目的 基于"成分反映活性，活性指向功效"的中药质量控制研究思路，以网络药理学筛选得到的活性成分为评价指标，对六味地黄系列制剂进行再评价研究。方法 采用网络药理学技术筛选出六味地黄系列制剂，如丸剂（大蜜丸、浓缩丸）、胶囊剂（胶囊、软胶囊）、颗粒剂及口服液治疗2型糖尿病、高血压和肾病综合征的共有核心活性成分，并以其中度值较高的13种活性成分（槲皮素、山柰酚、β-谷甾醇、泽泻醇B、泽泻醇B23乙酸酯、花旗松素、羟基莞花素、豆甾醇、啤酒甾醇、常春藤苷皂元、儿茶素、薯蓣皂苷元及亚麻酸乙酯）的量作为考察指标，采用HPLC法通过切换波长同时测定，色谱柱为Waters 2695 Supersil C₁₈（250 mm×4.6 mm，5 μm），流动相为甲醇-0.08%磷酸水溶液，梯度洗脱，体积流量为1.0 mL/min，柱温为30℃，进样量为10 μL，检测波长：先在全波长200~400 nm下测定，后根据对照品最大吸收波长切换检测波长；并结合主成分分析（PCA）、相关性分析及聚类分析（CA）法综合评价和比较六味地黄系列制剂的质量差异。结果 相同生药量下，六味地黄系列制剂中成分的含量存在显著差异（P<0.05），且部分制剂中部分成分缺失，软胶囊未检测到槲皮素、儿茶素，仅大蜜丸和颗粒检测到β-谷甾醇；相关性分析结果中六味地黄系列制剂之间的相似度为0.170~0.897，且大部分集中在0.500~0.600，大蜜丸与颗粒剂相似度最高，浓缩丸和胶囊、软胶囊及口服液呈极显著相关（P<0.01），和大蜜丸、颗粒剂呈显著相关（P<0.05）；PCA和CA结果中六味地黄系列制剂被归为2类，其中大蜜丸、颗粒被归为一类，浓缩丸、胶囊、软胶囊、口服液被归为一类。结论 六味地黄系列制剂存在一定的内在质量差异，在一定程度上揭示了六味地黄系列制剂说明书中所标示功能主治完全一致的现象可能不合理。

Objective According to the thinking of research on quality control of traditional Chinese medicine based on "components reflect activity, activity points to efficacy", the active ingredients obtained through network pharmacology screening were used as evaluation indicators to conduct a re-evaluation study on Liuwei Dihuang series preparations (LDSP). Methods The network pharmacology technology was used to screen out LDSP, such as pills (big honey pills and concentrated pills), capsules (capsules and soft capsules), granules and oral liquids for the treatment of type 2 diabetes, hypertension and nephrotic syndrome of the common core active ingredients, and the amount of 13 active ingredients (quercetin, kaempferol, β-sitosterol, alisol B, alisol B23-acetate, taxifolin, hydroxygenkwanin, stigmasterol, cerevisterol, hederagenin, catechin, diosgenin and ethyl linolenate) with higher degrees was used as an index of investigation, the HPLC method was used to simultaneously measure the wavelength by switching, the determination was performed on Waters 2695 Supersil C₁₈ (250 mm×4.6 mm, 5 μm) column with mobile phase consisted of methanol-0.08% phosphoric acid (gradient elution), volume flow rate was 1.0 mL/min, column temperature was 30℃, sample size was 10 μL, detection wavelength:first measurement was at full wavelength 200-400 nm, then maximum absorption was switched to detect wavelength according to the reference wavelength; The principal components analysis (PCA) and cluster analysis (CA) method were used to comprehensively evaluate and compare the quality differences of LDSP. Results Under the same crude drug amount, the content of ingredients in LDSP was significantly different (P<0.05), and some ingredients were missing in some preparations. Quercetin and catechin were not detected in soft capsules, β-sitosterol were detected only in big honey pills and granules. In the correlation analysis results, the similarity between LDSP was 0.170-0.897, and most of them were concentrated in 0.500-0.600. Big honey pills had the highest similarity with granules, concentrated pills and capsules, soft capsules and the oral solution showed a very significant correlation (P<0.01), and was significantly related to big honey pills and granules (P<0.05); The PCA and CA results of LDSP were classified into two categories, big honey pills and granules were classified into one category, and concentrated pills, capsules, soft capsules, and oral liquids were classified into one category. Conclusion There are certain inherent quality differences in LDSP, which reveals that the phenomenon of completely consistent functional indications in the instructions of LDSP may not be reasonable.

R286.02

国家级大学生创新创业训练计划项目（202011079035X）；四川省科技计划项目（2018ZR0107）