臺灣博碩士論文加值系統

本實驗在探討利用非磷脂類脂質左旋C棕櫚酸脂製作微脂粒包覆熊
果素(arbutin)，藉由調控不同變因控制，例如濃度差、不同脂類、不同
界面活性劑等等，進行in vitro 藥物經皮輸送釋放效能，以及進行穿透係
數計算及統計分析、豬皮藥物殘留量測定、螢光測定界面活性劑對微脂
粒之影響等實驗之研究。
由實驗結果得知，包覆5%熊果素之微脂粒，其經皮輸送釋放速率
為19.60nmol/cm2/h；未經由微脂粒包覆之5%熊果素溶液經皮輸送釋放
速率14.79nmol/cm2/h，顯示微脂粒包覆對於親水性藥物具有促進輸送的
作用；在不同包覆濃度變因之下，藥物釋放速率隨濃度上升而增加，以
濃度5%的配方為佳，達到19.60nmol/cm2/h；不同界面活性劑變因之下，
以DA(deoxycholic acid)配方為最佳配方，釋放效能達到
26.32 nmol/cm2/h；不同脂類包覆變因之下，顯示本實驗中脂質不是影響
經皮釋放效能的變因。由穿透係數統計分析得知，熊果素經由包覆後輸
送速率顯著提高。
結果顯示，左旋C 棕櫚酸脂微脂粒在經皮藥物輸送的效能上具有促
進作用，所以利用左旋C 棕櫚酸脂製作微脂粒包覆熊果素是可行的方
法，在未來的發展中，可以利用左旋C 棕櫚酸脂包覆其他藥物來進行微
脂粒製作，同時對其藥物控制釋放上的行為模式進行實驗。

The aim for the research is to encapsulate arbutin by liposome based on
non-phospholipids “ascorbyl palmitate”, and then perform transdermal
delivery experiments by adjusting different factors, such as different drug
concentrations, encapsulating lipids, surfactants etc. Furthermore, we got the
physical data, such as permeability coefficients, skin-drug accumulation, and
so on.
From the result, we observed that the releasing rate of 5% arbutin
liposome and 5% non-encapsulated arbutin solution are 19.60nmol/cm2/h
and 14.79nmol/cm2/h respectively. It means the encapsulation of arbutin has
enhancing effects for transdermal delivery. By adjusting different drug
concentration, we observed that releasing rate rises with concentration under
saturation concentration range. The best formulation is 5% arbutin and it
comes to the number of 19.60nmol/cm2/h. By adjusting different surfactants,
DA is the best formulation and it comes to 26.32 nmol/cm2/h. By adjusting
different lipids, it showed that the lipid did not affect the release.
In conclusion, the non-phospholipids “ascorbyl palmitate” has effects in
improving the transdermal delivery efficiency and we could also apply it to
other drugs to investigate the behaviors for delivery in the future.

中文摘要I
英文摘要II
致謝III
目錄V
表目錄IX
圖目錄X
符號索引XII
壹、 緒論1
1.1 前言-研究背景1
1.2 研究動機與目的2
貳、 文獻回顧4
2.1 微脂粒藥物載體4
2.1.1 發展起源4
2.1.2 微脂粒構造介紹6
2.1.3 微脂粒之性質8
2.1.4 微脂粒在藥物輸送系統之應用10
2.1.5 影響藥物包覆率之因素10
2.1.6 微脂粒藥物載體原理11
2.1.7 微脂粒與細胞作用11
2.2 微脂粒經由皮膚進行藥物輸送15
2.2.1 皮膚結構介紹15
2.2.2 經皮藥物輸送理論18
2.2.3 經皮藥物輸送之促進21
2.2.4 微脂粒經皮藥物輸送之促進23
2.3 藥物經皮輸送實驗23
2.3.1 微脂粒形成機制23
2.3.2 微脂粒製備方法25
2.3.3 微脂粒藥物經皮輸送實驗28
2.4 利用非磷脂類脂質製作微脂粒30
2.5 包覆藥物熊果素31
2.5.1 熊果素簡介31
2.5.2 熊果素結構與性質31
2.5.3 熊果素美白作用機轉34
參、 實驗材料與方法36
3.1 實驗藥品與儀器36
3.1.1 實驗藥品36
3.1.2 實驗儀器36
3.2 試藥製備40
3.3 熊果素標準曲線41
3.4 豬皮前處理44
3.5 實驗方法44
3.5.1 微脂粒製備44
3.5.2 藥物經皮輸送釋放實驗47
3.6 分析方法47
3.6.1 包覆率測定47
3.6.2 藥物累積量測定48
3.6.3 豬皮藥物殘留量測定48
3.6.4 微脂粒螢光光譜分析49
3.6.5 藥物於猪皮中之穿透模式與穿透係數計算50
3.6.6 統計分析53
肆、 結果與討論54
4.1 包覆率56
4.2 左旋C 棕櫚酸脂包覆對經皮藥物輸送之影響58
4.3 藥物包覆濃度差異對經皮藥物輸送之影響61
4.4 不同界面活性劑包覆對經皮藥物輸送之影響64
4.5 不同脂類包覆對經皮藥物輸送之影響68
4.6 實驗後猪皮之藥物殘留量71
4.7 穿透係數73
4.8 以螢光光譜分析儀測定界面活性劑對微脂粒配方之影響75
伍、 結論與未來展望85
陸、 參考文獻88
附錄一、統計分析92

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