海藻、甘草配伍组合及其复方海藻玉壶汤的急性毒性实验比较研究

 比较单味海藻组、生甘草组、炙甘草组、海藻与生甘草合煎组、海藻与炙甘草合煎组、海藻玉壶汤(生甘草)组、海藻玉壶汤(炙甘草)组不同组别的小鼠急性毒性,进行单味药、反药组合及含反药组合复方的急性毒性观察与评价,为基于临床的十八反研究提供用药依据.分别制备海藻煎液、生甘草煎液、炙甘草煎液、海藻与生甘草合煎液、海藻与炙甘草合煎液、海藻玉壶汤(生甘草)煎液、海藻玉壶汤(炙甘草)煎液作为不同组别的受试药物,参照小鼠急性毒性试验方法,根据预实验结果,进行单味药、反药组合及含反药组合复方的小鼠急性毒性试验比较研究,试验数据用Bliss法计算半数致死量LD₅₀及LD_50(n),满足LD₅₀条件的海藻组、海藻与生甘草合煎液组、海藻与炙甘草合煎液组给药后连续观察7d,其余各组连续观察28d并记录体重.结果表明,实验各组对小鼠急性毒性强度为：海藻组＞海藻与炙甘草合煎组＞海藻与生甘草合煎组＞炙甘草组＞海藻玉壶汤(炙甘草)组＞海藻玉壶汤(生甘草)组>生甘草组.海藻组LD₅₀值为35.67g·kg^-1·d^-1,海藻与炙甘草合煎组LD₅₀值为44.29g·kg^-1·d^-1,海藻与生甘草合煎组LD₅₀值为50.98g·kg^-1·d^-1,分别相当于临床70kg人每kg体重日用量的145.2倍,182.6倍和211.5倍;在LD_50(n)实验中,炙甘草组连续给药第8天死亡数量达到半数,LD₅₀₍₈₎为70.69g·kg^-1·d^-1,生甘草组LD₅₀₍₁₉₎为82.98g·kg^-1·d^-1, 海藻玉壶汤(生甘草)组LD₅₀₍₇₎为79.24g·kg^-1·d^-1,海藻玉壶汤(炙甘草)组LD₅₀₍₆₎为77.49g·kg^-1·d^-1.由此得出结论：海藻煎液、海藻与炙甘草合煎液属小毒范畴,与文献记载相符.通过反药组合单味及复方的小鼠急性毒性试验比较研究,有利于为进一步锁定毒性物质基础及后续实验展开提供依据,亦也为临床安全用药提供依据.

Acute Toxicity of Incompatible Pair of Sargassum and Radix Glycyrrhizae and Its Compound Haizao Yuhu Decoction in Mice

To compare the acute toxicity of the decocted water solution of Sargassum, Radix Glycyrrhizae, the prepared Radix Glycyrrhizae, the Sargassum with Radix Glycyrrhizae, the Sargassum with the prepared Radix Glycyrrhizae, the Haizao Yuhu decoction (Radix Glycyrrhizae) and the Haizao Yuhu decoction(the prepared Radix Glycyrrhizae) in mice, the water extraction components of different groups were prepared, and comparisons were made in accordance with the classical acutetoxicity test methods. The LD₅₀ of the Sargassum water extraction is 35.67g·kg^-1·d^-1, the water extraction of the Sargassum with the prepared Radix Glycyrrhizae is 44.29g·kg^-1·d^-1and the water extraction of the Sargassum with the Radix Glycyrrhizae is 50.98g·kg^-1·d^-1, which are equal to, respectively, 145.2 times, 182.6 times and 211.5 times of 70kg adult's daily dried medicinal herb intake. In the experiment of LD_50(n), the death rate of the prepared Radix Glycyrrhizae reaches 50 % by the end of consecutive 8 days, and its LD₅₀₍₈₎ is 70.69g·kg^-1·d^-1.The LD₅₀₍₁₉₎ of the Radix Glycyrrhizae is 82.98g·kg^-1·d^-1; the LD₅₀₍₇₎ of the Haizao Yuhu decoction (Radix Glycyrrhizae) is 79.24g·kg^-1·d^-1; the LD₅₀₍₆₎ of the Haizao Yuhu decoction (the prepared Radix Glycyrrhizae) is 77.49g·kg^-1·d^-1. The acute toxicity of different groups in mice is: Sargassum > Sargassum with the prepared Radix Glycyrrhizae > Sargassum with Radix Glycyrrhizae > prepared Radix Glycyrrhizae > Haizao Yuhu decoction (the prepared Radix Glycyrrhizae) > Haizao Yuhu decoction (Radix Glycyrrhizae) > Radix Glycyrrhizae. However the toxic substances, the toxicity characteristics, and the toxicity mechanism are not yet entirely clear, and they should be further studied.