以甘草酸为稳定剂制备水飞蓟素纳米混悬剂及稳定机制研究  

Preparation of silymarin nanosuspension with glycyrrhizic acid as stabilizer and study of its stabilization mechanism

作　　者：唐海龙 李小芳[1] 龙家英 邓茂 谢龙 廖艳梅 TANG Hai-long;LI Xiao-fang;LONG Jia-ying;DENG Mao;XIE Long;LIAO Yan-mei(Key Laboratory of Research and Utilization of Chinese Medicinal Resources in Sichuan Province,Key Laboratory Breeding Base of Co-founded by Sichuan Province and Ministry of Science and Technology,Key Laboratory of Standardization of Chinese Herbal Medicine of Ministry of Education,College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院,中药材标准化教育部重点实验室,四川省中药资源系统研究与开发利用重点实验室——省部共建国家重点实验室培育基地,四川成都611137

出　　处：《中草药》2020年第4期971-977,共7页Chinese Traditional and Herbal Drugs

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

摘　　要：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19000 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.

关 键 词：纳米混悬剂 水飞蓟素 甘草酸 制备工艺 稳定机制 高速剪切-高压均质技术 释放特性 冷冻干燥法 溶解度 稳定性 

分 类 号：R283.6[医药卫生—中药学]