Zhang Xiu-Rong, Lin Tao, Wang Xiu-Li, Wang Xiao-Jie, Gu Heng
School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.
College of Bioengineering,Beijing Polytechnic Beijing 100176, China.
Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(17):4634-4642. doi: 10.19540/j.cnki.cjcmm.20220705.302.
Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.
采用高速分散法结合超声乳化法制备了丹酚酸B（Sal B）、丹参酮Ⅱ_A（TSNⅡ_A）和甘草次酸（GA）脂质乳剂（GTS-LE）。以乳剂的外观、离心稳定性和粒径为评价指标，采用单因素法和D-最优法对乳剂的制备工艺进行优化，随后进行验证。通过反向透析法考察GTS-LE中Sal B、TSNⅡ_A和GA的体外释放情况。在小鼠体内进行药代动力学评价。用对乙酰氨基酚诱导急性肝损伤模型。通过小鼠血清肝功能指标和肝组织病理变化研究口服GTS-LE对急性肝损伤的影响。结果表明，在最佳制备工艺下，GTS-LE的平均粒径为（145.4±9.25）nm，Zeta电位为（-33.6±1.45）mV。GTS-LE中Sal B、TSNⅡ_A和GA的载药效率均高于95%，体外药物释放符合Higuchi方程。药代动力学结果显示，GTS-LE中Sal B、TSNⅡ_A和GA的C_(max)分别是GTS-S组的3.128、2.7和2.85倍，GTS-LE中Sal B、TSNⅡ_A和GA的AUC_(0-t)分别是GTS-S组的3.09、2.23和1.9倍。灌胃给予GTS-LE后，丙氨酸氨基转移酶和天冬氨酸氨基转移酶的活性受到显著抑制，丙二醛含量降低，肝细胞结构恢复正常。综上所述，GTS-LE可延缓Sal B的释放，促进TSNⅡ_A和GA的释放。三种药物成分包封于乳剂中可不同程度提高口服生物利用度，并能有效预防对乙酰氨基酚所致的急性肝损伤。
