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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘子明(Tzu-Ming Pan) | |
| dc.contributor.author | Ji-Syun Sun | en |
| dc.contributor.author | 孫基訓 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:20:00Z | - |
| dc.date.available | 2020-08-28 | |
| dc.date.copyright | 2015-08-28 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-17 | |
| dc.identifier.citation | 行政院衛生福利部。2012。食品化學檢驗方法之確效規範。
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52601 | - |
| dc.description.abstract | 紅麴色素為紅麴次級代謝物之一，近年來有文獻指出紅麴之黃色素 monascin 與 ankaflavin 具有良好的生理活性功能，例如免疫抑制的效果，而 monascin 亦被證實具有抗發炎以及抑制皮膚癌的作用；ankaflavin 則可誘發癌細胞走向細胞凋亡而具有抗癌的效果，為極具保健功效潛力的天然化合物。Monascin 與 ankaflavin 具多種生理功效，然而目前對於 monascin 與 ankaflavin 在動物模式之藥物動力學研究仍然缺乏，故本研究乃探討 monascin 與 ankaflavin 於大鼠模式下的藥物動力學、組織分佈與排除情形，來瞭解兩物質之藥物動力學參數及生物可利用率、尋找與確認其標靶器官、尋找新的作用途徑以及體內的積蓄情形。本研究藥物動力學試驗的結果顯示，以管餵方式給予大鼠 150 mg/kg BW monascin 或 ankaflavin 後，以極致效能液相層析串聯質譜儀 (ultra performance liquid chromatography-tandem mass spectrometer, UPLC-MS/MS) 在血漿測得之血漿最高濃度 Cmax 分別為 0.62 ± 0.08 μg/mL 及 0.95 ± 0.28 μg/mL，半衰期分別為 230.64 ± 104.54 min 及 184.13 ± 57.99 min。以股靜脈注射給予大鼠 15 mg/kg BW 之 monascin 或 ankaflavin 後，在血漿測得之 Cmax 分別為 4.25 ± 3.91 μg/mL 及 4.55 ± 4.23 min，半衰期分別為 123.44 ± 40.96 min 及 78.91 ± 42.54 min。經公式計算後得 monascin 與 ankaflavin 之口服生物可利用率分別為 15.67% 與 20.36%。組織分佈試驗結果顯示，monascin 與 ankaflavin 皆可分佈至大腦、心臟、肺臟、肝臟、腎臟、胰臟、胃、腸道及脂肪。在腦中可發現 monascin 與 ankaflavin 的存在，推測兩化合物皆可通過血腦障壁。管餵後 0.5 小時在腸胃道即含有大量的 monascin 與 ankaflavin，尤其以胃中含量最高。排除試驗結果顯示，糞便為 monascin 與 ankaflavin 的主要排除途徑。管餵後 12－16 小時為 monascin 及 ankaflavin 於糞便中之主要排除期。管餵後 48 小時內，分別有給予劑量的 24.70% 及 1.10% 以原型態型式經由糞便排出體外。藉由本研究瞭解 monascin 與 ankaflavin 於大鼠模式下之藥物動力學參數、口服生物可利用率、組織臟器分佈與排除情形，可提供未來臨床應用的參考。 | zh_TW |
| dc.description.abstract | Recently, the research of Monascus-fermented secondary metabolites, monascin and ankaflavin, was gradually popular. The functions of monascin and ankaflavin include anti-inflammation, cancer prevention, hypolipidemic effect, blood glucose regulation and reducing the steatosis effect. There are many bioactivities of monascin and ankaflavin, however, the information on pharmacokinetics, distribution and excretion of monascin and ankaflavin is still absent. The aim of this study was to investigate the pharmacokinetics, distribution and excretion characteristics of monascin and ankaflavin in Sprague-Dawley rats after intravenous or oral administration. After the UPLC-MS/MS analysis, the pharmacokinetic study showed that after oral administration of 150 mg/kg BW of monascin or ankaflavin, the pharmacokinetic parameter Cmax of monascin and ankaflavin were 0.62 ± 0.08 μg/mL and 0.95 ± 0.28 μg/mL, respectively. T1/2 were 230.64 ± 104.54 min and 184.13 ± 57.99 min respectively. After intravenous injection of 15 mg/kg BW of monascin or ankaflavin, results showed that Cmax were 4.25 ± 3.91 μg/mL and 4.55 ± 4.23 min, T1/2 were 123.44 ± 40.96 min and 78.91 ± 42.54 min, respectively. The bioavailability of monascin and ankaflavin were 15.67% and 20.36%, respectively. The distribution study showed that monascin and ankaflavin were distributed widely in various tissues. After oral administration of monascin or ankaflavin in a dose of 150 mg/kg, they could be found in brain, heart, liver, lung, kidney, pancreas, stomach, intestine and fat. Higher concentrations of monascin and ankaflavin were found in the gastrointestinal tract after oral administration for half hours. The excretion study showed that after oral administration of monascin or ankaflavin, the fecal excretion was found to be the major excretion route of these two compounds. The major excretion period of monascin and ankaflavin occurred in 12-16 hours after oral administration. Furthermore, 24.70% of the oral administered monascin was excreted as unconverted form in fecal excretion and ankaflavin was 1.10%. This study improved the understanding of the tissue distribution and excretion of monascin and ankaflavin in rats and may provide a meaningful basis for clinical application of these bioactive compounds. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:20:00Z (GMT). No. of bitstreams: 1 ntu-104-R02b22013-1.pdf: 5196369 bytes, checksum: 35dd4d408bd3317d6e1698521c65232c (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 目錄
縮寫表…………………………………………………………………………………… III 中文摘要………………………………………………………………………………… VI 英文摘要………………………………………………………………………………… VIII 目錄……………………………………………………………………………………… X 圖目錄…………………………………………………………………………………… XII 表目錄…………………………………………………………………………………… XV 第壹章 文獻回顧…………………………………………………………………….…. 1 ㄧ、紅麴菌……………………………………………………………………………… 1 (一) 紅麴菌之特性……………………………………………………………………… 1 (二) 紅麴固態發酵……………………………………………………………………… 1 (三) Monascus purpureus NTU 568 紅麴菌株於預防醫學之相關研究與應用............ 1 二、紅麴菌之二次代謝產物……………………………………………….…………... 8 (ㄧ) 紅麴二次代謝產物簡介…………………………………………………………... 8 (二) 紅麴二次代謝產物 monascin 與 ankaflavin………………………………......... 11 (三) 紅麴二次代謝產物 monascin 與 ankaflavin 之生理功效…………….……….. 13 三、藥物動力學 (pharmacokinetics)............................................................................. 15 (一) 藥物動力學簡介…………………..……………………………………………….. 15 (二) 藥物動力學參數……………….....………………………………………………... 20 (三) 生物可利用率 (bioavailabilty, BA).......................................................................... 22 (四) 植物二次代謝物之藥物動力學研究……………………………………………… 24 第貳章 研究目的與實驗架構………………………………………………………….. 27 一、 研究目的…………………......…………………………………………………... 二、 實驗架構…………………......…………………………………………………... 27 27 第參章 材料與方法…………………………………………………………………….. 33 ㄧ、藥品試劑…………………………………………………………………………… 33 二、儀器設備…………………………………………………………………………… 33 (一) 一般儀器設備………………….…………………………………………………... 33 (二) 化學分析相關儀器設備………………….............………………………………... 33 (三) 資料分析軟體……………….....…………………………………………………... 34 三、實驗方法…………………………………………………………………………… 34 (一) Monascin 與 ankaflavin 藥物動力學參數測定…………………………………. 34 (二) Monascin 與 ankaflavin 於大白鼠之組織分佈試驗……………………….…… 39 (三) Monascin 與 ankaflavin 於大白鼠的排除試驗…………………………………. 41 第肆章 結果與討論…………………………………………………………………….. 45 一、以大鼠模式探討 monascin 與 ankaflavin 之藥物動力學參數…….................. 45 (一) 實驗材料 monascin 與 ankaflavin 之與純度分析與質譜圖……………............ 45 (二) Monascin 與 ankaflavin 分析方法之確效……………………………................. 50 (三) 血漿中 monascin 與 ankaflavin 之藥物動力學參數及口服生物可利用率…… 56 二、 以大鼠模式探討 monascin 與 ankaflavin 之分佈試驗……………………….. 76 (一) Monascin 與 ankaflavin 分析方法之確效……………………............................. 76 (二) Monascin 與 ankaflavin 於大鼠各組織臟器之萃取回收率試驗…..................... 79 (三) Monascin 與 ankaflavin 於大鼠各組織臟器之分佈情形………………………. 82 三、以大鼠模式探討 monascin 與 ankaflavin 之排除試驗………………………… 99 (一) Monascin 與 ankaflavin 於大鼠之尿液排除結果………………………………. 99 (二) Monascin 與 ankaflavin 於大鼠之糞便排除結果………………………………. 100 第伍章 結論…………………………………………………………………………….. 110 第陸章 參考文獻……………………………………………………………………….. 111 圖目錄 圖 1-1 紅麴米之生產..................................................................................................... 2 圖 1-2 紅麴菌產生之色素結構..................................................................................... 10 圖 1-3 紅麴色素之橘色素 rubropunctatin、黃色素 monascin、紅色素 rubropunctamine 及水溶性色素之推測生合成途徑…………..………................... 12 圖 1-4 口服投予藥物後血漿中藥物濃度對時間之曲線…….……………………… 21 圖 1-5 藥物之首渡效應…............................................................................................. 23 圖 2-1 本論文研究架構................................................................................................. 29 圖 2-2 藥物動力學試驗研究架構……………………………………………………. 30 圖 2-3 組織分佈試驗研究架構………...……….......................................................... 31 圖 2-4 排除試驗研究架構……………………………………………………………. 32 圖 4-1 本實驗使用之 monascin 標準品之 HPLC 層析圖譜……………………... 46 圖 4-2 本實驗使用之 ankaflavin 標準品之 HPLC 層析圖譜…………………….. 47 圖 4-3 Monascin 之層析圖 (ESI+－MS)..................................................................... 48 圖 4-4 Ankaflavin 之層析圖 (ESI+－MS)…………………………………………... 49 圖 4-5 Monascin 之基質效應層析圖………………………………………………. 51 圖 4-6 Ankaflavin 之基質效應層析圖……………………………………………... 52 圖 4-7 管餵大鼠 150 mg/kg BW 之 monascin 後 24 小時內，SD 大鼠血漿中之 monascin 濃度隨時間變化……………………………………………...………….. 58 圖 4-8 大鼠血漿中之 monascin 質譜圖……………………………………………. 59 圖 4-9 管餵大鼠 150 mg/kg BW 之 ankaflavin 後 24 小時內，SD 大鼠血漿中之 ankaflavin 濃度隨時間變化…………………………………….………………….. 60 圖 4-10 大鼠血漿中之 ankaflavin 質譜圖………………………………………….. 61 圖 4-11 管餵大鼠 monascin 後血漿中 monascin 濃度對時間關係圖…………… 62 圖 4-12 管餵大鼠 ankaflavin 後血漿中ankaflavin 濃度對時間關係圖………….. 64 圖 4-13 股靜脈注射大鼠 15 mg/kg BW 之 monascin 後 24 小時內，SD 大鼠血漿中 monascin 濃度隨時間變化之 UPLC-MS/MS 分析圖譜...…………… 69 圖 4-14 靜脈注射 monascin 後大白鼠血漿中 monascin 濃度對時間關係圖…… 70 圖 4-15 股靜脈注射大鼠 15 mg/kg BW ankaflavin 後 24 小時內，SD 大鼠血漿中 ankaflavin 濃度隨時間變化之 UPLC-MS/MS 分析圖譜…….......…………... 71 圖 4-16 靜脈注射 ankaflavin 後大白鼠血漿中 ankaflavin 濃度對時間關係圖…. 72 圖 4-17 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠心臟之 HPLC 圖譜………………...……......……………………………………………….. 83 圖 4-18 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠肝臟之 HPLC 圖譜……………...………......……………………………………………….. 84 圖 4-19 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠脾臟之 HPLC 圖譜……………………….....……………………………………………….. 85 圖 4-20 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠肺臟之 HPLC 圖譜……………...………......……………………………………………….. 86 圖 4-21 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠腎臟之 HPLC 圖譜………………………….....…………………………………………….. 87 圖 4-22 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠大腦之 HPLC 圖譜……………...………......……………………………………………….. 88 圖 4-23 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠胃之 HPLC 圖譜………………...……......……………………………………………….. 89 圖 4-24 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠腸道之 HPLC 圖譜……………...………......……………………………………………….. 90 圖 4-25 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠胰臟之 HPLC 圖譜……………………......…………………………………………...…….. 91 圖 4-26 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，大鼠脂肪之 HPLC 圖譜………………...……......……………………………………………….. 92 圖 4-27 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後在大鼠組織之分佈情形…………….…………......………………………………………………… 95 圖 4-28 物質通過血腦屏障之特性....…………………………………………..….… 98 圖 4-29 腎臟的藥物排泄..……………………………………………………………. 101 圖 4-30 管餵大鼠 150 mg/kg BW 之 monascin 後，在不同時間區段下糞便中 monascin 之排除比較………..…………….……………………………………….. 102 圖 4-31 管餵大鼠 150 mg/kg BW 之 ankaflavin 後，在不同時間區段下 ankaflavin 之糞便排除比較……...……………………………………...………….. 103 圖 4-32 管餵大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，各時間區段糞 便中 monascin 與 ankaflavin 之累積排除速率………………...………………… 105 圖 4-33 管餵 SD 大鼠 150 mg/kg BW 之 monascin 或 ankaflavin 後，各時間區段糞便中 monascin 與 ankaflavin 之排除情形………...……………………… 109 表目錄 表 1-1 藥物投予及吸收之部位………………………………………………………. 17 表 1-2 體內常見之一相及二相代謝反應……………………………………………. 19 表 3-1 以 UPLC-MS/MS 分析大鼠血漿中 monascin 與 ankaflavin 之沖提梯度 37 表 3-2 以 HPLC-PDA 分析 monascin 與 ankaflavin 之沖提梯度條件…………. 43 表 4-1 Monascin 之極致效能液相層析質譜儀分析方法於同日內及異日間之精密度及精確性……...………………………………………………………………… 54 表 4-2 Ankaflavin 之極致效能液相層析質譜儀分析方法於同日內及異日間之精密度及精確性……...……………………....……………………………….…........... 55 表 4-3 以管餵與靜脈注射 monascin 後大鼠血漿中 monascin 之藥物動力學參數……………………………….....…………………………….................................. 65 表 4-4 以管餵與靜脈注射 ankaflavin 後大鼠血漿中 ankaflavin 之藥物動力學參數………………………......………………….…………........................................ 66 表 4-5 Statin 類藥物之生物可利用率比較………………………………................. 74 表 4-6 Monascin 之高效液相層析分析方法於同日內及異日間之精密度及精確性……………………………….……………………………….................................. 77 表 4-7 Ankaflavin 之高效液相層析分析方法於同日內及異日間之精密度及精確性………………………….....………………………………...................................... 78 表 4-8 Monascin 於大鼠各組織臟器之回收率…………….………………….......... 80 表 4-9 Ankaflavin 於大鼠各組織臟器之回收率………………………………......... 81 表 4-10 管餵大鼠 150 mg/kg BW monascin 後於不同時間點各組織臟器 monascin 之分佈情形……………………….…....………………………...………. 93 表 4-11 管餵大鼠 150 mg/kg BW ankaflavin 後於不同時間點各組織臟器 ankaflavin 之分佈情形…………………………......………………………...……... 94 表 4-12 管餵大鼠 150 mg/kg BW monascin 後在不同時間區段下 monascin 於糞便之排除濃度、排除總量及佔餵食量之百分比……………..….……………… 106 表 4-13 管餵大鼠 150 mg/kg BW ankaflavin 後在不同時間區段下 ankaflavin 於糞便之排除濃度、排除總量及佔餵食量之百分比………..……………………. 107 | |
| dc.language.iso | zh-TW | |
| dc.subject | 紅麴 | zh_TW |
| dc.subject | monascin | zh_TW |
| dc.subject | ankaflavin | zh_TW |
| dc.subject | 藥物動力學 | zh_TW |
| dc.subject | Monascus | en |
| dc.subject | monascin | en |
| dc.subject | ankaflavin | en |
| dc.subject | pharmacokinetics | en |
| dc.title | 紅麴聚酮二次代謝產物 monascin 與 ankaflavin 之藥物動力學研究 | zh_TW |
| dc.title | Study on the pharmacokinetics of Monascus secondary polyketide metabolites, monascin and ankaflavin | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 盧重光(Chung-Kuang Lu),李俊霖(Chun-Lin Lee),林志輝(Chih-Hui Lin),許雅雯(Ya-Wen Hsu) | |
| dc.subject.keyword | 紅麴,monascin,ankaflavin,藥物動力學, | zh_TW |
| dc.subject.keyword | Monascus,monascin,ankaflavin,pharmacokinetics, | en |
| dc.relation.page | 119 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-17 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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