CN114404646A - CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶 - Google Patents

CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶 Download PDF

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CN114404646A
CN114404646A CN202111630532.XA CN202111630532A CN114404646A CN 114404646 A CN114404646 A CN 114404646A CN 202111630532 A CN202111630532 A CN 202111630532A CN 114404646 A CN114404646 A CN 114404646A
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杨建军
许雨芩
吴庆云
吴明元
张建安
刘久逸
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Abstract

本发明公开了一种CM‑β‑CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶，涉及抗菌水凝胶技术领域，按重量组分计，包括80‑100份丙烯酰胺、40‑50份马来酸酐、16‑20份壳聚糖、4‑8份羧甲基化β‑环糊精和2‑4份单宁酸；本发明制备出具有结构适应性强、孔隙率高、粘附性能优异、抗氧化能力强和抗菌活性强等优点的复合双网络型水凝胶，有望作为支架材料应用于更广泛的生物医学领域。

Description

CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶
技术领域：
本发明涉及抗菌水凝胶技术领域，具体涉及一种CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶及其制备方法。
背景技术：
遭受机械创伤、烧伤、手术、战斗创伤等造成的皮肤创伤通常伴随着伤口出血和细菌感染，有时还会导致死亡。因此，使用伤口敷料来有效控制出血、细菌感染和保护内脏器官是创伤创面治疗的迫切需要。迄今为止，伤口敷料已开发成不同形式，如海绵、水凝胶、薄膜和纳米纤维垫。在这些敷料中，水凝胶由于其高比表面积、互连网络、不同孔径的高孔隙率以及模拟天然细胞外基质的结构而得到了更多的研究。水凝胶通常不具有较强的粘附能力，甚至同一种水凝胶的胶块之间也不会产生粘附，水凝胶的强附着力必须依赖于水凝胶内部的聚合物网络，因此制备具有优异粘附性的水凝胶仍然是一个具有挑战性的问题。
壳聚糖是自然界中仅次于纤维素的第二丰富的生物高聚物，是一种天然、无毒、生物相容、可生物降解的多糖。此外，由于其独特的止血和抗菌活性，壳聚糖广泛用于伤口愈合，但它本身的细胞亲和力较差，机械强度不足，这限制了它在生物医学应用中的应用。
环糊精是由α-(1-4)糖苷键连接的6、7或8个D-葡萄糖单元组成的环状低聚糖。它们具有疏水性的内部空间和亲水性的外部表面，可与多种分子产生主客体相互作用，但β-环糊精溶解度低，且影响其与客体形成包容物的水溶性，限制其应用范围；因此需要将β-环糊精改性处理。单宁酸在各种植物中含量丰富，其分子结构中含有高含量的邻苯二酚和邻苯三酚片段，因此具有高抗氧化性、高粘附性、抗菌性和抗炎性。
现有技术中，例如专利CN 109762182B公开了一种抗菌水凝胶的制备方法，该水凝胶以聚乙烯醇和单宁酸为原料，采用冻融法制备，步骤繁琐，需多次冷冻-解冻，耗时长，制备的水凝胶形成的抑菌圈较小，抗菌性能较差；专利CN 113274543A公开了一种黏附抗菌温度耐受功能水凝胶的制备方法，但是其引入了常见抗菌剂聚赖氨酸、季铵盐壳聚糖、聚六亚甲基胍盐酸盐等高分子抑菌剂，粘附性能不强，制得的抗菌水凝胶的生物相容性较差，对皮肤具有一定的刺激性。
因此，如何制备出抗菌性能优异、粘附性强且力学性能较好的抗菌型水凝胶，是本领域技术人员急需解决的技术问题。本发明在壳聚糖水溶液中通过丙烯酰胺和马来酸酐单体的原位聚合，在壳聚糖和P(MAH-r-AM)之间进行离子配位，提出了一类新型的超分子纳米纤维结构杂化水凝胶。
发明内容：
本发明所要解决的技术问题在于提供一种CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶及其制备方法，以解决现有技术中制备的抗菌型水凝胶黏附性能差、抗菌性能不强、生物相容性不高等问题。
本发明所要解决的技术问题采用以下的技术方案来实现：
本发明的一个目的是提供一种CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶，按重量组分计，包括80-100份丙烯酰胺、40-50份马来酸酐、16-20份壳聚糖、4-8份羧甲基化β-环糊精和2-4份单宁酸。
本发明的另一个目的是提供一种上述水凝胶的制备方法，包括如下步骤：
(1)羧甲基化β-环糊精的干法制备：取β-环糊精研细，加碱研磨，再滴入无水乙醇和水研磨，碱化后加入氯乙酸，研磨一段时间后放入烘箱中，取出后继续研磨，如此反复进行醚化反应，最后用乙醇洗涤，烘干；
(2)羧甲基化β-环糊精/单宁酸分散液的制备：将步骤(1)制备的羧甲基化β-环糊精粉末加入到去离子水中，搅拌后超声处理，并加入单宁酸，制得羧甲基化β-环糊精/单宁酸分散液；
(3)水凝胶的制备：将马来酸酐溶解于去离子水中，再加入壳聚糖混合，得到壳聚糖-马来酸酐溶液；然后将丙烯酰胺、步骤(2)制备的羧甲基化β-环糊精/单宁酸分散液加入到壳聚糖-马来酸酐溶液中，反应一段时间后，降温加入引发剂、交联剂进行反应，得到CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶。
所述步骤(1)中碱为NaOH。
所述步骤(1)中碱化时间为0.5-1.5h。
所述步骤(1)中碱与β-环糊精的重量比为(0.2-0.25):1。
所述步骤(1)中醚化反应时的烘箱温度为40℃-50℃。
所述步骤(1)中β-环糊精与氯乙酸的摩尔用量比为(4-6):1。
所述步骤(3)中反应温度为50-60℃，反应时间为2-3h，降低温度至30-40℃。
所述步骤(3)中引发剂为过硫酸钾。
所述步骤(3)中交联剂为N,N’-亚甲基双丙烯酰胺。
本发明的有益效果是：
1、本发明利用壳聚糖水溶液中马来酸酐和丙烯酰胺单体的原位聚合，在壳聚糖和聚合(丙烯酰胺-马来酸酐)之间进行离子配位，制备了一类新型的超分子纳米纤维结构杂化水凝胶；壳聚糖在高浓度或高温度下倾向于通过平行排列聚集成纳米纤维，是形成杂化水凝胶刚性部分的理想组分。而软P(MAH-r-AM)链可以为杂化水凝胶提供弹性和亲水性，进一步增强水凝胶的机械性能；再通过羧甲基化改性β-环糊精，加入单宁酸(鞣酸)，增强其与客体单宁酸形成包容物的水溶性，进一步提高了对细菌的抗菌活性以及体外抗氧化能力；制备出具有结构适应性强、孔隙率高、粘附性能优异、抗氧化能力强和抗菌活性强等优点的复合双网络型水凝胶，有望作为支架材料应用于更广泛的生物医学领域。
2、本发明利用原位聚合的方法，在壳聚糖和聚合(丙烯酰胺-马来酸酐)之间进行离子配位，先利用马来酸酐和丙烯酰胺发生自由基聚合生成长链，再利用P(MAH-r-AM)聚电解质链中丰富的-COOH基团与壳聚糖的-NH2偶联形成动态离子交联超分子网络；引入羧甲基化β-环糊精嵌入单宁酸的结构，再利用羧甲基化β-环糊精中羟基与壳聚糖中羟基和氨基通过静电吸附以及氢键作用连接在一起，形成双网络复合水凝胶；单宁酸中高含量的邻苯二酚和邻苯三酚使复合水凝胶具有类似贻贝的贴附性；由此，本发明制备的羧甲基β-环糊精负载单宁酸的壳聚糖/马来酸酐-丙烯酰胺双网络抗菌水凝胶具有优异的抗菌性，良好的生物相容性，贴附性强，在人造皮肤、韧带以及作为伤口绷带敷料等领域具有广阔的前景。
附图说明：
图1为本发明制备的水凝胶的扫描电镜图。
具体实施方式：
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解，下面结合具体实施例和图示，进一步阐述本发明。
空白对照
壳聚糖/丙烯酰胺-马来酸酐水凝胶的制备：室温下，将1g马来酸酐溶解于7.5g去离子水中，再加入0.2g壳聚糖，磁力搅拌12h，得到壳聚糖-马来酸酐溶液；于60℃恒温水浴锅中将2g丙烯酰胺加入到壳聚糖-马来酸酐溶液中，磁力搅拌反应2h后，降低温度至40℃加入0.6ml 56.8mmol/ml过硫酸铵作为引发剂、0.1ml 10mmol/ml N,N’-亚甲基双丙烯酰胺作为交联剂混合均匀，反应2h，即得水凝胶。
实施例1
(1)羧甲基化β-环糊精的干法制备：取6.0gβ-环糊精于研钵中研细，加入1.26gNaOH均匀混合后，滴入无水乙醇和水再均匀混合研磨，碱化1h后加入0.08g氯乙酸，研磨30min后放入40℃烘箱中30min，取出研磨30min，如此反复进行醚化反应4h，最后用乙醇洗涤3次，放入60℃烘箱中烘干。
(2)羧甲基化β-环糊精/单宁酸分散液的制备：室温下称取0.1g步骤(1)制备的羧甲基化β-环糊精粉末加入到1g去离子水中，机械搅拌1h后超声处理30min，并于机械搅拌30min时加入25mg单宁酸，制得羧甲基化β-环糊精/单宁酸分散液。
(3)水凝胶的制备：室温下将1g马来酸酐溶解于7.5g去离子水中，再加入0.2g壳聚糖，磁力搅拌12h，得到壳聚糖-马来酸酐溶液；于60℃恒温水浴锅中将2g丙烯酰胺、步骤(2)制备的羧甲基化β-环糊精/单宁酸分散液加入到壳聚糖-马来酸酐溶液中，磁力搅拌反应2h后，降低温度至40℃加入0.6ml 56.8mmol/ml过硫酸铵作为引发剂、0.1ml 10mmol/ml N,N’-亚甲基双丙烯酰胺作为交联剂混合均匀，反应2h，即得目标水凝胶。
实施例2
(1)羧甲基化β-环糊精的干法制备：取6.0gβ-环糊精于研钵中研细，加入1.26gNaOH均匀混合后，滴入无水乙醇和水再均匀混合研磨，碱化1h后加入0.08g氯乙酸，研磨30min后放入40℃烘箱中30min，取出研磨30min，如此反复进行醚化反应4h，最后用乙醇洗涤3次，放入60℃烘箱中烘干。
(2)羧甲基化β-环糊精/单宁酸分散液的制备：室温下称取0.1g步骤(1)制备的羧甲基化β-环糊精粉末加入到1g去离子水中，机械搅拌1h后超声处理30min，并于机械搅拌30min时加入50mg单宁酸，制得羧甲基化β-环糊精/单宁酸分散液。
(3)水凝胶的制备：室温下将1g马来酸酐溶解于7.5g去离子水中，再加入0.2g壳聚糖，磁力搅拌12h，得到壳聚糖-马来酸酐溶液；于60℃恒温水浴锅中将2g丙烯酰胺、步骤(2)制备的的羧甲基化β-环糊精/单宁酸分散液加入到壳聚糖-马来酸酐溶液中，磁力搅拌反应2h后，降低温度至40℃加入0.6ml56.8mmol/ml过硫酸铵作为引发剂、0.1ml 10mmol/ml N,N’-亚甲基双丙烯酰胺作为交联剂混合均匀，反应2h，即得目标水凝胶。
实施例3
(1)羧甲基化β-环糊精的干法制备：取6.0gβ-环糊精于研钵中研细，加入1.26gNaOH均匀混合后，滴入无水乙醇和水再均匀混合研磨，碱化1h后加入0.08g氯乙酸，研磨30min后放入40℃烘箱中30min，取出研磨30min，如此反复进行醚化反应4h，最后用乙醇洗涤3次，放入60℃烘箱中烘干。
(2)羧甲基化β-环糊精/单宁酸分散液的制备：室温下称取0.05g步骤(1)制备的羧甲基化β-环糊精粉末加入到1g去离子水中，机械搅拌1h后超声处理30min，并于机械搅拌30min时加入25mg单宁酸，制得羧甲基化β-环糊精/单宁酸分散液。
(3)水凝胶的制备：室温下将1g马来酸酐溶解于7.5g去离子水中，再加入0.2g壳聚糖，磁力搅拌12h，得到壳聚糖-马来酸酐溶液；于60℃恒温水浴锅中将2g丙烯酰胺、步骤(2)制备的羧甲基化β-环糊精/单宁酸分散液加入到壳聚糖-马来酸酐溶液中，磁力搅拌反应2h后，降低温度至40℃，依次加入0.6ml56.8mmol/ml过硫酸铵作为引发剂、0.1ml 10mmol/mlN,N’-亚甲基双丙烯酰胺作为交联剂混合均匀，反应2h，即得目标水凝胶。
对上述空白对照、实施例1、实施例2和实施例3制备的水凝胶进行抗菌试验，具体结果见表1。
表1抗菌水凝胶的抗菌率
Figure BDA0003440102970000061
抗菌试验表明，单宁酸作为一种多酚类物质，具有较强的清除自由基能力以及强抗氧化性。增加羧甲基β-环糊精负载的单宁酸含量，可以显著提升水凝胶的抗菌性。可见，利用本发明制备的抗菌水凝胶产品，抗菌性能较好。
通过红细胞的溶血实验来探究生物相容性，在红细胞溶血实验中，在红细胞中加入所测的样品，如果样品的生物相容性较差，就会使得红细胞破裂并释放出血红蛋白，通过测定其的释放量，可以计算出样品的溶血率，从而评价材料的生物相容性。以红细胞的溶血实验来评价改性氧化石墨烯负载纳米银/聚乙烯醇基抗菌水凝胶的生物相容性。
表2水凝胶的生物相容性
溶血率/％
实施例1 0.25
实施例2 0.38
实施例3 0.44
与阳性对照组(非离子型表面活性剂即0.1％TritonX-100处理过的红细胞)相比，羧甲基β-环糊精负载单宁酸的壳聚糖/马来酸酐-丙烯酰胺双网络抗菌水凝胶溶血率均低于10％，说明羧甲基β-环糊精负载单宁酸的壳聚糖/马来酸酐-丙烯酰胺双网络抗菌水凝胶具有良好的生物相容性。
综上表明，本发明提供了一种利用壳聚糖水溶液中马来酸酐和丙烯酰胺单体的原位聚合，在壳聚糖和聚合(丙烯酰胺-马来酸酐)之间进行离子配位，制备了一类新型的超分子纳米纤维结构杂化水凝胶。通过羧甲基化改性β-环糊精，加入单宁酸，增强其与客体单宁酸形成包容物的水溶性，进一步提高了对细菌的抗菌活性以及体外抗氧化能力，制备出具有结构适应性强、孔隙率高、粘附性能优异，抗氧化能力强和抗菌活性强等优点的复合双网络型水凝胶，有望作为支架材料应用于更广泛的生物医学领域。
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明精神和范围的前提下，本发明还会有各种变化和改进，这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。

Claims (10)

1.一种CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶，其特征在于：按重量组分计，包括80-100份丙烯酰胺、40-50份马来酸酐、16-20份壳聚糖、4-8份羧甲基化β-环糊精和2-4份单宁酸。
2.权利要求1所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于，包括如下步骤：
(1)羧甲基化β-环糊精的干法制备：取β-环糊精研细，加碱研磨，再滴入无水乙醇和水研磨，碱化后加入氯乙酸，研磨一段时间后放入烘箱中，取出后继续研磨，如此反复进行醚化反应，最后用乙醇洗涤，烘干；
(2)羧甲基化β-环糊精/单宁酸分散液的制备：将步骤(1)制备的羧甲基化β-环糊精粉末加入到去离子水中，搅拌后超声处理，并加入单宁酸，制得羧甲基化β-环糊精/单宁酸分散液；
(3)水凝胶的制备：将马来酸酐溶解于去离子水中，再加入壳聚糖混合，得到壳聚糖-马来酸酐溶液；然后将丙烯酰胺、步骤(2)制备的羧甲基化β-环糊精/单宁酸分散液加入到壳聚糖-马来酸酐溶液中，反应一段时间后，降温加入引发剂、交联剂进行反应，得到CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶。
3.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(1)中碱为NaOH。
4.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(1)中碱化时间为0.5-1.5h。
5.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(1)中碱与β-环糊精的重量比为(0.2-0.25):1。
6.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(1)中醚化反应时的烘箱温度为40℃-50℃。
7.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(1)中β-环糊精与氯乙酸的摩尔用量比为(4-6):1。
8.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(3)中反应温度为50-60℃，反应时间为2-3h，降低温度至30-40℃。
9.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(3)中引发剂为过硫酸钾。
10.根据权利要求2所述的CM-β-CD负载鞣酸聚丙烯酰胺型双网络抗菌水凝胶的制备方法，其特征在于：所述步骤(3)中交联剂为N,N’-亚甲基双丙烯酰胺。
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CN114940493A (zh) * 2022-06-08 2022-08-26 安徽大学 石墨烯的剥离方法、石墨烯柔性膜及其制备方法
CN114940493B (zh) * 2022-06-08 2024-04-19 合肥艾克思维新材料科技有限公司 石墨烯的剥离方法、石墨烯柔性膜及其制备方法
CN115887738A (zh) * 2022-12-16 2023-04-04 湖南师范大学 一种聚丙烯酰胺-壳聚糖/高岭土多孔材料及其制备方法
CN115887738B (zh) * 2022-12-16 2024-05-10 湖南师范大学 一种聚丙烯酰胺-壳聚糖/高岭土多孔材料及其制备方法

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