CN108096631A - 一种具有黏附性和抑菌性的温敏性水凝胶的制备方法 - Google Patents
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Abstract
本发明公开了一种具有黏附性和抑菌性的温敏性水凝胶的制备方法。首先对天然壳聚糖进行羟丁基化改性,使其具有温敏性(专利号201110214776.X)。其次,对羟丁基壳聚糖接枝左旋多巴(L‑DOPA),其化学名为3‑羟基‑L‑酪氨酸,含有儿茶酚基团,从而使水凝胶具有良好的黏附性。再次,对羟丁基壳聚糖接枝ε‑聚‑L‑赖氨酸(EPL),ε‑聚‑L‑赖氨酸是一种多肽,利用质子化的氨基使其具有抑菌功效。该复合凝胶材料具有黏附性、抑菌性,在组织工程和皮肤修复方面可能具有广泛的应用前景。
Description
技术领域
本发明属于医用材料技术领域,具体涉及一种具有黏附性和抑菌性的温敏性水凝胶的制备方法。
背景技术
皮肤是人体最大的器官,覆盖全身,保护体内各种组织和器官免受物理损伤、化学损伤和病原微生物的侵袭。皮肤大面积裸露于外部环境,很容易受到损伤。传统的皮肤伤口敷料有纱布、绷带等,但都具有一定的局限性,不能完全满足慢性伤口愈合的需要。理想的皮肤修复产品本身应具有一定的黏附性、抗菌性和生物相容性,不会对机体造成伤害。因此开发出有效的皮肤修复产品具有重要意义。
壳聚糖作为一种天然阳离子聚合物,由于其生物可降解性、抑菌性、低毒性和非免疫原性而受到了广泛关注,但壳聚糖水溶性差的性质限制了其在许多方面的应用。经羟丁基化修饰的壳聚糖水溶性好且具有温敏性,但是其形成的水凝胶机械性能差、抑菌效果不理想且组织黏附性低。受海洋中贻贝黏附岩石的能力所启发,采用左旋多巴修饰羟丁基壳聚糖赋予其一定的黏附性。然而,固体黏合性能的水凝胶易黏附细菌,不利于伤口愈合。由此在对羟丁基壳聚糖进行儿茶酚基团修饰后,又对其接枝了ε-聚-L-赖氨酸(一种具有广谱抑菌活性的多肽),弥补了其抑菌性差的特点。
本发明研制了一种模拟贻贝丝足黏附性的并可抑菌的温敏性水凝胶的制备方法,该水凝胶具有固有的抗菌性、水溶性和良好的组织黏附性,作为新型壳聚糖基材料用于皮肤修复具有巨大的潜力和应用前景。。
发明内容
本发明的目的是提供一种具有黏附性和抑菌性的温敏性水凝胶的制备方法,该法制备的水凝胶具有一定的黏附性和抗菌功能,在组织工程和皮肤修复方面可能具有广泛的应用前景。
本发明实现其发明目的所采用的技术方案具体步骤如下:
1. 羟丁基壳聚糖(HBC)的制备(参考专利CN201110214776.X);
2. 称取ε-聚-L-赖氨酸(EPL)和左旋多巴(L-DOPA)分别溶于去离子水中,得到EPL溶液和L-DOPA溶液,向溶液中加入N-羟基琥珀酰亚胺(NHS)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC),活化羧基;将活化后的EPL溶液和L-DOPA溶液加入到浓度(w/v)为0.1%~2%的HBC溶液中,其中EPL与HBC的质量比为0.01~10:1,L-DOPA与HBC的质量比为0.1~10:1,磁力搅拌过夜;反应结束后透析,冷冻干燥,得到聚赖氨酸-左旋多巴-羟丁基壳聚糖(eLHBC);
3. eLHBC在低温下溶于去离子水中,其浓度(w/v)为3%~8%,升温后制得水凝胶。
附图说明
图1为eLHBC对金黄色葡萄球菌(Staphylococcus aureus)的抑菌性,另设有空白对照组和HBC组;
图2为eLHBC对大肠杆菌(E.coli)的抑菌性,另设有空白对照组和HBC组;
图3为HBC和eLHBC黏性测试。
具体实施方式
下面结合实施例对本发明作进一步的描述,但本发明不仅限于下列实例。
实施例1
1. HBC的制备采用现有技术(参考专利CN201110214776.X),其步骤如下:
首先称取一定量壳聚糖粉末分散于50%的NaOH水溶液中进行碱化处理,NaOH水溶液用量为每克壳聚糖10mL,N2保护下搅拌作用24h,挤干除去液体,得到固形物;然后将固形物加入到异丙醇水溶液中,异丙醇水溶液的用量为每克壳聚糖20mL,随后加入一定体积的1,2-环氧丁烷,反应1小时,用功率600W-1200W微波作用,提升至一定的反应温度,继续保温搅拌一定时间进行反应,停止微波结束反应,冷却至升温前的温度;最后调节体系的pH至中性,滤去不溶物,加入乙醇,离心,真空干燥,得到HBC;
2. 将15mg EPL溶于1mL去离子水中得到EPL溶液,向溶液中加入4.60mg NHS、7.67mgEDC,在黑暗条件下反应活化;将3.94mg L-DOPA溶于 2mL去离子水中得到L-DOPA溶液,向溶液中加入4.60mg NHS、7.67mg EDC,活化羧基;将活化后的EPL溶液和L-DOPA溶液加入到5mL浓度(w/v)为1%的HBC溶液中,磁力搅拌过夜;反应结束后透析,冷冻干燥,得到eLHBC;
3. eLHBC在低温下溶于去离子水中,其浓度(w/v)为4%,升温后得到水凝胶。
实施例2
1. HBC的制备同实例1中1步;
2. 将15mg EPL溶于1mL去离子水中得到EPL溶液,向溶液中加入4.60mg NHS、7.67mgEDC,在黑暗条件下反应活化;将19.72mg L-DOPA溶于10mL去离子水中得到L-DOPA溶液,向溶液中加入23.02mg NHS、38.34mg EDC,活化羧基;将活化后的EPL溶液和L-DOPA溶液加入到5mL浓度(w/v)为1%的HBC溶液中,磁力搅拌过夜;反应结束后透析,冷冻干燥,得到eLHBC;
3. eLHBC在低温下溶于去离子水中,其浓度(w/v)为4%,升温后得到水凝胶。
实施例3
1. HBC的制备同实例1中1步;
2. 将15mg EPL溶于1mL去离子水中得到EPL溶液,向溶液中加入4.60mg NHS、7.67mgEDC,在黑暗条件下反应活化;将39.44mg L-DOPA溶于 20mL去离子水中得到L-DOPA溶液,向溶液中加入46.04mg NHS、76.68mg EDC,活化羧基;将活化后的EPL溶液和L-DOPA溶液加入到5mL浓度(w/v)为1%的HBC溶液中,磁力搅拌过夜;反应结束后透析,冷冻干燥,得到eLHBC;
3. eLHBC在低温下溶于去离子水中,其浓度(w/v)为4%,升温后得到水凝胶。
Claims (3)
1.一种带有黏附性和抑菌性的温敏性水凝胶的制备方法,包括如下步骤:(1)羟丁基壳聚糖(HBC)的制备(参考专利201110214776.X);(2)称取ε-聚-L-赖氨酸(EPL)和左旋多巴(L-DOPA)分别溶于去离子水得到EPL溶液和L-DOPA溶液,向溶液中加入N-羟基琥珀酰亚胺(NHS)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC),活化羧基;将活化后的EPL溶液和L-DOPA溶液加入到预先溶解的HBC溶液中,磁力搅拌过夜;反应结束后透析,冷冻干燥,得到聚赖氨酸-左旋多巴-羟丁基壳聚糖(eLHBC);(3)eLHBC在低温条件下溶于去离子水中,升温后制得水凝胶。
2.根据权利要求1所述的抗菌性自黏附水凝胶eLHBC,其特征在于:HBC的相对分子质量为500~2000kDa, EPL的相对分子质量为2~6kDa;在反应过程中EPL与HBC的质量比为0.01~10:1,L-DOPA与HBC的质量比为0.1~10:1。
3.根据权利要求1所述的抗菌性自黏附水凝胶eLHBC,其特征在于: HBC在低温条件下溶于去离子水中的浓度(w/v)为0.1%~2%;eLHBC在低温条件下溶于去离子水中的浓度(w/v)为3%~8%。
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CN110368527A (zh) * | 2018-07-18 | 2019-10-25 | 尹静波 | 一种温敏粘附性脱钙骨复合组织工程支架及制备方法 |
CN112472865A (zh) * | 2020-12-03 | 2021-03-12 | 广东工业大学 | 一种温敏抗菌止血水凝胶及其制备方法和应用 |
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