以天然产物双半乳糖基二酰甘油酯为乳化剂的亚微乳的制备及稳定性研究

目的：探讨双半乳糖脂二酰甘油酯(digalactosyl diglyceride，DGDG)作为一种乳化剂使用的可行性。方法：以香叶油为模型药物，油中乳化法制备初乳，通过单因素考察优化制备工艺，采用星点设计-效应面法(central composite design-response surface methodology，CCD-RSM)对处方进行优化，并对其稳定性进行初步研究。结果：确定的最终制备工艺为：60 ℃，油中乳化法制备初乳，于组织匀浆机中匀浆10 min，高压均质于80 Pa下循环10次，0.22 μm微乳滤膜滤过灭菌，充氮灌封即得。最优处方为：DGDG用量1.6%；大豆油用量1.1%；油酸钠用量0.16%。其中香叶油用量为0.3%。所得亚微乳外观细腻洁白，所制3批样品粒径为168.0～169.3 nm，Zeta电位为-25.53～24.90 mV，pH 8.48～8.52，最佳处方的验证结果与预测值相差1.8%。在高温、光照条件下稳定性良好。结论：DGDG可作为香叶油亚微乳的乳化剂使用。

Preparation and stability of sub-micro-emulsion of which the emulsifier is digalactosyl diglyceride from natural product

Objective: To study the effect of combination components on pharmacokinetics of Shuxiong tablet to provide evidence for the new recipe. Method: Six groups of rats (6 for each group) were orally administered with co-extractum of chuanxiong and honghua (CHE), mixed solution of hydroxysafflor yellow A (HSYA) and ferulic acid (FA) (HFM). Panax notoginseng saponins solution (PNS), mixed solution of PNS and CHE (PCHE), mixed solution of PNS and HFM (PHFM) and mixed emulsion of Chuanxiong volatile oil (CVO) and PHFM (CVO-PHFM), respectively. The concentrations of HSYA, FA, ginsnenoside Rg₁ and Rb1 in rat plasma were determined by HPLC. Pharmacokinetic parameters (K_a, K_el, C_max, T_max and AUC) were calculated by model simulation. The differences of HSYA, FA, Rg₁ and Rb₁ in pharmacokinetics parameters after administration of six preparations were demonstrated by statistical analysis. Result: After oral administration of six preparations to rats, the concentration-time curve of HSYA and Rg₁ fitted to one-compartment model, and that of FA fitted to double-compartment model. After oral administration of CHE, K_el of FA reduced; C_max decreased; but K₁₂ increased, significantly, compared with oral administration of HFM. Other parameters were not significant differences. After co-administration of PNS and CHE (PCHE) or PNS and HFM (PHFM), K_a of HSYA increased; T_max reduced, significantly. After oral administration of PNS and HFM (PHFM), K_a of Rg₁ improved, T_max decreased, significantly. However, the parameters of FA and Rb₁ were not significantly changed. After co-administration of CVO and PHFM (CVO-PHFM), C_max of Rb₁ decreased, K₁₂ improved, significantly. Meanwhile, the oral bioavailability of HSYA, FA and Rg₁ was improved by 6.056, 2.854 and 2.055 folds, respectively. Conclusion: After oral administration of different combinations of Shuxiong tablet constituents, some pharmacokinetics parameters of active ingredients are significantly changed, but the bioavailability is improved only when CVO is co-administered.