.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) In the present invention, resveratrol is encapsulated in the hydrophobic cavity of hydroxypropyl-β-cyclodextrin through hydrophobic interaction to obtain modified resveratrol. Itaconic acid is grafted onto 3-mercaptopropyltrimethoxysilane through a thiol-ene click reaction to obtain carboxylated silane. The carboxylated silane undergoes hydrolysis and condensation to form a Si-O-Si network, and the modified resveratrol is embedded in the Si-O-Si network through hydrogen bonding to obtain modified silane; chitosanase is used to degrade quaternary ammonium salt chitosan to obtain low-viscosity modified chitosan, and polyurethane polymer is obtained with dimethylolpropionic acid and modified carboxymethyl chitosan as chain extenders. The polyurethane polymer and the modified silane are mixed and then extruded and molded to produce a high-temperature resistant and antibacterial sputum aspirator catheter; this system stabilizes the antibacterial activity of resveratrol through cyclodextrin embedding technology, improves the thermal stability of the material with the silicone oxygen network, and the modified chitosan as a chain extender enhances the mechanical properties while also having good antibacterial effects. Multiple effects cooperate with each other to finally achieve that the antibacterial catheter has good mechanical properties and antibacterial activity.

[0024] (3) The hydrophilic groups in the modified silane and the polyurethane polymer in the present invention can reduce the friction on the surface of the sputum aspirator catheter and reduce vascular endothelial damage; in addition, the quaternary ammonium salt structures in resveratrol and modified chitosan can jointly disrupt the metabolism of bacteria to achieve good antibacterial effects, and the combined non-antibiotic antibacterial strategy can delay the generation of drug-resistant bacteria. Specific Embodiments

[0025] The technical solutions of the present invention will be clearly and completely described below through embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts fall within the scope of protection of the present invention.

[0026] Unless otherwise specified, the raw materials and reagents used in the present invention below are all commercially available products or can be prepared by known methods.

[0027] Preparation Example 1: The preparation method of the modified silane includes the following steps: 2 parts by weight of hydroxypropyl-β-cyclodextrin are dispersed in 60 parts by weight of deionized water and stirred and dispersed at 60 °C for 10 min to obtain stock solution A. 1.5 parts by weight of resveratrol are dispersed in 50 parts by weight of absolute ethanol to obtain stock solution B. Stock solution B is dropped into stock solution A, and the reaction is stirred in the nitrogen protection environment and protected from light at 55 °C for 8 h to obtain modified resveratrol; 19 parts by weight of 3-mercaptopropyltrimethoxysilane, 13 parts by weight of itaconic acid and 0.3 part by weight of benzoin diethyl ether are dispersed in parts by weight of absolute ethanol and stirred and mixed for 15 min. Then, in the nitrogen protection environment, while stirring, it is irradiated with ultraviolet light of 365 nm for 30 min. After the reaction is completed, absolute ethanol is removed by rotary evaporation. The product is collected after washing with cold diethyl ether and vacuum dried at 40 °C to obtain carboxylated silane; 1 part by weight of modified resveratrol is dispersed in a mixed solvent (V 无水乙醇 :V 去离子水 = 5:3) and stirred and mixed at 35 °C for 10 min. Then, 9 parts by weight of carboxylated silane are added and stirred and mixed for 10 min. Then, the pH is adjusted to 3.5 with a 0.1 M dilute hydrochloric acid solution, and the reaction is stirred at 45 °C at a rotation speed of 200 r / min for 8 h. After the reaction is completed, it is left standing at 24 °C for 24 h, and washed alternately 3 times with a mixed solution (V 无水乙醇 :V 去离子水 = 1:1), and vacuum dried at 40 °C for 24 h to obtain an intermediate product. The intermediate product is dispersed in a sodium bicarbonate solution with a pH of 8.0, soaked and treated at 24 °C for 2 h, washed with deionized water to neutrality and vacuum dried to obtain the modified silane.

[0028] Preparation Example 2: The preparation method of the modified silane includes the following steps: 2.3 parts by weight of hydroxypropyl-β-cyclodextrin was dispersed in 60 parts by weight of deionized water and stirred at 60 °C for 12 min to obtain stock solution A. 1.7 parts by weight of resveratrol was dispersed in 50 parts by weight of absolute ethanol to obtain stock solution B. Stock solution B was added dropwise to stock solution A, and the mixture was stirred and reacted at 57 °C in a nitrogen protection environment in the dark for 9 h to prepare modified resveratrol; 20 parts by weight of 3-mercaptopropyltrimethoxysilane, 14 parts by weight of itaconic acid and 0.34 parts by weight of benzoin diethyl ether were dispersed in anhydrous ethanol and stirred and mixed for 16 min. Then, in a nitrogen protection environment, while stirring, it was irradiated with ultraviolet light at 365 nm for 40 min. After the reaction ended, anhydrous ethanol was removed by rotary evaporation. The product was collected after washing with cold diethyl ether and vacuum dried at 42 °C to obtain carboxylated silane; 1.5 parts by weight of modified resveratrol was dispersed in a mixed solvent (V 无水乙醇 :V 去离子水 = 5:3) and stirred and mixed at 36 °C for 12 min. Then, 9.5 parts by weight of carboxylated silane was added and stirred and mixed for 12 min. Then, the pH was adjusted to 3.7 with a 0.1 M dilute hydrochloric acid solution, and the mixture was stirred and reacted at 47 °C at a rotation speed of 220 r / min for 9 h. After the reaction ended, it was left to stand at 25 °C for 24 h and washed alternately 3 times with a mixed solution (V 无水乙醇 :V 去离子水 = 1:1), and vacuum dried at 40 °C for 24 h to obtain an intermediate product. The intermediate product was dispersed in a sodium bicarbonate solution with a pH of 8.1 and soaked at 25 °C for 2.3 h, then washed with deionized water until neutral and vacuum dried to obtain modified silane.

[0029] Preparation Example 3: The preparation method of modified silane includes the following steps: 2.6 parts by weight of hydroxypropyl-β-cyclodextrin was dispersed in 60 parts by weight of deionized water and stirred at 60 °C for 16 min to obtain stock solution A. 2.1 parts by weight of resveratrol was dispersed in 50 parts by weight of absolute ethanol to obtain stock solution B. Stock solution B was added dropwise to stock solution A, and the mixture was stirred and reacted at 58 °C in a nitrogen protection environment in the dark for 10 h to prepare modified resveratrol; 21 parts by weight of 3-mercaptopropyltrimethoxysilane, 14 parts by weight of itaconic acid and 0.38 parts by weight of benzoin diethyl ether were dispersed in anhydrous ethanol and stirred and mixed for 18 min. Then, in a nitrogen protection environment, while stirring, it was irradiated with ultraviolet light at 365 nm for 50 min. After the reaction ended, anhydrous ethanol was removed by rotary evaporation. The product was collected after washing with cold diethyl ether and vacuum dried at 47 °C to obtain carboxylated silane; 2 parts by weight of modified resveratrol was dispersed in a mixed solvent (V 无水乙醇 :V 去离子水= 5:3) Stir and mix at 38 °C for 13 min, then add 10 parts by weight of carboxylated silane and stir and mix for 14 min. Then, adjust the pH to 4.2 with a 0.1 M dilute hydrochloric acid solution, and stir and react at 52 °C at a rotation speed of 250 r / min for 10 h. After the reaction is completed, let it stand at 26 °C for 24 h, and use the mixed solution (V 无水乙醇 :V 去离子水 = 1:1) Wash alternately 3 times, vacuum dry at 40 °C for 24 h to obtain an intermediate product. The intermediate product is dispersed in a sodium bicarbonate solution with a pH of 8.3, soaked at 26 °C for 3 h, then washed with deionized water until neutral and vacuum dried to obtain the modified silane.

[0030] Preparation Example 4: The preparation method of the modified silane includes the following steps: 3 parts by weight of hydroxypropyl-β-cyclodextrin are dispersed in 60 parts by weight of deionized water and stirred and dispersed at 60 °C for 20 min to obtain stock solution A. 2.5 parts by weight of resveratrol are dispersed in 50 parts by weight of absolute ethanol to obtain stock solution B. Stock solution B is dropped into stock solution A, and stirred and reacted in a nitrogen protection environment at 60 °C in the dark for 12 h to obtain modified resveratrol; 22 parts by weight of 3-mercaptopropyltrimethoxysilane, 15 parts by weight of itaconic acid and 0.4 parts by weight of benzoin diethyl ether are dispersed in parts by weight of absolute ethanol and stirred and mixed for 20 min. Then, in a nitrogen protection environment, while stirring, irradiate with 365 nm ultraviolet light for 60 min. After the reaction is completed, remove the absolute ethanol by rotary evaporation, wash with cold ether, collect the product, and vacuum dry at 50 °C to obtain carboxylated silane; 3 parts by weight of modified resveratrol are dispersed in a mixed solvent (V 无水乙醇 :V 去离子水 = 5:3) Stir and mix at 40 °C for 15 min, then add 11 parts by weight of carboxylated silane and stir and mix for 15 min. Then, adjust the pH to 4.5 with a 0.1 M dilute hydrochloric acid solution, and stir and react at 55 °C at a rotation speed of 300 r / min for 12 h. After the reaction is completed, let it stand at 26 °C for 24 h, and use the mixed solution (V 无水乙醇 :V 去离子水 = 1:1) Wash alternately 3 times, vacuum dry at 40 °C for 24 h to obtain an intermediate product. The intermediate product is dispersed in a sodium bicarbonate solution with a pH of 8.3, soaked at 26 °C for 3 h, then washed with deionized water until neutral and vacuum dried to obtain the modified silane.

[0031] Preparation Example 5: The preparation method of the modified silane includes the following steps: 3 parts by weight of β-cyclodextrin was dispersed in 60 parts by weight of deionized water and stirred at 60 °C for 20 min to obtain stock solution A. 2.5 parts by weight of resveratrol was dispersed in 50 parts by weight of absolute ethanol to obtain stock solution B. Stock solution B was added dropwise to stock solution A, and the mixture was stirred and reacted in a nitrogen protection environment at 60 °C in the dark for 12 h to prepare modified resveratrol; 22 parts by weight of 3-mercaptopropyltrimethoxysilane, 15 parts by weight of itaconic acid and 0.4 parts by weight of benzoin diethyl ether were dispersed in parts by weight of absolute ethanol and stirred and mixed for 20 min. Then, in a nitrogen protection environment, while stirring, it was irradiated with 365 nm ultraviolet light for 60 min. After the reaction ended, absolute ethanol was removed by rotary evaporation, and the product was collected after washing with cold diethyl ether and dried in vacuo at 50 °C to obtain carboxylated silane; 3 parts by weight of modified resveratrol was dispersed in a mixed solvent (V 无水乙醇 :V 去离子水 =5:3) and stirred and mixed at 40 °C for 15 min. Then, 11 parts by weight of carboxylated silane was added and stirred and mixed for 15 min. Then, the pH was adjusted to 4.5 with a 0.1 M dilute hydrochloric acid solution, and the mixture was stirred and reacted at 55 °C at a rotation speed of 300 r / min for 12 h. After the reaction ended, it was allowed to stand at 26 °C for 24 h, and washed alternately 3 times with a mixed solution (V 无水乙醇 :V 去离子水 =1:1), and dried in vacuo at 40 °C for 24 h to obtain an intermediate product. The intermediate product was dispersed in a sodium bicarbonate solution with a pH of 8.3, soaked and treated at 26 °C for 3 h, washed with deionized water until neutral and dried in vacuo to obtain modified silane.

[0032] Preparation Example 6: The preparation method of the modified silane comprises the following steps: 3 parts by weight of hydroxypropyl-β-cyclodextrin was dispersed in 60 parts by weight of deionized water and stirred at 60 °C for 20 min to obtain stock solution A. 2.5 parts by weight of resveratrol was dispersed in 50 parts by weight of absolute ethanol to obtain stock solution B. Stock solution B was added dropwise to stock solution A, and the mixture was stirred and reacted in a nitrogen protection environment at 60 °C in the dark for 12 h to prepare modified resveratrol; 3 parts by weight of modified resveratrol was dispersed in a mixed solvent (V 无水乙醇 :V 去离子水 =5:3) and stirred and mixed at 40 °C for 15 min. Then, 11 parts by weight of 3-mercaptopropyltrimethoxysilane was added and stirred and mixed for 15 min. Then, the pH was adjusted to 4.5 with a 0.1 M dilute hydrochloric acid solution, and the mixture was stirred and reacted at 55 °C at a rotation speed of 300 r / min for 12 h. After the reaction ended, it was allowed to stand at 26 °C for 24 h, and washed alternately 3 times with a mixed solution (V 无水乙醇 :V 去离子水=1: 1) Wash alternately three times, dry in vacuum at 40 °C for 24 h to obtain an intermediate product. The intermediate product is dispersed in a sodium bicarbonate solution with a pH of 8.3, soaked at 26 °C for 3 h, washed with deionized water until neutral, and dried in vacuum to obtain the modified silane.

[0033] Preparation Example 7: The preparation method of the modified silane comprises the following steps: 22 parts by weight of 3-mercaptopropyltrimethoxysilane, 15 parts by weight of itaconic acid, and 0.4 part by weight of benzoin diethyl ether are dispersed in anhydrous ethanol by weight, stirred and mixed for 20 min, then irradiated with 365 nm ultraviolet light for 60 min while stirring in a nitrogen protection environment. After the reaction, anhydrous ethanol is removed by rotary evaporation, the product is collected after washing with cold ether, and dried in vacuum at 50 °C to obtain carboxylated silane; 11 parts by weight of carboxylated silane are dispersed in a mixed solvent (V 无水乙醇 :V 去离子水 =5:3) After stirring and mixing at 40 °C for 15 min, the pH is adjusted to 4.5 with a 0.1 M dilute hydrochloric acid solution, and the reaction is stirred at 300 r / min in an environment at 55 °C for 12 h. After the reaction, it is left to stand at 26 °C for 24 h, and washed with a mixed solution (V 无水乙醇 :V 去离子水 =1:1) Wash alternately three times, dry in vacuum at 40 °C for 24 h to obtain an intermediate product. The intermediate product is dispersed in a sodium bicarbonate solution with a pH of 8.3, soaked at 26 °C for 3 h, washed with deionized water until neutral, and dried in vacuum to obtain the modified silane.

[0034] Example 1: The preparation method of a high-temperature resistant antibacterial sputum suction catheter comprises the following steps: After mixing a 0.2 M acetic acid solution and a 0.2 M sodium acetate solution in a weight ratio of 1:1 and adjusting the pH to 5.0 to obtain an acetic acid - sodium acetate buffer solution, 2 parts by weight of quaternary ammonium salt chitosan is dispersed in 100 parts by weight of the acetic acid - sodium acetate buffer solution. After stirring and reacting at 25°C for 2 h, 0.02 parts by weight of chitosanase is added and stirred and reacted at 45°C for 4 h. After the reaction is completed, the temperature is raised to 75°C and kept warm for 10 min, and then purified by centrifugation to remove impurities and dialysis to obtain modified chitosan; 45 parts by weight of polytetrahydrofuran (Mn = 1000) and 25 parts by weight of polyethylene glycol (Mn = 2000) are dehydrated in a vacuum environment at 100°C for 2 h, then the temperature is lowered to 60°C, 9 parts by weight of hexamethylene diisocyanate is added, and the reaction is stirred at 80°C for 3 h in a nitrogen - protected environment to obtain a prepolymer. After the reaction is completed, the temperature is lowered to 55°C, 3 parts by weight of dimethylolpropionic acid and 1.5 parts by weight of modified chitosan are added and stirred and reacted for 4 h, then cooled to 24°C and precipitated with ionized water, and then filtered and vacuum - dried in sequence to obtain a polyurethane polymer; the internal mixer is preheated to 180°C, 30 parts by weight of the modified silane prepared in Preparation Example 1 and 70 parts by weight of the polyurethane polymer are mixed at a speed of 60 r / min for 15 min to obtain a mixture. After the mixture is extruded and formed by a single - screw extruder according to the setting that the temperature of the first zone is 175°C, the temperature of the second zone is 185°C, the temperature of the third zone is 190°C, the temperature of the fourth zone is 190°C, and the die head temperature is 185°C, it is sequentially subjected to high - pressure sterilization, drying, and packaging to obtain a high - temperature - resistant antibacterial sputum suction catheter.

[0035] Example 2: A preparation method of a high - temperature - resistant antibacterial sputum suction catheter comprises the following steps: A 0.2 M acetic acid solution and a 0.2 M sodium acetate solution are mixed in a weight ratio of 1:1, and the pH is adjusted to 5.0 to obtain an acetic acid-sodium acetate buffer solution. 2 parts by weight of quaternary ammonium salt chitosan is dispersed in 100 parts by weight of the acetic acid-sodium acetate buffer solution. After stirring and reacting at 25°C for 2 h, 0.02 parts by weight of chitosanase is added and stirred and reacted at 45°C for 4.5 h. After the reaction is completed, the temperature is raised to 78°C and kept warm for 11 min, and then purified by centrifugation to remove impurities and dialysis to obtain modified chitosan; 47 parts by weight of polytetrahydrofuran (Mn = 1000) and 28 parts by weight of polyethylene glycol (Mn = 2000) are dehydrated in a vacuum environment at 100°C for 2.3 h, then the temperature is lowered to 63°C, 11 parts by weight of isophorone diisocyanate is added, and the mixture is stirred and reacted at 83°C for 3.4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction is completed, the temperature is lowered to 58°C, 3.5 parts by weight of dimethylolpropionic acid and 1.9 parts by weight of modified chitosan are added and stirred and reacted for 4.5 h, then cooled to 25°C and precipitated with ionized water, and then filtered and dried in vacuum to obtain a polyurethane polymer; the internal mixer is preheated to 183°C, 33 parts by weight of the modified silane prepared in Preparation Example 2 and 75 parts by weight of the polyurethane polymer are mixed at a rotation speed of 63 r / min for 18 min to obtain a mixture. The mixture is extruded and molded by a single-screw extruder according to the settings of the first zone temperature of 175°C, the second zone temperature of 185°C, the third zone temperature of 190°C, the fourth zone temperature of 190°C, and the die head temperature of 185°C, and then sequentially subjected to high-pressure sterilization, drying, and packaging to obtain a high-temperature resistant and antibacterial sputum suction catheter.

[0036] Example 3: A method for preparing a high-temperature resistant and antibacterial sputum suction catheter includes the following steps: After mixing a 0.2 M acetic acid solution and a 0.2 M sodium acetate solution in a weight ratio of 1:1 and adjusting the pH to 5.0 to obtain an acetic acid - sodium acetate buffer solution, 2 parts by weight of quaternary ammonium salt chitosan is dispersed in 100 parts by weight of the acetic acid - sodium acetate buffer solution. After stirring and reacting at 25 °C for 2 h, 0.02 parts by weight of chitosanase is added and stirred and reacted at 45 °C for 5 h. After the reaction is completed, the temperature is raised to 82 °C and kept warm for 13 min, and then purified by centrifugation to remove impurities and dialysis to obtain modified chitosan; 52 parts by weight of polytetrahydrofuran (Mn = 1000) and 32 parts by weight of polyethylene glycol (Mn = 2000) are dehydrated in a vacuum environment at 100 °C for 2.8 h, then cooled to 67 °C, 13 parts by weight of hexamethylene diisocyanate is added, and stirred and reacted at 87 °C for 3.6 h in a nitrogen protection environment to obtain a prepolymer. After the reaction is completed, the temperature is cooled to 62 °C, 4 parts by weight of dimethylolpropionic acid and 2.1 parts by weight of modified chitosan are added and stirred and reacted for 5 h, then cooled to 26 °C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer; the internal mixer is preheated to 187 °C, 37 parts by weight of the modified silane prepared in Preparation Example 3 and 80 parts by weight of the polyurethane polymer are mixed at a rotation speed of 68 r / min for 22 min to obtain a mixture. After the mixture is extruded and formed by a single - screw extruder with the set temperatures of the first zone being 175 °C, the second zone being 185 °C, the third zone being 190 °C, the fourth zone being 190 °C, and the die head temperature being 185 °C, it is successively subjected to high - pressure sterilization, drying, and packaging to obtain a high - temperature - resistant and antibacterial sputum suction catheter.

[0037] Example 4: A preparation method of a high - temperature - resistant and antibacterial sputum suction catheter comprises the following steps: After mixing a 0.2 M acetic acid solution and a 0.2 M sodium acetate solution in a weight ratio of 1:1 and adjusting the pH to 5.0 to obtain an acetic acid-sodium acetate buffer solution, 2 parts by weight of quaternary ammonium salt chitosan is dispersed in 100 parts by weight of the acetic acid-sodium acetate buffer solution. After stirring and reacting at 25 °C for 2 h, 0.02 parts by weight of chitosanase is added and stirred and reacted at 45 °C for 6 h. After the reaction is completed, the temperature is raised to 85 °C and kept warm for 15 min, and then centrifuged to remove impurities and dialyzed for purification to obtain modified chitosan; 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) are dehydrated in a vacuum environment at 100 °C for 3 h, and then cooled to 70 °C. 15 parts by weight of isophorone diisocyanate is added and stirred and reacted at 90 °C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction is completed, the temperature is cooled to 65 °C, 5 parts by weight of dimethylolpropionic acid and 2.5 parts by weight of modified chitosan are added and stirred and reacted for 6 h, and then cooled to 26 °C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer; the internal mixer is preheated to 190 °C, 40 parts by weight of the modified silane prepared in Preparation Example 4 and 90 parts by weight of the polyurethane polymer are mixed at a rotation speed of 70 r / min for 25 min to obtain a mixture. After the mixture is extruded and formed by a single-screw extruder according to the setting of the first zone temperature of 175 °C, the second zone temperature of 185 °C, the third zone temperature of 190 °C, the fourth zone temperature of 190 °C, and the die head temperature of 185 °C, high-pressure sterilization, drying, and packaging are successively carried out to prepare a high-temperature resistant antibacterial sputum suction catheter.

[0038] Comparative Example 1: A method for preparing a high-temperature resistant antibacterial sputum suction catheter comprises the following steps: After mixing a 0.2 M acetic acid solution and a 0.2 M sodium acetate solution in a weight ratio of 1:1 and adjusting the pH to 5.0 to obtain an acetic acid-sodium acetate buffer solution, 2 parts by weight of quaternary ammonium salt chitosan is dispersed in 100 parts by weight of the acetic acid-sodium acetate buffer solution. After stirring and reacting at 25 °C for 2 h, 0.02 parts by weight of chitosanase is added and stirred and reacted at 45 °C for 6 h. After the reaction is completed, the temperature is raised to 85 °C and kept warm for 15 min, and then purified by centrifugation to remove impurities and dialysis to obtain modified chitosan; 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) are dehydrated in a vacuum environment at 100 °C for 3 h, then cooled to 70 °C, 15 parts by weight of isophorone diisocyanate is added, and stirred and reacted at 90 °C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction is completed, the temperature is cooled to 65 °C, 5 parts by weight of dimethylolpropionic acid and 2.5 parts by weight of modified chitosan are added and stirred and reacted for 6 h, then cooled to 26 °C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer; the internal mixer is preheated to 190 °C, 40 parts by weight of the modified silane prepared in Preparation Example 5 and 90 parts by weight of the polyurethane polymer are mixed at a rotation speed of 70 r / min for 25 min to obtain a mixture. The mixture is extruded and molded by a single-screw extruder according to the settings of the first zone temperature of 175 °C, the second zone temperature of 185 °C, the third zone temperature of 190 °C, the fourth zone temperature of 190 °C, and the die head temperature of 185 °C, and then successively subjected to high-pressure sterilization, drying, and packaging to obtain a high-temperature resistant and antibacterial sputum suction catheter.

[0039] Comparative Example 2: A method for preparing a high-temperature resistant and antibacterial sputum suction catheter comprises the following steps: After mixing a 0.2 M acetic acid solution and a 0.2 M sodium acetate solution in a weight ratio of 1:1, the pH was adjusted to 5.0 to obtain an acetic acid-sodium acetate buffer solution. 2 parts by weight of quaternary ammonium salt chitosan was dispersed in 100 parts by weight of the acetic acid-sodium acetate buffer solution. After stirring and reacting at 25 °C for 2 h, 0.02 parts by weight of chitosanase was added and stirred and reacted at 45 °C for 6 h. After the reaction was completed, the temperature was raised to 85 °C and kept warm for 15 min, and then centrifuged to remove impurities and dialyzed for purification to obtain modified chitosan; 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) were dehydrated in a vacuum environment at 100 °C for 3 h, then cooled to 70 °C, 15 parts by weight of isophorone diisocyanate was added, and the mixture was stirred and reacted at 90 °C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction was completed, the temperature was cooled to 65 °C, 5 parts by weight of dimethylolpropionic acid and 2.5 parts by weight of modified chitosan were added and stirred and reacted for 6 h, then cooled to 26 °C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer; the internal mixer was preheated to 190 °C, 40 parts by weight of the modified silane prepared in Preparation Example 6 and 90 parts by weight of the polyurethane polymer were mixed at a rotation speed of 70 r / min for 25 min to obtain a mixture. The mixture was extruded and formed by a single-screw extruder according to the settings of the first zone temperature of 175 °C, the second zone temperature of 185 °C, the third zone temperature of 190 °C, the fourth zone temperature of 190 °C, and the die head temperature of 185 °C, and then successively subjected to high-pressure sterilization, drying and packaging to obtain a high-temperature resistant and antibacterial sputum suction catheter.

[0040] Comparative Example 3: A preparation method of a high-temperature resistant and antibacterial sputum suction catheter comprises the following steps: After mixing a 0.2M acetic acid solution and a 0.2M sodium acetate solution in a weight ratio of 1:1, the pH was adjusted to 5.0 to obtain an acetic acid-sodium acetate buffer solution. 2 parts by weight of quaternary ammonium salt chitosan was dispersed in 100 parts by weight of the acetic acid-sodium acetate buffer solution. After stirring and reacting at 25°C for 2 h, 0.02 parts by weight of chitosanase was added and stirred and reacted at 45°C for 6 h. After the reaction, the temperature was raised to 85°C and kept warm for 15 min, and then centrifuged to remove impurities and dialyzed and purified to obtain modified chitosan; 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) were dehydrated in a vacuum environment at 100°C for 3 h, then cooled to 70°C, 15 parts by weight of isophorone diisocyanate was added, and stirred and reacted at 90°C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction, the temperature was cooled to 65°C, 5 parts by weight of dimethylolpropionic acid and 2.5 parts by weight of modified chitosan were added and stirred and reacted for 6 h, then cooled to 26°C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer; the internal mixer was preheated to 190°C, 40 parts by weight of the modified silane prepared in Preparation Example 7 and 90 parts by weight of the polyurethane polymer were mixed at a rotation speed of 70 r / min for 25 min to obtain a mixture. The mixture was extruded and molded by a single-screw extruder according to the settings of the first zone temperature of 175°C, the second zone temperature of 185°C, the third zone temperature of 190°C, the fourth zone temperature of 190°C, and the die head temperature of 185°C, and then successively subjected to high-pressure sterilization, drying and packaging to obtain a high-temperature resistant antibacterial sputum suction catheter.

[0041] Comparative Example 4: A preparation method of a high-temperature resistant antibacterial sputum suction catheter comprises the following steps: 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) were dehydrated in a vacuum environment at 100°C for 3 h, then cooled to 70°C, 15 parts by weight of isophorone diisocyanate was added, and stirred and reacted at 90°C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction, the temperature was cooled to 65°C, 5 parts by weight of dimethylolpropionic acid and 2.5 parts by weight of quaternary ammonium salt were added and stirred and reacted for 6 h, then cooled to 26°C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer; the internal mixer was preheated to 190°C, 40 parts by weight of the modified silane prepared in Preparation Example 4 and 90 parts by weight of the polyurethane polymer were mixed at a rotation speed of 70 r / min for 25 min to obtain a mixture. The mixture was extruded and molded by a single-screw extruder according to the settings of the first zone temperature of 175°C, the second zone temperature of 185°C, the third zone temperature of 190°C, the fourth zone temperature of 190°C, and the die head temperature of 185°C, and then successively subjected to high-pressure sterilization, drying and packaging to obtain a high-temperature resistant antibacterial sputum suction catheter.

[0042] Comparative Example 5: A preparation method of a high-temperature resistant antibacterial sputum suction catheter comprises the following steps: 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) were dehydrated in a vacuum environment at 100 °C for 3 h, then cooled to 70 °C, and 15 parts by weight of isophorone diisocyanate was added. The mixture was stirred and reacted at 90 °C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction, the temperature was cooled to 65 °C, 5 parts by weight of trimethylolpropane was added, and the mixture was stirred and reacted for 6 h. Then, it was cooled to 26 °C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer. The internal mixer was preheated to 190 °C, 40 parts by weight of the modified silane prepared in Preparation Example 4 and 90 parts by weight of the polyurethane polymer were mixed at a rotation speed of 70 r / min for 25 min to obtain a mixture. After the mixture was extruded and formed by a single-screw extruder according to the settings of the first zone temperature of 175 °C, the second zone temperature of 185 °C, the third zone temperature of 190 °C, the fourth zone temperature of 190 °C, and the die head temperature of 185 °C, it was successively subjected to high-pressure sterilization, drying, and packaging to obtain a high-temperature resistant and antibacterial sputum suction catheter.

[0043] Comparative Example 6: A preparation method of a high-temperature resistant and antibacterial sputum suction catheter includes the following steps: After a 0.2 M acetic acid solution and a 0.2 M sodium acetate solution were mixed at a weight ratio of 1:1, the pH was adjusted to 5.0 to obtain an acetic acid-sodium acetate buffer solution. 2 parts by weight of quaternary ammonium salt chitosan was dispersed in 100 parts by weight of the acetic acid-sodium acetate buffer solution, and after stirring and reacting at 25 °C for 2 h, 0.02 parts by weight of chitosanase was added and stirred and reacted at 45 °C for 6 h. After the reaction, the temperature was raised to 85 °C and kept warm for 15 min, and then successively centrifuged to remove impurities and dialyzed and purified to obtain modified chitosan. 55 parts by weight of polytetrahydrofuran (Mn = 1000) and 35 parts by weight of polyethylene glycol (Mn = 2000) were dehydrated in a vacuum environment at 100 °C for 3 h, then cooled to 70 °C, and 15 parts by weight of isophorone diisocyanate was added. The mixture was stirred and reacted at 90 °C for 4 h in a nitrogen protection environment to obtain a prepolymer. After the reaction, the temperature was cooled to 65 °C, 5 parts by weight of dimethylolpropionic acid and 2.5 parts by weight of modified chitosan were added, and the mixture was stirred and reacted for 6 h. Then, it was cooled to 26 °C and precipitated with ionized water, and successively filtered and vacuum dried to obtain a polyurethane polymer. The internal mixer was preheated to 190 °C, 90 parts by weight of the polyurethane polymer was processed at a rotation speed of 70 r / min for 25 min, and after being extruded and formed by a single-screw extruder according to the settings of the first zone temperature of 175 °C, the second zone temperature of 185 °C, the third zone temperature of 190 °C, the fourth zone temperature of 190 °C, and the die head temperature of 185 °C, it was successively subjected to high-pressure sterilization, drying, and packaging to obtain a high-temperature resistant and antibacterial sputum suction catheter.

[0044] Test Example 1: Hydrophilicity test The high-temperature resistant and antibacterial sputum suction catheters prepared in Examples 1 to 4 and Comparative Examples 1 to 6 were cut open, and a contact angle tester was used to test the surface water contact angle. The test results are shown in Table 1.

[0045] Table 1. Hydrophilicity test From the test results in Table 1, it can be seen that the high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-4 of the present invention have good hydrophilicity. The decrease in the hydrophilic performance of Comparative Examples 1-3 may be due to the reduction of hydrophilic groups in the modified silane.

[0046] Test Example 2: Antibacterial test The high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-4 and Preparation Examples 1-6 were used as samples. The bacterial strains were diluted with sterile water into a bacterial suspension with an appropriate concentration for standby. 0.2 ml of the bacterial suspension was dropped on the surface of the sample, and a polyethylene film with a thickness of 0.1 mm was covered on it to form a uniform liquid film between the bacterial suspension, the sample and the film. After culturing at 37°C with a relative humidity of 90% for 18-24 hours, the bacterial liquid was washed off with sterile water, diluted into an appropriate concentration gradient, and 0.1 ml was taken and evenly coated on the prepared sterile light medium, and cultured at 37°C for 18-24 hours to observe the results. The negative control was replaced with a sterile petri dish, and other operations were the same. The test bacteria were Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC6538. The test results are shown in Table 2.

[0047] Table 2. Antibacterial performance detection From the test results in Table 2, it can be seen that the high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-4 of the present invention have good antibacterial properties. The decrease in the antibacterial performance of Comparative Example 3 may be due to the absence of modified resveratrol, which weakens its antibacterial performance. The decrease in the antibacterial performance of Comparative Example 5 may be due to the lack of modified chitosan, resulting in the absence of quaternary ammonium salt groups, and thus leading to a decrease in its antibacterial performance.

[0048] Test Example 3: Heat distortion temperature detection Referring to the ISO 75-2:2013 standard, the heat distortion temperatures of the high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-4 and Preparation Examples 1-6 were detected. The test results are shown in Table 3.

[0049] Table 3. Heat distortion temperature detection From the data in Table 3, it can be observed that the heat distortion temperatures of the high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-4 of the present invention are higher than those of the high-temperature resistant antibacterial sputum suction catheters prepared in Comparative Examples 1-6. The lower heat distortion temperature of Comparative Example 3 may be due to the absence of hydroxypropyl-β-cyclodextrin, resulting in a decrease in its heat resistance. The lower heat distortion temperature of Comparative Example 6 may be due to the simultaneous absence of hydroxypropyl-β-cyclodextrin and silicone network, resulting in a decrease in its thermal stability.

[0050] Test Example 4: Mechanical Property Detection Using an Instron 5567 universal material testing machine, place the high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-5 and Comparative Examples 1-6 on the testing machine respectively. Align the longitudinal axis of the specimen with the centerlines of the upper and lower clamps. The test speed is 10 mm / min, and stop when the specimen breaks. The test results are shown in Table 4.

[0051] Table 4. Mechanical Property Detection It can be seen from the test results in Table 4 that the high-temperature resistant antibacterial sputum suction catheters prepared in Examples 1-4 of the present invention have good mechanical properties, and the mechanical properties of Comparative Examples 1-6 have significantly decreased. This may be because the flexibility and high elongation at break of the modified silane complement the high tensile strength of the polyurethane polymer. The two form a homogeneous structure through hydrogen bonding or physical interaction, and synergistically improve the mechanical properties of the high-temperature resistant antibacterial sputum suction catheter. The lack of some raw materials may affect this synergistic effect, resulting in a decrease in the mechanical properties of the high-temperature resistant antibacterial sputum suction catheter.

[0052] The above embodiments have described the technical solutions and beneficial effects of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed.

Claims

1. A preparation method of a high-temperature resistant and antibacterial sputum suction catheter, characterized in that, The preparation method comprises the following steps: Quaternary ammonium salt chitosan is treated with chitosanase to obtain modified chitosan. Polytetrahydrofuran, polyethylene glycol and diisocyanate react to obtain a prepolymer. The prepolymer, dimethylolpropionic acid and modified chitosan react to obtain a polyurethane prepolymer. Modified silane and the polyurethane prepolymer are mixed to obtain a mixture, and the mixture is extruded into a high-temperature resistant and antibacterial sputum suction catheter.

2. The preparation method of a heat-resistant antibacterial sputum suction catheter as described in claim 1, wherein The preparation method of the modified silane comprises the following steps: Hydroxypropyl-β-cyclodextrin and resveratrol react to obtain modified resveratrol. 3-mercaptopropyltrimethoxysilane, itaconic acid and an initiator react to obtain carboxylated silane. The modified resveratrol and the carboxylated silane are mixed and then sequentially subjected to acid treatment and alkali treatment to obtain modified silane.

3. The preparation method of a heat-resistant antibacterial sputum suction catheter according to claim 2, wherein, The reaction conditions for the reaction of hydroxypropyl-β-cyclodextrin and resveratrol include a reaction temperature of 55-60°C and a reaction time of 8-12 h.

4. The preparation method of a high-temperature resistant and antibacterial sputum suction catheter according to claim 2, wherein, The initiator is benzoin diethyl ether.

5. The preparation method of a heat-resistant antibacterial sputum suction catheter according to claim 2, characterized in that, The reaction conditions for the reaction of 3-mercaptopropyltrimethoxysilane, itaconic acid and the initiator are ultraviolet irradiation treatment with 365 nm ultraviolet light for 30-60 min.

6. The preparation method of a high-temperature resistant and antibacterial sputum suction catheter according to claim 2, wherein, The weight ratio of the modified resveratrol to the carboxylated silane is 1-3:9-11.

7. The preparation method of a high-temperature resistant and antibacterial sputum suction catheter according to claim 1, characterized in that, The diisocyanate includes hexamethylene diisocyanate or isophorone diisocyanate.

8. The preparation method of a heat-resistant antibacterial sputum suction catheter according to claim 1, wherein, The reaction conditions for the reaction of the prepolymer, dimethylolpropionic acid and modified chitosan include a reaction temperature of 55-65°C and a reaction time of 4-6 h.

9. The preparation method of a high-temperature resistant and antibacterial sputum suction catheter according to claim 1, characterized in that, The mixing conditions for the modified silane and the polyurethane prepolymer include a mixing temperature of 180-190°C and a mixing time of 15-25 min.

10. A high-temperature resistant and antibacterial sputum suction catheter, characterized in that, It is prepared by the preparation method of a high-temperature resistant and antibacterial sputum suction catheter according to any one of claims 1-9.

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