CN106729940B - 一种缓释型长效抗菌载银敷料及其制备方法 - Google Patents
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Abstract
本发明公开了一种缓释型长效抗菌载银敷料,该辅料具有纳米银缓释性能,可实现长效抗菌。其制备方法是:利用儿茶酚接枝壳聚糖还原银离子获得复合溶胶;利用酸溶碱凝沉析法制备得到壳聚糖凝胶;再利用复合溶胶表面的儿茶酚与壳聚糖凝胶反应将复合纳米银固定在壳聚糖凝胶网络中;冷冻干燥后得到缓释型长效抗菌载银辅料。相比传统载银海绵,本发明的载银海绵中纳米银释放时间延迟了3倍以上。儿茶酚的存在成功实现了纳米银的缓释,解决了传统载银海绵存在的暴释问题。该缓释型抗菌敷料可以完全抑制细菌增殖长达4天以上,实现了长效抗菌,在抗菌敷料的临床使用中具有巨大的应用前景。
Description
技术领域
本发明属于医用抗菌敷料领域,具体涉及一种缓释型长效抗菌载银敷料及其制备方法。
背景技术
皮肤作为人体的最大器官,可以有效防止水分、电解质和血浆蛋白的流失,抵御细菌入侵,防止毒物进入,抵挡机械性损伤。然而在日常生活中,皮肤会因创伤、烧伤、烫伤和溃疡等发生缺损。因此迫切需要研制出创伤敷料,替代缺损皮肤,覆盖在创伤表面,促进伤口愈合。在创伤愈合中存在两大难题亟待解决,即不断渗出的组织液和被细菌感染的风险。因此,一种理想的创伤敷料,应该能够有效吸收组织渗出液,创造有利于创面愈合的微湿环境,且能避免或控制伤口感染。
传统的创伤敷料,如纤维素纱布、绷带等,已经得到了广泛应用。但此类敷料的吸湿性能差,吸除组织渗出液的效果不理想。与之相比,多孔海绵敷料,吸水性能强,使创面始终保持微湿。迄今为止,大量的海绵状敷料已经被制备出来并广泛应用于临床治疗中。
其中壳聚糖基海绵敷料,由于具有生物相容性、止血性、抗菌性和促伤口愈合的能力,被认为是最有前景的一类创伤敷料。然而纯壳聚糖海绵抗菌性能不足,需添加抗菌剂。在现有抗菌剂中,纳米银由于其广谱灭菌性、无耐药性等优点,备受关注。因此通过负载纳米银可以有效增强壳聚糖海绵的抗菌性能。但现有的壳聚糖基载银海绵,主要通过机械共混负载纳米银,使得银的释放速度过快,抗菌时间不长,增加了换药频率,给患者带来了较大的痛苦。因此研究制备出一种新型壳聚糖基载银海绵,通过纳米银的缓释实现长效抗菌,是一个充满前景与挑战的课题。
发明内容
本发明的目的是提供一种缓释型长效抗菌载银敷料及其制备方法,以解决现有的载银壳聚糖海绵,纳米银释放速度过快,抗菌时间过短的问题,本发明的新型的壳聚糖基载银海绵,通过纳米银的缓释实现长效抗菌,降低换药频率,减少病患痛苦。
本发明通过以下技术方案实现:首先利用儿茶酚接枝壳聚糖作为还原剂和稳定剂与银离子反应制备得到儿茶酚接枝壳聚糖-纳米银复合溶胶;再利用酸溶碱凝沉析法制备壳聚糖凝胶;然后利用上述复合溶胶表面的儿茶酚与壳聚糖凝胶链上的氨基发生交联反应,将复合纳米银牢牢固定在壳聚糖凝胶网络中;将该凝胶冷冻干燥后得到一种具有纳米银缓释性能的新型壳聚糖基载银海绵,即本发明的缓释型长效抗菌载银敷料。
上述方案中的儿茶酚接枝壳聚糖是通过酰胺化反应将3-(2,4-二羟基)苯基丙酸与壳聚糖上的氨基进行缩合反应制得,结构式如下所示:
上述方案中的纳米银的固定是通过儿茶酚与壳聚糖上氨基的反应实现的,本发明的具体机理图详见附图1。
本发明具体通过以下步骤实现:
1)分别配置质量浓度为1~3%的儿茶酚接枝壳聚糖的水溶液和质量浓度为20~30%的硝酸银水溶液。在搅拌下,将10~100μL硝酸银水溶液加入到儿茶酚接枝壳聚糖溶液中,反应1~5h后即制得了儿茶酚接枝壳聚糖-纳米银溶胶;
2)选取分子量为30000~800000的壳聚糖,溶解在质量浓度为1~2%的醋酸溶液中,配制成质量浓度为0.1~10%的壳聚糖酸溶液,加入氢氧化钠溶液,调节pH为8.5,使壳聚糖凝胶析出;
3)将步骤1)中制备得到的儿茶酚接枝壳聚糖-纳米银溶胶,加入到步骤2)中制备得到的壳聚糖凝胶中,在搅拌下,反应12~24h后,筛网过滤得到载银凝胶;
4)将步骤3)中制备得到的载银凝胶用水洗至中性,冷冻干燥后得到壳聚糖基载银海绵。
上述方法制得的载银海绵具有三维多孔结构,吸水性能强,纳米银释放速度缓慢而稳定,无暴释现象,可实现长效抗菌。
本发明相对于现有技术具有以下优点:
1)本发明利用儿茶酚与壳聚糖凝胶网络中的氨基形成交联作用,将纳米银颗粒牢牢固定在壳聚糖网络中。释放测试结果表明,相比传统载银海绵,该新型壳聚糖基载银海绵的纳米银释放时间延迟了3倍以上。儿茶酚的存在成功实现了纳米银缓释的目的,解决了传统载银海绵存在的暴释问题。
2)本发明制备得到的新型壳聚糖基载银海绵敷料,在体外抑菌测试中表现出了长效抑菌性能,可以完全抑制细菌增殖长达至少4天以上,意味着无需频繁更换敷料,减少了病患的痛苦,节省治疗费用。
3)本发明制备得到的新型壳聚糖基载银海绵敷料,孔隙率高,可吸除12倍于自重的组织渗出液,创伤接触面可始终保持微湿环境,且易脱除,不会造成二次伤害,解决了传统纱布、绷带等创伤愈合后产生肉痂的问题,不会产生伤疤。
附图说明
图1是本发明方法的具体机理示意图。
具体实施方式
以下结合实例进一步说明本发明。
实施例1:
1)分别配置质量浓度为1%的儿茶酚接枝壳聚糖的水溶液和质量浓度为20%的硝酸银水溶液。在高速磁力搅拌下,将10μL硝酸银水溶液缓缓加入到儿茶酚接枝壳聚糖溶液中,反应1h后即制得了儿茶酚接枝壳聚糖-纳米银溶胶;
2)选取分子量为30000的壳聚糖,溶解在质量浓度为1%的醋酸溶液中,配制成质量浓度为10%的壳聚糖酸溶液。加入氢氧化钠溶液,调节pH为8.5,使壳聚糖凝胶析出。
3)将步骤1中制备得到的儿茶酚接枝壳聚糖-纳米银溶胶,加入到步骤2中制备得到的壳聚糖凝胶中,在机械搅拌下,反应12h后,筛网过滤得到载银凝胶。
4)将步骤3中制备得到的载银凝胶用水洗至中性,冷冻干燥后得到壳聚糖基载银海绵。该缓释型抗菌敷料可以在4天内完全抑制细菌增殖,实现了长效抗菌的目的。
实施例2:
1)分别配置质量浓度为2%的儿茶酚接枝壳聚糖的水溶液和质量浓度为25%的硝酸银水溶液。在高速磁力搅拌下,将60μL硝酸银水溶液缓缓加入到儿茶酚接枝壳聚糖溶液中,反应3h后即制得了儿茶酚接枝壳聚糖-纳米银溶胶;
2)选取分子量为200000的壳聚糖,溶解在质量浓度为1.5%的醋酸溶液中,配制成质量浓度为2%的壳聚糖酸溶液。加入氢氧化钠溶液,调节pH为8.5,使壳聚糖凝胶析出。
3)将步骤1中制备得到的儿茶酚接枝壳聚糖-纳米银溶胶,加入到步骤2中制备得到的壳聚糖凝胶中,在机械搅拌下,反应18h后,筛网过滤得到载银凝胶。
4)将步骤3中制备得到的载银凝胶用水洗至中性,冷冻干燥后得到壳聚糖基载银海绵。该缓释型抗菌敷料可以在7天内完全抑制细菌增殖,实现了长效抗菌的目的。
实施例3:
1)分别配置质量浓度为3%的儿茶酚接枝壳聚糖的水溶液和质量浓度为30%的硝酸银水溶液。在高速磁力搅拌下,将100μL硝酸银水溶液缓缓加入到儿茶酚接枝壳聚糖溶液中,反应5h后即制得了儿茶酚接枝壳聚糖-纳米银溶胶;
2)选取分子量为800000的壳聚糖,溶解在质量浓度为2%的醋酸溶液中,配制成质量浓度为0.1%的壳聚糖酸溶液。加入氢氧化钠溶液,调节pH为8.5,使壳聚糖凝胶析出。
3)将步骤1中制备得到的儿茶酚接枝壳聚糖-纳米银溶胶,加入到步骤2中制备得到的壳聚糖凝胶中,在机械搅拌下,反应24h后,筛网过滤得到载银凝胶。
4)将步骤3中制备得到的载银凝胶用水洗至中性,冷冻干燥后得到壳聚糖基载银海绵。该缓释型抗菌敷料可以在10天内完全抑制细菌增殖,实现了长效抗菌的目的。
Claims (2)
1.一种缓释型长效抗菌载银敷料的制备方法,其特征在于,该方法为:以儿茶酚接枝壳聚糖作为还原剂和稳定剂与银离子反应制备儿茶酚接枝壳聚糖-纳米银复合溶胶;利用酸溶碱凝沉析法制备得到壳聚糖凝胶;然后采用儿茶酚接枝壳聚糖-纳米银复合溶胶表面的儿茶酚与壳聚糖凝胶中的氨基发生交联反应;将产物冷冻干燥后得到缓释型长效抗菌载银敷料;具体包括如下步骤:
1)分别配置质量浓度为1~3%的儿茶酚接枝壳聚糖的水溶液和质量浓度为20~30%的硝酸银水溶液,在搅拌下,将10~100μL硝酸银水溶液加入到儿茶酚接枝壳聚糖溶液中,反应1~5h后制得儿茶酚接枝壳聚糖-纳米银溶胶;
2)选取分子量为30000~800000的壳聚糖,溶解在质量浓度为1~2%的醋酸溶液中,配制成质量浓度为0.1~10%的壳聚糖酸溶液;加入氢氧化钠溶液,调节 pH 为8.5,使壳聚糖凝胶析出;
3)将步骤1)中制备得到的儿茶酚接枝壳聚糖-纳米银溶胶,加入到步骤2)中制备得到的壳聚糖凝胶中,在搅拌下,反应12~24h后,筛网过滤得到载银凝胶;
4)将步骤3)中制备得到的载银凝胶用水洗至中性,冷冻干燥后得到缓释型长效抗菌载银敷料。
2.一种缓释型长效抗菌载银敷料,其特征在于,采用如权利要求1的方法制备获得。
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