芍要甘草湯之研究

Syudent

陳立奇(C L-C)

指導教授 ： 楊玲玲

臺北醫學大學/藥學院/生藥學研究所/碩士(1998年)

摘要

芍藥具有理想的鎮痙、止痛作用，是中醫治療腹部拘急疼痛的重要處方成份之一。 本論文從生物生藥學的角度，分別就芍藥之藥物藥效及藥物動力學性質進行探討。論文第 一部份之研究，評估芍藥及其配佐甘草之芍藥甘草湯與芍藥主成份paeoniflorin於天竺鼠 離體迴腸的藥理作用。研究結果顯示：(1)對離體迴腸自發性收縮及acetylcholine所誘生 興奮性攣縮，芍藥、芍藥甘草湯及paeoniflorin均具明顯的抑制作用，並具劑量依存性(d ose-dependence)。(2)對自發性收縮，芍藥萃取物之IC50為3.07mg/ml；芍藥甘草湯萃取 物之IC50為1.72mg/ml；另芍藥主成份paeoniflorin之IC50為0.54mg/ml。(3)對acetylcho line所誘生興奮性攣縮，芍藥萃取物之IC50為2.89mg/ml；芍藥甘草湯萃取物之IC50為1.4 5mg/ml；paeoniflorin之IC50為0.46mg/ml。綜合以上研究結果，驗證芍藥對腸道平滑肌 具有抑制作用，而paeoniflorin為其活性成份之一。 本論文第二部份以芍藥活性成份 之一paeoniflorin作為指標成份，應用HPLC分析技術進行芍藥及芍藥甘草湯之藥物動力學 研究。首先定量芍藥及芍藥甘草湯萃取物之paeoniflorin含量各為13.00%及9.31%，調製 芍藥及芍藥甘草湯水萃取物，以含10mg/kg paeoniflorin的劑量分別口服投予鼷鼠，測定 paeoniflorin之血中濃度。研究結果顯示：(1)口服投予芍藥水萃取物組，paeoniflorin 最高血中濃度(Cmax) 86.34 ng/ml、達最高血中濃度時間(Tmax) 14.00min、濃度時間曲 線下面積(AUC0-t) 8126.97 ng.min/ml、排除半衰期(T1/2) 94.16 min、清除率(CL/F) 1 113.35 ml/min.kg 、擬似分佈體積(Vd/F) 147.44L/kg及平均滯留時間(MRT) 135.64min 。(2)投予芍藥甘草湯水萃取物組，paeoniflorin之 Cmax 111.56ng/ml、Tmax 17.00min 、AUC0-t 12293.42 ng.min/ml、T1/2 116.17 min、CL/F 644.74 ml/min.kg、Vd/F 103. 05 L/kg 及 MRT 169.64 min。綜合以上結果，芍藥萃取物組之paeoniflorin動力學參數C max、AUC、CL/F及Vd/F與芍藥甘草湯組間的差異，具有統計學上之意義(p<0.05)。芍藥在 甘草的配佐之下，可明顯增加paeoniflorin之吸收，由此可驗證中藥方劑臨床治療之意義

關鍵字

芍藥

並列摘要

Paeoniae Radix is one of the most important constituents of traditional p rescriptions for treatment of abdominal pain and syndromes such as stiffness o f abdominal muscles. The first part of this bio-pharmacognosy study was conduc ted to evaluate the impact of aqueous extract of Paeoniae Radix on the viscera l muscle contraction of isolated guinea pig ileum in vitro and to describe the dose-response relationship. The experimental results indicated that Paeoniae Radix have significant anticontractile effect. For spontaneous contraction an d acetylcholine-induced spasmodic contraction of guinea pig ileum, the IC50 of Paeoniae Radix extracts were 3.07mg/ml and 2.89mg/ml, the IC50 of Shao-yaw-ga n-tsao-tang extracts were 1.72mg/ml and 1.45mg/ml, the IC50 of paeoniflorin, t he major constituent in Paeoniae Radix, were 0.54mg/ml and 0.46mg/ml, respecti vely. The second part of this study described the plasma profiles and phar macokinetic properties of paeoniflorin in mice after oral administration of aq ueous extracts of Paeoniae Radix and Shao-yaw-gan-tsao-tang (equal in dose of 10mg/kg paeoniflorin). Serum concentrations of paeoniflorin were estimated by high-performance liquid chromatography (HPLC) method. The serum concentration- time curves were fitted with mean terminal half-lives (T1/2) of 94.16 and 116. 17min, respectively. The maximum serum concentrations (Cmax) of paeoniflorin w ere 86.34 and 111.56ng/ml, time to maximum concentration (Tmax) were 14.00 and 17.00min, the AUC0-t were 8126.97 and 12293.42ng.min/ml, clearance (CL/F) val ues were 1113.35 and 644.74 ml/min.kg, volume of distribution (Vd/F) values we re 147.44 and 103.05 L/kg, and the mean residence time (MRT) were 135.64 and 1 69.64 min, respectively. There were significant differences in Cmax, AUC, CL/F and Vd/F of paeoniflorin between oral doses of aqueous extracts of Paeoniae R adix and Shao-yaw-gan-tsao-tang.