CN112891640B - 一种Zn-Mg系锌合金血管支架及其制备方法 - Google Patents
一种Zn-Mg系锌合金血管支架及其制备方法 Download PDFInfo
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Abstract
本发明提供了一种Zn‑Mg系锌合金血管支架及其制备方法，所述锌合金血管支架由内部的锌合金基体和外层的可降解涂层构成，所述锌合金基体由Zn、Mg、Li和Mn构成，质量百分比组成为4‑11％Mg，0.15‑0.35％Li，0.7‑1.0％Mn，余量为Zn和不可避免的杂质。本发明所述的锌合金血管支架的力学性质符合医用植入体材料的强度和韧性的要求，无毒，可在人体环境下吸收，能避免二次手术给患者带来的痛苦；所述支架降解分步进行，既保证降解过程中材料的力学性能，又使降解速率和血管支架服役时间相匹配，从而达到可控降解的目的。
Description
技术领域
本发明涉及医用植入材料领域，特别涉及一种Zn-Mg系锌合金血管支架及其制备方法。
背景技术
人体内可降解医用材料正在成为研究和开发的重点，其中可降解高分子材料、纯铁及铁基合金、纯镁及镁基合金是近年研究最为深入的材料。可降解高分子材料强度过低，在临床使用过程中经常会发生断裂等事故，临床适用性受到极大限制。纯铁和铁基合金强度和韧性远高于高分子材料，但是铁降解速度太慢，完全降解可能长达数年。更为严重的是，铁降解过程中生成的铁锈状物质体积膨胀了数倍，并有明显的迁移趋势。纯镁及镁基合金的降解产物无毒、可降解，但其耐蚀性非常差，在人体内很快就会被降解，无法提供足够的力学支撑时间。
腐蚀行为研究表明，与镁、铁相比，锌可能更适宜用作可降解植入材料。锌离子是人体必须的营养元素，参与人体很多的新陈代谢活动，美国临床创新机构推荐人体每天必须摄入2.5到6.4毫克的锌，成年人每天大约摄入300毫克锌，才可能会有一定的毒性反应。研究还发现，锌离子在人体组织中的运输非常迅速，因此锌基可降解植入器械附近不会出现锌富集、细胞毒性或坏死。但是纯Zn的力学性能较差，抗压强度小于20MPa，延伸率仅为0.2％，远远达不到临床的需求，而植入性医疗器械(如骨板骨钉、心脏冠脉支架、外周血管支架等)要求材料在服役期间能够具有足够的力学性能。合金化是提高锌力学性能的有效方法和主要手段，因此，有必要提供一种腐蚀降解速率适宜，机械强度足够的锌合金血管支架。
发明内容
本发明提供了一种Zn-Mg系锌合金血管支架及其制备方法，其目的是为了解决现有植入型锌合金无法兼顾降解速率和机械强度的问题。
为了达到上述目的，本发明的提供了一种Zn-Mg系锌合金血管支架，所述锌合金血管支架由内部的锌合金基体和外层的可降解涂层构成，所述锌合金基体由Zn、Mg、Li和Mn构成，质量百分比组成为6-9％Mg，0.05-0.25％Li，0.5-0.9％Mn，余量为Zn和不可避免的杂质。
进一步的，所述可降解涂层包括高分子材料涂层、陶瓷涂层和药物涂层中的一种或多种。
进一步的，所述高分子材料涂层为聚己酸内酯、聚乳酸、聚羟基戊酸酯、L-聚乳酸、聚氰基丙烯酸酯、丝素蛋白和壳聚糖中的一种或多种；所述陶瓷涂层为羟基磷灰石、磷酸三钙和磷酸氧四钙中的一种或多种；所述药物涂层为负载骨形成蛋白、血管内皮细胞生长因子、辛伐他汀、雷帕霉素、紫杉醇和万古霉素中的一种或多种。
进一步的，所述可降解涂层的厚度为0.01－5mm。
本申请还提供了一种Zn-Mg系锌合金血管支架的制备方法，包括如下步骤：
一、按照锌合金组成进行配料、熔化，再经搅拌、静置和浇注，得到Zn-Mg系锌合金铸锭；
二、将所得锌合金铸锭依次经过外层切削、旋锻、挤出、拉拔和退火，得到具有超塑性特征的锌合金圆柱棒材；
三、将所得锌合金圆柱棒材进行钻孔机械加工、常温拉拔、激光雕刻、化学抛光、涂覆涂层，得到所述的Zn-Mg系锌合金血管支架。
进一步的，所述步骤一中搅拌速率为500-1500r/min，搅拌时间为5-10min。
进一步的，所述步骤一得到的锌合金铸锭为外径40mm*80mm。
进一步的，所述步骤二得到的锌合金棒材外径为15mm。
进一步的，所述步骤三中钻孔机械加工的钻孔内径为12mm。
进一步的，所述步骤三中常温拔拉工艺采用带芯减壁减径拉拔，得到外径2-2.5mm，壁厚0.15-0.20mm的锌合金管材。
本发明的方法利用Zn合金易于腐蚀的特点，选择了Zn-Mg系合金作为可降解材料应用于血管支架。本发明的Zn-Mg系合金的力学性质符合血管支架的强度和韧性的要求，同时又可体内降解，不仅可以克服医用高分子材料强度低和316L不锈钢、钛及钛合金等传统医用金属材料不降解的弱点，还可以克服镁及镁合金降解速率过快导致植入体内力学性能丧失的缺陷，作到兼具有“可生物腐蚀降解特性”和“适宜的腐蚀速率保证提供长期有效的力学支撑”双重特性。
镁在人体中释放出的Mg2+能促进成骨细胞的生长、增殖及分化，具有良好的骨诱导效应。但是，镁在体内是可降解金属，但是其活性很高，在体内降解快，在降解时也会产生氢气，形成气泡，导致愈合和炎症等问题。锌也是可降解的，但速率较慢。现有技术提供了一种含有Mg15.5-48.5wt.％的锌镁合金，用以协调锌和镁的降解性，锌镁合金在体液中的降解速率适宜，既克服了镁降解快，产生氢气泡的问题，也克服了锌降解偏慢，影响骨生长的问题。然而，添加如此大量的镁明显增加了生产成本；而Mn、Li等常作为合金元素少量地添加到锌合金中便可以实现锌合金降解速率的控制，并可以改善锌合金的强度、塑性以及耐腐蚀性。
通过研究Zn基合金相图，发现当Mn含量低于0.5％时，合金的强度提高不明显，当Mn含量超过0.9％时，合金的凝固组织中会出现大量形状不规则的MnZn13第二相颗粒，MnZn13第二相颗粒链状组织，弱化晶界，成为裂纹扩展和应力腐蚀的快速通道，显著降低所述锌合金的塑性和耐蚀性能，加速所述锌合金的降解速度；因此，本发明提出所述锌合金中Mn含量0.5-0.9％，可以显著改善合金的强度、韧性和耐腐蚀性能。
实验发现，将Li加入Zn-Mg-Mn合金，可以起到显著强化基体的效果，且Mn和Li的综合作用可以更显著地增强锌镁合金的强度和塑性。通过研究发现，Zn-Li二元合金中Li含量超过0.5％才能使合金的屈服强度250MPa和抗拉强度〉350MPa，但是在所述Zn-Mg-Mn-Li四元合金中，Li含量在0.05％即可使合金的屈服强度〉250MPa和抗拉强度〉350MPa，这得益于所述Mn和Li的综合作用。发明人还发现，当Li含量超过0.25％之后，虽然Zn-Mg-Mn-Li合金的强度进一步提高，但对合金组织的不均匀性和耐腐蚀性有显著影响，这不利于使用所述锌合金批量制备性能稳定的产品，且加大了对表面光洁度有要求的产品的表面处理难度。因此，综合考虑Li元素加入的利弊，本发明提出所述锌合金中Li含量为0.05-0.25％。
本发明所述的锌合金血管支架的力学性质符合医用植入体材料的强度和韧性的要求，无毒，可在人体环境下吸收，能避免二次手术给患者带来的痛苦；耐蚀性远高于镁合金，降解速度大幅度降低，可提供更长时间的力学支撑，避免血管支架提前失效。另外，其机械强度远高于多聚物，韧性高、易于制造，弹性模量与人体匹配好，可以同时满足高耐蚀性和高强韧两个要求。
具体实施方式
为使本发明要解决的技术问题、技术方案和优点更加清楚，下面将结合具体实施例进行详细描述。
本发明针对现有的问题，提供了一种Zn-Mg系锌合金血管支架，所述锌合金血管支架由内部的锌合金基体和外层的可降解涂层构成，所述锌合金基体由Zn、Mg、Li和Mn构成，质量百分比组成为4-11％Mg，0.15-0.35％Li，0.7-1.0％Mn，余量为Zn和不可避免的杂质。
所述锌合金血管支架的制备方法包括如下步骤：
一、按照锌合金组成进行配料、熔化，再经搅拌、静置和浇注，得到Zn-Mg系锌合金铸锭；所述搅拌速率为500-1500r/min，搅拌时间为5-10min，所述锌合金铸锭为外径40mm*80mm。
二、将所得锌合金铸锭依次经过外层切削、旋锻、挤出、拉拔和退火，得到具有超塑性特征的锌合金圆柱棒材；经过表层切削、旋锻、挤出后的锌合金棒材外径为15mm。
三、将所得锌合金圆柱棒材进行钻孔机械加工、常温拉拔、激光雕刻、化学抛光、涂覆涂层，得到所述的Zn-Mg系锌合金血管支架。所述锌合金棒材钻孔内径为12mm,所述拉拔工艺在常温下进行，采用带芯减壁减径拔拉，得到外径2-2.5mm，壁厚0.15-0.20mm的锌合金管材。
实施例1
通过上述制备方法得到基体质量百分比组成为6％Mg，0.05％Li，0.5％Mn，余量为Zn，可降解涂层为壳聚糖、药物为紫杉醇的可降解锌合金血管支架。
实施例2
通过上述制备方法得到基体质量百分比组成为9％Mg，0.1％Li，0.6％Mn，余量为Zn，可降解涂层为聚己内酯、药物为肝素的可降解锌合金血管支架。
实施例3
通过上述制备方法得到基体质量百分比组成为8％Mg，0.15％Li，0.7％Mn，余量为Zn，可降解涂层为丝素蛋白、药物为依维莫司的可降解锌合金血管支架。
表1为实施例与对比例力学性能数据结果(可根据需要更改测试的属性)
| 序号 | 实验材料 | 抗拉强度/MPa | 断后伸长率 |
| 1 | 实施例1 | 323 | 46 |
| 2 | 实施例2 | 370 | 49 |
| 3 | 实施例3 | 412 | 37 |
表2为实施例与对比例腐蚀性能数据结果
| 序号 | 实验材料 | 降解速度(毫米/年) |
| 1 | 实施例1 | 0.022 |
| 2 | 实施例2 | 0.027 |
| 3 | 实施例3 | 0.031 |
根据实验数据可见经过多道强化加工工艺改善，锌合金晶粒细化后获得了强韧性较高的合金棒材。本方案制备的锌合金血管支架具有优良的强韧性、延伸率及降解性能，可以提供良好力学性能的同时不需要二次取出，降低患者的痛苦和治疗成本。
以上所述是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明所述原理的前提下，还可以作出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (8)
1.一种Zn-Mg系锌合金血管支架，其特征在于，所述锌合金血管支架由内部的锌合金基体和外层的可降解涂层构成，所述锌合金基体由Zn、Mg、Li和Mn构成，质量百分比组成为6-9％Mg，0.05-0.25％Li，0.5-0.9％Mn，余量为Zn；
所述可降解涂层包括高分子材料涂层、陶瓷涂层和药物涂层中的一种或多种；
所述高分子材料涂层为聚己酸内酯、聚羟基戊酸酯、聚氰基丙烯酸酯、丝素蛋白中的一种或多种；所述陶瓷涂层为羟基磷灰石、磷酸三钙和磷酸氧四钙中的一种或多种；所述药物涂层为负载骨形成蛋白、血管内皮细胞生长因子、辛伐他汀、紫杉醇和万古霉素中的一种或多种。
2.根据权利要求1所述的锌合金血管支架，其特征在于，所述可降解涂层的厚度为0.01-5mm。
3.一种如权利要求1所述的锌合金血管支架的制备方法，其特征在于，所述锌合金血管支架的制备方法包括如下步骤：
一、按照锌合金组成进行配料、熔化，再经搅拌、静置和浇注，得到Zn-Mg系锌合金铸锭；
二、将所得锌合金铸锭依次经过外层切削、旋锻、挤出、拉拔和退火，得到具有超塑性特征的锌合金圆柱棒材；
三、将所得锌合金圆柱棒材进行钻孔机械加工、常温拉拔、激光雕刻、化学抛光、涂覆涂层，得到所述的Zn-Mg系锌合金血管支架。
4.根据权利要求3所述的制备方法，其特征在于，所述步骤一中搅拌速率为500-1500r/min，搅拌时间为5-1Omin。
5.根据权利要求3所述的制备方法，其特征在于，所述步骤一得到的锌合金铸锭为外径40mm*80mm。
6.根据权利要求3所述的制备方法，其特征在于，所述步骤二得到的锌合金棒材外径为15mm。
7.根据权利要求3所述的制备方法，其特征在于，所述步骤三中钻孔机械加工的钻孔内径为12mm。
8.根据权利要求3所述的制备方法，其特征在于，所述步骤三中常温拔拉工艺采用带芯减壁减径拉拔，得到外径2-2.5mm，壁厚0.15-0.20mm的锌合金管材。
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