CN112795058A - 一种可德胶/埃洛石复合水凝胶及其应用和制备方法 - Google Patents
一种可德胶/埃洛石复合水凝胶及其应用和制备方法 Download PDFInfo
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- CN112795058A CN112795058A CN202110023239.0A CN202110023239A CN112795058A CN 112795058 A CN112795058 A CN 112795058A CN 202110023239 A CN202110023239 A CN 202110023239A CN 112795058 A CN112795058 A CN 112795058A
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- curdlan
- halloysite
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- probucol
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Abstract
本发明公开了一种可德胶/埃洛石复合水凝胶及其应用和制备方法。现有多糖凝胶透气性及缓释效果差的问题，常规改性往往要添加化学助剂，增加了毒性。本发明可德胶/埃洛石复合水凝胶具备多孔状结构，所用材料包括可德胶和埃洛石，负载的药物为阿司匹林和普罗布考。本发明利用可德胶的低温可逆和高温不可逆的独特成胶特性，及其在水中能形成良好的分散体系与在碱溶液中良好溶解这三大特点，同时结合埃洛石特殊的管状结构，在碱性条件下形成具有良好载药效果的可德胶/埃洛石复合水凝胶。该款水凝胶材料所用材料都是天然材料，无毒无害，并可生物降解，可提高药物利用率，减轻毒副作用，在生物医用高分子材料具有良好的应用前景。
Description
技术领域
本发明属于复合材料技术领域，具体涉及一种负载普罗布考/阿司匹林的可德胶/埃洛石复合水凝胶制备方法及其在生物领域的应用。
背景技术
可德胶(Curdlan)是由粪产碱杆菌(Alcaligenesfaecalis)发酵产生的微生物多糖。可德胶是由β-(1,3)糖苷键连接而成的D-葡聚糖，是β-(1-3)-D-葡聚糖家族中最具特色的一种，中性、没有分支、重复单位简单，可以被人体细胞降解吸收。可德胶于1964年被原田笃也教授发现,其商业化生产历史不长。1989年始于日本武田公司，1996年可德胶获美国食品和药物管理局(FDA)认证,可在食品中用作添加剂。可德胶凝胶特性独特，是热可逆低强度凝胶，在80℃以上时形成的是热不可逆高强度凝胶。埃洛石是无机矿物质，具有生物相容性，廉价，工艺简单等优点。另外，埃洛石还具有独特的纳米管状结构，可负载小分子药物。
阿司匹林和普罗布考是两种应用广泛和效果显著的抗血栓药物，对很多常见的疾病都有很好的治疗作用。如阿司匹林口服过程中最大的问题是因集中释药，使局部药物浓度过高，在体内水解成水杨酸后对胃肠道黏膜有刺激作用，严重时甚至出现水肿、糜烂溃疡和出血的现象。
发明内容
本发明的目的在于提供一种负载阿司匹林/普罗布考的可德胶/埃洛石复合水凝胶制备及应用。
第一方面，本发明提供一种可德胶/埃洛石复合水凝胶，其包括可德胶和埃洛石。埃洛石与可德胶在氢键作用下交联。复合水凝胶中可德胶的质量分数为0.5％～2.5％，埃洛石的质量分数为0.125％～0.625％。
作为优选，本发明一种可德胶/埃洛石复合水凝胶还负载有阿司匹林。阿司匹林与埃洛石在蒸馏水中进行负载；
作为优选，本发明一种可德胶/埃洛石复合水凝胶还负载有普罗布考；普罗布考的二氯甲烷溶液与可德胶、埃洛石的溶胶进行负载。
第二方面，本发明提供前述可德胶/埃洛石复合水凝胶作为皮肤表面创伤敷料，或肠溶液药物缓释载体或治疗抑制心脏血管扩张术后再狭窄(PTCA术后)的支架涂层的应用。可德胶/埃洛石复合水凝胶具有较高的强度，且负载在其上的心血管药物的释放时间较长，能够起到药物缓释的效果。
第三方面，本发明提供前述可德胶/埃洛石复合水凝胶的制备方法，具体步骤如下：
步骤一、将可德胶分散在水溶液或溶解在碱溶液中，得到可德胶水分散液或可德胶碱溶液；
步骤二、将埃洛石溶液滴加到搅拌的可德胶水分散液或可德胶碱溶液中，得到溶胶体系。再利用溶胶体系获得可德胶/埃洛石复合水凝胶。
作为优选，步骤一中，可德胶溶解在碱溶液的情况下，可德胶的质量浓度0.83％～4.2％；可德胶溶解在碱溶液中的情况下，可德胶与碱溶液质量比为1:119～1:23；可德胶分散到水或溶解在碱溶液的过程持续搅拌，搅拌速度为600～800rpm。所述的碱溶液采用氨水、氢氧化钠水溶液、磷酸三钠水溶液或磷酸三钙水溶液，碱溶液的质量浓度为0.0001％～1.0％。步骤二中的埃洛石与可德胶的比例为1:6～1:2，整个过程搅拌速度为600～800rpm。
作为优选，步骤二中，埃洛石溶液与可德胶水分散液或可德胶碱溶液混合前，将埃洛石加入阿司匹林溶液，使得阿司匹林与埃洛石在40℃～60℃水溶液进行负载，得到负载阿司匹林的埃洛石溶液。
作为优选，步骤二中所述的阿司匹林溶液的质量浓度为5mg/mL～25mg/mL；埃洛石与阿司匹林的质量比为1:1～1:5；所需要蒸馏水的负载温度为40℃～60℃；
作为优选，步骤二得到溶胶后，执行步骤三和四；具体如下：
步骤三、将普罗布考溶于二氯甲烷配制成的普罗布考的二氯甲烷溶液，然后将其缓慢滴加到步骤二中所述的溶胶中。
步骤四、将步骤三获得的溶胶置于70～80℃恒温水浴中，放置6～24h，充分挥发二氯甲烷，得到负载有普罗布考的可德胶/埃洛石复合水凝胶。
作为优选，步骤三中所述的普罗布考的二氯甲烷溶液的质量浓度为5mg/mL～25mg/mL；普罗布考与二氯甲烷的质量比1:264～1:52，需要逐步滴加，1～5min内滴加完毕；且持续搅拌，且搅拌速度为200～500rpm。
作为优选，步骤四中，所述溶剂挥发为二氯甲烷溶剂挥发，挥发所需时间为0.5h～2h，加热控温为70℃～85℃，复合凝胶中可德胶的质量分数为0.5％～2.5％。
本发明具有的有益效果是：
1、本发明利用不同温度下可德胶的成胶特型不同，通过温度条件改变制备温度响应型凝胶；利用埃洛石与可德胶的羟基形成氢键作用，埃洛石刚性结构起到物理交联的作用，提高可德胶凝胶的力学性能。
2、本发明利用油溶性溶剂二氯甲烷挥发产生气泡从而形成多气孔性复合水凝胶，表面气孔数量最高为3.07个/cm2，因此气凝胶达到很好的透气性，作为敷料或支架涂层使用能够能够有效保证透气，减少炎症。
3、本发明通过将水溶性药物阿司匹林，油溶性药物普罗布考协同负载进入可德胶/埃洛石缓释体系，实现了水/油双性药物协同负载，且均能达到缓释的效果，建立了新的缓释体系，增加药物利用率和药物的协同作用，同时降低毒副作用及突释损害。
4、本发明所得到的协同负载普罗布考/阿司匹林的可德胶/埃洛石复合水凝胶，可以有多种形式应用。作为表面涂层时，可应用于表面创伤辅料，防止材料拆换导致的疼痛伤害；作为缓释材料时，可应用于肠溶液药物缓释载体和治疗抑制心脏血管扩张术后再狭窄(PTCA术后)的支架缓释涂层。
5、本发明所使用的原料来源丰富，无毒，可被人体吸收降解，价格低廉，同时生产条件温和，工艺简单，生产效率高，适合大规模工业化生产，具有良好的经济效益。
附图说明
图1a-1e分别为本发明实施例1-5所述的搭载有药物的复合水凝胶的示意图；
图1a-1e分别为本发明实施例1-5所述的搭载有药物的复合水凝胶的示意图；
图2为本发明实施例3所得的复合水凝胶中阿司匹林、普罗布考的缓释曲线图。
具体实施方式
可德胶/埃洛石负载水油两性药物复合凝胶的制备方法具体如下:
以下结合附图对本发明作进一步说明。
实施例1
步骤一、在搅拌下将0.084g可德胶(分子量为5万)溶解在质量浓度为0.0001％的氢氧化钠溶液中，得到质量分数为0.83％的可德胶氢氧化钠溶液，溶液流动性好。
步骤二、将0.05g阿司匹林溶于10mL蒸馏水中，配制成5mg/mL的阿司匹林溶液，加入0.025g埃洛石，阿司匹林在40℃蒸馏水中与埃洛石进行负载，得到的载药缓释颗粒，缓慢加到搅拌中的可德胶氢氧化钠溶液中，在可德胶氢氧化钠溶液中均匀分散，得到溶胶。
步骤三、将0.025g普罗布考溶于5mL二氯甲烷中，形成浓度为5mg/mL普罗布考二氯甲烷溶液，然后缓慢滴加到步骤二所得到的溶胶中，搅拌，分散均匀，得到复合溶胶。
步骤四、对步骤三所得的复合溶胶置于70℃水浴锅控温加热，挥发二氯甲烷，得到搭载有药物的复合水凝胶。所得复合水凝胶中可德胶的质量分数为0.5％，两种药物释放的最长时间为19h。
实施例1最终制得的负载普罗布考/阿司匹林的可德胶/埃洛石复合水凝胶的成胶结果为部分成胶，形成一种溶胶-凝胶体系。
实施例2
步骤一、在搅拌下将0.17g可德胶(分子量为20万)溶解在质量浓度为0.001％的氢氧化钠溶液中，得到质量分数为1.7％的可德胶氢氧化钠溶液，溶液流动性好。
步骤二、将0.1g阿司匹林溶于10mL蒸馏水中，配制成10mg/mL溶液，加入0.05g埃洛石，阿司匹林在50℃蒸馏水中与埃洛石进行负载，得到的载药缓释颗粒，缓慢滴加到搅拌中的可德胶氢氧化钠溶液中，在可德胶氢氧化钠溶液中均匀分散，得到溶胶。
步骤三、将0.05g普罗布考溶于5mL二氯甲烷中，形成浓度为10mg/mL普罗布考的二氯甲烷溶液，然后缓慢滴加到步骤二所得到的溶胶中，搅拌，分散均匀，得到复合溶胶。
步骤四、对步骤三所得的复合溶胶置于80℃水浴锅加热，挥发二氯甲烷，上表面具有流动性。所得水凝胶中可德胶的质量分数为1％，得到搭载有药物的复合水凝胶。
实施例2最终所制得的复合水凝胶的邵氏硬度计测量值55度，气孔2.95个/cm2，气孔直径1mm-4mm，透气性为0.128g/cm2*h，两种药物释放时间为21h。
实施例3
步骤一、在搅拌下将0.26g可德胶(分子量为40万)溶解在质量浓度为0.01％的氢氧化钠溶液中，得到质量分数为2.5％的可德胶氢氧化钠溶液，溶液流动性较差。
步骤二、将0.15g阿司匹林溶于10mL蒸馏水中，配制成15mg/mL溶液，加入0.075g埃洛石，阿司匹林在60℃蒸馏水中与埃洛石进行负载，得到的载药缓释颗粒，缓慢滴加到搅拌中的可德胶氢氧化钠溶液中，在可德胶氢氧化钠溶液中均匀分散，得到溶胶。
步骤三、将0.075g普罗布考溶于5mL二氯甲烷中，形成浓度为15mg/mL普罗布考的二氯甲烷溶液，然后缓慢滴加到步骤二所得到的溶胶中，搅拌，分散均匀，得到复合溶胶。
步骤四、对步骤三所得的复合溶胶置于80℃水浴锅加热，挥发二氯甲烷，上表面具有流动性。所得水凝胶中可德胶的质量分数为1.5％，得到搭载有药物的复合水凝胶。
实施例3最终所制得的复合水凝胶的邵氏硬度计测量值43.5度，气孔3.07个/cm2，气孔直径0.8mm-3mm，透气性为0.192g/cm2*h。阿司匹林的释放时间大概为25h，再往后药物释放达到和普罗布考的一样的缓释平台；其中阿司匹林的突释比普罗布考的突释要更加明显，还显示出多层级的程序性释放；普罗布考在5-25h之间显现出较好的缓释特征(具体缓释曲线见说明书附图2)
实施例4
步骤一、在搅拌下将0.35g可德胶(分子量为60万)溶解在质量浓度为0.1％的氢氧化钠溶液中，得到质量分数为3.4％的可德胶氢氧化钠溶液，溶液一般黏稠。
步骤二、将0.2g阿司匹林溶于10mL蒸馏水中，配制成20mg/mL溶液，加入0.10g埃洛石，阿司匹林在60℃蒸馏水中与埃洛石进行负载，得到的载药缓释颗粒，缓慢滴加到搅拌中的可德胶氢氧化钠溶液中，在可德胶氢氧化钠溶液中均匀分散，得到溶胶。
步骤三、将0.1g普罗布考溶于5mL二氯甲烷中，形成浓度为20mg/mL普罗布考的二氯甲烷溶液，然后缓慢滴加到步骤二所得到的溶胶中，搅拌，分散均匀，得到复合溶胶。
步骤四、对步骤三所得的复合溶胶置于85℃水浴锅加热，挥发二氯甲烷，上表面具有流动性。所得水凝胶中可德胶的质量分数为2％，得到搭载有药物的复合水凝胶。
实施例4最终所制得的复合水凝胶的邵氏硬度计测量值26，气孔2.77个/cm2，气孔直径约0.5mm-2mm，透气性为0.128g/cm2*h，两种药物缓释时间为24h。
实施例5
步骤一、在搅拌下将0.44g可德胶(分子量为80万)溶解在质量浓度为1％的氢氧化钠溶液中，得到质量分数为4.2％的可德胶氢氧化钠溶液，溶液较为黏稠。
步骤二、将0.25g阿司匹林溶于10mL蒸馏水中，配制成25mg/mL溶液，加入0.125g埃洛石，阿司匹林在60℃蒸馏水中与埃洛石进行负载，得到的载药缓释颗粒，缓慢滴加到搅拌中的可德胶氢氧化钠溶液中，在可德胶氢氧化钠溶液中均匀分散，得到溶胶。
步骤三、将0.125g普罗布考溶于5mL二氯甲烷中，形成浓度为25mg/mL普罗布考的二氯甲烷溶液，然后缓慢滴加到步骤二所得到的溶胶中，搅拌，分散均匀。
步骤四、对步骤三所得的复合溶胶置于85℃水浴锅加热，挥发二氯甲烷，上表面具有流动性。所得水凝胶中可德胶的质量分数为2.5％，得到搭载有药物的复合水凝胶。
实施例5最终所制得的复合水凝胶的邵氏硬度计测量值为7，气孔1.92个/cm2，气孔直径0.2mm-1mm，透气性为0.064g/cm2*h，两种药物缓释时间为23h。
Claims (10)
1.一种可德胶/埃洛石复合水凝胶，其特征在于：包括可德胶和埃洛石；埃洛石与可德胶在氢键作用下交联；复合水凝胶中可德胶的质量分数为0.5％～2.5％，埃洛石的质量分数为0.125％～0.625％。
2.根据权利要求1所述的一种可德胶/埃洛石复合水凝胶，其特征在于：还负载有阿司匹林；阿司匹林与埃洛石在蒸馏水中进行负载。
3.根据权利要求1或2所述的一种可德胶/埃洛石复合水凝胶，其特征在于：还负载有普罗布考；普罗布考的二氯甲烷溶液与可德胶、埃洛石的溶胶进行负载。
4.如权利要求1或2所述的一种可德胶/埃洛石复合水凝胶作为皮肤表面创伤敷料，或肠溶液药物缓释载体或治疗抑制心脏血管扩张术后再狭窄的支架涂层的应用。
5.如权利要求3所述的一种可德胶/埃洛石复合水凝胶作为皮肤表面创伤敷料，或肠溶液药物缓释载体或治疗抑制心脏血管扩张术后再狭窄的支架涂层的应用。
6.如权利要求1所述的一种可德胶/埃洛石复合水凝胶的制备方法，其特征在于：步骤一、将可德胶分散在水溶液或溶解在碱溶液中，得到可德胶水分散液或可德胶碱溶液；
步骤二、将埃洛石溶液滴加到搅拌的可德胶水分散液或可德胶碱溶液中，得到溶胶体系；再利用溶胶体系获得可德胶/埃洛石复合水凝胶。
7.根据权利要求1所述的一种可德胶/埃洛石复合水凝胶的制备方法，其特征在于：步骤一中，可德胶分散在水中的情况下，可德胶的质量浓度0.83％～4.2％；可德胶溶解在碱溶液中的情况下，可德胶与碱溶液质量比为1:119～1:23；可德胶分散到水或溶解在碱溶液的过程持续搅拌，搅拌速度为600～800rpm；所述的碱溶液采用氨水、氢氧化钠水溶液、磷酸三钠水溶液或磷酸三钙水溶液，碱溶液的质量浓度为0.0001％～1.0％；步骤二中的埃洛石与可德胶的比例为1:6～1:2，整个过程搅拌速度为600～800rpm。
8.根据权利要求1所述的一种可德胶/埃洛石复合水凝胶的制备方法，其特征在于：步骤二中，埃洛石溶液与可德胶水分散液或可德胶碱溶液混合前，将埃洛石加入阿司匹林溶液，使得阿司匹林与埃洛石在40℃～60℃水溶液进行负载，得到负载阿司匹林的埃洛石溶液。
9.根据权利要求1所述的一种可德胶/埃洛石复合水凝胶的制备方法，其特征在于：步骤二得到溶胶后，执行步骤三和四；具体如下：
步骤三、将普罗布考溶于二氯甲烷配制成的普罗布考的二氯甲烷溶液，然后将其缓慢滴加到步骤二中所述的溶胶中；
步骤四、将步骤三获得的溶胶置于70～80℃恒温水浴中，放置6～24h，充分挥发二氯甲烷，得到负载有普罗布考/阿司匹林的可德胶/埃洛石复合水凝胶。
10.根据权利要求1所述的一种可德胶/埃洛石复合水凝胶的制备方法，其特征在于：步骤三中所述的普罗布考的二氯甲烷溶液的质量浓度为5mg/mL～25mg/mL；普罗布考与二氯甲烷的质量比1:264～1:52，需要逐步滴加，1～5min内滴加完毕；且持续搅拌，且搅拌速度为200～500rpm；二氯甲烷溶剂挥发的所需时间为0.5h～2h，加热控温为70℃～85℃，复合凝胶中可德胶的质量分数为0.5％～2.5％。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115154409A (zh) * | 2022-07-04 | 2022-10-11 | 杭州师范大学钱江学院 | 一种负载nmn的埃洛石/羧甲基纤维素钠/可德胶复合水凝胶及其应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101602814A (zh) * | 2009-07-09 | 2009-12-16 | 上海交通大学 | 羧甲基可德胶物理水凝胶及其制备方法 |
| CN102702537A (zh) * | 2012-05-16 | 2012-10-03 | 吉武科 | 一种增加可得然胶凝胶强度的方法 |
| CN103520113A (zh) * | 2012-07-03 | 2014-01-22 | 中国科学院兰州化学物理研究所 | 一种埃洛石纳米复合凝胶微球及其制备方法 |
| CN108503861A (zh) * | 2018-05-25 | 2018-09-07 | 江南大学 | 一种可得然胶/淀粉复合水凝胶及其制备方法和应用 |
| CN110157047A (zh) * | 2019-06-12 | 2019-08-23 | 杭州师范大学钱江学院 | 可德胶-二氧化硅复合水/气凝胶及其制备方法及应用 |
| CN110511401A (zh) * | 2019-08-23 | 2019-11-29 | 广州暨南生物医药研究开发基地有限公司 | 一种高韧性可得然胶水凝胶的制备方法与应用 |
-
2021
- 2021-01-08 CN CN202110023239.0A patent/CN112795058B/zh active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101602814A (zh) * | 2009-07-09 | 2009-12-16 | 上海交通大学 | 羧甲基可德胶物理水凝胶及其制备方法 |
| CN102702537A (zh) * | 2012-05-16 | 2012-10-03 | 吉武科 | 一种增加可得然胶凝胶强度的方法 |
| CN103520113A (zh) * | 2012-07-03 | 2014-01-22 | 中国科学院兰州化学物理研究所 | 一种埃洛石纳米复合凝胶微球及其制备方法 |
| CN108503861A (zh) * | 2018-05-25 | 2018-09-07 | 江南大学 | 一种可得然胶/淀粉复合水凝胶及其制备方法和应用 |
| CN110157047A (zh) * | 2019-06-12 | 2019-08-23 | 杭州师范大学钱江学院 | 可德胶-二氧化硅复合水/气凝胶及其制备方法及应用 |
| CN110511401A (zh) * | 2019-08-23 | 2019-11-29 | 广州暨南生物医药研究开发基地有限公司 | 一种高韧性可得然胶水凝胶的制备方法与应用 |
Non-Patent Citations (1)
| Title |
|---|
| SHARIFZADEH, GHORBANALI等: "Kappa-carrageenan/halloysite nanocomposite hydrogels as potential drug delivery systems", 《JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115154409A (zh) * | 2022-07-04 | 2022-10-11 | 杭州师范大学钱江学院 | 一种负载nmn的埃洛石/羧甲基纤维素钠/可德胶复合水凝胶及其应用 |
| CN115154409B (zh) * | 2022-07-04 | 2024-03-01 | 杭州师范大学钱江学院 | 一种负载nmn的埃洛石/羧甲基纤维素钠/可德胶复合水凝胶及其应用 |
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