脯氨酸丹参素冰片酯对小鼠急性毒性研究

doi:10.19803/j.1672-8629.20220529

中国药物警戒 ›› 2023, Vol. 20 ›› Issue (7): 754-757.
DOI: 10.19803/j.1672-8629.20220529

脯氨酸丹参素冰片酯对小鼠急性毒性研究

王荣¹, 刘自群¹, 王娜娜¹, 谭雄^1,2, 张怡心^1,2, 杨宽¹, 秦蓓^1,*

¹西安医学院药学院药物研究所,西安市多靶协同抗高血压创新药物研制重点实验室,陕西西安 710021;
²成都医学院药学院,四川成都 610500

收稿日期:2022-09-09 出版日期:2023-07-15 发布日期:2023-07-14
通讯作者: ^*秦蓓,女,博士,教授·硕导,药物化学合成与新药临床前研究。E-mail：qinbei0526@163.com
作者简介:王荣,女,博士,副教授,药物安全性评价。
基金资助:
国家自然科学基金资助项目（81903288）; 陕西省重点研发计划项目（2021ZDLSF03-05）; 西安医学院校级科技创新团队（2021TD03、2021TD07）; 陕西省大学生创新创业训练计划项目（S202111840030）; 西安医学院校级重点药学学科（西医发[2019]96号）; 西安医学院校级大学生创新创业训练计划项目（121522107）

Acute toxicity of proline Danshensu borneol ester in mice

WANG Rong¹, LIU Ziqun¹, WANG Nana¹, TAN Xiong^1,2, ZHANG Yixin^1,2, YANG Kuan¹, QIN Bei^1,*

¹Institute of Drug Research, Xi’an Medical College, Xi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Shaanxi 710021, China;
²College of Pharmacy, Chengdu Medical College, Chengdu Sichuan 610500, China

Received:2022-09-09 Online:2023-07-15 Published:2023-07-14

摘要/Abstract

摘要： 目的探究抗高血压1类新药脯氨酸丹参素冰片酯的急性毒性,评价其安全性。方法 24只小鼠,雌雄各半,随机分为溶剂对照组和给药组,根据脯氨酸丹参素冰片酯溶液的最大浓度（150 mg·mL^-1）,单次灌胃,连续观察7 d,记录小鼠毒性反应、体重及饮食饮水量,7 d后小鼠处死,观察主要脏器变化,测定心、肝、肾、肺脏等主要脏器指数,HE染色观察脏器病理性改变。结果实验过程中,脯氨酸丹参素冰片酯给药后小鼠均未出现死亡。与溶剂对照组相比,脯氨酸丹参素冰片酯给药后7 d内,小鼠活动、体重、饮食饮水量均无显著性差异。给药组肝、肾、肺脏指数与对照组相比无显著差异（P>0.05）。与溶剂对照组小鼠相比,雄性小鼠给药组心脏指数无显著差异（P>0.05）,而雌性小鼠给药组的心脏指数具有显著降低（P<0.05）,且心肌细胞排列紊乱。结论测得脯氨酸丹参素冰片酯对小鼠灌胃的最大耐受量为3 000 mg·kg^-1。脯氨酸丹参素冰片酯毒性小,安全性较好。

关键词: 脯氨酸丹参素冰片酯, 高血压, 急性毒性, 半数致死量, 最大耐受量, 安全性, 小鼠, 灌胃给药

Abstract: Objective To explore the acute toxicity of anti-hypertensive drug proline-Danshensu borneol ester-in mice, and to evaluate its safety. Methods Twenty-four mice were randomly divided into the test group and control group. The maximum tolerated dose (MTD) was determined via single intragastrical administration of the maximal concentration of proline Danshensu borneol ester (150 mg·mL^-1). Toxic reactions, body weight and intakes of foods and water were observed for seven consecutive days until the mice were sacrificed. Visceral changes were observed and index of the heart, liver, kidney and lung were recorded. Pathological histology was observed via HE staining. Results There was no death of mice after intragastrical administration of different concentrations of proline Danshensu borneol ester. Compared with the control group, the daily activities, body weight and intakes of foods and water in the test group of mice were not significantly different (P>0.05), so were the indexes of the liver, kidney or lung (P>0.05). The heart indexes of male mice in the test group were not significantly different from those of the control group (P>0.05), but the heart indexes of female mice were significantly decreased (P<0.05) and myocardial cells were disorderly. Conclusion The MTD of proline Danshensu borneol ester in mice is orally 3 000 mg·kg^-1, which leads to low toxicity in mice.

Key words: proline Danshensu borneol ester, hypertension, acute toxicity, median lethal dose, maximum tolerated dose, safety, mice, intragastric administration

中图分类号:

R965

王荣, 刘自群, 王娜娜, 谭雄, 张怡心, 杨宽, 秦蓓. 脯氨酸丹参素冰片酯对小鼠急性毒性研究[J]. 中国药物警戒, 2023, 20(7): 754-757.

WANG Rong, LIU Ziqun, WANG Nana, TAN Xiong, ZHANG Yixin, YANG Kuan, QIN Bei. Acute toxicity of proline Danshensu borneol ester in mice[J]. Chinese Journal of Pharmacovigilance, 2023, 20(7): 754-757.

参考文献

[1] CHENG GL.A review of different blood pressure indices for carotid target organ damage[J]. China Continuing Medical Education(中国继续医学教育), 2021, 13(20): 195-198.
[2] NCD Risk Factor Collaboration. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants[J]. The Lancet, 2021, 398(10304): 957-980.
[3] WANG Z, CHEN Z, ZHANG L, et al.Status of hypertension in China: results from the China hypertension survey, 2012-2015[J]. Circulation, 2018, 137(22): 2344-2356.
[4] ZHENG XH, JIA P, BAI YJ.Research strategy for combination of traditional Chinese medicine molecular chemistry based on the traditional theory of‘Jun-Chen-Zuo-Shi’[J]. Journal of Northwest University (Natural Science Edition)(西北大学学报自然科学版), 2015, 45(3): 405-412.
[5] NMPA. Guidance for acute toxicity testing of drug combinations[S]. NMPA, 2005.
[6] TIAN HL, ZHOU XW, CHEN M.Asymmetric synthesis of Danshensu borneol ester[J]. Chinese Journal of Medicinal Chemistry(中国药物化学杂志), 2012, 22(2): 113-116.
[7] LIU P, QIN FG, BAI YJ, et al.Synthesis and chiral separation of isopropyl and bornyl β (3,4-dihydroxyphenyl)-α-hydroxypropionate[J]. Journal of Northwest University (Natural Science Edition)(西北大学学报自然科学版), 2015, 45(3): 413-417.
[8] WU YZ.Study on the metabolism of bornyl protocatechuate, a novel bioactive compound derived from the compatibility of herb-pair guangzao-borneol”[D]. Xi’an: Northwest University, 2014.
[9] HUANG FH, WANG QL.Interpretation of guidance on single dose toxicity study for pharmaceuticals[J]. Chinese Journal of New Drugs(中国新药杂志), 2015, 24(4): 386-389.
[10] MO ZH, CHEN MX, WANG PC, et al.Acute toxicity of Huoxin pills in mice[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2021, 18(10): 924-929.
[11] HUANG CH, FAN HY, DAI XL.Study of single-dose toxicity of dexrabeprazole sodium in mice[J]. Journal of Pharmaceutical Research(药学研究), 2018, 37(10): 572-574.

[1]	孙绮悦, 赵荣华, 包蕾, 郭姗姗, 耿子涵, 李舒冉, 徐英莉, 张敬升, 崔晓兰, 孙静. 基于多动物模型药效评价体系研究羚羊感冒口服液儿童用药剂量[J]. 中国药物警戒, 2024, 21(2): 121-126.
[2]	孙绮悦, 赵荣华, 郭姗姗, 包蕾, 耿子涵, 李舒冉, 徐英莉, 张敬升, 崔晓兰, 孙静. 羚羊感冒口服液多重药理作用研究[J]. 中国药物警戒, 2024, 21(2): 127-131.
[3]	赵荣华, 孙静, 包蕾, 耿子涵, 陶夏莉, 张敬升, 庞博, 徐英莉, 曹姗, 李舒冉, 郭姗姗, 王道涵, 崔晓兰. 基于免疫调节探讨葛根汤颗粒治疗小鼠病毒性肺炎的作用机制[J]. 中国药物警戒, 2024, 21(2): 132-136.
[4]	贾茵茵, 张财树, 周颖, 刘丽, 耿颖, 魏宁漪, 钮思静, 陈华, 许卉. 吸入制剂微细粒子空气动力学粒径分布评价方法研究[J]. 中国药物警戒, 2024, 21(2): 141-146.
[5]	柏兆方, 湛小燕, 姚清, 陈思敏, 赵旭, 肖小河. 中药安全性评价理论创新与技术突破：病证毒理学[J]. 中国药物警戒, 2024, 21(1): 6-14.
[6]	方志娥, 李承贤, 柏兆方, 赵旭, 王伽伯, 肖小河. 马兜铃酸致肝癌的客观性研究与思考[J]. 中国药物警戒, 2024, 21(1): 20-24.
[7]	曹姗, 庞博, 徐英莉, 张敬升, 陈梦苹, 张宇, 王雅欣, 包蕾, 耿子涵, 郭姗姗, 赵荣华, 崔晓兰. 疏风解毒胶囊预防给药对流感病毒感染小鼠模型TLR4介导肺组织炎性损伤的影响[J]. 中国药物警戒, 2024, 21(1): 45-50.
[8]	张敬升, 高双荣, 庞博, 刘莉娜, 徐英莉, 曹姗, 陈梦苹, 张宇, 赵荣华, 崔晓兰. 散寒化湿颗粒对人冠状病毒229E和OC43感染致小鼠肺炎的作用机制研究[J]. 中国药物警戒, 2024, 21(1): 51-54.
[9]	张亮亮, 胡昌坤, 吴泽坤, 周维, 廖泽彬, 高月. 富马酸二甲酯对肠道辐射损伤防护作用及机制研究[J]. 中国药物警戒, 2024, 21(1): 83-88.
[10]	熊玮仪, 任经天. 抗肿瘤药说明书安全性信息上市后修订的考虑要点[J]. 中国药物警戒, 2024, 21(1): 94-97.
[11]	刘敏, 陈艳, 刘文东, 王海学. 药物临床试验期间安全性数据快速报告的更新与思考[J]. 中国药物警戒, 2024, 21(1): 98-101.
[12]	陈华炎, 江东波, 郭春连, 杨家琪, 黎雨欣, 蔡伟明. 326例奈玛特韦片/利托那韦片治疗新型冠状病毒感染安全性分析[J]. 中国药物警戒, 2024, 21(1): 107-110.
[13]	里筱竹, 王蔷, 逄瑜, 张轶菁. 个例药品不良反应报告管理浅析与思考[J]. 中国药物警戒, 2023, 20(9): 975-977.
[14]	刘倩, 胡晶, 李博, 杨小静. 荆花胃康胶丸联合四联疗法治疗幽门螺旋杆菌相关性胃炎的系统评价及Meta分析[J]. 中国药物警戒, 2023, 20(9): 1039-1045.
[15]	于洪礼, 于冬梅, 肖爱丽, 朱兰, 宋海波. 清开灵口服制剂安全性风险分析[J]. 中国药物警戒, 2023, 20(9): 1046-1048.

脯氨酸丹参素冰片酯对小鼠急性毒性研究

Acute toxicity of proline Danshensu borneol ester in mice

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics