臺灣博碩士論文加值系統

摘 要
本研究之目的在探討海菜（Monostroma nitidum）水溶性粗多醣之流變、成膠性質，與藥物在海菜水溶性粗多醣膠之控制釋放之應用。模式藥物為Promethazine、Tolbutamide、Indomethacin。本研究分為三個部份︰第一部份為探討海菜水溶性粗多醣之流變性質，受剪速率、濃度、pH、剪力作用時間、硼酸添加濃度與硼酸添加於不同pH海菜水溶性粗多醣溶液影響的效應；第二部份為探討海菜水溶性粗多醣成膠性質，受硼酸添加濃度、pH、氯化鈉添加濃度與氯化鈣添加濃度影響的效應；第三部份為利用海菜水溶性粗多醣膠控制藥物的釋放，受基質結構及不同部位的裸鼠皮膚對藥物的控制釋放。結果如下︰
海菜水溶性粗多醣溶液的流變模式為非牛頓型的假塑性流體，其視黏度會隨著剪速率的增加而下降呈剪稀現象(shear thinning），且剪稀性質會隨粗多醣溶液濃度上升而變得較顯著；隨著 pH 的上升海菜水溶性粗多醣溶液表面黏度有增加的趨勢。隨著剪力作用時間的增加，低濃度海菜水溶性粗多醣溶液之表面黏度有小幅下降之趨勢，但在高濃度海菜水溶性粗多醣溶液表面黏度有增加的趨勢。不同濃度的海菜水溶性粗多醣溶液隨著硼酸濃度增加表面黏度會上升，但大於70mM時在連續剪力作用一段時間後表面黏度會開始下降；在含40mM硼酸的海菜水溶性粗多醣溶液在pH 7於連續剪力作用一段時間後時表面黏度增加最多。
2% 海菜水溶性粗多醣溶液添加40mM 以下之硼酸溶液pH大於7 時所製成之海菜膠，其膠體結構是屬於較為彈性的。另外添加鹽類對於膠體之黏彈性質也會影響：添加適度的氯化鈉（35-50mM）或氯化鈣（8.5-10.2mM）會提高凝膠的貯存模數（G’）和得到較低的相角正切值（tanδ）；而且和水分散失率也有相關，較彈性的膠體其水分散失率較少。
Promethazine-HCl、Tolbutamide、Indomethacin的釋放速率在含0.85 mM氯化鈣的海菜膠較快，而且基質結構對於非水溶性藥物的釋放速率影響最為明顯。另外藥物在不同部位的裸鼠皮膚釋放速率會有差異，即在腹部的釋放速率是較快的。

Abstract
The objectives of this study are to explore the rheological and gel formation properties of crude polysaccharide aqueous solution of Monostroma nitidum (aqueous solution) and it’s application in drug controlled release. The model drugs are Promethazine, Tolbutanide and Indomethacin. The study includes 1. To explore the effects of shear rate, solute concentration, solution pH, shearing time, boric acid concentration and boric acid in different pH solution on the rheological properties of aqueous solution; 2. To explore the effect of boric acid concentration, solution pH, sodium chloride concentration and calcium chloride concentration on the gel formation properties of aqueous solution; 3. To explore the effect of different matrixs made from aqueous solution and different parts (abdominal vs dorsal) of fresh skins of nude mice on the release rates of model drugs. The results obtained are as following:
The flow behavior of aqueous solutions are pseudoplastic fluid. Increasing the solute concentration enhanced shear thinning properties of those aqueous solutions. The apparent viscosity of different concentrations aqueous solution increased with increasing solution pH. The apparent viscosity of lower concentration aqueous solution decreased slightly with increasing shearing time but the high concentration one increased with shearing time. The apparent viscosity of aqueous solution increased with increasing boric acid concentration but at a concentration higher than 70 mM, the apparent viscosity decreased after shearing for certain period of time. The apparent viscosity of aqueous solution containing 40mM boric acid increased with increasing solution’s pH. The apparent viscosity of aqueous solution of pH 7 was higher than those either higher or lower solution pH ones.
Storage modulus of the gels prepared from aqueous solution containing 40mM boric acid at different solution pHs increased with increasing solution pH. Gel prepared from aqueous solution containing 40mM boric acid had higher storage modulus than those containing either higher or lower concentration of boric acid. Addition of sodium or calcium salts in the solution affected viscoelastic properties of the prepared gels. Sodium chloride concentration between 35-50 mM or calcium chloride concentration between 8.5-10.2 mM elevated gel’s storage module (G’) and lower its phase angle (tanδ). The elastic properties of the gel affected its water loss rate. The more elastic gel, the less water loss rate.
Release rate of model drugs of Promethazine、Tolbutanide、Indomethacin were faster in gel containing lower calcium chloride concentration and was lower to pass through fresh abdominal than through dorsal skin of nude mice. The results indicated that the structure of the matrix affected drugs release rate especial for those hydrophobic drugs.

目 錄
中文摘要 1
Abstract 3
一、前言 5
二、文獻整理 8
1. 海藻之多醣類 8
2. 海藻之蛋白質 8
3. 海藻多醣類的萃取與劃分 9
3.1. 多醣類的萃取 9
3.2. 多醣類的劃分 10
4. 海藻多醣類在化妝品上之應用 11
5. 海藻多醣之功能特性 12
6. 多醣類混合系統之凝膠機制 13
7. 水溶膠之定義、種類與應用方法 14
8. 鹽類對帶電多醣膠質凝膠性之影響 16
9. 控制釋放技術 20
9.1. 目前利用控制釋放技術所研製而成的藥物 20
10. 穿皮輸藥系統簡介 21
10.1 發展經皮吸收劑型所需具備三個要素 23
10.2 經皮吸收劑型隨著藥物特性而採用不同的設計 24
11. 穿皮輸藥系統之限制與優點 26
12. 人體皮膚結構 27
13. 藥物穿透皮膚之基本理論 30
13.1 被動式穿皮輸藥系統之穿透路徑 30
13.2 穿皮輸藥系統經由皮膚釋放藥物之原理 31
14. 影響經皮吸收之因素 32
15. 模式藥物簡介 33
三、材料與方法 34
1. 材料 34
1.1. 海菜原料 34
1.2. 化學藥品 34
2. 方法 34
2.1. 海菜水溶性粗多醣之製備 34
2.2. 一般組成份測定 35
2.3. 海菜水溶性粗多醣流變性質之測定 36
2.3.1. 濃度與剪速率效應 36
2.3.2. pH 效應 36
2.3.3. 剪力作用時間效應 37
2.3.4. 硼酸添加濃度效應 37
2.3.5. 硼酸添加於不同pH多醣溶液效應 37
2.4. 海菜水溶性粗多醣膠的黏彈性質 37
2.4.1. 硼酸添加濃度效應 37
2.4.2. 硼酸添加於不同pH多醣溶液效應 38
2.4.3. 氯化鈉添加濃度效應 38
2.4.4. 氯化鈣添加濃度效應 38
2.5. 海菜水溶性粗多醣膠之水分散失率 39
2.6. 海菜水溶性粗多醣膠在藥物控制釋放之應用 39
四、結果與討論 40
1. 海菜水溶性粗多醣之成份分析及產率 40
2. 海菜水溶性粗多醣之流變性質 40
2.1. 濃度與剪速率效應 40
2.2. pH 效應 41
2.3. 剪力作用時間效應 42
2.4. 硼酸添加濃度效應 43
2.5. 硼酸添加於不同pH多醣溶液效應 43
3. 海菜水溶性多醣之黏彈性質 44
3.1. 硼酸添加濃度效應 44
3.2. 硼酸添加於不同pH多醣溶液效應 44
3.3. 氯化鈉添加濃度效應 45
3.4. 氯化鈣添加濃度效應 46
4. 海菜水溶性粗多醣膠之水分散失率 46
5. 海菜水溶性多醣膠在藥物控制釋放之應用 47
5.1. 不同基質結構對藥物制放之影響 47
5.1.1. Promethazine-HCl 47
5.1.2. Tolbutamide 47
5.1.3. Indomethacin 47
5.2. 裸鼠腹部皮膚及背部皮膚對藥物制放之影響 48
5.2.1. Promethazine-HCl 48
5.2.2. Tolbutamide 48
5.2.3. Indomethacin 48
五、結論 50
六、參考文獻 51
七、圖 63
八、表 104

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