CN117281915A - 一种血管介入凝聚层栓塞剂及制备方法和应用 - Google Patents
一种血管介入凝聚层栓塞剂及制备方法和应用 Download PDFInfo
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- CN117281915A CN117281915A CN202311239389.0A CN202311239389A CN117281915A CN 117281915 A CN117281915 A CN 117281915A CN 202311239389 A CN202311239389 A CN 202311239389A CN 117281915 A CN117281915 A CN 117281915A
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Abstract
本申请属于肿瘤治疗技术领域,尤其涉及一种血管介入凝聚层栓塞剂及制备方法和应用;本申请提供的血管介入凝聚层栓塞剂能够稳定负载显影剂和化疗药物,有利于经动脉灌注化疗栓塞术前、术后定位监测栓塞剂,并能改善化疗药物缓释效果,也具有出色的血管内弥散性,并且血管介入凝聚层栓塞剂制备方法简单方便,从而解决现有技术中缺乏能和显影剂以及药物稳定结合,且血管内弥散性好的栓塞剂的技术问题。
Description
技术领域
本申请属于肿瘤治疗技术领域,尤其涉及一种血管介入凝聚层栓塞剂及制备方法和应用。
背景技术
经动脉灌注化疗栓塞术(Transcatheter arterial chemoembolization,TACE)旨在将导管选择性插入肿瘤供血动脉内灌注化疗药物,随即栓塞供血动脉以导致恶性肿瘤缺血坏死。目前,经动脉灌注化疗栓塞术已经用于原发性肝癌、肺癌、以及肠癌肝转移等恶性肿瘤治疗;经动脉灌注化疗栓塞术所使用的栓塞剂主要包括碘化油、明胶海绵颗粒、聚乙烯醇空白微球以及聚乙烯醇药物洗脱微球等材质的栓塞剂。
碘化油、明胶海绵颗粒以及聚乙烯醇空白微球等栓塞剂存在无法有效载药,而明胶海绵颗粒、聚乙烯醇空白微球及其药物洗脱微球等栓塞剂在注射过程中易团聚导致无法有效弥散至微血管,且碘化油、明胶海绵颗粒、聚乙烯醇空白微球及其药物洗脱微球等栓塞剂不能和显影剂稳定结合不利于定位栓塞剂,因此,现有技术缺乏能和显影剂以及药物稳定结合,且血管内弥散性好的栓塞剂,现有栓塞剂的性能有待提高。
发明内容
有鉴于此,本申请提供了一种血管介入凝聚层栓塞剂及制备方法和应用,用于解决现有技术中缺乏能和显影剂以及药物稳定结合,且血管内弥散性好的栓塞剂的技术问题。
本申请第一方面提供了一种血管介入凝聚层栓塞剂,成分包括季铵化壳聚糖/阿拉伯胶凝聚层、显影剂以及化疗药物;
所述显影剂通过化学键或氢键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中;
所述化疗药物通过化学键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中。
优选的,所述显影剂选自碘对比剂、液态金属以及能通过金属螯合作用掺杂在季铵化壳聚糖/阿拉伯胶凝聚层中的显影剂中的至少一种。
优选的,所述碘对比剂选自碘海醇、碘克沙醇、碘帕醇、欧奈派克、碘普罗胺、优维显、碘佛醇中的至少一种;
所述液态金属选自金属镓的合金;
优选的,所述能通过金属螯合作用掺杂在季铵化壳聚糖/阿拉伯胶凝聚层中的显影剂选自钽粉微颗粒。
优选的,所述化疗药物选自蒽环类化疗药物、喜树碱及其衍生物中的至少一种。
优选的,所述蒽环类化疗药物选自阿霉素、表柔比星、吡柔比星、柔红霉素、米托蒽醌、卡柔比星中的至少一种;
所述喜树碱及其衍生物选自拓扑替康、伊立替康中的至少一种。
本申请第二方面提供了一种血管介入凝聚层栓塞剂的制备方法,用于制备第一方面所述血管介入凝聚层栓塞剂;制备方法包括步骤:
步骤S1、将季铵化壳聚糖水溶液和阿拉伯胶水溶液混合后静置或离心,得到季铵化壳聚糖/阿拉伯胶凝聚层;
步骤S2、将季铵化壳聚糖/阿拉伯胶凝聚层、显影剂以及化疗药物混合,得到血管介入凝聚层栓塞剂。
优选的,步骤S1中,所述季铵化壳聚糖水溶液的质量浓度分别为0.5~10wt%,所述阿拉伯胶水溶液的质量浓度分别为2~20wt%;
所述季铵化壳聚糖水溶液和所述阿拉伯胶水溶液的体积比为1:9~9:1。
优选的,步骤S1中,所述季铵化壳聚糖水溶液的质量浓度分别为4wt%,所述阿拉伯胶水溶液的质量浓度分别为8wt%;
所述季铵化壳聚糖水溶液和所述阿拉伯胶水溶液的体积比为4:6。
优选的,步骤S2中,所述季铵化壳聚糖/阿拉伯胶凝聚层和所述显影剂的质量比为1:9~9:1。
优选的,所述季铵化壳聚糖/阿拉伯胶凝聚层和所述化疗药物的质量比为1:9~9:1。
优选的,步骤S2中,所述季铵化壳聚糖/阿拉伯胶凝聚层和所述显影剂的质量比为7:3。
优选的,步骤S2中,所述季铵化壳聚糖/阿拉伯胶凝聚层和所述化疗药物的质量比为1:2。
本申请第三方面提供了一种血管介入凝聚层栓塞剂在恶性肿瘤治疗领域中的应用。
优选的,所述恶性肿瘤包括原发性肝癌、肝转移瘤、肺癌、舌癌、鼻咽癌、前列腺癌、宫颈癌或子宫内膜癌。
综上所述,本申请提供了一种血管介入凝聚层栓塞剂及制备方法和应用,本申请提供的血管介入凝聚层栓塞剂中季铵化壳聚糖/阿拉伯胶凝聚层的高分子网络由带正电荷的季铵化壳聚糖和带负电荷的阿拉伯胶形成,且高分子网络分布有羟基基团,从而能和碘对比剂等显影剂上的羟基形成氢键相结合、能和带正电荷的液态金属和钽粉微颗粒等显影剂通过静电作用或金属螯合作用形成化学键相结合,能和带正电荷的阿霉素等化疗药物通过静电作用形成化学键相结合,显影剂通过化学键或氢键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中后,能够在经动脉灌注化疗栓塞术过程中,准确监测定位栓塞剂位置,避免出现异位栓塞等情况,还能在术后进行疗效监测;化疗药物通过化学键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中后,提高了化疗药物的稳定性,避免了药物突释,提高了化疗药物的缓释效果;同时,季铵化壳聚糖/阿拉伯胶凝聚层的具有的剪切变稀特性使得栓塞剂在血管内弥散性好,从而解决了现有技术中缺乏能和显影剂以及药物稳定结合,且血管内弥散性好的栓塞剂的技术问题。
附图说明
为了更清楚地说明本申请具体实施方式或现有技术中的技术方案,下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图是本申请的一些实施方式,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1为本申请实施例中负载化疗药物阿霉素的季铵化壳聚糖/阿拉伯胶凝聚层的制备流程示意图;
图2为本申请实施例中不同体积比例的季铵化壳聚糖水溶液(4wt%QCS)和阿拉伯胶水溶液(8wt%GA)制备得到的季铵化壳聚糖/阿拉伯胶凝聚层示意图;
图3为本申请实施例中负载不同质量的显影剂的季铵化壳聚糖/阿拉伯胶凝聚层X射线计算机断层扫描以及CT值示意图;
图4为本申请实施例中负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层缓释效果示意图;
图5为本申请实施例中负载显影剂和化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层在负载前后的红外光谱示意图;
图6为本申请实施例中负载显影剂和化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层在负载前后的注射力测试示意图;
图7为本申请实施例中负载显影剂和化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层在负载前后的流变学测试示意图;
图8为本申请实施例中负载显影剂和化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层的血液相容性、细胞相容性以及体外杀灭肿瘤细胞测试示意图;
图9为本申请实施例中新西兰兔右肾动脉栓塞实验示意图;
图10为本申请实施例中新西兰兔右肝动脉栓塞实验示意图。
具体实施方式
本申请提供了一种血管介入凝聚层栓塞剂及制备方法和应用,用于解决现有技术中缺乏能和显影剂以及药物稳定结合,且血管内弥散性好的栓塞剂的技术问题。
下面将结合附图对本申请的技术方案进行清楚、完整地描述,显然,所描述的实施例是本申请一部分实施例,而不是全部的实施例。基于本申请中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本申请保护的范围。
实施例1
鉴于现有技术中栓塞剂存在的缺陷,本申请实施例1提供了血管介入凝聚层栓塞剂;血管介入凝聚层栓塞剂的组成成分包括季铵化壳聚糖/阿拉伯胶凝聚层、显影剂以及化疗药物;栓塞剂成分中季铵化壳聚糖为水速溶性阳离子型天然高分子聚合物,可与其他阴离子化合物形成静电作用,同时含有的羟基基团易与其他分子的羟基、羧基或醛基等形成氢键;阿拉伯胶为带负电荷的天然高分子聚合物,可与其他阳离子化合物形成静电作用,同时含有的羟基基团易与其他分子的羟基、羧基或醛基等形成氢键,因此,碘海醇、金属镓的合金以及钽粉微颗粒等显影剂能通过化学键或氢键掺杂在季铵化壳聚糖/阿拉伯胶凝聚层,显影剂稳定结合季铵化壳聚糖/阿拉伯胶凝聚层后,有利于在经动脉灌注化疗栓塞术前和术后对栓塞剂进行定位,避免异位栓塞等情况发生;而阿霉素等化疗药物通过静电作用与季铵化壳聚糖/阿拉伯胶凝聚层形成化学键相结合使得化学药物能够稳定负载,改善了化疗药物的缓释效果,并且季铵化壳聚糖/阿拉伯胶凝聚层具有的剪切变稀特性使得栓塞剂在血管内弥散性好,从而克服了现有技术中缺乏能和显影剂以及药物稳定结合,且血管内弥散性好的栓塞剂的缺陷,有利于经动脉灌注化疗栓塞术发挥更好的疗效,在肿瘤治疗领域发挥更大的作用。
对于显影剂的种类,本申请优选碘对比剂、金属镓的合金(镓铟合金或镓铟锡合金等)以及钽粉微颗粒;其中,碘海醇、碘克沙醇、碘帕醇、欧奈派克、碘普罗胺、优维显、碘佛醇等碘对比剂苯环上都含有大量的羟基,有利于与季铵化壳聚糖/阿拉伯胶凝聚层形成大量氢键,而金属镓的合金熔点为37℃以下,有利于低温保存,碘对比剂等显影剂赋予凝聚层不透X射线的能力。
对于化疗药物的种类,可根据恶性肿瘤来针对性的负载药物,本申请优选阿霉素等蒽环类化疗药物或拓扑替康等喜树碱及其衍生物;化疗药物与季铵化壳聚糖/阿拉伯胶凝聚层通过静电作用形成大量化学键,有利于化疗药物的缓释。
实施例2
本申请实施例2提供了一种血管介入凝聚层栓塞剂的制备方法,可用于制备实施例1所述血管介入凝聚层栓塞剂;制备方法包括制备季铵化壳聚糖/阿拉伯胶凝聚层的步骤、负载显影剂以及负载化疗药物的步骤。
其中,制备季铵化壳聚糖/阿拉伯胶凝聚层的步骤包括:按照2:8、3:7、4:6、5:5、6:4、7:3以及8:2的体积比例分别将季铵化壳聚糖水溶液(4wt%QCS)和阿拉伯胶水溶液(8wt%GA)混合后,静置(≥12h)或离心(转速≥1000rpm,时间≥5min),利用静电作用出现液-液相分离,得到季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA),得到的产物如图2所示,本申请提供的凝聚层制备方法仅通过简单的混合后静置离心即可得到,不需要额外的试剂和工艺步骤,制备方便,且当季铵化壳聚糖和阿拉伯胶的体积比为4:6时,能够得到高产率的凝聚层。
负载显影剂以及负载化疗药物的步骤包括:按照显影剂和季铵化壳聚糖/阿拉伯胶凝聚层的质量比为7:3、化疗药物和季铵化壳聚糖/阿拉伯胶凝聚层的质量比为2:1,分别将碘对比剂(Iohexol)和阿霉素(DOX)与季铵化壳聚糖/阿拉伯胶凝聚层(4:6)充分混合,得到季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I/DOX)。
实施例3
本申请实施例3提供了负载不同质量的显影剂的季铵化壳聚糖/阿拉伯胶凝聚层的制备方法,用于确定显影剂负载量对显影效果的影响。
负载不同质量的显影剂的季铵化壳聚糖/阿拉伯胶凝聚层的制备方法包括:按照0:100、15:85、20:80、25:75、30:70的质量比例,将碘海醇(Iohexol)显影剂与季铵化壳聚糖/阿拉伯胶凝聚层混合,得到负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I),通过X射线计算机断层扫描测试负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层和单纯碘海醇(Iohexol),并计算其CT值,其结果如图3所示。
从图3可以看出,随着碘海醇显影剂比例的提高,其显影效果也随之提升,当碘海醇和季铵化壳聚糖/阿拉伯胶凝聚层的质量比为30:70时,其显影效果和CT数值和单纯碘海醇(100%)相当,说明负载30wt%的碘海醇的季铵化壳聚糖/阿拉伯胶凝聚层可以取得较好的显影效果。
实施例4
本申请实施例4提供了负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层的制备方法,用于确定季铵化壳聚糖/阿拉伯胶凝聚层负载化疗药物后的缓释效果。
负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层的制备方法包括:将4mg DOX溶解于2mg QCS/GA中并充分混合,得到负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/DOX);然后将QCS/GA/DOX于37℃条件下孵育24h后,将上述溶液注射于10mL的不同pH值的磷酸缓冲盐溶液(PBS)中。在设置的时间点取2μL上清液,测量其在480nm波长下的吸光度,根据标准曲线得到DOX释放量,其结果如图4所示。
从图4可以看出,在不同的pH值环境中,负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层均能实现缓慢释放,且第35天释放量约80%左右,说明负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层具有超过35天的药物释放时间。
实施例5
本申请实施例5提供了负载显影剂和化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层在负载前后的变化。
其中,对季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA)、负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I)、负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/DOX)进行傅立叶转换红外光谱测试的结果如图5所示;
从图5可以看出,QCS的NH3+(1656cm-1)与GA的C=O(1610cm-1)于QCS/GA上移位至1602cm-1,提示QCS与GA形成静电作用。加入DOX后,其-NH2基团由1635cm-1移位至1644cm-1,提示GA与DOX形成静电作用;同时QCS的-OH(3340cm-1)与GA的-OH(3434cm-1)于QCS/GA上移位至3376cm-1,提示QCS与GA氢键形成。加入Iohexol后,其-OH基团由3257cm-1移位至3361cm-1,提示Iohexol与QCS、GA之间氢键形成;上述结果说明本申请提供的栓塞剂中显影剂是通过化学键或氢键掺杂在季铵化壳聚糖/阿拉伯胶凝聚层中,而化疗药物是通过化学键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中。
对季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA)、负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I)、负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I/DOX)进行注射力测试,如图6A所示,将1mL螺口注射器放置在自制的测试仪器上,注射器上端跟上压板接触,下端被夹具垂直固定并连接不同规格的导管,分别将1mL季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA)、1ml负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I)、1ml负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I/DOX)以及1mlPBS添加到注射器内,下端连接1.7F微导管。然后,使用上压板匀速地(流量:1mL/min)按压注射器,同时记录上压板压力的变化,结果如图6B、C所示;
从图6B、C可以看出,QCS/GA凝聚层于1.7微导管内的松脱力为12N左右,注射力为10N左右,证实其易于注射。另外QCS/GA/I、QCS/GA/DOX/I与QCS/GA于各种导管内注射力无明显差异,证实添加对比剂及装载化疗药物后均未改变凝聚层的注射力。
对季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA)、负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I)、负载化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I/DOX)进行流变学测试,测试采用Anton PaarMCR 92流变仪和平行板系统(直径=25mm)进行流变实验。在恒定应变(1%)、恒定角频率(ω=10rad/s)下进行时间振荡扫描,在剪切速率0.1~100s-1范围内进行变剪切速率测试,所有测试均在T=37±0.2℃下重复三次;
测试结果如图7所示,QCS/GA、QCS/GA/I、QCS/GA/DOX/I的损耗模量(lossmodulus,G”)高于储能模量(storage modulus,G’),证实其为凝聚层,且具有剪切变稀特性,提示其易于注射。
实施例6
本申请实施例6提供了负载显影剂和化疗药物的季铵化壳聚糖/阿拉伯胶凝聚层的血液相容性、细胞相容性以及体外杀灭肿瘤细胞的实验,用于说明血管介入凝聚层栓塞剂生物相容性好,可用于介入治疗灭杀肿瘤细胞。
其中,血液相容性实验包括:先通过离心(200×g,10min)收集兔全血红细胞,用生理盐水稀释至5%(v/v),然后分别将50μL mL QCS/GA、QCS/GA/I、QCS/GA/DOX/I、生理盐水(阴性对照)和去离子水(阳性对照)加到1mL上述血细胞溶液中,并在37℃孵育48h;再将红细胞悬液离心(500×g,15min)后,将上清液转移到96孔板,使用酶标仪测试溶液在540nm处的吸光度;其中,溶血率计算如下:溶血率(%)=(As-An)/(Ad-An)×100%(As、An和Ad分别为样品、生理盐水和去离子水组的吸光度);
结果如图8A和8B所示,QCS/GA、QCS/GA/I、QCS/GA/DOX/I溶血率小于5%,具有良好的血液相容性。
细胞生物相容性实验包括:先将L929细胞加入12孔板(25000个/孔),并在37℃培育箱孵育12h,然后分别将1mL QCS/GA、QCS/GA/I加入含有细胞的孔中,将正常添加培养基的组作为阳性对照,待孵育24h后,用活/死细胞染色法评估细胞活力;
结果如图8C所示,所有的组细胞存活率均大于98%,且细胞呈现正常铺展的梭形,该结果说明凝聚层无细胞毒性,具有良好的细胞生物相容性。
体外杀灭肿瘤细胞的实验包括:先将Hepa 1-6肝癌细胞加入12孔板(25000个/孔),并在37℃培育箱孵育12h,然后将1mL QCS/GA/I、QCS/GA/DOX/I(其中DOX量为100μg)及100μg DOX分别加入含有细胞的孔中,将正常添加培养基的组作为阳性对照,待孵育24h后,用活/死细胞染色法评估细胞活力;
结果如图8D所示,DOX组、QCS/GA/DOX/I组细胞均死亡,证实凝聚层加载化疗药可以达到与化疗药直接杀伤肿瘤细胞的效果。
实施例7
本申请实施例7提供了负载显影剂的季铵化壳聚糖/阿拉伯胶凝聚层(QCS/GA/I)进行新西兰兔肾动脉和肝动脉栓塞,用于说明血管介入凝聚层栓塞剂在血管内弥散性好。
新西兰兔肾动脉栓塞包括:先依次将实验兔全麻、左侧腹股沟区备皮、消毒铺巾后,切开皮肤、肌肉、筋膜,逐层钝性分离出股动脉;然后将股动脉远端使用2-0缝线结扎,近端预留2-0缝线,再将动脉夹夹闭近端股动脉,使用显微剪剪开股动脉前壁,随即插入1.7F微导管,微导管使用预留缝线打活结固定,此时松开动脉夹并继续推进微导管,微导管在微导丝引导下选择性插入右侧肾动脉,数字减影血管造影(digital subtractionangiography,DSA)确认其血管通畅后(图9A),严密X线透视监测下缓慢注入0.2mL左右QCS/GA/I(图9B)。栓塞完毕后复查造影见右肾动脉及其小分支显影消失(图9C);术后7天复查腹部增强CT,经过术前(图9D-G)及术后(图9E-H)对比,可见右肾完全坏死,无强化(图D-H);附图9所示结果表明QCS/GA/I可以有效的栓塞肾动脉及出色的血管内弥散性。
新西兰兔肝动脉栓塞包括:股动脉插管步骤如肾动脉栓塞,1.7F微导管在微导丝引导下超选择进入腹腔干造影,明确肝固有动脉开口(图10A);随后导管分别超选择进入肝固有(图10B)、左肝动脉(图10C);首先缓慢注射QCS/GA/I栓塞左肝动脉,然后微导管退至右肝动脉开口行右肝动脉栓塞。栓塞完毕后DSA确认左、右肝动脉及其分支显影消失(图10D,短箭头)。以上结果证实QCS/GA/I可以有效地栓塞肝动脉及弥散至远端小血管。
以上各实施例仅用以说明本申请的技术方案,而非对其限制;尽管参照前述各实施例对本申请进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分或者全部技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本申请各实施例技术方案的范围。
Claims (10)
1.一种血管介入凝聚层栓塞剂,其特征在于,包括季铵化壳聚糖/阿拉伯胶凝聚层、显影剂以及化疗药物;
所述显影剂通过化学键或氢键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中;
所述化疗药物通过化学键掺杂在所述季铵化壳聚糖/阿拉伯胶凝聚层中。
2.根据权利要求1所述的一种血管介入凝聚层栓塞剂,其特征在于,所述显影剂选自碘对比剂、液态金属以及能通过金属螯合作用掺杂在季铵化壳聚糖/阿拉伯胶凝聚层中的显影剂中的至少一种。
3.根据权利要求2所述的一种血管介入凝聚层栓塞剂,其特征在于,所述碘对比剂选自碘海醇、碘克沙醇、碘帕醇、欧奈派克、碘普罗胺、优维显、碘佛醇中的至少一种。
4.根据权利要求1所述的一种血管介入凝聚层栓塞剂,其特征在于,所述化疗药物选自蒽环类化疗药物、喜树碱及其衍生物中的至少一种。
5.根据权利要求4所述的一种血管介入凝聚层栓塞剂,其特征在于,所述蒽环类化疗药物选自阿霉素。
6.权利要求1-5任一项所述的一种血管介入凝聚层栓塞剂的制备方法,其特征在于,包括步骤:
步骤S1、将季铵化壳聚糖水溶液和阿拉伯胶水溶液混合后静置或离心,得到季铵化壳聚糖/阿拉伯胶凝聚层;
步骤S2、将季铵化壳聚糖/阿拉伯胶凝聚层、显影剂以及化疗药物混合,得到血管介入凝聚层栓塞剂。
7.根据权利要求6所述的一种血管介入凝聚层栓塞剂的制备方法,其特征在于,步骤S1中,所述季铵化壳聚糖水溶液的质量浓度分别为4wt%,所述阿拉伯胶水溶液的质量浓度分别为8wt%;
所述季铵化壳聚糖水溶液和所述阿拉伯胶水溶液的体积比为4:6。
8.根据权利要求6所述的一种血管介入凝聚层栓塞剂的制备方法,其特征在于,步骤S2中,所述季铵化壳聚糖/阿拉伯胶凝聚层和所述显影剂的质量比为7:3。
9.根据权利要求6所述的一种血管介入凝聚层栓塞剂的制备方法,其特征在于,步骤S2中,所述季铵化壳聚糖/阿拉伯胶凝聚层和所述化疗药物的质量比为1:2。
10.权利要求1-5任一项所述的一种血管介入凝聚层栓塞剂在恶性肿瘤治疗领域中的应用。
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