| 摘要: | 目前臺灣中醫臨床上使用之中藥劑型主要為傳統水煎劑及濃縮製劑。其中濃縮製劑為全民健保給付的劑型，因此中藥濃縮製劑之應用佔健保費支出比率相當可觀。然而自從中醫界使用濃縮製劑以來，鮮見有評估濃縮製劑與傳統水煎劑在療效上相等性之研究。故臨床中醫師在使用濃縮製劑時，似無一定的準則與客觀依據。若僅依據藥廠之建議劑量是否可達與傳統水煎劑相等的口服吸收率與療效，是一個值得關注的研究課題。三黃瀉心湯出於金匱要略，包含大黃、黃連及黃芩，其苦寒瀉火，為治療熱盛吐衂証要方，為一常用之中藥方劑。近代藥理學研究顯示，三黃瀉心湯具抗病原微生物之作用，可用於急性肺炎、急性化膿性扁桃腺炎及眼部炎症等疾病，另外尚有治療缺血性腦血管疾病、鎮靜、降壓、降血脂、抑制大鼠胃潰瘍形成、保護胃黏膜、抑制胃酸分泌、抗發炎等作用。且此方目前亦於台灣進行抗癌之臨床試驗中。另外，組成此方之藥物大黃、黃連及黃芩均為富含多酚類成分之中藥，此些藥物及其成分亦多具抗菌、抗腫瘤、抗病毒、抗發炎、抗氧化等活性，因此三黃瀉心湯應具開發成為治療癌症、心血管疾病、抗SARS等相關疾病藥物之潛力。本計畫於93年度正進行三黃瀉心湯水煎劑及濃縮製劑，其中所含aloe-emodin、emodin、chrysophanol、rhein、baicalin、baicalein、wogonin、berberine等活性成分含量之分析。並以大鼠為實驗動物，進行動物口服三黃瀉心湯水煎劑與市售濃縮製劑後，藥物吸收之藥物動力學參數分析，藉以比較濃縮方劑與水煎劑中活性指標成分於大鼠體內之相對生可用率；在94年度的計畫中，將以第一年動物試驗所得之相關數據研究結果為基礎，並在「研究用人體檢體採集與使用注意事項」及「藥品生體可用率暨生體相等性試驗基準」等原則規範下，以健康志願者進行「建立人體口服水煎方劑與濃縮方劑中活性指標成分相對生可用率之規劃研究」，藉以比較傳統水煎劑與濃縮製劑兩種劑型代謝動力學之異同。並擬利用此兩年之研究結果，進一步評估人體與動物實驗數據結果之相關性，作為後續相關研究試驗模式之選擇參考。本計畫之目的，在希望透過此一規劃性研究，建立中藥方劑生體可用率（Bioavailability）及生體相等性（Bioequivalence）試驗之模式，以了解中藥方劑不同劑型於人體內之生體歷程，提供臨床應用時，藥物發揮最佳療效之給藥間隔、劑型、劑量決定等之參考依據，同時亦可提供與臨床療效相關性更高之中藥製劑品質評估模式，做為健保局藥品給付決策之參考，而期能加速中醫藥現代化之腳步。
At present, traditional decoction and commercial herbal extract are two dosage forms used in clinical Chinese medicine. While the only dosage form that can covered by Bureau of National Health Insurance is commercial herbal extract and thus costs a considerable part of National Health Insurance expenses. However, there are no reports concerning the bioequivalence between these two dosage forms. In order to provide the data base for clinical application, this study attempts to assess the bioequivalence between herbal concentrate and traditional decoction, and at least six commercial herbal extract will be purchased from the market. The contents of San Huang Xie Jin Tang (aloe-emodin, emodin, chrysophanol, rhein, baicalin, baicalein, wogonin and berberine) will be determined by HPLC methods established in our laboratory. The administrations of traditional decoction and commercial herbal extract will be carried out in a crossover design with one week interval for washout. Urine samples withdrawed at predetermined time points post administration are assayed for the concentrations of aloe-emodin, emodin, chrysophanol, rhein, baicalin, baicalein, wogonin and berberine and its conjugate metabolites with using our developed method, respectively. WINNONLIN is used for pharmacokinetic parameters and bioavailability calculations. Statistical tests are used to compare the difference in bioavailabilities of aloe-emodin, emodin, chrysophanol, rhein, baicalin, baicalein, wogonin and berberine and its conjugate metabolites between traditional decoction and commercial herbal extract, respectively. Hopefully, the results of this project could provide useful information for clinical application of Chinese medicine. Moreover, it could also raise the necessity for the research and improvement of manufacturing of Chinese herbal concentrates. |
