十五種常用中藥之亞急性毒性

Subacute Toxicity of 15 Commonly Used Chinese Drugs(I)

中藥應用在亞洲之傳統醫學上具有不可抹滅的歷史價值；目前仍與西方醫療並存，廣泛的運用於傳統醫療。現今海峽兩岸的關係逐步開放及中醫健診之開放，台灣中藥村之消費量亦與日俱增。衛生署出版之「中華民國中藥典範」中列有400種常用中藥，但對毒理作用均未述及；為「評估中藥之亞急性毒性」，以應證藥典記載之虛實並得以實驗澄清，並為將來有關藥效及毒理評估奠定實驗的基礎，而擬定此實驗。於急性一半致死劑量1/5至1/10當亞急性毒性最大耐受量之參考劑量下；本實驗觀察連續口服＋四天（每日一劑）白芍藥(1, 5g/kg)，柴胡(5, 10g/kg)，當歸(5, 10g/kg)，丹參(5, 10g/kg)，獨活(5, 10g/kg)，防風(5, 10g/kg)，葛根(5, 10g/kg)，桂枝(1, 5g/kg),黃柏(0.1, 0.59/kg)，黃連(0.1, 0.5g/kg)，黃芩(0.5, 1g/kg)，牡丹皮(0.5, 1g/kg)，熟地黃(5, 10g/kg)，酸棗仁(1, 5g/kg)，梔子(1, 5g/kg)等十五種常用中藥材50%乙醚抽提液對大白鼠血液、臨床生化、行為、及整體之亞急性毒性。其臨床生化結果顯示：白芍藥(5g/kg)，丹參(10g/kg)，獨活(10g/kg)，防風(10g/kg)，葛根(10g/kg)，桂枝(1, 5g/kg)，黃柏(0.5g/kg)，黃連(0.5g/kg)，黃芩(1g/kg)，牡丹皮(1g/kg)，熟地黃(10g/kg)，酸棗仁(10g/kg)，梔子(1g/kg)等導致全身營養標準之參考值，如血漿總蛋白質，血清白蛋白，及尿蛋白含量增加；柴胡、當歸、葛根、黃連、酸棗仁等影響肝功能SGPT值；於實驗結束解剖發現柴胡、當歸、丹參、黃柏、黃連、黃芩、熟地黃、酸棗仁、梔子等導致心、肝、肺、或腎臟器之組織重或含水量等病理指標之改變。於行為毒理評估發現丹參(10g/kg)，獨活(5, 10g/kg)，黃柏(0.5g/kg)，熟地黃(10g/kg)，酸棗舛(5, 10g/kg)等導致中等至強度之抑制自發性運動作用。於此連續十五天亞急性毒性實驗中，十五種常用中藥被試之劑量下均未發現任何非可逆性、肉眼可視之病理及死亡毒性副作用。藉由此實驗計劃希望對近百種常用中藥之安全性評估及毒性資料，提供中醫健保的用藥基準。

Traditional Chinese herbal drugs have been used for thousands of years among Chinese people. It is currently still serving as one of the most important health resources, and arc still proscribed in parallel with Western medical treatment. The annual consumption of traditional Chinese herbs is increased tremendously. With the improvement of relationship between mainland China and Taiwan, the Chinese medicines are now sanctioned by the National Health Insurance Program. Of the 400 commonly-used Chinese medicinal drugs listed in the ”Standards of Chinese Drugs, ROC.” receive no mention on their toxicity characteristics. Within this limited survey, this 5-year project ”Subacute Toxicity of Commonly Used Chines Drugs” was proposed to evaluate the safety of about 100 Chinese drugs. It is anticipated that these information on subacute toxicity obtained from this systemic evaluation will stimulate future research investigation which is designed to evaluate the chronic toxicity. The subacute toxicological and behavioral effects of 50% ethanol crude extracts of the following traditional Chinese medicinal drugs administered in single dosage (p. o. per day for 14 days) were evaluated quantitatively: 1. Baishaoyao (1, 5 g/kg) 2, Chaihu (5, 10g/kg) 3. Dangqin(5, 10g/kg) 4. Danshen (5, 10g/kg) 5. Duhuo (5, 10g/kg) 6. Fangfeng (5, 10g/kg) 7. Gegen (5, 10g/kg) 8. Guizhi (1, 5 g/kg) 9. Huangbai (0.1, 0.5 g/kg) 10.1-luanglian (0.1, 0.5 g/kg) 11. Hangqin (0.5, 1g/kg) 12. Mudanpi (0.5, 1 g/kg) 13. Shudi (5, 10 g/kg) 14. Suanzaoren (5, 10 g/kg) and 15. Zhizi (0.5, 1 g/kg), respectively. The maximal tolerate doses range from 1/10 to 1/5 of LD50 as the reference dosages in this subacute experiments. The following results were found: the whole body nutrient standard references values such as plasma total protein, serum albumin & urinary protein content increased by Baishaoyao (5 g/kg), Danshen (10 g/kg), Duhuo (10 g/kg), Fangfeng (10 g/kg), Gegen (10 g/kg), Guizhi (1, 5 g/kg), Huanghai (0.5 g/kg), Huanglian (0.5 g/kg), Huangqin (1 g/kg), Mudanpi (1 g/kg), Shudi (10 g/kg), Suanzaoren (10 g/kg), Zhizi (1 g/kg). The liver functional standard test such as SGPT were affected by Chaihu, Danggui, Gegen, Huanglian & Suanzaoren. The tissue pathological references standards such as the net tissue weight or water content of heart, liver, lung or kidney after post-mortem examination were affected by Chaihu, Danggui, Danshen, Huangbai, Huanglian, Hang qin, Shudi, Suanzaoren, & Zhizi. In behavioral toxicological evaluations, it was found that Danshen (10 g/kg), Duhuo (5, 10 g/kg), Huangbai (0.5 g/kg), Shudi (10 g/kg), Suanzaoren (5, 10 g/kg) elicited a moderate to marked degree of inhibition on the locomotor activity, while all the other herbal extracts caused no significant changes compared with control group. There is no evidences that any irreversible visible pathological or mortality occur during the experimental period (15-day period) in all tested doses among those 15 commonly used Chinese herbs. It is anticipated that these information on subacute toxicity obtained from this study will provide a reliable toxicological profile of those Chinese drugs which are commonly prescribed within the National Health Insurance Program in ROC.