CN110343284B - 一种聚氨酯介入导管表面抗菌抗凝涂层制备方法 - Google Patents
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Abstract
本发明涉及医疗器械领域,具体涉及一种聚氨酯介入导管表面抗菌抗凝涂层制备方法。本发明利用丙烯磺酸和醋酸乙烯酯在聚氨酯管材表面交联反应,有利于增强涂层在管材表面的附着力,同时引入具有抗凝作用的磺酸基团。皂化反应引入羟基后,进一步与PEG‑PAMAM反应,引入具有强亲水性及抗凝作用的PEG片段。由于引入的PAMAM能够通过配位作用与具有抗菌效果的Ag+络合,可以实现较好的抗菌效果。本发明使用的原料成本低,涂层能够兼具抗菌抗凝双重效果,同时涂层通过交联反应形成网络结构固载于管材表面,保证了涂层的耐久性。
Description
技术领域
本发明涉及医疗器械领域,具体涉及一种聚氨酯介入导管表面抗菌抗凝涂层制备方法。
背景技术
血管内介入导管是血管内介入技术的主要器械之一。根据用途,可以将血管内介入导管分为造影介入导管、给药介入导管、血管成形术介入导管等。近年来,血管内介入诊疗技术在临床的成功运用极大地减轻了病人的痛苦,减轻了医护人员的工作难度,介入诊疗导管的应用日益广泛。导管制造技术也已相对成熟,性能也逐步提高。作为与血液接触的医疗器械,血管内介入导管必须具有良好的生物相容性和血液相容性,一定的力学性能,表面光滑性能等。
聚氨酯(PU)是主链上含有-NHCOO-重复结构单元的一类嵌段共聚物。由于其主链由刚性链段(硬段)和柔性链段(软段)交替组成,形成的微相分离结构使其具有比其它高分子材料好的生物相容性(包括血液相容性和组织相容性),同时它具有优异的耐疲劳性、耐磨性、高弹性和高强度,因而聚氨酯被广泛用作介入导管材料。聚氨酯介入导管在具有上述优异性能的同时,也引起诸多并发症,其中,引发凝血和感染一直是困扰医务人员的一个棘手问题,因此,对聚氨酯导管表面进行抗凝血性能、亲水性、抗菌性、润滑性改性的研究其已成为该领域的研究热点。
磺酸基团改性的PU具有一定的抗凝血性能。将端磺酸基聚氧乙烯(PEO-SO3)接枝于聚氨酯表面,血小板粘附实验结果表明PU-PEO-SO3表面具有更好的抗血小板粘附的能力,该表面在阻抗其他蛋白质吸附的同时可极大地提高白蛋白的吸附,而PU-PEO表面只体现了非特异性抗蛋白粘附的性能,证明了磺酸基团的抗凝性能。聚乙二醇(PEG)是一种具有代表性抗凝高分子材料。PEG可溶于水和多种有机溶剂,无毒性,己被美国FDA批准应用于人体内。PEG的一个重要性质是它可以连接到其它分子上或细胞表面,提供一个生物相容性的保护层,这个保护层可以减少蛋白质、细胞和细菌的吸附。因此,在抗凝血材料的研究与开发中,PEG一直被选为改性材料,通过各种方法引入到其它高分子上或接枝到材料表面,以减少材料表面的血浆蛋白吸附和血小板粘附。
PAMAM树状分子是一种人工合成的球形的,高度分枝的高分子聚合物,其结构特点是以中心核分子作为出发点向外扩散,具有大量的表面官能团、分子内存在空腔、相对分子质量可控、分子量分布可达单分散性、分子本身具有纳米尺寸等特点。聚酰胺胺(PAMAM)树状分子的结构特点使其具有独特的性质:良好的相容性和易修饰性,良好的渗透性及稳定性,可用于载药技术,聚酰胺胺(PAMAM)树状大分子在基因载体、纳米复合材料等方面也具有良好的前景。
作为常用的抗菌基团,Ag+靠库仑引力牢固吸附于细胞膜上,然后击穿细胞壁进入细胞内使细菌蛋白质凝固,细胞就会丧失***增殖能力而死亡。此外,Ag+也能破坏微生物电子传输***、呼吸***、物质传输***,当菌体失去活性后,Ag+又从菌体中游离出来,重复杀菌,因此其抗菌效果持久。通过把抗菌基团引入材料中,赋予材料抗菌性。引入Ag+方法很多,包括用配位键固定,Takamasa等利用带有三乙基四胺或硫醇基团的树脂与Ag+、Cu2+、Zn2+等离子络合,制备了具有抗菌性的材料。
目前,由于血栓和感染仍然是聚氨酯导管应用中发生率较高的两大并发症,因此如何赋予聚氨酯导管抗菌和抗凝性能是目前临床应用中亟待解决的问题。本发明通过在导管表面组建交联结构,有效地将导管和涂层相结合,同时结合其他的技术对导管表面进行抗菌抗凝改性,为获得高性能的抗菌抗凝聚氨酯医用介入导管提供了新的技术途径。
发明内容
本发明针对提高聚氨酯导管抗菌抗凝性能,提出了一种抗菌抗凝涂层的制备及应用方法,该涂层能够有效抗菌抗凝。
1.一种聚氨酯介入导管表面抗菌抗凝涂层的制备方法,其特征在于,包括以下步骤:
(1)采用去离子水或蒸馏水对聚氨酯导管表面进行清洁后烘干,冷却待用;
(2)取n份丙烯磺酸,加入DMSO搅拌溶解,取m份精制醋酸乙烯酯加入圆底烧瓶,搅拌下加入少量催化剂偶氮二异丁腈,将聚氨酯导管在该溶液中浸泡后取出反应,反应结束后先用DMSO洗涤,洗去残留单体,再用丙酮进行清洗,除去残留溶剂,得到表面含有醋酸乙烯酯和丙烯磺酸共聚物聚醋酸乙烯磺酸钠PVAc(SO3)Na的聚氨酯导管,干燥至恒重;
(3)将表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管浸入甲醇溶液后取出,经皂化反应得到PVA(SO3)Na,室温干燥除去甲醇;
(4)将PEG-PAMAM 溶于0.2mol/L PBS缓冲溶液,将表面含有PVA(SO3)Na的聚氨酯导管在PEG-PAMAM 的PBS缓冲溶液中浸泡后取出反应,用丙酮多次洗涤,除去过量未反应物质后烘干;
(5)将表面含有PAMAM-PEG-PVA(SO3)Na的聚氨酯导管浸泡在AgNO3水溶液中,反应完成后将得到的表面含有Ag-PAMAM-PEG-PVA(SO3)Na的聚氨酯导管Ag-PAMAM-PEG-PVA(SO3)Na@PU在室温下真空干燥。
优选的,步骤(1)采用去离子水或蒸馏水对聚氨酯导管表面进行超声洗涤,烘箱温度为30-45℃,烘干时间1-2h;
优选的,步骤(2)中丙烯酸与醋酸乙烯酯反应的的摩尔比n:m为(2~7):1;
优选的,步骤(2)聚氨酯导管在反应物溶液中浸泡时间为1-3min,反应温度为60-75℃,反应时间为5-10h;
优选的,步骤(3)聚氨酯导管浸入的甲醇溶液的温度为40-60℃,时间为30-60s;
优选的,步骤(3)聚氨酯导管自甲醇溶液取出后反应温度为室温,,反应时间为2-5h;
优选的,步骤(4)所用步骤(3)得到的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液中浸泡时间为1-2min取出,与PEG-PAMAM 反应温度为60-80℃,反应时间为3-6h;
优选的,步骤(4)洗涤后烘干温度为20-40℃烘干时间为12-48h;
优选的,步骤(5)聚氨酯导管表面PAMAM-PEG-PVA(SO3)Na与AgNO3水溶液反应温度为室温,搅拌下反应时间为12-36h;
优选的,步骤9所用AgNO3水溶液浓度为0.001-0.01mol/L。
反应过程如下:
本发明利用丙烯磺酸和醋酸乙烯酯在聚氨酯管材表面交联反应,有利于增强涂层在管材表面的附着力,同时引入具有抗凝作用的磺酸基团。皂化反应引入羟基后,进一步与PEG-PAMAM反应,引入具有强亲水性及抗凝作用的PEG片段。由于引入的PAMAM能够通过配位作用与具有抗菌效果的Ag+络合,可以实现较好的抗菌效果。本发明使用的原料成本低,涂层能够兼具抗菌抗凝双重效果,同时涂层以通过交联反应形成网络结构固载于管材表面,保证了涂层的耐久性。
上述聚合物分子式分别如下:
PVAc(SO3)Na:
PAMAM-PEG:
PAMAM-PEG-PVA(SO3)Na:
Ag-PAMAM-PEG-PVA(SO3)Na:
附图说明
图1是本发明产品的结构示意图。
具体实施方式
为了更好地说明本发明,下面结合本发明实施例对本发明中的技术方案进行清楚、完整地描述:
实施实例1
(1)采用去离子水或蒸馏水对聚氨酯导管表面进行清洁。
(2)取5份丙烯磺酸,加入DMSO搅拌溶解,取1份精制醋酸乙烯酯加入圆底烧瓶,搅拌下加入少量催化剂偶氮二异丁腈,将聚氨酯导管在该溶液中浸泡2min后取出,65℃条件下反应4h。反应结束后先用DMSO洗涤,洗去残留单体,再用丙酮进行清洗,除去残留溶剂,得到表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管,干燥至恒重。
(3)将表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管浸入50℃甲醇溶液60s,室温反应3h,经皂化反应得到PVA(SO3)Na,室温干燥除去甲醇。
(4)将PEG-PAMAM溶于0.2mol/L PBS缓冲溶液,,将表面含有PVA(SO3)Na的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液中浸泡1-2min取出,70℃反应4h,用丙酮多次洗涤,除去过量未反应物质后40℃烘干24h。
(5)将表面含有PAMAM-PEG-PVA(SO3)Na的聚氨酯导管浸泡在0.005mol/L AgNO3水溶液中,室温搅拌反应24小时后将导管在25℃真空容器中干燥24h,得到改性聚氨酯导管Ag-PAMAM-PEG-PVA(SO3)Na@PU。
实施实例2
(1)采用去离子水或蒸馏水对聚氨酯导管表面进行清洁。
(2)取6份丙烯磺酸,加入DMSO搅拌溶解,取1份精制醋酸乙烯酯加入圆底烧瓶,搅拌下加入少量催化剂偶氮二异丁腈,将聚氨酯导管在该溶液中浸泡3min后取出,65℃条件下反应2h。反应结束后先用DMSO洗涤,洗去残留单体,再用丙酮进行清洗,除去残留溶剂,得到表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管,干燥至恒重。
(3)将表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管浸入50℃甲醇溶液30s,室温反应3h,经皂化反应得到PVA(SO3)Na,室温干燥除去甲醇。
(4)将PEG-PAMAM 溶于0.2mol/L PBS缓冲溶液,,将表面含有PVA(SO3)Na的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液溶液中浸泡1-2min取出,70℃反应6h,用丙酮多次洗涤,除去过量未反应物质后40℃烘干24h。
(5)将表面含有PAMAM-PEG-PVA(SO3)Na的聚氨酯导管浸泡在0.001mol/L AgNO3水溶液中,室温搅拌反应24小时后将导管在25℃真空容器中干燥24h得到改性聚氨酯导管Ag-PAMAM-PEG -PVA(SO3)Na@PU。
实施实例3
(1)采用去离子水或蒸馏水对聚氨酯导管表面进行清洁。
(2)取7份丙烯磺酸,加入DMSO搅拌溶解,取1份精制醋酸乙烯酯加入圆底烧瓶,搅拌下加入少量催化剂偶氮二异丁腈,将聚氨酯导管在该溶液中浸泡1min后取出,60℃条件下反应6h。反应结束后先用DMSO洗涤,洗去残留单体,再用丙酮进行清洗,除去残留溶剂,得到表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管,干燥至恒重。
(3)将表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管浸入50℃甲醇溶液40s,室温反应3h,经皂化反应得到PVA(SO3)Na,室温干燥除去甲醇。
(4)将PEG-PAMAM溶于0.2mol/L PBS缓冲溶液,,将表面含有PVA(SO3)Na的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液溶液中浸泡2min取出,60℃反应3h,用丙酮多次洗涤,除去过量未反应物质后40℃烘干24h。
(5)将表面含有PAMAM -PEG -PVA(SO3)Na的聚氨酯导管浸泡在0.01mol/L AgNO3水溶液中,室温搅拌反应24小时后将导管在25℃真空容器中干燥24h得到改性聚氨酯导管Ag-PAMAM-PEG -PVA(SO3)Na@PU。
实施实例4
(1)采用去离子水或蒸馏水对聚氨酯导管表面进行清洁。
(2)取4份丙烯磺酸,加入DMSO搅拌溶解,取1份精制醋酸乙烯酯加入圆底烧瓶,搅拌下加入少量催化剂偶氮二异丁腈,将聚氨酯导管在该溶液中浸泡3min后取出,60℃条件下反应6h。反应结束后先用DMSO洗涤,洗去残留单体,再用丙酮进行清洗,除去残留溶剂,得到表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管,干燥至恒重。
(3)将表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管浸入50℃甲醇溶液30s-60s,室温反应2h,经皂化反应得到PVA(SO3)Na,室温干燥除去甲醇。
(4)将PEG-PAMAM 溶于0.2mol/L PBS缓冲溶液,,将表面含有PVA(SO3)Na的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液溶液中浸泡2min取出,70℃反应8h,用丙酮多次洗涤,除去过量未反应物质后40℃烘干24h。
(5)将表面含有PAMAM-PEG-PVA(SO3)Na 的聚氨酯导管浸泡在0.008mol/L AgNO3水溶液中,室温搅拌反应24小时后将导管在25℃真空容器中干燥24h得到改性聚氨酯导管Ag-PAMAM-PEG-PVA(SO3)Na@PU。
实施实例5
取浓度为106cfu/mL的金黄色葡萄球菌在LB培养基中培养24h,稀释后取一定量的稀释样液涂布到平板上培养48h,测定实施例1-4制备的医用聚氨酯导管表面的细菌数量,3次测试结果平均值如表1所示。
样品 | 未改性导管 | 实施例1 | 实施例2 | 实施例3 | 实施例4 |
细菌数量 | 9.4×10<sup>8</sup> | 8.9×10<sup>4</sup> | 2.6×10<sup>5</sup> | 5.4×10<sup>5</sup> | 6.6×10<sup>5</sup> |
由表中数据可知,当对医用聚氨导管表面进行改性后,导管表面细菌的数量明显低于未改性导管表面细菌数量。
Claims (9)
1.一种聚氨酯介入导管表面抗菌抗凝涂层的制备方法,其特征在于,包括以下步骤:
(1)采用去离子水或蒸馏水对聚氨酯导管表面进行清洁后烘干,冷却待用;
(2)取n份丙烯磺酸,加入DMSO搅拌溶解,取m份精制醋酸乙烯酯加入圆底烧瓶,所述丙烯磺酸与醋酸乙烯酯加入的摩尔比n:m为(2~7):1,搅拌下加入少量催化剂偶氮二异丁腈,将聚氨酯导管在该溶液中浸泡后取出反应,反应结束后先用DMSO洗涤,洗去残留单体,再用丙酮进行清洗,除去残留溶剂,得到表面含有醋酸乙烯酯和丙烯磺酸共聚物聚醋酸乙烯磺酸钠PVAc(SO3)Na的聚氨酯导管,干燥至恒重;
(3)将表面含有醋酸乙烯酯和丙烯磺酸共聚物PVAc(SO3)Na的聚氨酯导管浸入甲醇溶液后取出,经皂化反应得到PVA(SO3)Na,室温干燥除去甲醇;
(4)将PEG-PAMAM溶于0.2mol/L PBS缓冲溶液,将表面含有PVAc(SO3)Na的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液中浸泡后取出反应,用丙酮多次洗涤,除去过量未反应物质后烘干;
(5)将表面含有PAMAM-PEG-PVA(SO3)的聚氨酯导管浸泡在AgNO3水溶液中,反应完成后将得到的Ag-PAMAM-PEG-PVA(SO3)Na@PU室温下真空干燥。
2.根据权利要求1所述的制备方法,其特征在于所述步骤(1)采用去离子水或蒸馏水对聚氨酯导管表面进行超声洗涤,烘箱温度为30-45℃,烘干时间1-2h。
3.根据权利要求1所述的制备方法,其特征在于所述步骤(2)聚氨酯导管在反应物溶液中浸泡时间为1-3min,反应温度为60-75℃,反应时间为5-10h。
4.根据权利要求1所述的制备方法,其特征在于所述步骤(3)聚氨酯导管浸入的甲醇溶液的温度为40-60℃,时间为30-60s。
5.根据权利要求1所述的制备方法,其特征在于所述步骤(3)聚氨酯导管自甲醇溶液取出后反应温度为室温,反应时间为2-5h。
6.根据权利要求1所述的制备方法,其特征在于所述步骤(4)所用步骤(3)得到的聚氨酯导管在PEG-PAMAM的PBS缓冲溶液中浸泡时间为1-2min,与PEG-PAMAM反应温度为60-80℃,反应时间为3-6h。
7.根据权利要求1所述的制备方法,其特征在于所述步骤(4)洗涤后烘干温度为20-40℃,烘干时间为12-48h。
8.根据权利要求1所述的制备方法,其特征在于聚氨酯导管表面PAMAM-PEG-PVA(SO3)Na与AgNO3水溶液反应温度为室温,搅拌下反应时间为12-36h。
9.根据权利要求8所述的制备方法,其特征在于所述AgNO3水溶液浓度为0.001-0.01mol/L。
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Publication number | Priority date | Publication date | Assignee | Title |
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CN101011605A (zh) * | 2006-11-28 | 2007-08-08 | 武汉理工大学 | 抗凝血聚氨酯材料及其制备和用途 |
CN102357265A (zh) * | 2011-07-29 | 2012-02-22 | 中山大学 | 一种表面改性聚氨酯中心静脉导管及其制备方法 |
CN102380130A (zh) * | 2011-07-29 | 2012-03-21 | 中山大学 | 纳米银表面改性聚氨酯中心静脉导管及其制备方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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CN102357265A (zh) * | 2011-07-29 | 2012-02-22 | 中山大学 | 一种表面改性聚氨酯中心静脉导管及其制备方法 |
CN102380130A (zh) * | 2011-07-29 | 2012-03-21 | 中山大学 | 纳米银表面改性聚氨酯中心静脉导管及其制备方法 |
CN107537069A (zh) * | 2017-09-05 | 2018-01-05 | 泉州市科茂利通智能科技有限公司 | 一种聚乙二醇表面改性的纳米银聚氨酯医用材料及其制备方法 |
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