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香芍散结口服液 3 种入血成分在乳腺增生症模型大鼠体内的药
动学研究
Δ
张 宇 1, 2* ,李家明 ,彭 丹 ,傅若秋 ,明 月 ,刘正碧 ,王晶晶 ,程诗奇 ,谢红军 ,刘 耀 (1. 西藏大学
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医学院,拉萨 850011;2.陆军特色医学中心药剂科,重庆 400042;3.陆军特色医学中心实验动物中心,重庆
400042)
中图分类号 R969.1 文献标志码 A 文章编号 1001-0408(2025)06-0680-06
DOI 10.6039/j.issn.1001-0408.2025.06.07
摘 要 目的 探究香芍散结口服液3种入血成分(阿魏酸、芍药苷、迷迭香酸)在乳腺增生(HMG)模型大鼠体内的药动学特征。
方法 选择雌性SD大鼠,按体重分为对照组和HMG组,每组6只。HMG组以雌激素+孕激素联合诱导构建HMG模型。造模后,
两组大鼠均灌胃香芍散结口服液1.485 g/kg(以生药量计),每天1次,连续7 d。分别于首次给药前(0 h)以及末次给药后5、15、30
min和1、2、4、8、12、24 h采血,以氯唑沙宗为内标,采用超高效液相色谱-四极杆飞行时间质谱技术检测大鼠体内阿魏酸、芍药苷、
迷迭香酸的血药浓度。运用Phoenix WinNonlin 8.1软件,以非房室模型计算其药动学参数[药时曲线下面积(AUC0-24 h、AUC0-∞)、
平均滞留时间(MRT0-∞)、半衰期(t1/2 )、达峰时间(tmax )、峰浓度(cmax )]。结果 与对照组比较,HMG 组大鼠体内阿魏酸的 AUC0-24 h、
AUC0-∞、cmax均显著升高(P<0.05);芍药苷的AUC0-24 h、AUC0-∞、MRT0-∞、t1/2、cmax虽有上升或延长趋势,但组间比较差异均无统计学
意义(P>0.05);迷迭香酸的AUC0-24 h、MRT0-∞均显著升高或延长(P<0.05)。结论 在HMG 模型大鼠体内,香芍散结口服液中的
阿魏酸、芍药苷、迷迭香酸的体内暴露量均有所增加,迷迭香酸的体内滞留时间明显延长。
关键词 香芍散结口服液;乳腺增生;阿魏酸;芍药苷;迷迭香酸;药动学;超高效液相色谱-四极杆飞行时间质谱
Pharmacokinetic study of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with
hyperplasia of mammary gland
ZHANG Yu ,LI Jiaming ,PENG Dan ,FU Ruoqiu ,MING Yue ,LIU Zhengbi ,WANG Jingjing ,CHENG
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Shiqi ,XIE Hongjun ,LIU Yao (1. School of Medicine, Tibet University, Lhasa 850011, China;2. Dept. of
Pharmacy, Army Medical Center of PLA, Chongqing 400042, China;3. Laboratory Animal Center, Army
Medical Center of PLA, Chongqing 400042, China)
ABSTRACT OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie
oral liquid in rats with hyperplasia of mammary gland (HMG). METHODS Female SD rats were divided into control group and
HMG group according to body weight, with 6 rats in each group. The HMG group was given estrogen+progesterone to construct
HMG model. After modeling, two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid (calculated by crude drug)
intragastrically, once a day, for 7 consecutive days. Blood samples were collected before the first administration (0 h), and at 5,
15, 30 minutes and 1, 2, 4, 8, 12, 24 hours after the last administration, respectively. Using chlorzoxazone as the internal
standard, the plasma concentrations of ferulic acid, paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS.
The pharmacokinetic parameters [area under the drug time curve (AUC0-24 h, AUC0-∞), mean residence time (MRT0-∞), half-life
(t1/2 ), peak time (tmax ), peak concentration (cmax )] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1
software. RESULTS Compared with the control group, the AUC0-24 h, AUC0-∞ and cmax of ferulic acid in the HMG group were
significantly increased (P<0.05); the AUC0-24 h, AUC0-∞ , MRT0-∞ , t1/2 and cmax of paeoniflorin increased, but there was no
significant difference between 2 groups (P>0.05); the AUC0-24 h and MRT0-∞ of rosmarinic acid were significantly increased or
prolonged (P<0.05). CONCLUSIONS In HMG model rats, the exposure of ferulic acid, paeoniflorin and rosmarinic acid in
Xiangshao sanjie oral liquid all increase, and the retention
Δ 基金项目 重 庆 市 科 卫 联 合 医 学 中 医 药 科 研 项 目(No.
time of rosmarinic acid is significantly prolonged.
2023ZDXM032) KEYWORDS Xiangshao sanjie oral liquid; hyperplasia of
*第一作者 中药师,硕士研究生。研究方向:中药药动学。E-
mammary gland; ferulic acid; paeoniflorin; rosmarinic acid;
mail:zhangyu0501@tmmu.edu.cn
pharmacokinetics; UPLC-Q/TOF-MS
# 通信作者 副主任药师,博士。研究方向:中药药效物质基础与
药动学。E-mail:liuyao@tmmu.edu.cn
· 680 · China Pharmacy 2025 Vol. 36 No. 6 中国药房 2025年第36卷第6期