CN114591543A - 一种硫酸软骨素生物凝胶及其制备方法和应用 - Google Patents
一种硫酸软骨素生物凝胶及其制备方法和应用 Download PDFInfo
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Abstract
本发明公开了一种硫酸软骨素生物凝胶及其制备方法和应用，属于生物新材料领域，以硫酸软骨素为起始原料，加入修饰后的聚甘油交联剂，制得交联CS生物凝胶，使用交联剂将硫酸软骨素分子链之间互相链接，形成连续稳定的网状结构，在水中可以溶胀但不溶解，得到的硫酸软骨素生物凝胶肤感柔软、无黏腻感，生物相容性好，可以应用于冷敷凝胶、面贴膜、退热贴基质等，符合绿色环保的市场趋势，具有良好的应用前景。
Description
技术领域
本发明属于生物新材料领域，尤其涉及一种硫酸软骨素生物凝胶及其制备方法和应用。
背景技术
硫酸软骨素，简称CS，是一类硫酸化的酸性粘多糖，由葡糖醛酸和N-乙酰氨基半乳糖二糖单位重复组成。硫酸软骨素分布于人和动物的很多组织器官如软骨、韧带、肌腱、角膜等不同组织中。CS主要与氨基葡萄糖配合使用，作为治疗关节疾病的药品，具有止痛、促进软骨再生的功效。现有技术中，尚无CS在生物凝胶方面的应用。
发明内容
本发明提供了一种硫酸软骨素生物凝胶及其制备方法和应用，使用交联剂将CS分子链之间互相链接，形成连续稳定的网状结构，在水中可以溶胀但不溶解，其肤感柔软、无黏腻感，生物相容性好，可以应用于冷敷凝胶、面贴膜、退热贴基质等，符合绿色环保的市场趋势，具有良好的应用前景。
为实现以上目的，本发明采用以下技术方案：
一种硫酸软骨素生物凝胶，所述凝胶为交联硫酸软骨素，所述硫酸软骨素分子链之间通过交联剂互相链接，形成连续稳定的网状结构，
以上所述凝胶中，所述硫酸软骨素和交联剂的质量比为1:1.1-1:3,所述的硫酸软骨素为粉末，来源于动物，平均分子量为5000-10万Da，优选5万至7万Da；所述硫酸软骨素是由葡萄糖醛酸和N-乙酰半乳糖胺聚合而成的糖胺聚糖，包括硫酸软骨素钠、硫酸软骨素钾或硫酸软骨素钙等；所述硫酸软骨素来源于动物的软骨，如鲨鱼、牛、猪、鸡等；
所述交联剂为聚甘油和二环氧辛烷反应的产物，所述聚甘油为聚甘油-6到聚甘油-14的一种，优选聚甘油-8至聚甘油-12，所述聚甘油为线性或环状结构。
一种硫酸软骨素生物凝胶的制备方法，包括以下步骤：
(1)将聚甘油和纯化水按质量比1:5-1:10的比例混合溶解，调节pH至11-14；
(2)将0.01-1g的二环氧辛烷加入步骤(1)得到的溶液中，40℃下反应10分钟后，冰浴降至室温，得交联剂；
(3)将步骤(2)所得交联剂投入硫酸软骨素水溶液中，在25℃-30℃搅拌2-4小时，调节pH至中性；
(4)将步骤(3)得到的物质投入至纯化水中，直至膨胀透明得交联硫酸软骨素凝胶。
以上所述步骤中，步骤(1)中采用氢氧化钠调节pH，步骤(3)中硫酸软骨素水溶液质量浓度为1-10％，步骤(4)中得到凝胶后可过10-50μm筛网，得凝胶颗粒，灭菌、真空干燥即得交联硫酸软骨素粉末易于保存。
上述得到的硫酸软骨素生物凝胶可以应用于冷敷凝胶、面贴膜、退热贴基质中。
有益效果：本发明提供了一种硫酸软骨素生物凝胶及其制备方法和应用，以CS为起始原料，加入修饰后的聚甘油交联剂，制得交联CS生物凝胶，使用聚甘油为交联剂，降低了交联剂的毒性，增强了凝胶的溶胀度和保水性能(聚甘油大量的羟基)，本发明使用交联剂将CS分子链之间互相链接，形成连续稳定的网状结构，在水中可以溶胀但不溶解，得到的凝胶具有很好的吸水性和保水能力，其肤感柔软、无黏腻感、生物相容性好、可降解，可以应用于冷敷凝胶、面贴膜、退热贴基质等，符合绿色环保的市场趋势，具有良好的应用前景。
具体实施方式
下面结合具体实施例对本发明进行详细说明：
实施例1
将聚甘油-8和纯化水按1：5的比例(w/w)混合均匀，用NaOH调节pH至12.5，取此溶液5ml，加入0.02g二环氧辛烷，40℃反应10min，立刻冰浴至室温，得交联剂，然后加入10ml纯化水得交联剂溶液；
取平均分子量为5万的CS，配制成5％(w/w)的CS水溶液，调节pH至12.5，取20g加入到交联剂溶液中室温搅拌3小时，加入150ml纯化水，调节pH至中性，溶胀透明，得交联CS凝胶；
除去纯化水，加压过10-50μm筛网，得凝胶颗粒；灭菌、真空干燥即得交联硫酸软骨素粉末。
实施例2
将聚甘油-10和纯化水按1：8的比例(w/w)混合均匀，用NaOH调节pH至12.5。取此溶液5ml，加入0.02g二环氧辛烷，40℃反应10min，立刻冰浴至室温，得交联剂，然后加入10ml纯化水得交联剂溶液；
取平均分子量为5万的CS，配制成5％(w/w)的CS水溶液，调节pH至12.5，取20g加入到交联剂溶液中室温搅拌3小时，加入150ml纯化水，调节pH至中性，溶胀透明，得交联CS凝胶；
除去纯化水，加压过10-50μm筛网，得凝胶颗粒；灭菌、真空干燥即得交联硫酸软骨素粉末。
实施例3
将聚甘油-12和纯化水按1：10的比例(w/w)混合均匀，用NaOH调节pH至12.5。取此溶液5ml，加入0.02g二环氧辛烷，40℃反应10min，立刻冰浴至室温，得交联剂。然后加入10ml纯化水得交联剂溶液；
取平均分子量为5万的CS，配制成5％(w/w)的CS水溶液，调节pH至12.5，取20g加入到交联剂溶液中室温搅拌3小时，加入150ml纯化水，调节pH至中性，溶胀透明，得交联CS凝胶；
除去纯化水，加压过10-50μm筛网，得凝胶颗粒；灭菌、真空干燥即得交联硫酸软骨素粉末。
实施例4
将聚甘油-12和纯化水按1：10的比例(w/w)混合均匀，用NaOH调节pH至12.5，取此溶液5ml，加入0.02g二环氧辛烷，40℃反应10min，立刻冰浴至室温，得交联剂，然后加入10ml纯化水得交联剂溶液；
取平均分子量为7万的CS，配制成5％(w/w)的CS水溶液，调节pH至12.5，取20g加入到交联剂溶液中室温搅拌3小时，加入150ml纯化水，调节pH至中性，溶胀透明，得交联CS凝胶；
除去纯化水，加压过10-50μm筛网，得凝胶颗粒；灭菌、真空干燥即得交联硫酸软骨素粉末。
实施例5
将聚甘油-10和纯化水按1：8的比例(w/w)混合均匀，用NaOH调节pH至12.5，取此溶液5ml，加入0.02g二环氧辛烷，40℃反应10min，立刻冰浴至室温，得交联剂，然后加入10ml纯化水得交联剂溶液；
取平均分子量为6万的CS，配制成5％(w/w)的CS水溶液，调节pH至12.5，取20g加入到交联剂溶液中室温搅拌3小时，加入150ml纯化水，调节pH至中性，溶胀透明，得交联CS凝胶；
除去纯化水，加压过10-50μm筛网，得凝胶颗粒；灭菌、真空干燥即得交联硫酸软骨素粉末。
交联CS性能检测
取1g交联CS凝胶，精密称量(W0)，加入生理盐水中，常温密封放置24小时，待充分膨胀后，取出凝胶，迅速吸干其表面游离水分，称重Wa，计算溶胀度＝Wa/W0x100％。并且测定透光率。
取溶胀后的凝胶5g，精密称量(W1)，在35℃烘箱中放置4小时，称量得W2，计算保水率＝W2/W1x100％。结果见表1。
表1各实施例交联前后的CS参数和性能对比
| 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | |
| 交联前MW | 5.4万 | 5.4万 | 5.4万 | 7.6万 | 6.5万 |
| 交联后MW | 10.2万 | 13.1万 | 14.9万 | 15.8万 | 13.8万 |
| 透光率 | 99.5％ | 99.2％ | 99.2％ | 99.2％ | 99.1％ |
| 溶胀度 | 2300 | 3500 | 3800 | 4500 | 4200 |
| 保水率 | 80.5％ | 82.7％ | 86.1％ | 90.1％ | 83.2％ |
从表1可以看出，交联CS的分子量显著增大，且随着分子量的增大，其溶胀度和保水率也在增强，聚甘油来源天然且还有多个羟基，也能够结合水分，增强容胀度和保水率。上述得到的交联CS凝胶来源天然，绿色环保可降解，符合现代环保的趋势。可应用于冷敷贴，面贴膜中。
以上所述仅是本发明的优选实施方式，应当指出：对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种硫酸软骨素生物凝胶，其特征在于，所述凝胶为交联硫酸软骨素，所述硫酸软骨素分子链之间通过交联剂互相链接，形成连续稳定的网状结构。
2.根据权利要求1所述的硫酸软骨素生物凝胶，其特征在于，所述硫酸软骨素和交联剂的质量比为1:1.1-1:3。
3.根据权利要求1或2所述的硫酸软骨素生物凝胶，其特征在于，所述的硫酸软骨素为粉末，平均分子量为5000-10万Da。
4.根据权利要求3所述的硫酸软骨素生物凝胶，其特征在于，所述的硫酸软骨素平均分子量为5万至7万Da。
5.根据权利要求3所述的硫酸软骨素生物凝胶，其特征在于，所述的硫酸软骨素来源于动物或由葡萄糖醛酸和N-乙酰半乳糖胺聚合而成的糖胺聚糖。
6.一种硫酸软骨素生物凝胶的制备方法，其特征在于，包括以下步骤：
(1)将聚甘油和纯化水按质量比1:5-1:10的比例混合溶解，调节pH至11-14；
(2)将0.01-1g的二环氧辛烷加入步骤(1)得到的溶液中，40℃下反应10分钟后，冰浴降至室温，得交联剂；
(3)将步骤(2)所得交联剂投入硫酸软骨素水溶液中，在25℃-30℃搅拌2-4小时，调节pH至中性；
(4)将步骤(3)得到的物质投入至纯化水中，直至膨胀透明得交联硫酸软骨素凝胶。
7.根据权利要求6所述的硫酸软骨素生物凝胶的制备方法，其特征在于，步骤(1)中所述聚甘油为聚甘油-6到聚甘油-14中的一种线性或环状结构。
8.根据权利要求6所述的硫酸软骨素生物凝胶的制备方法，其特征在于，步骤(3)中硫酸软骨素水溶液质量浓度为1-10％。
9.根据权利要求6所述的硫酸软骨素生物凝胶的制备方法，其特征在于，步骤(4)中得到凝胶后可过10-50μm筛网，得凝胶颗粒，灭菌、真空干燥即得交联硫酸软骨素粉末易于保存。
10.权利要求1-5任一项所述的硫酸软骨素生物凝胶可以应用于冷敷凝胶、面贴膜、退热贴基质中。
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