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研究生:簡啟恆
研究生(外文):Jian Chi Heng
論文名稱:純化蒙脫石做為5-FU藥物載體於大腸癌治療之研究
論文名稱(外文):A study on purified Montmorilonite intercalated with 5-Fluorouracil as drug carrier for Colon Cancer
指導教授:李源弘林峰輝林峰輝引用關係
指導教授(外文):Lee Yung HongLin Feng Huei
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:材料科學與工程學研究所
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2000
畢業學年度:88
語文別:中文
論文頁數:93
中文關鍵詞:蒙脫石長效型釋放
外文關鍵詞:5-FluorouracilMTT Assay
相關次數:
  • 被引用被引用:12
  • 點閱點閱:287
  • 評分評分:
  • 下載下載:49
  • 收藏至我的研究室書目清單書目收藏:1
5-Fluorouracil(5-FU)在臨床上為治療大腸癌(colon cancer)最有用的藥物,由於直接服用或是經由靜脈注射,經由肝臟的代謝時,對生體的毒害相當的大。近來有相當多關於5-FU藥物載體的研究,絕大部分皆是高分子劑型的開發,我們試著利用蒙脫石特有的層間性質與生物惰性,做為無機藥物載體,經由消化道使5-FU能在大腸中做長效型的釋放(sustained release),以減低5-FU的毒性。我們試著製備出適合5-FU與蒙脫石複合物,並試著找出5-FU插入或吸附於蒙脫石的條件,並以XRD、FT-IR、UV/Vis、DTA/TGA進一步証實蒙脫石的插入行為,以利之後的釋放結果分析。
經一系列之分析,求得5-FU插入蒙脫石之適當條件為:
(1) 浸泡時間:2小時
(2) 反應溫度:80℃
(3) 反應pH值:11.6
(4) 反應之5-FU起始濃度:1.185wt%
當5-FU與蒙脫石複合物於模擬消化道模式釋放時,在5th至24th小時模擬大腸釋放結果發現,所釋放的5-FU濃度每小時可達到相當於有效治療濃度的1/20。爾後利用WiDr大腸癌細胞與5-FU/蒙脫石複合物及其釋放液進行細胞培養實驗,利用MTT Assay群落比色分析與TEM觀察細胞切片,可証明5-FU的釋放作用足以有效抑制大腸癌細胞增生繁殖,而達到有效的治療效果。
In the recent decade, the most useful drug for the therapy of colon cancer is 5-Fluorouracil(5-FU). It has been reported to have considerable toxicity administered by intravenous injections or via alimentary treat. Though many materials have developed for drug carrier of 5-FU, there was no clinically acceptable carrier for 5-FU till now. Montmorillonite, one of clay minerals, consists of hydrated aluminum silicates that are fined grained and usually have a large space between the layers. Isomorphous substitution of cations is common. We try to intercalate 5-FU into interlayer of montmorillonite through ion-exchange. Montmorillonite with 5-FU intercalation is expected to achieve in-situ release for colon cancer therapy. In the study, 5-FU was dissolved in 100ml distilled water as 5-FU solution. Purified montmorillonite powder will soak in 5-FU solution for a period of time at different pH value and temperature. The intercalated amount of 5-FU in montmorillonite is measured and confirmed by scanning differential thermal (SDT) analysis and ultraviolet visble analysis (UV) analysis. The results showed that 4g purified montmorillonite soaked in 0.6% 5-FU solution for 2 hours had an optimum condition for intercalation. The total amount of 5-FU in montmorillonite is about 87.5mg in 4g montmorillonite.
In the gastrointestine(GI) simulated releasing model, the releasing amount of 5-FU in 5-FU/Mont. Composite, which is capsulated with gelatin between 5th to 24th hour, could achieve 1/20 the clinical effective concentration and thoroughly in vitro inhibition to WiDr. In use of the method of MTT assay, population analysis and transmission electron microscope (TEM) analysis, we could confirm the proliferous inhibition of WiDr by the releasing 5-FU and effective therapy to colon cancer.
摘要-------------------------------------------------------------------------------------Ⅰ
英文摘要------------------------------------------------------------------------------Ⅱ
目錄-------------------------------------------------------------------------------------Ⅲ
圖目錄---------------------------------------------------------------------------------Ⅴ
表目錄---------------------------------------------------------------------------------Ⅷ
第一章 緒論-------------------------------------------------------------------------1
1-1 前言---------------------------------------------------------------------------------1
1-2 文獻回顧---------------------------------------------------------------------------1
1-2-1 5-Fluorouracil(5-FU)合成----------------------------------------------2
1-2-2 5-FU之藥物特性及發展---------------------------------------------2
1-3 研究目的-------------------------------------------------------------------------10
第二章 理論基礎------------------------------------------------------------------11
2-1 蒙脫石的純化、理論構造及應用------------------------------------------11
2-1-1 蒙脫石的分離純化----------------------------------------------------11
2-1-2 蒙脫石的理論構造及礦物特性------------------------------------12
2-2 擴散理論(Diffusion theory) -------------------------------------------------------17
2-2-1 費克(Fick)第一定律----------------------------------------------------------17
第三章 實驗步驟與方法--------------------------------------------------------19
3-1 實驗儀器-------------------------------------------------------------------------19
3-2 實驗藥品-------------------------------------------------------------------------20
3-3 實驗方法及流程---------------------------------------------------------------21
3-3-1 蒙脫石之純化-----------------------------------------------------------21
3-3-2 純化後蒙脫石陽離子交換量之測定------------------------------23
3-3-3 5-FU/蒙脫石複合物之製備-------------------------------------------25
3-3-4 5-FU/蒙脫石複合物性質分析---------------------------------------27
3-3-5 5-FU/蒙脫石複合材料之藥物釋放---------------------------------30
3-3-5.1 5-FU/蒙脫石在不同pH值下之釋放------------------------30
3-3-5.2 腸胃道模擬釋放(Gastric-intestine simulated releasing)--32
3-3-6 細胞活性測試與生物電子顯微鏡觀察---------------------------34
3-3-6.1 細胞群落分析(Population analysis) -------------------------34
3-3-6.2 MTT藥物濃度測試---------------------------------------------36
3-3-6.3 TEM切片觀察---------------------------------------------------38
第四章 結果與討論--------------------------------------------------------------41
4-1 5-FU/蒙脫石複合物之製備--------------------------------------------------41
4-1-1 陽離子交換量(CEC)之測定-----------------------------------------41
4-1-2 5-FU插入或吸附於蒙脫石之適當反應條件-------------------42
4-1-3 5-FU/蒙脫石複合物之材料分析-----------------------------------44
4-2 藥物釋放曲線-------------------------------------------------------------------46
4-2-1 5-FU/蒙脫石複合物之釋放曲線---------------------------------46
4-2-2 5-FU/蒙脫石以Gelatin膠囊包覆之釋放曲線-----------------46
4-2-3 Gelatin膠囊與蒙脫石之作用機制-------------------------------48
4-2-4 模擬人體消化道之藥物釋放(GI-Simulated Releasing)------49
4-3 細胞活性實驗-------------------------------------------------------------------49
4-3-1 群落分析(Population analysis) -------------------------------------49
4-3-2 MTT測試(MTT test) ------------------------------------------------50
4-3-3 穿透式電子顯微鏡分析(TEM analysis) ------------------------50
第五章 結論------------------------------------------------------------------------83
第六章 未來展望------------------------------------------------------------------85
第七章 參考文獻------------------------------------------------------------------86
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