臺灣博碩士論文加值系統

中文摘要
中藥由於成份複雜，且一藥多效，故需經適當的處理，才能達到預期的效果。特別是含有刺激性和有毒性的藥物，若不經過加工炮製，在臨床上應用，就可能產生副作用和中毒的現象。藥物經不同的炮製處理後，所含化學成分和理化性質，往往會產生不同的量變和質變。炮製在中醫藥上具有舉足輕重的地位，幾乎中藥所有臨床應用都與炮製有關。
附子為毛茛科烏頭屬植物烏頭(Aconitum carmichaeli Debx.)的側根。本實驗經由大陸四川成都進口生附子，以外觀、組織切片、TLC、HPLC等方式，基原鑑定確定後，經由不同炮製方法製成鹽附子、黑順片、白附子。本實驗觀察附子炮製前後成分及毒性變化研究，及藥理活性。
經由HPLC定量結果顯示aconitine在1 g生附子、鹽附子、黑順片及白附子中含量分別為0.05 mg、0.006 mg、0.002 mg及0.002 mg；lappaconitine含量在1 g生附子、鹽附子、黑順片及白附子中含量分別為0.119 mg、0.0003 mg、0.005 mg及0.004 mg。生附子、鹽附子、黑順片及白附子的半致死劑量（LD50）分別為1.4 g/kg、9.9 g/kg、10.6 g/kg及20.2 g/kg。
在鎮痛表現上：附子能明顯增加疼痛閾值，其作用機轉與μ-opoid receptor有關。炮製品中則以鹽附子鎮痛效果最好，最接近生附子，且鎮痛效果會隨著時間增長而效果越佳。
在降血糖表現上：由streptozotocin（STZ）所誘導的糖尿病大鼠，分別以口服50 mg/kg的劑量兩小時後，生附子、鹽附子及黑順片所產生的降血糖百分比分別為17.8 ± 2.7 %, 16.3 ± 2.4 % 及 17.6 ± 3.1 %。然而，白附子在STZ大鼠則無法有效的產生降血糖的作用，所產生的降血糖百分比僅達0.8 ± 1.8 %。
經由本實驗所得結果，可知附子經過炮製後，毒性確實降低，達到炮製的目的。附子的炮製品，在鎮痛及降血糖上的藥理活性表現，則以鹽附子為最佳。
關鍵字：附子、炮製、鹽附子、黑順片、白附子

Abstract
The active ingredients of the Chinese herb are too complex to evaluate. One prescription used in the Chinese traditional medicine might use to cure different disorders. The ingredients extract from an herb will be different with different preparation. The therapeutic effect will be potentate with proper preparation; however, the toxicity might be obtained if the preparation is not well. Therefore, the quality control in the preparation of Chinese herbs is very important. Preparation is important in Chinese traditional medicine, almost clinical use are about preparation.
In the present study, the botanical origin of the Fuzei (Aconitum carmichaeli Debx.) obtained from Chengdu, the capital of Sichuan Province, was investigated by physiognomy, anatomy method, Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography (HPLC). Then, crude Fuzei was prepared to Salt-Fuzei, Hei-Swong-Peng and Pai-Swong-Peng to compare the toxicity and pharmacology activity between these preparations.
The content of aconitine in Fuzei without preparation was about 0.05 mg/g obtained from quantitative analysis by HPLC. However, the contents of aconitine in Salt-Fuzei, Hei-Swong-Peng and Pai-Swong-Peng were 0.006 mg/g、0.002 mg/g and 0.002 mg/g , respectively. The content of lappaconitine in Fuzei without preparation was about 0.119 mg/g obtained from quantitative analysis by HPLC. However, the contents of lappaconitine in Salt-Fuzei, Hei-Swong-Peng and Pai-Swong-Peng were 0.0003 mg/g、0.005 mg/g and 0.004 mg/g , respectively. The median lethal dose（LD50）in Fuzei without preparation was 1.4 g/kg. In contrast, the LD50 was increased to 9.9 g/kg, 10.6g/kg and 20.2 g/kg in Salt-Fuzei, Hei-Swong-Peng and Pai-Swong-Peng, respectively.
Fuzei possess the ability to increase the threshold of pain that is centrally mediated by opioid receptors. Among the processed products, the analgesic effect of Yan-Fuzei was the most potent, which was nearly that obtained from crude Fuzei.
Oral administration of streptozotocin-induced diabetic rats (STZ-diabetic rats) with Fuzei at the dosage of 50 mg/kg for 2 h, the plasma glucose lowering activity of Fuzei without preparation, Salt-Fuzei and Hei-Swong-Peng were 17.8 ± 2.7 %, 16.3 ± 2.4 % and 17.6 ± 3.1 %, respectively. However, the plasma glucose lowering activity of Pai-Swong-Peng in STZ-diabetic rats was only 0.8 ± 1.8 %.
In fact, the concentrations of aconitine were significantly less in processed Fuzei than that in crude Fuzei. The biological effect of Yan-Fuzei, the salt baking product, was most potent among the processed products. The present study will be helpful in clinic to apply Fuzei safety.
Key words : Fuzei ，preparation，Salt-Fuzei ，Hei-Swong-Peng，Pai-Swong-Peng

目錄
頁次
誌謝…………………………………………………………………………Ⅰ
摘要…………………………………………………………………………Ⅱ
ABSTRACT…………………………………………………………………Ⅳ
目錄…………………………………………………………………………Ⅵ
表錄…………………………………………………………………………Ⅶ
圖錄…………………………………………………………………………Ⅷ
縮寫表………………………………………………………………………Ⅹ
一、緒論……………………………………………………………………01
二、研究內容與方法………………………………………………………21
三、實驗結果………………………………………………………………43
四、討論……………………………………………………………………91
五、結論……………………………………………………………………95
參考文獻……………………………………………………………………97
簡歷………………………………………………………………………105


表 錄


表 1－1　附子歷代的炮製方法…………………………………………17
表 1－2　鎮痛系統圖……………………………………………………20
表 2－1　aconitine 移動相之沖提梯度…………………………………42
表 3－1　1g生附子、鹽附子、黑順片、白附子中aconitine含量…… 53
表 3－2　1g 生附子、鹽附子、黑順片、白附子中lappacon含量…………………………………………………………………54
表3－3　生附子、鹽附子、黑順片、白附子之LD50值…………………55
表3－4　生附子、鹽附子、黑順片、白附子在Wistar大白鼠給藥和給予
嗎啡μ型受體阻斷劑對鎮痛作用之影響………………………56
表3－5　生附子、鹽附子、黑順片、白附子在嗎啡μ型受體未剔除小鼠及嗎啡μ型受體剔除小鼠所產生的鎮痛作用比較值……57
表3－6　生附子、鹽附子、黑順片、白附子在STZ糖尿病大白鼠的降血糖活性…………………………………………………………58






圖 錄


圖 3－1　生附子外觀……………………………………………………59
圖 3－2　生附子組織切片(縱切) ………………………………………60
圖 3－3　生附子組織切片(縱切) ………………………………………61
圖 3－4　生附子TLC(aconitine為指標成分) …………………………62
圖 3－5　生附子TLC(lappaconitine為指標成分) ……………………63
圖 3－6　生附子指紋圖譜(aconitine為指標成分) ……………………64
圖 3－7　生附子指紋圖譜(lappaconitine為指標成分) …………………65
圖 3－8　生附子及炮製品與aconitine TLC圖…………………………66
圖 3－9　生附子及炮製品與lappaconitine TLC圖…………………67
圖 3－10　aconitine標準品HPLC圖譜…………………………………68
圖 3－11　lappaconitine標準品HPLC圖譜………………………………69
圖3－12　生附子之aconitine HPLC圖譜…………………………70
圖3－13　生附子之lappaconitine HPLC圖譜……………………71
圖 3－14　鹽附子之aconitine HPLC圖譜…………………………72
圖3－15　鹽附子之lappaconitine HPLC圖譜……………………73
圖3－16　黑順片之aconitine HPLC圖譜…………………………74
圖3－17　黑順片之lappaconitine HPLC 圖譜……………………75
圖3－18　白附子之aconitine HPLC圖譜…………………………76
圖3－19　白附子之lappaconitine HPLC圖譜……………………77
圖 3－20　生附子CH2Cl2層ES/MS圖……………………………78
圖 3－21　生附子 H2O層ES/MS圖………………………………79
圖 3－22　鹽附子 CH2Cl2層ES/MS圖…………………………80
圖3－23　鹽附子 H2O層ES/MS圖………………………………81
圖 3－24　黑順片 CH2Cl2層ES/MS圖……………………………82
圖 3－25　黑順片 H2O層ES/MS圖………………………………83
圖 3－26　白附子 CH2Cl2層ES/MS圖……………………………84
圖 3－27　白附子 H2O層ES/MS圖………………………………85
圖 3－28　生附子LD50圖……………………………………………86
圖 3－29　鹽附子LD50圖……………………………………………87
圖 3－30　黑順片LD50圖……………………………………………88
圖 3－31　白附子LD50圖……………………………………………89
圖 3－32　以口服60mg生附子、鹽附子、黑順片、白附子在不同時間產生的鎮痛圖……………………………………………… 90

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