15種常用中藥之亞急性毒性(II)   全文下載

Subacute Toxicity of 15 Commonly Used Chinese Drugs（II）

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，台灣中藥材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，以印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當亞急性毒牲最大耐受量之參考劑量下；本實驗觀察連續口服十四天（每日一劑）車前子（5，10 g／kg），地骨皮（5，10 g／kg），茯苓（5，10 g／kg），厚朴（5，10 g／kg），馬兜鈴（5，10 g／kg），木通（5，10 g／kg），牛膝（5，10 g／kg），青箱子（5，10 g／kg），前胡（5，10 g／kg），山豆根（5，10g／kg），天南星（5，10 g／kg），威靈仙（5，10 g／kg），夏枯草（5，10 g／kg），仙茅（5，10 g／kg）,辛夷（5，10 g／kg）等十五種常用中藥材之50%乙醇抽提液，並對大白鼠進行血液常規檢驗、臨床生化、自發性運動行為、及整體之亞急性毒性之觀察。其臨床生化結果顯示：車前子、馬兜鈴、牛膝、青箱子、山豆根、仙茅等影響全身營養標準之參考值，如血漿總蛋白質，血清白蛋白；地骨皮、茯苓、厚朴、前胡、山豆根、天南星、夏枯草、辛夷等影響蛋白質代謝最終產物BUN；車前子、厚朴、木通、牛膝、天南星、威靈仙、夏枯草、仙茅等影響肝功能SGPT值；車前子、厚朴、馬兜鈴等影響腎功能creatinine值。於實驗結束解剖發現車前子、地骨皮、茯苓、馬兜鈴、木通、青箱子、前胡、山豆根、天南星、威靈仙、夏枯草、仙茅、辛夷等導致心、肝、肺、或腎臟器之組織重或含水量等病理指標之改變。血液學評估發現地骨皮、馬兜鈴、木通、青箱子、威靈仙、辛夷等影響白血球總數。於行為毒理評估發現車前子、茯苓、牛膝、青箱子、山豆根、天南星、仙茅等導致中等至強度之抑制自發性運動作用；而前胡、夏枯草卻可導致中等之自發性運動興奮作用。於此連續十五天之亞急性毒性實驗中，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。"

As befitting the esoteric designation of 'the art of healing', traditionally the development of professional acumen in the practice of traditional Chinese medicine relies heavily on years of accumulated clinical observations. The shortcomings are the relative lack of hard evidence, systemic documentation and uniformity in interpretation, which result in the unfortunate aura of mystique and reluctance in general acceptance. Relatively little is known about the toxicological profiles of the 400-commonly-used Chinese medicinal drugs listed in the 'Standard of Chinese Drugs, ROC'. The present projected, entitled 'the evaluation of the subacute toxicity of commonly used Chinese medicinal drugs', of which the present report was a part, was initiated to provide experimental evidence to support or refute vague claims in traditional Chinese pharmacopoeias and reference for future studies. The subacute toxicological and behavioral effects of 50% ethanol crude extracts of the following traditional Chinese medicinal drugs administered in single dosage (5, 10 g/kg, p.o., per day for 14 days) were quantitatively evaluated: 1. Cheqianze 2. Digupi 3. Puling 4. Houpo 5. Madouling 6. Mutong 7. Niuxi 8.Qingxiangzi 9. Qianhu 10. Shandougen 11. Tainnanxing 12. Weilingxian 13. Xiakucao 14. Xianmao and 15. Xinyi, respectively. The maximal tolerable doses ranging from 1/10 to 1/5 of LD50 were used as the reference dosages in the subacute experiments. The following results were found: the whole body nutrient standard reference values such as plasma total protein, or serum albumin content were affected by Cheqianze, Madouling, Niuxi, Qingxiangzi, Shandougen, & Xianmao. The reference standard for protein catabolism such as BUN was affected by Digupi, Puling, Houpo, Qianhu, Shandougen, Tiannanxing, Xiakucao, and Xinyi. The liver standard functional test such as SGPT showed changes elicited by Cheqianze, Houpo, Mutong, Niuxi, Tainnanxing, Weilingxian, Xiakucao, and Xianmao. The kidney standard functional test such as creatinine were affected by Cheqinze, Houpo, and Madouling. Pathological references standards of tissue such as the net tissue weight or water content of heart, liver, lung or kidney after post-mortem examination were affected by Cheqianze, Digupi, Puling, Madouling, Mutong, Qingxiangzi, Qianhu, Shandougen, Tainnanxing, Weilingxian, Xiakucao, Xianmao, and Xinyi. Hematological assessment showed that total WBC counts were affected by Digupi, Madouling, Mutong, Qingxiangzi, Weilingxian, and Xinyi. In behavioral toxicological evaluations, it was found that Cheqianze, Puling, Niuxi, Qingxiangzi, Shandougen, & Tiannanxing, & Xianmao elicited a moderate to marked degree of inhibition, while Qianhu, & Xiakucao elicited moderate degree of stimulation on the locomotor activity when compared with control group. No evidence of any irreversible visible pathological damage or mortality attributable to any of the test drugs occurred during the experimental period of 15 days. It is anticipated that these retrospective studies on subacute toxicity will provide reliable toxicological profiles of those Chinese drugs approved by the National Health Insurance Program in R. O. C. 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，台灣中藥材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，以印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當亞急性毒牲最大耐受量之參考劑量下；本實驗觀察連續口服十四天（每日一劑）車前子（5，10 g／kg），地骨皮（5，10 g／kg），茯苓（5，10 g／kg），厚朴（5，10 g／kg），馬兜鈴（5，10 g／kg），木通（5，10 g／kg），牛膝（5，10 g／kg），青箱子（5，10 g／kg），前胡（5，10 g／kg），山豆根（5，10g／kg），天南星（5，10 g／kg），威靈仙（5，10 g／kg），夏枯草（5，10 g／kg），仙茅（5，10 g／kg）,辛夷（5，10 g／kg）等十五種常用中藥材之50%乙醇抽提液，並對大白鼠進行血液常規檢驗、臨床生化、自發性運動行為、及整體之亞急性毒性之觀察。其臨床生化結果顯示：車前子、馬兜鈴、牛膝、青箱子、山豆根、仙茅等影響全身營養標準之參考值，如血漿總蛋白質，血清白蛋白；地骨皮、茯苓、厚朴、前胡、山豆根、天南星、夏枯草、辛夷等影響蛋白質代謝最終產物BUN；車前子、厚朴、木通、牛膝、天南星、威靈仙、夏枯草、仙茅等影響肝功能SGPT值；車前子、厚朴、馬兜鈴等影響腎功能creatinine值。於實驗結束解剖發現車前子、地骨皮、茯苓、馬兜鈴、木通、青箱子、前胡、山豆根、天南星、威靈仙、夏枯草、仙茅、辛夷等導致心、肝、肺、或腎臟器之組織重或含水量等病理指標之改變。血液學評估發現地骨皮、馬兜鈴、木通、青箱子、威靈仙、辛夷等影響白血球總數。於行為毒理評估發現車前子、茯苓、牛膝、青箱子、山豆根、天南星、仙茅等導致中等至強度之抑制自發性運動作用；而前胡、夏枯草卻可導致中等之自發性運動興奮作用。於此連續十五天之亞急性毒性實驗中，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。