臺灣博碩士論文加值系統

台灣是自由醫藥的巿場，中、西醫藥並存由來已久。關於便秘問題，許多常用西藥瀉劑缺乏醫學實證或有副作用，長照機構之便秘患者與醫療人員對便秘處置多不滿意，結果同時向中、西醫求診的情形也很普遍。本研究目的在匯集傳統典籍和專業中、西醫師的經驗，選用有臨床療效之中藥組成複方(加味溫脾湯)，先以安慰劑作對照以證實其臨床療效，再與具實證基礎的西藥瀉劑Lactulose作比較，進一步驗證其療效與安全性。

研究皆採隨機、雙盲、安慰劑對照的平行試驗設計，以長照機構中慢性便秘成人為收案對象，治療期八週，停藥後追蹤四週。結果在中藥與安慰劑對照之研究結果顯示：在治療期間，可增加每週自發性解便頻率（6.2 vs 3.4, weeks 1-4, p < 0.001）、減少每週肛門處置頻率（0.4 vs 0.9, weeks 1-8, p = 0.003）和拯救性瀉劑用量（14.4 vs 33.4 MgO/wk, weeks 5-8, p < 0.001）。

而中藥與Lactulose之比較研究顯示：加味溫脾湯在每週自發性解便頻率（6.9 vs 4.5, weeks 1-4, p < 0.001）、每週肛門處置頻率（0.4 vs 0.8, weeks 1-8, p = 0.007）、每週拯救性瀉劑用量（1.7 vs 10.4, weeks 5-8, p = 0.002）及瀉劑花費方面（42.8 vs 142.5 NTD/wk, weeks 5-8, p < 0.001）優於Lactulose組；排便量、軟硬度與整體性療效分析，兩者則無顯著差異，但Lactulose組有較多嚴重不良反應事件及難治性便秘的個案數。

本研究證實加味溫脾湯是安全有效的中藥複方，且可替代Lactulsoe作為長照機構治療便秘的藥物，更是未來便秘新藥研發時重要之參考依據。但其維持效果、對一般社區民眾的療效、有效成份、作用機制等，則有待進一步的研究探討。

Constipation is a common gastrointestinal complaint in long-term care. However, many institutionalized patients and their healthcare providers are dissatisfied with current laxative therapy and, therefore, seek help from complementary and alternative medicine. We conducted two clinical trials aimed to evaluate the therapeutic efficacy and safety of CCH1, modified from an ancient herbal formula of Wen-Pi-Tang in traditional Chinese medicine, for the residents with constipation in long-term care.

In the first randomized, double-blind, placebo-controlled trial, we randomized 90 residents from three long-term care units to 8 weeks of treatment with CCH1 or placebo and then followed up the subjects for an additional 4 weeks. The mean numbers of weakly spontaneous bowel movement (SBM) in the CCH1 group were greater than in the placebo group during the treatment phase of 8 weeks ( p < 0.05); the greatest difference was during weeks 1-4 (6.2 ± 2.2 vs 3.4 ± 2.1, p < 0.001). Smaller mean numbers of weekly rectal treatments (RT) were observed with CCH1 compared with placebo during weeks 1-8 (p < 0.05). The mean numbers of weekly rescue laxative tablets of magnesium oxide (MgO) were significantly less in the CCH1 group than in the placebo group during entire 12-week period (p < 0.01), with the greatest difference during weeks 5-8 (14.4 ± 16.3 vs 33.4 ± 23.5, p < 0.001). No significant safety concerns were noted.

The second study is a randomized, double-blind, double dummy controlled trial. We compared therapeutic efficacy, safety, and laxative cost of CCH1 and lactulose for 93 residents with chronic constipation in two long-term care facilities. Baseline characteristics of patients were similar between the two treatment groups in 2-week run-in period. Mean numbers of weekly SBM in CCH1 group were greater than those in lactulose group during 8-week treatment phase (6.8 vs 5.0, p = 0.001); greatest difference was during weeks 1-4 (6.9 vs 4.5, p < 0.001). CCH1 group was superior to lactulose group in RT frequency (0.4 vs 0.8 per week during weeks 1-8, p = 0.007), amount of additional laxative use (1.7 vs 10.4 tablets/wk during weeks 5-8, p = 0.002) and average laxative cost (42.8 vs 142.5 NTD/wk during weeks 5-8, p < 0.001). No significant differences were found in stool consistency, stool amount, global assessment, and safety concerns.

In conclusion, the six-herb formula (CCH1), compared with placebo, is safe and effective on the treatment of constipation in long-term care. Both CCH1 and lactulose were efficacious and well tolerated but CCH1 produced more frequent spontaneous bowel movements, less frequent rectal treatments, lower amounts of additional laxative and lower laxative cost than lactulose. Although the maintenance effect of CCH1 was uncertain or limited, it still provided a good alternative laxative to lactulose as a treatment option in long-term care and suggested good value for new drug development. Further clinical studies may be necessary to evaluate the safety and cost-effectiveness of CCH1 fot the polulation in the community, particularly with regard to concerns about quality of life and subjective outcomes.

目　錄
第一章 前言 1
第二章 文獻探討 6
第一節 西方醫學對便秘的認識 6
第二節 中國醫學對便秘的認識 17
第三章 材料與方法 25
第一節 加味溫脾湯與安慰劑比較之研究 25
一、 研究對象 25
二、 研究藥物製備 26
三、 研究設計 27
四、 樣本數估計 32
五、 統計分析 33
第二節 加味溫脾湯與Lactulose比較之研究 34
一、 研究對象 34
二、 研究藥物製備 36
三、 研究設計 37
四、 樣本數估計 43
五、 統計分析 43
第四章 結果 45
第一節 加味溫脾湯與安慰劑比較之研究 45
第二節 加味溫脾湯與Lactulose比較之研究 58
第五章 討論 71
第六章 結論 79
參考文獻 80
附錄一 衛生署藥品許可證及仿單 (附子理中湯) 88
附錄二 衛生署藥品許可證及仿單 (大黃) 90
附錄三 臨床試驗許可書 (加味溫脾湯與安慰劑比較之研究) 92
附錄四 受試者說明及同意書 (加味溫脾湯與安慰劑比較之研究) 93
附錄五 臨床試驗登錄 (加味溫脾湯與安慰劑比較之研究) 98
附錄六　加味溫脾湯的高效液相層析圖（HPLC） 101
附錄七 給藥紀錄單(加味溫脾湯與安慰劑比較之研究) 102
附錄八 排便紀錄單(加味溫脾湯與安慰劑比較之研究) 103
附錄九 臨床試驗許可書(加味溫脾湯與Lactulose比較之研究) 104
附錄十 受試者說明及同意書(加味溫脾湯與Lactulose比較之研究) 105
附錄十一 臨床試驗登錄(加味溫脾湯與Lactulose比較之研究) 111
附錄十二 衛生署藥品許可證及仿單(Lactulose) 114
附錄十三 給藥紀錄單(加味溫脾湯與Lactulose比較之研究) 116
附錄十四 排便紀錄單(加味溫脾湯與Lactulose比較之研究) 117
英文摘要 118
作者簡歷 120
謝辭 123

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