CN113041408A - 一种新型生物可降解心血管涂层支架的制备方法 - Google Patents

一种新型生物可降解心血管涂层支架的制备方法 Download PDF

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CN113041408A
CN113041408A CN201911374282.0A CN201911374282A CN113041408A CN 113041408 A CN113041408 A CN 113041408A CN 201911374282 A CN201911374282 A CN 201911374282A CN 113041408 A CN113041408 A CN 113041408A
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李瑞瑞
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Abstract

本发明一种新型生物可降解心血管涂层支架的制备方法涉及心血管支架制备领域，具体涉及一种新型生物可降解心血管涂层支架的制备方法，包括以下步骤：肝素化材料的合成，在脱保护聚合物加入四氢呋喃溶解，同时加入有机溶剂搅拌溶解，再将肝素钠溶解在水中，接着加入HCl，将pH值调节到4～5，将两者混合，在4℃下搅拌反应24h；本发明以二环己基碳二亚胺为偶联剂，通过共价键成功的将肝素接枝到吗啉二酮衍生物与聚乳酸共聚物材料上，并这种材料喷涂到心血管金属裸支架上，表面光滑，扩张后无撕裂。这种材料具有很好的生物相容性，无血栓和再狭窄情况的发生。本发明的产物可以作为药物洗脱支架的良好载体材料，且有着广阔的应用前景。

Description

一种新型生物可降解心血管涂层支架的制备方法
技术领域
本发明涉及心血管支架制备领域，具体涉及一种新型生物可降解心血管涂层支架的制备方法。
背景技术
冠心病已成为危害世界人民健康最常见、最严重的疾病之一。介入治疗是目前治疗冠心病的最有效方法之一，但术后靶血管的再狭窄却严重影响了其远期疗效。随着2000年药物洗脱支架的问世，介入术后再狭窄得到了显著的控制，目前的药物支架可使再狭窄率下降到5％。即便如此，由于现今药物支架的载体材料大都是不可降解的聚合物材料，如聚甲基丙烯酸丁酯；聚乙烯醋酸酯聚羟基苯乙烯、异丁烯、羟基苯乙烯的嵌断共聚物等。经过长时间的人体腐蚀，材料本身会老化、脱落，就会在血管组织内形成小块，从而可能引起晚期的不良反应。而如果采用生物可降解的材料作为药物载体材料，那么就有可能减少晚期不良反应的出现。
肝素是一种非常有效的抑制血栓形成的药物。许多研究证明，它可以用来改性一些材料的抗凝血性能。以聚乳酸端基为可反应基团，成功共价连接了肝素，但是由于受到聚乳酸端基数量的限制，无法大量的连接肝素。
发明内容
本发明目的在于提供一种新型生物可降解心血管涂层支架的制备方法，这种材料喷涂到心血管金属裸支架上，表面光滑，扩张后无撕裂。这种材料具有很好的生物相容性，无血栓和再狭窄情况的发生。本发明的产物可以作为药物洗脱支架的良好载体材料，且有着广阔的应用前景。
本发明一种新型生物可降解心血管涂层支架的制备方法，其特征在于，包括以下步骤：
第一步，肝素化材料的合成，在脱保护聚合物加入四氢呋喃溶解，同时加入有机溶剂搅拌溶解，再将肝素钠溶解在水中，接着加入HCl，将pH值调节到4～5，将两者混合，在4℃下搅拌反应24h，反应结束后，滤去不溶物，在过量的石油醚中沉淀，接枝药物的聚合物，最后在室温下，真空干燥24h，得到混合肝素的聚合物材料，将得到的部分产物在蒸馏水中搅拌20min，去除未反应的肝素钠，在常温下干燥24h，得到肝素化聚合物材料；
第二步，取0.5g肝素化聚合物材料和混合肝素的聚合物材料，并在混合肝素的聚合物材料中加入15％的肝素钠，肝素化聚合物材料和混合肝素的聚合物材料分别溶解在10mL的四氢呋哺中，等完全溶解之后，将溶液倒入培养皿中，然后将溶液在计算机控制的喷涂设备上对金属裸支架进行喷涂。
优选地，在混合肝素的聚合物材料中加入的肝素钠的重量百分比为15％。
优选地，第一步中脱保护聚合物为0.8g，四氢呋喃为40ml。
优选地，第一部中肝素钠为0.2g溶解在4mL水中。
优选地，有机溶剂为二环己基碳二亚胺。
本发明以二环己基碳二亚胺为偶联剂，通过共价键成功的将肝素接枝到吗啉二酮衍生物与聚乳酸共聚物材料上，并这种材料喷涂到心血管金属裸支架上，表面光滑，扩张后无撕裂。这种材料具有很好的生物相容性，无血栓和再狭窄情况的发生。本发明的产物可以作为药物洗脱支架的良好载体材料，且有着广阔的应用前景。
具体实施方式
实施例一
本发明一种新型生物可降解心血管涂层支架的制备方法，包括以下步骤：
第一步，肝素化材料的合成，在脱保护聚合物加入四氢呋喃溶解，同时加入有机溶剂搅拌溶解，再将肝素钠溶解在水中，接着加入HCl，将pH值调节到4～5，将两者混合，在4℃下搅拌反应24h，反应结束后，滤去不溶物，在过量的石油醚中沉淀，接枝药物的聚合物，最后在室温下，真空干燥24h，得到混合肝素的聚合物材料，将得到的部分产物在蒸馏水中搅拌20min，去除未反应的肝素钠，在常温下干燥24h，得到肝素化聚合物材料；
第二步，取0.5g肝素化聚合物材料和混合肝素的聚合物材料，并在混合肝素的聚合物材料中加入15％的肝素钠，肝素化聚合物材料和混合肝素的聚合物材料分别溶解在10mL的四氢呋哺中，等完全溶解之后，将溶液倒入培养皿中，然后将溶液在计算机控制的喷涂设备上对金属裸支架进行喷涂。
在混合肝素的聚合物材料中加入的肝素钠的重量百分比为15％。
实施例二
本发明一种新型生物可降解心血管涂层支架的制备方法，其特征在于，包括以下步骤：
第一步，肝素化材料的合成，在脱保护聚合物加入四氢呋喃溶解，同时加入有机溶剂搅拌溶解，再将肝素钠溶解在水中，接着加入HCl，将pH值调节到4～5，将两者混合，在4℃下搅拌反应24h，反应结束后，滤去不溶物，在过量的石油醚中沉淀，接枝药物的聚合物，最后在室温下，真空干燥24h，得到混合肝素的聚合物材料，将得到的部分产物在蒸馏水中搅拌20min，去除未反应的肝素钠，在常温下干燥24h，得到肝素化聚合物材料；
第二步，取0.5g肝素化聚合物材料和混合肝素的聚合物材料，并在混合肝素的聚合物材料中加入15％的肝素钠，肝素化聚合物材料和混合肝素的聚合物材料分别溶解在10mL的四氢呋哺中，等完全溶解之后，将溶液倒入培养皿中，然后将溶液在计算机控制的喷涂设备上对金属裸支架进行喷涂。
在混合肝素的聚合物材料中加入的肝素钠的重量百分比为15％。
第一步中脱保护聚合物为0.8g，四氢呋喃为40ml。
第一部中肝素钠为0.2g溶解在4mL水中。
有机溶剂为二环己基碳二亚胺。
本发明以二环己基碳二亚胺为偶联剂，通过共价键成功的将肝素接枝到吗啉二酮衍生物与聚乳酸共聚物材料上，并这种材料喷涂到心血管金属裸支架上，表面光滑，扩张后无撕裂。这种材料具有很好的生物相容性，无血栓和再狭窄情况的发生。本发明的产物可以作为药物洗脱支架的良好载体材料，且有着广阔的应用前景。

Claims (5)

1.一种新型生物可降解心血管涂层支架的制备方法，其特征在于，包括以下步骤：
第一步，肝素化材料的合成，在脱保护聚合物加入四氢呋喃溶解，同时加入有机溶剂搅拌溶解，再将肝素钠溶解在水中，接着加入HCl，将pH值调节到4～5，将两者混合，在4℃下搅拌反应24h，反应结束后，滤去不溶物，在过量的石油醚中沉淀，接枝药物的聚合物，最后在室温下，真空干燥24h，得到混合肝素的聚合物材料，将得到的部分产物在蒸馏水中搅拌20min，去除未反应的肝素钠，在常温下干燥24h，得到肝素化聚合物材料；
第二步，取0.5g肝素化聚合物材料和混合肝素的聚合物材料，并在混合肝素的聚合物材料中加入15％的肝素钠，肝素化聚合物材料和混合肝素的聚合物材料分别溶解在10mL的四氢呋哺中，等完全溶解之后，将溶液倒入培养皿中，然后将溶液在计算机控制的喷涂设备上对金属裸支架进行喷涂。
2.如权利要求1所述一种新型生物可降解心血管涂层支架的制备方法，其特征在于，所述在混合肝素的聚合物材料中加入的肝素钠的重量百分比为15％。
3.如权利要求2所述一种新型生物可降解心血管涂层支架的制备方法，其特征在于，所述第一步中脱保护聚合物为0.8g，四氢呋喃为40ml。
4.如权利要求3所述一种新型生物可降解心血管涂层支架的制备方法，其特征在于，所述第一部中肝素钠为0.2g溶解在4mL水中。
5.如权利要求1所述一种新型生物可降解心血管涂层支架的制备方法，其特征在于，所述有机溶剂为二环己基碳二亚胺。
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CN115707489A (zh) * 2022-10-29 2023-02-21 金傅(北京)医疗科技有限公司 一种能够防止肉芽组织增生的加药方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115707489A (zh) * 2022-10-29 2023-02-21 金傅(北京)医疗科技有限公司 一种能够防止肉芽组织增生的加药方法

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