WO2020181857A1 - 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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WO2020181857A1
WO2020181857A1 PCT/CN2019/124944 CN2019124944W WO2020181857A1 WO 2020181857 A1 WO2020181857 A1 WO 2020181857A1 CN 2019124944 W CN2019124944 W CN 2019124944W WO 2020181857 A1 WO2020181857 A1 WO 2020181857A1
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solution
polyether block
block amide
levodopa
coating
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PCT/CN2019/124944
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English (en)
French (fr)
Inventor
秦明林
李兆敏
柳逸凡
张新华
李瑞培
邓智华
阙亦云
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脉通医疗科技(嘉兴)有限公司
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Application filed by 脉通医疗科技(嘉兴)有限公司 filed Critical 脉通医疗科技(嘉兴)有限公司
Priority to US17/423,734 priority Critical patent/US20220062510A1/en
Priority to EP19919483.8A priority patent/EP3939629A4/en
Publication of WO2020181857A1 publication Critical patent/WO2020181857A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04—Macromolecular materials
    • A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/08—Coatings comprising two or more layers

Definitions

  • the invention relates to the technical field of medical devices, in particular to a medical tube and a preparation method thereof.
  • Polyether block amide is a type of thermoplastic elastomer (TPE), which consists of polyamide (PA) as the hard segment and polyether (PE) As a type of thermoplastic multi-block copolymer composed of flexible soft segments.
  • TPE thermoplastic elastomer
  • PA polyamide
  • PE polyether
  • Polyether block amide (Pebax) has good biodegradability, shape memory and biocompatibility, and has been widely used in the biomedical field.
  • the biological properties of the polyether block amide (Pebax) and the bonding performance with other materials still have certain deficiencies. Therefore, the surface of the polyether block amide (Pebax) pipe needs to be modified to improve its biocompatibility , Hydrophilicity and bonding performance with other materials.
  • the technical problem to be solved by the present invention is to provide a medical pipe and a preparation method thereof, which can improve the biocompatibility, hydrophilicity and interface bonding performance of the pipe surface.
  • the method for preparing medical tubing includes the following steps: S1: self-polymerizing levodopa to obtain a polylevodopa solution; S2: soaking polyether block amide tubing in cations In the polyelectrolyte solution, introduce positive ions into the surface of the polyether block amide pipe; S3: soak the polyether block amide pipe treated in step S2 in the poly-levodopa solution made in step S1, The surface of the amide pipe is attached to form a poly-levodopa coating; S4: a polyether block amide pipe with a poly-levodopa coating is placed in the modified material solution to react to obtain a coated modified polyether block amide pipe .
  • the step S1 includes: dissolving levodopa in water to obtain a levodopa solution, adjusting the pH of the solution to 8.0-9.0, and obtaining a polylevodopa solution from the polymerization reaction.
  • At least one of sodium hydroxide, tris(hydroxymethyl)aminomethane or sodium carbonate compound is added to the levodopa solution to adjust the pH of the solution to 8.0-9.0.
  • the self-polymerization reaction time in step S1 is 16-24 hours.
  • the concentration of the cationic polyelectrolyte in the step S2 is 1.0-3.0 mg/mL.
  • the cationic polyelectrolyte solution in step S2 contains sodium chloride, and the concentration of the sodium chloride is 1.0-3.0 mg/ml.
  • the cationic polyelectrolyte solution in step S2 is a polydimethyldiallylammonium chloride solution or a sodium polyacrylate solution.
  • the soaking time in step S2 and step S3 is both 5-20 min, and after soaking, it is washed with water and dried with nitrogen.
  • the steps S2 and S3 are performed 1-8 times in a loop.
  • the modified material in step S4 is selected from at least one of heparin, polyethylene glycol, phosphorylcholine, glycidyl methacrylate, hydroxyethyl methacrylate, phosphorylcholine and albumin .
  • the step S4 includes: immersing the polyether block amide pipe with polylevodopa coating in the modified material solution, adjusting the pH of the solution to 8.5-9.0, reacting for 8-24 hours, and then washing with water to obtain Coating modified polyether block amide pipe.
  • the modified material is heparin, and the concentration of the heparin solution is 20-40 mg/mL.
  • the polyether block amide pipe material with the poly-levodopa coating is put into the modified material solution of different concentration, so that the outside of the poly-levodopa coating has the modified material of different thickness coating.
  • the present invention also provides a medical tube prepared by the above preparation method.
  • the present invention has the following beneficial effects: the medical tubing provided by the present invention and the preparation method thereof use levodopa self-polymerization to introduce active functional groups such as hydroxyl and amino groups on the surface of the polyether block amide (Pebax) tubing, and then Reacts with modified materials such as heparin, polyethylene glycol (PEG), phosphocholine, glycidyl methacrylate (GMA), hydroxyethyl methacrylate (HEMA), albumin, etc. to improve the polyether block
  • modified materials such as heparin, polyethylene glycol (PEG), phosphocholine, glycidyl methacrylate (GMA), hydroxyethyl methacrylate (HEMA), albumin, etc.
  • the present invention uses mussel secretion levodopa to form a coating on the surface of a polyether block amide (Pebax) pipe, and then modifies the coating by grafting to improve the biocompatibility of precision pipes for interventional medical devices Properties, hydrophilicity and interface bonding properties.
  • a polyether block amide Pebax
  • Mussels are a kind of crustaceans that are ubiquitous in coastal waters, especially in cold waters. They can secrete super adhesion proteins to firmly adhere themselves to any material surface, such as metals, glass, polymers, and minerals.
  • the adhesive protein can quickly solidify in a humid environment and form a strong interaction with the matrix material. Among them, levodopa is the key to the mussel adhesive protein's adhesion behavior.
  • the preparation method of the medical tubing provided by the present invention uses levodopa to improve the biocompatibility, hydrophilicity and interface bonding performance of the medical tubing, including the following steps:
  • Step S1 self-polymerization reaction of levodopa.
  • the alkali can It is at least one of sodium hydroxide, tris(hydroxymethyl)aminomethane (Tris), or sodium carbonate.
  • Step S2 introduce positive ions on the surface of the pipe.
  • the cationic polyelectrolyte solution may be a polydimethyldiallylammonium chloride (PDDA) solution or a sodium polyacrylate solution.
  • PDDA polydimethyldiallylammonium chloride
  • the cationic polyelectrolyte solution may contain sodium chloride, and the concentration of the sodium chloride may be 1.0-3.0 mg/ml.
  • Step S3 the surface of the pipe is attached with a poly-levodopa coating.
  • step S2 The pipe treated in step S2 is immersed in the polylevodopa solution prepared in step S1 for 5-20 minutes, and then washed with water and dried with nitrogen.
  • polylevodopa since polylevodopa has negative carboxylic acid ions, it can be combined with positive ions on the surface of the pipe. In this way, polylevodopa can be effectively bound to the surface of the pipe. Moreover, due to electrostatic adsorption, polylevodopa is adsorbed on the surface of the pipe to form a dense coating, thereby introducing a large number of active functional groups, such as hydroxyl, carboxyl, and amino groups, on the surface of the pipe.
  • Step S4 modification of the poly-levodopa coating on the surface of the pipe.
  • the modified material is selected from heparin, At least one of polyethylene glycol (PEG), phosphorylcholine, glycidyl methacrylate (GMA), hydroxyethyl methacrylate (HEMA), phosphorylcholine, and albumin.
  • PEG polyethylene glycol
  • GMA glycidyl methacrylate
  • HEMA hydroxyethyl methacrylate
  • albumin albumin.
  • the modified material can be heparin, and the concentration of the heparin solution can be 20-40 mg/mL.
  • the active functional groups on the poly-levodopa coating easily react with the functional groups carried by the above-mentioned modified material, so that the outside of the poly-levodopa coating has a layer of modified material coating, which improves the biological performance of the pipe. React 8-24 at room temperature After h, wash with distilled water and dry to obtain the coating modified polyether block amide (Pebax) pipe.
  • the thickness of the modified material coating on the outside of the poly-levodopa coating is related to the concentration of the modified material solution, the polyether block amide pipe with the poly-levodopa coating can be put into the modified material of different concentrations. It reacts in the solution of the flexible material to obtain polyether block amide pipes with different coating thicknesses of the modified material to meet the needs of different products.
  • steps S2 and S3 can be executed cyclically, and the number of cyclic executions is different, and polyether block amide (Pebax) pipes with different thicknesses of polylevodopa coating on the surface can be obtained.
  • the cycle repeat times of steps S2 and S3 are preferably 1 -8 times.
  • Example 1 Pebax medical tubing was cut into a size of 15 cm in length, and the surface of the tubing was washed with 75% ethanol and deionized water to remove impurities, and then placed in a vacuum oven to a constant weight, and the temperature was set to 80°C. Dissolve levodopa in water to obtain a levodopa solution, adjust the pH of the solution to 8.0-9.0 with a base, and auto-polymerize at room temperature for 16-24 h to obtain a polylevodopa solution.
  • the base can be sodium hydroxide, tris(hydroxymethyl)aminomethane (Tris) or sodium carbonate.
  • 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 that of Embodiment 1, except that the concentration of heparin is different.
  • the concentration of the heparin solution in this embodiment is 40 mg/mL.
  • the preparation method provided by the present invention can ensure the precision of the pipe material, so that large-scale batch production can be carried out to meet the needs of different products, and at the same time, the biological compatibility of the pipe material can be improved, and the production process can be simplified and the production capacity can be increased.
  • the medical tubing can be a thermoplastic elastomer with a low hard segment, such as a 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 growth rate must reach 85% or more, so that it can be used as a medical tube. It can be seen from Table 1 that the polyether block amide tubing after soaking in the modified material 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 surface of the pipe has a poly-levodopa coating by layer-by-layer coating of polylevodopa.
  • the coating has a large number of active functional groups, so it is easy to chemically react with the functional groups of the modified material, so that The exterior of the poly-levodopa coating is coated with a modified material to improve the biological performance of the pipe.
  • the thickness of the coating is controllable, which is conducive to regulating the adhesion between the coating and the pipe. In addition, it retains the characteristics of high toughness and high flexibility of medical polymer pipes, and also imparts biocompatibility and lubricity. It can also meet the clinical requirements of precision tubing for minimally invasive interventional medical devices.

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Abstract

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：将左旋多巴进行自聚合反应，得到聚左旋多巴溶液；S2：将聚醚嵌段酰胺管材浸泡在阳离子聚电解质中，使聚醚嵌段酰胺管材表面引入正离子；S3：将步骤S2处理后的聚醚嵌段酰胺管材浸泡在步骤S1制成的聚左旋多巴溶液中，在聚醚嵌段酰胺管材表面附着形成聚左旋多巴涂层；S4：将具有聚左旋多巴涂层的聚醚嵌段酰胺管材置于改性材料溶液中反应，得到涂层改性的聚醚嵌段酰胺管材。通过使用左旋多巴在聚醚嵌段酰胺管材表面形成聚左旋多巴涂层，然后通过接枝的方法对涂层进行改性，来提高医用管材的生物相容性、亲水性以及界面粘结性能。

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
聚醚嵌段酰胺 (Pebax) 是热塑性弹性体 (TPE) 的一种，是由聚酰胺 (PA) 作为硬链段以及聚醚 (PE) 作为柔性软链段构成的一类热塑性多嵌段共聚物。聚醚嵌段酰胺 (Pebax)具有良好的生物降解性，形状记忆性以及生物相容性，已经广泛应用在生物医学领域。然而聚醚嵌段酰胺 (Pebax) 的生物学性能以及与其他材料的粘结性能仍存在一定的不足，因此需要对聚醚嵌段酰胺 (Pebax) 管材表面进行改性，提高其生物相容性、亲水性以及与其他材料的粘结性能。
 技术问题
传统的处理方法比如等离子体、化学接枝、化学刻蚀虽然在管材表面引入活性基团，增强了管材与其他基体的界面粘结性能，但是它们有不同的缺点，比如对管材本体的损伤，造成其力学性能下降，反应条件苛刻，对设备的要求较高，容易造成环境污染等。因此，寻求新的方法来制备管材具有重要的意义。
 技术解决方案
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，能够提升管材表面的生物相容性、亲水性以及界面粘结性能。
为解决上述技术问题，本发明提供的医用管材的制备方法，包括如下步骤：S1：将左旋多巴进行自聚合反应，得到聚左旋多巴溶液；S2：将聚醚嵌段酰胺管材浸泡在阳离子聚电解质溶液中，使聚醚嵌段酰胺管材表面引入正离子；S3：将步骤S2处理后的聚醚嵌段酰胺管材浸泡在步骤S1制成的聚左旋多巴溶液中，在聚醚嵌段酰胺管材表面附着形成聚左旋多巴涂层；S4：将具有聚左旋多巴涂层的聚醚嵌段酰胺管材置于改性材料溶液中反应，得到涂层改性的聚醚嵌段酰胺管材。
优选地，所述步骤S1包括：将左旋多巴溶解在水中，得到左旋多巴溶液，调节溶液pH值至8.0-9.0，自聚合反应得到聚左旋多巴溶液。
优选地，在所述左旋多巴溶液中加入氢氧化钠、三(羟甲基)氨基甲烷或碳酸钠化合物中的至少一种，调节溶液pH值至8.0-9.0。
优选地，所述步骤S1中自聚合反应时间为16-24小时。
优选地，所述步骤S2中阳离子聚电解质的浓度为1.0-3.0mg/mL。
优选地，所述步骤S2中的阳离子聚电解质溶液中包含氯化钠，所述氯化钠的浓度为1.0-3.0mg/ml。
优选地，所述步骤S2中的阳离子聚电解质溶液为聚二甲基二烯丙基氯化铵溶液或聚丙烯酸钠溶液。
优选地，所述步骤S2和步骤S3中的浸泡时间均为5-20min，浸泡完后再用水清洗以及氮气干燥。
优选地，所述步骤S2和步骤S3循环执行1-8次。
优选地，所述步骤S4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、磷酸胆碱和白蛋白中的至少一种。
优选地，所述步骤S4包括：将具有聚左旋多巴涂层的聚醚嵌段酰胺管材浸泡在改性材料溶液中，调节溶液pH值为8.5-9.0，反应8-24小时，然后水洗得到涂层改性的聚醚嵌段酰胺管材。
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S4中将具有聚左旋多巴涂层的聚醚嵌段酰胺管材分别放入不同浓度的改性材料溶液中，使聚左旋多巴涂层外部具有不同厚度的改性材料涂层。
为解决上述技术问题，本发明还提供了一种医用管材，由上述制备方法制取。
 有益效果
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，通过使用左旋多巴自聚在聚醚嵌段酰胺 (Pebax) 管材表面引入羟基、氨基等活性官能团，然后与改性材料如肝素、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）、白蛋白等发生反应，提高聚醚嵌段酰胺(Pebax)管材的生物相容性、亲水性以及界面粘结性能，并且可以进行规模化批量生产、满足不同产品的需求、简化生产工序、提高产能。
 本发明的实施方式
下面结合实施例对本发明作进一步的描述。
本发明通过使用贻贝类分泌物左旋多巴在聚醚嵌段酰胺(Pebax)管材表面形成涂层，然后通过接枝的方法对涂层进行改性，来提高介入医疗器械精密管材生物相容性、亲水性以及界面粘结性能。
贻贝是一种普遍存在于近海岸尤其是冷水海域的甲壳类动物，它们能够分泌超强粘附蛋白将自己牢固粘附在任何材料表面上，比如金属、玻璃、聚合物及矿物等。该粘附蛋白可以在潮湿的环境中迅速固化，与基体材料形成较强的相互作用，其中，左旋多巴是使贻贝粘性蛋白产生粘附行为的关键。
本发明提供的医用管材的制备方法，使用左旋多巴来提高医用管材的生物相容性、亲水性以及界面粘结性能，包括以下步骤：
步骤S1、左旋多巴的自聚合反应。
将预定量的左旋多巴溶解在预定量的水中，得到左旋多巴溶液，使用碱调节溶液pH值至8.0-9.0，在室温下自聚合反应16-24 h得到聚左旋多巴溶液，碱可以为氢氧化钠、三(羟甲基)氨基甲烷（Tris）或碳酸钠等中的至少一种。
步骤S2、在管材表面引入正离子。
将清洗后的聚醚嵌段酰胺（Pebax）管材浸泡在阳离子聚电解质溶液中5-20 min，然后用水清洗以及氮气干燥。阳离子聚电解质溶液可以为聚二甲基二烯丙基氯化铵(PDDA)溶液或聚丙烯酸钠溶液。阳离子聚电解质溶液中可以包含氯化钠，所述氯化钠的浓度可以为1.0-3.0mg/ml。
步骤S3、管材表面附着聚左旋多巴涂层。
将步骤S2处理后的管材浸泡在步骤S1制成的聚左旋多巴溶液中5-20 min，然后再用水清洗以及氮气干燥。
在该步骤中，由于聚左旋多巴有羧酸负离子，可以与管材表面的正离子发生结合，通过这种方式，聚左旋多巴可以有效地结合在管材表面。并且，由于静电吸附的作用,将聚左旋多巴吸附在管材的表面上,形成一层致密的涂层，从而在管材表面引入大量的活性官能团，如羟基、羧基、氨基。
步骤S4、管材表面聚左旋多巴涂层的改性。
将具有聚左旋多巴涂层的聚醚嵌段酰胺 (Pebax) 管材放入配制好的改性材料溶液中，使用磷酸盐缓冲液调节溶液pH值为8.5-9.0，改性材料选自肝素、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、白蛋白中的至少一种。改性材料可以为肝素，肝素溶液的浓度可以为20-40mg/mL。聚左旋多巴涂层上的活性官能团容易与上述改性材料所带的官能团反应，使聚左旋多巴涂层的外部具有一层改性材料涂层，提高管材的生物学性能。在室温下反应8-24 h后，用蒸馏水清洗、干燥得到涂层改性的聚醚嵌段酰胺（Pebax）管材。另外，由于聚左旋多巴涂层外部的改性材料涂层的厚度与改性材料溶液的浓度有关，可以将具有聚左旋多巴涂层的聚醚嵌段酰胺管材分别放入不同浓度的改性材料溶液中反应，得到具有不同改性材料涂层厚度的聚醚嵌段酰胺管材，满足不同产品的需求。
另外，上述步骤S2和S3可以循环执行，循环执行的次数不同，可以得到表面具有不同聚左旋多巴涂层厚度的聚醚嵌段酰胺 (Pebax) 管材，步骤S2和S3循环重复次数优选为1-8次。
实施例 1将Pebax医疗管材剪成长度15 cm的尺寸，分别用75%乙醇和去离子水清洗管材表面除杂，然后置于真空烘箱至恒重，温度设定为80℃。将左旋多巴溶解在水中，得到左旋多巴溶液，使用碱调节溶液pH值至8.0-9.0，在室温下自聚合反应16-24 h得到聚左旋多巴溶液。碱可以为氢氧化钠、三(羟甲基)氨基甲烷（Tris）或碳酸钠等。将经过清洗的管材浸泡在浓度为1.0mg/mL的聚二甲基二烯丙基氯化铵（PDDA）溶液中5 min，然后用水清洗以及氮气干燥，再将管材浸泡在聚左旋多巴溶液中5min（pH=8.0-9.0，质量体积浓度C=1.0-3.0g/L），然后再用水清洗以及在真空下干燥，如此循环重复上一操作步骤（1-8次），得到不同聚左旋多巴涂层厚度的聚醚嵌段酰胺管材，然后将聚醚嵌段酰胺管材浸泡在配置好的20mg/mL的肝素溶液中（使用磷酸盐缓冲液调节pH=9.0），在室温下反应8-24h，然后水洗得到改性后的聚醚嵌段酰胺管材。
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。
本发明提供的制备方法，能够保证管材的精密度，从而可以进行规模化批量生产，满足不同产品的需求，同时能够提高管材的生物学相容性，并且可以简化生产工序、提高产能。该医用管材可以为低硬链段的热塑性弹性体，如聚醚嵌段酰胺（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。
Figure 953727dest_path_image001
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
其中，溶血率为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。 细胞增殖率为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%，细胞增值率要能达到85%以上，这样才能作为医用管材使用。从表1可以看出，经过改性材料肝素溶液浸泡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）通过层层涂覆聚左旋多巴的方法使管材表面具有聚左旋多巴涂层，该涂层具有大量的活性官能团，因此，容易与改性材料所带的官能团发生化学反应，使聚左旋多巴涂层的外部具有改性材料涂层，提高管材的生物学性能。
（2）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）涂层的厚度可控，有利于调控涂层与管材的粘结力，此外在保留医用高分子管材高韧性及高柔软性的特点上，又赋予了生物相容性和润滑性，能同时满足微创伤介入医疗器械精密管材在临床上的要求。
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 (14)

  1. 一种医用管材的制备方法，其特征在于，包括如下步骤：
    S1：将左旋多巴进行自聚合反应，得到聚左旋多巴溶液；
    S2：将聚醚嵌段酰胺管材浸泡在阳离子聚电解质溶液中，使聚醚嵌段酰胺管材表面引入正离子；
    S3：将步骤S2处理后的聚醚嵌段酰胺管材浸泡在步骤S1制成的聚左旋多巴溶液中，在聚醚嵌段酰胺管材表面附着形成聚左旋多巴涂层；
    S4：将具有聚左旋多巴涂层的聚醚嵌段酰胺管材置于改性材料溶液中反应，得到涂层改性的聚醚嵌段酰胺管材。
  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S1包括：将左旋多巴溶解在水中，得到左旋多巴溶液，调节溶液pH值至8.0-9.0，自聚合反应得到聚左旋多巴溶液。
  3. 如权利要求2所述的医用管材的制备方法，其特征在于，在所述左旋多巴溶液中加入氢氧化钠、三(羟甲基)氨基甲烷或碳酸钠化合物中的至少一种，调节溶液pH值至8.0-9.0。
  4. 如权利要求2所述的医用管材的制备方法，其特征在于，所述步骤S1中自聚合反应时间为16-24小时。
  5. 如权利要求1所述的医用管材的制备方法，其特征在于，所述步骤S2中阳离子聚电解质溶液的浓度为1.0-3.0mg/mL。
  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S2中的阳离子聚电解质溶液中包含氯化钠，所述氯化钠的浓度为1.0-3.0mg/ml。
  7. 如权利要求1、5或6所述的医用管材的制备方法，其特征在于，所述步骤S2中的阳离子聚电解质溶液为聚二甲基二烯丙基氯化铵溶液或聚丙烯酸钠溶液。
  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S2和步骤S3中的浸泡时间均为5-20min，浸泡完后再用水清洗以及氮气干燥。
  9. 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和步骤S3循环执行1-8次。
  10. 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S4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、磷酸胆碱和白蛋白中的至少一种。
  11. 如权利要求10所述的医用管材的制备方法，其特征在于，所述步骤S4包括：将具有聚左旋多巴涂层的聚醚嵌段酰胺管材浸泡在改性材料溶液中，调节溶液pH值为8.5-9.0，反应8-24小时，然后水洗得到涂层改性的聚醚嵌段酰胺管材。
  12. 如权利要求10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。
  13. 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S4中将具有聚左旋多巴涂层的聚醚嵌段酰胺管材分别放入不同浓度的改性材料溶液中，使聚左旋多巴涂层外部具有不同厚度的改性材料涂层。
  14. 一种医用管材，其特征在于，由权利要求1-13任一项所述的医用管材的制备方法制取。
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