- 學位論文
中藥標準湯劑中白芍指標成分之移行率探討
The Turnover Rates of Marker Substances from Paeonia lactiflora in Traditional Chinese Medicine Decoctions
摘要
白芍為毛茛科(Ranunculaceae)植物芍藥Paeonia lactiflora Pall.之去皮乾燥根，為常用中藥材之一。依據臺灣中藥典規範，合格之白芍藥材所含芍藥苷(paeoniflorin)不得少於1.0%，然而藥典中尚未規範含白芍之中藥濃縮製劑指標成分含量標準。本論文以高效液相層析法分析定量芍藥苷(paeoniflorin)、芍藥內酯苷(albiflorin)、苯甲酸(benzoic acid)及沒食子酸(gallic acid)等四個白芍指標成分，於芍藥甘草湯、四物湯及四逆散等三種含白芍之中藥基準方各湯劑中的含量變化、移行率及含量比之差異。分析結果顯示：(1)芍藥苷於各湯劑間之移行率介於73.8-86.1%之間、含量比分別為芍藥甘草湯89.5%、四物湯89.1-101.8%及四逆散88.6-97.9%；(2)芍藥內酯苷於各湯劑間之移行率介於77.8-97.6%之間、含量比分別為芍藥甘草湯89.4%、四物湯82.0-99.0%及四逆散94.6-113.6%；(3)苯甲酸於各湯劑間之移行率介於154.7-325.0%之間、含量比分別為芍藥甘草湯77.3%、四物湯45.1-97.3%及四逆散90.0-171.6%；(4)沒食子酸於各湯劑間之移行率介於106.9-177.9%之間、含量比分別為芍藥甘草湯84.6%、四物湯67.6-90.0%及四逆散89.3-96.8%。四個指標成分於三種方劑之含量比差異範圍由小至大依序為芍藥苷、芍藥內酯苷、沒食子酸及苯甲酸。繼而利用檢品溶液pH值及植物化學成分含量，探討對指標成分含量比之影響，結果發現：(1)檢品溶液pH值會影響苯甲酸及沒食子酸之含量比，但不影響芍藥苷及芍藥內酯苷；(2)檢品溶液粗多醣含量可能會影響芍藥內酯苷、苯甲酸及沒食子酸之含量比；(3)檢品溶液總多酚及縮合型單寧含量可能會影響苯甲酸之含量比；(4)檢品溶液總皂苷含量可能會影響苯甲酸及沒食子酸之含量比。綜上，芍藥內酯苷、苯甲酸及沒食子酸於各標準湯劑中之含量比變動較大，較不適宜作為濃縮製劑品質管制之指標成分，而芍藥苷之含量比較不受配伍藥共煎之影響，適合當做濃縮製劑品質管制之指標成分。 另進行市售白芍、芍藥甘草湯、四物湯及四逆散濃縮製劑之指標成分定量，結果顯示：(1)苯甲酸於四種市售濃縮製劑之含量差距最大，芍藥內酯苷、沒食子酸及芍藥苷則較小；(2)市售四逆散濃縮製劑之白芍指標成分含量差距最小，市售白芍及四物湯濃縮製劑之含量差距則較大。若以藥典規範之最低芍藥苷含量(1.0%)及本論文之芍藥苷移行率結果來計算濃縮製劑指標成分規格範圍之下限值，其一日量濃縮製劑之芍藥苷含量應不少於0.5%，且四種市售濃縮製劑之含量結果約70%通過，顯示以固定之移行率(70%)制定芍藥甘草湯、四物湯及四逆散等濃縮製劑指標成分含量規格範圍之下限值應屬可行。
並列摘要
Peony root (PR), one of the most well-known medicinal material, is the peeled and dried root of Paeonia lactiflora Pall. (Fam. Ranunculaceae). According to Taiwan Herbal Pharmacopoeia, paeoniflorin content in PR should not be less than 1.0%. However, there is no standard for the quantitation of analytical markers in PR related concentrated extract preparations (CEPs). In this study, three formulae, Shao Yao Gan Cao Tang (SYGCT), Si Wu Tang (SWT) and Si Ni San (SNS), in which PR serves as a basic ingredient were selected. Four makers - paeoniflorin, albiflorin, benzoic acid and gallic acid were quantitated by HPLC, then computed the turnover rates and concentration rates in all three decoctions. The turnover rates of paeoniflorin, albiflorin, benzoic acid and gallic acid in decoctions were 73.8-86.1%, 77.8-97.6%, 154.7-325.0% and 106.9-177.9% respectively. The concentration rates of paeoniflorin in SYGCT, SWT and SNS were 89.5%, 89.1-101.8% and 88.6-97.9%, respectively. For (1) albiflorin, (2) benzoic acid and (3) gallic acid the concentration rates in SYGCT, SWT and SNS were (1) 89.4%, 82.0-99.0% and 94.6-113.6%, (2) 77.3%, 45.1-97.3% and 90.0-171.6%, (3) 84.6%, 67.6-90.0% and 89.3-96.8%, respectively. Paeoniflorin displayed the lowest concentration rates which indicated the great stability. The followings were albiflorin, gallic acid and benzoic acid. Also, this study found the pH and the contents of phytochemicals of samples varied the concentration rates. The pH significantly altered the concentration rates of benzoic acid and gallic acid, but not albiflorin and paeoniflorin. Total polysaccharides influenced the concentration rates of albiflorin, benzoic acid and gallic acid. Total polyphenols and condensed tannins modified the concentration rates of benzoic acid. Total saponins also changed the concentration rates of benzoic acid and gallic acid. Therefore, the fluctuating concentration rates of albiflorin, benzoic acid and gallic acid made them poor candidates to be selected as quality control markers. Paeoniflorin was thus the most suitable analytical marker for PR related CEPs. In this study, quantitative analysis for marker components in four commercial CEPs (PR, SYGCT, SWT and SNS) were conducted. The results showed benzoic acid significantly fluctuated while albiflorin, benzoic acid and paeoniflorin performed relatively stabilities. SNS CEPs were seen small variations in four markers compared to PR, SYGCT and SWT. According to the turnover rates and content (1.0%) of paeoniflorin in PR regulated in Taiwan Herbal Pharmacopoeia, this study suggested a 70% turnover rate and a 0.5% of paeoniflorin content that could be set as lower limits for the standard of PR related CEPs.