环糊精对青蒿素的包合工艺研究

Optimization of Inclusion Reactions of β-Cyclodextrin and Its Derivatives with Artemisinin

通过单因素及正交试验确定青蒿素与3种环糊精形成包合物的最佳条件,在此条件下利用相溶解度法测定青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数并计算包合反应前后的吉布斯自由能。结果表明:青蒿素与环糊精形成包合物的最佳条件为配比1:1(mol/mol)、包合温度40℃、包合时间5h、包合反应时溶液pH7,青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为80.06、58.68、116.96L/mol,反应前后的吉布斯自由能变化分别为-11.76、-10.93、-12.78kJ/mol。表明青蒿素与环糊精可以形成1:1型稳定的包合物,环糊精可以增大青蒿素的溶解度。

One-factor-at-a-time method and orthogonal array design were used to establish the optimal reaction conditions for inclusion complexes of β-cyclodextrin and its derivatives with artemisinin. Formation constants for inclusion complexes of artemisinin with fl-cylcodextrin （fl-CD）, hydroxypropyl-β-cyclodextrin （HP-β-CD） and γ-cyclodextrin γ-CD） were measured by phase solubility analysis and Gibbs free energy differences were also calculated before and after reactions. The optimal reaction conditions for artemisinin/cyclodextrin inclusion complexes were 1：1, 40 ℃, 5 h and 7 for artemisinin-to-cyclodextrin molar ratio, temperature, reaction time and medium pH, respectively. The formation constants of the inclusion complexes of artemisinin with β-CD, HP-β-CD and γ-CD were 80.06, 58.68 L/ tool and 116.96 L/mol, respectively, and the corresponding Gibbs free energy differences were -11.76, -10.93 kJ/mol and -12.78 kJ/mol, respectively. In this study, we have succeeded in preparing 1：1 artemisinin/cyclodextrin inclusion complexes with improved solubility of artemisinin.