WO2021103747A1 - 一种医用管材及其制备方法 - Google Patents

一种医用管材及其制备方法 Download PDF

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Publication number
WO2021103747A1
WO2021103747A1 PCT/CN2020/115127 CN2020115127W WO2021103747A1 WO 2021103747 A1 WO2021103747 A1 WO 2021103747A1 CN 2020115127 W CN2020115127 W CN 2020115127W WO 2021103747 A1 WO2021103747 A1 WO 2021103747A1
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medical tubing
medical
reaction kettle
preparing
pipe material
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PCT/CN2020/115127
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English (en)
French (fr)
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秦明林
李兆敏
刘敏
张新华
阙亦云
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脉通医疗科技(嘉兴)有限公司
创脉医疗科技(上海)有限公司
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Publication of WO2021103747A1 publication Critical patent/WO2021103747A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12—Chemical modification
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2323/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
    • C08J2323/02—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers not modified by chemical after treatment
    • C08J2323/04—Homopolymers or copolymers of ethene
    • C08J2323/06—Polyethene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2323/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
    • C08J2323/02—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers not modified by chemical after treatment
    • C08J2323/10—Homopolymers or copolymers of propene
    • C08J2323/12—Polypropene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2327/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers
    • C08J2327/02—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment
    • C08J2327/12—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment containing fluorine atoms
    • C08J2327/18—Homopolymers or copolymers of tetrafluoroethylene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2375/00—Characterised by the use of polyureas or polyurethanes; Derivatives of such polymers
    • C08J2375/04—Polyurethanes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2377/00—Characterised by the use of polyamides obtained by reactions forming a carboxylic amide link in the main chain; Derivatives of such polymers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids

Definitions

  • the invention relates to the technical field of medical devices, in particular to a medical tube and a preparation method thereof.
  • Thermoplastic medical tubing has a wide range of applications in the biomedical field due to its good biocompatibility, such as small-diameter medical catheters, angiography catheters, urinary catheters, catheter sheaths and catheter tips.
  • biocompatibility such as small-diameter medical catheters, angiography catheters, urinary catheters, catheter sheaths and catheter tips.
  • the medical catheter After the medical catheter enters the human body, its biological performance is mainly determined by the interaction between human tissues, body fluids and the surface of the medical catheter.
  • the lubricity of the tubing determines the convenience during the operation.
  • the biological and mechanical properties of the existing thermoplastic medical tubing still have certain defects. Therefore, the surface of the medical tubing can be modified to improve its mechanical properties and biocompatibility.
  • the technical problem to be solved by the present invention is to provide a medical tube and a preparation method thereof, which can improve the biological performance of the medical tube.
  • the present invention provides a method for preparing medical tubing, including the following steps: S1: obtaining medical tubing; S2: placing the medical tubing and isocyanate solution in a reactor, and charging carbon dioxide into the reaction vessel. Kettle, adjust the temperature and pressure in the reaction kettle to make the carbon dioxide in the reaction kettle in a supercritical state, and obtain medical tubing with isocyanate groups after the reaction; S3: put the medical tubing treated in step S2 into the reformer It reacts in the solution of the sexual material to obtain a modified medical tube.
  • the reaction time is 30-90 minutes.
  • the temperature in the reactor is adjusted to 90-120°C, and the pressure in the reactor is adjusted to 8-14Mpa, so that the carbon dioxide in the reactor is in a supercritical state.
  • the method further includes the following steps: depressurizing the reaction kettle, washing and drying the medical tubing with acetone and deionized water.
  • the isocyanate is hexamethylene diisocyanate or toluene diisocyanate.
  • the modified material in step S3 is selected from at least one of heparin, polyethylene glycol, phosphorylcholine, glycidyl methacrylate, hydroxyethyl methacrylate, phosphorylcholine, and albumin .
  • the modified material is heparin, and the concentration of the heparin solution is 20-40 mg/mL.
  • the reaction temperature between the medical tubing processed in the step S2 and the modified material is 25-30° C., and the reaction time is 8-24 h.
  • the material of the medical tube is at least one of polyether block amide, polyethylene, polypropylene, polyamide, thermoplastic polyurethane and polytetrafluoroethylene.
  • the present invention also provides a medical tube made by the above preparation method.
  • the present invention has the following beneficial effects: the medical pipe provided by the present invention and the preparation method thereof, introduce active functional groups on the surface of the medical pipe through the method of carrying isocyanate with supercritical carbon dioxide, and then chemically react with the modified material to achieve Surface modification of medical tubing to improve the biological performance of medical tubing.
  • the method provided by the present invention is simple in process, environmentally friendly, and pollution-free, and can carry out continuous large-scale production; while retaining the advantages of high toughness and high flexibility of medical polymer pipes, it also imparts biocompatibility and lubricity, It can meet the clinical requirements of minimally invasive interventional medical tubing.
  • the medical tubing provided by the present invention uses supercritical carbon dioxide to carry isocyanate to introduce active functional groups on the surface of the tubing, and then combines with heparin, polyethylene glycol (PEG), phosphorylcholine, glycidyl methacrylate (GMA), and polyvinylpyrrolidone (PVP). ), hydroxyethyl methacrylate (HEMA) or albumin and other modified materials react to improve the biological performance of medical tubing.
  • PEG polyethylene glycol
  • GMA glycidyl methacrylate
  • PVP polyvinylpyrrolidone
  • HEMA hydroxyethyl methacrylate
  • albumin other modified materials react to improve the biological performance of medical tubing.
  • supercritical carbon dioxide When the temperature of carbon dioxide exceeds 31.26°C and the pressure exceeds 72.9 standard atmosphere (atm), it enters the state of supercritical carbon dioxide.
  • Supercritical carbon dioxide has the advantages of non-toxic and environmental protection, density close to liquid, viscosity close to gas, high diffusion coefficient, and large dissolving and penetrating ability.
  • the use of supercritical carbon dioxide can dissolve a variety of substances and has important uses in the fields of drug extraction, foaming, and sewage treatment. When modifying the surface of medical tubing, the use of supercritical carbon dioxide also has great advantages.
  • the method for preparing medical tubing provided by the present invention includes the following steps:
  • Step S1 Obtain medical tubing.
  • the medical tube is cut into a predetermined length, and the predetermined length can be set according to actual needs. Then, the surface of the medical tube is cleaned with ethanol solution and deionized water to remove impurities.
  • the ethanol solution may be an ethanol solution with a concentration of 75% by mass percentage.
  • the medical tube is dried in a vacuum oven. The temperature of the vacuum oven can be set to 90°C.
  • Step S2 Place the medical tubing and the isocyanate solution in a reactor, fill the reactor with carbon dioxide gas, adjust the temperature and pressure in the reactor, and make the carbon dioxide in the reactor in a supercritical state After the reaction, a medical tube with isocyanate groups is obtained.
  • the temperature in the reactor can be adjusted to 90-120°C.
  • the medical tube may be polyether block amide (PEBA), polyethylene (PE), polypropylene (PP), polyamide (PA) (such as nylon 6 (PA6), nylon 12 (PA12)) and at least one of thermoplastic polyurethane (TPU), polytetrafluoroethylene (PTFE) and other materials.
  • PEBA polyether block amide
  • PE polyethylene
  • PP polypropylene
  • PA polyamide
  • PA6 nylon 6
  • PA12 nylon 12
  • TPU thermoplastic polyurethane
  • PTFE polytetrafluoroethylene
  • the isocyanate can be hexamethylene diisocyanate (HDI) or toluene diisocyanate (TDI).
  • Step S3 Put the medical tubing processed in step S2 into the modified material solution to react; obtain a modified medical tubing.
  • the medical tube with isocyanate groups is added to the modified material solution, and the reaction is carried out at a temperature of 25-30° C. for 8-24 hours. After the reaction, the modified medical tubing is obtained after washing with distilled water and drying.
  • the modified material may be selected from heparin, polyethylene glycol (PEG), phosphocholine, glycidyl methacrylate (GMA), hydroxyethyl methacrylate (HEMA) , At least one of phosphocholine and albumin.
  • the concentration of the modified material is different.
  • the thickness of the coating formed on the surface of the medical tube is also different.
  • the higher the concentration of the modified material the thicker the coating formed on the surface of the medical tube.
  • the isocyanate active functional group on the medical pipe can react with the functional group in the modified material, thereby realizing the surface modification of the medical pipe and improving the biological performance of the medical pipe.
  • Pebax polyether block polyamide
  • the Pebax medical tubing was placed in a vacuum oven to a constant weight, and the temperature of the vacuum oven was set to 90°C; the cleaned and dried medical tubing and the isocyanate dissolved in acetone were placed in a stainless steel autoclave. Adjust the temperature in the reactor to 90°C.
  • An air compressor is used to charge carbon dioxide into the reactor, and the pressure in the reactor is adjusted to 10 MPa, so that the carbon dioxide inside the reactor is in a supercritical state.
  • the pressure of the reaction kettle was immediately relieved.
  • Use acetone to clean the unreacted isocyanate on the medical tubing then clean the medical tubing with deionized water to remove impurities, and finally dry it with nitrogen to obtain the medical tubing with isocyanate groups.
  • the medical tubing with isocyanate groups is immersed in a configured 20 mg/mL heparin solution, reacted at a temperature of 25-30° C. for 8-24 hours, and then washed with water to obtain a modified Pebax medical tubing.
  • the heparin solution is prepared by using PBS (phosphate buffered saline) with a pH of 9.0.
  • the product structure and production process of this embodiment are the same as those of Embodiment 1, except that the concentration of heparin is different.
  • the concentration of the heparin solution is 30 mg/mL.
  • the product structure and production process of this embodiment are the same as those of Embodiment 1, except that the concentration of heparin is different.
  • the concentration of the heparin solution is 40 mg/mL.
  • the medical tubing provided by the present invention is preferably a low-hard segment thermoplastic elastomer polyether block amide (Pebax 3533) tubing, and its biocompatibility is significantly improved.
  • the biological properties are shown in Table 1.
  • the hemolysis rate refers to the percentage of the pipe that dissolves into the blood after the pipe enters the human body.
  • the cell proliferation rate refers to the percentage of new cells produced by the human body after the pipe enters the human body. After the tube enters the human body, the hemolysis rate should not be too high.
  • the hemolysis rate is preferably 0 to 0.1%, and the cell proliferation rate must be above 85%, so that it can be used as a medical tube. It can be seen from Table 1 that the polyether block amide tubing modified by heparin solution can greatly reduce the hemolysis rate and increase the cell proliferation rate, significantly improve the biological compatibility of the tubing, and meet the requirements of medical tubing.
  • the medical tubing provided by the present invention and the preparation method thereof have the following advantages:
  • the present invention introduces active functional groups on the surface of medical tubing by supercritical carbon dioxide carrying isocyanate, which can chemically react with the functional groups in the modified material to improve the biological performance of the medical tubing.
  • the preparation method provided by the present invention is simple in process, environmentally friendly, pollution-free, and can be used for continuous large-scale production.
  • the present invention not only retains the advantages of high toughness and high flexibility of medical polymer tubing, but also imparts biocompatibility and lubricity, which can meet the clinical requirements of minimally invasive interventional medical tubing.

Abstract

本发明公开了一种医用管材及其制备方法，所述医用管材的制备方法包括如下步骤：S1：获取医用管材；S2：将所述医用管材以及异氰酸酯溶液置于反应釜内，将二氧化碳充入所述反应釜，调节所述反应釜内的温度和压力，使所述反应釜内的二氧化碳处于超临界状态，反应后得到具有异氰酸酯基团的医用管材；S3：将步骤S2处理后的医用管材放入改性材料溶液中反应；得到涂层改性的医用管材。本发明通过超临界二氧化碳携带异氰酸酯的方法在医用管材表面引入活性官能团，使其能够与改性材料中的官能团发生化学反应，实现对医用管材的表面改性，提高医用管材的生物学性能。

Description

一种医用管材及其制备方法 技术领域
本发明涉及医疗器械技术领域，尤其涉及一种医用管材及其制备方法。
背景技术
热塑性医用管材由于其具有良好的生物相容性，在生物医学领域有着广泛的应用，如小直径的医用导管、血管造影导管、泌尿导管、导管鞘和导管尖端等。医用导管进入人体后，其生物学性能的好坏主要是由人体组织、体液等与医用导管表面的相互作用来决定。同时，管材的润滑性又决定手术操作过程中的便利性。现有的热塑性医用管材的生物学性能和力学性能仍存在一定的缺陷，因此，可以通过对医用管材表面进行改性，提高其力学性能和生物相容性。
传统的处理方法比如等离子体、化学接枝、化学刻蚀虽然在医用管材的表面引入活性官能团，增强了管材与其他基体的界面粘结性能，但是这些方法往往导致对医用管材的机械强度的破坏，且生产成本高，工艺程序复杂。因此，寻求一种简单又有效的医用管材改性方法具有重要的意义。
发明内容
本发明所要解决的技术问题是提供一种医用管材及其制备方法，能够提升医用管材的生物学性能。
为解决上述技术问题，本发明提供一种医用管材的制备方法，包括如下步骤：S1：获取医用管材；S2：将所述医用管材以及异氰酸酯溶液置于反应釜内，将二氧化碳充入所述反应釜，调节所述反应釜内的温度和压力，使所述反应釜内的二氧化碳处于超临界状态，反应后得到具有异氰酸酯基团的医用管材；S3：将步骤S2处理后的医用管材放入改性材料溶液中反应，得到改性的医用管材。
优选地，所述步骤S2中，所述反应的时间为30-90分钟。
优选地，所述步骤S2中，调节所述反应釜内的温度至90-120℃，调节所 述反应釜内的压力至8-14Mpa，使所述反应釜内的二氧化碳处于超临界状态。
优选地，在所述步骤S2之后，还包括以下步骤：对所述反应釜进行泄压，使用丙酮和去离子水清洗并干燥所述医用管材。
优选地，所述异氰酸酯为六亚甲基二异氰酸酯或甲苯二异氰酸酯。
优选地，所述步骤S3中的改性材料选自肝素、聚乙二醇、磷酸胆碱、甲基丙烯酸缩水甘油酯、甲基丙烯酸羟乙酯、磷酸胆碱、白蛋白中的至少一种。
优选地，所述改性材料为肝素，所述肝素溶液的浓度为20-40mg/mL。
优选地，所述步骤S3中，所述步骤S2处理后的医用管材与所述改性材料的反应温度为25-30℃，反应时间为8-24h。
优选地，所述医用管材的材料为聚醚嵌段酰胺、聚乙烯、聚丙烯、聚酰胺、热塑性聚氨酯和聚四氟乙烯中的至少一种。
为解决上述技术问题，本发明还提供一种医用管材，由上述的制备方法制取。
本发明对比现有技术有如下的有益效果：本发明提供的医用管材及其制备方法，通过超临界二氧化碳携带异氰酸酯的方法在医用管材表面引入活性官能团，然后与改性材料发生化学反应，从而实现对医用管材的表面改性，提高医用管材的生物学性能。本发明提供的方法工艺简单、环境友好、无污染，可以进行连续性的规模化生产；在保留医用高分子管材高韧性及高柔软性优势的同时，又赋予了生物相容性和润滑性，能够满足微创伤介入医用管材的临床要求。
具体实施方式
下面结合实施例对本发明作进一步的描述。
本发明提供的医用管材利用超临界二氧化碳携带异氰酸酯在管材表面引入活性官能团，然后与肝素、聚乙二醇(PEG)、磷酸胆碱、甲基丙烯酸缩水甘油酯(GMA)、聚乙烯吡咯烷酮(PVP)、甲基丙烯酸羟乙酯(HEMA)或白蛋白等改性材料发生反应，提高了医用管材的生物学性能。
当二氧化碳的温度超过31.26℃，压力超过72.9标准大气(atm)时，即进入超临界二氧化碳状态。超临界二氧化碳具有无毒环保、密度近于液体， 粘度近于气体、扩散系数高、溶解渗透能力大等优点。使用超临界二氧化碳可以溶解多种物质，在药物提取、发泡、污水处理等领域具有重要用途。在对医用管材的表面进行改性时，使用超临界二氧化碳也具有很大优势。
本发明提供的医用管材的制备方法，包括以下步骤：
步骤S1：获取医用管材。
首先，将医用管材剪成预定长度的尺寸，所述预定长度可以根据实际需求设置。然后，使用乙醇溶液和去离子水清洗所述医用管材的表面，以除去杂质。所述乙醇溶液可以选择质量百分比浓度为75％的乙醇溶液。最后，将所述医用管材置于真空烘箱中烘干。真空烘箱的温度可以设置为90℃。
步骤S2：将所述医用管材以及异氰酸酯溶液置于反应釜内，将二氧化碳气体充入所述反应釜，调节所述反应釜内的温度和压力，使所述反应釜内的二氧化碳处于超临界状态，反应后得到具有异氰酸酯基团的医用管材。
将清洗并干燥过的医用管材以及丙酮溶解的异氰酸酯置于不锈钢高压反应釜内。在本发明的实施例中，可以调节反应釜内的温度至90-120℃。采用空压机将二氧化碳充入反应釜中，调节反应釜内的压力至8-14MPa，使反应釜内的二氧化碳处于超临界状态，反应30-90min后，立即泄压。使用丙酮清洗所述医用管材上未反应的异氰酸酯，然后使用去离子水清洗所述医用管材以去除杂质，最后使用氮气干燥所述医用管材。在本发明的实施例中，所述医用管材可以是聚醚嵌段酰胺(PEBA)、聚乙烯(PE)、聚丙烯(PP)、聚酰胺(PA)(如尼龙6(PA6)、尼龙12(PA12))以及热塑性聚氨酯(TPU)、聚四氟乙烯(PTFE)等材料中的至少一种，异氰酸酯可以是六亚甲基二异氰酸酯(HDI)或甲苯二异氰酸酯(TDI)等。
步骤S3：将步骤S2处理后的医用管材放入改性材料溶液中反应；得到改性的医用管材。
将具有异氰酸酯基团的医用管材加入改性材料溶液中，在25-30℃温度下反应8-24h。反应结束后，使用蒸馏水清洗并干燥后得到改性的医用管材。在本发明的实施例中，所述改性材料可以是选自肝素、聚乙二醇(PEG)、磷酸胆碱、甲基丙烯酸缩水甘油酯(GMA)、甲基丙烯酸羟乙酯(HEMA)、磷酸胆碱和白蛋白中的至少一种。并且，改性材料的浓度不同，在与医用管材反 应后，在医用管材表面上形成的涂层厚度也不同，通常改性材料的浓度越高，在医用管材表面上形成的涂层越厚。医用管材上的异氰酸酯活性官能团能够与所述改性材料中的官能团反应，从而实现对医用管材的表面改性，提高医用管材的生物学性能。
实施例1
将Pebax(聚醚嵌段聚酰胺)医用管材剪成长度15cm的尺寸。分别用质量百分比浓度为75％的乙醇和去离子水清洗医用管材的表面，以除去附着在管材表面的杂质。然后，将Pebax医用管材置于真空烘箱至恒重，真空烘箱的温度设定为90℃；将清洗并干燥过的医用管材以及丙酮溶解的异氰酸酯置于不锈钢高压反应釜内。调节所述反应釜内的温度至90℃。采用空气压缩机将二氧化碳充入所述反应釜中，并调节所述反应釜内的压力至10MPa，使所述反应釜内部的二氧化碳处于超临界状态。反应30分钟后，立即对所述反应釜泄压。使用丙酮清洗所述医用管材上未反应的异氰酸酯，然后使用去离子水清洗医用管材以去除杂质，最后使用氮气干燥后即获得具有异氰酸酯基团的医用管材。将具有异氰酸酯基团的医用管材浸泡在配置好的20mg/mL的肝素溶液中，在25-30℃的温度下下反应8-24h，然后水洗得到改性的Pebax医用管材。在本发明的实施例中，所述肝素溶液使用pH值为9.0的PBS(磷酸盐缓冲液)配制得到。
实施例2
本实施例与实施例1的产品结构和生产工艺相同，不同点在于肝素的浓度不同，本实施例中肝素溶液的浓度为30mg/mL。
实施例3
本实施例与实施例1的产品结构和生产工艺相同，不同点在于肝素的浓度不同，本实施例中肝素溶液的浓度为40mg/mL。
本发明提供的医用管材优选为低硬链段的热塑性弹性体聚醚嵌段酰胺(Pebax 3533)管材，其生物相容性得到显著的改善，生物学性能如表1所示。
表1.不同肝素浓度下聚醚嵌段酰胺(Pebax 3533)管材的生物学性能
Figure PCTCN2020115127-appb-000001
Figure PCTCN2020115127-appb-000002
其中，溶血率是指管材进入人体后溶解到血液里的管材占整体管材的百分比。细胞增殖率是指管材进入人体后人体新产生的细胞占原来人体细胞的百分比。管材进去人体后溶血率不能太高，溶血率较佳为0到0.1％，细胞增殖率要能达到85％以上，这样才能作为医用管材使用。从表1可以看出，经过肝素溶液改性后的聚醚嵌段酰胺管材能够大幅降低溶血率及提升细胞增殖率，显著提高管材的生物学相容性，达到医用管材的要求。
综上所述，本发明提供的医用管材及其制备方法，具有如下优点：
(1)本发明通过超临界二氧化碳携带异氰酸酯的方法在医用管材表面引入活性官能团，能够与改性材料中的官能团发生化学反应，提高医用管材的生物学性能。
(2)本发明提供的制备方法工艺简单、环境友好、无污染，可以进行连续性的规模化生产。
(3)本发明在保留医用高分子管材高韧性及高柔软性优势的同时，又赋予了生物相容性和润滑性，能够满足微创伤介入医用管材的临床要求。
虽然本发明已以较佳实施例揭示如上，然其并非用以限定本发明，任何本领域技术人员，在不脱离本发明的精神和范围内，当可作些许的修改和完善，因此本发明的保护范围当以权利要求书所界定的为准。

Claims (10)

  1. 一种医用管材的制备方法，其特征在于，包括如下步骤：
    S1：获取医用管材；
    S2：将所述医用管材以及异氰酸酯溶液置于反应釜内，将二氧化碳充入所述反应釜，调节所述反应釜内的温度和压力，使所述反应釜内的二氧化碳处于超临界状态，反应后得到具有异氰酸酯基团的医用管材；
    S3：将步骤S2处理后的医用管材放入改性材料溶液中反应，得到改性的医用管材。
  2. 如权利要求1所述的医用管材的制备方法，其特征在于，所述步骤S2中，所述反应的时间为30-90分钟。
  3. 如权利要求1所述的医用管材的制备方法，其特征在于，所述步骤S2中，调节所述反应釜内的温度至90-120℃，调节所述反应釜内的压力至8-14Mpa，使所述反应釜内的二氧化碳处于超临界状态。
  4. 如权利要求1所述的医用管材的制备方法，其特征在于，在所述步骤S2之后，还包括以下步骤：对所述反应釜进行泄压，使用丙酮和去离子水清洗并干燥所述医用管材。
  5. 如权利要求1所述的医用管材的制备方法，其特征在于，所述异氰酸酯为六亚甲基二异氰酸酯或甲苯二异氰酸酯。
  6. 如权利要求1所述的医用管材的制备方法，其特征在于，所述步骤S3中的改性材料为肝素、聚乙二醇、磷酸胆碱、甲基丙烯酸缩水甘油酯、甲基丙烯酸羟乙酯、磷酸胆碱、白蛋白中的至少一种。
  7. 如权利要求6所述的医用管材的制备方法，其特征在于，所述改性材料为肝素，所述肝素溶液的浓度为20-40mg/mL。
  8. 如权利要求1所述的医用管材的制备方法，其特征在于，所述步骤S3中，所述步骤S2处理后的医用管材与所述改性材料的反应温度为25-30℃，反应时间为8-24h。
  9. 如权利要求1-8中任一项所述的医用管材的制备方法，其特征在于，所述医用管材的材料为聚醚嵌段酰胺、聚乙烯、聚丙烯、聚酰胺、热塑性聚 氨酯和聚四氟乙烯中的至少一种。
  10. 一种医用管材，其特征在于，由权利要求1-9中任一项所述的医用管材的制备方法制取。
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