CN116041800B - 一种具有抗菌、抗炎、抗氧化功能的水凝胶及其制备方法和应用 - Google Patents
一种具有抗菌、抗炎、抗氧化功能的水凝胶及其制备方法和应用 Download PDFInfo
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- CN116041800B CN116041800B CN202310063690.4A CN202310063690A CN116041800B CN 116041800 B CN116041800 B CN 116041800B CN 202310063690 A CN202310063690 A CN 202310063690A CN 116041800 B CN116041800 B CN 116041800B
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- Medicinal Preparation (AREA)
Abstract
本发明提供了一种具有抗菌、抗炎、抗氧化功能的水凝胶及其制备方法和应用,该水凝胶的制备方法包括以下步骤:将鞣花酸溶液和巯基β环糊精溶液于无氧环境中搅拌,然后过滤并进行干燥,制得包合物;将包合物、二巯基化合物、聚乙二醇降冰片烯加入水中,混匀,向其中加入引发剂,然后将混合物溶液置于紫外光照环境中,反应制得水凝胶。该水凝胶具有原位成胶的优点,可填充不规则的创口,并且该水凝胶同时具有抗菌、抗炎、抗氧化的特性,可有效解决现有的伤口敷料存在应用范围窄,生物相容性差以及存在耐药性等问题。
Description
技术领域
本发明属于水凝胶技术领域,具体涉及一种具有抗菌、抗炎、抗氧化功能的水凝胶及其制备方法和应用。
背景技术
组织损伤经常发生在日常生活中。皮肤伤口愈合的过程极其复杂,包括止血、炎症、组织增生和重塑四个阶段,组织损伤在愈合进程极易受自身条件和外界环境的干扰而受阻。一旦伤口过大或者在伤口表面发生细菌感染进而转变成慢性伤口,皮肤的修复功能将严重降低。由于持续的炎症,细胞的抗氧化能力不足以应对过量的活性氧(ROS)产生,限制了伤口的愈合过程,因此必须控制伤口微环境中的ROS浓度,以克服所造成的氧化应激损害。因此,大量的努力集中在开发具有抗菌、抗炎、抗氧化多功能伤口敷料,目前市面上伤口敷料主要存在以下缺点:
a.纱布、海绵敷料在使用时可能会与伤口处产生粘连,导致替换时发生伤口的二次拉扯,在伤口感染时需要借助其他药物联合使用;现有的透明敷料虽然阻止了环境中的微生物接触创面,但无法清除已经存在于创面处的细菌,不具杀菌作用;现有的水凝胶、水胶体敷料为固定形状,不能原位成胶,无法填充伤口不规则缺陷。
b.部分敷料不适用于感染伤口,无法同时提供抗菌、抗炎、抗氧化功能,需要与药物联合使用。
而且,目前,添加有抗菌物质的水凝胶敷料大致分为两类:(1)固有抗菌材料水凝胶敷料,如带有季铵盐等官能团的季铵化壳聚糖和抗菌肽的水凝胶,通过破坏细菌细胞膜来达到抗菌效果,但其缺点是并不能区分正常细胞和细菌的细胞膜,致使正常细胞被杀死,因此,用于生物体内时需要综合考虑其生物相容性;(2)加载抗菌剂的水凝胶伤口敷料,如添加无机抗菌剂、有机抗菌剂和天然抗菌剂等,由于细菌的耐药性以及部分抗菌剂的细胞毒性并不适用于生物材料,导致其应用受限。
发明内容
针对现有技术中存在的上述问题,本发明提供一种具有抗菌、抗炎、抗氧化功能的水凝胶及其制备方法和应用,该水凝胶具有原位成胶的优点,可填充不规则的创口,并且该水凝胶同时具有抗菌、抗炎、抗氧化的特性,可有效解决现有的伤口敷料存在应用范围窄,生物相容性差以及存在耐药性等问题。
为实现上述目的,本发明解决其技术问题所采用的技术方案是:
一种具有抗菌、抗炎、抗氧化功能的水凝胶的制备方法,包括以下步骤:
(1)将鞣花酸溶液和巯基β环糊精溶液于无氧环境中搅拌,然后过滤并进行干燥,制得包合物;
(2)将包合物、二巯基化合物、聚乙二醇降冰片烯加入水中,混匀,向其中加入引发剂,然后将混合物溶液置于紫外光照环境中照射,制得水凝胶。
进一步地,步骤(1)中具体操作为:将鞣花酸的乙醇溶液滴加至巯基β环糊精水溶液中,超声处理,然后于室温无氧条件下搅拌30-45h,然后用0.45μm滤膜过滤混合溶液,将滤过物冷冻干燥,制得包合物。
进一步地,步骤(1)中鞣花酸和巯基β环糊精的摩尔比为1:1-3。
进一步地,步骤(2)中当硫醇基:烯基=1时,二巯基化合物和包合物的摩尔比为1-9:1-9。
进一步地,步骤(2)中二巯基化合物包括二硫苏糖醇和巯基聚乙二醇硫醇;聚乙二醇降冰片烯包括双臂聚乙二醇降冰片烯、四臂聚乙二醇降冰片烯和八臂聚乙二醇降冰片烯。
进一步地,步骤(2)中光引发剂包括I2959和LAP。
进一步地,步骤(2)中光引发剂在混合物溶液中的质量占比为0.04-0.5%。
进一步地,步骤(2)中混合物溶液中聚乙二醇降冰片烯的质量浓度为6-10wt%。
进一步地,步骤(2)光照强度为5-10mW/cm2。
一种具有抗菌、抗炎、抗氧化功能的水凝胶,采用上述的制备方法制得。
上述的具有抗菌、抗炎、抗氧化功能的水凝胶在外用敷料或细胞外培养基质中应用。
本发明所产生的有益效果为:
1、本发明中将鞣花酸(EA)与包裹在单巯基β环糊精(SH-β-CD)的腔体内形成包合物,包合物和二巯基化合物中均含有巯基,将包合物与二巯基化合物充当交联剂,在紫外光与光引发剂存在的条件下与大分子聚合物聚乙二醇降冰片烯发生硫醇-烯点击化学,将大分子聚合物聚乙二醇降冰片烯交联起来从而形成网络凝胶结构,交联的过程中,将EA负载至水凝胶内,以增加EA的溶解度,进而提高EA的生物利用度。
2、本发明中采用天然多酚物质鞣花酸(EA)作为主要的抗菌、抗炎、抗氧化物质,用于制备一种同时具有抗菌、抗炎、抗氧化功能的水凝胶,EA可以减少巨噬细胞中脂多糖诱导的促炎细胞介质NO、TNF-α、IL-6的产生,限制金黄色葡萄球菌生物膜的形成,并且可以增强抗生素的敏感性,其具有较强的广谱抗菌性;同时,其还能通过激活内源凝血途径XII因子来促进血液凝固,具有促进伤口愈合特性。
3、本发明中聚乙二醇降冰片烯(PEGNB)与二硫醇进行硫醇-烯光点击化学交联以逐步生长式聚合方式形成水凝胶,逐步生长式水凝胶聚合过程消耗ROS,减少了对细胞有害物质ROS的积累,具有优良细胞相容性。
4、本发明中可先将混合物溶液涂抹在创口表面,然后进行紫外光照射,利用逐步生长式聚合方式形成的水凝胶具有快速的反应速率,聚合反应可以在特定的时间和位置被激发的特点,可在不规则的创口表面原位生成水凝胶,提高对创口的填充效果,进而提高治疗效果。
5、本发明中,SH-β-CD中含有多个羟基基团,可以与水分子之间形成氢键,增强水凝胶保水能力,维持创面湿润环境,此方法形成的水凝胶具有抗菌、抗炎、抗氧化活性,在促进感染伤口愈合方面具有广泛的应用前景。
6、本发明中制得的水凝胶具有良好的生物相容性,可应用于外用敷料和细胞外基质的制备中。
附图说明
图1为包合物SH-β-CD(EA)、混合物(SH-β-CD/EA)、EA和SH-β-CD的红外光谱图;
图2为包合物SH-β-CD(EA)、混合物(SH-β-CD/EA)、EA和SH-β-CD的X射线衍射图;
图3为包合物SH-β-CD(EA)、混合物(SH-β-CD/EA)、EA和SH-β-CD的扫描电镜图;
图4为PDCE0.1-0.9水凝胶的弹性模量及粘性模量统计图;
图5为细胞活性统计图;
图6为水凝胶杀菌效果对比图;
图7为水凝胶抗炎效果统计图;
图8抗氧化效果对比图;
图9为伤口愈合效果图。
具体实施方式
下面结合附图对本发明的具体实施方式做详细的说明。
实施例1
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:1,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将双臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为9:1,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.1。
实施例2
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为8:2,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.2。
实施例3
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:3,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将八臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为7:3,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.3。
实施例4
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入巯基聚乙二醇硫醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整巯基聚乙二醇硫醇和SH-β-CD(EA)的摩尔比为6:4,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.4。
实施例5
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为5:5,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.07wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为6wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.5。
实施例6
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为4:6,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.4wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为10wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.6。
实施例7
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为3:7,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为5mW/cm2,形成水凝胶,编号为PDCE0.7。
实施例8
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌36h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为2:8,然后向EP管中加入LAP光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为7mW/cm2,形成水凝胶,编号为PDCE0.8。
实施例9
一种具有抗菌、抗炎、抗氧化功能的水凝胶,其制备方法如下:
A、鞣花酸环糊精包合物的制备:称取EA和SH-β-CD,使其摩尔比为1:2,将EA溶于乙醇中,在N2、搅拌环境下,将EA乙醇溶液缓慢滴入SH-β-CD水溶液中,超声20min后,在室温下搅拌42h;然后用0.45μm微孔滤膜过滤混合溶液,将过滤后的包合物溶液冷冻干燥得到包合物SH-β-CD(EA);
B、将四臂聚乙二醇降冰片烯溶液添加进EP管中,然后在EP管中加入二硫苏糖醇和SH-β-CD(EA),在硫醇:烯=1的前提下调整二硫苏糖醇和SH-β-CD(EA)的摩尔比为1:9,然后向EP管中加入I2959光引发剂,最后添加水,得混合物溶液,使得光引发剂在混合物溶液中的质量浓度为0.05wt%,四臂聚乙二醇降冰片烯在混合物溶液中的质量浓度为8wt%;然后将混合物溶液于紫外光下照射,紫外光强度为10mW/cm2,形成水凝胶,编号为PDCE0.9。
试验例
一、性能测试
以实施例7中的制得的包合物SH-β-CD(EA)为例,分别对包合物SH-β-CD(EA)、粉末物理混合物(SH-β-CD/EA)、EA和SH-β-CD等物质进行测试,具体结果见图1-3。
图1为包合物SH-β-CD(EA)、混合物(SH-β-CD/EA)、EA和SH-β-CD的红外光谱图,通过图1可知,EA的-OH伸缩振动在3477cm-1处可被观察到,C=O伸缩振动在1720cm-1处,苯环的特征吸收峰在1616-1509cm-1处观察到。在物理混合物(SH-β-CD/EA)中的红外谱图是EA和SH-β-CD红外谱图的简单叠加,EA的-OH伸缩振动峰未被完全掩盖。而在包合物中EA的酚-OH峰被SH-β-CD的-OH宽峰所遮盖,EA中C=O基团伸缩振动在包合物的红外图谱中消失。
图2为包合物SH-β-CD(EA)、混合物(SH-β-CD/EA)、EA和SH-β-CD的X射线衍射图,通过图2可知,EA为晶体,表现出明显的晶体特征尖峰,在物理混合物中由于EA并未被包裹进SH-β-CD中,仍出现了较弱的特征峰,包合物和SH-β-CD的峰形相似,EA的特征峰被完全掩盖。
图3为包合物SH-β-CD(EA)、混合物(SH-β-CD/EA)、EA和SH-β-CD的扫描电镜图,通过图3可知,SH-β-CD呈多边形结构,鞣花酸呈不规则形状的晶体颗粒。在物理混合物中,鞣花酸的特征晶体与CD的平行四边形结构同时存在,单个物质的物理形态没有变化。而在包合物扫描电镜图中可以看出与EA和CD结构都不相同,这表明形成了新的物相。
综上,结合红外光谱图、X射线衍射图结果证明包合物SH-β-CD(EA)制备成功。
二、机械强度测试
分别对实施例1-9中的PDCE0.1-0.9水凝胶的机械强度进行测试,具体结果见图4。
图4为PDCE0.1-0.9水凝胶的弹性模量及粘性模量统计图,通过图4可知,PDCE0.1-0.9水凝胶的机械强度随DTT和SH-β-CD(EA)比例的变化而变化,具有可调的机械强度。PDCE0.7此比例形成的水凝胶的弹性模量(G'为弹性模量,G”为粘性模量)与皮肤弹性模量相当(300-2000pa),该比例的水凝胶具有适用于伤口敷料的理想机械强度,应用于伤口部位时,既不会由于过强的机械性能导致水凝胶脆性断裂,也不会由于过弱的机械性而使水凝胶敷料撕裂、剥落和变形。
本发明中的制得具有可调机械强度的水凝胶,可根据实际使用需要进行调整,进一步提高该水凝胶使用的便捷性和可操作性。
三、生物相容性、抗菌、抗炎、抗氧化性能测试
(1)水凝胶的L929成纤维细胞细胞相容性检测
检测方法:以PDCE0.7水凝胶为例,水凝胶成胶后用PBS清洗3次,该步骤用来除去未反应的物质,接着水凝胶被浸泡在含有15%FBS和1%青霉素/链霉素的高糖DMEM中,37℃孵育24h,过滤,得到水凝胶萃取液。L929成纤维细胞培养在含有15%FBS和1%青霉素/链霉素的高糖DMEM中,待细胞生长至汇合度为90%时,细胞被接种于细胞培养板96孔板中,密度为105/孔。待细胞贴壁后,将培养基更换为含有水凝胶萃取液的培养基,在37℃含有5%CO2大气的细胞孵箱内培养1d、2d、3d后,使用cck-8试剂盒测定细胞活性,具体结果见图5。
图5为细胞活性统计图,通过图5可知,水凝胶PDCE0.7无细胞毒性,对细胞友好。
(2)水凝胶的抗菌性能检测
检测方法:以PDCE0.7水凝胶为例,使用大肠杆菌和金黄色葡萄球菌来探究伤口敷料的抗菌能力。首先制备PDCE0.7水凝胶,吸取10μL菌液(1×105CFU/mL)滴加于PDCE0.7水凝胶表面,37℃孵育4h后,用100μL无菌PBS将未被杀死的细菌重新悬浮,吸取30μL细菌悬浮液涂于营养琼脂板上,将10μL菌液用100μL PBS稀释后取30μL涂于营养琼脂板,作为对照组。将以上琼脂板于37℃放置24h后数菌落数,具体结果见图6。
图6为水凝胶杀菌效果对比图,通过图6可知,PDCE0.7水凝胶杀死了全部的大肠杆菌与金黄色葡萄球菌,抗菌能力为100%。
(3)水凝胶的抗炎性能检测
检测方法:以PDCE0.7水凝胶为例,使用小鼠IL-6Elisa试剂盒来测定PDCE0.7水凝胶体外抗炎作用。将水凝胶与含有15% FBS的DMEM高糖培养基在37℃含有5% CO2大气的培养箱中共孵育24h,得到水凝胶浸提液。将Raw264.7巨噬细胞接种到96孔板中,待细胞贴壁后将培养基替换为水凝胶浸提液,同时加入100ng/mL的LPS进入每孔中,未作任何处理的组为阴性对照,只加了LPS的组为阳性对照,24h后收集细胞上清,使用小鼠IL-6、TNF-αElisa试剂盒来检测每组IL-6、TNF-α浓度,具体结果见图7。
图7为水凝胶抗炎效果统计图,通过图7可知,PDCE0.7水凝胶具有良好的抗炎能力,可以减少小鼠巨噬细胞中炎症因子IL-6、TNF-α的产生。
(4)水凝胶的抗氧化性能检测
检测方法:以PDCE0.7水凝胶为例,使用DPPH自由基清除法测定水凝胶的抗氧化活性,将DPPH溶解在无水乙醇中配置成0.1mM的DPPH溶液。制备PDCE0.7水凝胶,将水凝胶放置于2mL DPPH溶液中,避光静置30min,通过在517nm处的吸光度来计算水凝胶的DPPH自由基清除能力,具体结果见图8。
图8为抗氧化效果对比图,通过图8可知,PDCE0.7水凝胶具有优良的抗氧化性能,DPPH自由基清除率为84%。
(5)水凝胶的伤口愈合能力检测
检测方法:以PDCE0.7水凝胶为例,使用体重在180-200g的雄性SD大鼠,随机将大鼠分为三组,使用3%的戊巴比妥钠麻醉,背部剃毛后使用打孔器在皮肤上制造直径为8mm的圆形伤口,使皮肤全层缺损。然后将每个伤口处滴加20μL金黄色葡萄球菌细菌悬液(1*106CFU/mL),随即用PBS、商用3M水凝胶液体敷料、PDCE0.7水凝胶处理伤口,在0、3、7、10、14、21天拍摄伤口处照片,具体结果见图9。
图9为伤口愈合效果图,通过图9可知,在第三天时PBS组和商用3M水凝胶组伤口表面有黄色粘稠脓液渗出,原因是伤口处发生感染,机体组织炎症中伴随形成的浓稠混合物,而PDCE0.7水凝胶组没有感染现象的发生,无组织液渗出,已出现伤口收缩趋势。对照组和商用3M水凝胶组在第七天和第十天伤口表面有血痂生成,而PDCE0.7组伤口表面较为干净,伤口面积已快速缩小,在第21天PDCE0.7水凝胶组伤口已愈合完整,其他两组仍残留少量血痂。PDCE0.7水凝胶组相比于其他两组具有更快速的创面愈合效率。
Claims (9)
1.一种具有抗菌、抗炎、抗氧化功能的水凝胶的制备方法,其特征在于,包括以下步骤:
(1)将鞣花酸溶液和巯基β环糊精溶液于无氧环境中搅拌,然后过滤并进行干燥,制得包合物;
(2)将包合物、二巯基化合物、聚乙二醇降冰片烯加入水中,混匀,向其中加入引发剂,然后将混合物溶液置于紫外光照环境中照射,制得水凝胶;
步骤(2)中二巯基化合物包括二硫苏糖醇和巯基聚乙二醇硫醇;聚乙二醇降冰片烯包括双臂聚乙二醇降冰片烯、四臂聚乙二醇降冰片烯和八臂聚乙二醇降冰片烯。
2.如权利要求1所述的制备方法,其特征在于,步骤(1)中具体操作为:将鞣花酸的乙醇溶液滴加至巯基β环糊精水溶液中,超声处理,然后于室温无氧条件下搅拌30-45h,然后用0.45μm滤膜过滤混合溶液,将滤过物冷冻干燥,制得包合物。
3.如权利要求1或2所述的制备方法,其特征在于,步骤(1)中鞣花酸和巯基β环糊精的摩尔比为1:1-3。
4.如权利要求1所述的制备方法,其特征在于,步骤(2)中当硫醇基:烯基=1时,二巯基化合物和包合物的摩尔比为1-9:1-9。
5.如权利要求1所述的制备方法,其特征在于,步骤(2)中光引发剂在混合物溶液中的质量占比为0.04-0.5%。
6.如权利要求4所述的制备方法,其特征在于,步骤(2)中混合物溶液中聚乙二醇降冰片烯的质量浓度为6-10wt%。
7.如权利要求1所述的制备方法,其特征在于,步骤(2)光照强度为5-10mW/cm2。
8.一种具有抗菌、抗炎、抗氧化功能的水凝胶,其特征在于,采用权利要求1-7中任一项所述的制备方法制得。
9.权利要求8中所述的具有抗菌、抗炎、抗氧化功能的水凝胶在制备外用敷料或细胞外培养基质中应用。
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