CN117653747A - 一种纳米马达复合材料及其制备方法和应用 - Google Patents
一种纳米马达复合材料及其制备方法和应用 Download PDFInfo
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- CN117653747A CN117653747A CN202311817503.3A CN202311817503A CN117653747A CN 117653747 A CN117653747 A CN 117653747A CN 202311817503 A CN202311817503 A CN 202311817503A CN 117653747 A CN117653747 A CN 117653747A
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Abstract
本发明公开了一种纳米马达复合材料及其制备方法和应用,该方法是在氨基化介孔二氧化硅‑铂复合材料表面,先修饰乳酸氧化酶,再通过酰胺化反应接枝乳酸链球菌素,即得DMSNs‑Pt‑LOX@Nisin复合材料。该制备方法简单,反应条件温和,成本低,可进行大规模的制备,得到的纳米马达材料在应用于制备抗生物膜感染促进糖尿病伤口愈合的药物中表现出级联推进并可特异性靶向耐甲氧西林金黄色葡萄球菌,可快速渗透到生物膜中,能够通过消除生物膜、促进血管生成和减轻炎症来加快糖尿病患者的伤口愈合过程。
Description
技术领域
本发明涉及一种纳米马达复合材料及其制备方法和应用,特别涉及基于多级模拟酶活性制备具有特异性靶向能力的纳米马达复合材料,及其用于促进糖尿病伤口愈合,属于抗菌纳米材料开发技术领域。
背景技术
表现出延迟愈合的慢性伤口对糖尿病患者的健康构成了巨大风险,给社会带来了值得注意的经济和医疗负担。由于复杂的创伤微环境,如细菌感染、缺氧状态、过度炎症和血管损伤,糖尿病足溃疡(DFU)的常见并发症已成为全球关注的重要治疗问题。值得注意的是,入侵细菌在复杂的致病环境中往往形成难以处理的生物膜,导致抗生素剂量增加,有效浓度降低。此外,长期注射抗生素可能会诱导多药耐药(MDR)细菌,并对其他器官造成系统性损伤。除了细菌感染,炎症应激增加和毛细血管损伤是导致糖尿病伤口愈合困难的另外两个重要因素。在患有糖尿病的患者中,巨噬细胞有从促炎(M1)表型向抗炎(M2)表型分化受损的趋势,导致伤口愈合延迟。此外,受损的血管阻止营养物质和氧气到达伤口部位,从而加剧了愈合过程的障碍。因此,迫切需要开发能够有效根除MDR细菌生物膜、促进血管生成、缓解伤口缺氧和减轻炎症应激的DFU新治疗方法。
纳米电机具有将来自当地疾病环境或外部来源的能量转化为机械力的能力,从而实现自推进运动。相比之下,传统的纳米药物通过依赖布朗运动和被动扩散而局限于疾病治疗。采用各种技术来激活纳米电机,包括外部光和磁场的应用。然而,这些物理刺激可能会对器官产生不利影响。因此,利用天然酶作为催化剂活化生物环境中的现有燃料,以推动纳米马达成为解决上述问题的有效方法。例如,文章(Wang L,Ana/>HuangX,et al.Lipase-Powered Mesoporous Silica Nanomotors for TriglycerideDegradation[J].AngewandteChemie International Edition,2019.DOI:10.1002/anie.201900697)的作者Sanchez及其同事,将脂肪酶负载到介孔二氧化硅中,并通过在体内使用脂肪酶催化的甘油三乙酸酯来驱动它。此外,由于其有效的组织穿透性和优异的药物转运性,纳米马达在细菌感染治疗中显示出良好的应用前景。值得注意的是,细菌微环境中的高乳酸浓度可以用作驱动纳米电机的燃料。然而,目前用于治疗细菌感染的大多数纳米电机的一个显著限制是它们缺乏细菌靶向功能。这种缺陷可能导致不良后果,例如:非靶向纳米马达无法到达细菌感染的特定部位,导致抗菌效率低下;以及纳米马达中缺乏细菌靶向可能导致对器官的不可避免的伤害。
因此,迫切需要开发一种能够特异性靶向细菌的纳米马达,用于制备治疗细菌感染的药物。
发明内容
针对现有技术中纳米马达无法到达细菌感染的特定部位及纳米马达制备方法存在的缺陷,本发明的第一个目的是提供一种纳米马达复合材料的制备方法,该方法通过在氨基化介孔二氧化硅-铂复合材料表面修饰具有动力自推动功能的乳酸氧化酶,使其能够在尾部产生氧气运动,同时通过酰胺化反应键合对甲氧西林金黄色葡萄球菌(MRSA)以及多药耐药细菌(MDR)抑制作用的乳酸链球菌素,增加了复合材料对耐甲氧西林金黄色葡萄球菌的靶向性。
本发明的第二个目的是提供一种纳米马达复合材料,该材料可以进行多级酶联反应,在伤口处催化过氧化氢产生氧气,从而提高生物组织处的氧含量,利用靶向性和自推进运动特性,提高了其药性。同时,该复合材料还具有乳酸酶模拟酶活性、过氧化氢酶活性和靶向性。
本发明的第三个目的是在于提供一种纳米马达复合材料的应用,作为催化推进纳米马达应用于制备抗生物膜感染促进糖尿病伤口愈合的药物,表现出良好的生物安全性,使得药物具有根除MRSA生物膜,促进细胞迁移、促进血管生成和减轻炎症反应来增强伤口愈合过程的能力。
为了实现上述技术目的,本发明提供了一种纳米马达复合材料的制备方法,该方法是在氨基化介孔二氧化硅-铂复合材料表面,先修饰乳酸氧化酶,再通过酰胺化反应接枝乳酸链球菌素,即得DMSNs-Pt-LOX@Nisin复合材料。
在本发明的技术方案中,首先采用具有大量孔隙结构、生物相容性高和生物可降解特性的氨基化介孔二氧化硅-铂(Pt-DMSNs)复合材料作为基体,通过复合材料表面的氨基与乳酸氧化酶中的羧基进行反应接枝修饰具有动力自推动功能的乳酸氧化酶;再通过酰胺化反应键合具有对甲氧西林金黄色葡萄球菌(MRSA)以及多药耐药细菌(MDR)抑制作用的乳酸链球菌素乳酸链球菌素(Nisin),最终制备得到介孔二氧化硅-铂负载乳酸氧化酶和乳酸链球菌素乳酸链球菌素纳米马达复合材料(DMSNs-Pt-LOX@Nisin,简称DPLN)。该制备方法简单,反应条件较为温和,成本低,应用前景大,可进行大规模的制备,得到的纳米马达材料能够在无外界干扰的条件下实现自推进运动,具有多级模拟酶活性,具有靶向作用。
作为一种优选的方案,所述氨基化介孔二氧化硅-铂复合材料通过以下方法制备得到:将十六烷基三甲基甲苯磺酸铵模板剂和三乙醇胺溶于水中后加入正硅酸发生水解反应,所得产物经酸液回流去除模板剂,得到介孔二氧化硅(DMSNs);所述介孔二氧化硅分散到甲苯中并与3-氨基丙基三乙氧基硅烷(APTES)进行回流反应,得到氨基化介孔二氧化硅(DMSNs-NH2);所述氨基化介孔二氧化硅溶解于十二烷基硫酸钠中,再加入固体石蜡加热并高速均质乳化,得到含石蜡涂层的氨基化介孔二氧化硅;所述含石蜡涂层的氨基化介孔二氧化硅分散于水中形成溶液后与铂纳米分散液混合,加入氯仿除去石蜡,即得;所述铂纳米分散液由氯铂酸(H2PtCl6)和聚乙烯吡咯烷酮(PVP)溶解于水中,经抗坏血酸还原得到。本发明的技术方案中加入固体石蜡的目的是在于在高温高速匀浆下与水形成Pickering乳液,从而在冷却后形成石蜡微球,而其中加入的DMSNs-NH2则会半包覆在石蜡微球表面,以有利于进一步单边修饰Pt纳米。
作为一个优选的方案,所述乳酸氧化酶和氨基化介孔二氧化硅-铂复合材料的质量比为(1~2):1。若质量比过低会导致乳酸氧化酶的负载降低,导致复合材料的多级酶联反应和自推动能力下降;而质量比过高会导致多余的乳酸氧化酶无法加载到纳米粒子,从而导致催化性能下降。
作为一个优选的方案,所述乳酸链球菌素乳酸链球菌素和氨基化介孔二氧化硅-铂复合材料的质量比为(1~2):1。若质量比过低会导致复合材料的抗菌性能显著下降;而质量比过高会导致多余的乳酸链球菌素无法加载到纳米粒子。
作为一个优选的方案,所述乳酸氧化酶溶液浓度为0.2~20mg/ml,体积为10~100mL;所述乳酸链球菌素溶液浓度为0.2~20mg/ml,体积为10~100mL。
作为一个优选的方案,所述酰胺化反应采用1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)和N-羟基琥珀酰亚胺(NHS)作为活化剂。本发明通过加入EDC和NHS可以先活化乳酸链球菌素乳酸链球菌素上的羧基,增加其活性,然后高效催化羧基进一步与氨基化介孔二氧化硅-铂复合材料上的氨基发生缩合反应,从而负载乳酸链球菌素乳酸链球菌素。
作为一个优选的方案,所述酰胺化反应的条件为:温度为2~6℃,时间为40~80min,pH为5.5~6.7。由于本发明所使用的乳酸氧化酶属于一种天然酶,为了尽可能保证乳酸氧化酶的活性,选择在低温和中性的条件进行反应。
作为一个优选的方案,所述含石蜡涂层的氨基化介孔二氧化硅在水溶液中的浓度为10~300mg/ml。
作为一个优选的方案,所述铂纳米分散液的浓度为0.1~2.5mg/ml。
作为一个优选的方案,所述含石蜡涂层的氨基化介孔二氧化硅和铂纳米分散液的固液比为1:(10~20)g/ml。通过控制固液比可以控制负载的Pt含量,固液比过大时,负载的Pt含量过小,所制备的复合材料单侧Pt纳米枝晶催化H2O2产生O2速率下降,不能为纳米马达提供充足的动力。
本发明还提供一种纳米马达复合材料,由上述制备方法得到。该材料具有乳酸酶模拟酶活性,其能够催化氧化乳酸产生丙酮酸;具有过氧化氢酶模拟酶活性,能够催化H2O2产生氧气;具有靶向性,能够靶向细菌膜中脂质II单元;还具有还具有纳米马达的特点,能在尾部产生氧气运动。
作为一个优选的方案,所述纳米马达复合材料的粒径为0.7~1.2nm。发明人研究发现,包含纳米尺寸的DPLN材料在应用时具有根除MRSA生物膜,促进细胞迁移、促进血管生成和减轻炎症反应来增强伤口愈合过程的能力。
本发明还提供了一种纳米马达复合材料的应用,将其作为应用于制备抗生物膜感染促进糖尿病伤口愈合的药物。
采用本发明所提供的纳米马达制备的糖尿病患者伤口愈合的药物的作用机理如下:发明人发现,在药物中,DPLN表现出级联推进并可特异性靶向耐甲氧西林金黄色葡萄球菌(MRSA),同时可以促进糖尿病伤口中丰富乳酸的转化,从而产生过氧化氢(H2O2)作为运动燃料。且单侧Pt纳米枝晶(Pt-DNs)催化H2O2产生O2,驱动纳米马达快速渗透到生物膜中。此外,通过装载选择性结合革兰氏阳性菌的尼辛,纳米马达通过自驱动过程主动靶向MRSA。体外和体内实验都表明,含DPLN纳米马达的药物可以根除MRSA生物膜。最后,动物研究也表明,含DPLN纳米马达的药物能够通过消除生物膜、促进血管生成和减轻炎症来加快糖尿病小鼠的伤口愈合过程。
作为一种优选的方案,所述药物包括纳米马达复合材料、生理盐水及辅料。辅料包括注射制剂常用的辅料如磷酸盐缓冲液、苯酚、葡萄糖等。
作为一种优选的方案,所述药物为注射制剂,进一步优选为药学上可接受的局部注射制剂。具体使用过程为:在使用过程中,可采用生理盐水对DPLN纳米球进行分散;将得到的分散溶液再通过注射施药。
作为一种优选的方案,所述的DPLN纳米复合材料不低于药学有效量。
作为一种优选的方案,所述药剂量为1~200mg/kg。每只施药对象(例如小鼠)优选施加DPLN纳米复合材料的剂量为5mg。
与现有技术相比,本发明的技术方案带来的有益技术效果:
1)本发明提供的纳米马达复合材料的制备方法,通过在氨基化介孔二氧化硅-铂复合材料表面修饰具有动力自推动功能的乳酸氧化酶,使其能够在尾部产生氧气运动,同时通过缩合反应键合对甲氧西林金黄色葡萄球菌(MRSA)以及多药耐药细菌(MDR)抑制作用的乳酸链球菌素,增加了复合材料对耐甲氧西林金黄色葡萄球菌的靶向性。
2)本发明提供的DPLN纳米复合材料该材料可以进行多级酶联反应,在伤口处催化过氧化氢产生氧气,从而提高生物组织处的氧含量,利用靶向性和自推进运动特性,提高了其药性。同时,该复合材料还具有乳酸酶模拟酶活性、过氧化氢酶活性和靶向性。此外,DPLN纳米复合材料良好的生物相容性使其对小鼠糖尿病伤口治疗表现出很好的生物安全性。
3)本发明制备的DPLN纳米复合材料通过Nisin实现靶向细菌作用,并可通过多级酶联反应应用于制备抗生物膜感染促进糖尿病伤口愈合的药物。
4)本发明的制备方法简单,反应条件较为温和,成本低,应用前景大,可进行大规模的制备。
附图说明
图1为本发明实施例1制得的DPLN纳米马达复合材料的TEM mapping图。
图2为本发明实施例1制得的DPLN纳米马达复合材料的为XRD图。
图3为本发明实施例1制得的DPLN纳米马达复合材料检测模拟乳酸酶活性图。
图4为本发明实施例1制得的DPLN纳米马达复合材料检测模拟过氧化氢酶活性图。
图5为本发明实施例1制得的DPLN纳米马达复合材料检测模拟纳米马达运动图。
图6为本发明实施例1制得的DPLN纳米马达复合材料靶向MRSA效果研究的TEM图。
图7为不同种类药剂处理后MRSA和大肠杆菌的24h细菌存活率。其中(1)为PBS的空白对照组,(2)为DP,(3)为DPL,(4)为DPLN(-NAL),(5)为DPLN。
图8为不同种类药剂小鼠糖尿病伤口愈合的伤口愈合图。
图9为本发明实施例2制得的DPLN纳米马达复合材料的TEM图。
具体实施方式
以下实施例仅就本发明的优选实施方案进行具体描述,并非对本发明的实施范围进行限定,对于技术领域的普通技术人员,在不脱离本发明的前提下,所作出的改进应当视为本发明的保护范围内。
实施例1
(1)DMSNs的制备:
十六烷基三甲基甲苯磺酸铵(0.96g)先与三乙醇胺(TEA)(0.17g)和水(50mL)混合,再与正硅酸(TEOS)溶液(7.8mL)混合。在80℃下搅拌2小时后,以10000rpm离心收集DMSNs。然后用水和乙醇洗涤,在60℃的烤箱中干燥。为了消除模板剂,DMSNs(1g)分散于50ml乙醇中,加入HCl(7.5mL),将混合物在70℃下回流24h。
(2)DMSNs-NH2的制备:
将DMSNs(0.5g)分散到50ml甲苯中,混合物搅拌30分钟;然后,将APTES(2ml)加入混合物中,随后在80℃下回流12小时,用乙醇洗涤三次;最后,产品在60℃真空下干燥过夜。
(3)Pt的制备:
将H2PtCl6(164mg)和PVP(20mg)溶解于20mL水中,然后加入10ml(500mg)抗坏血酸溶液,在45℃下磁力搅拌24小时。铂纳米粒子的颜色由淡黄色变为黑色。
(4)Pt-DMSNs的制备:
将DMSNs(50mg)溶解于十二烷基硫酸钠(SDS)(10mL,1.25mg mL-1)中,然后,加入1.0g固体石蜡,80℃加热,用高速均质机乳化5分钟。将乳剂冷却至室温,过滤,用水冲洗后,得到石蜡涂层的DMSNs。
将石蜡涂层的DMSNs(1g)分散在20mL水中,然后,将Pt纳米分散液(15ml)加入上述分散液中室温搅拌24h后,用氯仿除去石蜡,离心洗涤得到Pt-DMSNs。
(5)Pt-LOX-DMSNs的制备:
将乳酸氧化酶(LOX)100μL原液(2mg mL-1)与100μL Pt-DMSNs混合悬液(2mg mL-1),4℃过夜。
(6)DPLN的制备:
将Pt-LOX-DMSNs(5mg)分散液加入MES缓冲溶液(5ml,pH=5.5)中。随后,加入1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)和N-羟基琥珀酰亚胺(NHS)(2mg),溶液在4℃下搅拌60分钟。随后,将乳酸链球菌素(5mg)加入混合物中,搅拌4h。最后,离心洗涤获得装载乳酸链球菌素的纳米马达(DPLN)。
由图1可见本实施例的纳米马达复合材料为纳米粒径的球状结构。
将实施例1所制得的纳米马达材料进行模拟乳酸酶活性性能的测试:
将DPLN和天然乳酸氧化酶加入5mM乳酸钠溶液中,在37℃的水浴中孵育。采用乳酸试剂盒检测乳酸。由图3可知DPLN随着时间的延长消耗乳酸,证明其具有乳酸酶活性。
将实施例1所制得的纳米马达复合材料模拟过氧化氢酶活性性能的测试:
将DPLN(0.1mg)分别与过氧化氢(0、0.25、0.5、1、2、5mM)混合,用氧气计(JPSJ-605F)分别检测样品产出量。由图4可知DPLN随着时间的延长产氧量增加,证明其具有过氧化氢酶活性。
将实施例1所制得的纳米马达材料进行模拟纳米马达性能的测试:
将DPLN(1mg)与2%罗丹明B溶液,搅拌24小时,离心去除多余的罗丹明B,最后分散在1ml水中。将DPLN与含有不同浓度的乳酸钠(NaL)(0、1、2、5mM)的溶液混合,然后用共聚焦荧光显微镜观察,利用Video Spot跟踪软件分析了DPLN在不同浓度NaL溶液中的运动轨迹和速度均值,利用MATLAB软件生成并分析了均方位移(MSD)。由图5可知DPLN纳米球具有纳米马达的性能。
将实施例1所制得的纳米马达材料进行靶向MRSA测试:
在室温下,将相同数量的细菌(MRSA和大肠杆菌)(106CFU mL-1)与罗丹明B(红色荧光)标记的DPLN共培养。用低速离心以去除未结合的DPLN,然后用PBS(磷酸盐缓冲液)冲洗三次。用STOY9对微生物进行绿色荧光染色。最后,用三维共聚焦激光显微镜测量了MRSA和大肠杆菌溶液中的红色荧光的强度。
由图6可见,如红色箭头所示,DPLN与MRSA细胞膜的结合,相比之下,大肠杆菌组的细菌表面缺乏DPLN,表明DPLN具有靶向MRSA的性能。
将实施例1所制得的纳米马达材料进行细胞层面抗菌能力检测:
在整个抗菌实验中使用MRSA和大肠杆菌。在24孔板中加入细菌(1ml,108CFU ml-1)。在37℃孵育48h,每24h更换一次。最后用无菌PBS洗涤三次,获得细菌生物膜。采用不同种类药剂纳米颗粒(0.1mg mL-1)处理MRSA和大肠杆菌生物膜,其中(1)为PBS的空白对照组,(2)为DP,(3)为DPL,(4)为DPLN(-NAL),(5)为DPLN。生物膜经旋流3min,超声20min分离,进行标准平板计数。
DP即由实施例1步骤(1)~(4)制备得到的Pt-DMSNs材料;DPL即由实施例1步骤(1)~(5)制备得到的Pt-LOX-DMSNs材料;DPLN(-NAL)为加入2mM乳酸钠的的DPLN。
由图7可见,只有DPLN具有优异的抗菌性能,且对MRSA具有靶向性。其中,相比之下第四组中的DPLN(-NaL)处理后的MRSA和大肠杆菌的CFU与PBS对照组相比没有明显降低。表明在没有燃料的情况下,DPLN表现为自由扩散,穿透生物膜的能力有限,导致抗菌效果不理想。
将实施例1所制得的纳米马达材料进行动物实验测试:
动物实验在中南大学湘雅医学院动物中心实验室按照实验规程和伦理规则完成。
以BALB/c雄鼠为动物模型。小鼠在给药前禁食12~14小时,采用50mg/kg剂量链脲佐菌素(STZ)腹腔注射诱导糖尿病模型。注射后禁食2小时,持续5天。1周后测尾静脉血糖,血糖≥16.7mmol/L为成功诱导小鼠糖尿病模型。
小鼠背部刮胡子、清创、消毒,腹腔注射戊巴比妥溶液6单位(6mgmL-1)麻醉,建立糖尿病创面细菌感染模型,然后在每只小鼠的背侧做一个直径约8.0mm的椭圆形切口,并在每个伤口注射MRSA(108CFU)。之后,小鼠再培养两天,以便皮下生物膜的形成。分别用生理盐水和无菌PBS、DP、DPL、DPLN和万古霉素(Van)配制成注射制剂进行局部注射,剂量为5mgkg-1,连续4天。采用平板菌落计数法对创面细菌进行计数,观察DPLN的效果。将小鼠创面组织置于无菌PBS(1.0mL)中,用低倍超声分散匀浆,37℃孵育过夜。将菌液逐级稀释,取100μL于琼脂培养基中孵育16h,计数。在第0、2、6、10和15天对每个伤口进行拍照和记录。15天计划完成后,对小鼠实施安乐死,进一步对创面组织进行组织形态学分析,评估DPLN在体内消除生物膜、促进糖尿病溃疡愈合的速率。
将小鼠背部皮肤损伤8mm,接种10μL MRSA,浓度为108CFU/mL,培养2天形成MRSA成熟生物膜。随后对MRSA感染的伤口分别进行PBS、DP、DPL、DPLN和万古霉素(Van)作用。Van是抵抗MRSA感染的最后一道防线,作为阳性对照,PBS作为阴性对照(也即图8中的Control组)。结果见图8,与其他参照组相比,DPLN作用的糖尿病伤口愈合速度明显加快。15d后,DPLN组创面基本完全愈合。相比之下,其他组的伤口继续显示出明显的创伤区域。
实施例2
本实施例与实施例1的区别仅在于将步骤(6)中的乳酸链球菌素含量替换为10mg,其余步骤和条件均一致。所制备的纳米马达(DPLN)材料的形貌特征如图9所示,和实施例1一致,且也具有乳酸酶活性性能、过氧化氢酶活性性能、纳米马达性能以及靶向MRSA性能。
Claims (10)
1.一种纳米马达复合材料的制备方法,其特征在于:在氨基化介孔二氧化硅-铂复合材料表面,先修饰乳酸氧化酶,再通过酰胺化反应接枝乳酸链球菌素,即得DMSNs-Pt-LOX@Nisin复合材料。
2.根据权利要求1所述的一种纳米马达复合材料的制备方法,其特征在于:所述氨基化介孔二氧化硅-铂复合材料通过以下方法制备得到:将十六烷基三甲基甲苯磺酸铵模板剂和三乙醇胺溶于水中后加入正硅酸发生水解反应,所得产物经酸液回流去除模板剂,得到介孔二氧化硅;所述介孔二氧化硅分散到甲苯中并与3-氨基丙基三乙氧基硅烷进行回流反应,得到氨基化介孔二氧化硅;所述氨基化介孔二氧化硅溶解于十二烷基硫酸钠中,再加入固体石蜡加热并高速均质乳化,得到含石蜡涂层的氨基化介孔二氧化硅;所述含石蜡涂层的氨基化介孔二氧化硅分散于水中形成溶液后与铂纳米分散液混合,加入氯仿除去石蜡,即得;
所述铂纳米分散液由氯铂酸和聚乙烯吡咯烷酮溶解于水中,经抗坏血酸还原得到。
3.根据权利要求1所述的一种纳米马达复合材料的制备方法,其特征在于:
所述乳酸氧化酶和氨基化介孔二氧化硅-铂复合材料的质量比为(1~2):1;
所述乳酸链球菌素和氨基化介孔二氧化硅-铂复合材料的质量比为(1~2):1。
4.根据权利要求1~3任一项所述的一种纳米马达复合材料的制备方法,其特征在于:所述酰胺化反应采用1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和N-羟基琥珀酰亚胺作为活化剂。
5.根据权利要求4所述的一种纳米马达复合材料的制备方法,其特征在于:所述酰胺化反应的条件为:温度为2~6℃,时间为40~80min,pH为5.5~6.7。
6.根据权利要求2所述的一种纳米马达复合材料的制备方法,其特征在于:
所述含石蜡涂层的氨基化介孔二氧化硅在水溶液中的浓度为10~300mg/ml;
所述铂纳米分散液的浓度为0.1~2.5mg/ml;
所述含石蜡涂层的氨基化介孔二氧化硅和铂纳米分散液的固液比为1:(10~20)g/ml。
7.一种纳米马达复合材料,其特征在于:由权利要求1~6任一项所述的制备方法得到。
8.根据权利要求7所述的一种纳米马达复合材料,其特征在于:所述纳米马达复合材料的粒径为0.7~1.2nm。
9.权利要求7或8所述的一种纳米马达复合材料的应用,其特征在于:应用于制备抗生物膜感染促进糖尿病伤口愈合的药物。
10.根据权利要求9所述的一种纳米马达复合材料的应用,其特征在于:所述药物包括纳米马达复合材料、生理盐水及辅料。
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