CN112500528B - 一种具有抑菌效果的载药接触镜及其制备方法 - Google Patents
一种具有抑菌效果的载药接触镜及其制备方法 Download PDFInfo
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Abstract
本发明提供一种具有抑菌效果的载药淀粉水凝胶接触镜及其制备方法，具体是将淀粉、抑菌药物、水凝胶混合液、交联剂、热引发剂通过自由基聚合反应一步制备，所提供的接触镜具有抑制细菌增殖，防治眼部细菌感染的效果。本发明所提供的载药淀粉水凝胶接触镜，是将淀粉、表没食子儿茶素没食子酸、甲基丙烯酸羟基乙酯、甲基丙烯酸、蒸馏水、交联剂和热引发剂混合并超声均匀，然后将其注入接触镜模具发生自由基聚合反应一步制备具有抑菌效果的载药淀粉水凝胶接触镜。本发明提供一种具有抑菌效果的载药淀粉水凝胶接触镜及其制备方法，该接触镜具有药物缓释、抑制细菌生长保护眼部健康、制备简便的优点。
Description
技术领域
本发明属于镜片制备技术领域，具体涉及一种具有抑菌效果的载药接触镜及其制备方法。
背景技术
接触镜因其薄而轻、运动便利、不影响外观、视野开阔、可以有效矫正屈光不正等优点得到广泛使用，但由于接触镜会增加角膜感染的风险，因此其对角膜带来的不良作用不容忽视。在角膜接触镜所引发的角膜感染中，细菌性角膜炎是最为常见的并发症，其中绿脓杆菌性角膜炎是一种眼科急症，临床上病情发展极为迅速，如果不及时诊断与治疗，可造成永久性视力丧失甚至眼球摘除的严重后果。
目前角膜感染主要靠传统眼科药物进行治疗，而传统眼科药物存在生物利用度低、药物副作用大等弊端，角膜感染的治疗仍然是角膜病中较为棘手的问题。开发安全有效的给药方式，发展具有抑制效果的接触镜可以从源头改善眼部健康问题。近年来，淀粉作为一种常见的食用性多糖，因其优异的生物相容性、良好的降解性能,在制药领域和生物医学工程领域被广泛应用。以淀粉为材料加入抑菌药物发展具有抑菌效果的药物缓释淀粉水凝胶接触镜对于临床预防和治疗细菌性角膜炎有着重要的应用价值，可为接触镜广泛使用提供保障。
发明内容
本发明的目的是提供一种具有抑菌效果的载药淀粉水凝胶接触镜，是将淀粉、抑菌药物、水凝胶混合液、交联剂、热引发剂通过自由基聚合反应一步制备的，所提供的接触镜具有抑制细菌增殖，防治眼部细菌感染的效果。
本发明所提供的载药淀粉水凝胶接触镜，是将淀粉、表没食子儿茶素没食子酸、甲基丙烯酸羟基乙酯、甲基丙烯酸、蒸馏水、交联剂和热引发剂混合并超声均匀，然后将其注入接触镜模具发生自由基聚合反应一步制备具有抑菌效果的载药淀粉水凝胶接触镜。
所述的交联剂为二甲基丙烯酸乙二醇酯，热引发剂为偶氮二异丁腈；
所述的制备方法，其一种具体过程如下：
1)向淀粉中加入蒸馏水，超声均匀并水浴加热使其预糊化制成质量浓度为16.7％-33.3％的淀粉溶液；
2)向步骤1)中所得到的溶液中加入表没食子儿茶素没食子酸(0.3％-1％，w/w)、甲基丙烯酸羟基乙酯(50.84％-50.93％,w/w)、甲基丙烯酸(19.22％-19.26％,w/w)、二甲基丙烯酸乙二醇酯(0.45％-0.46％,w/w)，在常温下超声使其混合均匀；
3)向步骤2)中所得到的混合溶液中加入热引发剂偶氮二异丁腈(0.145％-0.146％,w/w)，将上述混合体系在常温下超声使其混合均匀；
4)将步骤3)的混合体系加入接触镜模具中；置于65℃水浴反应；随后沸水调价下除去为反应的单体；冷却后完成制备。
本发明提供一种具有抑菌效果的载药淀粉水凝胶接触镜，该接触镜具有药物缓释、抑制细菌生长保护眼部健康、制备简便的优点。
附图说明
图1为实施例1制备的不同含药量的载药淀粉水凝胶接触镜的透明度检测图。
图2为实施例1制备的具有抑菌效果的载药淀粉水凝胶接触镜的药物缓释曲线。
图3为实施例1、实施例2制备的接触镜的抑菌效果图。
具体实施方式
下面结合实施例和附图对本发明进行详细的描述。
实施例1
1)向5g红薯淀粉中加入300μl蒸馏水，在常温下超声10-15min使其混合均匀，水浴加热使其预糊化；
2)向步骤1)中所得到的溶液中加入1mg、2mg、4mg表没食子儿茶素没食子酸、水凝胶混合物(490μl甲基丙烯酸羟基乙酯：210μl甲基丙烯酸，70:30)、4.5μl二甲基丙烯酸乙二醇酯，在常温下超声3-5min使其混合均匀；
3)向步骤2)中所得到的混合溶液中加入1.5mg热引发剂偶氮二异丁腈，将上述混合体系在常温下超声2-3min使其混合均匀；
4)将步骤3)的混合体系加入接触镜模具中；置于65℃水浴锅中反应30h，随后沸水煮5min除去为反应的单体；
5)将接触镜从模具中小心取出即可。
实施例2
1)300μl蒸馏水、水凝胶混合物(490μl甲基丙烯酸羟基乙酯：210μl甲基丙烯酸，70:30)、4.5μl二甲基丙烯酸乙二醇酯，在常温下超声3-5min使其混合均匀；
2)向步骤1)中所得到的混合溶液中加入1.5mg热引发剂偶氮二异丁腈，将上述混合体系在常温下超声2-3min使其混合均匀；
3)将步骤2)的混合体系加入接触镜模具中；置于65℃水浴锅中反应30h，随后沸水煮5min除去为反应的单体；
4)将接触镜从模具中小心取出即可。
对所制备的接触镜进行了材料表征检测、透明性及溶胀性检测、细胞毒性检测、药物缓释以及体外抑菌性检测，产品的部分检测结果如下：
1)透明度
用紫外-可见分光光度计(SpectraMax M2,Molecular Devices,MD,USA)在250-800nm波长范围内以50nm间隔测量接触镜的透光率(图1)。检测发现，淀粉对接触镜透明度没有影响，表没食子儿茶素没食子酸会影响接触镜的透明度，随着含量的增加，接触镜的透明度不断下降；因此选用表没食子儿茶素没食子酸的浓度为0.3％-1％。
2)药物缓释性
将接触镜浸泡在4ml的去离子水中，置于35℃、100rpm的摇床培养箱中。在预定的时间间隔，取1mL缓释液，用新鲜去离子水代替。在263nm波长下测定表没食子儿茶素没食子酸的含量。
绘制表没食子儿茶素没食子酸累积释放量随时间的变化曲线，评价表没食子儿茶素没食子酸的释放量曲线(图2)。检测发现表没食子儿茶素没食子酸的释放量随着接触镜载药量的增大而增大，不同载药量的接触镜持续缓释药物可达12天。
3)体外抑菌试验
将实施例1和实施例2制备的接触镜与铜绿假单胞菌共培养。铜绿假单胞菌生长至OD值为1.5左右，PBS洗3遍后稀释至106CFU/ml，将接触镜和菌液在37℃培养箱120rpm培养箱震荡孵育24小时。随后取出接触镜用PBS轻柔的洗3遍，磨碎接触镜后用平板计数法检测细菌数量。检测结果如下表1所示。
表1：体外抑菌试验结果表
上述结果表明加入淀粉表现出较弱的抑菌性，加入表没食子儿茶素没食子酸，抑菌性增强且随着表没食子儿茶素没食子酸含量的增多抑菌性不断增强。
Claims (2)
1.一种具有抑菌效果的载药淀粉水凝胶接触镜，其特征在于，所述接触镜的制备方法如下：
1)向淀粉中加入蒸馏水，超声均匀并水浴加热使其预糊化制成淀粉溶液；其中淀粉溶液的浓度为16.7％-33.3％；
2)向步骤1)中所得到的溶液中加入表没食子儿茶素没食子酸、甲基丙烯酸羟基乙酯、甲基丙烯酸、交联剂二甲基丙烯酸乙二醇酯，在常温下超声使其混合均匀；
其中表没食子儿茶素没食子酸的浓度为0.3％-1％，甲基丙烯酸羟基乙酯的浓度为50.84％-50.93％，甲基丙烯酸的浓度为19.22％-19.26％，二甲基丙烯酸乙二醇酯的浓度为0.45％-0.46％；
3)向步骤2)中所得到的混合溶液中加入热引发剂偶氮二异丁腈，将上述混合体系在常温下超声使其混合均匀；
4)将步骤3)的混合体系加入接触镜模具中；置于65℃水浴反应；随后沸水条件下除去未反应的单体；冷却后完成制备。
2.如权利要求1所述的接触镜，其特征在于，所述的3)中热引发剂偶氮二异丁腈的浓度为0.145％-0.146％。
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