目的 引入f₂相似因子法对银杏酮酯(GBE)缓释微丸的大类成分总黄酮和各类成分(包括黄酮类和萜内酯类)的释放曲线进行分析,以能较全面地评价其体外释放。方法 运用紫外分光光度法、高效液相-质谱联用(HPLC-MS)测定GBE缓释微丸中大类成分(总黄酮)和各类成分(槲皮苷、异鼠李素、芦丁、槲皮素、银杏内酯A、银杏内酯B、银杏内酯C、白果内酯)的体外释放率,并进行f₂相似因子计算;采用扫描电镜法观察微丸释药前后的微观结构,结合方程拟合分别对微丸中总黄酮和各类成分的释药机制解析,以验证f₂相似因子法的可靠性。结果 优化工艺的GBE微丸黄酮类和内酯类的各成分与大类成分总黄酮的f₂均大于50,说明大类成分总黄酮与各类成分体外释放曲线具有较好的相关性。释药机制解析进一步验证了该结果的可靠性。结论 f₂相似因子法可运用于多组分中药缓释制剂大类成分和各类成分的体外释放评价。

Objective To find a new method to evaluate the in vitro release of Ginkgo biloba extract (GBE) sustained-release pellets, f₂ fit factor method was used to study the correlation of in vitro release between total flavonoids and different ingredients (including flavonoids and terpenoids). Methods The release rates in vitro of total flavonoids and different ingredients (quercitrin, isorhamnetin, lutin, quercetin, ginkgolide A, ginkgolide B, ginkgolide C, and bilobalide) were detected by UV and HPLC-MS respectively, and then f₂ fit factor was calculated between total flavonoids and different ingredients. Also the micro-structures of pellets before and after drug release were detected by scanning electron microscopy (SEM), which could explain the drug release mechanism combined with the fitted equation. Results All f₂ values were greater than 50 between the total flavonoids and different ingredients of the in vitro release from GBE pellets of optimized preparation, which indicated that there might be a good correlation between them. The drug release mechanism further verified the reliability of the results. Conclusion The f₂ fit factor method could be applied in the evaluation of in vitro release for multi-component sustained-release preparations of Chinese materica medicine.

国家自然科学基金面上项目(81473434,81274090);国家自然科学基金青年基金(81202926,81503206)