目的 制备以甘草酸为稳定剂的水飞蓟素纳米混悬剂（silymarin nanosuspension，SM-NS），并考察体外释放特性和电荷稳定机制。方法 用高速剪切-高压均质法制得SM-NS，用冷冻干燥法制成SM-NS冻干粉并进行理化特性表征和体外释放特性评价。从离子强度，pH值的角度对SM-NS进行了稳定机制研究。结果 稳定剂甘草酸（GA）用量为0.15%，制备工艺为剪切速率19 000 r/min、剪切时间4 min、均质压力100 MPa、均质次数12次，冻干保护剂为甘露醇，其用量3%，制得的SM-NS冻干粉平均粒径为（516.4±10.4）nm，多分散指数（PDI）为0.260±0.046；体外释放结果表明SM-NS冻干粉的溶出速率和溶解度显著提高；电荷稳定机制研究表明甘草酸能提供良好的电荷稳定作用，抗环境冲击能力较强。结论 SM-NS是一种潜在的安全性高的新型纳米药物，其通过甘草酸的电荷稳定作用显著提高水飞蓟素的溶解度及稳定性。

Objective To prepare silymarin nanosuspension (SM-NS) with glycyrrhizic acid as stabilizer, and investigate the in vitro release characteristics and charge stabilization mechanism. Methods SM-NS was prepared by high-speed shear-high pressure homogenization method. SM-NS lyophilized powder were prepared by freeze-drying method and characterized by physical and chemical characterization and in vitro release. The stability mechanism of SM-NS was studied from the ionic strength and pH value. Results The dosage of glycyrrhizic acid (GA) was 0.15%. The preparation process was shear rate of 19 000 r/min, shear time of 4 min, homogenization pressure of 100 MPa, homogenization times of 12 times, and lyoprotectant was mannitol 3%, the average particle size of SM-NS lyophilized powder was (516.4±10.4) nm, PDI was (0.260±0.046); The in vitro release results showed that the dissolution rate and solubility of SM-NS lyophilized powder were significantly higher than the physical mixture; The study of charge stability mechanism showed that licorice acid can provide good charge stabilization and strong resistance to environmental impact. Conclusion SM-NS is a potential and new nano-drug with high safety, which is formed by the charge stability of GA to significantly improve the solubility and stability of silymarin.

R283.6

四川省科技厅项目（2019YFS0113）；国家中医药管理局项目（2018ZYO3O02）