摘要:
目的: 考察多西他赛(docetaxel,DTX)与β-环糊精(β-CD)及羟丙基-β-环糊精(HP-β-CD)的包合作用。 方法: 采用冷冻干燥法和研磨法制备DTX-β-CD和DTX-HP-β-CD包合物,差示扫描量热法(DSC)和红外光谱法(IR)对包合物进行鉴定;摩尔连续递变法测定包合物的组成比例,相溶解度法测定DTX在25、37、45℃恒温条件下在不同浓度β-CD、HP-β-CD水溶液中的包合稳定常数及相关的热力学常数。 结果: DTX与β-CD、HP-β-CD形成了稳定的包合物;摩尔包合比均为1:1,相溶解度曲线为AN型,表观稳定常数K随着温度的升高而下降,包合过程中的吉不斯自由能变化(ΔG)、焓变(ΔH)和熵变(ΔS)均为负值。β-CD对DTX的增溶作用强于HP-β-CD,且DTX-β-CD包合物的稳定常数高于DTX-HP-β-CD包合物。 结论: DTX与β-CD、HP-β-CD可以自发形成可溶性包合物,且低温有利于包合物的形成和稳定。β-CD对DTX的增溶作用及与DTX形成包合物的稳定常数均高于HP-β-CD。
Abstract:
Objective: To study the inclusion effects of β-CD and HP-β-CD on docetaxel. Methods: The inclusion compound was prepared by the free-drying method and trituration.The measurements of the inclusion molar ratio of the host to guest molecules,apparent complexation constant,the thermodynamic parameters and the identication of the inclusion complex were carried out by the methods such as continuous variation method,UV absorption spectroscopy,phase solubility diagram,differential scanning calorimeter(DSC) and infrared spectra(IR) methods,respectively. Results: The continuous variation method suggested the formation of aqueous soluble complexes with 1-1 molar ratio.AN-type phase solubility curves were obtained.The apparent complexation constant K decreased when the temperature increased.All thermodynamic parameters of ΔG,ΔH and ΔS in the complexations gave negative values.The solubility of docetaxel complexed with β-CD was higher than that of docetaxel complexed with HP-β-CD,also the apparent complexation constant of docetaxel-β-CD was higher than that of docetaxel-HP-β-CD. Conclusion: The inclusion complex of DTX-Cyclodextrin could be formed spontaneously,and lower temperature is a benefit to the formation and the stability of the inclusion complex.The solubility and the stability constant of docetaxel complexed with β-CD is higher than that of docetaxel complexed with HP-β-CD.
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