桔皮素与β-环糊精及其衍生物的包合行为研究

Study on inclusion behavior of tangeretin withβ-cyclodextrin and its derivatives

以β-环糊精(β-CD)、2-羟丙基-β-环糊精(HP-β-CD)及1,3,6-β-环糊精(TM-β-CD)为主体,桔皮素(TAN)为客体,通过饱和溶液法成功制备了3种新型主客体包合物.采用傅里叶红外光谱(FT-IR)、X射线粉末衍射分析(XRD)及扫描电镜(SEM)等分析方法对主−客体包合物进行了表征.通过核磁共振氢谱(1H NMR、2D NMR)及分子对接计算推测了包合物可能的包合模式.运用紫外−可见光谱法(UV-Vis)研究了TAN与3种环糊精的包合比、包合物的水溶性和稳定性.实验结果表明,3种包合物TAN/β-CD、TAN/HP-β-CD及TAN/TM-β-CD均制备成功,主−客体包合分子比均为1∶1,TAN均以A环从环糊精的大口端进入空腔,且整个药物分子贯穿在环糊精的空腔中.此外,TAN包合后的水溶性和稳定性都明显提高,且在pH=3.0的条件下更易形成包合物,这为TAN的药物制剂研究提供了理论依据.

Usingβ-cyclodextrin,2-hydroxypropyl-β-cyclodextrin and 2,3,6-trimethyl-β-cyclodextrin as the host and tangeretin(TAN)as the guest,three new host-guest inclusion complexes were successfully prepared by the saturated solution method.The host-guest inclusion complexes were characterized by X-ray diffraction(XRD),Fourier transform infrared(FT-IR)and scanning electron microscopy(SEM).The possible inclusion mode of the inclusion complexes were deduced by proton nuclear magnetic resonance spectroscopy(1H NMR,2D NMR)and molecular docking calculations.The inclusion stoichiometric ratio,water solubility and stability of TAN and three cyclodextrins were studied by ultraviolet-visible spectroscopy(UV-Vis).The experimental results showed that the three inclusion complexes were successfully prepared.The inclusion host-guest stoichiometric ratio was 1∶1.The TAN entered the cavity from the wide side end of the cyclodextrin by the A ring of the TAN,and the TAN penetrated the cavity of CDs.In addition,TAN and three kinds of cyclodextrins are easier to form inclusion complexes at pH=3.0.The water solubility and stability of TAN were significantly improved after inclusion,which provided a theoretical basis for the pharmaceutical preparation of TAN.