以天然交聯劑genipin交聯明膠的藥物制放微粒載體：體外與體內性質評估

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梁晃千(Huan-Qian Lia) 查詢紙本館藏

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化學工程與材料工程學系

論文名稱

以天然交聯劑genipin交聯明膠的藥物制放微粒載體：體外與體內性質評估

相關論文

★ 以天然交聯劑Genipin交聯幾丁聚醣材料的體外及體內性質評估	★ 以Genipin或Carbodiimide交聯生物組織材料的交聯結構與交聯性質探討
★ 由中藥梔子果實裡萃取純化天然交聯劑 Genipin及其在生醫材料上的應用

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摘要(中)

文獻上記載明膠曾被用來當做製備藥物制放微粒載體的材料。但是過去的臨床經驗指出，明膠為一易溶於水且澎潤度相當高的水膠，因此以明膠包覆藥物的微粒載體，通常只能用於短效性的藥物制放。為了克服此一問題，臨床上常以formaldehyde或gluteraldehyde之類的化學交聯劑來交聯明膠微粒載體，藉以控制其澎潤度及水解速率，使得藥物能達到緩釋與長效的效果。但是formaldehyde及gluteraldehyde的細胞毒性太強，因此限制了明膠製成的微粒載體在臨床上的用途。為了解決這個問題，我們使用從中藥梔子果實裡萃取純化出來的一種天然交聯劑genipin，來交聯明膠製備藥物制放微粒載體。
本研究分別以體外實驗與體內實驗兩大部份，來評估以genipin交聯明膠製備藥物制放微粒載體(GP微粒載體)，當做肌肉注射劑型藥物制放的可行性。實驗?，我們的實驗對照組是以glutaraldehyde交聯明膠製備的藥物制放微粒載體(GA微粒載體)。體外實驗主要是探討以不同製備程序製備出來的GP微粒載體的表面形態、交聯程度及其粒徑大小與分佈情形，以找出製備GP微粒載體的較佳製程條件。較佳製程的選擇則是以以下幾個條件來判斷：(1)微粒表面光滑且不產生糾結的現象；(2)由於本研究希望能延長明膠微粒載體的水解時間，所以微粒載體的交聯程度將愈高愈好；(3)由於文獻上曾提及，理想的肌肉注射劑型微粒載體的粒徑大小約為20-100

關鍵字(中)

★ 藥物制放
★ 明膠

關鍵字(英)

★ Genipin

論文目次

目錄
頁數
摘要 I
目錄III
圖索引VI
表索引 IX
第一章緒論1
1.1藥物在生物體內的傳輸路徑1
1.2藥物制放技術2
1.3藥物輸送劑型與材料之簡介及文獻回顧2
1.4免疫反應及發炎修復4
1.5 研究動機與目的5
第二章 GP微粒載體的製備7
2.1研究目的7
2.2實驗材料7
2.2.1微粒載體的組成成份7
2.2.2 微粒載體的製備7
2.3 實驗方法9
2.3.1 粒徑大小與分佈情形9
2.3.2 交聯指數13
2.3.2.1 方法一的交聯指數14
2.3.2.2 方法二的交聯指數14
2.3.2.3 方法三的交聯指數14
2.3.3 SEM微粒載體表面形態觀察15
2.4 實驗結果與討論15
2.4.1 粒徑大小與分佈情形15
2.4.2 交聯指數17
2.4.2.1 方法一的交聯指數17
2.4.2.2 方法二的交聯指數17
2.4.2.3 方法三的交聯指數18
2-5結論25
第三章GP微粒載體在動物體內的生物相容性評估27
3.1研就目的27
3.2材料與方法27
3.2.1微粒載體製備27
3.2.2 實驗方法28
3.2.2.1 微粒載體被分解情形觀察29
3.2.2.2 SEM表面形態觀察31
3.2.2.3 病理顯微觀察31
3.3實驗結果與討論34
3.3.1微粒載體被分解情形34
3.3.2 SEM表面形態觀察34
3.3.3 病理切片觀察40
3.4交聯反應機制47
3.5結論48
第四章GP微粒載體體外性質探討50
4.1研究目的50
4.2材料與方法
4.2.1微粒載體製備50
4.2.2實驗方法
4.2.2.1微粒載體膨潤速率觀察與膨潤動力學
分析51
4.2.2.2微粒載體體外抗酵素分解實驗56
4.2.2.3 被酵素分解後的微粒載體表面形態觀察56
4.2.2.4不同製備條件對藥物包覆率的影響56
4.3實驗結果與討論57
4.3.1微粒載體膨潤速率觀察與膨潤動力學分析57
4.3.2微粒載體體外抗酵素分解實驗59
4.3.3被酵素分解後的微粒載體表面形態觀察59
4.3.4不同製備條件對藥物包覆率的影響61
4.4、結論63
參考文獻65

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指導教授

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審核日期

2000-6-28

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