臺灣博碩士論文加值系統

花青素為水溶性色素，具有抗氧化、抗癌、降血脂等生理功能，存在於自然界之花青素極為不穩定，容易在加工及貯存過程中發生變色，影響色澤及品質。「錠劑」為保健食品常用之劑型，其中以間質釋控錠(Matrix tablet)常被運用在緩釋劑型上，其透過不同膠體及金屬離子的添加來形成水膠體以達到藥物延緩釋放之效果，而目前許多緩釋劑型研究其常超過24小時不會崩解，進而影響體內腸胃道之吸收及消化，如何達到3 – 6小時完全釋放之間質釋控錠成為重要研究主題。
紫甘藷花青素之最適萃取條件試驗，得到以60%乙醇+5 %檸檬酸、溫度80℃加熱40分鐘、固液比1:15能得到較高的花青素萃取含量(93.16mg/100g)，且其萃取液具有良好的DPPH、ABTS自由基清除能力與還原鐵能力，並以降解動力學探討其活化能，另紫甘藷花青素萃取液較好的貯存條件是在低溫低pH並且避光。以低甲氧基果膠為主體之錠劑配方(LMP / Starch / Chitosan)，經過模擬腸胃道處理會形成保護層，其殘留質量(RM %值)隨時間減少，從0.5小時84.2 %下降至1小時76.98 %、8小時56.2 %，膨潤力則從0.5小時81.0%上升至1小時120 %、8小時455.1 %，藉此達到連續釋放24小時錠劑不崩散之效果。近年來許多研究指出，錠劑不崩散可能會導致腸胃不舒服、腸阻塞等副作用。因此，本試驗另以鹿角菜膠為配方主體，添加氯化鈣及氯化鉀能使錠劑達到緩釋並能在4 – 6小時崩解，經胃液模擬釋放2小時後，其釋放含量為61.89%，因CA在中性環境中較穩定，因此在腸液模擬釋放中能達到緩慢釋放的特性，3小時釋放量為71.20%、6小時為92.24%。因此試驗配方錠劑能在腸胃中 4 – 6小時達到緩釋崩解的效果，有效解決目前緩釋劑型在腸胃不崩散之副作用。

Anthocyanins are water-soluble pigments with physiological functions such as anti-oxidation, anti-cancer and blood lipid lowering. They are widely found in vegetables and fruit. However, anthocyanins in nature are extremely unstable and easy to discolor during process and storage. Tablets are one of the commonly used solutions for health foods, and matrix tablets are more important dosage form in which use different colloids to form hydrocolloids to achieve drug delayed release. At present, many sustained-release dosage forms are often not disintegrated for more than 24 hours, which affects the absorption and digestion of the gastrointestinal tract in the body. How to achieve the release of the controllable tablets within 3-6 hours of complete release has become an important research topic.
Under the optimum extraction conditions, the best anthocyanin extraction content (93.16mg/100g) was obtained by heating with 60% ethanol + 5 % citric acid, heating at 80 ° C for 40 minutes, and solid-liquid ratio 1:15. The extract has good DPPH, ABTS free radical scavenging ability and reduced iron capacity, and the degradation conditions are analyzed that the better storage conditions of anthocyanins are low temperature and low pH and protection from light. The low methoxy pectin-based tablet formulation (LSC) will form a protective layer after simulated gastrointestinal treatment, and the residual mass decreases with time, from 84.2% in 0.5 hours to 76.98% in one hour , 56.2% in eight hours. The swelling power increased from 0.5 hour 81.0% to 1 hour 120%, 8 hours 455.1%, thereby achieving the effect of continuous release of the tablet for 24 hours without disintegration. In recent years, more and more studies have pointed out that the non-disintegration of tablets can cause side effects such as gastrointestinal discomfort and intestinal obstruction. Therefore, this experiment intends to use carrageenan as the main component of the formula. The addition of calcium chloride and potassium chloride can achieve sustained release of the tablet and can disintegrate in 4-6 hours. After 2 hours of simulated release from gastric juice, the release content was 61.89%. Because carrageenan is stable in neutral environment, it can achieve slow release characteristics in simulated release of intestinal fluid. The release comulation in 3 hours is 71.20%, and 6 hours is 92.24%. The test formulation can achieve the effect of sustained release disintegration in the stomach for 4-6 hours, effectively solving the side effects of the sustained release which can’t disintegrate.

摘要 i
Abstract ii
目次 iv
表次 xi
圖次 xiii
壹、引言 1
貳、文獻回顧 2
一、甘藷(Sweet potato)之介紹 2
1. 農藝及產量 2
2. 紫甘藷(Purple sweet potato) 6
(一)、育種過程 6
(二)、紫甘藷特性 6
二、 花青素(Anthocyanin) 9
1. 花青素生理活性: 10
2. 花青素之影響因素: 14
3. 花青素生物利用及消化代謝: 16
三、營養保健市場概況: 23
1. 全球市場概況 23
2. 中國市場概況 23
3. 台灣市場概況 24
四、錠劑(Tablets) 28
1. 錠劑種類 29
2. 錠劑配方設計 33
3. 間質型及多顆粒劑型之釋放 39
五、釋放動力學 44
1. 釋放動力學模式 44
參、實驗目的 47
肆、實驗架構 48
伍、材料與方法 49
一、材料: 49
(一)原料: 49
(二)賦形劑 49
(三)試驗藥品 50
二、實驗方法 51
(一)紫甘藷萃取試驗: 51
(二)機能成分分析: 51
1. 花青素含量分析: 51
(三)抗氧化能力 52
1. DPPH (1,1-diphenyl-2-picrylhydrazyl)自由基清除能力 52
2. ABTS+ (2,2'-azino-bis(3-ethylbenz thiazoline-6-sulphonic acid))自由基清除能力 52
3. FRAP (Ferric ion reducing antioxidant power assay) 鐵螯合抗氧化力檢測 53
(四)紫甘藷花青素安定性評估: 53
1. 花青素萃取液全波長掃描 53
2. 色澤分析: 53
3. 花青素裂解指數測定(Degradation index, DI) 54
4. 對熱評估降解動力學 54
5. 花青素熱力學分析 55
6. 花青素貯存試驗 55
(五)錠劑製備 56
(六)配方粉體測試 56
1. 水分(Water content) 56
2. 粉體假密度(Bulk density, ρb) 56
3. 粉體振實密度( Tapped density, ρtapb) 56
4. 粉體流動性(Fluidity) 60
(七)錠劑物性測試 60
1. 重量差異性(Variance of tablet weight) 60
2. 厚度(Thickness) 60
3. 直徑(Diameter) 60
4. 硬度(Hardness) 60
5. 磨損(碎)度(Friability) 61
6. 崩散時間(Disintegration time) 61
7. 色澤(Color) 61
8. 水活性(Water activity, Aw) 61
9. 熱性質分析(Differential scanning calorimetry, DSC) 61
10. 傅裡葉轉換紅外光譜(Fourier transform infrared spectrometer, FT-IR) 62
11. 掃描式電子顯微鏡(Scanning electron microscope, SEM) 62
12. X光繞射分析 (X-ray diffraction analysis, XRD ) 62
(八)體外模擬試驗 64
1. 配製模擬胃液 (Formulating simulated gastric fluid) 64
2. 配製模擬腸液 (Formulating simulated intestinal fluid) 64
3. 模擬腸胃釋放及侵蝕試驗 (Simulated gastrointestinal release and erosion test) 64
三、數據分析 65
陸、結果與討論 66
第一章「利用pH及溫度參數評估紫甘藷花青素降解動力學及其貯存品質變化」 66
一、花青素在不同pH色澤之品質變化 67
二、紫甘藷花青素萃取條件 71
(1) 萃取溶液對花青素之影響 71
(2) 溫度對花青素萃取之影響 71
(3) 固、液比對花青素萃取之影響 72
三、抗氧化力評估 76
四、花青素萃取液安定性探討 78
(1)花青素萃取液對溫度之安定性 78
(2)花青素萃取液對pH之安定性 78
(3)不同溫度及pH處理之裂解指數(Degradation index, DI) 79
五、花青素萃取液之降解動力學評估 83
六、貯存試驗 86
第一章小結 89
第二章 「果膠、幾丁聚醣、澱粉間質錠構型及其釋放特性探討」 94
一、 配方粉體觀察及流動性 95
二、 錠劑物性品質分析 99
1. 錠劑大小、重量及色澤分析 99
2. 物性因數 100
二、 錠劑之熱性質及傅裡葉轉換紅外光譜分析(FT-IR)分析 104
1. 熱性質(DSC) 104
2. 傅裡葉轉換紅外光譜分析(FT-IR) 106
三、 體外模擬釋放試驗 112
第二章小結 116
第三章「紫甘藷花青素間質釋控錠研發及其釋放動力學評估」 117
一、配方粉體物性分析 118
1. 水分及流動性 118
2. 微細構造觀察 119
二、錠劑物性品質分析 122
1. 錠劑大小、重量 122
2. 錠劑外觀及色澤 124
3. 錠劑之物性因數 126
三、錠劑熱性質分析比較 128
四、傅裡葉轉換紅外光譜分析(FT-IR) 133
五、X光繞射分析(XDR) 140
六、體外溶離試驗 145
1. 間質釋控錠於模擬腸胃液之釋放特性 145
2. 侵蝕、膨潤力 148
3. 微細構造 153
4. 體外模擬試驗之花青素釋放 157
5. 釋放動力學 159
第三章小節 164
柒、結論 165
捌、參考文獻 166

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