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.

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