CN116570735A - 一种药物纳米多级结构涂层及其制备方法 - Google Patents
一种药物纳米多级结构涂层及其制备方法 Download PDFInfo
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- CN116570735A CN116570735A CN202310859599.3A CN202310859599A CN116570735A CN 116570735 A CN116570735 A CN 116570735A CN 202310859599 A CN202310859599 A CN 202310859599A CN 116570735 A CN116570735 A CN 116570735A
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Abstract
本发明属于生物医用功能材料技术领域,具体涉及一种药物纳米多级结构涂层及其制备方法。在本发明制备方法中,多酚、多胺基化合物在氧化剂的作用下发生氧化、交联和聚合反应,在纳米药物载体外生成一层多酚纳米颗粒膜层,该多酚纳米膜层既充当纳米药物载体的“保护层”及其之间的交联物质,也可将纳米药物载体固定在基底材料表面,与纳米药物载体一起提供涂层的纳米多级结构。再通过金属离子与多酚纳米颗粒膜层中的酚羟基发生螯合作用,将金属离子引入到涂层中,进一步增加了涂层中纳米药物载体的稳定性,延长了降解速率和酚羟基的氧化速率并使涂层获得生物学功能,也由于阳离子的存在使得涂层可以结合水分子,增强涂层的润湿性。
Description
技术领域
本发明属于生物医用功能材料技术领域,具体涉及一种药物纳米多级结构涂层及其制备方法。
背景技术
表面工程策略作为赋予生物医用材料/器械表面多功能活性的一种有效手段而被广泛研究。目前实现医用材料表面抗凝血、抗感染、抗蛋白非特异性粘附、调控炎症、选择性促进细胞生长的方法主要包括:被动防御和主动防御。
被动防御的表面工程策略被广泛研究,与疏水表面相比,亲水表面具有更优异的生物相容性,因此此类涂层研究比较多的主要是亲水性表面,如聚乙二醇涂层、两亲性离子分子刷表面,两类涂层通过与水分子的有效结合在表面形成水合层,从而抵抗蛋白质、细胞和细菌的非特异性粘附和增殖,使得涂层材料具有优异的抗污性能,包括阻抗蛋白质粘附、细胞及细菌的粘附及生长。主动防御策略主要是将活性成分负载在涂层,通过如金属离子(Au、Ag+、Cu2+等)、生物活性分子或药物、蛋白质/多肽等的释放实现表面的杀菌、抗血栓、调控炎症及选择性促进细胞生长。
虽然被动防御涂层和主动防御涂层都具有优异的生物学性能,但研究发现涂层在长期服役时面临着结构稳定性(如亲水性分子刷的降解导致材料表面亲润性变差等)、功能时效性(如超亲水/超疏水表面的水合层/空气层被破坏后,阻抗性能会大大降低等)和药效性不足(一旦涂层中负载的药物完全释放后,由药物维持的生物学功能也将随之消失)等问题,最终导致植入器械失效而无法满足治疗效果。
另外,目前研究较多的在材料表面构建拓扑结构的方法主要有:阳极氧化、飞秒激光刻蚀、等离子刻蚀、碱活化、溶胶-凝胶法等,然而此类方法不仅对基底材料有要求还会一定程度对其造成损伤,且此类方法所构建的微/纳拓扑结构大多都是非活性材料构建(如纳米管、硅柱或基底材料等),不具有生物功能性。
故基于此,提出本发明技术方案。
发明内容
为了解决现有技术存在的问题,本发明提供了一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将纳米药物载体分散于溶剂中,得到纳米药物载体悬浊液;
(2)将多酚类化合物、多胺基化合物、氧化剂和金属离子分别溶解于酸性缓冲液中,分别得到多酚类缓冲液、多胺基缓冲液、氧化剂缓冲液和金属离子缓冲液;
(3)在基底材料表面依次加入所述纳米药物载体悬浊液、所述多酚类缓冲液、所述多胺基缓冲液、所述氧化剂缓冲液,于基底材料表面反应后进行清洗,得到反应样品;
(4)将所述反应样品浸没于所述金属离子缓冲液中,经反应后依次清洗、干燥,即得所述药物纳米多级结构涂层。
为便于理解本发明,对本发明的反应原理进行说明:
本发明首先将纳米药物载体颗粒均匀分散在溶剂中,在酸性环境下,再通过多酚类化合物、多胺基化合物在氧化剂的作用下氧化、交联、聚合,生成多酚纳米颗粒(十纳米级)结构膜层,纳米膜层将纳米药物载体(百纳米级)均匀包裹的同时将其牢固固定在基底材料表面;再在酸性溶液中,使金属离子与纳米膜保护层中的酚羟基螯合,此时金属离子能充当“螺钉”连接的作用,并增加纳米药物载体保护层的结构和功能稳定性,最终形成一个以药物为主体的药物纳米多级结构涂层。
优选地,步骤(1)中,所述纳米药物载体为高分子纳米粒(高分子纳米球和纳米囊)、固体脂质纳米粒、纳米脂质体、聚合物胶束、树枝状大分子、无机纳米粒子中的一种。
优选地,步骤(1)中,所述溶剂为水溶液、乙醇溶液、乙醇/水混合液中的一种;所述乙醇/水混合液中,乙醇与水的体积比为0.1~5:0.1~5。
优选地,步骤(2)中,所述多酚类化合物为单宁酸、没食子酸、丹酚酸B、表没食子儿茶素没食子酸酯、表儿茶素没食子酸酯、表儿茶素、表没食子儿茶素、邻苯二酚、邻苯三酚、黄酮类中的一种或两种以上的组合;所述多胺基化合物为乙二胺、戊二胺、2,2,4-三甲基六亚甲基二胺、1,8-二氨基辛烷、甲基环己烷二胺、1,3-二氨基甲基环己烷、2,4,6-三氨甲基环己烷、1,4-双二氨已基环己烷、2-(3,4-二羟基苯基)乙胺中的一种或两种以上的组合;所述氧化剂为过氧化氢、过硫酸铵、浓硝酸、高碘酸钠、高锰酸钾、重铬酸钾中的一种或两种以上的组合;所述金属离子为铜离子、银离子、锌离子和铁离子中的一种或两种以上的组合。
优选地,步骤(2)中,所述酸性缓冲液的pH为3~7;所述酸性缓冲液为乙酸-乙酸盐缓冲液、2-(N-吗啡啉)乙磺酸缓冲液、甘氨酸-盐酸缓冲液、邻苯二甲酸-盐酸缓冲液、邻苯二甲酸氢钾-氢氧化钠缓冲液、磷酸氢二钠-柠檬酸缓冲液、柠檬酸-氢氧化钠-盐酸缓冲液、柠檬酸-柠檬酸钠缓冲液中的一种。
优选地,步骤(3)中,所述纳米药物载体悬浊液、所述多酚类缓冲液、所述多胺基缓冲液、所述氧化剂缓冲液组成的混合液中,所述纳米药物载体的浓度为0.5~10 mg/mL,所述多酚类化合物的浓度为0.5~20 mg/mL,所述多胺基化合物的浓度为0.1~10 mg/mL,所述氧化剂的浓度为0.1~10 mg/mL。更优选地,所述混合液中,所述纳米药物载体的浓度为2 mg/mL,所述多酚类化合物的浓度为1 mg/mL,所述多胺基化合物的浓度为0.5 mg/mL,所述氧化剂的浓度为0.5 mg/mL。
优选地,步骤(3)中,所述基底材料为金属基生物材料、陶瓷基生物材料、高分子基生物材料、复合生物材料中的一种。
优选地,步骤(4)中,所述金属离子缓冲液中,金属离子的浓度为0.05~5 mg/mL。更优选地,金属离子的浓度为0.5 mg/mL。
优选地,步骤(3)和步骤(4)中,反应的温度为10~40℃,反应的时间为0.1~10h。更优选地,步骤(3)中,反应温度为30℃,反应时间为1 h;步骤(4)中,反应温度为30℃,反应时间为2 h。
基于相同的技术构思,本发明的再一方案是提供一种由上述制备方法得到的药物纳米多级结构涂层。
本发明的有益效果为:
1、本发明基于多酚类和多胺基化合物在氧化剂的作用下发生氧化、交联、聚合和沉积,只需要简单的“one-pot”法即可在纳米药物载体表面形成一层均匀的多酚纳米颗粒膜层,该多酚纳米颗粒膜层不但增加了纳米药物载体的稳定性,同时将纳米药物载体牢固固定在基底材料表面,实现了以药物为涂层构建的本体材料,只要涂层存在就有药物存在并能长效发挥生物学功能,且该多酚纳米颗粒膜层具有非材料依赖性,可以在不同形状和性能的基底材料表面(如导管、心血管支架、骨科、眼科、伤口敷料等材料及器械的表面)进行修饰、改性,具有广泛的适用性。
2、区别于传统的拓扑结构制备方法,本发明所述的药物纳米多级结构涂层中多酚/金属复合纳米颗粒尺寸在十纳米级,而纳米药物载体的尺寸在百纳米级,不同尺寸的纳米颗粒共同使得涂层具有拓扑结构,且所构建的拓扑结构不会损伤基底,且具有生物活性和生物学功能。
3、本发明所述药物纳米多级结构涂层中的多酚/金属复合纳米颗粒,其含有大量的亲水性基团如酚羟基、羧基、胺基等,可与多级纳米结构一起,使药物结构涂层获得优异的亲水性,且涂层表面呈负电荷,能够协同提高其在体内的生物相容性。
4、在机体内的病理组织环境中,常伴随着大量的活性氧自由基和炎症细胞浸润,多酚纳米颗粒膜层带有多酚类化合物相关的生物学功能,如抗氧化、清除自由基、调节炎症等,可以调节病理微环境并与纳米药物载体中的药物协同发挥治疗作用。
5、本发明所述药物纳米多级结构涂层中的金属离子与酚羟基螯合具有诸多作用:金属离子本身的生物学功能(如铜离子具有催化血液中一氧化氮供体释放NO,使涂层具有优异的血液相容性、抗菌性等);螯合的金属离子充当一个铆钉的作用,将多酚纳米颗粒进一步连接,增加了纳米药物载体保护层的结构稳定性,延缓了涂层中药物释放速率;与金属离子螯合后的酚羟基,其被氧化的速度减缓,延长其保存时间和多酚的生物学功能;金属离子作为阳离子存在涂层中可以结合水分子,协同增强涂层的润湿性。
6、本发明所述药物纳米多级结构涂层中的多酚纳米颗粒/金属复合层具有pH响应性,可在细菌感染环境下(弱酸性),加速解离多酚/金属复合纳米颗粒,打开纳米药物载体中药物的释放窗口,所释放的药物与多酚可协同作用对病理组织进行治疗。
7、本发明所述制备方法操作简单,反应高效、条件温和,具有广谱实用性,可以将不同的纳米药物载体修饰在不同材料和形状的基底表面,能够制备出只要涂层存在就有药物存在并长效发挥生物学功能的药物纳米多级结构涂层。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例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,下面描述中的附图仅仅是本发明的一些实施例,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为实施例1制得的药物纳米多级结构的形貌扫描电子显微镜(SEM)图(标尺10μm)。
图2为图1的放大图(标尺1μm)。
图3为用EDS能谱仪检测涂层中C、O、N和Cu元素的分布图。
图4为用EDS能谱仪检测涂层中C、O、N和Cu元素的含量图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚,下面将对本发明的技术方案进行详细的描述。显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动的前提下所得到的所有其它实施方式,都属于本发明所保护的范围。
实施例1
本实施例提供一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将载药吐温-80(聚合物胶束)均匀分散于乙醇/水混合液中,得到载药吐温-80悬浊液;其中,乙醇与水的体积比为1:4;
(2)将单宁酸、乙二胺、高碘酸钠和铜离子分别溶解于pH为5的乙酸钠缓冲液中,分别得到单宁酸缓冲液、乙二胺缓冲液、高碘酸钠缓冲液和铜离子缓冲液;
(3)在基底材料表面依次加入所述载药吐温-80悬浊液、所述单宁酸缓冲液、所述乙二胺缓冲液、所述高碘酸钠缓冲液,在25℃下于基底材料表面恒温反应3h后,经RO水充分清洗,得到反应样品;其中,所述载药吐温-80悬浊液、所述单宁酸缓冲液、所述乙二胺缓冲液、所述高碘酸钠缓冲液组成的混合液中,载药吐温-80的浓度为2 mg/mL、单宁酸的浓度为1 mg/mL,乙二胺的浓度为0.5 mg/mL、高碘酸钠的浓度为0.5 mg/mL;
(4)将所述反应样品浸没于浓度为0.5 mg/mL所述铜离子缓冲液中,在25℃下恒温反应3h后,再经RO水充分清洗,氮气干燥,即得所述药物纳米多级结构涂层。
实施例2
本实施例提供一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将载药聚乳酸纳米球(高分子纳米粒)均匀分散于水中,得到载药聚乳酸纳米球悬浊液;
(2)将表没食子儿茶素没食子酸酯、戊二胺、高锰酸钾和铜离子分别溶解于pH为4的乙酸钠缓冲液中,分别得到表没食子儿茶素没食子酸酯缓冲液、戊二胺缓冲液、高锰酸钾缓冲液和铜离子缓冲液;
(3)在基底材料表面依次加入所述载药聚乳酸纳米球悬浊液、所述表没食子儿茶素没食子酸酯缓冲液、所述戊二胺缓冲液、所述高锰酸钾缓冲液,在20℃下于基底材料表面恒温反应6h后,经RO水充分清洗,得到反应样品;其中,所述载药聚乳酸纳米球悬浊液、所述表没食子儿茶素没食子酸酯缓冲液、所述戊二胺缓冲液、所述高锰酸钾缓冲液组成的混合液中,载药聚乳酸纳米球的浓度为5 mg/mL、表没食子儿茶素没食子酸酯的浓度为2 mg/mL,戊二胺的浓度为2 mg/mL、高锰酸钾的浓度为2 mg/mL;
(4)将所述反应样品浸没于浓度为1 mg/mL所述铜离子缓冲液中,在20℃下恒温反应6h后,再经RO水充分清洗,氮气干燥,即得所述药物纳米多级结构涂层。
实施例3
本实施例提供一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将载药卵磷脂(固体脂质纳米粒)均匀分散于水中,得到载药卵磷脂悬浊液;
(2)将没食子酸、2,2,4-三甲基六亚甲基二胺、高碘酸钠和铁离子(Fe3+)分别溶解于pH为3.5的邻苯二甲酸-盐酸缓冲液中,分别得到没食子酸缓冲液、2,2,4-三甲基六亚甲基二胺缓冲液、高碘酸钠缓冲液和铁离子缓冲液;
(3)在基底材料表面依次加入所述载药卵磷脂悬浊液、所述没食子酸缓冲液、所述2,2,4-三甲基六亚甲基二胺缓冲液、所述高碘酸钠缓冲液,在15℃下于基底材料表面恒温反应10h后,经RO水充分清洗,得到反应样品;其中,所述载药卵磷脂悬浊液、所述没食子酸缓冲液、所述2,2,4-三甲基六亚甲基二胺缓冲液、所述高碘酸钠缓冲液组成的混合液中,载药卵磷脂的浓度为6 mg/mL、没食子酸的浓度为3 mg/mL,2,2,4-三甲基六亚甲基二胺的浓度为3 mg/mL、高碘酸钠的浓度为3 mg/mL;
(4)将所述反应样品浸没于浓度为1 mg/mL所述铁离子缓冲液中,在10℃下恒温反应10h后,再经RO水充分清洗,氮气干燥,即得所述药物纳米多级结构涂层。
实施例4
本实施例提供一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将载药纳米脂质体均匀分散于水中,得到载药纳米脂质体悬浊液;
(2)将邻苯三酚、1,8-二氨基辛烷、过硫酸铵和银离子分别溶解于pH为4的柠檬酸-柠檬酸钠缓冲液中,分别得到邻苯三酚缓冲液、1,8-二氨基辛烷缓冲液、过硫酸铵缓冲液和银离子缓冲液;
(3)在基底材料表面依次加入所述载药纳米脂质体悬浊液、所述邻苯三酚缓冲液、所述1,8-二氨基辛烷缓冲液、所述过硫酸铵缓冲液,在35℃下于基底材料表面恒温反应1h后,经RO水充分清洗,得到反应样品;其中,所述载药纳米脂质体悬浊液、所述邻苯三酚缓冲液、所述1,8-二氨基辛烷缓冲液、所述过硫酸铵缓冲液组成的混合液中,载药纳米脂质体的浓度为2 mg/mL、邻苯三酚的浓度为2 mg/mL,1,8-二氨基辛烷的浓度为1.5 mg/mL、过硫酸铵的浓度为2 mg/mL;
(4)将所述反应样品浸没于浓度为0.1 mg/mL所述银离子缓冲液中,在35℃下恒温反应1h后,再经RO水充分清洗,氮气干燥,即得所述药物纳米多级结构涂层。
实施例5
本实施例提供一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将载药多孔二氧化硅纳米粒子(无机纳米粒子)均匀分散于水中,得到载药多孔二氧化硅纳米粒子悬浊液;
(2)将表儿茶素没食子酸酯、1,3-二氨基甲基环己烷、重铬酸钾和锌离子分别溶解于pH为6的甘氨酸-盐酸缓冲液中,分别得到表儿茶素没食子酸酯缓冲液、1,3-二氨基甲基环己烷缓冲液、重铬酸钾缓冲液和锌离子缓冲液;
(3)在基底材料表面依次加入所述载药多孔二氧化硅纳米粒子悬浊液、所述表儿茶素没食子酸酯缓冲液、所述1,3-二氨基甲基环己烷缓冲液、所述重铬酸钾缓冲液,在35℃下于基底材料表面恒温反应0.5h后,经RO水充分清洗,得到反应样品;其中,所述载药多孔二氧化硅纳米粒子悬浊液、所述表儿茶素没食子酸酯缓冲液、所述1,3-二氨基甲基环己烷缓冲液、所述重铬酸钾缓冲液组成的混合液中,载药多孔二氧化硅纳米粒子的浓度为6 mg/mL、表儿茶素没食子酸酯的浓度为2 mg/mL,1,3-二氨基甲基环己烷的浓度为2 mg/mL、重铬酸钾的浓度为2 mg/mL;
(4)将所述反应样品浸没于浓度为1.5 mg/mL所述锌离子缓冲液中,在35℃下恒温反应0.5h后,再经RO水充分清洗,氮气干燥,即得所述药物纳米多级结构涂层。
实施例6
本实施例提供一种药物纳米多级结构涂层的制备方法,所述制备方法包括如下步骤:
(1)将载药泊洛沙姆纳米药物载体(聚合物胶束)均匀分散于水中,得到载药泊洛沙姆纳米药物载体悬浊液;
(2)将表没食子儿茶素、甲基环己烷二胺、30 %过氧化氢和锌离子分别溶解于pH为6.5的乙酸-乙酸盐缓冲液中,分别得到表没食子儿茶素缓冲液、甲基环己烷二胺缓冲液、30%过氧化氢缓冲液和锌离子缓冲液;
(3)在基底材料表面依次加入所述载药泊洛沙姆纳米药物载体悬浊液、所述表没食子儿茶素缓冲液、所述甲基环己烷二胺缓冲液、所述30 %过氧化氢缓冲液,在15℃下于基底材料表面恒温反应8h后,经RO水充分清洗,得到反应样品;其中,所述载药泊洛沙姆纳米药物载体悬浊液、所述表没食子儿茶素缓冲液、所述甲基环己烷二胺缓冲液、所述30 %过氧化氢缓冲液组成的混合液中,载药泊洛沙姆纳米药物载体的浓度为8 mg/mL、表没食子儿茶素的浓度为6 mg/mL,甲基环己烷二胺的浓度为4 mg/mL、30 %过氧化氢的浓度为5 %;
(4)将所述反应样品浸没于浓度为4 mg/mL所述锌离子缓冲液中,在15℃下恒温反应8h后,再经RO水充分清洗,氮气干燥,即得所述药物纳米多级结构涂层。
实验例
对实施例1所得药物纳米多级结构涂层进行SEM观测,结果如图1和图2所示,从图中可以看出在基底材料表面生成了一层由纳米药物载体为主体的纳米多级结构涂层,该涂层中纳米药物载体外表面由粒径为10~20 nm的多酚纳米颗粒均匀覆盖,且该反应过程并未对纳米药物载体形态造成改变,具有纳米多级结构。
从图3和图4的药物纳米多级结构涂层的EDS图谱可以看出,金属Cu2+均匀分布在涂层中。
以上所述,仅为本发明的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,可轻易想到变化或替换,都应涵盖在本发明的保护范围之内。因此,本发明的保护范围应以所述权利要求的保护范围为准。
Claims (10)
1.一种药物纳米多级结构涂层的制备方法,其特征在于,所述制备方法包括如下步骤:
(1)将纳米药物载体分散于溶剂中,得到纳米药物载体悬浊液;
(2)将多酚类化合物、多胺基化合物、氧化剂和金属离子分别溶解于酸性缓冲液中,分别得到多酚类缓冲液、多胺基缓冲液、氧化剂缓冲液和金属离子缓冲液;
(3)在基底材料表面依次加入所述纳米药物载体悬浊液、所述多酚类缓冲液、所述多胺基缓冲液、所述氧化剂缓冲液,于基底材料表面反应后进行清洗,得到反应样品;
(4)将所述反应样品浸没于所述金属离子缓冲液中,经反应后依次清洗、干燥,即得所述药物纳米多级结构涂层。
2.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(1)中,所述纳米药物载体为高分子纳米粒、固体脂质纳米粒、纳米脂质体、聚合物胶束、树枝状大分子、无机纳米粒子中的一种。
3.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(1)中,所述溶剂为水溶液、乙醇溶液、乙醇/水混合液中的一种;所述乙醇/水混合液中,乙醇与水的体积比为0.1~5:0.1~5。
4.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(2)中,所述多酚类化合物为单宁酸、没食子酸、丹酚酸B、表没食子儿茶素没食子酸酯、表儿茶素没食子酸酯、表儿茶素、表没食子儿茶素、邻苯二酚、邻苯三酚、黄酮类中的一种或两种以上的组合;所述多胺基化合物为乙二胺、戊二胺、2,2,4-三甲基六亚甲基二胺、1,8-二氨基辛烷、甲基环己烷二胺、1,3-二氨基甲基环己烷、2,4,6-三氨甲基环己烷、1,4-双二氨已基环己烷、2-(3,4-二羟基苯基)乙胺中的一种或两种以上的组合;所述氧化剂为过氧化氢、过硫酸铵、浓硝酸、高碘酸钠、高锰酸钾、重铬酸钾中的一种或两种以上的组合;所述金属离子为铜离子、银离子、锌离子和铁离子中的一种或两种以上的组合。
5.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(2)中,所述酸性缓冲液的pH为3~7;所述酸性缓冲液为乙酸-乙酸盐缓冲液、2-(N-吗啡啉)乙磺酸缓冲液、甘氨酸-盐酸缓冲液、邻苯二甲酸-盐酸缓冲液、邻苯二甲酸氢钾-氢氧化钠缓冲液、磷酸氢二钠-柠檬酸缓冲液、柠檬酸-氢氧化钠-盐酸缓冲液、柠檬酸-柠檬酸钠缓冲液中的一种。
6.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(3)中,所述纳米药物载体悬浊液、所述多酚类缓冲液、所述多胺基缓冲液、所述氧化剂缓冲液组成的混合液中,所述纳米药物载体的浓度为0.5~10 mg/mL,所述多酚类化合物的浓度为0.5~20mg/mL,所述多胺基化合物的浓度为0.1~10 mg/mL,所述氧化剂的浓度为0.1~10 mg/mL。
7.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(3)中,所述基底材料为金属基生物材料、陶瓷基生物材料、高分子基生物材料、复合生物材料中的一种。
8.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(4)中,所述金属离子缓冲液中,金属离子的浓度为0.05~5 mg/mL。
9.根据权利要求1所述药物纳米多级结构涂层的制备方法,其特征在于,步骤(3)和步骤(4)中,反应的温度为10~40℃,反应的时间为0.1~10h。
10.权利要求1~9任一项所述制备方法得到的药物纳米多级结构涂层。
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