技术领域technical field
本发明涉及一种改善生物医用不锈钢装置生物相容性的方法。The invention relates to a method for improving the biocompatibility of biomedical stainless steel devices.
背景技术Background technique
随着现代医学的飞速发展，各种医疗装置广泛地应用各种医疗手段中。各类聚合物医用导管(Catheter)、手术导引线(Guidewires)、金属支架(Stents)和其他非侵入装置的使用极大地丰富了现代医学诊疗手段。然而，现有的装置在临床应用中，依然不同程度地存在感染、凝血和术后组织增生等问题。这些非生物相容性反应直接来源于医用装置表面和生体组分的不可控的相互作用。通过对生物医用装置的表面修饰，在保持原有性能的条件下，改善生物医用装置生物相容性成为现代医疗装置应用中的重要问题。With the rapid development of modern medicine, various medical devices are widely used in various medical methods. The use of various polymer medical catheters (Catheter), surgical guide wires (Guidewires), metal stents (Stents) and other non-invasive devices has greatly enriched the means of modern medical diagnosis and treatment. However, in the clinical application of the existing devices, problems such as infection, blood coagulation and postoperative tissue proliferation still exist to varying degrees. These non-biocompatibility reactions result directly from uncontrolled interactions between medical device surfaces and biological components. Through the surface modification of biomedical devices, improving the biocompatibility of biomedical devices while maintaining the original performance has become an important issue in the application of modern medical devices.
磷脂分子自组装形成具有双层膜的血红细胞膜，细胞生物学研究结果表明，在细胞膜外层带有等量正电荷和负电荷的卵磷脂不会激活内源性凝血途径，所以含有磷脂酰胆碱基团(PC)的表面而被公认为血液相容性良好的生物惰性表面。据此，人们合成了一系列含有PC基团的材料模拟细胞膜外层的卵磷脂层，而MPC分子就是其中合成最多的一种分子。聚氧乙烯(PEG)作为一种高水溶性的生物惰性的柔性大分子也常被用于提高材料的血液相容性，这是因为PEG的这种结构会影响材料与血液界面的微观动力学环境，阻碍血浆蛋白的吸附从而阻止血栓的形成。Phospholipid molecules self-assemble to form a red blood cell membrane with a double membrane. The results of cell biology research show that lecithin with equal positive and negative charges on the outer layer of the cell membrane will not activate the endogenous coagulation pathway, so it contains phosphatidyl bile The surface of the base group (PC) is recognized as a biologically inert surface with good blood compatibility. Accordingly, a series of materials containing PC groups have been synthesized to simulate the lecithin layer of the outer layer of cell membranes, and MPC molecules are the most synthesized molecules among them. Polyoxyethylene (PEG), as a highly water-soluble, biologically inert, flexible macromolecule, is also often used to improve the blood compatibility of materials, because the structure of PEG can affect the microdynamics of the interface between materials and blood. The environment hinders the adsorption of plasma proteins and thus prevents the formation of thrombus.
在目前的研究应用中，人们采用包括涂层、表面光化学接枝、表面臭氧接枝等多种表面技术，对材料表面进行了修饰，将PC基团或者PEG分子引入到材料表面，改善材料的抗凝血、抗感染性，取得了较好的成果。然而，由于这些表面修饰手段普遍存在着溶剂毒性、工艺过程复杂、可调节能力差等弱点，不仅大大限制了材料表面的可设计性，而且无法实现对具有复杂几何外形的医用装置的修饰，导致目前的表面修饰方法多停留在对“材料”的表面修饰，无法形成面对“装置”的生物相容性修饰手段，不能满足医用装置飞速发展的需要。In the current research and application, people use various surface technologies including coating, surface photochemical grafting, surface ozone grafting, etc. to modify the surface of the material, introduce PC groups or PEG molecules into the surface of the material, and improve the surface properties of the material. Anticoagulation, anti-infection, and achieved good results. However, due to the common weaknesses of these surface modification methods, such as solvent toxicity, complicated process, and poor adjustability, not only the designability of the material surface is greatly limited, but also the modification of medical devices with complex geometric shapes cannot be realized, resulting in The current surface modification methods mostly focus on the surface modification of "materials", which cannot form a biocompatible modification method for "device", and cannot meet the needs of the rapid development of medical devices.
发明内容Contents of the invention
本发明的目的是提供一种可应用于具有复杂几何外形的医用装置表面，并显著改善生物医用装置生物相容性的方法。The object of the present invention is to provide a method that can be applied to the surface of medical devices with complex geometric shapes and significantly improve the biocompatibility of biomedical devices.
它是将清洗干净的医用316L不锈钢基材浸入10-20mM含氨基的偶联剂的有机溶剂溶液中反应，反应时间为1-4小时，反应温度为25-40℃，经有机溶剂溶液清洗，氮气吹干后于100～130℃下固化1-4小时；再浸入浓度为5-10mg/ml的磷酸胆碱双键单体单分子或聚氧乙烯功能双键单体单分子溶液中反应，反应时间为2-48小时，反应温度为20～50℃，反应完成后乙醇超声清洗3-5次，氮气吹干后40-80℃下抽真空干燥24-48h。It is to immerse the cleaned medical 316L stainless steel substrate in an organic solvent solution of 10-20mM amino-containing coupling agent for reaction, the reaction time is 1-4 hours, and the reaction temperature is 25-40°C. After cleaning with an organic solvent solution, After blowing dry with nitrogen, cure at 100-130°C for 1-4 hours; then immerse in a single molecule solution of phosphorylcholine double-bond monomer or polyoxyethylene functional double-bond monomer with a concentration of 5-10mg/ml to react. The reaction time is 2-48 hours, and the reaction temperature is 20-50°C. After the reaction is completed, the ethanol is ultrasonically cleaned for 3-5 times, and after being blown dry with nitrogen, it is vacuum-dried at 40-80°C for 24-48h.
本发明的优点是：The advantages of the present invention are:
1)所获的表面具有良好的生物相容性；1) The obtained surface has good biocompatibility;
2)化学结构稳定，能适应人体的内环境；2) The chemical structure is stable and can adapt to the internal environment of the human body;
3)条件温和，操作简单，可工业实现，对具有复杂体型结构的生物医用装置进行涂层修饰；3) The conditions are mild, the operation is simple, and it can be realized industrially, and the coating modification of biomedical devices with complex body structures is carried out;
4)化学接枝使得涂层具有优异的物理机械性能；4) Chemical grafting makes the coating have excellent physical and mechanical properties;
5)有效改善生物医用装置的表面亲水性、润滑性、抗凝血性和生物相容性。5) Effectively improve the surface hydrophilicity, lubricity, anticoagulation and biocompatibility of biomedical devices.
具体实施方式Detailed ways
本发明是将具有良好抗凝血性的磷酸胆碱或聚氧乙烯功能基的含双键单体通过化学加成反应固定到生物医用装置的表面的方法，将清洗干净的医用316L不锈钢基材浸入10-20mM含氨基的偶联剂的有机溶剂溶液中反应，反应时间为1-4小时，反应温度为25-40℃，经有机溶剂溶液清洗，氮气吹干后于100～130℃下固化1-4小时；再浸入浓度为5-10mg/ml的磷酸胆碱双键单体单分子或聚氧乙烯功能双键单体单分子溶液中反应，反应时间为2-48小时，反应温度为20～50℃，反应完成后乙醇超声清洗3-5次，氮气吹干后40-80℃下抽真空干燥24-48h。其中磷酸胆碱双键单体单分子为甲基丙烯酸磷酸胆碱酯，分子结构式为CH2＝C(CH3)COO-CH2CH2OOPOOCH2CH2N(CH3)3；或丙烯酸磷酸胆碱酯，分子结构式为CH2＝CHCOO-CH2CH2OOPOOCH2CH2N(CH3)3。聚氧乙烯功能双键单体单分子为甲基丙烯酸聚氧乙烯酯，分子结构式为CH2＝C(CH3)COO-[CH2CH2O]n-OH，其中n＝6-200，或丙烯酸聚氧乙烯酯，分子结构式为CH2＝CHCOO-[CH2CH2O]n-OH，其中n＝6-200。磷酸胆碱双键单体单分子溶液的溶剂为乙醇或水。聚氧乙烯功能双键单体单分子溶液有机溶剂或水。有机溶剂为甲苯或乙醇。The present invention is a method for fixing double bond-containing monomers with good anticoagulant properties, such as phosphorylcholine or polyoxyethylene functional group, to the surface of biomedical devices through chemical addition reaction. The cleaned medical 316L stainless steel substrate is immersed in Reaction in organic solvent solution of 10-20mM amino-containing coupling agent, reaction time is 1-4 hours, reaction temperature is 25-40°C, washed with organic solvent solution, dried with nitrogen, and cured at 100-130°C for 1 -4 hours; then immerse in the phosphorylcholine double bond monomer single molecule or polyoxyethylene functional double bond monomer single molecule solution with a concentration of 5-10mg/ml to react, the reaction time is 2-48 hours, and the reaction temperature is 20 ~50°C. After the reaction is completed, the ethanol is ultrasonically cleaned for 3-5 times, and then dried with nitrogen and then vacuum-dried at 40-80°C for 24-48h. Among them, the single molecule of phosphorylcholine double bond monomer is phosphorylcholine methacrylate, and the molecular structure formula is CH2 =C(CH3 )COO-CH2 CH2 OOPOOCH2 CH2 N(CH3 )3 ; or phosphoric acid acrylate Choline ester, the molecular structure formula is CH2 =CHCOO-CH2 CH2 OOPOOCH2 CH2 N(CH3 )3 . The single molecule of polyoxyethylene functional double bond monomer is polyoxyethylene methacrylate, and its molecular structure is CH2 =C(CH3 )COO-[CH2 CH2 O]n -OH, where n=6-200, Or polyoxyethylene acrylate, the molecular formula is CH2 =CHCOO-[CH2 CH2 O]n -OH, wherein n=6-200. The solvent of the monomolecular solution of phosphorylcholine double bond monomer is ethanol or water. Polyoxyethylene functional double bond monomer single molecule solution organic solvent or water. The organic solvent is toluene or ethanol.
实施例1：Example 1:
将清洗干净的医用316L不锈钢基材浸入10mM γ-氨丙基三乙氧基硅烷，分子结构式为(CH3CH2O)3SiCH2CH2CH2NH2的甲苯溶液反应，反应时间3h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为5mg/ml的甲基丙烯酸磷酸胆碱酯的乙醇溶液中，25℃保持反应24h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.13×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 10mM γ-aminopropyltriethoxysilane, the molecular structure is (CH3 CH2 O)3 SiCH2 CH2 CH2 NH2 toluene solution reaction, reaction time 3h, The reaction temperature is 25°C, washed with toluene and ethanol in sequence, dried with nitrogen, and cured at 110°C for 1 hour. Then immerse in an ethanol solution of phosphorylcholine methacrylate with a concentration of 5 mg/ml, and keep reacting at 25°C for 24h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.13×104 /mm2 .
实施例2Example 2
将清洗干净的医用316L不锈钢基材浸入20mM γ-氨丙基三乙氧基硅烷，分子结构式为(CH3CH2O)3SiCH2CH2CH2NH2的甲苯溶液反应，反应时间1h，反映温度30℃，经甲苯、乙醇依次清洗，氮气吹干后于130℃下固化1h。再浸入浓度为10mg/ml的甲基丙烯酸磷酸胆碱酯的水溶液中，25℃保持反应48h，反应完成后乙醇超声清洗3次，氮气吹干后70℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.15×104个/mm2。The cleaned medical 316L stainless steel substrate was immersed in 20mM γ-aminopropyltriethoxysilane, and the molecular structure was (CH3 CH2 O)3 SiCH2 CH2 CH2 NH2 in toluene solution for reaction, the reaction time was 1h, The reaction temperature is 30°C, washed with toluene and ethanol in sequence, dried with nitrogen, and cured at 130°C for 1 hour. Then immerse in an aqueous solution of phosphorylcholine methacrylate with a concentration of 10mg/ml, and keep reacting at 25°C for 48h. After the reaction is completed, ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 70°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.15×104 /mm2 .
实施例3Example 3
将清洗干净的医用316L不锈钢基材浸入15mM γ-氨丙基甲基二乙氧基硅烷，分子结构式为(CH3CH2O)2CH3SiCH2CH2CH2NH2的乙醇溶液中反应，反应时间2h，反映温度40℃，经甲苯、乙醇依次清洗，氮气吹干后于120℃下固化4h。再浸入浓度为7mg/ml的甲基丙烯酸磷酸胆碱酯乙醇溶液中，25℃保持反应48h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于0.93×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in 15mM γ-aminopropylmethyldiethoxysilane, the molecular formula is (CH3 CH2 O)2 CH3 SiCH2 CH2 CH2 NH2 ethanol solution for reaction , The reaction time is 2h, the reaction temperature is 40°C, washed with toluene and ethanol in turn, dried with nitrogen, and cured at 120°C for 4h. Then immerse in the ethanol solution of phosphorylcholine methacrylate with a concentration of 7mg/ml, and keep the reaction at 25°C for 48h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 0.93×104 /mm2 .
实施例4Example 4
将清洗干净的医用316L不锈钢基材浸入10mM γ-氨丙基三乙氧基硅烷的乙醇溶液反应，反应时间3h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为5mg/ml的甲基丙烯酸磷酸胆碱酯的乙醇溶液中，30℃保持反应24h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.20×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in 10mM ethanol solution of γ-aminopropyltriethoxysilane for reaction. The reaction time is 3h, and the reaction temperature is 25°C. After washing with toluene and ethanol in sequence, blow dry with nitrogen and store at 110°C. Cured for 1h. Then immerse in an ethanol solution of phosphorylcholine methacrylate with a concentration of 5mg/ml, and keep reacting at 30°C for 24h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.20×104 /mm2 .
实施例5Example 5
将清洗干净的医用316L不锈钢基材浸入15mM γ-氨丙基甲基二甲氧基硅烷，分子结构式为(CH3O)2CH3SiCH2CH2CH2NH2的乙醇溶液反应，反应时间3h，反映温度30℃，经甲苯、乙醇依次清洗，氮气吹干后于120℃下固化1h。再浸入浓度为5mg/ml的甲基丙烯酸磷酸胆碱酯的水溶液中，40℃保持反应12h，反应完成后乙醇超声清洗5次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.03×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 15mM γ-aminopropylmethyldimethoxysilane, the molecular structure is (CH3 O)2 CH3 SiCH2 CH2 CH2 NH2 ethanol solution reaction, the reaction time 3h, the reaction temperature is 30°C, washed with toluene and ethanol in turn, dried with nitrogen, and cured at 120°C for 1h. Then immerse in an aqueous solution of phosphorylcholine methacrylate with a concentration of 5mg/ml, and keep reacting at 40°C for 12h. After the reaction is completed, it is ultrasonically cleaned with ethanol for 5 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.03×104 /mm2 .
实施例6Example 6
将清洗干净的医用316L不锈钢基材浸入20mM γ-氨丙基三乙氧基硅烷甲苯溶液反应，反应时间3h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为5mg/ml的丙烯酸磷酸胆碱酯的乙醇溶液中，25℃保持反应2h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.23×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in 20mM γ-aminopropyltriethoxysilane toluene solution for reaction, the reaction time is 3h, the reaction temperature is 25°C, washed with toluene and ethanol in sequence, dried with nitrogen, and cured at 110°C 1h. Then immerse in an ethanol solution of phosphorylcholine acrylate with a concentration of 5 mg/ml, and keep reacting at 25°C for 2h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.23×104 /mm2 .
实施例7Example 7
将清洗干净的医用316L不锈钢基材浸入10mM N-β(氨乙基)-γ-氨丙基甲基二乙氧基硅烷，分子结构式为(CH3CH2O)2CH3SiCH2CH2CH2NHCH2CH2NH2的甲苯溶液反应，反应时间3h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为8mg/ml的丙烯酸磷酸胆碱酯的水溶液中，30℃保持反应12h，反应完成后乙醇超声清洗5次，氮气吹干后60℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.15×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 10mM N-β(aminoethyl)-γ-aminopropylmethyldiethoxysilane, the molecular formula is (CH3 CH2 O)2 CH3 SiCH2 CH2 CH2 NHCH2 CH2 NH2 was reacted in toluene solution, the reaction time was 3 hours, the reaction temperature was 25°C, washed with toluene and ethanol in sequence, dried with nitrogen, and solidified at 110°C for 1 hour. Then immerse in an aqueous solution of phosphorylcholine acrylate with a concentration of 8mg/ml, and keep reacting at 30°C for 12h. After the reaction is completed, it is ultrasonically cleaned with ethanol for 5 times, blown dry with nitrogen, and then vacuum-dried at 60°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.15×104 /mm2 .
实施例8Example 8
将清洗干净的医用316L不锈钢基材浸入15mM γ-氨丙基三乙氧基硅烷的乙醇溶液反应，反应时间3h，反映温度40℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为10mg/ml的丙烯酸磷酸胆碱酯的乙醇溶液中，50℃保持反应2h，反应完成后乙醇超声清洗4次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.14×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in 15mM ethanol solution of γ-aminopropyltriethoxysilane for reaction, the reaction time is 3h, the reaction temperature is 40°C, washed with toluene and ethanol in sequence, blown dry with nitrogen, and then placed at 110°C Cured for 1h. Then immerse in an ethanol solution of phosphorylcholine acrylate with a concentration of 10mg/ml, and keep reacting at 50°C for 2h. After the reaction is completed, the ethanol is ultrasonically cleaned 4 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.14×104 /mm2 .
实施例9Example 9
将清洗干净的医用316L不锈钢基材浸入10mM N-β(氨乙基)-γ-氨丙基三甲氧基硅烷，分子结构式为(CH3O)3SiCH2CH2CH2NHCH2CH2NH2的甲苯溶液中反应，反应时间4h，反映温度30℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为5mg/ml的丙烯酸磷酸胆碱酯的乙醇溶液中，25℃保持反应48h，反应完成后乙醇超声清洗3次，氮气吹干后80℃下抽真空干燥36h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.01×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 10mM N-β(aminoethyl)-γ-aminopropyltrimethoxysilane, the molecular structure is (CH3 O)3 SiCH2 CH2 CH2 NHCH2 CH2 NH2 in toluene solution, reaction time 4h, reaction temperature 30°C, washed with toluene and ethanol in turn, dried with nitrogen, and solidified at 110°C for 1h. Then immerse in an ethanol solution of phosphorylcholine acrylate with a concentration of 5mg/ml, and keep reacting at 25°C for 48h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 80°C for 36h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.01×104 /mm2 .
实施例10Example 10
将清洗干净的医用316L不锈钢基材浸入10mM γ-氨丙基三乙氧基硅烷，甲苯溶液中反应，反应时间1h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于130℃下固化1h。再浸入浓度为10mg/ml的丙烯酸磷酸胆碱酯的乙醇溶液中，25℃保持反应24h，反应完成后乙醇超声清洗3次，氮气吹干后80℃下抽真空干燥48h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.03×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in 10mM γ-aminopropyltriethoxysilane and toluene solution for reaction. The reaction time is 1h, and the reaction temperature is 25°C. After washing with toluene and ethanol in sequence, dry it with nitrogen and place it at 130°C. Under curing 1h. Then immerse in the ethanol solution of phosphorylcholine acrylate with a concentration of 10mg/ml, and keep the reaction at 25°C for 24h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 80°C for 48h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.03×104 /mm2 .
实施例11Example 11
将清洗干净的医用316L不锈钢基材浸入12mM γ-氨丙基三乙氧基硅烷的甲苯溶液反应，反应时间1h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为5mg/ml的甲基丙烯酸聚氧乙烯酯(n＝6)的水溶液中，25℃保持反应24h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.31×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in 12mM γ-aminopropyltriethoxysilane toluene solution for reaction, the reaction time is 1h, the reaction temperature is 25°C, washed with toluene and ethanol in sequence, dried with nitrogen, and placed at 110°C Cured for 1h. Then immerse in an aqueous solution of polyoxyethylene methacrylate (n=6) with a concentration of 5 mg/ml, and keep the reaction at 25°C for 24h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, and after being blown dry with nitrogen, it is vacuum-dried at 40°C for 24h. . The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the number of adhered platelets was lower than 1.31×104 /mm2 .
实施例12Example 12
将清洗干净的医用316L不锈钢基材浸入10mM N-(β-氨乙基)-γ-氨丙基三乙氧基硅烷，分子结构式为(CH3CH2O)3SiCH2CH2CH2NHCH2CH2NH2的乙醇溶液中反应，反应时间2h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化3h。再浸入浓度为10mg/ml的甲基丙烯酸聚氧乙烯酯(n＝50)的水溶液中，30℃保持反应48h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.33×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 10mM N-(β-aminoethyl)-γ-aminopropyltriethoxysilane, the molecular formula is (CH3 CH2 O)3 SiCH2 CH2 CH2 NHCH React in ethanol solution of2 CH2 NH2, reaction time 2h, reaction temperature 25°C, wash with toluene and ethanol in turn, dry with nitrogen, and solidify at 110°C for 3h. Then immerse in an aqueous solution of polyoxyethylene methacrylate (n=50) with a concentration of 10mg/ml, and keep the reaction at 30°C for 48h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, and after being blown dry with nitrogen, it is vacuum-dried at 40°C for 24h. . The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.33×104 /mm2 .
实施例13Example 13
将清洗干净的医用316L不锈钢基材浸入15mM γ-氨丙基三乙氧基硅烷的甲苯溶液中反应，反应时间4h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为10mg/ml的甲基丙烯酸聚氧乙烯酯(n＝200)的水溶液中，25℃保持反应48h，反应完成后乙醇超声清洗3次，氮气吹干后70℃下抽真空干燥48h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.29×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in a toluene solution of 15mM γ-aminopropyltriethoxysilane for reaction, the reaction time is 4h, and the reaction temperature is 25°C, washed with toluene and ethanol in sequence, dried with nitrogen, and then placed at 110°C Under curing 1h. Then immerse in an aqueous solution of polyoxyethylene methacrylate (n=200) with a concentration of 10mg/ml, and keep the reaction at 25°C for 48h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, and then dried in nitrogen and vacuum-dried at 70°C for 48h. . The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.29×104 /mm2 .
实施例14Example 14
将清洗干净的医用316L不锈钢基材浸入20mM γ-氨丙基三乙氧基硅烷的乙醇溶液中反应，反应时间4h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于130℃下固化1h。再浸入浓度为5mg/ml的丙烯酸聚氧乙烯酯(n＝10)的水溶液中，25℃保持反应2h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.35×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate in the ethanol solution of 20mM γ-aminopropyltriethoxysilane for reaction, the reaction time is 4h, the reaction temperature is 25°C, washed with toluene and ethanol in sequence, dried with nitrogen, and placed at 130°C Under curing 1h. Then immersed in an aqueous solution of polyoxyethylene acrylate (n=10) with a concentration of 5 mg/ml, and kept reacting for 2 hours at 25°C. After the reaction was completed, it was ultrasonically cleaned three times with ethanol, blown dry with nitrogen, and then vacuum-dried at 40°C for 24 hours. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.35×104 /mm2 .
实施例15Example 15
将清洗干净的医用316L不锈钢基材浸入15mM γ-二乙烯三氨丙基甲基二甲氧基硅烷，分子结构式为(CH3O)2CH3Si(CH2)3NHCH2CH2NHCH2CH2NH2的甲苯溶液中反应，反应时间3h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于120℃下固化1h。再浸入浓度为7mg/ml的丙烯酸聚氧乙烯酯(n＝70)的水溶液中，25℃保持反应24h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥48h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.27×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 15mM γ-diethylenetriaminopropylmethyldimethoxysilane, the molecular formula is (CH3 O)2 CH3 Si(CH2 )3 NHCH2 CH2 NHCH2 React in CH2 NH2 toluene solution, reaction time 3h, reaction temperature 25°C, wash with toluene and ethanol in sequence, blow dry with nitrogen, and solidify at 120°C for 1h. Then immerse in an aqueous solution of polyoxyethylene acrylate (n=70) with a concentration of 7mg/ml, keep the reaction at 25°C for 24h, after the reaction is completed, wash with ethanol ultrasonically for 3 times, blow dry with nitrogen, and then vacuum dry at 40°C for 48h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.27×104 /mm2 .
实施例16Example 16
将清洗干净的医用316L不锈钢基材浸入10mM N-(β-氨乙基)-γ-氨丙基甲基二甲氧基硅烷，分子结构式为(CH3O)2CH3Si(CH2)3NHCH2CH2NH2的甲苯溶液中反应，反应时间1h，反映温度30℃，经甲苯、乙醇依次清洗，氮气吹干后于130℃下固化1h。再浸入浓度为10mg/ml的丙烯酸聚氧乙烯酯(n＝150)的水溶液中，25℃保持反应48h，反应完成后乙醇超声清洗5次，氮气吹干后80℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于1.21×104个/mm2。Immerse the cleaned medical 316L stainless steel substrate into 10mM N-(β-aminoethyl)-γ-aminopropylmethyldimethoxysilane, the molecular structure is (CH3 O)2 CH3 Si(CH2 )3 NHCH2 CH2 NH2 reacted in toluene solution, reaction time 1h, reaction temperature 30°C, washed with toluene and ethanol in sequence, dried with nitrogen, and solidified at 130°C for 1h. Then immerse in an aqueous solution of polyoxyethylene acrylate (n=150) with a concentration of 10 mg/ml, and keep the reaction at 25°C for 48h. After the reaction is completed, the ethanol is ultrasonically cleaned for 5 times, blown dry with nitrogen, and then vacuum-dried at 80°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 1.21×104 /mm2 .
实施例17Example 17
将清洗干净的激光雕刻316L不锈钢冠脉支架浸入10mM γ-氨丙基三乙氧基硅烷的甲苯溶液反应，反应时间3h，反映温度25℃，经甲苯、乙醇依次清洗，氮气吹干后于110℃下固化1h。再浸入浓度为5mg/ml的甲基丙烯酸磷酸胆碱酯的乙醇溶液中，25℃保持反应24h，反应完成后乙醇超声清洗3次，氮气吹干后40℃下抽真空干燥24h。所得材料表面性质通过接触角和XPS表征。体外全血实验显示，无血栓形成，血小板粘附实验表明血小板粘附数量低于0.85×104个/mm2。The cleaned laser-engraved 316L stainless steel coronary stent was immersed in a toluene solution of 10mM γ-aminopropyltriethoxysilane for reaction. The reaction time was 3 hours, and the reaction temperature was 25°C. It was washed with toluene and ethanol in sequence, and dried with nitrogen at 110°C. Cure at 1h for 1h. Then immerse in an ethanol solution of phosphorylcholine methacrylate with a concentration of 5 mg/ml, and keep reacting at 25°C for 24h. After the reaction is completed, the ethanol is ultrasonically cleaned for 3 times, blown dry with nitrogen, and then vacuum-dried at 40°C for 24h. The surface properties of the obtained materials were characterized by contact angle and XPS. The whole blood test in vitro showed no thrombus formation, and the platelet adhesion test showed that the platelet adhesion number was lower than 0.85×104 /mm2 .
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| CNB2005100506758ACN100345601C (en) | 2005-07-12 | 2005-07-12 | Method for improving biocompatibility of biological medical stainless steel device |
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