一种抗肿瘤中药复方制剂的小鼠急性毒性试验及对血液生理生化指标的影响研究
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摘要
【目的】研究一味中药复方制剂的安全性,为人体肿瘤临床治疗用药提供参考。【方法】本试验对复方制剂进行了经口急性毒性、最大耐受量及其28 d经口毒性方面的研究。经口急性毒性预试验对各组小鼠一次灌服剂量0.2、0.6、1.8、5.4、16.2 g/kg (bw)的提取液,最大耐受量试验提取液按1.25、1.00、0.80、0.64、0.51 g/mL的质量浓度、0.04 mL/g (bw)的灌胃量对各组小鼠24 h之内灌胃3次,对小鼠连续观察7 d;将40只小鼠随机分为高、中、低剂量组及对照组,连续28 d灌服等体积不同含量[15、7.5、3.75、0 g/kg (bw)]的复方制剂,测定小鼠的血液生理生化指标。【结果】急性毒性结果表明:该复方制剂粗提物经口LD50>5 g/kg(bw),小鼠对其最大耐受量达到150 g/kg (bw),最大耐受量为人用剂量的1 050倍;28 d经口毒性试验中各组小鼠体重、血液生理指标与对照组相比差异不显著(P>0.05)。血液生化指标仅中剂量组LDH与对照、低、高剂量组差异显著(P<0.05),GPT、GOT、Cr和BUN各指标无显著差异(P>0.05)。【结论】该复方制剂对小鼠无毒性作用,对血液生理生化部分指标无影响,临床使用安全。
[Purpose]To study the safety of a traditional Chinese medicine compound formulation,and to provide a reference for clinical treatment of human tumor.[Method]The acute toxicity, the maximum tolerated dose and the 28 d oral toxicity of the compound formulations were studied. The mice were given a dose of 0.2, 0.6, 1.8, 5.4, 16.2 g/kg(bw) at the same time for oral acute toxicity test. The maximum tolerated test extract with the concentrations of 1.25, 1.00, 0.80, 0.64, 0.51 g/mL0.04 mL/g(bw) was administered orally to the mice in each group within 3 hours, and the mice were continuously observed for 7 days. Forty mice were randomly divided into high, medium, low and control dose group. In the control group, the compound preparations of different concentrations [15, 7.5,3.75, 0 g/kg(bw)] were administered for 28 days, and the blood physiological and biochemical indexes of the mice were determined.[Result]The results of acute toxicity showed that the crude extract of the compound preparation had an oral tolerance of LD50>5 g/kg(bw), and the maximum tolerance of the mice was 150 g/kg(bw), and the maximum tolerated dose was 1 050 times of the human dose. The body weight and blood physiological indexes of the mice in each group were not significantly different(P>0.05). The blood biochemical parameters only showed significant difference between the LDH and the control, low and high dose groups(P<0.05), and there were no significant differences in GPT, GOT, Cr and BUN(P>0.05).[Conclusion]The compound preparation has no toxic effect, has no effect on blood physiological and biochemical indexes, and is safe for clinical use.
[Purpose]To study the safety of a traditional Chinese medicine compound formulation,and to provide a reference for clinical treatment of human tumor.[Method]The acute toxicity, the maximum tolerated dose and the 28 d oral toxicity of the compound formulations were studied. The mice were given a dose of 0.2, 0.6, 1.8, 5.4, 16.2 g/kg(bw) at the same time for oral acute toxicity test. The maximum tolerated test extract with the concentrations of 1.25, 1.00, 0.80, 0.64, 0.51 g/mL0.04 mL/g(bw) was administered orally to the mice in each group within 3 hours, and the mice were continuously observed for 7 days. Forty mice were randomly divided into high, medium, low and control dose group. In the control group, the compound preparations of different concentrations [15, 7.5,3.75, 0 g/kg(bw)] were administered for 28 days, and the blood physiological and biochemical indexes of the mice were determined.[Result]The results of acute toxicity showed that the crude extract of the compound preparation had an oral tolerance of LD50>5 g/kg(bw), and the maximum tolerance of the mice was 150 g/kg(bw), and the maximum tolerated dose was 1 050 times of the human dose. The body weight and blood physiological indexes of the mice in each group were not significantly different(P>0.05). The blood biochemical parameters only showed significant difference between the LDH and the control, low and high dose groups(P<0.05), and there were no significant differences in GPT, GOT, Cr and BUN(P>0.05).[Conclusion]The compound preparation has no toxic effect, has no effect on blood physiological and biochemical indexes, and is safe for clinical use.
引文
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[2]马立秀,陈永忠.论中药汤剂的煎煮方法与服用方法[J].临床医药文献电子杂志,2017,4(12):2311.DOI:10.16281/j.cnki.jocml.2017.12.109.
[3]戴璐.寒性中药对实热证疗效的表述及大黄、黄连对实热证大鼠效应的实验研究[D].济南:山东中医药大学,2011.
[4]GB 15193.1-2014.食品安全性毒理学评价程序和方法[S].
[5]王冉.复方中药对肉用犊牛生长性能和免疫功能的影响研究[D].重庆:西南大学,2015.
[6]刘伟,程波,蒋瑞东,等.中药催情散的急性和亚慢性毒性研究[J].西北农林科技大学学报(自然科学版),2018,46(5):43.DOI:10.13207/j.cnki.jnwafu.2018.05.007.
[7]杨露苗.中兽药丹连花子宫灌注液的安全性评价[D].杨凌:西北农林科技大学,2017.
[8]信晨曦,梁洁,周昱杉,等.中药复方制剂配伍机理的研究概况[J].中国新药杂志,2018(24):2895.
[9]杨志杰,李秀丽.中医药诱导细胞凋亡治疗恶性肿瘤的研究进展[J].中医学报,2013,28(1):18.DOI:10.16368/j.issn.1674-8999.2013.01.027.
[10]HOR S Y,AHMAD M,FARSI E,et al.Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats[J].Journal of Ethnopharmacology,2011,137(3):1067.DOI:10.1016/j.jep.2011.07.007.
[11]IHSAN A,WANG X,HUANG X J,et al.Acute and subchronic toxicological evaluation of Mequindox in Wistar rats[J].Regulatory Toxicology&Pharmacology,2010,57(2/3):307.DOI:10.1016/j.yrtph.2010.03.011.
[12]万贞元,王造昌,温月红,等.血尿素氮与肌酐联合血清胱抑素C与β_2微球蛋白检测在肾功能损伤中的诊断应用[J].实验与检验医学,2014,32(5):595.DOI:10.3969/j.issn.1674-1129.2014.05.045.