CN111286043A - 一种可注射温敏水凝胶及其制备方法 - Google Patents
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Abstract
本发明涉及一种可注射温敏水凝胶及其制备方法。该水凝胶由巯基改性的己酰化乙二醇壳聚糖构成,所述巯基改性的己酰化乙二醇壳聚糖由己酰化乙二醇壳聚糖和3‑巯基丙酸通过硫醇化反应制得,反应物3‑巯基丙酸与己酰化乙二醇壳聚糖上氨基摩尔比为0.1∶1~0.5∶1。本发明方法反应条件较温和,操作简单安全,更易于被研究人员接受。反应制得的巯基改性的己酰化乙二醇壳聚糖具有温敏性溶胶‑凝胶转变行为,且通过控制反应时间、摩尔比、硫醇化酰基乙二醇壳聚糖溶液浓度等因素,可以使其在室温下呈现自由流动的溶胶状态,而在体温下转变为凝胶状态,此外,本材料具有高黏着性、低细胞毒性和良好的生物可降解性,在可注射药物缓释载体方面具有潜在的应用价值。
Description
技术领域
本发明涉及一种可注射温敏性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在化学键、氢键或范德华力等作用下形成的交联网络,它具有“不溶于水,但是可以吸收大量水而发生溶胀,且在溶胀之后仍然保持原有结构”的特点。与其他合成材料相比,水凝胶更接近活体组织,其表面对蛋白质和细胞的粘附能力较弱,与人体组织、血液和体液接触时,具有很好的生物相容性。此外,由于水凝胶具有三维网状结构,代谢产物可以通过它排出体外,并不会影响到生命体的代谢过程。由于水凝胶具有上述特性,使其在组织工程、生物医药(如药物缓释载体、组织工程支架)等领域具有光明的应用前景。
物理交联水凝胶,是通过非共价键作用(如氢键、疏水作用、静电作用、范德华力等)进行交联的一类水凝胶,这种凝胶一般具有可逆性,可以通过一定操作(如加热,调节pH等)使凝胶转变为可以自由流动的溶液。与化学交联水凝胶相比,它通过非共价键来形成三维网络,避免了化学交联剂的使用,更适合生物医学领域的应用。特别是可注射水凝胶,其易于应用到微创手术特异性位点的引入和对患者便利性,因此在可注射载体领域引起了广泛关注,尤其是通过疏水相互作用获得的可注射温敏性水凝胶在生物医学应用领域得到了广泛的研究。
本研究以己酰化乙二醇壳聚糖为原料,通过巯基化反应制备新型可注射温敏性巯基改性的己酰化乙二醇壳聚糖,本材料具有良好的可注射,可生物降解和温敏性质,在可注射药物缓释载体等领域具有潜在的应用价值。
发明内容
本发明的目的是解决化学交联水凝胶使用化学交联剂的问题,提供一种具有可注射温度敏感性的物理交联水凝胶,以及该水凝胶的制备方法。
本发明的技术方案:
一种可注射温敏水凝胶,该水凝胶由巯基改性的己酰化乙二醇壳聚糖构成,所述巯基改性的己酰化乙二醇壳聚糖由己酰化乙二醇壳聚糖和3-巯基丙酸通过硫醇化反应制得,反应物3-巯基丙酸与己酰化乙二醇壳聚糖上氨基的摩尔比为0.1∶1~0.5∶1。
一种上述可注射温敏水凝胶的制备方法,该方法的具体步骤为:
称取己酰化乙二醇壳聚糖分散到50毫升去离子水中,浓度为0.1wt%~1wt%,置于磁力搅拌器上室温搅拌充分溶解。将3-巯基丙酸,1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和N-羟基琥珀酰亚胺加入到2-吗啉乙磺酸缓冲液中并用盐酸将pH调节至5.2-6.2,其中1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐与N-羟基琥珀酰亚胺质量之比为1∶1-1∶5,3-巯基丙酸与2-吗啉乙磺酸缓冲液体积之比为1∶100-1∶500,该过程主要是激活3-巯基丙酸的羧酸用于与己酰化乙二醇壳聚糖进一步的反应。2-4小时后,将活化的3-巯基丙酸溶液加入到己酰化乙二醇壳聚糖溶液中。然后在室温下搅拌进行反应,时间为20-30小时。然后将得到的反应液倒入渗析袋中用水渗析两天,最后将透析后的溶液进行冷冻干燥,得到巯基改性的己酰化乙二醇壳聚糖;将巯基改性的己酰化乙二醇壳聚糖溶于去离子水中,将环境温度升至溶胶-凝胶转变温度以上,制得巯基改性的己酰化乙二醇壳聚糖温敏性水凝胶。
本发明的优点和有益效果:
本发明通过巯基化反应制得的巯基改性的己酰化乙二醇壳聚糖具有温敏性溶胶-凝胶转变行为,且通过控制反应时间、摩尔比、硫醇化酰基乙二醇壳聚糖溶液浓度等因素,可以使其在室温下呈现自由流动的溶胶状态,而在体温下转变为凝胶状态,此外,本材料具有高黏着性、低细胞毒性和良好的生物可降解性,在可注射药物缓释载体方面具有潜在的应用价值。
附图说明:
图1是巯基改性的己酰化乙二醇壳聚糖红外图。
具体实施方式
实例1
称取0.5克己酰化乙二醇壳聚糖分散到50毫升去离子水中,置于磁力搅拌器上室温搅拌充分溶解。将0.01毫升的3-巯基丙酸,60毫克的1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和60毫克的N-羟基琥珀酰亚胺加入到10毫升的2-吗啉乙磺酸缓冲液中并用0.1mol/L盐酸将pH调节至6.0,该过程主要是激活3-巯基丙酸的羧酸用于与己酰化乙二醇壳聚糖进一步的反应。2小时后,将活化的3-巯基丙酸溶液加入到己酰化乙二醇壳聚糖溶液中。然后在室温下搅拌进行反应24小时。然后将得到的反应液倒入渗析袋中用水渗析两天,最后将透析后的溶液进行冷冻干燥,得到巯基改性的己酰化乙二醇壳聚糖,将巯基改性的己酰化乙二醇壳聚糖溶于去离子水中,将环境温度升至溶胶-凝胶转变温度以上,制得巯基改性的己酰化乙二醇壳聚糖温敏性水凝胶,其红外谱图如图1。
实例2
称取0.5克己酰化乙二醇壳聚糖分散到50毫升去离子水中,置于磁力搅拌器上室温搅拌充分溶解。将0.02毫升的3-巯基丙酸,60毫克的1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和60毫克的N-羟基琥珀酰亚胺加入到10毫升的2-吗啉乙磺酸缓冲液中并用0.1mol/L盐酸将pH调节至6.0,该过程主要是激活3-巯基丙酸的羧酸用于与己酰化乙二醇壳聚糖进一步的反应。2小时后,将活化的3-巯基丙酸溶液加入到己酰化乙二醇壳聚糖溶液中。然后在室温下搅拌进行反应24小时。然后将得到的反应液倒入渗析袋中用水渗析两天,最后将透析后的溶液进行冷冻干燥,得到巯基改性的己酰化乙二醇壳聚糖,将巯基改性的己酰化乙二醇壳聚糖溶于去离子水中,将环境温度升至溶胶-凝胶转变温度以上,制得巯基改性的己酰化乙二醇壳聚糖温敏性水凝胶。
Claims (2)
1.一种可注射温敏水凝胶,其特征在于该水凝胶由巯基改性的己酰化乙二醇壳聚糖构成,所述巯基改性的己酰化乙二醇壳聚糖由己酰化乙二醇壳聚糖和3-巯基丙酸通过硫醇化反应制得,反应物3-巯基丙酸与己酰化乙二醇壳聚糖上氨基的摩尔比为0.1∶1~0.5∶1。
2.权利要求1所述可注射温敏水凝胶的制备方法,其特征在于该方法的具体步骤如下:
称取己酰化乙二醇壳聚糖分散到50毫升去离子水中,浓度为0.1wt%~1wt%,置于磁力搅拌器上室温搅拌充分溶解。将3-巯基丙酸,1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和N-羟基琥珀酰亚胺加入到2-吗啉乙磺酸缓冲液中并用盐酸将pH调节至5.2-6.2,其中1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐与N-羟基琥珀酰亚胺质量之比为1∶1-1∶5,3-巯基丙酸与2-吗啉乙磺酸缓冲液体积之比为1∶100-1∶500,该过程主要是激活3-巯基丙酸的羧酸用于与己酰化乙二醇壳聚糖进一步的反应。2-4小时后,将活化的3-巯基丙酸溶液加入到己酰化乙二醇壳聚糖溶液中。然后在室温下搅拌进行反应,时间为20-30小时。然后将得到的反应液倒入渗析袋中用水渗析两天,最后将透析后的溶液进行冷冻干燥,得到巯基改性的己酰化乙二醇壳聚糖;将巯基改性的己酰化乙二醇壳聚糖溶于去离子水中,将环境温度升至溶胶-凝胶转变温度以上,制得巯基改性的己酰化乙二醇壳聚糖温敏性水凝胶。
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