CN115340698B - 一种医用抗菌材料及其制备方法和应用 - Google Patents
一种医用抗菌材料及其制备方法和应用 Download PDFInfo
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- CN115340698B CN115340698B CN202210980079.3A CN202210980079A CN115340698B CN 115340698 B CN115340698 B CN 115340698B CN 202210980079 A CN202210980079 A CN 202210980079A CN 115340698 B CN115340698 B CN 115340698B
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Classifications
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Abstract
本发明属于医用生物材料领域,一种医用抗菌硅橡胶及其制备方法和应用。该抗菌硅橡胶材料表面具有抗菌涂层,其工艺为:首先制备了一种同时含有季铵盐和卤代胺两种抗菌官能团的前驱体分子,再通过自由基聚合反应将其引入经等离子活化处理的硅橡胶材料表面,构建了一种具有接触—释放双重抗菌功能的新型医用硅橡胶材料。本发明所得抗菌硅橡胶材料制备方法高效、简便、可控,硅橡胶表面的抗菌涂层稳定且覆盖均匀。该抗菌硅橡胶材料作为医用材料,可显著减少常见细菌等致病性微生物增殖,有效降低由生物膜引发的感染风险。
Description
技术领域
本发明涉及一种医用抗菌材料及其制备方法和应用,属于医用生物材料领域。
背景技术
新冠疫情在全国范围内多点发生、局部暴发,共同催生了大规模、多层次的植入医疗产品需求,同时也衍生出一系列医疗感染问题。硅橡胶以其低毒、良好的血液相容性和生理稳定性而被广泛应用于植入或介入治疗的生物医学领域中。然而由于大部分植入硅橡胶医疗产品在人体内留置时间较长,尽管经过了严格的无菌化处置,但在治疗过程中材料表面接触到的病原菌来源复杂、传播渠道众多等,极大地增加了继发性感染发生的风险。由此引发的植入治疗失败导致治疗周期延长、经济负担加重甚至是死亡率攀升等一系列严重后果。临床上常采用广谱抗生素来应对病原菌继发性感染。然而,研究显示:65%以上的细菌感染与植入医疗材料表面细菌生物膜的形成有关。相比于浮游菌,生物膜对抗生素的敏感程度要低大约10—1000倍,因此常规抗生素疗法往往对生物膜感染失效,而滥用抗生素可能引发的耐药性问题则更加不可忽视。权威期刊《The Lancet》2022年1月19日报道了一项针对全球204个国家和地区的抗生素耐药性影响评估研究。结果表明:抗生素耐药性已成为全球主要死因,新冠疫情的持续爆发加剧了抗生素耐药性的严重程度。
生物材料表面抗菌改性一直是材料领域研究的热点之一。但其在实际应用中仍面临着诸多挑战。目前商品化的抗菌医用硅橡胶产品仍以抗生素(米诺环素/利福平,Journalof the American College of Surgeons,2015,221:739-747.)或银(磺胺嘧啶银,Colloids and Surfaces A:Physicochemical and Engineering Aspects,2022,643:128737.)等释放型抗菌表面为主。然而,其在释放抗菌成分过程中,往往存在初期“爆发式释放”而后期缓慢少量释放的问题,难以实现长效抗菌。另一方面,抗生素和银的无序和过度释放易引起耐药性。CN109912982A将石墨烯量子点包覆纳米银抗菌剂溶液加入到液体硅橡胶中,通过固化得到抗菌性良好的生物医用硅橡胶。然而抗菌纳米银不断溶出和在环境中累积,产生细胞毒性,导致材料缺乏良好的生物相容性。CN110128828A使用化学还原法,含醛基水溶液作为还原剂,β-CD作为稳定剂制备出复合抗菌剂,通过物理共混加入到液体硅橡胶中得到抗菌硅橡胶,制备出的抗菌硅橡胶具有较好的抗菌性。然而物理共混会导致抗菌涂层与材料表面结合较弱,稳定性差,不利于抗菌的长效性。这些问题限制了抗菌硅橡胶产品的深度应用。功能化硅橡胶抗菌表面设计应充分考虑实际应用的需求:即具有持久有效的抗菌效力同时避免引起耐药性,最大程度地延缓硅橡胶材料表面生物膜形成和降低感染及耐药性发生的风险。
发明内容
为解决现有硅橡胶等产品在作为植介入医用材料时无法有效兼顾抗菌的高效和持久性,从而无法应对细菌生物膜感染问题,本发明的目的在于提供一种医用抗菌材料及其制备方法和应用。
以医用硅橡胶材料为例,实现本发明目的的技术方案是(其它医用抗菌材料制备方法同下):
一种医用抗菌硅橡胶及其制备方法,具有以下步骤:
(1)5,5-二甲基海因依次通过取代反应和季铵化反应制得含有5,5-二甲基海因的季铵化卤代胺前驱体分子;
(2)将硅橡胶片用溶剂预处理洗净并在真空下采用等离子技术处理活化表面;
(3)将活化处理的硅橡胶置于季铵化卤代胺前驱体溶液中,在一定条件下在材料表面引发聚合,获得接枝改性的硅橡胶材料;
(4)将改性硅橡胶材料浸泡于次氯酸钠溶液中,在一定条件下氯化获得抗菌硅橡胶材料。
本发明步骤(1)具体为:5,5-二甲基海因和KOH溶于80-100mL乙醇溶液(乙醇溶液的体积分数为95%)中并加热回流30-40min。将上述混合溶液逐滴滴入溶有1,2-二溴乙烷的乙醇溶液中,得到的混合液继续回流反应8-12h(回流反应温度为80-100℃),反应结束后纯化得3-(2-溴乙烷)-5,5-二甲基海因中间体。
1,2-二溴乙烷相比于同等条件下的1,2-二氯乙烷,具有更好的杀菌活性和低毒性。
纯化方法具体为:反应完毕后旋蒸得到的粗产物溶解于乙酸乙酯,用10%的NaOH溶液、纯水分别洗涤三次,无水硫酸钠干燥过夜后旋蒸,得到3-(2-溴乙烷)-5,5-二甲基海因中间体。
二甲氨基丙基甲基丙烯酰胺溶于丙酮中并通入氮气30-60min。溶有海因中间体的丙酮溶液逐滴滴入上述混合液中,50-70℃回流搅拌12-18h。反应结束后冷却至室温,并纯化得季铵化产物。
纯化方法具体为:产物从混合液中分离并用乙醇反复洗涤数次,60℃下真空干燥过夜得到产物5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵。
优选地,步骤(1)中5,5-二甲基海因、KOH、1,2-二溴乙烷反应摩尔比为1:1:1.6,回流反应温度为80℃,海因中间体、二甲氨基丙基甲基丙烯酰胺摩尔比为1:1.4,回流反应温度为60℃,有利于提高3-(2-溴乙烷)-5,5-二甲基海因中间体和季铵化卤代胺前驱体的产率,减少副反应的发生。
步骤(1)中,在季铵化反应中,特定地选择二甲氨基丙基甲基丙烯酰胺与3-(2-溴乙烷)-5,5-二甲基海因参与季铵化反应的目的是二甲氨基丙基甲基丙烯酰胺结构中含有一个仲胺(—NH),这就为后续的氯化反应增加了一个可用于载氯的活性位点,进而提高抗菌的有效性。同时,获得的季铵化卤代胺前驱体分子在氯化后兼具海因环上卤代胺的释放杀菌性能和季铵盐基团的接触杀菌性能。
进一步的,本发明中,步骤(2)还包括步骤:将硅橡胶样品置于等离子增强化学沉积仪中,在真空条件下处理,通入O2并采用转子流量计控制流量,保持反应室中气压稳定;最后关闭电源取出样品。
优选地,步骤(2)中所述转子流量计控制流量为0.06m3/min,保持反应室中气压稳定在50Pa。
本发明中,步骤(3)具体为:将表面处理过的硅橡胶浸泡于去离子水中并加入引发剂,向混合液通入氮气30-60min排除溶解的氧气,升温至50-80℃,然后逐滴滴入5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵和交联剂N,N-亚甲基双丙烯酰胺的混合水溶液,氮气保护下搅拌反应4-8h。反应结束后用去离子水冲洗数次并用95%的乙醇反复洗涤除去吸附的均聚物并真空干燥(干燥温度优选50℃)。
作为本发明的优选实施例,所述的引发剂为过硫酸铵,过硫酸铵、N,N-亚甲基双丙烯酰胺质量比为4:1,更优选的控制反应温度为70℃,氮气保护下搅拌反应6h在该条件下引发聚合有利于获得交联密度高的抗菌涂层。
本发明中,步骤(4)具体为:将聚合物改性的硅橡胶片浸泡于次氯酸钠溶液中,氯化静置0.5-2h后用去离子水多次冲洗后真空干燥(一般冲洗三遍即可,干燥温度优选40℃)。
作为本发明的优选实施例,所述的氯化反应温度为0℃~8℃(更优选4℃,反应时间为1.5h),该条件下,材料载氯含量可保持较高的水平。
本发明具有以下显著优点:1.本发明中制备工艺简单,条件温和,有利于工业化推广应用。
2.本发明获得了一种带乙烯基的新型季铵化卤代胺抗菌前驱单体,不仅可用于硅橡胶,还可用于金属钛、聚酯纤维、聚乙烯等材料表面的抗菌涂层构筑。
3.本发明获得的双重抗菌功能的医用硅橡胶材料兼具卤代胺的释放杀菌性能和季铵盐基团的接触杀菌性能,有利于提高材料抗菌的长效性和高效性,减少对抗生素的依赖,降低耐药性发生的风险。
4.抗细菌生物膜研究结果表明:本发明获得的双重抗菌功能的医用硅橡胶材料能够有效破坏生物膜的结构和杀灭细菌,具有良好的抗生物膜感染应用前景。
附图说明
下面结合附图和实施例对本发明进一步说明。
图1为本发明实施例1中5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵红外谱图。
图2为本发明实施例1中5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵核磁共振谱图。
图3为本发明实施例4中抗菌硅橡胶片的XPS图。
图4为本发明实施例4中抗菌硅橡胶片的氯储存稳定性曲线图。
图5为本发明实施例4中抗菌硅橡胶片的氯可再生性曲线图。
图6为本发明实施例4中抗菌硅橡胶片表面S.aureus生物膜生长状况的场发射电镜扫描图。
具体实施方式
本发明不局限于下列具体实施方式,本领域一般技术人员根据本发明公开的内容,可以采用其他多种具体实施方式实施本发明的,或者凡是采用本发明的设计结构和思路,做简单变化或更改的,都落入本发明的保护范围。需要说明的是,在不冲突的情况下,本发明中的实施例及实施例中的特征可以相互组合。
下面结合实例详细说明本发明一种医用抗菌硅橡胶及其制备方法和应用。这些实施例仅用于说明本发明而不限制于本发明的范围。
实施例1
结合5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵(化合物3)的合成路线:
5,5-二甲基海因(化合物1,0.012mol,1.6g)和KOH(0.012mol,0.7g)溶于50mL95%的乙醇溶液中并加热回流30min。常温下将上述混合溶液逐滴滴入溶有1,2-二溴乙烷(0.02mol,3.7g)的乙醇溶液中,得到的混合液继续回流反应8h。反应完毕后旋蒸得到的粗产物溶解于乙酸乙酯,用质量分数为10%的NaOH溶液、纯水分别洗涤三次,无水硫酸钠干燥过夜后旋蒸,得到3-(2-溴乙烷)-5,5-二甲基海因(化合物2),产率约为79%;
2.6mL二甲氨基丙基甲基丙烯酰胺溶于30mL丙酮中并通入氮气30min。溶有1.18g3-(2-溴乙烷)-5,5-二甲基海因的丙酮溶液50mL逐滴滴入上述混合液中,升温至60℃回流搅拌12h。反应结束后冷却至室温,产物从混合液中分离并用乙醇反复洗涤数次,60℃下真空干燥过夜得到5,5-二甲海因-(3-乙基甲酰胺)-丙基二甲氨基溴化铵(化合物3),产率约为62%。
实施例2
将厚度为2mm的硅橡胶裁成面积为1cm×1cm的片状样品,然后用去离子水超声、丙酮清洗15min,最后用无水乙醇超声清洗20min,晾干备用。将洗净的硅橡胶样品置于等离子增强化学沉积仪中,在真空条件下处理,通入O2并采用转子流量计控制流量为0.06m3/min,保持反应室中气压稳定在50Pa。最后关闭电源取出样品。
实施例3
将表面处理过的硅橡胶浸泡于去离子水中并加入0.04g引发剂过硫酸铵,向混合液通入氮气30min排除溶解的氧气。升温至70℃,将0.15g 5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵和0.01g交联剂N,N-亚甲基双丙烯酰胺溶于去离子水中,并逐滴滴入上述混合液中,氮气保护下搅拌反应6h。反应结束后用去离子水冲洗数次并用质量分数为95%的乙醇反复洗涤除去吸附的均聚物并在50℃真空干燥。
实施例4
将聚合物改性的硅橡胶片浸泡于20g质量分数为10%的次氯酸钠溶液中,氯化反应温度为4℃,氯化静置1.5h后用去离子水冲洗三遍,40℃真空干燥。
通过本方法制备获得的季铵化卤代胺抗菌前驱单体结构通过FTIR和1HNMR进行表征;得到的抗菌硅橡胶材料通过XPS、Zeta电位进行表征。
1.红外谱图分析
图1中,1779、1770cm-1处的吸收峰分别对应单体中海因环上两个羰基的伸缩振动,1654cm-1处的吸收峰归属于单体分子中脂肪酰胺羰基的伸缩振动峰。1609cm-1处的吸收是单体中的C=C键的伸缩振动引起的。2931和2870cm-1处的吸收峰对应单体中亚甲基的伸缩振动。这些结果初步表明单体的成功制备。
2.核磁共振分析
在化学位移为1.31和3.14ppm左右出现的质子峰分别对应海因环上的和与季铵氮相连的两个甲基中的氢;在化学位移为8.13和8.5ppm左右出现的质子峰分别对应与脂肪酰胺氮和海因环上氮相连的氢原子,这两处的氢同时也是氯化的活性位点。这些特征峰以及对应的峰面积积分表明单体中存在海因环和脂肪酰胺的结构。
3.XPS谱图分析
对N1s进行分峰处理得到位于399.9,401.0和402.2eV的三个特征峰,其中399.9和402.2eV分别对应于海因环上酰胺氮和季铵氮,401.0eV特征峰则归属于氯化后N-Cl中的氮元素。对制备的抗菌硅橡胶表面元素及官能团进行了表征,证实了产品的成功制备。
4.Zeta电位分析
表1
表1中,未改性硅橡胶片的电势为-2.1mV,表明等离子活化处理后样品表面由于含氧基团而带有负电荷,聚合物改性后硅橡胶电势增加为34.6mV,表明季铵化卤代胺聚合物确实已成功包覆在材料表面。经次氯酸钠溶液处理后,其Zeta电位略微减小,表明活性氯的成功负载。
将制备好的抗菌硅橡胶加入10 mL体积比为9:1的乙醇/醋酸混合溶剂中(醋酸溶液浓度为0.1 mol/L),无色溶液立即变为黄色。静置10 min后,用浓度为0.0025 mol/L的硫代硫酸钠标准溶液进行滴定,直至溶液的颜色消失,记录滴定过程中消耗硫代硫酸钠的体积,活性氯百分含量(Cl%)可按计算公式计算得到:
式中:V——滴定用硫代硫酸钠体积
N——硫代硫酸钠溶液浓度
W——被测样品质量
5.氯储存稳定性分析
如图4所示,经过氯含量滴定计算可知,抗菌硅橡胶材料的含氯量为1.79%。这是由于在制备该材料时,选择了一种含有两个N-H氯化位点的季铵化卤代胺聚合物,因而显著地提高了氧化性氯的装载量。在储存实验周期的前6天内,硅橡胶材料的含氯量下降速率较快,随着储存时间的延长,含氯量继续缓慢减少。经过长达30天的储存后,抗菌硅橡胶的含氯量仅仅下降了20%,表明制备的抗菌硅橡胶在自然环境下具有较好的储存稳定性。在此过程中出现的活性氯含量的降低一方面是在自然环境储存时,空气中水蒸气的存在引起的损失;另一方面可能来自紫外可见光引发的N-Cl的断裂,导致活性氯的损失。
6.载氯循环性能分析
如图5所示,经过五轮释氯/载氯的循环后抗菌硅橡胶的载氯含量从1.79%减少到1.61%,表明该材料具有良好的载氯可再生能力,并有望用于循环抗菌。
将实施例1-4制备的抗菌硅橡胶分别对革兰氏阴性细菌—大肠杆菌(E.coli)以及革兰氏阳性细菌—金黄色葡萄球菌(S.aureus)抗菌性能进行评价。本发明分别进行了抗菌动力学和抗生物膜实验。具体步骤如下:
(1)LB液体培养基配制
分别称取5g酵母提取物、10g胰蛋白胨、10g氯化钠加入到1000mL烧杯中,再加入950mL去离子水超声搅拌10min使其完全溶解。然后用5mol/L的NaOH溶液将其pH调节至7.4,转移溶液至1L容量瓶中,放入高压灭菌锅中进行灭菌,121℃高压蒸汽灭菌30min。
(2)LB固体培养基配制
分别称取5g酵母提取物、10g胰蛋白胨、10g氯化钠、15g琼脂加入到1000mL烧杯中,再加入950mL去离子水并加热其完全溶解。然后用5mol/L的NaOH溶液将其pH调节至7.4,转移溶液至1L容量瓶中,放入高压灭菌锅中进行灭菌,121℃高压蒸汽灭菌30min。
(3)PBS缓冲液的配制
分别称取0.27g磷酸二氢钾、1.42g磷酸氢二钠、8g氯化钠、0.2g氯化钾加入到1000mL烧杯中,再加入800mL离子水超声搅拌10min使其充分溶解,然后滴加浓盐酸调节溶液pH至7.4,转移溶液至1L容量瓶中,放入高压灭菌锅中进行灭菌,121℃高压蒸汽灭菌30min。
(4)平板培养基的制备
将LB固体培养基加热融化成液态,向每个无菌培养皿中快速加入约10mL左右LB培养基,水平放置在无菌工作台上,室温下冷却固化,制成固态LB平板培养基。
(5)细菌悬浮液的制备
将接种环放在酒精灯火焰上烧灼,对其进行灭菌处理,用接种环从已培养了细菌的平板上挑取单菌落,加入有100mL LB液体培养基的锥形瓶中,在37℃,160rpm条件的摇床中培养16-24h。
抗菌动力学测试
将抗菌硅橡胶样品置于4.5mL培养液中,将500μL新鲜菌液加入样品分散液中。从加入菌液时开始计时,初始时间记为0min,分别在接触时间为30min、60min、90min、120min和150min时取100μL菌液与900μL PBS溶液,并按照1:10的比例逐级稀释。取100μL适当级数的稀释液涂布在LB琼脂板上,培养皿在37℃下培养20h,对琼脂板上形成的细菌菌落计数,细菌存活率=A/B,A是指样品接触后菌落的数量,B是指空白组的菌落数。据此计算得到不同时间下的活菌数并计算样品的抗菌效率。
表2
硅橡胶样品氯化前抗菌官能团均为单一的季铵盐,氯化后样品具有季铵化卤代胺双重抗菌效果。通过抗菌动力学实验比较两种材料的抗菌效率和抗菌持久性。从表2中可以看出,与金黄色葡萄球菌接触30min后,氯化前、后样品中细菌的存活率分别下降至91.5%和60.4%,90min后,氯化前、后样品中细菌的存活率分别下降至59.3%和1.3%,继续延长接触至120和150min时,氯化前样品中细菌的存活率未出现继续下降的趋势,表明此时样品几乎不具有显著的抗菌性,而氯化后样品中细菌的存活率均为0。与大肠杆菌接触60min时,氯化前样品几乎丧失抗菌性能,而氯化后样品中细菌的存活率随时间延长而下降显著,表明氯化后样品具有更持久的抗菌活性。
抗生物膜测试
首先按照固定配方配制新鲜TSBg胰蛋白胨大豆肉汤并在高压灭菌锅121℃高压蒸汽灭菌15min备用。采用TSBg培养液将新鲜的金黄色葡萄球菌菌液稀释至约106–107CFU/mL,随后取100μL该菌液加入预先放置有方形硅橡胶片的12孔板中,并在每孔中加入900μLTSBg营养培养液。在37℃的条件下静态培养48h,每24h更换一次新鲜的营养培养液。待成熟的细菌生物膜形成后,用少量PBS缓冲液轻轻冲洗样品表面移除表面的浮游细菌。并依次用浓度为30%,50%,70%,80%,90%和100%的乙醇脱水15min,脱水完毕后利用超临界点干燥仪对玻璃片冷冻干燥4h,喷金镀膜处理后用场发射扫描电镜观察生物膜的形貌。
如图6所示,未改性硅橡胶组(不存在抗菌涂层)中的生物膜生长非常致密,细菌堆积层完整,表明未经处理的生物膜生长状态良好。氯化前的改性硅橡胶组(仅有季铵盐抗菌涂层)表面生物膜结构开始出现劈裂和瓦解,但整体结构依然维持,这可能是由于仅有季铵盐抗菌基团材料抗菌能力有限,同时带负电荷的细菌会通过静电作用吸附到阳离子季铵盐硅橡胶材料表面,使其失去抗菌持久性。而氯化后改性硅橡胶组表面生物膜结构已完全破坏,仅有少量游离的细菌,这是由于氯化后强氧化性活性氯持续释放提高了杀菌效率,减少了细菌对材料表面的吸附,发挥了协同的抗菌功能,表明利用本发明制备的双重抗菌功能硅橡胶在治疗生物膜引发的感染方面具有良好的应用前景。
以上所述仅为本发明较佳的具体实施方式,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,根据本发明的技术方案及其构思加以等同替换或改变,都应涵盖在本发明的保护范围之内。
Claims (9)
1.一种医用抗菌材料的制备方法,其特征在于:包括以下步骤:
(1)5,5-二甲基海因依次通过取代反应和季铵化反应制备含有5,5-二甲基海因的季铵化卤代胺前驱体分子,取代反应是指5,5-二甲基海因与1,2-二溴乙烷在反应条件下生成3-(2-溴乙烷)-5,5-二甲基海因;季铵化反应是指3-(2-溴乙烷)-5,5-二甲基海因与二甲氨基丙基甲基丙烯酰胺在反应条件下生成5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵;
(2)将基底材料用溶剂预处理洗净并在真空下采用等离子技术处理活化表面;
(3)将活化处理的基底材料置于含有5,5-二甲基海因的季铵化卤代胺前驱体分子溶液中,在一定条件下在材料表面引发聚合,获得接枝改性的基底材料;
(4)将接枝改性的基底材料浸泡于次氯酸钠溶液中,在一定条件下氯化获得医用抗菌材料;
步骤(3)中:将步骤(2)活化处理后的基底材料浸泡于去离子水中并加入引发剂,向混合液通入氮气30-60 min排除溶解的氧气,升温至50-80℃,然后逐滴滴入5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵和交联剂N,N-亚甲基双丙烯酰胺的混合水溶液,氮气保护下搅拌反应4-8 h;反应结束后用去离子水冲洗数次并用质量分数为 95%的乙醇反复洗涤除去吸附的均聚物,然后真空干燥,得到接枝改性的基底材料;引发剂为过硫酸铵,过硫酸铵、N,N-亚甲基双丙烯酰胺质量比为3-5:1;
步骤(4)中:将步骤(3)中接枝改性的基底材料浸泡于次氯酸钠溶液中,氯化静置0.5-2h后用去离子水多次冲洗后真空干燥。
2. 根据权利要求1所述的医用抗菌材料的制备方法,其特征在于:还包括以下步骤:步骤(1)中:取代反应包括步骤:5,5-二甲基海因和KOH溶于80-100 mL 95%的乙醇溶液中并加热回流30-40min,然后逐滴滴入溶有1,2-二溴乙烷的乙醇溶液中,得到的混合液于80-100℃继续回流反应8-12 h,反应结束后纯化得到3-(2-溴乙烷)-5,5-二甲基海因中间体;
季铵化反应包括步骤:二甲氨基丙基甲基丙烯酰胺溶于丙酮中并通入氮气30-60 min,再逐滴滴入3-(2-溴乙烷)-5,5-二甲基海因中间体的丙酮溶液,50-70℃下回流搅拌反应12-18 h;反应结束后纯化、干燥得到产物5,5-二甲海因-(3-乙基甲基丙烯酰胺)-丙基二甲氨基溴化铵;
步骤(2)中:将基底材料置于等离子增强化学沉积仪中,在真空条件下处理,通入 O2并采用转子流量计控制流量,保持反应室中气压稳定;最后关闭电源取出样品。
3.根据权利要求2所述的医用抗菌材料的制备方法,其特征在于:步骤(1)中5,5-二甲基海因、KOH、1,2-二溴乙烷摩尔比为1:1:1.5-2。
4.根据权利要求2所述的医用抗菌材料的制备方法,其特征在于:步骤(1)中3-(2-溴乙烷)-5,5-二甲基海因中间体、二甲氨基丙基甲基丙烯酰胺摩尔比为1:1.2-1.5。
5. 根据权利要求2所述的医用抗菌材料的制备方法,其特征在于:步骤(2)中所述转子流量计控制流量为0.02-0.08 m3/min,保持反应室中气压稳定在 40-80 Pa。
6.根据权利要求2所述的医用抗菌材料的制备方法,其特征在于:步骤(4)氯化静置温度为0℃~8℃;次氯酸钠溶液的质量浓度为10%。
7.根据权利要求1所述的医用抗菌材料的制备方法,其特征在于:基底材料为硅橡胶、金属钛、聚酯纤维或聚乙烯中的任意一种。
8.一种根据权利要求1-7中任一项所述制备方法得到的医用抗菌材料。
9.根据权利要求8所述的医用抗菌材料作为植介入医用生物材料的应用。
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