CN105559944B - 覆膜血管支架 - Google Patents
覆膜血管支架 Download PDFInfo
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- CN105559944B CN105559944B CN201510929040.9A CN201510929040A CN105559944B CN 105559944 B CN105559944 B CN 105559944B CN 201510929040 A CN201510929040 A CN 201510929040A CN 105559944 B CN105559944 B CN 105559944B
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Abstract
本发明公开了一种覆膜血管支架，该覆膜血管支架包括模拟血管形状的第一层覆膜和套装在所述第一层覆膜的外部的支架骨架，所述支架骨架的至少部分外表面包覆有第二层覆膜；所述第一层覆膜和所述第二层覆膜相结合，使得所述支架骨架的至少部分包覆在所述第一层覆膜和所述第二层覆膜之间，其中，所述第一层覆膜和/或所述第二层覆膜为聚偏氟乙烯树脂覆膜。该覆膜支架的聚偏氟乙烯树脂覆膜降低了成本，并且具有良好的力学性能和生物性能。
Description
技术领域
本发明涉及介入治疗医疗器械领域，具体地，涉及一种覆膜血管支架。
背景技术
血管支架的介入治疗在血管阻塞等心脑血管疾病的治疗中应用广泛。例如在主动脉等大血管中经常需要植入覆膜支架，以及其他小血管的金属支架等等。覆膜支架既保留了普通支架的支撑功能，又能有效地改善病变血管的异常血流动力学。目前的覆膜支架一般采用聚四氟乙烯树脂材料成膜，需利用高温将聚四氟乙烯树脂熔融，然后在压力作用下使薄膜与支架基体发生粘合。热作用下，覆膜中间易形成悬浮，造成覆膜不均匀，且整个过程耗能较大，使得现有的覆膜支架成本较高。
发明内容
本发明的目的是提供一种覆膜血管支架，以克服传统聚四氟乙烯树脂覆膜需经高温处理导致成膜不均匀的缺陷。
为了实现上述目的，本发明提供一种覆膜血管支架，所述覆膜血管支架包括模拟血管形状的第一层覆膜和套装在所述第一层覆膜的外部的支架骨架，所述支架骨架的至少部分外表面包覆有第二层覆膜；所述第一层覆膜和所述第二层覆膜相结合，使得所述支架骨架的至少部分包覆在所述第一层覆膜和所述第二层覆膜之间，其中，所述第一层覆膜和/或所述第二层覆膜为聚偏氟乙烯树脂覆膜。
优选地，所述第一层覆膜的厚度为0.01-0.1mm；所述第二层覆膜的厚度为0.01-0.1mm。
优选地，所述支架骨架为金属支架骨架和/或高分子支架骨架。
优选地，所述金属支架骨架中的金属包括不锈钢和/或镍钛合金。
优选地，所述第一层覆膜和/或所述第二层覆膜由聚偏氟乙烯树脂溶液经成膜处理后所得。
优选地，所述聚偏氟乙烯树脂溶液中聚偏氟乙烯树脂与溶剂的重量比为1：(4-100)。
优选地，所述聚偏氟乙烯树脂的熔体质量流动速率为1-20g/10min。
优选地，所述溶剂为二甲基甲酰胺、二甲基乙酰胺、二甲基亚砜和甲乙酮中的至少一种。
优选地，所述成膜处理包括流延法成膜处理、可控沉积法成膜处理和喷涂法成膜处理。
优选地，所述喷涂法成膜处理的温度为10-90℃。
通过上述技术方案，本发明将聚偏氟乙烯树脂溶于二甲基甲酰胺等溶剂中即可得到覆膜，克服了传统聚四氟乙烯树脂材料做覆膜时需经高温处理导致成膜不均匀的缺陷，操作简单，节约成本，本发明的覆膜血管支架具有良好的力学性能和生物性能。
本发明的其他特征和优点将在随后的具体实施方式部分予以详细说明。
具体实施方式
以下对本发明的具体实施方式进行详细说明。应当理解的是，此处所描述的具体实施方式仅用于说明和解释本发明，并不用于限制本发明。
本发明提供一种覆膜血管支架，所述覆膜血管支架包括模拟血管形状的第一层覆膜和套装在所述第一层覆膜的外部的支架骨架，所述支架骨架的至少部分外表面包覆有第二层覆膜；所述第一层覆膜和所述第二层覆膜相结合，使得所述支架骨架的至少部分包覆在所述第一层覆膜和所述第二层覆膜之间，其中，所述第一层覆膜和/或所述第二层覆膜为聚偏氟乙烯树脂覆膜。
在本发明的优选实施方式中，可以首先根据待植入支架的血管结构设计加工型芯，然后在型芯上加工覆膜支架，再将型芯与覆膜支架分离得到本发明所述的覆膜血管支架。其中，为了精确方便地得到与血管结构切合的型芯，优选地，可以通过3D打印技术加工型芯。具体地，在设计型芯时，可以通过造影等医学手段得到带植入支架部分的血管结构，例如CT造影，然后根据该待植入支架部位的血管结构在计算机中构建与该血管结构切合的三维模型，然后通过3D打印机完成型芯的加工制造。其中需要注意的是，由于最终得到的血管支架需要与血管内壁相适应，因此在保证该型芯的外表面结构与血管的内壁结构相适应的同时，型芯的尺寸规格可以根据医生所需的误差精度来设计，对于不同误差精度的加工方法均应落在本发明的保护范围内。即，由于覆膜支架是以型芯的外表面为基准而制造的，覆膜支架需要植入到血管的内壁上，因此还需在加工型芯时，需要根据医生的要求，设计使得型芯外表面尺寸以所需误差小于血管内壁的尺寸，以使得最终的覆膜支架适应血管内壁。其中，型芯其可以为空心结构也可以为实心结构，对此本发明不做限制。其中考虑到方便加工，型芯优选为实心结构体。所述型芯根据待植入支架的人体血管结构设计加工形成，在该型芯上加工覆膜支架后需将该型芯与覆膜支架分离，从而得到具有空腔结构的覆膜血管支架。
为了完成覆膜支架的加工，需要在型芯上将支架骨架和覆膜相互结合。为了便于将二者相结合，首先在型芯上加工第一层覆膜，然后将支架骨架套装在加工有第一层覆膜的所述型芯上，再在支架骨架上加工第二层覆膜，并使得该第二层覆膜与所述第一层覆膜结合，以实现所述覆膜材料和所述支架骨架的结合。即，通过前后的两层覆膜将支架骨架牢固夹在之中，以实现二者稳定的结合。
其中为了便于型芯的加工，可以采用可溶解材料加工型芯，例如采用水溶性材料加工型芯。更具体地，可以使用糖类物质加工型芯，这样可以方便地得到固态的型芯。优选地，所述糖类物质可以包括单糖、双糖和水溶性多糖中的至少一种。另外重要地，使用液溶性材料加工型芯是为了更好地实现型芯和制造完毕的覆膜支架相互分离。其中优选地，为了快捷地将型芯与覆膜支架分离，可以使用能够溶解所述型芯的液体对所述型芯进行去除，以使得型芯与覆膜支架分离。在其他实施方式中，型芯还可以采用可熔化材料制成，只要在分离型芯时，采用加热设备将型芯熔化即可，对于此种变形方式也应落在本发明的保护范围中。
根据本发明，所述第一层覆膜和/或所述第二层覆膜为聚偏氟乙烯树脂覆膜。聚偏氟乙烯树脂覆膜的厚度过薄会使得隔膜的强度降低，导致隔膜易破裂。本发明所述第一层覆膜的厚度优选为0.01-0.1mm；所述第二层覆膜的厚度优选为0.01-0.1mm。
根据本发明，所述支架骨架可以选自本领域常规骨架材料，例如可以为金属支架骨架和/或高分子支架骨架。所述金属支架骨架中的金属可以包括不锈钢和/或镍钛合金。所述支架骨架可以为单圈的环件，根据型芯的规格选用不同规格的支架环以备与在套装到型芯上后与覆膜相结合。此外，支架骨架也可以为整条丝线，以通过缠绕包覆的方式套装到型芯的外表面上，从而得到适宜的支架骨架。
根据本发明，所述第一层覆膜和/或所述第二层覆膜由聚偏氟乙烯树脂溶液经成膜处理后所得。所述聚偏氟乙烯树脂溶液中聚偏氟乙烯树脂与溶剂的重量比在较宽范围内都可以起到使聚偏氟乙烯树脂溶解的作用，例如所述聚偏氟乙烯树脂与溶剂的重量比可以为1：(4-100)。
根据本发明，所述聚偏氟乙烯树脂(PVDF)主要是指偏氟乙烯均聚物或者偏氟乙烯与其他少量含氟乙烯基单体的共聚物。对同一类高聚物可通过熔体质量流动速率(MFR)比较分子量的大小，聚合度越大即分子量越大则熔体质量流动速率越小，反之分子量小则熔体流动速率大。本发明所述聚偏氟乙烯树脂的熔体质量流动速率可以为1-20g/10min。
聚偏氟乙烯树脂在溶剂中的溶解性随着聚偏氟乙烯树脂的聚合工艺及配方的不同而变化。常规的溶剂有丙酮、四氢呋喃、甲乙酮、二甲基甲酰胺、二甲基乙酰胺、四甲基脲、二甲基亚砜、磷酸三甲酯、N-甲基吡咯烷酮、、丁内酯、异佛尔酮、醋酸卡必醇酯、甲基异丁基酮、醋酸丁酯、环己酮、二异丁基酮、乙酰醋酸乙酯和磷酸三乙酯等。根据本发明，所述溶剂优选为二甲基甲酰胺、二甲基乙酰胺、二甲基亚砜和甲乙酮中的至少一种。
根据本发明，所述成膜处理可以采用本领域常用的聚合物成膜处理方法，例如流延法、电纺丝法、可控沉积法或喷涂法等。流延法是指将聚合物溶液在干燥、光滑且洁净的基体上均匀流延，然后在恒温烘箱中干燥成膜的方法。电纺丝法是将聚合物溶液在高压静电场下克服表面张力而产生带电喷射流，喷射流细化、***，最终固化的高聚物纤维落在基体上形成纤维膜。可控沉积法是指将成膜材料沉积在载体上，控制条件形成薄膜的方法。喷涂法是指采用气压喷枪，利用高压空气将溶液雾化，雾滴在载荷气体推动下到达基体沉积并干燥成膜的方法；采用喷涂法进行本发明所述的成膜处理时，在较低温度下即可在型芯上喷涂形成覆膜，优选地，所述喷涂法成膜处理的温度为10-90℃。
以下通过实施例进一步进行说明，但并不因此而限制本发明。
实施例1
通过CT造影得到待植入支架部分的血管结构，然后根据该待植入支架部位的血管结构在计算机中构建与该血管结构切合的三维模型，然后通过3D打印机完成型芯的加工制造，型芯采用麦芽糖、蔗糖和果糖按质量比为1：1：1进行混合。
将聚偏氟乙烯树脂FR901(购自上海三爱富，熔体质量流动速率16g/10min)与二甲基甲酰胺按重量比为1:10混合，搅拌4h后静置消泡，得到聚偏氟乙烯树脂溶液。
采用气压喷枪在0.3MPa气压、30℃温度下，喷嘴与型芯表面距离150mm时，将所得聚偏氟乙烯树脂溶液喷涂于型芯表面形成连续的第一层厚度为0.05mm的支架覆膜。
将不锈钢支架骨架套装在喷涂有第一层支架覆膜的型芯上，然后用气压喷枪，在同样的上述工作条件下将聚偏氟乙烯树脂溶液沿着不锈钢支架骨架的表面再次喷涂形成不连续的第二层厚度为0.05mm的支架覆膜，第二层支架覆膜与第一层支架覆膜结合，并将不锈钢支架骨架包覆于其中。
用水将型芯溶解，得到本发明的覆膜血管支架。
将所得覆膜支架植入实验动物(兔)的主动脉内，4周、12周、24周后进行动脉血管造影检查，观察覆膜支架植入血管通畅情况、支架贴壁性能、有无移位等。
动物植入实验表明，所有实验动物(兔)在随访期存活良好，支架植入部位血管保持通畅，无血栓形成。覆膜无皱缩、破裂等现象，无并发症、血液渗漏、支架移位，覆膜支架贴壁较好且具备良好的生物相容性。
实施例2
通过CT造影得到待植入支架部分的血管结构，然后根据该待植入支架部位的血管结构在计算机中构建与该血管结构切合的三维模型，然后通过3D打印机完成型芯的加工制造，型芯采用麦芽糖、蔗糖和葡萄糖按质量比为1：2：5进行混合。
将聚偏氟乙烯树脂FR921(购自上海三爱富，熔体质量流动速率2g/10min)与二甲基乙酰胺按重量比为1:80混合，搅拌4h后静置消泡，得到聚偏氟乙烯树脂溶液。
将所得聚偏氟乙烯树脂溶液浇注至放有型芯的模具内，使聚偏氟乙烯树脂溶液流延于型芯表面形成连续的第一层厚度为0.1mm的支架覆膜。
将镍钛合金支架骨架套装在流延成膜有第一层支架覆膜的型芯上，然后再次放入模具内，使聚偏氟乙烯树脂溶液再次流延形成第二层厚度为0.1mm的支架覆膜，第二层支架覆膜与第一层支架覆膜结合，并将镍钛合金支架骨架包覆于其中。
用水将型芯溶解，得到本发明的覆膜血管支架。
将所得覆膜支架植入实验动物(兔)的主动脉内，4周、12周、24周后进行动脉血管造影检查，观察覆膜支架植入血管通畅情况、支架贴壁性能、有无移位等。
动物植入实验表明，所有实验动物(兔)在随访期存活良好，支架植入部位血管保持通畅，无血栓形成。覆膜无皱缩、破裂等现象，无并发症、血液渗漏、支架移位，覆膜支架贴壁较好且具备良好的生物相容性。
Claims (10)
1.一种覆膜血管支架，其特征在于，所述覆膜血管支架包括模拟血管形状的第一层覆膜和套装在所述第一层覆膜的外部的支架骨架，所述支架骨架的至少部分外表面包覆有第二层覆膜；所述第一层覆膜和所述第二层覆膜相结合，使得所述支架骨架的至少部分包覆在所述第一层覆膜和所述第二层覆膜之间，其中，所述第一层覆膜和/或所述第二层覆膜为聚偏氟乙烯树脂覆膜。
2.根据权利要求1所述的覆膜血管支架，其中，所述第一层覆膜的厚度为0.01-0.1mm；所述第二层覆膜的厚度为0.01-0.1mm。
3.根据权利要求1所述的覆膜血管支架，其中，所述支架骨架为金属支架骨架和/或高分子支架骨架。
4.根据权利要求3所述的覆膜血管支架，其中，所述金属支架骨架中的金属包括不锈钢和/或镍钛合金。
5.根据权利要求1所述的覆膜血管支架，其中，所述第一层覆膜和/或所述第二层覆膜由聚偏氟乙烯树脂溶液经成膜处理后所得。
6.根据权利要求5所述的覆膜血管支架，其中，所述聚偏氟乙烯树脂溶液中聚偏氟乙烯树脂与溶剂的重量比为1：(4-100)。
7.根据权利要求6所述的覆膜血管支架，其中，所述聚偏氟乙烯树脂的熔体质量流动速率为1-20g/10min。
8.根据权利要求6所述的覆膜血管支架，其中，所述溶剂为二甲基甲酰胺、二甲基乙酰胺、二甲基亚砜和甲乙酮中的至少一种。
9.根据权利要求5所述的覆膜血管支架，其中，所述成膜处理包括流延法成膜处理、可控沉积法成膜处理和喷涂法成膜处理。
10.根据权利要求9所述的覆膜血管支架，其中，所述喷涂法成膜处理的温度为10-90℃。
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| CN101703812B (zh) * | 2009-11-20 | 2013-01-02 | 东华大学 | 一种聚酰胺66覆膜镍钛合金血管支架及其制备方法 |
| US10154918B2 (en) * | 2012-12-28 | 2018-12-18 | Cook Medical Technologies Llc | Endoluminal prosthesis with fiber matrix |
| CN203436435U (zh) * | 2013-07-01 | 2014-02-19 | 雅伦生物科技(北京)有限公司 | 一种脑血管药物洗脱支架 |
| CN106581785A (zh) * | 2014-11-04 | 2017-04-26 | 华瑞（福建）生物科技有限公司 | 血管支架及其制备方法 |
| CN105559944B (zh) * | 2015-12-14 | 2016-11-09 | 李雷 | 覆膜血管支架 |
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2015
- 2015-12-14 CN CN201510929040.9A patent/CN105559944B/zh active Active
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2016
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- 2016-10-19 JP JP2018532293A patent/JP2018538082A/ja active Pending
- 2016-10-19 US US16/061,587 patent/US10695164B2/en active Active
- 2016-10-19 EP EP16874640.2A patent/EP3384873A4/en not_active Withdrawn
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| CN105559944A (zh) | 2016-05-11 |
| US20180360590A1 (en) | 2018-12-20 |
| EP3384873A4 (en) | 2018-12-26 |
| JP2018538082A (ja) | 2018-12-27 |
| US10695164B2 (en) | 2020-06-30 |
| EP3384873A1 (en) | 2018-10-10 |
| WO2017101582A1 (zh) | 2017-06-22 |
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