摘要
目的比较亮菌甲素不同剂型及不同原辅料间细胞毒性。方法将已培养48~72 h生长旺盛的L929细胞消化稀释,并铺于12孔细胞培养板中,培养后给予亮菌甲素注射用粉针、注射液及原辅料溶液,72 h后观察,并用细胞计数仪计数,将亮菌甲素原辅料及其注射剂相应每种浓度的细胞数转换成细胞生长抑制率,用GraphPad Prism 5软件计算出50%细胞生长抑制浓度(IC50),并比较毒性。结果亮菌甲素注射液的L929细胞毒性(IC50值为0.00583~0.01025 mg·mL-1)明显大于注射用亮菌甲素(IC50值为0.06049~0.1753 mg·mL-1),辅料N,N-二甲基乙酰胺[主药活性药用成分(API)IC50为0.007172 mg·mL-1]及丙二醇(API IC50为0.01853 mg·mL-1)毒性较大,导致辅料总混液(API IC50为0.01659 mg·mL-1)细胞毒性增加,从而增加注射液的细胞毒性。结论有必要对亮菌甲素注射液处方和生产工艺进一步优化,降低药用辅料可能带来的不良反应,从而保障患者用药安全。
Objective To compare the cytotoxicity of raw materials,excipients and injection of armillarisin A on cells.Methods The vigorously proliferative L929 cells,which had been cultured for 48-72 hours,were digested,diluted and then cultured in 12-well cell culture plates.A series of raw materials,excipients and injections of armillarisin A was then incubated with the cultured cells in the plates.After 72 hours,the treated cells were observed and counted by cell counting instrument.The inhibitory rate on cell growth of each concentration was calculated.IC50 was then estimated by Graphpad Prism 5 software,and the cytotoxicity was compared.Results The cytotoxicity of armillarisin A injections was significantly higher than that of powder for injection against L929 cells.The IC50were 0.00583-0.01025 mg·mL-1,0.06049-0.1753 mg·mL-1,respectively.The toxicity of excipients,N,N-dimethyl acetamide(API IC50 was 0.007172 mg·mL-1)and propylene glycol(API IC50 was 0.01853 mg·mL-1),were relatively higher,which led to an increased cytotoxicity of the total mixture of excipients(API IC50was 0.01659 mg·mL-1),thus increasing the cytotoxicity of the injection.Conclusion It is necessary to further optimize the prescription and production process of armillarisin A injection to reduce the possible adverse reactions caused by pharmaceutical excipients,so as to ensure the drug safety for patients.
作者
汪玉馨
唐婉
刘洋
孟长虹
陆益红
史清水
王广基
WANG Yuxin;TANG Wan;LIU Yang;MENG Changhong;LU Yihong;SHI Qingshui;WANG Guangji(Key Lab of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China;Research Center of Pharmacology and Toxicology,Jiangsu Institute for Food and Drug Control,Nanjing 210019,China;Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China)
出处
《医药导报》
CAS
北大核心
2020年第2期135-139,共5页
Herald of Medicine
基金
重大新药创制专项(20152X09303001),2018年国家评价性抽验
关键词
亮菌甲素
原辅料
细胞毒性
L929细胞
Armillarisin A
Raw materials and excipients
Cytotoxicity
L929 Cells
作者简介
汪玉馨(1984-),女,江苏苏州人,副主任药师,硕士,药检药理毒理。ORCID:0000-0001-5078-274X,电话:025-86251278,E-mail:wyx_carrie@163.com;通信作者:王广基(1953-),男,江苏扬州人,教授,博士生导师,从事药物代谢动力学研究。电话:025-83271176,E-mail:guangjiwang@hotmail.com。
