臺灣博碩士論文加值系統

口服製劑仍是目前最被廣泛應用的劑型，從服用藥物後一直到藥物在消化道被吸收為止，藥物必須經過溶解及穿透腸壁，因此溶解度是一個頗重要的角色。親脂性高的藥物易穿透腸壁但溶解度較低，所以提高親脂性藥物的溶解度及單體濃度是重要的議題。SBE-CD可以和親脂性較高的脂溶性藥物單體結合，形成complex以增加脂溶性藥物的溶解度；但藥物的單體濃度和SBE-CD的定量關係卻沒有被深入的探討。
本實驗中以平衡透析法來探討SBE-CD和hydrocortisone、tolbutamide及estradiol等三種脂溶性藥物溶液之總濃度與單體濃度的關係。因為分子量的差異，只有hydrocortisone、tolbutamide及estradiol單體分子可以擴散通過透析膜，SBE-CD則因分子量較大而無法通過。依據菲克定律可求得不同SBE-CD及總藥物濃度下的穿透係數P值，進而估算出donor side的單體濃度；再根據質量守恆的原則，可得知SBE-CD和藥物單體形成complex的比例大小及平衡常數值。
三種脂溶性藥物中以hydrocortisone跟SBE-CD間的結合率最高，estradiol次之，tolbutamide則幾乎不和SBE-CD結合形成complex。會造成此差異現象，推測應跟其分子結構及官能基位置有關。

Oral dosage is the most popular way of administration of drugs. When taking medicine, the solubility of a drug plays an important role in the absorption in the digestive tract. Hydrophobic drugs are insoluable in water, but they can easily diffuse to the wall of small intestines. Therefore it is important to increase the solubility and monomer concentration of hydrophobic drugs. Sulfobutyl ether beta cyclodextrin (SBE-CD) can combine with molecules of hydrophobic drugs to form a complex; therefore, increase the solubility of hydrophobic drugs. However investigation of, the monomer concentration and it’s relation with the
SBE-CD are limited.
In this study, we used a diffusion cell to analyse the monomer concentration of hydrocortisone, tolbutamide and estradiol in SBE-CD solution. The monomers of hydrocortisone, tolbutamide and estradiol, due to small particles, can pass dialysis membrane, but the combined complex and the uncombined SBE-CD, due to large particles, can not. Then the Fick’s first law was used to estimate different permeability coefficients and monomer concentrations in donor side solution. According to mass balance and mass action laws, we estimated the ratios of the combined complex to the total SBE-CD and the equilibrium
constants.
Hydrocortisone exhibits the highest ratio among the three hydrophobic drugs. In contrast, the ratio for tolbutamide is nearly zero. The difference may attribute to different structure and different position
of fountional groups for these drug molecules.

頁次
中文摘要…………………………………………………i
英文摘要…………………………………………………ii
目錄………………………………………………………iii
圖目錄……………………………………………………vii
表目錄……………………………………………………x

第一章 緒論……………………………………………1
1.1 前言……………………………………………………1
第二章 相關文獻及背景說明…………………………3
2.1 口服藥物………………………………………………3
2.2 Hydrocortisone………………………………………5
2.2.1 Hydrocortisone簡介………………………………5
2.2.2 腎上腺及其功能……………………………………6
2.2.3 Hydrocortisone的應用……………………………7
2.3 Tolbutamide…………………………………………9
2.3.1 Tolbutamide簡介…………………………………9
2.3.2 糖尿病簡介………………………………………10
2.3.3 Tolbutamide的應用………………………………12
2.4 Estradiol……………………………………………13
2.4.1 雌激素簡介………………………………………13
2.4.2 雌激素和月經週期………………………………14
2.4.3 雌激素的應用……………………………………15
2.5 Cyclodextrin--環狀寡糖…………………………16
2.6 平衡透析法…………………………………………18
第三章 問題陳述…………………………………………19
第四章 材料方法…………………………………………20
4.1 實驗簡介……………………………………………20
4.2 SBE-CD及hydrocortisone之平衡與單體濃度分析……21
4.2.1 材料………………………………………………………21
4.2.2 裝置………………………………………………………21
4.2.3 方法………………………………………………………22
4.3 SBE-CD及tolbutamide之平衡與單體濃度分析………………24
4.3.1 材料………………………………………………………24
4.3.2 裝置………………………………………………………24
4.3.3 方法………………………………………………………25
4.4 SBE-CD及estradiol之平衡與單體濃度分析…………………27
4.4.1 材料………………………………………………………27
4.4.2 設備………………………………………………………29
4.4.3 方法………………………………………………………29
第五章 結果……………………………………………………………33
5.1 SBE-CD及hydrocortisone之平衡與單體濃度分析之結果……33
5.1.1 Hydrocortisone檢量線…………………………………33
5.1.2 Hydrocortisone平衡透析實驗結果……………………33
5.1.3 Hydrocortisone平衡常數的計算………………………35
5.1.4 Hydrocortisone與SBE-CD之結合率……………………36
5.1.5 結果探討…………………………………………………36
5.2 SBE-CD及tolbutamide之平衡與單體濃度分析之結果…………37
5.2.1 Tolbutamide檢量線………………………………………37
5.2.2 Tolbutamide平衡透析實驗結果…………………………37
5.2.3 Tolbutamide平衡常數的計算……………………………37
5.2.4 Tolbutamide與SBE-CD之結合率…………………………38
5.2.5結果探討……………………………………………………39
5.3 SBE-CD及estradiol之平衡與單體濃度分析之結果……………39
5.3.1 Estradiol之檢量線………………………………………39
5.3.2 Estradiol平衡透析實驗結果……………………………40
5.3.3 Estradiol平衡常數的計算………………………………40
5.3.4 Estradiol與SBE-CD之結合率……………………………41
5.3.5結果探討……………………………………………………41
第六章 討論……………………………………………………………43
第七章 參考文獻………………………………………………………45
第八章 附錄……………………………………………………………50

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