臺灣博碩士論文加值系統

益生菌是一類重要的微生物調節劑，對腸道健康具有極其重要的促進作用。益生菌不僅能調節腸道菌群環境、提供能量，還能啟動腸道自體免疫與細胞免疫系統，達到保護機體的目的。
本研究之益生菌腸溶配方為先將益生菌Clostridium butyricum晶球製備為不同比例粒徑圓型顆粒，再進行膜衣工程階段，由同粒徑顆粒包覆腸溶高分子材料(HPMCP)、黏合劑配方，分別以五種不同厚度成為控釋膜衣層包膜後成為益生菌腸溶包膜晶球，經與中和胃酸劑與益生菌腸溶包膜晶球混合後以打錠擠壓技術製成多層晶球錠劑，以供進行進一步的溶離測試評估。實驗結果顯示，在相同pH值之益生菌腸溶包膜晶球溶離速率隨各種製程及配方參數而改變，這些關鍵參數包括晶球大小、包膜晶球圓錠外包覆之控釋膜厚度及腸溶 聚合物的添加量比例，另外也發現不同溶離試驗用溶劑也會影響溶離益生菌釋放。
本研究中發現在益生菌晶球包膜較厚控釋膜衣之配方能在經過模擬胃液溶解後，維持較完整的益生菌腸溶包膜晶球外觀，經模擬胃液及腸液溶離試驗後評估腸溶錠內益生菌晶球控釋膜衣包覆較厚之配方在溶離實驗中能維持較穩定的益生菌釋放，此外，本研究也發現藉由調控相關的製程參數也能提升益生菌晶球在腸道的安定性。
由研究瞭解，藉由調整適合的製程中變因可控制藥物的釋放機制與藥品穩定度，使其可避免藥物在胃部之裂解及刺激，在到達腸道位置後再進行藥物的釋放。

Probiotic is an important kind of microorganism modifier which plays a very important role on the physical health of intestinal tract. Probiotics not only regulate microenvironment of gut, provide energy to gut, but also induce the mucosal, humoral and cellular immunity in intestinal tract to protect human body.
In this research the enteric formula was prepared by first making the probiotic bacteria Clostridium butyricum crystal ball into millions of spherical ingots by extrusion technology, then film-coating the spherical ingot separately with five different thicknesses of control-release layers. The film-coated spherical ingots were then mixed with enteric polymer material, binders and disintegrating agents, and were then subjected to wet granulation and tableting.
These enteric tablets were evaluated for dissolution in simulated gastric fluid and simulated intestinal fluid. The experimental results show that the dissolution profile of the enteric formula at the same pH value varied with various processes and formulation parameters, including the size of the crystal sphere, the thickness of the coating on the probiotic crystal ball ingot, and the mass ratio of the enteric coating material. It was also found that the dissolving solutions affect the release profile of probiotic.
In this study, it was found that thicker coating on the probiotic crystal ball ingots tended to maintain better appearance of the enteric tablet after dissolution test in the simulated gastric fluid. Overall, the formula with thicker coating on the probiotic crystal ball ingots seems to maintain more stable release of probiotic.
It is also learned from this research that by adjusting the suitable process parameters, both the release profile and the stability of the drug can be manipulated, so that the drug can be prevented from cracking and agitation in the stomach, and the drug can be released after reaching the intestinal site.

中文摘要 ………………………………………………………………….....…I
ABSTRACT…………………………………………………………….………II
致謝…………………………………………………………………….……….IV
目錄…………………………………………………………………….……….V
表目錄 ……………………………………………………………….………...VII
圖目錄 ……………………………………………………………….………..VIII
第一章、 緒論…………………………………………………….……………..1
第二章、 文獻回顧……………………………………………………….……..5
第一節、 膜衣材料- 羥丙基甲基纖維素鄰苯二甲酸酯之介紹 ……….…......5
第二節、 膜衣材料- 蟲膠介紹…………………………………….………......12
第三節、 微生物體學(Microbiome)簡介………………………….………....13
第四節、 主成分- 益生菌(丁酸梭菌益生菌)……………………….….……..15
第五節、 物理特性比對-丁酸梭菌晶球圓錠（Clostridium butyricum）...16
第六節、 市售益生菌比較…………………………………….……………....21
第三章、 研究目的…………………...………….……………………............34
第四章、 機台、儀器、材料及方…………………………….……...............35
第五章、 實驗機台與方法………………………….………………................50
第六章、 實驗結果與討論………………………….………………................70
第七章、 結論…………………………………….…………………................73
第八章、 參考文獻…………………………………….……………................74

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