目的 優(yōu)選桂枝芍藥知母顆粒的提取參數(shù)。方法 采用HPLC法和Elisa法，以桂皮醛、芍藥苷、芒果苷、甘草酸提取率，出膏率及炎癥因子白細(xì)胞介素-6（IL-6）水平為評價(jià)指標(biāo)，采用熵權(quán)法確定各指標(biāo)權(quán)重系數(shù)，結(jié)合Box-Behnken響應(yīng)面法結(jié)果優(yōu)化桂枝芍藥知母顆粒提取工藝參數(shù)。結(jié)果 桂皮醛、芍藥苷、芒果苷、甘草酸分別在3.27～104.64、8.16～261.03、1.39～89.27、1.00～33.00 μg/mL內(nèi)呈良好的線性關(guān)系，r分別為0.9999、1.000 0、0.999 9、0.999 9；桂枝芍藥知母提取液具有抑制類風(fēng)濕關(guān)節(jié)炎滑膜成纖維細(xì)胞MH7A細(xì)胞（由TNF-α造模）增殖的作用，半數(shù)抑制濃度（IC₅₀）為1.02 mg/mL，且具有抗炎活性，采用信息熵賦權(quán)法確定各指標(biāo)的客觀權(quán)重，按照其確定的權(quán)重系數(shù)進(jìn)行綜合評價(jià)，且考慮實(shí)際情況，確定桂枝芍藥知母顆粒的最佳提取工藝條件為加16倍量水，提取3次，每次1 h。驗(yàn)證試驗(yàn)結(jié)果顯示預(yù)測值與實(shí)測值相比，RSD小于3%。結(jié)論 優(yōu)選后的工藝穩(wěn)定可行，重復(fù)性好，可用于大批量生產(chǎn)。

Objective To optimize the extraction process parameters of Guizhi Shaoyao Zhimu Granules (GSZG). Methods Using high performance liquid chromatography and Elisa, the extraction rate of trans-cinnamaldehyde, paeoniflorin, mangiferin, glycyrrhizic acid, the dry extract yield of extracted herbs and inflammatory factor IL-6 were comprehensively evaluated. The information entropy weighting method was used to determine the objective weight of each index, and response surface methodology was adopted to optimize the extraction process parameters of GSZG. Results The method had good linear relationship within the range of 3.27-104.64 μg/mL for trans-cinnamaldehyde (r =0.999 9), 8.16-261.03 μg/mL for paeoniflorin (r=1.000 0), 1.39-89.27 μg/mL for mangiferin (r=0.999 9), and 1.00-33.00 μg/mL for glycyrrhizic acid ammonium salt (r=0.999 9). Guizhi-Shaoyao-Zhimu extraction had the effect of inhibiting the proliferation of MH7A cells (molded by TNF-α) with IC₅₀ of 1.02 mg/mL, and had anti-inflammatory activity. Entropy method was more scientific, reasonable and stable. According to the comprehensive scoring results and practical situation, it was determined that the best extraction process of the preparation was to add 16 times the amount of water, and decocted three times for 1 h each time. The RSD of the predicted value was less than 3% compared with the measured value. Conclusion The preferred process has high extraction rate, with good stability and repeatability, which is suitable for the mass production of GSZG.

國家科技部“重大新藥創(chuàng)制”科技重大專項(xiàng)（2018ZX09721004-009）