丹參萃取物之開發與應用(I)：丹參酮IIA之物性與動力學探討

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標題:	丹參萃取物之開發與應用(I)：丹參酮IIA之物性與動力學探討 Development and Utilization of The Extract of Salvia miltiorrhiza Bge. (I)： Studies on The Physical Properties and Pharmacokinetics of Tanshinone IIA
作者:	林南海 Nan-hei Lin
貢獻者:	楊竹茂嘉南藥理科技大學：生物科技研究所
關鍵字:	丹參丹參酮基原油/水分配係數藥物動力學排除半衰期首度效應 Tanshinone IIA oil/water partition coefficients (log P) Salvia miltiorrhiza origin elimination pharmacokinetics first pass-effect half-life
日期:	2006
上傳時間:	2008-11-24 17:01:05 (UTC+8)
摘要:	丹參萃取物之開發與應用(I)：丹參酮IIA之物性與動力學探討丹參藥材基原鑑定，自市面購買四批不同來源之丹參藥材，經組織切片切面重點顯微性狀鑑別，觀察到有木栓層、皮層、形成層及導管之形狀，另以薄層層析分析(TLC)、高壓液體色層分析指紋圖譜(HPLC)進行基原之鑑別，其結果與文獻資料紀載比對，顯示四批藥材均為丹參無誤。利用HPLC鑑定四批藥材，以乙醇／正己烷（1:1）萃取丹參中丹參酮I（Tanshinone I）及丹參酮IIA（Tanshinone IIA）之含量，分別為第一批和第二批藥材總含量為0.319％及0.082％（因量少兩批合併）；第三批總含量分別為0.49％及0.58％；第四批總含量分別為0.51％及0.74％。丹參酮IIA之油/水分配係數（log P）之測定，以傳統振搖法、逆向薄層層析法（RP-TLC）、高壓液相層析法（HPLC）方法測定，結果分別為1.28、5.015及4.741，以傳統振搖法所得之結果偏低，因為此種方法僅適用於極性較高的化合物，而丹參酮IIA為低極性分子。丹參酮IIA之藥物動力學探討：本實驗之目的旨在研究丹參酮IIA在動物體內之動態，包括吸收、分佈、代謝及排除，以了解口服丹參酮IIA後，存留動物體內之時間。Tanshinone IIA的吸收半衰期約為14分鐘，顯示其口服吸收相速率很快，然而其排除相半衰期約為2.3小時，屬於短效藥物，且血中最高濃度僅約為3.7μg/ml，究其原因可能由於遭受較大的首度效應(first pass effect)所致。從以上各種實驗結果顯示出，將來Tanshinone IIA開發成穿皮吸收的製劑將是合理的，而且可期待的，因為可以防阻首途效應，延長半衰期以及穩定的血中濃度以達到最佳的治療效果。 Development and Utilization of The Extract of Salvia miltiorrhiza Bge. (I)： Studies on The Physical Properties and Pharmacokinetics of Tanshinone IIA The present research was firstly carried on the identification of origins of four batches of the Salvia miltiorrhiza Bge. crude drugs that were purchased from local markets. The cross sections of plant tissues were microscopically examined and the structures including cork layers, cortex layers, cambia and vessels were observed; analyses of the indicating components and fingerprint spectra were subsequently performed, all the results were identical to those found over the authentic samples and the records in the scientific literature, indicating that the four batches of crude drugs were indeed salvia miltiorrhiza. The four batches of crude drugs were then consecutively extracted and partitioned with 50% alcohol and n-hexane, respectively. The contents of tanshinone I and IIA in the final extracts were quantitatively analyzed with RP-HPLC method and found approximately to be 0.32% and 0.08% (total contents in the first and second batches), 0.49% and 0.58% (the third batch) and 0.51% and 0.74% (the forth batch), respectively. In order to obtain the absolute datum of lipophilicity of Tanshinone IIA, as the reference for the further preparation of transdermal dosage form, the oil/water partition coefficients (log P) was determined by traditional flask-shaking, RP-TLC and RP-HPLC methods, and found to be 1.28, 5.015 and 4.741, respectively. A relatively low value was obtained through the flask-shaking method that seemed not suitable for the determination of the highly lipophilic compounds. Oppositely, similar higher log P value was obtained either from RP-TLC or RP-HPLC method, indicating that Tanshinone IIA is characterized with very high lipophilicy. Finally, in order to learn the pharmacokinetics of oral administration of Tanshinone IIA, the parameters including Ke, T1/2, Cmax, AUC0-t, etc. were estimated using one-compartment model under the aid of Nonlin software, after analyzing the plasma concentrations of Tanshinone IIA by HPLC. The results showed that the absorption half-life was 14 minutes, suggesting that Tanshinone IIA could be easily absorbed after oral administered; however, the elimination half-live was found to be 2.3 hours, demonstrating that it could be subjected a great first pass-effect before entering into blood circulation. In conclusion, the results obtained from above experiments suggested that it would be reasonable and expectable to develop transdermal preparations, by which the first pass-effect could be prevented, and a prolonged half-lives and stable plasma levels could be expected.
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