臺灣博碩士論文加值系統

最近國內外人士講究流行瘦身美容問題，特別是愛美的女性，因此常有攝食以減肥為目的之中、西藥品，因而常發生中毒病發症狀，更有因食用減肥菜而導致肺水腫中毒症狀。最近國外如比利時、加拿大、澳洲、德國、日本、英國和美國，都曾報導有人因食用中國藥草所生產之製劑而發生腎臟癌、泌尿系統癌症等，並命名為中藥腎病變（Chinese herb nephrophathy, CHN），同時指出此種中藥腎病變係因減肥藥中誤用中藥材料廣防己所致，此乃因廣防己含有馬兜鈴酸（Aristolochic acid, AA），具有腎臟毒。
為了了解一般中藥製劑以及中藥材中馬兜鈴酸(Aristolochic acid)之含量，乃研發分析馬兜鈴酸Ⅰ（Aristolochic acidⅠ, AAⅠ）及馬兜鈴酸Ⅱ（Aristolochic acidⅡ, AAⅡ）之方法。發現以高效能液相層析儀（high performance liquid chromatography , HPLC）利用ODS逆相層析管，溶媒系統0.3% ammonium carbonate / acetonitrile （75:25，V/V，pH 9.3），在10分鐘內即可有效分離檢測出2種成分，且其回收率可高達90%以上。實驗進一步分析由基隆地區所採集廣防己和馬兜鈴兩種中藥材以及由榮民總醫院所提供患有腎臟病之中藥減肥劑，結果發現廣防己含有馬兜鈴酸Ⅰ為437- 668 ppm，馬兜鈴酸Ⅱ為143- 414 ppm；馬兜鈴含有馬兜鈴酸Ⅰ為<1- 83 ppm，馬兜鈴酸Ⅱ為<1-115ppm；而中藥減肥劑之15個樣本中測出11個含有馬兜鈴酸之成分，其含量馬兜鈴酸Ⅰ為<1-39 ppm，馬兜鈴酸Ⅱ為<1-124 ppm，故推測台灣市售中藥減肥劑之主要藥材並非廣防己。其後，發現使用0.3% ammonium carbonate / acetonitrile (75:25，V/V/ pH 7.5)在20分鐘可有效分離馬兜鈴酸Ⅰ和Ⅱ，同時可改善層析管之使用期限。馬兜鈴酸Ⅰ和Ⅱ之混合物，經以雄性和雌性大白鼠以口胃管方式飼養4週後，發現雌性大白鼠之體重減輕，肝體比上升，腎體比下降，生化功能指標如creatinine、BUN上升，然而對雄性大白鼠之傷害不大，顯示馬兜鈴酸之毒作用對雌性大白鼠遠大於雄性大白鼠。

Recently people everywhere on earth talk about the question of losing weight, especially women loving beauty. They usually take of Chinese herbs and medicines for purpose of reducing weight. Therefore, the poisoning has often happened, such as the hydrophilic pneumonitis found in some people to eat obesity vegetable. Lately, someone in the foreign countries such as Belgium, Canada, Australia, Germany, Japan, England and the United States of America have been reported to take Chinese herb products resulting in kidney cancer and urinary system cancer which were named Chinese herb nephrophathy (CHN). The CHN disease was caused by misusing obesity vegetables such as Aristolochic fungchi which contains a nephrotoxic agent, aristolochic acid.
To investigate the level of aristolochic acid in Chinese herbs, and Chinese herb medicines, a HPLC procedure with silica gel RP-18 reversed-phase column for the determination of aristolochic acids I, II in the medicinal plants and slimming products was developed. The mobile system 0.3% ammonium carbonate solution-acetonitrile (75:25, v/v) with pH 9.3 was the optimal buffer to clearly separate aristolochic acids I, II within 10 min. The recovery of aristolochic acids I, II in the medicinal plants and slimming products was higher than 90% by extracting with methanol and purifying through a PHP-LH-20 column. The major component was aristolochic acid I in Aristolochia fangchi and the level ranged from 437 to 668 ppm. But aristolochic acid II was the major component in Aristolochia contorta and its range was <1-115ppm. Eleven out of fifteen samples of slimming pills and powders contained aristolochic acids I and/or II. The major component in the slimming products was aristolochic acid II and the level ranged from <1-148 ppm. It may indicate that slimming products were not mainly made of A. fangchi. Later, the same mobile system with pH 7.5 was better optimal buffer to clearly separate AAⅠand AAⅡ within 20 min. Meanwhile , this buffer could improve the usable period of column.
Furthermore, the effect of aristolochic acid in female and male rats was investigated. The results demonstrated that the level of creatinine, BUN, Na+ and K+ in the kidney and the activities of ALT and AST in plasma of female rats were increased with increasing dose of aristolochic acid. But the toxicity of aristolochic acid in male rats was not found. Therefore, the toxicity of aristolochic acid in female rats was more serious than in male.

中文摘要…………………………………………………………….…….1
英文摘要…………………………………………………………………..2
第一章文獻整理………………………………………………………4
一、馬兜鈴酸之基本特性………………………………………...5
二、攝食馬兜鈴酸所造成的病變………………………...………7
三、馬兜鈴酸致癌之機制………………………………..……….9
四、二烯丙基硫對馬兜鈴酸造成癌症之影響………………….12
五、處方藥材中馬兜鈴酸之含量……………………………….12
六、中藥藥材中馬兜鈴和廣防己之介紹……………………….13
七、馬兜鈴屬植物生物活性之研究概況……………………….16
第二章馬兜鈴酸在中藥材及中藥製劑之檢測……………………...22
一、前言………………………………………………………..…23
二、材料與方法…………………………………………………..24
三、結果……………………………………………………….….28
四、討論……………………………………………………….….30
五、圖表…………………………………………………………..
第三章馬兜鈴酸檢測方法之改良…………………………………...32
一、前言………………………………………………………..…33
二、材料與方法…………………………………………………..34
三、結果……………………………………………………….….36
四、討論……………………………………………………….….38
五、圖表…………………………………………………………...
第四章 馬兜鈴酸對大白鼠之毒理作用…………………………...……39
一、 前言……………………………………………………...……40
二、 材料與方法……………………………………………….…..41
三、 結果………………………………………………………..….48
四、 討論………………………………………………………..….52
五、 圖表…………………………………………………………..

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