CN114702698A - 一种双交联自愈合水凝胶及其制备方法 - Google Patents

一种双交联自愈合水凝胶及其制备方法 Download PDF

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CN114702698A
CN114702698A CN202210539744.5A CN202210539744A CN114702698A CN 114702698 A CN114702698 A CN 114702698A CN 202210539744 A CN202210539744 A CN 202210539744A CN 114702698 A CN114702698 A CN 114702698A
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闫洁
李征征
徐文静
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Abstract

一种双交联自愈合水凝胶及其制备方法。该水凝胶以乙二醇壳聚糖及甲基纤维素为原料,通过乙二醇壳聚糖与己酸酐反应生成己酰化乙二醇壳聚糖(HGC),将甲基纤维素通过高碘酸钠进行氧化得到氧化甲基纤维素(DAMC),然后利用DAMC的醛基与HGC上的氨基发生Schiff碱反应形成动态亚胺键,制备得到HGC‑DAMC水凝胶。本发明反应条件较温和,操作简单安全,更易于被研究人员接受。制得的HGC‑DAMC水凝胶具有良好的自愈合能力,解决了传统水凝胶在使用过程中结构易被破坏的问题,使其在无外界刺激条件下可实现自愈合,减少了化学交联剂的使用。HGC‑DAMC水凝胶在可注射药物缓释载体等领域具有潜在的应用价值。

Description

一种双交联自愈合水凝胶及其制备方法
技术领域
本发明属于高分子材料领域,具体涉及一种双交联自愈合水凝胶及其制备方法。
背景技术
水凝胶是一种由亲水性聚合物合成的具有三维网络状结构的高分子化合物,它具有吸水溶胀但不溶解的特点。与其他合成材料相比,水凝胶具有保水性能及良好的生物相容性,鉴于其独有的水溶性及亲水性特征,水凝胶成为模拟天然生物组织功能的最佳材料,但柔软特性使其容易受到损坏,且损坏后性能大大降低,例如由机械或化学因素引起的宏观或微观裂纹,无法继续满足使用要求。
自愈合水凝胶是指凝胶体系承受外界应力而被部分破坏后,能自发地或在一定外界刺激下恢复体系原有的部分或全部力学性能和形态的一类水凝胶,是一类重要的新型耐久性材料。与传统水凝胶相比,自愈合水凝胶具有更长的使用寿命和更好的力学性能,使得自愈合水凝胶在三维细胞培养、组织工程、药物传送等方面具有广阔的应用前景。
发明内容
本发明的目的是解决传统水凝胶在使用过程中结构易被破坏的问题,提供一种具有自愈合能力的双交联水凝胶,以及该水凝胶的制备方法。
本发明以己酰化乙二醇壳聚糖(HGC)以及氧化甲基纤维素(DAMC)反应制备,利用DAMC的醛基与HGC的氨基发生Schiff碱反应形成动态亚胺键使水凝胶材料具有自愈合能力。与传统水凝胶相比,本材料在可注射药物缓释载体等领域具有潜在的应用价值。
本发明的技术方案:
一种双交联自愈合水凝胶,该水凝胶以乙二醇壳聚糖以及甲基纤维素为原料制备,通过乙二醇壳聚糖与己酸酐反应生成己酰化乙二醇壳聚糖(HGC),将甲基纤维素通过高碘酸钠氧化合成氧化甲基纤维素(DAMC),然后利用DAMC的醛基与HGC上的氨基发生Schiff碱反应形成动态亚胺键,制备得到具有自愈合性能的HGC-DAMC双交联水凝胶。
一种上述双交联自愈合水凝胶的制备方法,该方法的具体步骤为:
1.合成己酰化乙二醇壳聚糖(HGC)。称取乙二醇壳聚糖于去离子水中,待磁力搅拌至粉末溶解后加入无水甲醇,磁力搅拌15~20min。移取0.25~0.43mL的己酸酐,并在磁力搅拌下,缓慢滴加到烧杯中,反应24小时后将溶液倒入渗析袋中,用大量去离子水渗析2天(每隔4h更换一次去离子水),在冷冻干燥机中经冷冻干燥后,得到白色絮状的HGC产物。
2.合成氧化甲基纤维素(DAMC)。在室温避光条件中将甲基纤维素和高碘酸钠按照质量比4:5添加到去离子水中。反应4小时后,添加5ml乙二醇以中和过量高碘盐。然后,将产物在透析管(MWCO,3500)中用蒸馏水渗析3天(每隔4h更换一次去离子水),经冷冻干燥机冷冻干燥后,得到白色絮状的DAMC产物。
3.制备HGC-DAMC双交联自愈合水凝胶。按照HGC与DAMC的质量比0.3~0.5称量量HGC与DAMC,然后在烧杯中加入去离子水,用磁力搅拌器搅拌5~10s,倒入圆柱形模具中后放置成型,制得HGC-DAMC双交联自愈合水凝胶样品。
本发明的优点和有益效果:
本发明制得的HGC-DAMC双交联水凝胶具有自愈合能力,解决了传统水凝胶在使用过程中结构易被破坏的问题,使其在无外界刺激条件下可发生自愈合现象,减少了化学交联剂的使用。HGC-DAMC双交联水凝胶在药物释放领域具有良好的应用前景。
附图说明:
图1为DAMC,HGC和HGC-DAMC双交联自愈合水凝胶的红外光谱图;
通过FT-IR分析DAMC-HGC的化学结构确认亚胺键的形成。具有二醛基团的DAMC与HGC链上的游离胺基通过席夫碱反应诱导形成可逆的亚胺键,如图1所示,在1735cm-1处的醛基吸收峰消失,1686cm-1处的亚胺键吸收峰增强,表明HGC的氨基与DAMC的醛基发生了席夫碱反应生成了HGC-DAMC;
图2为HGC-DAMC2双交联自愈合水凝胶的自愈合性能表征。在37℃的条件下,如图2(a,b)所示,将脱模成型后的DAMC-HGC水凝胶用刀片切成两段,并在分别经过亚甲基蓝和罗丹明B染色后贴合;在30分钟后,两部分水凝胶颜色发生扩散,成功地结合在一起,形成一个整体,如图2(c)所示;将自愈合的DAMC-HGC水凝胶浸入PBS溶液中后,未观察到凝胶发生分离,形态结构仍保持完整状态。用镊子夹取修复后的DAMC-HGC水凝胶,发现其可承载自身重量不发生断裂。此外,当手动拉伸修复的DAMC-HGC水凝胶时,水凝胶未从切口处断裂,如图2(d~f)所示。
图3显示了DAMC-HGC水凝胶的药物缓释曲线。负载抗癌药物吉西他滨的DAMC-HGC水凝胶的药物释放量达到78.1%~82.8%,药物释放时间可达96h。DAMC-HGC水凝胶对抗癌药物吉西他滨的药物释放具有缓释作用,因此DAMC-HGC水凝胶在可注射药物载体领域具有较好的应用前景。
具体实施方式
实例1
合成己酰化乙二醇壳聚糖(HGC)。称取0.2g乙二醇壳聚糖于25mL去离子水中,待磁力搅拌至粉末溶解后加入25mL无水甲醇,磁力搅拌15~20min。按移取0.25~0.43mL的己酸酐,并在磁力搅拌下,缓慢滴加到烧杯中,反应24h将溶液倒入渗析袋中,用大量去离子水渗析2天(每隔4h更换一次去离子水),在冷冻干燥机中经冷冻干燥后,得到白色絮状的己酰化乙二醇壳聚糖产物(HGC)。
合成氧化甲基纤维素(DAMC)。在室温避光条件中将甲基纤维素和高碘酸钠按照质量比4:5添加到100mL去离子水中。反应4小时后,添加5ml乙二醇以中和过量高碘盐。然后,将产物在透析管(MWCO,3500)中用蒸馏水渗析3天(每隔4h更换一次去离子水),经冷冻干燥机冷冻干燥后,得到白色絮状的DAMC产物。
制备HGC-DAMC双交联水凝胶。取30mg DAMC与15mg HGC于烧杯中,加入1mL去离子水,用磁力搅拌器搅拌5~10s,倒入圆柱形模具中后放置成型,制得HGC-DAMC1双交联自愈合水凝胶样品。红外光谱图如图1。
实例2
按照实例1的方法合成己酰化乙二醇壳聚糖。
按照实例1的方法合成氧化甲基纤维素。
制备HGC-DAMC双交联水凝胶。取40mg DAMC与15mg HGC于烧杯中,加入1mL去离子水,用磁力搅拌器(TDZ4-WS型,湖南湘仪离心机仪器有限公司)搅拌5~10s,倒入圆柱形模具中后放置成型,制得HGC-DAMC2双交联自愈合水凝胶样品。并以此为例,对其进行自愈合表征如图2(详见附图说明).
实例3
按照实例1的方法合成己酰化乙二醇壳聚糖。
按照实例1的方法合成氧化甲基纤维素。
制备HGC-DAMC双交联水凝胶。取50mg DAMC与15mg HGC于烧杯中,加入1mL去离子水,用磁力搅拌器(TDZ4-WS型,湖南湘仪离心机仪器有限公司)搅拌5~10s,倒入圆柱形模具中后放置成型,制得HGC-DAMC3双交联自愈合水凝胶样品。

Claims (2)

1.一种双交联自愈合水凝胶,该水凝胶以乙二醇壳聚糖以及甲基纤维素为原料进行制备,通过乙二醇壳聚糖与己酸酐反应生成己酰化乙二醇壳聚糖(HGC),将甲基纤维素(MC)通过高碘酸钠进行氧化得到氧化甲基纤维素(DAMC),然后利用DAMC的醛基与HGC上的氨基发生Schiff碱反应形成动态亚胺键,制备得到具有自愈合性能的HGC-DAMC双交联水凝胶。
2.权利要求1所述双交联自愈合水凝胶的制备方法,其特征在于该方法的具体步骤如下:
合成己酰化乙二醇壳聚糖(HGC);称取乙二醇壳聚糖于去离子水中,待磁力搅拌至粉末溶解后加入无水甲醇,磁力搅拌15~20min;按照己酸酐与乙二醇壳聚糖上氨基摩尔比移取0.25~0.43ml己酸酐,并在磁力搅拌下,缓慢滴加到烧杯中,反应24h后将溶液倒入渗析袋中,用去离子水渗析2天,每隔4h更换一次去离子水,,在冷冻干燥机中经冷冻干燥后,得到白色絮状的HGC产物;
合成氧化甲基纤维素(DAMC);在室温避光条件中将甲基纤维素和高碘酸钠按照质量比4:5添加到去离子水中;反应4小时后,添加5ml乙二醇以中和过量高碘盐;然后,将产物在透析管中用蒸馏水渗析3天,每隔4h更换一次去离子水,经冷冻干燥机冷冻干燥后,得到白色絮状的DAMC产物;
制备HGC-DAMC双交联水凝胶;按照HGC和DAMC的质量比0.3~0.5在烧杯中将HGC和DAMC溶于去离子水,用磁力搅拌器搅拌5~10s,倒入圆柱形模具中后放置成型,制得HGC-DAMC双交联自愈合水凝胶样品。
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CN113941026A (zh) * 2021-10-25 2022-01-18 浙江中医药大学 一种包载生物活性玻璃的壳聚糖纤维素衍生物基可注射水凝胶敷料及其制备方法

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CN115160538A (zh) * 2022-07-09 2022-10-11 四川大学 一种交联pdms/壳聚糖复合材料及其制备方法

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