目的 基于数据挖掘技术探讨国家专利中药外用制剂治疗脂溢性脱发的组方规律，并综合网络药理学与分子对接方法，初步揭示其核心药物组合的多成分-多靶点-多通路作用机制。方法 检索并筛选国家知识产权局专利数据库中治疗脂溢性脱发的中药外用制剂处方。运用Excel、SPSS Modeler18.0和SPSS Statistics27.0等软件对纳入的处方中药复方的高频中药、功效类别、性味归经进行频次以及关联规则和聚类分析，筛选出核心药物组合。通过BATMAN-TCM数据库、SwissADME筛选活性成分，并通过Swiss Target Prediction预测作用靶点，从GeneCards、OMIM等数据库获取脂溢性脱发疾病靶点，取交集后得到共同靶点；利用STRING数据库和Cytoscape 3.9.1软件构建蛋白质-蛋白质相互作用（PPI）网络，并进行拓扑分析筛选核心靶点；通过Metascape数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析；最后利用AutoDockTools1.5.7等软件对关键活性成分与核心靶点进行分子对接验证。结果 共纳入有效专利处方152首，涉及中药372味。高频中药包括何首乌、侧柏叶、当归等。中药药性以温性居多，药味以苦味为主，多归于肝经，功效以补虚清热为主。关联规则得到常用药对有何首乌-当归-侧柏叶、何首乌-人参-侧柏叶、何首乌-熟地黄等，聚类分析得到6类药物组合： C1（何首乌、侧柏叶、当归、人参、川芎、丹参、红花、生姜）、C2（苦参、花椒）、C3（黄芪、补骨脂、熟地黄）、C4（枸杞子）、C5（桃仁）、C6（墨旱莲、女贞子、生地黄），并筛选出核心药物组合为何首乌-侧柏叶-当归。网络药理学预测显示，核心组合通过ω-羟基大黄素-8-甲醚、N-反式-阿魏酰酪胺、木犀草素等关键成分，作用于AKT1、IL6、TP53、ESR1、EGFR等核心靶点，调控磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-Akt）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路等，在蛋白磷酸化、激素与应激应答、改善头皮局部微循环等方面中发挥协同作用。分子对接结果表明，关键活性成分与核心靶点具有良好的结合活性。结论 国家专利中药复方治疗脂溢性脱发以补虚为主，兼以清热等，其药物组合何首乌-侧柏叶-当归的ω-羟基大黄素-8-甲醚、N-反式-阿魏酰酪胺、木犀草素等成分可能通过作用于AKT1、IL6、TP53、ESR1、EGFR等多靶点，调控PI3K-Akt、MAPK等信号通路，发挥治疗脂溢性脱发的作用。

Objective To explore the formulation patterns of national patent traditional Chinese medicine (TCM) external preparations for treating seborrheic alopecia (SA) based on data mining technology, and to preliminarily reveal the multi-component, multi-target, multipathway mechanism of its core drug combination using integrated network pharmacology and molecular docking methods. Methods Prescriptions for TCM external preparations treating SA were retrieved and screened from the China National Intellectual Property Administration Patent Database. Software including Excel, SPSS Modeler 18.0, and SPSS Statistics 27.0 were used to analyze the included herbal compound prescriptions for high-frequency herbs, efficacy categories, property-flavor and channel tropism via frequency analysis, association rule analysis, and cluster analysis, to screen the core drug combination. Active ingredients were screened via the BATMANTCM database and SwissADME, and their action targets were predicted using Swiss Target Prediction. SA disease targets were obtained from databases like GeneCards and OMIM. Common targets were identified by intersecting the ingredient and disease targets. A proteinprotein interaction (PPI) network was constructed using the STRING database and Cytoscape3.9.1 software, followed by topological analysis to screen core targets. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using the Metascape database. Finally, molecular docking verification between key active ingredients and core targets was conducted using software such as AutoDockTools1.5.7. Results A total of 152 effective patent prescriptions were included, involving 372 distinct herbs. High-frequency herbs included Polygoni Multiflori Radix, Platycladi Cacumen, and Angelicae Sinensis Radix. Herbal properties were predominantly warm, flavors were mainly bitter, and herbs most frequently target the liver meridian. In terms of efficacy, tonifying deficiency herbs and heat-clearing herbs were most common. Association rules yielded commonly used herb pairs such as Polygoni Multiflori Radix-Angelicae Sinensis Radix-Platycladi Cacumen, Polygoni Multiflori Radix-Ginseng Radix et Rhizoma-Platycladi Cacumen, and Polygoni Multiflori Radix-Rehmanniae Radix Praeparata. Cluster analysis identified six drug clusters: C1 (Polygoni Multiflori Radix, Platycladi Cacumen, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Carthami Flos, Zingiberis Rhizoma Recens), C2 (Picriae Herba, Zanthoxyli Pericarpium), C3 (Astragali Radix, Psoraleae Fructus, Rehmanniae Radix Praeparata), C4 (Lycii Fructus), C5 (Persicae Semen), C6 (Ecliptae Herba, Ligustri Lucidi Fructus, Rehmanniae Radix Praeparata), from which the core drug combination Polygoni Multiflori Radix-Platycladi Cacumen-Angelicae Sinensis Radix was selected. Network pharmacology predictions revealed that the core combination acts through key components like questinol, N-trans-feruloyltyramine, and luteolin, targets core targets such as AKT1, IL6, TP53, ESR1, and EGFR, and regulates signaling pathways including the PI3K-Akt and MAPK pathways. This exerts synergistic effects in protein phosphorylation, hormone and stress response, and improving local scalp microcirculation. Molecular docking results indicated that the key active components and core targets generally possess good binding activity. Conclusion National patent TCM compounds for treating SA primarily focus on tonifying deficiency, combined with clearing heat. The core drug combination Polygoni Multiflori Radix-Platycladi Cacumen-Angelicae Sinensis Radix, containing components like questinol, N-trans-feruloyltyramine, and luteolin, likely treats SA by acting on multiple targets such as AKT1, IL6, TP53, ESR1, and EGFR, and regulating PI3K-Akt, MAPK, and other signaling pathways.

R285.5

国家自然科学基金面上项目（82574969）