顺丁烯二酸β-环糊精酯-N-乙烯基吡咯烷酮水溶性聚合物的合成及其吸附疏水性药物的研究

Synthesis of β-Cyclodextrin-N-vinyl-2-pyrrolidone Water-Soluble Copolymer and Its Adsorption of Hydrophobic Drugs

以γ射线引发顺丁烯二酸β-环糊精酯(CDM)和N-乙烯基吡咯烷酮(NVP)发生自由基链式反应,制备了顺丁烯二酸β-环糊精酯-N-乙烯基吡咯烷酮聚合物(CDM-NVP)。优化后的CDM-NVP聚合物的合成条件为:CDM∶NVP为1∶0.7(w/w,CDM 3.6 g和NVP 2.52 g),辐照剂量4 k Gy,DMF溶液用量为20 m L。在此条件下制备聚合物的产率为84%,重均分子量为20 k Da。结果表明,此聚合物可以同纳他霉素(NM)和多菌灵(MBC)形成稳定复合物。研究了复合物抑菌活性,测定了其表观稳定常数。利用紫外光谱、核磁图谱和相溶解度对药物复合物进行结构表征。303 K下,NM-CDM-NVP和MBC-CDM-NVP复合物的表观稳定系数分别为12988.54和865.94 L/mol。抑菌实验结果表明,NM-CDM-NVP和MBC-CDM-NVP复合物可以显著提高NM和MBC的溶解性和抑菌活性。

β-Cyclodextrin-N-vinyl-2-pyrrolidone( CDM-NVP) copolymer was prepared by free radical chain reaction of N-vinyl-2-pyrrolidone( NVP) and β-CD maleate( CDM) with γ-ray as initiator. The synthesis conditions of CDM-NVP polymer were as follows: mass ratio of CDM to NVP was 1∶ 0.7( CDM 3.6 g and NVP2.52 g),irradiation dosage was 4 k Gy,and DMF aqueous solution( 50%,V/V) was set at 20 m L. Under the synthesis conditions,the yield of CDM-NVP was 84% and the weight-average molecular weight was 20 k D.The natamycin( NM) and carbendazim( MBC) could form stable inclusion complexes with CDM-NVP copolymer,and the solubility and fungicidal activity of the complexes were investigated. The stability constant of NM·CDM-NVP and MBC·CDM-NVP complexes at 303 K were 12,988.54 L/mol and 865.94 L/mol,respectively. The complexes were characterized using phase solubility diagrams,nuclear magnetic resonance( NMR) spectra and ultraviolet( UV) spectra. The analysis of the biological activities of these two complexes indicated that they possessed enhancing fungicidal activities compared to NM and MBC alone.