CN114652903A - 一种快速聚合医用水凝胶及其制备方法 - Google Patents
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Abstract
本发明涉及一种快速聚合医用水凝胶，其由第一相溶液和第二相溶液聚合而成，所述第一相溶液由乙烯砜聚乙二醇溶解于第一缓冲溶液中形成，所述乙烯砜聚乙二醇为四臂乙烯砜聚乙二醇或八臂乙烯砜聚乙二醇，所述第二相溶液由氨基化合物或巯基聚乙二醇溶解于第二缓冲溶液中形成，所述氨基化合物为半胱氨酸、二赖氨酸、三赖氨酸或聚乙烯亚胺，所述巯基聚乙二醇为四臂巯基聚乙二醇或八臂巯基聚乙二醇。本发明还涉及上述快速聚合医用水凝胶的制备方法。根据本发明的快速聚合医用水凝胶，在聚合之前为两种不同的液体，即第一相溶液和第二相溶液，在使用时将两种液体混合后可快速交联聚合而成水凝胶，而且聚合后的水凝胶具有较高弹性，能够和组织密切贴合。
Description
技术领域
本发明涉及生物材料，更具体地涉及一种快速聚合医用水凝胶及其制备方法。
背景技术
水凝胶是一类具有亲水基团的三维网络结构的聚合物，由于聚合物间的物理交联和化学交联的作用，水凝胶可以被溶胀，但是并不溶于水，而且可保持一定的形状。同时水凝胶具有优良的理化性能和生物学特性，如生物相容性、高弹性、溶胀性等，广泛应用在医药领域、组织工程和医疗器械领域。
可用于制备水凝胶的材料有壳聚糖、海藻酸盐、聚乙二醇等。聚乙二醇是高分子聚合物，其本身具有很好的生物相容性和安全性，可用作药用辅料，对聚乙二醇端基进行改性，既增加了其成水凝胶的性能，又保留了聚乙二醇原有的安全特性，是理想的水凝胶材料。
有报道使用聚乙二醇琥珀酰亚胺酯和聚赖氨酸和聚乙烯亚胺成水凝胶的方法，但是该水凝胶容易水解，而且成水凝胶需要的时间较长。
发明内容
为了解决上述现有技术中的水凝胶的成胶时间较长等问题，本发明提供一种快速聚合医用水凝胶及其制备方法。
根据本发明的快速聚合医用水凝胶，其由第一相溶液和第二相溶液聚合而成，所述第一相溶液由乙烯砜聚乙二醇(PEG-VS)溶解于第一缓冲溶液中形成，所述乙烯砜聚乙二醇(PEG-VS)为四臂乙烯砜聚乙二醇(4臂-PEG-VS)或八臂乙烯砜聚乙二醇(8臂-PEG-VS)，所述第二相溶液由氨基化合物或巯基聚乙二醇(PEG-SH)溶解于第二缓冲溶液中形成，所述氨基化合物为半胱氨酸、二赖氨酸、三赖氨酸或聚乙烯亚胺，所述巯基聚乙二醇(PEG-SH)为四臂巯基聚乙二醇(4臂-PEG-SH)或八臂巯基聚乙二醇(8臂-PEG-SH)。
本申请的发明人通过大量的创造性劳动，最终选定由第一相溶液中的四臂乙烯砜聚乙二醇(4臂-PEG-VS)或八臂乙烯砜聚乙二醇(8臂-PEG-VS)和第二相溶液中的半胱氨酸、二赖氨酸、三赖氨酸、聚乙烯亚胺、四臂巯基聚乙二醇(4臂-PEG-SH)或八臂巯基聚乙二醇(8臂-PEG-SH)进行聚合，可以满足快速聚合形成水凝胶的效果。
优选地，所述氨基化合物中的氨基和乙烯砜聚乙二醇中的乙烯砜基团的摩尔量的比介于1-2：1之间。
优选地，所述巯基聚乙二醇中的巯基和乙烯砜聚乙二醇中的乙烯砜基团的摩尔量的比介于1-2：1之间。
优选地，所述第一相溶液的质量百分浓度介于1.0％-20％之间。
优选地，所述第一缓冲溶液的PH＝4.0-7.0。
优选地，所述第二相溶液的质量百分浓度介于1.0％-20％之间。
优选地，所述第二缓冲溶液的PH＝7.5-10.0。
优选地，所述乙烯砜聚乙二醇(PEG-VS)的分子量介于5K-20K之间。
优选地，所述巯基聚乙二醇(PEG-SH)的分子量介于5K-20K之间。
根据本发明的快速聚合医用水凝胶的制备方法，其包括通过双腔微导管分别将第一相溶液和第二相溶液输送待聚合位置，第一相溶液和第二相溶液在该位置一旦混合即聚合成水凝胶。
优选地，聚合时间介于0.5-10s之间。
根据本发明的快速聚合医用水凝胶，可用于例如前列腺癌放射治疗时的隔离保护。放射治疗时，射线会穿过癌组织，对于邻近正常组织会有不可避免的放射损伤，比如直肠。而在前列腺和直肠之间形成一个水凝胶垫片可以有效阻隔多余的射线，避免正常组织受到放射损伤。应该理解，该根据本发明的快速聚合医用水凝胶还可用于例如宫颈癌等放射治疗时的隔离保护，将待聚合位置设定为需放射隔离位置即可。
根据本发明的快速聚合医用水凝胶，在聚合之前为两种不同的液体，即第一相溶液和第二相溶液，在使用时将两种液体混合后可快速(例如0.5s-10s内)交联聚合而成水凝胶，而且聚合后的水凝胶具有较高弹性，能够和组织密切贴合。
具体实施方式
下面给出本发明的较佳实施例，并予以详细描述。
实施例1
配置第一相溶液
首先，用磷酸二氢钠、10％磷酸、纯化水配制PH＝4.0-7.0的第一缓冲溶液。然后，按下表1量称取乙烯砜聚乙二醇(PEG-VS)，用第一缓冲溶液溶解，配制成质量百分浓度介于1.0％-20％之间的第一相溶液。
在例1-例2，例8-例9和例14-例15中，该乙烯砜聚乙二醇(PEG-VS)为四臂乙烯砜聚乙二醇(4臂-PEG-VS)，其分子式如下：
其中，R1为季戊四醇，n＝1-250。
在例3-例7和例10-例13中，该乙烯砜聚乙二醇(PEG-VS)为八臂乙烯砜聚乙二醇(8臂-PEG-VS)，其分子式如下：
其中，R2为三季戊四醇，n＝1-250。
配置第二相溶液
首先，用四硼酸钠与10％磷酸或20％氢氧化钠配制PH＝7.5-10.0的第二缓冲溶液。然后，按下表1量称取氨基化合物或巯基聚乙二醇(PEG-SH)，用第二缓冲溶液溶解，配制成质量百分浓度介于1.0％-20％之间的第二相溶液。
在例1、例7和例14中，氨基化合物为半胱氨酸。
在例2、例8和例15中，氨基化合物为二赖氨酸。
在例3、例9和例11中，氨基化合物为三赖氨酸。
在例4、例10和例12中，氨基化合物为聚乙烯亚胺。
在例6中，该巯基聚乙二醇(PEG-SH)为四臂巯基聚乙二醇(4臂-PEG-SH)，其分子式如下：
其中，R3为季戊四醇，n＝1-250。
在例5和例13中，该乙烯砜聚乙二醇(PEG-SH)为八臂巯基聚乙二醇(8臂-PEG-SH)，其分子式如下：
其中，R4为三季戊四醇，n＝1-250。
制备水凝胶
将2.0ml第一相溶液抽取至3ml的第一注射器中，将2.0ml第二相溶液抽取至3ml的第二注射器中，将第一和第二注射器分别和双腔微导管连接，同时推动注射器，待双腔微导管远端流出溶液时计时开始，观察到流出溶液成凝胶后计时结束，得到的聚合时间如下表1所示：
表1
以上所述的，仅为本发明的较佳实施例，并非用以限定本发明的范围，本发明的上述实施例还可以做出各种变化。即凡是依据本发明申请的权利要求书及说明书内容所作的简单、等效变化与修饰，皆落入本发明专利的权利要求保护范围。本发明未详尽描述的均为常规技术内容。
Claims (10)
1.一种快速聚合医用水凝胶，其特征在于，该快速聚合医用水凝胶由第一相溶液和第二相溶液聚合而成，所述第一相溶液由乙烯砜聚乙二醇溶解于第一缓冲溶液中形成，所述乙烯砜聚乙二醇为四臂乙烯砜聚乙二醇或八臂乙烯砜聚乙二醇，所述第二相溶液由氨基化合物或巯基聚乙二醇溶解于第二缓冲溶液中形成，所述氨基化合物为半胱氨酸、二赖氨酸、三赖氨酸或聚乙烯亚胺，所述巯基聚乙二醇为四臂巯基聚乙二醇或八臂巯基聚乙二醇。
2.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述氨基化合物中的氨基和乙烯砜聚乙二醇中的乙烯砜基团的摩尔量的比介于1-2：1之间。
3.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述巯基聚乙二醇中的巯基和乙烯砜聚乙二醇中的乙烯砜基团的摩尔量的比介于1-2：1之间。
4.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述第一相溶液的质量百分浓度介于1.0％-20％之间。
5.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述第一缓冲溶液的PH＝4.0-7.0。
6.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述第二相溶液的质量百分浓度介于1.0％-20％之间。
7.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述第二缓冲溶液的PH＝7.5-10.0。
8.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述乙烯砜聚乙二醇的分子量介于5K-20K之间。
9.根据权利要求1所述的快速聚合医用水凝胶，其特征在于，所述巯基聚乙二醇的分子量介于5K-20K之间。
10.一种根据权利要求1-9中任一项所述的快速聚合医用水凝胶的制备方法，其特征在于，该制备方法包括通过双腔微导管分别将第一相溶液和第二相溶液输送待聚合位置，第一相溶液和第二相溶液在该位置一旦混合即聚合成水凝胶。
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| CN102049067A (zh) * | 2009-11-10 | 2011-05-11 | 清华大学 | 一种可原位交联的高分子水凝胶玻璃体替代材料 |
| CN102858845A (zh) * | 2010-04-22 | 2013-01-02 | Q吉尔股份有限公司 | 水凝胶前体制剂及其制备方法 |
| CN103249433A (zh) * | 2010-11-19 | 2013-08-14 | 弗赖堡大学医院 | 生物功能化的刺激应答型可溶性peg水凝胶 |
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| CN102858845A (zh) * | 2010-04-22 | 2013-01-02 | Q吉尔股份有限公司 | 水凝胶前体制剂及其制备方法 |
| CN103249433A (zh) * | 2010-11-19 | 2013-08-14 | 弗赖堡大学医院 | 生物功能化的刺激应答型可溶性peg水凝胶 |
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