CN117137543A - 一种可降解封堵器及制备方法与应用 - Google Patents
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- A—HUMAN NECESSITIES
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Abstract
本发明属于医疗器械领域,公开了一种可降解封堵器及制备方法与应用;包括:阻流膜和封堵器支架,其特征在于,所述阻流膜采用可降解胶原膜,所述封堵器支架采用可降解锌基合金编织而成;本发明的锌基合金支架显影性强,提高了内植入物的影像学诊断准确性;胶原膜的亲水性、生物相容性及细胞亲和性优异,此外二者不同的降解速率与组织再生能力,可以更快的相匹配,此外,还能促进组织内皮化,降低炎症发生的风险。
Description
技术领域
本发明属于医疗器械领域,涉及一种可降解封堵器及制备方法与应用。
背景技术
大多数卵圆孔未闭患者无症状,且对心脏血流动力学基本没有影响,但对健康或寿命有潜在的威胁。当因各种原因如咳嗽、憋气、潜水等导致胸腔压力增加时,卵圆孔未闭可致心脏内血流出现明显的右向左异常分流,这时来源于全身静脉***的栓子(包括血栓、空气栓、脂肪栓等)可通过未闭的卵圆孔进入体循环发生反常性栓塞,从而导致一系列临床症状,包括偏头痛、缺血性脑卒中、心肌梗死、外周血管栓塞、减压综合征等。
介入封堵手术已成为房间隔缺损、室间隔缺损、卵圆孔未闭等先天性心脏病患者首选治疗方法。在第二十届中国心脏大会期间,海军军医大学附属长海医院秦永文教授就可降解封堵器的研发现状做了简要分析,并结合丰富的可降解封堵器植入经验,剖析可降解封堵器临床应用前景、局限性以及发展方向;目前广泛使用的传统金属卵圆孔封堵器多为镍钛合金材料,植入后在患者体内存留终身,植入人体后可能会导致传导阻滞、瓣膜损伤、引发镍离子析出、心内组织磨蚀、血栓形成、房性心律失常等并发症;镍钛封堵器永久阻断了房间隔径路,使得今后无法进行某些介入治疗如心房颤动射频消融术等;而可降解封堵器采用可降解材料,植入缺损部位后可以自行降解消失,降解产物为二氧化碳、水以及乳酸,对人体无害,这种装置避免了金属封堵器终身留于体内可能带来的并发症风险,有效降低心源卒中发生率,减轻偏头痛、头晕等症状,也为未来穿刺房间隔等介入治疗留出安全通路,带给患者长远期健康获益和生命质量的提升。
CN113616266A公开了一种可吸收封堵器,其特征在于,所述阻流膜采用经过辐照处理的可降解材料,所述骨架采用可降解纤维编织而成。本发明的优点是可吸收封堵器引导心脏组织再生,封堵器各部的不同降解速度与心脏不同部位的组织再生能力匹配,缺点是聚合物组织支架存在碎片栓塞风险、聚乳酸降解产物造成局部酸性,引起炎症反应。
CN116726263A公开了一种新型可降解聚合物封堵器阻流膜,它由如下重量份的组分组成:天然聚合物1-5份、合成聚合物1-5份。本发明优点多层结构的封堵器阻流膜不仅具有与纯天然聚合物相当的亲水性、生物相容性及细胞亲和性,缺点是聚乳酸降解产物造成局部酸性,引起化学反应;化学试剂残留等问题。
CN114652366A公开了一种可降解的复合膜及其制备方法和应用;该可降解的复合膜包括高分子材料膜,在所述高分子材料膜的上表面和下表面分别覆盖有水凝胶膜,所述高分子材料膜和所述水凝胶膜通过共价键连接;本发明的优点是能够促进内皮细胞的粘附和生长,有利于正常新生组织在膜表面生成;缺点是聚乳酸降解产物造成局部酸性,引起局部反应;金属离子铈的引入会引起间质性肺疾病,氧化铈参与人体代谢活动时,会形成不溶性的磷酸铈。
虽然现在可降解封堵器可实现完全降解,但是尚存在不足之处:1.可降解高分子材料的骨架,刚性差,选择封堵器尺寸时需偏大。2.可降解高分子骨架X光显影性差,要依靠超声指引,对术者能力要求高,植入操作需程序化;不利于观察封堵器的植入和形态观察。3.聚合物组织支架仍存在碎片栓塞风险、降解过程中的局部刺激或炎症及残余分流等问题。4.可降解阻流膜在体内降解时会导致氧化应激反应,诱发局部炎症反应,妨碍正常新生组织的生成。5.可降解阻流膜具有血栓原性,植入血液后容易诱发血栓。此外,封堵器在内皮未完全覆盖之前,与周围心房肌的运动可能会不一致,心房肌局部受摩擦引起炎症、水肿,在心房内产生异位兴奋灶引起异常折返,从而导致房颤等严重心律失常。
发明内容
基于背景技术存在的技术问题,本发明提供了一种可降解封堵器;该封堵器具有良好的力学性能、显影性强、降解产物安全等,还能够促进内皮细胞的粘附和生长,有利于正常新生组织在膜表面生成。
为了实现以上目的,本发明采用以下技术方案: 所述可降解封堵器,其特征在于,包括:封堵器支架、阻流膜;其中封堵器支架为锌基合金支架、阻流膜为胶原膜;其制备方法:
(1)将锌、铜、锂、硼、硒粉末按一定比例均匀混合,在真空熔炼炉中熔炼获得锌基合金棒材,棒材经表面氧化处理、加热、拉拔、热处理、再拉拔、退火、编织、热处理定型获得封堵器支架;
(2)将胶原材料、可降解聚合物微纳米级纤维、细胞生长因子、多糖添加到溶剂中,经过工艺处理获得胶原膜;
(3)采用蛋白线将封堵器支架与阻流膜缝制连接。
为了更好地实现本发明,进一步的,所述锌、铜、锂、硼、硒粉末按质量百分含量:铜优选为0.2%-3%,硼优选为0.02%-0.08%,硒优选为0.3%-0.5%,锂优选为0.1%-1%,其余为锌。
为了更好地实现本发明,进一步的,所述锌、铜、锂、硼、硒的纯度为>99.999%。
为了更好地实现本发明,进一步的,所述真空熔炼温度为680-900℃。
为了更好地实现本发明,进一步的,所述棒材加热温度为300-500℃。
为了更好地实现本发明,进一步的,所述热处理温度为200-600℃。
为了更好地实现本发明,进一步的,所述胶原材料为胶原蛋白、丝素蛋白、弹性蛋白、纤连蛋白、动物源胶原蛋白中的一种或多种组合。
为了更好地实现本发明,进一步的,所述可降解聚合物微纳米级纤维为乙交酯-丙交酯共聚物、聚己内酯、聚羟基乙酸、聚乳酸-己内酯共聚物、聚乳酸-羟基乙酸共聚物、聚对二氧环己酮、聚乙醇酸、聚羟基脂肪酸脂、聚酰胺、聚酸酐、聚二恶烷酮、聚醚氨酯、聚磷酸酯、聚氨酯、聚碳酸酯中的一种或多种组合。
为了更好地实现本发明,进一步的,所述细胞生长因子为心房心肌细胞生长因子、心室心肌细胞生长因子、成纤维细胞生长因子、内皮细胞生长因子、周皮细胞生长因子、平滑肌细胞生长因子中的一种或多种组合。
为了更好地实现本发明,进一步的,所述多糖为透明质酸、肝素、甲壳素、聚多糖纳米晶、淀粉、纤维素、壳聚糖、改性壳聚糖中的一种或多种组合。
为了更好地实现本发明,进一步的,所述工艺处理为溶液流延法或静电纺丝。
为了更好地实现本发明,进一步的,所述胶原材料:可降解聚合物微纳米级纤维的质量比优选为8:2-6:4。
为了更好地实现本发明,进一步的,所述细胞生长因子优选0.01-1μg/ml。
为了更好地实现本发明,进一步的,所述多糖溶液浓度优选0.5-5μg/ml。
为了更好地实现本发明,进一步的,所述静电纺丝电压优选15-20kV,接收距离为优选15-20cm,纺丝液推进速度优选0.5-2mL/h,转速优选1000-4000rpm。
为了更好地实现本发明,进一步的,作为卵圆孔未闭封堵器、房间隔封堵器、室间隔封堵器、左心耳封堵器、动脉导管未闭封堵器中的应用。
因此,与现有技术相比,本发明的可降解封堵器具有以下有益效果:
1、采用可降解锌基合金材料及胶原膜制成,植入人体后锌基合金将起到临时桥梁作用,引导自体组织生物修复后,1个月形成完整的新生内膜,内皮化完成,6个月内保持支架完整性,2-3年逐步完全降解,降解产物ZnO还具有抗菌作用。
可降解锌基合金生物材料具有良好的生物相容性和可降解性,降解速度可控,降解产物安全,降低了局部或***性损伤或慢性炎症的风险,避免了传统金属材料经常需要进行二次手术取出的问题,此外显影性强,大大提高了植入患者影响学诊断的准确性,为患者提供更安全、更便捷的治疗方式。
与聚乳酸材料植入物相比,可降解锌基合金的加工成型性好,力学性能稳定,不会永久存在于体内。
动物实验显示:锌基合金支架的降解速率与周围组织愈合过程相吻合。
2、本发明中引入铜元素,可使锌基合金具备如下功能:①铜的降解产物Cu 2+具有一定的抗菌作用,能够防止以器械为中心的感染;②铜的降解产物Cu2+能够促进内皮型一氧化氮合酶(eNOS)的分泌,维持血管内皮完整和内皮细胞功能;有利 于刺激VEGF(血管内皮生长因子)的分泌,促进血管内皮细胞增值和迁移,因此能够促进植入部位的快速再内皮化及血管内皮正常功能的恢复和维持、诱导血管新生。
3、本发明中引入硒元素,可使锌基合金具备如下功能:①硒的加入使合金的结构更加致密,提高它们的机械性能,能够改善合金的加工性能,加工的支架表面更光洁;②硒可以降低炎性因子的数量和水平,改善血管氧化状态,可保护缺氧的心脑细胞,保护心肌和血管内壁细胞,减少外周血管的阻力,防止心肌纤维化,缩小心肌梗塞面积,改善心室收缩和舒张的功能,调整心率,防止心肌缺血缺氧性损伤,起到保护心脏的作用;③硒能提高人体免疫,促进淋巴细胞的增殖及抗体和免疫球蛋白的合成;④硒对结肠癌、皮肤癌、肝癌、乳腺癌等多种癌症具有明显的抑制和防护的作用,其在机体内的中间代谢产物甲基烯醇具有较强的抗癌活性;⑤硒具有减轻和缓解重金属毒性的作用;⑥硒与维生素E、锌等营养素具有协同抗氧化的功效,增加抗氧化活性;⑦硒元素可以让癌细胞中毒,通过抑制合成途径中产生的代谢酶,让癌细胞不能顺利生长和扩散,最后慢慢死亡。
4、本发明中引入锂元素,可使锌基合金具备如下功能:①降解的锂能保护生物膜,能增加膜结构的稳定性;②锂的引入能改善造血功能,提高人体免疫机能;③锂对中枢神经活动有调节作用,是有效的镇定剂,能镇静、安神,控制神经紊乱;④锂也可用于心血管疾病的防治。
5、胶原膜具有高拉伸强度、生物降解性能、低抗原活性、低刺激性、低细胞毒性,还能促进细胞生长、促进细胞粘附、与新生细胞和组织协同修复创伤;同时为酶提供额外的胶原蛋白来源,从而使身体的天然胶原蛋白可用于新组织的生长;胶原膜柔软丝滑,在心房肌运动过程中,减少心房肌的局部摩擦,降低了炎症、水肿的发生率。
6、锌铜锂三离子之间具有协同作用,降解的铜离子促进内皮化形成新生组织至成膜,降解的锂离子能增强膜的结构稳定性,在心房肌运动中,锌离子的抗炎特性能降低微弱的局部摩擦造成的炎症,减弱内膜增生。
具体实施方式
以下通过特定的具体实例说明本发明的实施方式,本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用,本说明书中的各项细节也可以基于不同观点与应用,在没有背离本发明的精神下进行各种修饰或改变。需说明的是,在不冲突的情况下,以下实施例及实施例中的特征可以相互组合。
实施例1:
锌基合金粉末混合:将高纯度(99.999%)合金铜为0.2%,硼为0.02%,硒为0.3%,锂为0.1%,其余为锌,按照一定的质量比例称量。把称量好的粉末在高能球磨机中混合均匀,其中球料质量比10:1。将放入粉末的球磨罐依次用真空泵进行抽真空,再通入氩气,使其充满整个球磨罐。球磨运行模式设定为顺、逆向交替间隔运行,转速为400-600 r/min,球磨总时间为10-48 h。
锌基合金熔炼:将混合均匀的原材料放在石墨坩埚中,然后在氮气气氛下,在680°C下熔化。将熔融合金充分搅拌以尽量减少成分偏析,然后倒入直径10厘米的圆柱形铁模中。
锌基合金拉拔:将锌铜锂硼硒合金铸锭进行表面处理,去除氧化膜,再加热至300°C,保持3小时,然后立即拉拔成直径8mm;然后将棒材切割成120mm,并进行热处理200℃,再次进行拉拔,退火处理,获得锌基合金单丝。
锌基合金支架编织:将长度为锌基合金单丝编织成网管并放入设计好的模具中,热处理定型,冷却至室温获得封堵器支架。
胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选8:2、细胞生长因子浓度优选0.01μg/ml、肝素浓度优选0.5μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选15kV,接收距离为优选15cm,纺丝液推进速度优选0.5mL/h,转速优选1000rpm。
封堵器制备:采用蛋白缝线将胶原膜与锌基合金支架缝合到一起。
实施例2:
锌基合金粉末混合:将高纯度(99.999%)合金铜为0.8%,硼为0.03%,硒为0.35%,锂为0.2%,其余为锌;按照一定的质量比例称量。把称量好的粉末在高能球磨机中混合均匀,其中球料质量比10:1。将放入粉末的球磨罐依次用真空泵进行抽真空,再通入氩气,使其充满整个球磨罐。球磨运行模式设定为顺、逆向交替间隔运行,转速为400-600 r/min,球磨总时间为10-48 h。
锌基合金熔炼:将混合均匀的原材料放在石墨坩埚中,然后在氮气气氛下,在700°C下熔化。将熔融合金充分搅拌以尽量减少成分偏析,然后倒入直径10厘米的圆柱形铁模中。
锌基合金拉拔:将锌铜锂硼硒合金铸锭进行表面处理,去除氧化膜,再加热至350°C,保持3小时,然后立即拉拔成直径8mm;然后将棒材切割成120mm,并进行热处理300℃,再次进行拉拔,退火处理,获得锌基合金单丝。
锌基合金支架编织:将长度为锌基合金单丝编织成网管并放入设计好的模具中,热处理定型,冷却至室温获得封堵器支架。
胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选7:3、细胞生长因子浓度优选0.1μg/ml、肝素浓度优选1μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选16kV,接收距离为优选16cm,纺丝液推进速度优选0.8mL/h,转速优选1500rpm。
封堵器制备:采用蛋白缝线将胶原膜与锌基合金支架缝合到一起。
实施例3:
锌基合金粉末混合:将高纯度(99.999%)合金铜为1.4%,硼为0.04%,硒为0.4%,锂为0.4%,其余为锌;按照一定的质量比例称量。把称量好的粉末在高能球磨机中混合均匀,其中球料质量比10:1。将放入粉末的球磨罐依次用真空泵进行抽真空,再通入氩气,使其充满整个球磨罐。球磨运行模式设定为顺、逆向交替间隔运行,转速为400-600 r/min,球磨总时间为10-48 h。
锌基合金熔炼:将混合均匀的原材料放在石墨坩埚中,然后在氮气气氛下,在750°C下熔化。将熔融合金充分搅拌以尽量减少成分偏析,然后倒入直径10厘米的圆柱形铁模中。
锌基合金拉拔:将锌铜锂硼硒合金铸锭进行表面处理,去除氧化膜,再加热至400°C,保持3小时,然后立即拉拔成直径8mm;然后将棒材切割成120mm,并进行热处理400℃,再次进行拉拔,退火处理,获得锌基合金单丝。
锌基合金支架编织:将长度为锌基合金单丝编织成网管并放入设计好的模具中,热处理定型,冷却至室温获得封堵器支架。
胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选6:4、细胞生长因子浓度优选1μg/ml、肝素浓度优选5μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选17kV,接收距离为优选17cm,纺丝液推进速度优选1.2mL/h,转速优选2000rpm。
封堵器制备:采用蛋白缝线将胶原膜与锌基合金支架缝合到一起。
实施例4:
锌基合金粉末混合:将高纯度(99.999%)合金铜为1.8%,硼为0.05%,硒为0.45%,锂为0.6%,其余为锌;按照一定的质量比例称量。把称量好的粉末在高能球磨机中混合均匀,其中球料质量比10:1。将放入粉末的球磨罐依次用真空泵进行抽真空,再通入氩气,使其充满整个球磨罐。球磨运行模式设定为顺、逆向交替间隔运行,转速为400-600 r/min,球磨总时间为10-48 h。
锌基合金熔炼:将混合均匀的原材料放在石墨坩埚中,然后在氮气气氛下,在800°C下熔化。将熔融合金充分搅拌以尽量减少成分偏析,然后倒入直径10厘米的圆柱形铁模中。
锌基合金拉拔:将锌铜锂硼硒合金铸锭进行表面处理,去除氧化膜,再加热至450°C,保持3小时,然后立即拉拔成直径8mm;然后将棒材切割成120mm,并进行热处理500,再次进行拉拔,退火处理,获得锌基合金单丝。
锌基合金支架编织:将长度为锌基合金单丝编织成网管并放入设计好的模具中,热处理定型,冷却至室温获得封堵器支架。
胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选7:3、细胞生长因子浓度优选0.05μg/ml、肝素浓度优选1.5μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选18kV,接收距离为优选18cm,纺丝液推进速度优选1.6mL/h,转速优选2500rpm。
封堵器制备:采用蛋白缝线将胶原膜与锌基合金支架缝合到一起。
实施例5:
锌基合金粉末混合:将高纯度(99.999%)合金铜为2.4%,硼为0.06%,硒为0.5%,锂为0.8%,其余为锌;按照一定的质量比例称量。把称量好的粉末在高能球磨机中混合均匀,其中球料质量比10:1。将放入粉末的球磨罐依次用真空泵进行抽真空,再通入氩气,使其充满整个球磨罐。球磨运行模式设定为顺、逆向交替间隔运行,转速为400-600 r/min,球磨总时间为10-48 h。
锌基合金熔炼:将混合均匀的原材料放在石墨坩埚中,然后在氮气气氛下,在850°C下熔化。将熔融合金充分搅拌以尽量减少成分偏析,然后倒入直径10厘米的圆柱形铁模中。
锌基合金拉拔:将锌铜锂硼硒合金铸锭进行表面处理,去除氧化膜,再加热至500°C,保持3小时,然后立即拉拔成直径8mm;然后将棒材切割成120mm,并进行热处理450℃,再次进行拉拔,退火处理,获得锌基合金单丝。
锌基合金支架编织:将长度为锌基合金单丝编织成网管并放入设计好的模具中,热处理定型,冷却至室温获得封堵器支架。
胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选7:3、细胞生长因子浓度优选0.5μg/ml、肝素浓度优选3μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选19kV,接收距离为优选19cm,纺丝液推进速度优选2.0mL/h,转速优选3000rpm。
封堵器制备:采用蛋白缝线将胶原膜与锌基合金支架缝合到一起。
实施例6:
锌基合金粉末混合:将高纯度(99.999%)合金铜为3%,硼为0.08%,硒为0.5%,锂为1%,其余为锌;按照一定的质量比例称量。把称量好的粉末在高能球磨机中混合均匀,其中球料质量比10:1。将放入粉末的球磨罐依次用真空泵进行抽真空,再通入氩气,使其充满整个球磨罐。球磨运行模式设定为顺、逆向交替间隔运行,转速为400-600 r/min,球磨总时间为10-48 h。
锌基合金熔炼:将混合均匀的原材料放在石墨坩埚中,然后在氮气气氛下,在900°C下熔化。将熔融合金充分搅拌以尽量减少成分偏析,然后倒入直径10厘米的圆柱形铁模中。
锌基合金拉拔:将锌铜锂硼硒合金铸锭进行表面处理,去除氧化膜,再加热至500°C,保持3小时,然后立即拉拔成直径8mm;然后将棒材切割成120mm,并进行热处理600℃,再次进行拉拔,退火处理,获得锌基合金单丝。
锌基合金支架编织:将长度为锌基合金单丝编织成网管并放入设计好的模具中,热处理定型,冷却至室温获得封堵器支架。
胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选7:3、细胞生长因子浓度优选0.8μg/ml、肝素浓度优选4μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选20kV,接收距离为优选20cm,纺丝液推进速度优选2mL/h,转速优选4000rpm。
封堵器制备:采用蛋白缝线将胶原膜与锌基合金支架缝合到一起。
比较例1:
铜为0.1%,硼为0.01%,硒为0.2%,其余为锌,其制备方法同实施例6;胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选7:3、添加浓度为0.25μg/ml戊二醛交联剂,细胞生长因子浓度优选0.05μg/ml、肝素浓度优选1.5μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选18kV,接收距离为优选18cm,纺丝液推进速度优选1.6mL/h,转速优选2500rpm。
比较例2:
铜为4%,硼为1%,硒为0.6%,锂为1.2%,其余为锌,其制备方法同实施例6;胶原膜制备:将胶原蛋白与可降解聚合物微纳米级纤维按照质量比优选7:3、添加体积比为:1:1的1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)和N-羟基琥珀亚酰胺(NHC)交联剂,细胞生长因子浓度优选0.05μg/ml、肝素浓度优选1.5μg/ml添加到溶剂中,经静电纺丝获得胶原膜;静电纺丝电压优选18kV,接收距离为优选18cm,纺丝液推进速度优选1.6mL/h,转速优选2500rpm。
比较例3:
铜为3%,硒为0.5%,锂为1%,其余为锌,其制备方法同实施例6。
比较例4:
铜为3%,硼为0.08%,锂为1%,其余为锌,其制备方法同实施例6。
比较例5:
硼为0.08%,硒为0.5%,锂为1%,其余为锌,其制备方法同实施例6。
比较例6:
铜为3%,其余为锌,其制备方法同实施例6。
以上实施例及比较例测得的封堵器支架拉伸强度、断裂伸长率、血液相容性、细胞活性、炎症反应、血栓数据如下表示:
以上实施例及比较例测得的胶原膜的细胞活性、炎症反应、血栓、细胞增殖数据如下表示:
通过以上数据可以发现:硒元素添加能提高合金的血液相容性;硼元素添加量不在0.02%-0.08%范围时,会降低合金的强度和塑形;不添加铜元素会降低合金的内皮化效果;不添加锂元素会降低拉伸和断裂延伸率;本发明的胶原膜不含有任何化学试剂,不会引起试剂残留,采用交联剂戊二醛会降低降低细胞活性、细胞增殖的效果,同时还发现1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)和N-羟基琥珀亚酰胺(NHC)交联的胶原蛋白在细胞质基质中有毒残留物。
以上所述,仅是本发明的具体实施方式而已,并非对本发明作任何形式上的限制,任何熟悉本技术领域的技术人员对以上实施例所作的任何简单修改、等同变化与修饰,均仍属于本发明技术方案的范围内。
Claims (9)
1.一种可降解封堵器,其特征在于,包括:封堵器支架、阻流膜;其中封堵器支架为锌基合金支架、阻流膜为胶原膜;其制备方法:
(1)将锌、铜、锂、硼、硒粉末按一定比例均匀混合,在真空熔炼炉中熔炼获得锌基合金棒材,棒材经表面氧化处理、加热、拉拔、热处理、再拉拔、退火、编织、热处理定型获得封堵器支架;
(2)将胶原材料、可降解聚合物微纳米级纤维、细胞生长因子、多糖添加到溶剂中,经过工艺处理获得胶原膜;
(3)采用蛋白线将封堵器支架与阻流膜缝制连接。
2.一种权利要求1所述的可降解封堵器的制备方法,其特征在于,包括以下步骤:
(1)将锌、铜、锂、硼、硒粉末按一定比例均匀混合,在真空熔炼炉中熔炼获得锌基合金棒材,棒材经表面氧化处理、加热、拉拔、热处理、再拉拔、退火、编织、热处理定型获得封堵器支架;
(2)将胶原材料、可降解聚合物微纳米级纤维、细胞生长因子、多糖添加到溶剂中,经过工艺处理获得胶原膜;
(3)采用蛋白线将封堵器支架与阻流膜缝制连接。
3.根据权利要求2所述的可降解封堵器的制备方法,其特征在于,所述锌、铜、锂、硼、硒的纯度为>99.999%。
4.根据权利要求2所述的可降解封堵器的制备方法,其特征在于,所述胶原材料为胶原蛋白、丝素蛋白、弹性蛋白、纤连蛋白、动物源胶原蛋白中的一种或多种组合。
5.根据权利要求2所述的可降解封堵器的制备方法,其特征在于,所述细胞生长因子为心房心肌细胞生长因子、心室心肌细胞生长因子、成纤维细胞生长因子、内皮细胞生长因子、周皮细胞生长因子、平滑肌细胞生长因子中的一种或多种组合。
6.根据权利要求2所述的可降解封堵器的制备方法,其特征在于,所述多糖为透明质酸、肝素、甲壳素、聚多糖纳米晶、淀粉、纤维素、壳聚糖、改性壳聚糖中的一种或多种组合。
7.根据权利要求2所述的可降解封堵器的制备方法,其特征在于,所述工艺处理为溶液流延法或静电纺丝。
8.根据权利要求2所述的可降解封堵器的制备方法,其特征在于,所述可降解聚合物微纳米级纤维为乙交酯-丙交酯共聚物、聚己内酯、聚羟基乙酸、聚乳酸-己内酯共聚物、聚乳酸-羟基乙酸共聚物、聚对二氧环己酮、聚乙醇酸、聚羟基脂肪酸脂、聚酰胺、聚酸酐、聚二恶烷酮、聚醚氨酯、聚磷酸酯、聚氨酯、聚碳酸酯中的一种或多种组合。
9.一种权利要求1所述的可降解封堵器的应用,其特征在于,作为卵圆孔未闭封堵器、房间隔封堵器、室间隔封堵器、左心耳封堵器、动脉导管未闭封堵器中的应用。
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