CN112480433A - 一种粘性壳聚糖-海藻酸盐水凝胶及其制备和应用方法 - Google Patents
一种粘性壳聚糖-海藻酸盐水凝胶及其制备和应用方法 Download PDFInfo
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Abstract
本发明提供一种粘性壳聚糖‑海藻酸盐水凝胶及其制备和应用方法,该水凝胶具有良好的黏附性能,使得其在医药伤口敷料领域中具有很好的应用。本发明实施例的粘性壳聚糖‑海藻酸盐水凝胶,按照质量百分数,包括以下组分:1%~5%壳聚糖,1%~5%海藻酸,88%~97%一价金属盐溶液,壳聚糖的天然交联剂、海藻酸盐的离子交联剂和增粘剂;增粘剂为黏土、多巴胺或卡拉胶中的一种或多种;增粘剂的质量是水凝胶总质量的0.5%~10%。本发明实施例的粘性壳聚糖‑海藻酸盐水凝胶,相比于壳聚糖‑海藻酸盐多孔水凝胶,在黏附性能上有很大的提高。本发明的粘性壳聚糖‑海藻酸盐水凝胶可以在医药伤口敷料领域中具有很好的应用。
Description
技术领域
本发明属于高分子材料领域,具体来说,涉及一种粘性壳聚糖-海藻酸盐水凝胶及其制备和应用方法。
背景技术
水凝胶是在水中溶胀并保持大量的水分而又不溶解的聚合物。高分子水凝胶是由高分子骨架、水、交联剂组成的三维体系,具有复杂空间网状结构,有着广泛的应用。在医学领域:用作药物释放的载体,水凝胶兼备储存药物、控制释放速度、驱动释放三种功能,既能调节制剂的强度和硬度,又能起到促进分解、赋形的作用,还能遮蔽医药品的苦味和气味,可用于口服、鼻腔、口腔、直肠、眼部、注射等给药途径。用作伤口敷料,水凝胶材料直接用于与人体组织接触,可防止体外微生物的感染,抑制体液的损失,传输氧到伤口可加速上皮细胞生长,加速新微血管增生,隔绝细菌侵犯,抑制细菌繁殖,促进伤口的愈合。水凝胶因具有生物相容性、生物降解性、高含水量和细胞膜粘附性而应用于组织工程。但普通壳聚糖水凝胶因其粘附性能有限,当用作伤口敷料时容易出现滑落等现象,因此提高壳聚糖水凝胶的粘性对于增强壳聚糖水凝胶医用敷料的应用显得尤为急切和重要。
发明内容
本发明所要解决的技术问题是:提供一种粘性壳聚糖-海藻酸盐水凝胶及其制备和应用方法,该水凝胶具有良好的黏附性能,使得其在医药伤口敷料领域中具有很好的应用。
为解决上述技术问题,本发明采用的技术方案是:
第一方面,本发明实施例提供一种粘性壳聚糖-海藻酸盐水凝胶,按照质量百分数,包括以下组分:
壳聚糖:1%~5%,
海藻酸盐1%~5%,
一价金属盐溶液:88%~97%,
壳聚糖的天然交联剂、海藻酸盐的离子交联剂和增粘剂;
所述增粘剂为黏土、多巴胺或卡拉胶中的一种或多种;
所述一价金属盐溶液的质量浓度为0.01%~2%;
所述壳聚糖的天然交联剂的质量是所述壳聚糖质量的0.2%~4.5%;
所述海藻酸盐的离子交联剂为二价金属盐,所述二价金属盐的质量是所述海藻酸盐质量的1%~30%;
所述增粘剂的质量是所述粘性壳聚糖-海藻酸盐水凝胶总质量的0.5%~10%。
作为本发明实施例的进一步改进,所述一价金属盐溶液为氯化钠溶液或者氯化钾溶液。
作为本发明实施例的进一步改进,所述壳聚糖的天然交联剂为京尼平。
作为本发明实施例的进一步改进,所述二价金属盐为钙盐、锶盐或者钡盐,且金属盐具有可溶性或者微溶性。
作为本发明实施例的进一步改进,所述粘性壳聚糖-海藻酸盐水凝胶中形成三重网络,分别为壳聚糖和壳聚糖的天然交联剂形成的共价交联网络,海藻酸盐和海藻酸盐的离子交联剂之间形成的离子交联网络,壳聚糖上的-NH2和海藻酸钠上的-COOH之间的相互作用形成的第三重网络。
第二方面,本发明实施例提供上述粘性壳聚糖-海藻酸盐水凝胶的制备方法,该制备方法包括以下步骤:
步骤1)将壳聚糖加入一价金属盐的乙酸溶液中,搅拌均匀,使壳聚糖完全溶解,形成壳聚糖溶液;
将海藻酸盐加入一价金属盐溶液中,搅拌均匀,使海藻酸盐完全溶解,形成海藻酸盐溶液;
步骤2)搅拌步骤1)得到的海藻酸盐溶液,向所述海藻酸盐溶液中分别加入增粘剂和步骤1)得到的壳聚糖溶液,最后加入海藻酸盐的离子交联剂,搅拌1~15min,加冰袋冷却超声1~30min,形成均匀的粘性溶液体系;
步骤3)将步骤2)形成的粘性溶液体系于15~60℃水浴培养4~48h,得到粘性壳聚糖-海藻酸盐水凝胶。
作为本发明实施例的进一步改进,所述一价金属盐溶液的质量浓度为0.01%~2%;
所述壳聚糖的天然交联剂的质量是所述壳聚糖质量的0.2%~4.5%;
所述海藻酸盐的离子交联剂为二价金属盐,所述二价金属盐的质量是所述海藻酸盐质量的1%~30%;
所述增粘剂的质量是所述粘性壳聚糖-海藻酸盐水凝胶总质量的0.5%~10%。
第三方面,本发明实施例提供一种上述粘性壳聚糖-海藻酸盐水凝胶作为生物医用材料的应用。
与现有技术相比,本发明所制备出的粘性壳聚糖-海藻酸盐水凝胶,具有良好的黏附性能。本发明制备的粘性壳聚糖-海藻酸盐水凝胶具有三重网络的结构,分别为壳聚糖和壳聚糖的天然交联剂形成的共价交联网络,海藻酸盐和海藻酸盐的离子交联剂之间形成的离子交联网络,壳聚糖上的-NH2和海藻酸钠上的-COOH之间的相互作用形成的第三重网络。若增粘剂为多巴胺或包含多巴胺,多巴胺在碱性环境下,酚羟基被氧化成多巴醌,与壳聚糖中的氨基发生席夫碱反应,形成一个粘附层固化在基底表面,从而有效提高水凝胶的粘附性能。若增粘剂为黏土或包含黏土,黏土不仅有粘性,而且黏土的片层结构中间可以与三重网络互穿,提高水凝胶的整体黏附性,若增粘剂还包含多巴胺,同时可以控制多巴胺的氧化。若增粘剂为卡拉胶或包含卡拉胶,卡拉胶穿插在三重网络中,其中磺酸基团可以与壳聚糖的氨基作用,形成离子的相互作用,增强水凝胶的黏附性。本发明实施例的粘性壳聚糖-海藻酸盐水凝胶,相比于壳聚糖-海藻酸盐多孔水凝胶,在黏附性能上有很大的提高。因此,本发明的粘性壳聚糖-海藻酸盐水凝胶可以在医药伤口敷料领域中具有很好的应用。
附图说明
图1是本发明实施例1-6所制备的水凝胶与对照例制备的壳聚糖-海藻酸盐水凝胶的粘度测试的对比图。
具体实施方式
下面结合具体的实施例对本发明作进一步的描述,以便本领域的技术人员进一步理解本发明,但以下实施例并不以任何形式限制本发明。
本发明实施例提供粘性壳聚糖-海藻酸盐水凝胶,按照质量百分数,包括以下组分:
壳聚糖:1%~5%,
海藻酸盐1%~5%,
一价金属盐溶液:88%~97%,
壳聚糖的天然交联剂、海藻酸盐的离子交联剂和增粘剂;
所述增粘剂为黏土、多巴胺或卡拉胶中的一种或多种;
所述一价金属盐溶液的质量浓度为0.01%~2%;
所述壳聚糖的天然交联剂的质量是所述壳聚糖质量的0.2%~4.5%;
所述海藻酸盐的离子交联剂为二价金属盐,所述二价金属盐的质量是所述海藻酸盐质量的1%~30%;
所述增粘剂的质量是所述粘性壳聚糖-海藻酸盐水凝胶总质量的0.5%~10%。
上述实施例中,作为优选,所述一价金属盐溶液为氯化钠溶液或者氯化钾溶液,适当削弱海藻酸盐与壳聚糖之间强烈的离子相互作用,增强凝胶体系的均匀性。所述壳聚糖的天然交联剂为京尼平。所述二价金属盐为钙盐、锶盐或者钡盐,且金属盐具有可溶性或者微溶性。可溶性的钙盐、锶盐、钡盐,通过离子交联海藻酸盐结构中的G段或MG段形成离子交联网络;微溶性的钙盐、锶盐、钡盐,由于已溶解出的部分离子与海藻盐发生交联,从而促进微溶性盐在水中的溶解和电离,最终使微溶性盐中的二价离子全部释放出来,参与海藻酸盐的交联过程。
粘性壳聚糖-海藻酸盐水凝胶具有三重网络的结构,分别为壳聚糖和壳聚糖的天然交联剂形成的共价交联网络,海藻酸盐和海藻酸盐的离子交联剂之间形成的离子交联网络,壳聚糖上的-NH2和海藻酸钠上的-COOH之间的相互作用形成的第三重网络。若增粘剂为多巴胺或包含多巴胺,多巴胺在碱性环境下,酚羟基被氧化成多巴醌,与壳聚糖中的氨基发生席夫碱反应,形成一个粘附层固化在基底表面,从而有效提高水凝胶的粘附性能。若增粘剂为黏土或包含黏土,黏土不仅有粘性,而且黏土的片层结构中间可以与三重网络互穿,提高水凝胶的整体黏附性,增粘剂还包含多巴胺,同时可以控制多巴胺的氧化。若增粘剂为卡拉胶或包含卡拉胶,卡拉胶穿插在三重网络中,其中磺酸基团可以与壳聚糖的氨基作用,形成离子的相互作用,增强水凝胶的黏附性。
本发明实施例还提供一种上述粘性壳聚糖-海藻酸盐水凝胶的制备方法,该制备方法包括以下步骤:
步骤1)将壳聚糖加入一价金属盐的乙酸溶液中,搅拌均匀,使壳聚糖完全溶解,形成壳聚糖溶液;
将海藻酸盐加入一价金属盐溶液中,搅拌均匀,使海藻酸盐完全溶解,形成海藻酸盐溶液;
步骤2)搅拌步骤1)得到的海藻酸盐溶液,向所述海藻酸盐溶液中分别加入增粘剂和步骤1)得到的壳聚糖溶液,最后加入海藻酸盐的离子交联剂,搅拌1~15min,加冰袋冷却超声1~30min,形成均匀的粘性溶液体系;
步骤3)将步骤2)形成的粘性溶液体系于15~60℃水浴培养4~48h,得到粘性壳聚糖-海藻酸盐水凝胶。
上述制备方法中,按照如下质量百分数进行加入:
壳聚糖:1%~5%;海藻酸盐1%~5%;一价金属盐溶液:88%~97%,一价金属盐溶液的质量浓度为0.01%~2%;壳聚糖的天然交联剂的质量是所述壳聚糖质量的0.2%~4.5%;海藻酸盐的离子交联剂为二价金属盐,二价金属盐的质量是所述海藻酸盐质量的1%~30%;增粘剂的质量是粘性壳聚糖-海藻酸盐水凝胶总质量的0.5%~10%。
作为优选,一价金属盐溶液为氯化钠溶液或者氯化钾溶液;壳聚糖的天然交联剂为京尼平;二价金属盐为钙盐、锶盐或者钡盐,且金属盐具有可溶性或者微溶性。
以Ca2+作为离子交联剂、NaCl作为一价金属盐为例,按照上述制备方法制备的凝胶内部形成了四重网络结构,包括壳聚糖和京尼平形成的共价交联网络,海藻酸钠和离子交联剂之间形成的离子交联网络,壳聚糖上的-NH2和海藻酸盐上的-COOH之间的相互作用形成的第三重网络,纳米二氧化钛粒子与卡拉胶形成的第四重网络,且第四重网络穿插在第三重网络中。
在制备过程中,壳聚糖的天然交联剂可以与壳聚糖发生化学交联,形成第一重交联网络,二价金属离子可以与海藻酸盐结构中的G段和MG段交联形成第二重交联网络。同时当将壳聚糖和海藻酸盐混合后,由于二者因静电相互作用在相界面形成聚电解质,而不能使二者形成均匀的交联网络。在该体系中,一价金属盐的加入,减弱了壳聚糖和海藻酸盐的相互作用,同时海藻酸盐和壳聚糖之间仍存在离子的相互作用,形成第三重交联网络。若增粘剂为多巴胺或包含多巴胺,多巴胺在碱性环境下,酚羟基被氧化成多巴醌,与壳聚糖中的氨基发生席夫碱反应,形成一个粘附层固化在基底表面,从而有效提高水凝胶的粘附性能。若增粘剂为黏土或包含黏土,黏土不仅有粘性,而且黏土的片层结构中间可以与三重网络互穿,提高水凝胶的整体黏附性,增粘剂还包含多巴胺,同时可以控制多巴胺的氧化。若增粘剂为卡拉胶或包含卡拉胶,卡拉胶穿插在三重网络中,其中磺酸基团可以与壳聚糖的氨基作用,形成离子的相互作用,增强水凝胶的黏附性。相比于壳聚糖-海藻酸盐多孔水凝胶,本发明实施例的粘性壳聚糖-海藻酸盐水凝胶的黏附性能要高。
本发明实施例制备的粘性壳聚糖-海藻酸盐水凝胶具有较好的黏附性能,因此,本发明实施例的粘性壳聚糖-海藻酸盐水凝胶可作为生物医用材料,用于制作医药伤口敷料。
下面通过试验,来具体验证本发明实施例的凝较具有良好的黏附性能。
试验提供六个实施例和一个对比例。六个实施例都是按照本发明的制备方法制备的凝胶,对照例是不加增粘剂制备得到的壳聚糖-海藻酸盐多孔水凝胶。各实施例中各物质的用量,单位:mg,如表1所示。六个实施例和对照例中,壳聚糖的天然交联剂采用京尼平,海藻酸盐的离子交联剂采用二水硫酸钙。
表1
对上述六个实施例的凝胶和对照例的壳聚糖-海藻酸盐多孔水凝胶,分别进行粘性测试。
粘性测试采用安东帕公司生产的MCR302旋转流变仪测试水凝胶的粘弹性。采用直径为25mm的平行板,调节为振荡剪切变形模式,板间距为0.1mm,温度为37℃,剪切频率为10HZ、应变范围0.01%-100%。将粘度作为纵坐标,剪切速率为横坐标绘制曲线。结果如图1所示。
从图1中可以明显的看出,按照本发明实施例方法制备出的水凝胶的粘度均比对照例的壳聚糖-海藻酸盐多孔水凝胶的粘度高,且增加倍数显著。尤其增粘剂同时包含卡拉胶和多巴胺,粘度达到1000mPa·s以上。
Claims (8)
1.一种粘性壳聚糖-海藻酸盐水凝胶,其特征在于,按照质量百分数,包括以下组分:
壳聚糖:1%~5%,
海藻酸盐1%~5%,
一价金属盐溶液:88%~97%,
壳聚糖的天然交联剂、海藻酸盐的离子交联剂和增粘剂;
所述增粘剂为黏土、多巴胺或卡拉胶中的一种或多种;
所述一价金属盐溶液的质量浓度为0.01%~2%;
所述壳聚糖的天然交联剂的质量是所述壳聚糖质量的0.2%~4.5%;
所述海藻酸盐的离子交联剂为二价金属盐,所述二价金属盐的质量是所述海藻酸盐质量的1%~30%;
所述增粘剂的质量是所述粘性壳聚糖-海藻酸盐水凝胶总质量的0.5%~10%。
2.按照权利要求1中所述的粘性壳聚糖-海藻酸盐水凝胶,其特征在于,所述一价金属盐溶液为氯化钠溶液或者氯化钾溶液。
3.按照权利要求1所述的粘性壳聚糖-海藻酸盐水凝胶,其特征在于,所述壳聚糖的天然交联剂为京尼平。
4.按照权利要求1所述的粘性壳聚糖-海藻酸盐水凝胶,其特征在于,所述二价金属盐为钙盐、锶盐或者钡盐,且金属盐具有可溶性或者微溶性。
5.按照权利要求1中所述的粘性壳聚糖-海藻酸盐水凝胶,其特征在于,所述粘性壳聚糖-海藻酸盐水凝胶中形成三重网络,分别为壳聚糖和壳聚糖的天然交联剂形成的共价交联网络,海藻酸盐和海藻酸盐的离子交联剂之间形成的离子交联网络,壳聚糖上的-NH2和海藻酸钠上的-COOH之间的相互作用形成的第三重网络。
6.一种权利要求1中所述的粘性壳聚糖-海藻酸盐水凝胶的制备方法,其特征于,该制备方法包括以下步骤:
步骤1)将壳聚糖加入一价金属盐的乙酸溶液中,搅拌均匀,使壳聚糖完全溶解,形成壳聚糖溶液;
将海藻酸盐加入一价金属盐溶液中,搅拌均匀,使海藻酸盐完全溶解,形成海藻酸盐溶液;
步骤2)搅拌步骤1)得到的海藻酸盐溶液,向所述海藻酸盐溶液中分别加入增粘剂和步骤1)得到的壳聚糖溶液,最后加入海藻酸盐的离子交联剂,搅拌1~15min,加冰袋冷却超声1~30min,形成均匀的粘性溶液体系;
步骤3)将步骤2)形成的粘性溶液体系于15~60℃水浴培养4~48h,得到粘性壳聚糖-海藻酸盐水凝胶。
7.根据权利要求6所述的粘性壳聚糖-海藻酸盐水凝胶的制备方法,其特征于,
所述一价金属盐溶液的质量浓度为0.01%~2%;
所述壳聚糖的天然交联剂的质量是所述壳聚糖质量的0.2%~4.5%;
所述海藻酸盐的离子交联剂为二价金属盐,所述二价金属盐的质量是所述海藻酸盐质量的1%~30%;
所述增粘剂的质量是所述粘性壳聚糖-海藻酸盐水凝胶总质量的0.5%~10%。
8.一种权利要求1所述的粘性壳聚糖-海藻酸盐水凝胶作为生物医用材料的应用。
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CN114159586A (zh) * | 2021-11-10 | 2022-03-11 | 上海维洱生物医药科技有限公司 | 一种内镜用粘膜下注射标记物载体凝胶及其应用 |
CN114395147A (zh) * | 2022-01-29 | 2022-04-26 | 广东省科学院生物与医学工程研究所 | 水凝胶及其制备方法和应用 |
CN114395147B (zh) * | 2022-01-29 | 2024-04-26 | 广东省科学院生物与医学工程研究所 | 水凝胶及其制备方法和应用 |
CN115124739A (zh) * | 2022-07-12 | 2022-09-30 | 自然资源部第三海洋研究所 | 一种可注射海洋多糖全物理交联水凝胶及其制备方法 |
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