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研究生:吳姿慧
研究生(外文):Tzu- Hui Wu
論文名稱:六味地黃丸新劑型之研究
論文名稱(外文):A Study on the Novel Dosage Form of Liu-Wei-Di-Huang-Wan
指導教授:詹道明詹道明引用關係卓玟禾
指導教授(外文):Thau-Ming ChamWen-Ho Chuo
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:139
中文關鍵詞:六味地黃丸擠壓搓圓法直交配置法傳統中藥示差掃描卡計法
外文關鍵詞:Liu-Wei-Di-Huang-Wanextrusion-spheronizationorthogonal arrayTraditional Chinese Medicines (TCM)Differential Scanning Calorimetry(DSC)
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中文摘要
六味地黃丸為中國傳統的製劑,主要由熟地黃、山茱萸、山藥、茯苓、澤瀉及牡丹皮等六味藥所組成,本實驗將市售六種藥材研磨粉末分別與三種常用賦形劑(Era-Tab®、Lactose、Avicel PH102®)以擠壓搓圓機製備成中藥新劑型。並將所製得錠劑、圓粒與市售品置於三種溫度(30℃,37℃,45℃)及相對濕度(75%)的條件下貯存,並定時取出以高效率液相層析層析(HPLC)分析指標成分paeonol及loganin之含量變化情形,由實驗結果顯示,分析paeonol指標成分,錠劑安定性與市售品類似;但對分析loganin而言,錠劑及圓粒劑型皆有比市售品佳的安定性。
利用示差掃描熱分析法(DSC),針對六味地黃丸之二種主要成分(Paeonol,Loganin)來與三種常用賦形劑進行交互作用探討,結果發現賦形劑Avicel PH102®與兩種指標成分皆不會有交互作用情形發生,但Era-Tab®和Lactose卻會產生交互作用。
實驗之第二部分是以擠壓搓圓機進行六味地黃丸圓粒之製備並且利用直交配置表之製程設計進行新劑型之研究,評估六味地黃丸圓粒之圓度及產率而言,擠壓網口徑和搓圓轉速兩者為最具影響力之變因。此外,還利用適當壓力將圓粒壓製成錠劑,並與市售六味地黃丸進行體外溶離試驗之比較,由結果顯示自製錠劑與市售丸劑之溶離曲線是不相似的。

Abstract
Liu-Wei-Di-Huang-Wan, one of the Traditional Chinese Medicines (TCM), composed of rehmanniae radix, corni fructus, dioscoreae rhizoma, alismatis rhizoma, moutan cortex and polyporus. In this study, the powders of six herbs with three frequently used excipients (Era-Tab®, Lactose, Avicel PH102®) were made to be novel herbal dosage form by extrusion -spheronization method. The tablets, pellets and common products were then stored at three conditions (30℃/ 75% R.H., 37℃/ 75% R.H., 45℃/ 75% R.H.) for three months. The contents of two active ingredients paeonol, loganin of these six herbs were then analysed periodically by HPLC. The results show that the active ingredients of paeonol for tablets are as stable as common products. Another active ingredient, loganin, tablets and pellets are more stable than common products.
The possible interaction of the excipients (Era-Tab®, Lactose, Avicel PH102®) and active ingredients (paeonol, loganin) were studied by Differential Scanning Calorimetry(DSC). The result showed that Avicel PH102® had no interaction effect with the two active ingredients, but Era-Tab® and Lactose had the interaction effect.
The second part is the development of novel dosage form of Liu-Wei-Di-Huang-Wan by extrusion-spheronization using orthogonal array design. In the shape of pellets and yield study, the extrude screen and spheronization time are significantly variable. Then, the pellets are compressed at proper pressure and the dissolution rates of tablets are compared with TCM dosage forms. The result showed that the novel dosage forms of tablets and TCM dosage form had no similarity.

目錄
表次目錄------------------------------------------------------I
圖次目錄----------------------------------------------------III
中文摘要--------------------- --------------------------------X
英文摘要----------------------- -----------------------------XI
本文
壹、緒論------------------------------------------------------1
一、實驗背景--------------------------------------------------1
二、與傳統劑型做比較------------------------------------------6
三、中藥材之概述----------------------------------------------7
(一)地黃(Rehmanniae Radix)------------ -------------------7
(二)山茱萸(Corni Fructus)--------------------------------10
(三)山藥(Dioscoreae Rhizoma)--------- -------------------11
(四)澤瀉(Alismatis Rhizoma)------------------------------13
(五)牡丹皮(Moutan Cortex)--------------------------------15
(六)茯苓(Polyporus)--------------------------------------17
四、擠壓搓圓之技術-------------------------------------------19
五、實驗設計法-----------------------------------------------20
(一)複因子實驗設計法------------ --------------------------23
(二)2的3次方複因子實驗設計法-------------------------------24
(三)複因子試驗直交表之應用--------------- -----------------29
(四)2的3次方複因子之直交表構成-----------------------------29
(五)直交表之應用--------------------------- ---------------31
貳、實驗目的-------------------------------------------------33
參、材料與儀器設備-------------------------------------------35
一、藥品-------------------------------------------------35
二、內部標準品-------------------------------------------35
三、賦形劑與化學試藥-------------------------------------35
四、儀器設備---------------------------------------------36
肆、實驗方法-------------------------------------------------38
一、示差掃瞄熱分析法(DSC)--------------------- ------------38
二、以擠壓搓圓機進行六味地黃丸圓粒之製備--- -----------------38
三、製成圓粒之處方設計---------------------------------------39
(一)賦形劑Avicel PH102®之六味地黃丸圓粒---- ------------39
(二)賦形劑Era-Tab®之六味地黃丸圓粒-------------- -------40
(三)賦形劑Lactose之六味地黃丸圓粒--- -------------------40
四、六味地黃丸圓粒成品之外觀---------------------------------40
(一)照相式光學顯微鏡-----------------------------------------41
(二)掃瞄式電子顯微鏡- -----------------------------------41
五、圓粒產率分析---------------------------------------------41
六、圓度分析-------------------------------------------------42
七、膠囊劑型之製備-------------------------------------------42
八、錠劑劑型之製備-------------------------------------------42
九、體外溶離試驗---------------------------------------------43
十、高效能液相層析儀(HPLC)之分析---------------------------44
(一)Paeonol分析條件----------------------------------------45
(二)Paeonol檢量線的製作------------------------------------46
(三)Paeonol分析方法的確效----------------------------------46
(四)Loganin分析條件------ -------------------------------47
(五)Loganin檢量線的製作------------------------------------48
(六)Loganin分析方法的確效----------------------------------49
十一、安定性試驗------------------- -------------------------49
伍、結果與討論
一、同日間精密度與異日間精密度分析---------------------------55
二、利用示差掃瞄分析儀觀察中藥指標成分與賦形劑間的交互作用---57
三、以實驗設計法進行處方探討---------------------------------65
(一)賦形劑Avicel PH102®圓粒之圓度(E value)分析-------- 65
(二)Avicel PH102®圓粒之E value所採用的模式進行檢查-------66
(三)賦形劑Avicel PH102®圓粒之產率分析---- --------------67
(四)Avicel PH102®圓粒之產率分析所採用的模式進行檢查------69
(五)賦形劑Era-Tab®圓粒之圓度(E value)分析--------------76
(六)賦形劑Era-Tab®圓粒之E value所採用的模式進行檢查------76
(七)賦形劑Era-Tab圓粒之產率分析------------------------------77
(八)賦形劑Era-Tab®圓粒之產率分析所採用的模式進行檢查-----77
(九)賦形劑Lactose圓粒之圓度(E value)分析----------------- -85
(十)賦形劑Lactose圓粒之E value所採用的模式進行檢查-----------85
(十一)賦形劑Lactose圓粒之產率分析----------------------------86
(十二)賦形劑Lactose圓粒之產率所採用的模式進行檢查------------86
四、體外溶離試驗結果------------ ----------------------------95
五、三種賦形劑之溶離試驗結果運用統計分析Paeonol及Loganin----102
(一)Main effect A與C之分析------------------------------ -107
(二)Interaction effects A與C之分析------------------------108
(三)溶離模式線性探討 -------------------------------------111
六、三種賦形劑之自製處方與市售六味地黃丸的比較--------------114
七、安定性試驗----------------------------------------------123
陸、結論----------------------------------------------------131
柒、參考文獻------------------------------- -------------- -133

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