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研究生:楊智鈞
研究生(外文):Chih-Chun Yang
論文名稱:part1.Cinnamophilin 在大鼠體內的藥物動力學研究part2.Magnolol 在大鼠體內的藥物動力學研究
論文名稱(外文):part1.Pharmacokinetic study of cinnamophilin in rats.part2.Pharmacokinetic study of magnolol in rats
指導教授:林文鑫林文鑫引用關係
指導教授(外文):Wen-Hsin Lin
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:藥學系碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:79
中文關鍵詞:菲律賓樟樹缺血性中風藥物動力學
外文關鍵詞:Cinnamophilinischemic strokepharmacokinetic
相關次數:
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Cinnamophilin是從菲律賓樟樹( Cinnamomum philippinense )分離而萃取出來的化合物, 為一強而有效之自然抗氧化劑與自由基截取劑,且可抑制血小板聚集,對於急性缺血性腦中風後的神經行為表現有改善的作用。極有潛力發展成為治療急性缺血性中風的藥物。
本研究以大鼠為動物模型,分成兩組,靜脈給予不同劑量分別為40mg/kg和80mg/kg , 給藥後 5, 15, 30, 60, 120, 240分鐘及20小時採集血液、取腦等組織,利用高效液相層析系統來定量血液及組織中CINN原型及其結合態代謝物。
結果顯示靜脈注射後CINN快速被吸收及代謝,給藥後20小時,血中仍然可以偵測到代謝物的存在,我們發現在血漿中有兩種代謝物,而主要的是葡萄糖醛基結合態代謝物,比較兩種劑量的AUC結果發現, CINN在大鼠體內的吸收有劑量依賴的情形。另外,在腦中也有發現CINN原型藥物的存在,表示其確實可通過血腦障壁,但是在給藥60分鐘後就偵測不到。
此研究結果提供一個以大鼠為模型的CINN 藥物動力學研究,可以初步的了解CINN的代謝及組織分佈,提供一些資訊,也許未來可以利用藥物結構的修飾來增加藥物的吸收。

Cinnamophilin (CINN) isolated from Cinnamomum philippinense, is a strong novel antioxidant and free radical scavenger .It can decrease platelet aggregation and improve the post-stroke neurobehavioral outcome. CINN has the potential to develop into a new drug for treating acute ischemic stroke.
In this study, we use Sprague-Dawley rats for the pharmacokinetic model. They were divided into two groups and administrated via jugular vein injection at dose 40 and 80 mg/kg CINN respectively. Blood and tissue samples were collected at times of 5, 15, 30, 60, 120, 240mins and 20 hrs after intravenous administration. Then CINN and its metabolites in blood or tissue were detected by a high-performance liquid chromatography system.
The results showed that CINN was absorbed and metabolized rapidly in blood and its metabolites had been detected at 20 hours after administration. We found two metabolites of CINN in plasma, and the CINN glucuronides is the major metabolite. Comparison of two different doses of AUC data, we found that the dose-dependent relationship exists in the absorption of CINN. In addition, we found CINN in the brain tissue. It was proved that CINN can cross the blood-brain barrier but could not be detected at 60 min after administration.
The result provides an animal model for the pharmacokinetic study of CINN. It helps us to understand metabolism and distribution of CINN and is useful to modify chemical structure of CINN and increase its activity.


目錄 2
附圖目錄 7
附表目錄 9
縮寫對照表 10
中文摘要 11
英文摘要 12
第一部分 Cinnamophilin在SD鼠體內的藥物動力學研究 13
第一章 緒言 14
第一節 緣起 14
第二節 研究動機及目的 14
第二章 總論 15
第一節 腦血管疾病 15
一、 成因 15
二、 分類 16
三、 治療方法 16
第二節 缺血-再灌流傷害(ischemia-reperfusion injury) 26
第三節 實驗藥物 CINN 28
一、 基本資料 28
二、 藥理活性及相關研究 29
第三章 材料與方法 32
第一節 實驗材料 32
一、 試藥與溶媒 32
二、 儀器設備與耗材 33
三、 實驗藥物CINN 34
第二節 溶液配製 34
第三節 實驗方法 36
第四章 結果與討論 46
第五章 結論 51
第二部分 Magnolol 在SD鼠體內的藥物動力學研究 52
第一章 緒言 53
第一節 緣起 53
第二節 研究動機與目的 54
第二章 實驗藥物Magnolol 55
第三章 材料與方法 58
第一節 實驗材料 58
第二節 溶液配製 60
第三節 實驗方法 62
第四章 結果與討論 69
參考文獻 71
附圖 77
附表 84



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