CN111116942B - 一种可控自交联释氧水凝胶组合物及其应用 - Google Patents

一种可控自交联释氧水凝胶组合物及其应用 Download PDF

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CN111116942B
CN111116942B CN201911390687.3A CN201911390687A CN111116942B CN 111116942 B CN111116942 B CN 111116942B CN 201911390687 A CN201911390687 A CN 201911390687A CN 111116942 B CN111116942 B CN 111116942B
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耿志杰
刘群峰
于珊
裴大婷
鲁道欢
国翠平
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Abstract

本发明提供一种可控自交联释氧的水凝胶组合物,包含A组分和B组分,所述A组分的活性成分包含壳聚糖和/或其衍生物、大分子交联剂、过氧化氢源催化剂,所述B组分的活性成分包含亲水单体、光引发剂、交联剂、过氧化氢源。本发明中水凝胶是过氧化氢源及其催化剂的载体,则通过控制壳聚糖和/或其衍生物与大分子交联剂的配比和种类来控制水凝胶原位自交联的交联时间、水凝胶强度、水凝胶透气性等,来实现水凝胶释氧的可控性,又通过控制水凝胶中的过氧化氢源及其催化剂的比例来控制氧气释放的情况(如浓度与释氧持续性等)。

Description

一种可控自交联释氧水凝胶组合物及其应用
技术领域
本发明属于医药领域,尤其涉及一种可控自交联释氧水凝胶组合物及其应用。
背景技术
随着伤口愈合理论的发展,氧气的伤口愈合的影响得到了越来越多的理解。如糖尿病足等慢性伤口难以愈合的一个重要原因是,伤口部位血液供应匮乏导致氧气不能通过血液传递到伤口处。又如当伤口窄深、缺血、坏死组织多、引流不畅,并混有其他需氧菌感染而造成伤口局部缺氧时,破伤风便容易发生。氧气在伤口愈合过程中发挥的作用是多方面的,创面愈合是一个耗能的过程,氧气能够提供过程需要的能量支持;促进组织再生过程中胶原的合成和新生血管的生成;氧气在伤口的抗菌方面也发挥很大的作用,氧气的存在能杀死一些产生致病性和恶臭的细菌。虽然一定程度低氧可启动机体的生理修复过程,但不能忽视缺氧对伤口愈合的不良影响——低氧限制伤口愈合。伤口愈合需要受组织重组的血液灌注和供氧。通过改善氧供以纠正存在的低氧状态对伤口的愈合有明显益处。
创面敷料分为传统敷料、相互作用性敷料和生物活性敷料,现在广为使用的敷料多为生物活性敷料,为了预防炎症反应、加速创面愈合等,多加入药物、细胞因子。现有的生物活性敷料大多功能单一,多是提供保湿、隔离的作用,有些具有消炎、加速创面愈合的敷料是靠敷料中添加抗菌剂、细胞生长因子类的物质起作用,制备过程复杂,容易携带具有细胞毒性的小分子物质,生物相容性不好,添加了抗菌剂的敷料还存在耐药性的可能导致使用效果不佳,不是理想的生物活性敷料。而能够释放活性氧的敷料仍鲜有报道,专利申请CN104706659A公开了一种富氧创面保护涂抹的制备方法,形成了释放氧气的载体,但该体系的氧气是靠给载体充氧再释放实现的,释放氧气的过程比较复杂,不易操作。
发明内容
为了解决上述存在的问题,本发明的目的在于提供一种可控自交联释氧水凝胶组合物及其应用。
本发明所采取的技术方案是:
一种可控自交联释氧的水凝胶组合物,其特征在于:包含A组分和B组分,所述A组分的活性成分包含壳聚糖和/或其衍生物、大分子交联剂、过氧化氢源催化剂,所述B组分的活性成分包含亲水单体、光引发剂、交联剂、过氧化氢源。
优选的,上述壳聚糖和/或其衍生物和大分子交联剂的体积比为1:1-20,所述过氧化氢源催化剂和所述过氧化氢源的质量浓度比为1:10-50。
优选的,上述壳聚糖和/或其衍生物和大分子交联剂的体积比为1:5-15,上述过氧化氢源催化剂和所述过氧化氢源的质量浓度比为1:20-35。
优选的,上述壳聚糖和/或其衍生物的质量浓度为1%-10%,上述大分子交联剂的质量浓度为5%-20%。
优选的,上述B组分的活性成分包含10-30份亲水单体、0.1-2份光引发剂、0.1-2份交联剂、5-20份过氧化氢源。
优选的,上述壳聚糖衍生物选自羟乙基壳聚糖、羟丙基壳聚糖、羧甲基壳聚糖、羟乙基壳聚糖的至少一种;上述大分子交联剂选自氧化海藻酸钠、氧化葡聚糖、氧化透明质酸钠、氧化结冷胶、氧化果胶、双醛基聚乙二醇的至少一种。
优选的,上述亲水单体选自丙烯酰胺类化合物、丙烯酰化明胶类化合物的至少一种;上述过氧化氢源选自过氧化氢、过氧化氢络合物、过氧化钙、聚乙烯吡咯烷酮的至少一种。
优选的,上述A组分还可包含生长因子。
本发明还提供一种可控自交联释氧水凝胶,将上述B组分混匀光固化后,与A组分接触。
本发明还提供上述水凝胶组合物在制备皮肤护理药物中的应用。
本发明还提供上述水凝胶组合物在制备给皮肤输送氧气的药物的应用。
本发明还提供了上述可控自交联释氧水凝胶在制备给皮肤输送氧气的药物的应用。
本发明的有益效果是:
(1)本发明中水凝胶是过氧化氢源及其催化剂的载体,则通过控制壳聚糖和/或其衍生物与大分子交联剂的配比和种类来控制水凝胶原位自交联的交联时间、水凝胶强度、水凝胶透气性等,来实现水凝胶释氧的可控性,又通过控制水凝胶中的过氧化氢源及其催化剂的比例来控制氧气释放的情况(如浓度与释氧持续性等)。
(2)本发明的释放氧气的水凝胶是一种能够缓慢持续释放活性氧,具有保湿作用,能够为创面提供局部的低氧的湿性愈合环境,利于创面的愈合。该发明的水凝胶选用的原料自带抑菌功能,并且制备条件温和、简单易操作,体系中采用大分子交联剂,不含具有细胞毒性的小分子物质,无皮肤刺激性,具有良好的生物相容性,还可根据需要添加生长因子等促进创面愈合的物质,在促进创面愈合特别是慢性创面护理方面具有显著的优势。
(3)本发明的可控释氧水凝胶体系由A组分和B组分两部分凝胶组成,释放的氧气由凝胶体系发生温和的化学反应产生,不发生副反应、不产生副作用。
(4)本发明水凝胶在使用前A组分和B组分两部分凝胶可以独立保存,避免了释氧体系的实效,保证使用时活性氧的长效稳定释放。
具体实施方式
以下通过具体的实施例对本发明的内容作进一步详细的说明。实施例中所用的原料、试剂或装置如无特殊说明,均可从常规商业途径得到。除非特别说明,试验或测试方法均为本领域的常规方法。
本发明的水凝胶组合物及水凝胶的释氧机制:A组分和B组分两组分形成的凝胶接触即可触发化学反应发生,A组分的催化剂催化B组分的过氧化氢源分解反应释氧氧气,通过控制体系中A组分和B组分中壳聚糖和/或其衍生物以及大分子交联剂的配比,来调控其自交联的交联时间、水凝胶强度、水凝胶透气性等,以及通过控制A组分中催化剂和B组分中过氧化氢源的比例控制调节氧气的释氧速率和释放量。
氧气释放情况的测定方法:将反应装置放在集气瓶中,集气瓶与微量氧测试仪连接,经压力传感器即可得出反应过程氧气的释放情况。
实施例1:
称取一定量的过氧化氢源催化剂加入至质量浓度为2%的羟丙基壳聚糖溶液配成质量浓度为100ug/mL的溶液,按照溶液体积比为1:20的比例,与质量浓度为20%的氧化海藻酸钠溶液混合,搅拌混合均匀,注入模具中静置1min得A组分。
分别称取质量份额为30份的丙烯酰胺、0.1份的光引发剂、0.1份的交联剂、20份的聚乙烯吡咯烷酮/过氧化氢的络合物及余量超纯水,混合均匀后注入模具中,UV固化后得B组分。将B组分覆盖在A组分上,两者接触即可产生氧气,经测定,氧气的持续释放时间为72h,氧气流量达0.5mL/cm2·h,局部氧分压达40mmHg。
实施例2:
称取一定量的过氧化氢源催化剂加入至体积分数为4%的羧甲基壳聚糖溶液配成质量浓度为200ug/mL的溶液,按照溶液体积比为1:10的比例,与体积分数为10%的氧化葡聚糖溶液混合,搅拌混合均匀,注入模具中静置0.8min得A组分。
分别称取质量份额为20份的甲基丙烯酰胺、0.3份的光引发剂、0.2份的交联剂、10份的聚乙烯吡咯烷酮/过氧化氢的络合物及余量超纯水,混合均匀后注入模具中,UV固化后得B组分。将B组分覆盖在A组分上,两者接触即可产生氧气,经测定,氧气的持续释放时间为120h,氧气流量达0.4mL/cm2·h,局部氧分压达50mmHg。
实施例3:
称取一定量的过氧化氢源催化剂加入至体积分数为5%的壳聚糖溶液配成质量浓度为1000ug/mL的溶液,按照溶液体积比为1:5的比例,与体积分数为5%的双醛基的聚乙二醇溶液混合,搅拌混合均匀,注入模具中静置0.5min得A组分。
分别称取质量份额为10份的丙烯酰化的明胶、1.5份的光引发剂、0.5份的交联剂、5份的过氧化钙及余量超纯水,混合均匀后注入模具中,UV固化后得B组分。将B组分覆盖在A组分上,两者接触即可产生氧气,经测定,氧气的持续释放时间为56h,氧气流量达0.5mL/cm2·h,局部氧分压达30mmHg。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。

Claims (8)

1.一种可控自交联释氧的水凝胶组合物,其特征在于:包含A组分和B组分,所述A组分的活性成分包含壳聚糖和/或其衍生物、大分子交联剂、过氧化氢源催化剂,所述B组分的活性成分包含亲水单体、光引发剂、交联剂、过氧化氢源;所述壳聚糖和/或其衍生物和大分子交联剂的体积比为1:1-20,所述过氧化氢源催化剂和所述过氧化氢源的质量浓度比为1:10-50;所述壳聚糖和/或其衍生物的质量浓度为1%-10%,所述大分子交联剂的质量浓度为5%-20%;所述壳聚糖衍生物选自羟乙基壳聚糖、羟丙基壳聚糖、羧甲基壳聚糖的至少一种;所述大分子交联剂选自氧化海藻酸钠、氧化葡聚糖、氧化透明质酸钠、氧化结冷胶、氧化果胶、双醛基聚乙二醇的至少一种;所述亲水单体选自丙烯酰胺类化合物、丙烯酰化明胶类化合物的至少一种;所述过氧化氢源选自过氧化氢、过氧化钙、聚乙烯吡咯烷酮/过氧化氢络合物的至少一种。
2.根据权利要求1所述的水凝胶组合物,其特征在于:所述壳聚糖和/或其衍生物和大分子交联剂的体积比为1:5-15,所述过氧化氢源催化剂和所述过氧化氢源的质量浓度比为1:20-35。
3.根据权利要求1所述的水凝胶组合物,其特征在于:所述B组分的活性成分包含质量份为10-30份的亲水单体、0.1-2份的光引发剂、0.1-2份的交联剂、5-20份的过氧化氢源。
4.根据权利要求1所述的水凝胶组合物,其特征在于:所述A组分还可包含生长因子。
5.一种可控自交联释氧水凝胶,其特征在于:是通过如下步骤的方法制得:按照权利要求1-4任一项所述的水凝胶组合物的组成,将B组分混匀,光固化后,与A组分接触。
6.权利要求1-4任一项所述的水凝胶组合物在制备皮肤护理药物中的应用。
7.权利要求1-4任一项所述的水凝胶组合物在制备给皮肤输送氧气的药物的应用。
8.权利要求5所述可控自交联释氧水凝胶在制备给皮肤输送氧气的药物的应用。
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