基于数据挖掘对柴胡类方方证规律的研究

【作者】 冯石强；

【导师】 谢鸣；

【作者基本信息】 北京中医药大学 ， 方剂学， 2012， 博士

【摘要】 在“方证相关”理论的指导下,以柴胡类方为对象,建立柴胡类方的方证信息资料数据库；运用频次分析、关联规则、聚类分析对柴胡类方数据库进行数据挖掘以获得柴胡类方的方药证治规律及柴胡类方的方证类属关系。研究一：基于频次统计对柴胡类方方证规律的研究材料：《中医方剂大辞典》为本课题的资料来源,通过对类方的界定,选取符合条件的柴胡类方作为研究对象,得到类方共657首。方法：摘取资料中的方药(方名、方源、药物、剂量、剂型、用法)和病证的信息点(症征、病因、病机、病名等),依据《中医临床诊疗术语》、《中华本草》、《中医药学名词》、《中医证候鉴别诊断学》、《中医症状鉴别诊断学》等对资料进行信息规范化处理,建立柴胡类方的数据库,使用ACCESS查询功能统计柴胡类方信息。结果：(1)方药频次统计结果显示：柴胡类方配伍涉及185味药物,其中高频药物有：柴胡、黄芩、甘草、生姜、芍药、半夏、人参、茯芩、陈皮、大黄、当归、栀子、大枣、麦冬、枳壳、地黄、白术、知母、葛根、石膏、升麻、芒硝、川芎、黄连、枳实、桔梗、天花粉、厚朴、竹叶、防风、黄芪、地骨皮、肉桂、青皮、犀角、丹皮、桂枝、干姜、鳖甲、泽泻、龙胆草、茵陈、瓜萎、羌活、槟榔、苍术、木通、草果、猪芩、薄荷等；主要涉及补益、解表、清热、化痰、行气、利湿、泻下、化湿、温里、活血的配伍结构；高频药对有：黄芩+柴胡、甘草+黄芩、甘草+柴胡、生姜+黄芩、生姜+柴胡、芍药+黄芩、芍药+柴胡、半夏+黄芩、半夏+柴胡、生姜+甘草、人参+黄芩、人参+柴胡；高频药团有：甘草+黄芩+柴胡、生姜+黄芩+柴胡、芍药+黄芩+柴胡、半夏+黄芩+柴胡、生姜+甘草+柴胡、生姜+甘草+黄芩、人参+黄芩+柴胡等。剂型统计的结果显示,汤剂是使用最多的剂型,丸散剂的送药介质有米饮、姜汤、白汤、温水、粥饮、百沸汤、姜茶汤、麦冬汤、温酒9种。(2)病证频次统计结果显示：柴胡类方中,涉及症征532首,涉及病机155首,涉及病因259首,涉及病名433首。其中主治症征出现最多的是寒热往来、发热／潮热、头痛、口渴／口干、呕吐、心烦／烦躁、但热不寒、食欲不振、脉弦、脉数、大便秘结、咳嗽、四肢疼痛、胸闷、胁痛。高频症征组合主要有呕吐+寒热往来、脉数十脉弦、小便不利+大便秘结、口苦+寒热往来、脉弦+寒热往来、但热不寒+头痛、四肢疼痛+食欲不振、耳聋+口苦、食欲不振+寒热往来、呕吐+头痛、口渴+发热、心烦+呕吐；耳聋+口苦+寒热往来、脉数十脉弦+寒热往来、耳聋+口苦+胁痛、口苦+呕吐+寒热往来、口苦+脉数+脉弦、食欲不振+呕吐+寒热往来、耳聋+胁痛+寒热往来、口苦+胁痛+寒热往来、心烦+呕吐+寒热往来、口苦+脉数+寒热往来。类方主治病证中排在前10位的病机有热入血室、少阳不和、肝胆热盛、热扰胸膈、肝火上炎、胃热、脾胃气虚、热痰、血虚、少阳风热；排在前10位的病因有伤寒、疫疠、伤风、痰饮、妊娠疟邪、时气、怒气、体质、劳役、疟邪；排在前10位的病名是疟疾、伤寒、发热、瘟疫、虚劳、黄疸、感冒、外感热病、妊娠疟疾、小儿诸热。研究二：基于关联分析对柴胡类方方证规律的研究材料：同研究一。方法：使用研究一中的数据库,采用Excel和SQL Server绑定的购物篮分析工具挖掘药物之间、症征之间、药物和症征之间、药物和病机之间、药物和病名之间的关联规则。结果：(1)主要关联药对有猪苓(?)泽泻、草果→厚朴、麻黄→石膏、青皮→厚朴、麻黄→葛根、茵陈→栀子、芒硝→大黄、川芎→地黄、丹皮→当归、黄芪→人参、厚朴→陈皮、鳖甲→茯苓等；(2)主要关联症征有：口苦(?)耳聋、脉弦(?)脉数、大便秘结(?)小便不利、口苦→寒热往来；)(3)主要关联药-症组合有大便秘结→芒硝、大便秘结→大黄、发黄→栀子、心下痞→半夏、四肢疼痛→麦冬、小便不利→大黄、自汗→陈皮、耳聋→半夏、大便秘结→甘草&大黄、口干→芍药&甘草等；关联药-病组合有：黄疸→茵陈、虚劳→黄芪、闭经→当归、子烦→麦冬、妊娠疟疾→白术、虚劳→当归、发热→陈皮等。研究三：基于聚类分析对柴胡类方方证规律的研究材料：同研究一。方法：数据库同上,采用Excel和SQL Server绑定的类别检测工具,根据药物信息、症征信息和药-症信息进行聚类分析。结果：综合分析得到：(1)柴胡类方所含5类配伍结构：清解阳明+养阴退热配伍、理气燥湿化痰+健脾利水渗湿配伍、养血活血+凉血散瘀配伍、小柴胡汤原方配伍、泻热通腑+清利肝胆及升降气机配伍类。(2)柴胡类方所含7类证候：外寒里热证、少阳本证、少阳郁热+脾胃不和证、风热上扰证、心经热盛证、三焦热壅证、阴虚内热+三焦郁滞证。(3)柴胡类方中含有4类药-证组合：和胃降逆+清热活血配伍与少阳郁热证；益气养阴+清热泻火配伍与阴虚内热证；清利通腑配伍与三焦热闭证；祛湿化浊+健脾行滞配伍与湿热内阻+升降失司证。研究表明：柴胡类方主病有疟疾、瘟疫、虚劳、黄疸、外感热病等,涉及现代传染病、肺系疾病、脾胃病、肝胆病、脑病、寄生虫病、小儿疾病、妊娠产后病、耳鼻喉病、外科皮肤疾病等多科及多系统疾病；主要病因是风寒、疫疠、疟邪等外感之邪；病机的主要特征是寒热虚实夹杂,最多涉及热入血室、少阳不和、肝胆热盛、胸胃热扰、脾胃气虚、痰热等证；症征则以寒热往来、或口苦、或脉弦数三症为中心,与发热、头痛、口中干渴、心烦、呕吐、食欲不振、大便秘结、咳嗽、肢痛、胸闷、胁痛等症的不同组合为特征。柴胡类方以原类方的核心药物为基础,广泛涉及补益、解表、清热、化痰、行气、祛湿、泻下、温里、活血类药物的配伍。类方方药中的药对、药团、药组等与方证中的病名、病机、症征之间具有一定关联性。聚类分析结果提示柴胡类方内存在药物、症征方面的类属特征。结论：数据挖掘技术用于研究类方方证规律具有一定的可行性。更多还原

【Abstract】 The research of law between Formula and Syndrome about Bupleurum Analogous Formulas based on data mining methodWith the guidance of the theory of relation between Formula and Syndrome, using the Bupleurum Analogous Formulas as the study object, the researcher builds the data base of Bupleurum Analogous. Adopt frequencies, associative rules and cluster analysis to excavate the formula syndrome rules and category relationship of Bupleurum Analogous.Research 1:The research of law between Formula and Syndrome about Bupleurum Analogous Formulas based on frequency analysisMaterials:Using the Proprietary Chinese medicine dictionary as the material source, with the premise of Analogous Formulas definition. Methods:Select the eligibility formula, around the information of formula-medicine and disease -syndrome, which include the formula name, formula source, formula medicine, dosage, formulation, usage and symptom, disease reason, pathogenesis, disease name, etc. According to the Clinic Terminology of Traditional Chinese, the Chinese herbal, Noun of TCM, Differential diagnostics of TCM syndrome, TCM symptoms differential diagnostics, to standardizing the formula-syndrome information and build the Bupleurum Analogous data base.Using the function of query, achieve the statistics the frequencies of any kinds of the database. Results:(1) The formula-medicine frequency analysis shows that 185 medicines can be found in all the formulas. The frequency analysis shows that the high frequency medicine including:radix bupleuri, scutellaria, glycyrrhiza, ginger, peony, pinellia, ginseng, poria, tangerine peel, rhubarb, angelica, gardenia, jujube, radix ophiopogonis, bitter orange, rehmannia, atractylodes macrocephala, rhizoma anemarrhenae, radix puerariae, gypsum, rhizoma, mirabilite, ligusticum wallichii, rhizoma coptidis, fructus aurantii immaturus, platycodon grandiflorum, radices trichosanthis, mangnolia officinalis, bamboo leaf, radices sileris, radix astragali, cortex lycii radicis, cortex cinnamomi, pericarpium citri reticulatae viride, rhinoceros horn, cortex moutan, cassia twig, rhizoma zingiberis, turtle shell, rhizoma alismatis, felwort, oriental wormwood, trichosanthes kirilowii Maxim, rhizoma seu radix notopterygii, areca-nut, rhizoma atractylodis, akebiaquinata, amomum tsao-ko, grifola, mentha haplocalyx. The frequency statistic shows that the high frequency compatible structure including benefit, relieving exterior syndrome, clearing heat, reducing phlegm, promoting the circulation of qi, remove dampness through dieresis, galactic, resolving dampness, inner worming, invigorate the circulation of blood. The high frequency combination including:scutellaria +radix bupleuri, glycyrrhiza +scutellaria, glycyrrhiza +radix bupleuri, ginger +scutellaria, ginger +scutellaria, paeonia +scutellaria, paeonia +radix bupleuri, pinellia ternata+scutellaria, pinellia ternata+radix bupleuri, ginger +lycyrrhiza, ginseng +scutellaria, ginseng +radix bupleuri; glycyrrhiza +scutellaria +radix bupleuri, ginger +scutellaria +radix bupleuri, paeonia +scutellaria +radix bupleuri, pinellia ternate +scutellaria +radix bupleuri, ginger +glycyrrhiza +radix bupleuri, ginger+ glycyrrhiza +scutellaria, ginseng+ scutellaria +radix bupleuri. The dosage statistic shows that decoction is the most. Pill powder using transfer media include congee, ginger decoction, water soup, worm water, gruel, boiling soup, gingertea, Dwarf lilyturf soup, warm wine. (2) Disease and syndrome statistical results show that:disease signs involves in 532 formulas, the 657 formula involved in the pathogenesis of 155 formula, formulas involved in the etiology describe 259 formula, formulas involved in the disease narrative 433 formula, the most are alternate chills and fever, fever, headache, thirsty, vomiting, upset, only hot, loss of appetite, be agitated, pulse string, pulse fast, constipation, hot flashes, cough, limb pain, dry mouth, bosom frowsty, pleura pain. For the high frequency of disease combination appears for a major disease combination:vomiting+alternate chills and fever, pulse fast+pulse string, urination+constipation, mouth bitter+alternate chills and fever, pulse string+ alternate chills and fever, only hot+headache, limbs pain+loss of appetite, deafness +mouth bitter, loss of appetite+alternate chills and fever, vomiting+headache, thirsty+fever, upset+vomiting; deafness+mouth bitter+alternate chills and fever, pulse fast+pulse string+alternate chills and fever, deafness+mouth bitter+pleura pain, mouth bitter+vomiting+alternate chills and fever, mouth bitter+pulse fast+ pulse string, loss of appetite+vomiting+alternate chills and fever, deafness+pleura pain+alternate chills and fever, mouth bitter+pleura pain+alternate chills and fever, upset+vomiting+alternate chills and fever, mouth bitter+pulse fast+alternate chills and fever. The pathogenesis appear the top 10 times including heat into the blood room, less Yang unsuitable, liver and guts heat, chest with heat interference, suffered inflammation, stomach heat, spleen and stomach deficiency, hot phlegm, deficiency of blood, wind-heat of less Yang, etc.; the reasons of disease appear among them the top 10 times including the etiology of typhoid fever, epidemic disease, cold, phlegm retention, pregnancy anopheles evil, anger, constitution, fatigue, labor, anopheles evil; the disease appear among them the top 10 times including malaria, typhoid fever, fever, plague, virtual fatigue, jaundice, colds, exogenous febrile disease, pregnancy and malaria, wild diarrhea.Research 2:The research of law between Formula and Syndrome about Bupleurum Analogous Formulas based on correlation analysisMaterials:Ditto. Methoeds:With market basket analysis tool, find the association rules. Results:Correlation analysis shows that the main connection including agaric ? rhizoma alismatis, amomum tsao-ko→mangnolia officinalis, ephedra→gypsum, pericarpium citri reticulatae viride→mangnolia officinalis, ephedra→the root of kudzu vine, herba artemisiae capillaris→jasmine, mirabilite→rheum officinale, Ligusticum wallichii→rehmannia, the root bark of the peony tree→angelica sinensis, astragalus mongholicus→ginseng, mangnolia officinalis→pericarpium citri reticulatae, turtle shell→poria cocos, etc. The main correlation symptom including mouth bitter→deafness, pulse string? pulse fast, constipation ? urination, mouth bitter→alternate chills and fever; the main correlation between medicine and symptom including constipation→mirabilite, constipation→rheum officinale, jaundice→jasmine, urination→jasmine, painful abdominal mass→pinellia ternate, limbs pain→radix ophiopogonis, urination→rheum officinale, spontaneous perspiration→pericarpium citri reticulatae, deafness→pinellia ternate, constipation→glycyrrhiza and rheum officinale, mouth dry→paeonia and glycyrrhiza, etc.; the main correlation between medicine and disease including icterus→oriental wormwood, virtual fatigue→astragalus, amenorrhoea→angelica, contempt when pregnancy→radix ophiopogonis, malaria when pregnancy→rhizoma atractylodis macrocephalae, virtual fatigue→angelica, fever→pericarpium citri reticulatae, etc.Research 3:The research of law between Formula and Syndrome about Bupleurum Analogous Formulas based on cluster analysisMaterials:Ditto. Methods:With market category detection tool, find the category information. Results:Analysis by synthesis showed that:(1) The bupleurum analogous formulas shows 5 formations as clearing YangMing+nourish yin and abatement of fever, Qi dry wet+the wet water permeability spleen, nourishing blood and promoting blood flow+cool the blood dissipate blood stasis, Xiao Chaihu Tang’s structure, diarrhea fever and relaxing the bowels+clearing liver-gallbladder and adjust the movement of qi. (2) The bupleurum analogous formulas shows 7 syndromes as extra cool and inner hot, original of shaoyang, muggy of shaoyang+ incoordination between the spleen and the stomach, rising of wind-hot, heart sutra hot filled, tri-jiao hot filled, yin asthenia generating intrinsic heat+tri-jiao stasis. (3) The bupleurum analogous formulas shows 4 medicine-syndrome combinations as harmonize the stomach+clearing fever and promoting blood flow with muggy of shaoyang, tonifying qi and yin+clearing a way heat and reducing fire with yin asthenia generating intrinsic heat, clearing and relaxing the bowels with tri-jiao closed because of the heat, clearing damp+tonifying spleen with damp and hot resistance+ lift disorders.Indications:The study indicates that bupleurum analogous formulas was related to infectious disease, lung disease, taste of disease, liver disease, encephalopathy, parasitic diseases, pediatric diseases, pregnancy and postpartum disease, ent, surgery illness skin disease; the treatment of disease and syndrome involves the main causes are cold, epidemic disease, anopheles evil; chills and fever and deficiency-excess complication are the main pathogenesis feature, the most involving heat into the blood room, less Yang unsuitable, liver and gallbladder heat, stomach and chest heat, spleen and stomach deficiency, hot phlegm, etc. The center of the symptoms involves alternate chills and fever, mouth bitter, pulse string or fast which has the relationship of combination with fever, headache, thirsty, upset, vomiting, loss of appetite, constipation, cough, myalgia and bosom frowsty and hypochondriac pain.The above 3 researches showed that the compatibility of bupleurum analogous formulas was related to benefit, relieving exterior syndrome, clearing heat, reduce phlegm, promoting the circulation of qi, flow swiftly, resolving dampness, inner worm, invigorate the circulation of blood.The medicine group and the disease, pathogenesis, symptom showed some relevance. The clustering analysis hints of bupleurum analogous formulas within category features of medicine and symptom.Conclusion:The data mining technology used to study the formula syndrome rules of analogous formulas has certain feasibility.更多还原