CN105384941B - 一种可降解的光敏磷酸酯基共聚物 - Google Patents

一种可降解的光敏磷酸酯基共聚物 Download PDF

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CN105384941B
CN105384941B CN201510888863.1A CN201510888863A CN105384941B CN 105384941 B CN105384941 B CN 105384941B CN 201510888863 A CN201510888863 A CN 201510888863A CN 105384941 B CN105384941 B CN 105384941B
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陈明清
张藜
施冬健
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Jiangnan University
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Abstract

一种可降解的光敏性磷酸酯基共聚物，属于功能高分子材料技术领域。本发明以二氯磷酸乙酯(EDP)和己内酯(CL)为单体，不同分子量的双端羟基聚己内酯(PCL)为原料，通过熔融缩聚制备了一系列的磷酸酯基共聚物PPE‑PCL；进一步通过化学修饰反应，将肉桂酰基引入到聚合物链末端制得光敏性磷酸酯聚合物PPE‑PCL‑C。将磷酸酯聚合物在混合介质中自组装成胶束，所得的胶束具有一定的降解性和光敏性。本发明制得的聚合物具有良好的生物降解性和生物相容性，可应用于药物输送、组织工程等生物医学领域。

Description

一种可降解的光敏磷酸酯基共聚物
技术领域
一种可降解的光敏磷酸酯基共聚物，属于功能高分子材料领域。
背景技术
在众多的可降解聚合物材料中，聚磷酸酯由于结构与生命体当中的磷酸等结构相似，具有优异的生物相容性和生物降解性，因而引起人们的广泛关注。但是聚磷酸酯本身熔融温度及玻璃化转变温度较低，单纯用作聚合物材料的可操作性低，通常是将磷酸酯的共聚物制备成胶束、膜材料等。此外，目前关于磷酸酯聚合物制备的大部分报道中都采用的是开环聚合的方法，缩合聚合制备磷酸酯聚合物的研究还比较少。
聚己内酯是最早被研究、应用最为广泛的可降解材料之一，它具有良好的生物相容性、可完全降解、易加工的优点，但是其结晶性强、降解周期长、亲水性差，限制了其在生物医药领域的应用范围。
此外，光敏聚合物材料因其可在清洁能源-光的刺激下使聚合物的结构发生改变，以调控宏观性能，从而受到越来越多的关注。肉桂酸衍生物是一种植物性单体，具有光敏性、抗氧化性以及良好的热稳定性及力学性能，肉桂酸基团可以在体内代谢并且无毒。其可以在一定波长的紫外光照下(λ>280nm)发生光二聚反应，将双键打开而加聚形成环丁烷的结构，在波长小于260nm的紫外光的照射下，环状结构又可以被打开回复到原来的结构。
本发明以二氯磷酸乙酯(EDP)和己内酯(CL)为单体，不同分子量的双端羟基PCL为原料，通过熔融缩聚制备了一系列的磷酸酯共聚物(PPE-PCL)；进一步通过化学修饰反应，将肉桂酰基引入到聚合物链末端制得一系列光敏性磷酸酯聚合物(PPE-PCL-C)。
发明内容
本发明的目的是提供一种可降解的光敏磷酸酯基共聚物。
本发明的技术方案：一种可降解的光敏磷酸酯基共聚物，(1)选用不同分子量的双端羟基PCL与二氯磷酸乙酯为原料，通过熔融缩聚制备PPE-PCL，并进一步通过化学修饰反应将光敏的肉桂基团引入到聚合物链末端从而制得一系列不同组成的PPE-PCL-C；(2)在THF/水的混合介质中聚合物PPE-PCL-C自组装成胶束。
本发明的有益效果：本发明通过通过开环聚合和熔融缩聚制备了一系列光敏性磷酸酯聚合物；再在THF/水的混合介质中制得光敏性磷酸酯聚合物胶束。制得的光敏性共聚物胶束具有良好的生物降解性和生物相容性，这种光敏性共聚物胶束可用与药物负载和药物输送。
附图说明
图1光敏性磷酸酯聚合物PPE-PCL-C的核磁谱图。
图2紫外光照前(a)、后(b)PPE-PCL-C聚合物胶束的SEM图。
图3 PPE-PCL-C胶束在pH＝9.4环境中紫外光照(λ＝302nm)前后粒径随降解时间的变化曲线。
具体实施方式
实施例1、聚(ε-己内酯)(PCL)
按1：6的投料比，将引发剂EG(0.6206g,10mmol)、单体ε-CL(6.8412g，60mmol)和溶剂甲苯(50mL)让分别加入到100mL三口瓶中，在100℃、N2氛围下搅拌30分钟后，加入一定量的催化剂辛酸亚锡(Sn(Oct)2)，继续在100℃下搅拌反应24小时。反应结束后，将产物的甲苯溶液以一定的滴加速度滴加进无水乙醚中，沉淀，抽滤，再置于真空干燥箱中30℃下干燥至恒重。
实施例2、磷酸酯聚合物(PPE-PCL)
将预先合成好的分子量为1.70×103的双端羟基PCL(11.2g，10mmol)置于三口烧瓶中，升温至80℃使之熔融，通氮气以除去体系中的氧气，再在抽真空的状态下，通过橡皮隔膜塞用微量进样器滴加入当量的EDP(1.63g，10mmol)，将体系密封，再次抽真空并逐渐升温至160℃，在一定真空度的条件下保持反应24h后冷却至室温，用二氯甲烷溶解产物并用无水乙醚沉淀、过滤，真空烘箱中40℃烘干。
实施例3、光敏磷酸酯聚合物(PPE-PCL-C)
将PPE-PCL(4.11g，1mmol)、25mL二氯甲烷和1mL吡啶加入到50mL圆底烧瓶中，0℃下搅拌0.5小时，加入10倍当量的肉桂酰氯(1.665g，10mmol)，在0℃下搅拌反应1.5h后，在常温下继续搅拌反应24h。反应结束后，用无水乙醚沉淀过滤3次后，用乙醚洗涤沉淀直到滤液为完全透明的颜色，再用去离子水洗涤以除去吡啶盐酸盐及多余的吡啶，最后置于真空烘箱中40℃下干燥得到最终的产物。
实施例4、PPE-PCL与PPE-PCL-C胶束
以THF为溶剂，将不同组成的PPE-PCL及PPE-PCL-C配制成2mg/mL的溶液。在1000r/min的搅拌速度下，用微量进样器以1滴/秒的速度向共聚酯/THF溶液中缓慢滴加适量超纯水，初步制得胶束溶液，继续搅拌胶束溶液过夜，再将其逐滴滴加到大量的超纯水中以固定胶束的形态，然后置于去离子水中透析，每隔6h换一次去离子水，充分除去有机溶剂后得到聚酯胶束的水溶液，并将最终的浓度调整至0.4mg/mL。

Claims (5)

1.一种可降解的光敏性磷酸酯基共聚物，是以己内酯为单体，先用乙二醇开环制备不同分子量的双端羟基聚己内酯，再与二氯磷酸乙酯通过熔融缩聚制备一系列的磷酸酯基共聚物；进一步通过化学修饰反应，将肉桂酰基引入到聚合物链末端制得光敏性磷酸酯聚合物；进而将其在THF/水的混合介质中自组装成胶束。
2.根据权利要求1所述的光敏性磷酸酯基共聚物，其特征是以己内酯和磷酸酯重复单元为主链，以肉桂酰基为链末端基团；其中聚已内酯的分子量为0.10×103-3.20×103，光敏性聚(磷酸乙酯-己内酯)共聚物的分子量为6.10×103-25.90×103；所得光敏性聚(磷酸乙酯-己内酯)共聚物的结构为：
其中n＝6～26，X＝3～10，表示成PPE-PCL-C。
3.根据权利要求1所述的光敏性磷酸酯基共聚物，将其在THF/水的混合介质中自组装成球状胶束，胶束的粒径为180～630nm，粒径分布保持在0.3-0.4；对制备好的胶束用紫外光照射(λ＝302nm)足够长的时间后，其粒径减小至100～450nm，粒径分布保持在0.3-0.35。
4.根据权利要求3所述的光敏性磷酸酯基共聚物，其特征是具有可降解性，其降解的最初2-4天内，胶束粒径是减小的；之后随着降解时间增加，胶束粒径开始出现波动性变化；直到10天后，胶束的粒径开始明显不断减小；到60天后，胶束结构塌陷，几乎完全降解；并且，其降解行为可以通过控制PCL链段长度实现调控。
5.根据权利要求1所述的光敏性磷酸酯基共聚物，其特征是光敏性磷酸酯基共聚物有一定光敏感性和生物相容性；可以通过紫外光照射提高聚合物的热稳定性。这种光敏性可降解聚合物胶束具有亲水外壳和疏水内核，可用作环境和生物医药领域的载体。
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CN101787115A (zh) * 2009-12-28 2010-07-28 江南大学 一种具有光活性的三元双亲性聚酯的制备方法
CN102030889A (zh) * 2010-11-18 2011-04-27 江南大学 一种光响应型聚酯
CN102516506A (zh) * 2011-11-23 2012-06-27 江南大学 一种光敏性pcl基共聚物及其制备方法
CN103159956A (zh) * 2011-12-08 2013-06-19 江南大学 一种芳香族-脂肪族可降解接枝聚合物

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Publication number Priority date Publication date Assignee Title
CN101787115A (zh) * 2009-12-28 2010-07-28 江南大学 一种具有光活性的三元双亲性聚酯的制备方法
CN102030889A (zh) * 2010-11-18 2011-04-27 江南大学 一种光响应型聚酯
CN102516506A (zh) * 2011-11-23 2012-06-27 江南大学 一种光敏性pcl基共聚物及其制备方法
CN103159956A (zh) * 2011-12-08 2013-06-19 江南大学 一种芳香族-脂肪族可降解接枝聚合物

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