CN114479124B - 一种可自愈水凝胶、其制备方法及应用 - Google Patents
一种可自愈水凝胶、其制备方法及应用 Download PDFInfo
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- CN114479124B CN114479124B CN202210191075.7A CN202210191075A CN114479124B CN 114479124 B CN114479124 B CN 114479124B CN 202210191075 A CN202210191075 A CN 202210191075A CN 114479124 B CN114479124 B CN 114479124B
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Abstract
Description
技术领域
本发明涉及一种可自愈水凝胶、其制备方法及应用,属于水凝胶技术领域。
背景技术
随着生活水平的提高,人们越来越关注健康问题,由细菌感染引起的相关医学问题日益成为临床研究的热点。感染是创伤和其它开放性伤口普遍发生的严重并发症之一,细菌感染导致的伤口难以愈合是重大的临床问题。抗生素滥用导致的细菌耐药性给感染的治疗带来了极大的困难。随着材料学和工程技术的飞速发展,许多新型医用抗菌敷料应运而生,通过物理活化学的方法赋予生物医用材料一定的抗菌性,从而减少细菌的传播,最终减少细菌感染相关疾病的发生。
水凝胶是一类具有三维网络结构的新型功能高分子材料,是由水溶性或亲水性的高分子通过化学或物理交联作用得到。水凝胶材料具有良好的特性,在生物医学领域受到极大关注。第一,水凝胶具有类似细胞外基质的网状多孔结构,比其它类型的生物材料更接近生物组织;第二,水凝胶的表面不易黏附蛋白质等物质,故在与血液、体液以及人体组织接触时具有更好的生物相容性;第三,水凝胶含水量高,力学性能可调,根据需要更好地与周围组织仿生;第四,水凝胶的多孔结构使其具有较好的渗透性,便于营养物质以及代谢物的运输,可维持水凝胶周围细胞的生存环境。综上,水凝胶在诸多领域,如组织修复与再生、药物递送、人造皮肤等领域具有广泛的应用。
目前具有抗菌活性的水凝胶是目前创面敷料研究的热点。常用的抗菌剂分为无机抗菌剂和有机抗菌剂。常用的无机抗菌剂是银离子或纳米银,含有银粒子的抗菌剂虽然具有良好的抗菌活性,但是银粒子在体内富集,难于排出体外,具有潜在的生物安全性,阻碍了此类抗菌水凝胶的广泛应用。有机抗菌剂包括传统的抗生素、季铵盐等,含有抗生素的抗菌水凝胶可以用于预防感染,但是抗生素易导致细菌产生耐药性。季铵盐是另一类常用的外用抗菌生物制品,具有广谱的抗菌效果,但是其季铵盐细胞毒性较大,限制了其广泛应用。
因此,在不使用抗生素、细胞因子或治疗性细胞的情况下,迫切需要开发具有高效抗菌活性,并且能够促进创面愈合的水凝胶。鉴于此,有必要提供一种新的可自愈水凝胶的制备方法,以解决现有技术的不足。
发明内容
本发明的目的之一,是提供提供一种可自愈水凝胶。
本发明解决上述技术问题的技术方案如下:一种可自愈水凝胶,其化学结构式如式Ⅲ所示:
本发明的可自愈水凝胶的有益效果是:
1、本发明的可自愈水凝胶,由季铵化壳聚糖和氧化葡甘聚糖通过希夫碱键形成,不再需要额外的交联剂;只含有季铵化壳聚糖一个抗菌组分,与负载无机金属颗粒抗菌水凝胶相比,不需要外界光照可以发挥抗菌活性,有利于临床应用。
2、本发明的可自愈水凝胶,具有可降解性,可以在感染部位长期滞留,时间可控,无需多次给药,具有长期抗菌效果。
3、本发明的可自愈水凝胶,在体内可完全降解,最终不需要二次手术将材料去除,减少病人痛苦。
4、本发明的可自愈水凝胶,具有多孔结构,有利于细胞向凝胶内部迁移,促进伤口愈合,最终降解为季铵盐、葡萄糖、甘露糖和氨基葡萄糖,可吸收、无毒,不含有金属离子或金属纳米颗粒,无潜在的安全性问题。
本发明的目的之二,是提供上述可自愈水凝胶的制备方法。
本发明解决上述技术问题的技术方案如下:上述可自愈水凝胶的制备方法,包括如下步骤:
步骤1:制备氧化葡甘聚糖
按摩尔比为1:(0.1-1),分别称取葡甘聚糖与高碘酸钠,在避光条件下反应,加入乙二醇终止反应,高碘酸钠与乙二醇的摩尔比为1:(2-10),然后透析,冷冻干燥,得到如式Ⅱ所示的氧化葡甘聚糖;
步骤2:制备酯化季铵盐纯净物
按摩尔比为1:(2-4),分别称取季铵盐与对甲基苯磺酰氯,溶解在极性溶剂中,反应后,用非极性溶剂沉淀,干燥,得到酯化季铵盐纯净物;
步骤3:制备季铵化壳聚糖纯净物
按摩尔比为1:(0.5-5),分别称取步骤2得到的酯化季铵盐纯净物与壳聚糖,反应后,透析,冷冻干燥,得到季铵化壳聚糖纯净物;
步骤4:制备没食子酸季铵化壳聚糖
按摩尔比为1:0.5,分别称取步骤3得到的酯化季铵盐纯净物与没食子酸,进行反应,得到如式Ⅰ所示的没食子酸季铵化壳聚糖;
步骤5:制备可自愈水凝胶
按质量比1:(0.1-10),分别称取步骤1得到的氧化葡甘聚糖与步骤4得到的没食子酸季铵化壳聚糖,在室温条件下,混合均匀,静置,即得到如式Ⅲ所示的可自愈水凝胶;
其中,
本发明的可自愈水凝胶的制备方法的反应原理是:
第一点,葡甘聚糖可以调控巨噬细胞极化,调控组织修复过程中的免疫和炎症反应。目前大多数研究通过调节水凝胶的理化性质和结构特征来调节机体组织修复过程中的免疫反应,很少有通过调节材料自身生物活性来调节组织修复过程中的免疫反应,从而促进创伤愈合。
本发明的可自愈水凝胶能够通过甘露糖受体介导途径激活巨噬细胞M2极化,对耐甲氧西林金黄色葡萄球菌和大肠杆菌具有较好的抗菌活性。大鼠体内构建慢性感染伤口模型,给予水凝胶治疗,可以显著加速伤口愈合,并且明显提高M2型局势细胞比例,加速血管新生。
第二点,壳聚糖是天然存在的唯一碱性多糖,水溶性较差,在应用上受到很大限制,因此需对壳聚糖进行化学结构修饰,改善理化性质。通过季铵盐修饰的壳聚糖不仅保留了壳聚糖本身良好的生物相容性和可降解性等优点,而且赋予其新的性能,如良好的水溶性、更强的静电吸附性和抗菌性,在医药领域具有更广泛的应用。现有壳聚糖的季铵化改性主要是在-OH上引入环氧基季铵盐,但是通过取代反应在-OH和NH2上同时进行季铵化改性鲜有报道。
本发明的步骤3中,将含氮杂环季铵盐修饰在壳聚糖上,同时进行季铵化改性,不仅可以提高水溶性,而且也有助于提高抗菌活性,不需要负载额外的抗生素。
本发明的步骤4中,加入没食子酸,可以清除创伤部位过度表达的自由基,为伤口的愈合提供一个适宜的环境。将没食子酸修饰到季铵化壳聚糖壳聚糖上,赋予壳聚糖抗菌和抗氧化等功能,不需要反复给药。
本发明涉及到的反应路线是:
综上,本发明采用广谱抗菌活性高、生物相容性好的季铵盐、壳聚糖和葡甘聚糖为原料,制备得到可自愈水凝胶。该可自愈水凝胶与细菌细胞膜作用,破坏细胞膜的完整性,使细菌内容物泄露,导致细菌死亡。另外,葡甘聚糖可以诱导巨噬细胞极化为M2型,产生抗炎促修复作用。所以,本发明的可自愈水凝胶对细胞无毒、可降解,最终排出体外。而且,本发明的可自愈水凝胶具有多孔结构,可以促进细胞增殖,进一步促进伤口愈合。因此,本发明的可自愈水凝胶兼具抗菌和抗炎功效,可以作为很有前景的伤口敷料,用于难愈合伤口的处理,具有很大的应用潜力。
本发明的可自愈水凝胶的制备方法的有益效果是:
1、本发明制备得到的可自愈水凝胶,对革兰氏阳性菌、革兰氏阴性菌和真菌等微生物均具有良好的抗菌性能和优异的广谱抗菌性能,且具有良好的可降解性和生物相容性,具有广阔的应用前景。
2、本发明的反应条件温和,通过希夫碱反应即可实现,操作容易,成本低廉,市场前景广阔,适合规模化推广应用。
在上述技术方案的基础上,本发明还可以做如下改进。
进一步,步骤1中,所述葡甘聚糖的分子量为1000KDa-10000KDa。
采用上述进一步的有益效果是:采用上述参数,得到的可自愈水凝胶的性能更佳。
进一步,步骤1中,所述反应的时间为3h-12h。
采用上述进一步的有益效果是:采用上述参数,反应的更加彻底。
进一步,步骤1和步骤3中,所述透析均是指在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析48h-72h。
采用上述进一步的有益效果是:采用上述方式,透析的效果更佳。
进一步,步骤1和步骤3中,所述冷冻干燥的温度均为-20℃至60℃,时间均为48h-72h。
采用上述进一步的有益效果是:采用上述参数,干燥的效果更佳。
进一步,步骤2中,所述干燥的真空度为-0.05MPa至-0.08MPa,温度为室温,时间为24h。
采用上述进一步的有益效果是:采用上述参数,干燥的效果更佳。
进一步,步骤2和步骤3中,所述反应的温度均为室温,时间均为24h-48h。
采用上述进一步的有益效果是:采用上述参数,反应的更加彻底。
进一步,步骤2中,所述极性溶剂为N,N-二甲基甲酰胺、二甲基亚砜和异丙醇中的任意一种;所述非极性溶剂为苯、甲苯、石油醚和乙醚中的任意一种;所述极性溶剂与所述非极性溶剂的体积比为1:(5-20)。
采用上述进一步的有益效果是:上述溶剂来源广泛,成本低廉,效果明显。
进一步,步骤3中,所述壳聚糖的分子量为100KDa-1000KDa。
采用上述进一步的有益效果是:采用上述参数,得到的可自愈水凝胶的性能更佳。
进一步,步骤5中,所述静置的时间为1min以上。
采用上述进一步的有益效果是:采用上述参数,得到的可自愈水凝胶的性能更佳。
进一步,步骤5中,所述可自愈水凝胶的质量百分浓度为5%-20%。
采用上述进一步的有益效果是:上述参数的可自愈水凝胶的效果更加明显。
本发明的目的之三,是提供上述可自愈水凝胶的应用。
本发明解决上述技术问题的技术方案如下:上述可自愈水凝胶在制备伤口敷料中的应用。
本发明的可自愈水凝胶的应用的有益效果是:
本发明的可自愈水凝胶可以用于制备伤口敷料,无需多次给药,无安全性问题。
附图说明
图1为本发明实施例1的步骤1制备得到的氧化葡甘聚糖(简称为GM-CHO)的红外图谱;
图2为本发明实施例1的步骤4制备得到的没食子酸季铵化壳聚糖(简称为GA-QAS-CS)的核磁图谱;
图3为本发明实施例1的步骤4制备得到的没食子酸季铵化壳聚糖(简称为GA-QAS-CS)的红外图谱;
图4为本发明实施例1的步骤5制备得到的可自愈水凝胶(简称GA-QAS-CS@GM)的红外图谱;
图5为本发明实施例1的步骤5制备得到的可自愈水凝胶(简称GA-QAS-CS@GM)的外观图;
图6为本发明实施例1的步骤5制备得到的可自愈水凝胶(简称GA-QAS-CS@GM)的SEM图;
图7本发明的实验例中,空白对照组的抗菌活性测试;
图8本发明的实验例中,壳聚糖水凝胶(简称CS)的抗菌活性测试;
图9本发明的实验例中,可自愈水凝胶(简称GA-QAS-CS@GM)的抗菌活性测试;
图10本发明的实验例中,可自愈水凝胶(简称GA-QAS-CS@GM)的细胞相容性测试,其中,1为阴性对照,2为壳聚糖水凝胶,3为实验组;
图11本发明的实验例中,可自愈水凝胶(简称GA-QAS-CS@GM)的促进感染皮肤修复测试,其中,1为空白对照,2为壳聚糖组,3为实验组;
图12为本发明的实验例中,创伤部位修复空白对照组的H&E染色;
图13为本发明的实验例中,创伤部位修复壳聚糖组的H&E染色;
图14为本发明的实验例中,创伤部位修复实验组的H&E染色;
图15为本发明的实验例中,创伤部位修复空白对照组的Masson's染色;
图16为本发明的实验例中,创伤部位修复壳聚糖组的Masson's染色;
图17为本发明的实验例中,创伤部位修复实验组的Masson's染色。
图18为本发明的实验例中,凝血实验测试。
具体实施方式
以下结合附图对本发明的原理和特征进行描述,所举实例只用于解释本发明,并非用于限定本发明的范围。
实施例1
本实施例的可自愈水凝胶的制备方法,包括如下步骤:
步骤1:制备氧化葡甘聚糖
分别称取1g葡甘聚糖与0.13g高碘酸钠,所述葡甘聚糖的分子量为1000KDa-10000KDa;在避光条件下反应7.5h,加入1mL乙二醇终止反应,然后在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析60h,在温度为-20℃冷冻干燥48h,得到如式Ⅱ所示的氧化葡甘聚糖(简称为GM-CHO)。氧化葡甘聚糖(简称为GM-CHO)的红外图谱,如图1所示。
步骤2:制备酯化季铵盐纯净物
分别称取10g季铵盐与2g对甲基苯磺酰氯,溶解在50mL N,N-二甲基甲酰胺中,在室温反应36h后,用500mL苯沉淀,在真空度为-0.05MPa至-0.08MPa条件下真空干燥,温度为室温,时间为24h,得到酯化季铵盐纯净物。
步骤3:制备季铵化壳聚糖纯净物
分别称取3g步骤2得到的酯化季铵盐纯净物与0.4g壳聚糖,所述壳聚糖的分子量为100KDa-1000KDa,在室温反应36h后,在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析60h,在温度为20℃冷冻干燥60h,得到季铵化壳聚糖。
步骤4:制备没食子酸季铵化壳聚糖
分别称取1g步骤3得到的季铵化壳聚糖与0.2g没食子酸,进行反应,得到如式Ⅰ所示的没食子酸季铵化壳聚糖(简称为GA-QAS-CS)。
没食子酸季铵化壳聚糖(简称为GA-QAS-CS)的核磁图谱如图2所示。
没食子酸季铵化壳聚糖(简称为GA-QAS-CS)的红外图谱如图3所示。
1H NMR分析:采用氘代水为溶剂,在核磁共振仪Bruker400进行测试,如图4所示,化学位移4.0-3.6ppm、3.0ppm、1.9ppm时壳聚糖上的质子峰;化学位移在7.0ppm-8.0ppm处吸收峰时苯环的特征吸收峰。以上分析证明了步骤4制备得到的没食子酸季铵化壳聚糖化学结构的正确性。
红外光谱分析:采用KBr压片,在Nicolet MAGNA-IR 550型红外光谱仪上测得,如图5所示,3500cm-1-3300cm-1的宽峰是氨基和羟基的伸缩振动吸收峰。3000cm-1-2800cm-1的伸缩振动峰是-CH2-的吸收峰。1630cm-1、1390cm-1为壳聚糖的特征吸收峰,1154cm-1和1092cm-1是壳聚糖和壳聚糖季铵盐中C-O的伸缩振动峰。与壳聚糖相比,本实施例中的没食子酸季铵化壳聚糖在1468cm-1和1406cm-1出现的新的吸收峰,是季铵盐的特征吸收峰。另外,本实施例中壳聚糖季铵盐中苯环的吸收峰在750cm-1和690cm-1。1623处为希夫碱的特征吸收峰,说明壳聚糖衍生物与葡甘聚糖通过希夫碱化学键形成了水凝胶。
步骤5:制备可自愈水凝胶
分别称取0.1g步骤1得到的氧化葡甘聚糖与0.1g步骤4得到的没食子酸季铵化壳聚糖,在室温条件下,分别溶解在1mL蒸馏水中,然后分别取0.5mL液体,混合均匀,静置1min以上,即得到如式Ⅲ所示的可自愈水凝胶(简称GA-QAS-CS@GM),其质量百分浓度为10%。
将可自愈水凝胶(简称GA-QAS-CS@GM)冻干,得到冻干样品,其外观图如图5所示。
可自愈水凝胶(简称GA-QAS-CS@GM)的SEM图,如图6所示。可自愈水凝胶内部具有三维网状结构,孔径为微米级,有利于细胞迁移。
实验例
对实施例1制备得到的可自愈水凝胶进行体外抗菌活性和生物相容性测试实验。
体外抗菌活性测试:将实施例1制备得到的可自愈水凝胶进行辐射灭菌处理,取0.1mL耐甲氧西林金黄色葡萄球菌(MRSA)悬液(107CFU/mL)置于0.1mL可自愈水凝胶上,培养24h;然后将其均匀涂布于LB固体培养基上,培养0.5h后翻转,继续在37℃培养箱中培养24h。分成实验组、空白对照组和壳聚糖对照组,实验操作与实验组一致,空白组采用0.1mL的生理盐水,壳聚糖对照组采用0.1mL的壳聚糖水凝胶(市售购买自奇力康皮肤药业有限公司,规格为20g)。如图7-图9所示,实验组水凝胶没有菌落,而其它组别均有一定数量的菌落,说明实施例1制备得到的可自愈水凝胶具有较好的抗菌活性。
生物相容性测试:采用CCK-8法测试水凝胶对成纤维细胞(L929)的毒性。将水凝胶与成纤维细胞(L929)共培养,然后用CCK-8溶液作用24h。测试450nm的吸光度,计算其对细胞毒性的大小。如图10所示,细胞存活率在90%以上,说明该水凝胶对成纤维细胞(L929)没有明显的细胞毒性。
促进感染皮肤修复测试:将SD大鼠进行麻醉,背部手术区备皮后,固定于手术台上,在背部制造直径1cm的全层皮肤缺损模型,然后用MRSA感染,实验组分为3组,未治疗组、壳聚糖水凝胶组,没食子酸季铵化壳聚糖葡甘聚糖实验组;观察不同时间的创伤愈合情况。如图11所示,随着时间延长,各组创面均有明显减小,愈合率逐渐提高。在同一时间,实验组的愈合率明显高于对照组,且最终实现100%愈合。该结果说明本发明实施例1的可自愈水凝胶具有很好的抗菌活性,并且可以促进伤口愈合。
取材研究皮肤的修复情况,进行H&E染色和Masson's染色。如图12-图17所示,病理结果表明,第4天实验组创面部位的上皮细胞已经开始形成,并且具有较多的胶原纤维,炎症细胞相对较少。第12天,实验组的创面部位已经形成了相对有序的胶原纤维和完整的表皮,并且接近正常的皮肤组织。说明该水凝胶具有很好的抗菌效果,并且对MRSA具有杀伤作用,可以加速伤口的愈合。
凝血实验测试:在止血的研究中,血小板黏附、聚集形成血栓是重要的研究内容。具体操作步骤如下:用肝素采血管收集新鲜血液,然后取0.2mL的水凝胶与血液作用,将其放入37℃恒温摇床上孵育10min;缓缓地加入25mL蒸馏水稀释,取200μL上清液在545nm处测定吸光度,对照组的操作方法同上。结果如图18所示,壳聚糖水凝胶的凝血指数约为55%,而实验组的凝血指数约为26%,说明该水凝胶具有更好的凝血性能,更有利于止血。本发明水凝胶中的季铵化壳聚糖带有正电荷,可以通过静电作用聚集血细胞,达到快速止血的目的。
综上,本实施例所制备的可自愈水凝胶具有良好的抗菌活性,无细胞毒性,并且可以快速止血、促进组织修复与伤口愈合。因此,本实施例所制备的可自愈水凝胶可以用于制备伤口敷料,无需多次给药,无安全性问题。
实施例2
本实施例的可自愈水凝胶的制备方法,包括如下步骤:
步骤1:制备氧化葡甘聚糖
分别称取1g糖与0.3g碘酸钠,所述葡甘聚糖的分子量为1000KDa-10000KDa;在避光条件下反应7.5h,加入2mL醇终止反应,然后在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析48h,在温度为-20℃冷冻干燥48h,得到如式Ⅱ所示的氧化葡甘聚糖。
步骤2:制备酯化季铵盐纯净物
分别称取10g季铵盐与3g对甲基苯磺酰氯,溶解在50mL N,N-二甲基甲酰胺中,在室温反应24h后,用500mL苯沉淀,在真空度为-0.05MPa至-0.08MPa条件下真空干燥,温度为室温,时间为24h,得到酯化季铵盐纯净物。
步骤3:制备季铵化壳聚糖纯净物
分别称取3g步骤2得到的酯化季铵盐纯净物与0.6g壳聚糖,所述壳聚糖的分子量为100KDa-1000KDa,在室温反应24h后,在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析48h,在温度为-20℃冷冻干燥48h,得到季铵化壳聚糖纯净物。
步骤4:制备没食子酸季铵化壳聚糖
分别称取1g步骤3得到的酯化季铵化壳聚糖纯净物与0.4g没食子酸,进行反应,得到如式Ⅰ所示的没食子酸季铵化壳聚糖。
步骤5:制备可自愈水凝胶
分别称取0.2g步骤1得到的氧化葡甘聚糖与0.2g步骤4得到的没食子酸季铵化壳聚糖,在室温条件下,溶解在1mL蒸馏水中,然后混合均匀,静置1min以上,即得到如式Ⅲ所示的的可自愈水凝胶,其质量百分浓度为20%。
实施例3
本实施例的可自愈水凝胶的制备方法,包括如下步骤:
步骤1:制备氧化葡甘聚糖
分别称取1g葡甘聚糖与0.4g高碘酸钠,所述葡甘聚糖的分子量为1000KDa-10000KDa;在避光条件下反应7.5h,加入3mL乙二醇终止反应,然后在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析72h,在温度为-20℃冷冻干燥48h,得到如式Ⅱ式I所示的氧化葡甘聚糖。
步骤2:制备酯化季铵盐纯净物
分别称取10g季铵盐与3g对甲基苯磺酰氯,溶解在50mL N,N-二甲基甲酰胺中,在室温反应48h后,用500mL苯沉淀,在真空度为-0.05MPa至-0.08MPa条件下真空干燥,温度为室温,时间为24h,得到酯化季铵盐纯净物。
步骤3:制备季铵化壳聚糖纯净物
分别称取3g步骤2得到的酯化季铵盐纯净物与0.6g壳聚糖,所述壳聚糖的分子量为100KDa-1000KDa,在室温反应48h后,在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析72h,在温度为60℃冷冻干燥48h,得到季铵化壳聚糖纯净物。
步骤4:制备没食子酸季铵化壳聚糖
分别称取1g步骤3得到的酯化季铵盐纯净物与0.6g没食子酸,进行反应,得到如式I所示的没食子酸季铵化壳聚糖。
步骤5:制备可自愈水凝胶
分别称取0.05g步骤1得到的氧化葡甘聚糖与0.05g步骤4得到的没食子酸季铵化壳聚糖,在室温条件下,分别溶解在1mL蒸馏水中,然后混合均匀,静置1min以上,即得到如式Ⅲ所示的可自愈水凝胶,其质量百分浓度为5%。
以上所述仅为本发明的较佳实施例,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
2.权利要求1所述可自愈水凝胶的制备方法,其特征在于,包括如下步骤:
步骤1:制备氧化葡甘聚糖
按摩尔比为1:(0.1-1),分别称取葡甘聚糖与高碘酸钠,在避光条件下反应,加入乙二醇终止反应,高碘酸钠与乙二醇的摩尔比为1:(2-10),然后透析,冷冻干燥,得到如式Ⅱ所示的氧化葡甘聚糖;
步骤2:制备酯化季铵盐纯净物
按摩尔比为1:(2-4),分别称取季铵盐与对甲基苯磺酰氯,溶解在极性溶剂中,反应后,用非极性溶剂沉淀,干燥,得到酯化季铵盐纯净物;
步骤3:制备季铵化壳聚糖纯净物
按摩尔比为1:(0.5-5),分别称取步骤2得到的酯化季铵盐纯净物与壳聚糖,反应后,透析,冷冻干燥,得到季铵化壳聚糖纯净物;
步骤4:制备没食子酸季铵化壳聚糖
按摩尔比为1:0.5,分别称取步骤3得到的酯化季铵盐纯净物与没食子酸,进行反应,得到如式Ⅰ所示的没食子酸季铵化壳聚糖;
步骤5:制备可自愈水凝胶
按质量比1:(0.1-10),分别称取步骤1得到的氧化葡甘聚糖与步骤4得到的没食子酸季铵化壳聚糖,在室温条件下,混合均匀,静置,即得到如式Ⅲ所示的可自愈水凝胶;
其中,
3.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤1中,所述葡甘聚糖的分子量为1000KDa-10000KDa;所述反应的时间为3h-12h。
4.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤1和步骤3中,所述透析均是指在室温条件下,用截留分子量为5kDa的透析袋,在蒸馏水中透析48h-72h;所述冷冻干燥的温度均为-20℃至60℃,时间均为48h-72h。
5.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤2中,所述干燥的真空度为-0.05MPa至-0.08MPa,温度为室温,时间为24h。
6.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤2和步骤3中,所述反应的温度均为室温,时间均为24h-48h。
7.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤2中,所述极性溶剂为N,N-二甲基甲酰胺、二甲基亚砜和异丙醇中的任意一种;所述非极性溶剂为苯、甲苯、石油醚和乙醚中的任意一种;所述极性溶剂与所述非极性溶剂的体积比为1:(5-20)。
8.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤3中,所述壳聚糖的分子量为100KDa-1000KDa。
9.根据权利要求2所述可自愈水凝胶的制备方法,其特征在于,步骤5中,所述静置的时间为1min以上;所述可自愈水凝胶的质量百分浓度为5%-20%。
10.权利要求1所述的可自愈水凝胶在制备伤口敷料中的应用。
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