武艳雪　陈天丽　侯晓琳　闫妍　方晶　王孟聪　翁丽丽

中圖分类号 R285 文献标志码 A 文章编号 1001-0408（2021）21-2613-06

DOI 10.6039/j.issn.1001-0408.2021.21.09

摘 要 目的：优化酒赤芍炮制工艺，并考察其体外抗凝血效果。方法：以氧化芍药苷、芍药内酯苷、芍药苷、苯甲酸和水溶性浸出物的含量为考察指标，通过层次分析法（AHP）、指标相关性的指标权重确定方法（CRITIC）以及两者的混合加权法确定各指标的权重系数并计算综合评分，然后采用Box-Behnken响应面法优化酒赤芍的闷润时间、炒制时间和炒制温度等参数，再采用体外抗凝血实验对按最优炮制工艺所制备的酒赤芍进行初步药效学考察。结果：采用AHP-CRITIC混合加权法确定芍药内酯苷、氧化芍药苷、芍药苷、苯甲酸、水溶性浸出物的权重系数分别为0.233 9、0.131 7、0.183 3、0.078 9、0.372 3。酒赤芍的最优炮制工艺为闷润时间35 min、炒制时间20 min、炒制温度120 ℃。体外抗凝血实验结果显示，生赤芍和酒赤芍均能显著延长小鼠血浆的凝血酶时间、凝血酶原时间、活化部分凝血活酶时间，且酒赤芍的作用显著优于生赤芍（P<0.05）。结论：优化所得酒赤芍的炮制工艺稳定、可行;按此工艺所制酒赤芍的体外抗凝血作用较生品更好。

关键词 赤芍;酒赤芍;抗凝血作用;工艺优化;Box-Behnken响应面法

ABSTRACT   OBJECTIVE： To optimize the processing technology of Paeonia lactiflora stir-baked with wine， and to investigate its in vitro anticoagulant effect. METHODS： The weight coefficient of each index was determined and the comprehensive score was calculated with analytic hierarchy process （AHP）， Criteria Importance Though Intercrieria Correlation （CRITIC） and AHP-CRITIC weighting method， using the contents of oxypaeoniflorin， albiflorin， paeoniflorin， benzoic acid and water-soluble extract as index. Box-Behnken response surface methodology was used to optimize the parameters of P. lactiflora stir-baked with wine， such as moistening time， frying time and frying temperature. Then in vitro anticoagulant experiment was used to investigate the pharmacodynamics of P. lactiflora stir-baked with wine prepared according to the optimal processing technology. RESULTS： The weight coefficients of albiflorin， oxypaeoniflorin， paeoniflorin， benzoic acid and water-soluble extract determined by AHP-CRITIC weighting method were 0.233 9， 0.131 7， 0.183 3， 0.078 9， 0.372 3， respectively; the optimal processing technology of P. lactiflora stir-baked with wine included moistening time of 35 min， frying time of 20 min and frying temperature of 120 ℃. The results of in vitro anticoagulant test showed that P. lactiflora and P. lactiflora stir-baked with wine could significantly prolong the time of thrombin time， prothrombin time， activated partial thrombin time of plasma; the effects of P. lactiflora stir-baked with wine were significantly better than those of P. lactiflora （P<0.05）. CONCLUSIONS： The optimized processing technology of P. lactiflora stir-baked with wine is stable and feasible. The in vitro anticoagulant effect of P. lactiflora stir-baked with wine prepared by this tehcnology is better than that of raw products.

KEYWORDS   Paeonia lactiflora; Paeonia lactiflora stir-baked with wine; Anticoagulation; Technology optimization; Box-Behnken response surface methodology

赤芍为毛茛科植物芍药Paeonia lactiflora Pall. 或川赤芍Paeonia veitchii Lynch.的干燥根，味苦，微寒，归肝经[1]。赤芍的主要活性成分为芍药苷、芍药内酯苷、氧化芍药苷、苯甲酸等，具有抗肿瘤、抗凝、抗血栓、降血脂、抗动脉粥样硬化等药理作用[2]。赤芍的炮制方法有清炒、麸炒、酒制、醋制等，现代临床较为常用的有赤芍生品和酒制品[3]。酒制后可增强赤芍活血化瘀的功效[4]。虽然2020年版《中国药典》（一部）和多地的炮制规范均对酒赤芍有所记载[1，5]，但并未对其炮制工艺参数进行量化。……