目的 探讨治疗白癜风中药复方专利的用药规律及作用机制，为白癜风中药新药开发与专利申报工作提供思路。方法 借助中国专利公布公告网站、国家知识基础设施数据库、中国知识产权网(CNIPR)专利信息服务平台、佰腾(Baiten)专利平台分别检索建库至2023年9月30日治疗白癜风的中药复方专利，采用Microsoft Excel软件、中医传承计算平台(TCMICS)V3。0建立数据库并进行内服、外用专利药物频数统计、关联规则及聚类分析，并进一步通过中药系统药理数据库与分析平台(TCMSP)、中医药证候关联数据库(SymMap)、人类基因综合分析数据库(GeneCards)、蛋白质资源数据库(UniProt)、STRING、药物综合数据库(PDB)等数据库及 R Studio 4。2。2、Cytoscape 3。9。1等软件探讨内服专利核心高频药物组合治疗白癜风的作用靶点及机制，利用AutoDock Vina软件进行分子对接验证。结果 纳入335项内服专利，189项外用专利。内服与外用专利用药规律较为相似，高频药物均为蒺藜、补骨脂、当归、何首乌、红花、白芷等;关键功效均以补虚、活血化瘀为主;皆以性温、寒、平，味甘、苦、辛，归肝、脾、心、肾经为主。内服专利中高频药对有川芎-当归、黄芪-当归等，外用专利中高频药对有乌梅-补骨脂、菟丝子-补骨脂等;内服与外用专利的聚类核心药物均有补骨脂、蒺藜、当归、何首乌、白芷、红花等高频药物。内服专利的治疗关键靶点为白蛋白、蛋白激酶B1、胱天蛋白酶3等基因，主要活性成分可能为槲皮素、山柰酚、木犀草素等，治疗机制可能与糖基化终产物/糖基化终产物受体、肿瘤坏死因子信号通路、磷脂酰肌醇3-激酶/蛋白激酶B等信号通路等相关，并参与血脂与动脉粥样硬化、人类巨细胞病毒感染等过程。分子对接结果证实中药成分与关键受体蛋白具有对接活性。结论 治疗白癜风的内服与外用中药复方专利在用药、性味、归经方面具有相似性，提示临床可从补益肝肾、活血化瘀等方面入手改善患者的白蛋白、白细胞介素、肿瘤坏死因子等通路及指标。本研究也为治疗白癜风的新药研发、专利保护及临床遣方用药提供了参考。
Research of medication rules and multi-pathway mechanism of action in the treatment of vitiligo by traditional Chinese medicine compound patent
Objective To explore the medication rules and mechanism of action of traditional Chinese medicine compound patent formulas for vitiligo,and provide ideas for the development and the patent declaration work of new Chinese medicines for vitiligo.Methods China Patent Publication Bulletin website,National Knowledge Infrastructure Database,Patent Information Service Platform of China Intellectual Property Right Net(CNIPR),and Baiten Patent Platform were used to search for the patents of traditional Chinese medicine compound formulas for vitiligo from the establishment of the databases to 30th September,2023.Excel software and Traditional Chinese Medicine Inheritance Computing Platform(TCMICS V3.0)were used to establish a database of compound formulas,and carry out the statistics of frequency,association rules and clustering analysis of the formulas for internal and external prescriptions.The target and mechanism of action of the internal prescriptions of core high-frequency Traditional Chinese Medicine group for the treatment of vitiligo were further explored by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Symptom Mapping(Symmap),The Human Gene Database(Genecards),UniversalProtein(UniProt),STRING,Pharmaceutical DataBase(PDB)and other databases as well as software such as R Studio 4.2.2 and Cytoscape 3.9.1,and AutoDock Vina was used for molecular docking validation.Results The internal formulas included 335 patents and the external formulas included 189 patents.The rules of internal and external use are similar.The high-frequency traditional Chinese medicines are Tribuli Fructus,Psoraleae Fructus,Angelicae sinensis,Radix Polygoni Multiflori,Carthami Flos,Angelica dahurica,etc.;the key efficacies of the medicines are based on tonifying the deficiency,activating blood circulation and removing blood stasis;and the properties of the Chinese medicines are the nature of warmth,coldness and flatness,sweetness,bitterness,pungency and attribution to the liver,the spleen,the heart and the kidneys.Commonly used oral medicine pairs are Chuanxiong rhizome-Angelica,Astragalus-Angelica,etc.,high-frequency pairs of external medicines are Fructus mume-Psoraleae fructus,cuscuta-Psoraleae fructus,etc.;internal and external clustering of the core drugs are Psoraleae fructus,Tribuli Fructus,Angelica,Polygonum multiflorum,Angelica dahurica,Safflower,and other high-frequency medicines.The key targets of internal patents for the treatment of vitiligo are genes such as albumin,protein kinase B1,cystatinase 3,etc.The main active ingredients of the internal grouping for the treatment of vitiligo may be quercetin,kaempferol,luteolin,etc.,and the therapeutic mechanism may be related to the end products of glycosylation/receptor for glycosylation end products,tumour necrosis factor signalling pathway,phosphatidylinositol 3-kinase/protein kinase B and other signalling pathways,and involved in the process of blood lipids and atherosclerosis,human cytomegalovirus infection.The molecular docking results confirmed the docking activity of the herbal components with key receptor proteins.Conclusion This study reveals the similarity between the internal and external patented formulas of vitiligo in terms of medication,flavour,and meridian,suggesting that the pathways and indexes such as albumin,interleukin,and tumour necrosis factor of vitiligo patients can be improved by tonifying the liver and kidney,activating blood circulation and removing blood stasis,which also provides a reference for the research and development of new medicines for vitiligo,patent protection,and the use of clinical prescriptions.
VitiligoTraditional Chinese Medicine compound patentNetwork pharmacologyMolecular dockingMedication rulesMechanisms of action
万方数据
维普
