臺灣博碩士論文加值系統

洛神葵花萼具有鮮艷的色澤主要是因為富含花青素，許多研究已經證實花青素具有良好的抗氧化活性，具有抗發炎、抗腫瘤、抗癌症、保護視力等生理功效，以及目前人們對保健食品的熱衷追求，越來越多的具有生理功效的原料被用來開發出很多的保健食品，錠劑作為保健食品常見的劑型載體之一，具有體積小、方便攜帶、成本低等優點，本實驗欲開發一款具緩釋功能的花青素錠劑，使其能夠在胃部環境中緩慢釋放，避免被腸道鹼性環境的破壞，以提高身體利用率。本實驗結果如下：以30%乙醇，在75℃條件下加熱20分鐘可以有效萃取出洛神葵花萼中的花青素，以HPLC進行分析其主要的花青素為飛燕草素，含量為126.34mg/100 g乾燥洛神葵花萼，且萃取物具有良好的DPPH、ABTS自由基清除能力與Fe3+還原能力；選擇常用的賦形劑進行製備洛神葵萃取粉胃漂浮緩釋錠，選擇適當比例的賦形劑製備得之錠劑可以在體外模擬胃液環境中快速起漂，且能夠持續漂浮12小時以上，在漂浮的過程中錠劑不會崩散，保持膠體骨架緩慢釋放內部的指標成分，隨著載藥量的提高，12小時的累積釋放量提高，指標成分的釋放符合零級動力學(R2＞0.9)，與Higuchi動力學方程的擬合度最高，說明本實驗製備之胃漂浮緩釋錠中的指標成分是以擴散方式釋放，指標成分的釋放累積量與時間平方根之間呈正比關係，且錠劑中指標成分的比例不會改變其釋放行為；在Korsmeyer-Peppas 釋放動力學模型的擬合結果顯示指標成分的釋放屬於Anomalous transport的釋放機制，代表指標成分的釋出是由擴散作用和骨架溶蝕協同作用，期待本實驗結果可為未來投入開發花青素緩釋錠奠定理論基礎。

Rosell calyxes are bright red due to their rich anthocyanin. Many studies have confirmed that anthocyanins have good antioxidant activity. They have many physiological functions such as anti-inflammatory, anti-tumor, anti-cancer, and protection of eyesight. At present, people are eagerly pursuing health foods, and more and more raw materials with physiological effects are used to develop a lot of health foods. Tablet is one of the common types of health foods, with advantages of small size, convenient carrying, low cost, etc. This experiment aims to develop sustained-release tablets by roselle extract powder, and it can be slowly released in the stomach while avoiding damage by the alkaline environment of the intestine to improve the bioavailability. The anthocyanins can be effectively extracted by heating at 75 ℃ for 30 minutes by 30% ethanol. HPLC results showed that the main anthocyanin type of extract was delphinidin, and its content was 126.34 mg/100 g of dried roselle calyces. Also, the DPPH, ABTS free radical scavenging capacity and Fe3+ reducing ability of extract were good. The roselle extract gastro-floating sustained-release tablets prepared with the appropriate proportion of excipients can be quickly floated, and can continuously floating over 12 hours in vitro simulated gastric fluid environment. During the process, the tablets will not disintegrate, keeping the colloidal skeleton slowly releasing the internal index components.With the content of extract powder increased, the cumulative release at 12 hours will increase, and the release of the index components will follow the zero-order kinetics (R2>0.9). The value of R2 with Higuchi kinetic equation was the highest, indicating that the index component in the gastric floating sustained-release tablets prepared in this experiment were released in a diffusion manner, and the release of index components was accumulated. There is a positive relationship between the square root of the time and the cumulative release, and the content of extract powder not change the release behavior. In the Korsmeyer-Peppas release kinetic model showed that the release mechanism of the index component was anomalous transport, representing there was a synergistic effect of diffusion and skeleton erosion.
The results of this experiment can lay a theoretical foundation for future development of anthocyanin sustained-release tablets.

摘 要 i
Abstract ii
目次 iv
圖表索引 xi
表次 xi
圖次 xiii
壹、引言 1
貳、文獻回顧 2
一、洛神葵（Roselle）之介紹 2
(一) 主要簡介 2
(二) 洛神葵之機能成分、營養 4
(三) 洛神葵之主要產品 4
二、花青素之介紹 7
(一) 花青素之簡介 7
(二) 花青素之結構 7
(三) 花青素之消化吸收 8
(四) 花青素之保健功效 11
1. 預防心血管疾病 11
2. 抗癌症 11
3. 抗腫瘤 11
4. 改善視力 11
5. 抗糖尿病 12
6. 保護肝臟健康 12
（五）花青素之發展前景 12
（六）花青素之影響因子 14
1. pH 14
2. 溫度（Temperature） 14
3. 光（Light） 15
4. 酵素（Enzyme） 15
5. 氧氣（Oxygen） 15
6. 其他因素 15
三、保健食品之介紹 19
（一）保健食品之簡介 19
（二）保健食品市場 21
1. 台灣 21
2. 中國大陸 21
3. 全球 21
四、錠劑之介紹 27
（一）錠劑之簡介 27
（二）錠劑之類型 27
（三）錠劑之配方組成（賦形劑） 32
（四）壓製錠劑之製程 32
1. 直接壓錠法( Direct compression ) 32
2. 溼式造粒法( Wet granulation ) 32
3. 乾式造粒法( Dry granulation ) 32
五、胃滯留給藥系統之介紹 34
（一）胃滯留給藥系統之常見類型 34
1. 胃漂浮型（Gastric retenting-floating drug delivery system，GRFDDS） 34
2. 體積膨脹型（Size-increasing drug delivery systems） 34
3. 生物粘附型（Bioadhesive drug delivery systems） 34
（二）胃滯留給藥系統之特性： 35
六、藥物釋放動力學 36
（一）藥物釋放動力學介紹 36
（二）釋放動力學模型 36
1. 零級動力學（zero-order kinetics） 36
2. 一級動力學（first-order kinetics） 36
3. Higuchi動力學（Higuchi kinetics） 37
4. Korsmeyer–Peppas動力學（Korsmeyer–Peppas kinetics） 37
叁、實驗目的 39
肆、實驗架構 40
伍、材料與方法 41
一、實驗材料 41
(一)主原料 41
1. 洛神葵花萼 41
2. 洛神葵萃取粉 41
（二）賦形劑 41
1. 羥丙甲基纖維素（HPMC） 41
2. 碳酸氫鈉（NaHCO3） 41
3. 乳糖 (Lactose) 41
4. 微晶纖維素 ( Microcrystalline cellulose, MCC ) 41
5. 硬脂酸鎂 ( Magnesium stearate ) 42
6. 聚乙烯比咯烷酮K30 (Polyvinylpyrrolidone, PVP K30) 42
7. 玉米澱粉 (Corn starch) 42
（三）試驗藥品 42
1. 沒食子酸 42
2. Trolox 42
3. DPPH（2,2-diphenyl-1-picrylhydrazyl） 42
4. ABTS（3-ethylbenzthiazoline-6-sulfonic acid） 42
5. HPLC標準品: 42
二、實驗方法 43
（一）洛神葵乙醇萃取物製備 43
（二）機能成分分析 43
1. 總花青素含量 43
2. 矢車菊素及飛燕草素含量分析 44
3. 總酚含量( Total polyphenol ) 44
（三）抗氧化能力分析 45
1. DPPH自由基清除能力 45
2. ABTS+自由基清除能力 45
3. 亞鐵離子抗氧化能力(Ferric ion reducing antioxidant power, FRAP) 45
（四）降解安定性評估 46
1. 不同pH環境之萃取物樣品處理 46
2. 全波長掃描 46
3. 降解動力學 46
4. 色澤測定(Color analysis) 47
（五）洛神葵萃取粉胃漂浮緩釋錠製備 48
（六）配方粉體物性探討 51
1. 水分（Water content） 51
2. 粉體假密度( Bulk density , ρb) 51
3. 粉體振實密度( Tapped density, ρtap ) 51
4. 流動性 51
（七）錠劑物性品質分析 52
1. 重量差異度分析 (Variance of tablet weight ) 52
2. 直徑厚度 ( Diameter & Thickness ) 52
3. 硬度試驗 ( Hardness ) 52
4. 脆碎度試驗 ( Friability ) 54
5. 色澤分析 ( Color ) 54
6. 示差熱掃描儀( Differential scanning calorimetry, DSC) 54
7. 傅里葉轉換紅外光譜（Fourier transform infrared spectrometer , FTIR） 54
8. X光繞射 ( X-ray diffraction analysis, XRD ) 55
（八）錠劑體外模擬試驗 55
1. 體外釋放試驗（In vitro drug release test） 55
2. 錠劑漂浮性能（Tablet floating capacity） 55
3. 侵蝕膨潤試驗（Swelling and erosion studies） 55
4. 掃描式電子顯微鏡（SEM） 56
5. 釋放動力學評估（Release kinetics assessment） 56
（九）數據分析 57
陸、結果與討論 58
第一章「洛神葵花青素乙醇萃取物抗氧化活性及其降解特性分析」 58
（一）不同濃度乙醇萃取結果 59
二、萃取物之機能成分 61
1. 總酚含量 61
2. 總花青素含量 61
3. HPLC分析 62
三、抗氧化分析 64
1. DPPH自由基清除能力 64
2. ABTS自由基清除能力 64
3. FRAP還原能力 64
四、熱安定性探討 66
五、pH影響 66
1. 全波長掃描 66
2. 不同pH環境下熱降解安定性 71
3. 動力學評估 73
4. 色澤分析 77
本章小結 79
第二章 「洛神葵（花青素）胃漂浮錠-構型及製備技術評估」 83
一、HPMC含量對錠劑之影響 84
1. 物性品質及漂浮性能 84
2. 體外模擬釋放分析 88
二、NaHCO3含量對錠劑之影響 90
1. 物性品質 90
2. 體外模擬釋放分析 90
三、乳糖對錠劑之影響 94
1. 物性品質 94
2. 體外模擬釋放分析 94
本章小結 98
第三章「洛神葵（花青素）胃漂浮錠釋放特性評估」 99
一、配方粉體物性分析 100
1. 水分及流動性 100
2. 微細構造觀察 100
二、錠劑物性品質分析 104
1. 外觀及色澤分析 104
2. 硬度及脆碎度分析 104
3. 熱性質、FTIR及XRD分析 108
三、體外模擬釋放特性評估 121
1. 漂浮性能分析 121
2. 釋放量分析 121
3. 微細構造觀察 121
4. 侵蝕膨潤分析 127
5. 釋放動力學評估 130
本章小結 136
柒、結論 137
捌、參考文獻 138

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