摘要
“方证相关”是方剂学科的一个重要命题,也是方剂文献研究中应当遵循的逻辑。本课题以历代补益方剂为切入点,以《中医方剂大辞典》为信息源,运用频数分析、关联规则、模糊聚类及比较分析等方法,对收集的1738首补益方进行了其药-方-效-证规律方面的研究。
方法：设立选方标准筛选出其中的补益方剂；设定方剂的24个信息点(方剂编号、方名、方源、朝代、异名(出处)、药物组成、剂型、用法、特殊煎法、特殊服法、服药时间、用药剂量、主治病、主治证、主治症状、功用、制剂、加减、宜忌、备注、备考、方论选录、临证举例、现代研究等)；参考《中医临床诊疗术语》、《中医证候鉴别诊断学》、《中医症状鉴别诊断学》、《简明中医病证辞典》、《中华本草》、《中药学》、《中药大辞典》、《中药别名词典》、古今度量衡标准等工具书,制定中医病名、证候名、症状名、方剂功效、药名、药性、药物功效、分类等标准化文本,对被选方剂所涉相关核心信息进行标准化处理；建立历代补益方剂的方证信息数据库；运用频繁项集、关联规则、聚类分析等技术对数据库中的相关信息进行全面分析。同时还参考《中国医籍提要》、《宋以前医籍考》、《医籍考》等,从源流演变的角度考察了不同时代的补益剂特点。
结果：(1)补益方的药物分析显示,补益方中的补益类药使用占56.75%,依次为补气药>补血药>补阳药>补阴药,同时还涉及其他非补益药10余类；补益方的高频药谱主要涉及经典古方如四君子汤、四物汤、六味地黄丸的药味；常用药对、药团、药组、药群亦多是出自上述方剂中的2-5味的组合。对补益方的结构分析显示,补益方的结构是以补气、补血、补阳、补阴药为主及补气与补血药的配伍最为常见,其中补益五脏/阳气方以补气、补阳为主,配伍补血、补阴药；补益五脏/阴血方以补血、补阴药为主,同时配伍补气、补阳药；气血双补方与补气、补血方在主体配伍上并无根本区别,只在补气、补血侧重上有所差异；阴阳两虚证的治方结构以补阳、补血为主,与部分气虚、气血两虚、阳虚证的组方相类似。证型与组方结构的分析显示,同一证型可以对应不同的组方结构,相同的组方结构也可以对应不同的证型。补益方的功效分析显示,补益方功效含括了补益与非补益二类,前者以补气、养血、养阴、助阳等作用,或补脾、补肾、补肝、补肺等为主,补心功效因频数较低而未在分析中显示,但所涉安神可作为互补；后者则主要涉及活血止痛、利水渗湿、涩精止遗、温化寒痰、养心安神、活血调经、涩肠止泻、理气、发散风寒、敛肺止咳药等。从五脏阴阳气血角度归类显示,补益方主要有补益肝肾类,补益气血类,健脾补肺类,滋补肺肾类,补血和营五类。剂型与用法分析表明,补益方的汤剂和丸剂使用频率高达80.61%,散剂的运用也占一定比例；多于空心或食前服用；其中的丸、散剂常用酒、盐汤、米饮送服。
(2)补益剂主治对象的分析表明,补益方主要用于内科疾病,此外还常用于男科、妇科、儿科、外科、眼科等多科。所主证候中的五脏虚证中以肾虚证和心虚证多见,前者涉及到阴、阳、气、精亏损,后者涉及血虚和气虚。阴阳气血虚证中的气虚证主要涉及脾胃、肺、肾,血虚主要涉及心、肝,阴虚证主要涉及肾、肝肾、心肾,阳虚证主要涉及脾(胃)、肾,阴阳两虚则主要涉及肾。补益方所主症状主要有虚损症(疲乏、食欲不振、消瘦等)、相关症(腰痛、发热、咳嗽等)及非虚症(呕吐、脉数等)三类。上述症状中2～4个症状的组合在一定程度上反映了症-证之间的关联性,如与脾胃气虚有关的两个症状组合为疲乏+食欲不振、少气、消瘦；与肾虚有关的三个症状组合为耳鸣+眩晕+膝酸、腰酸、腰痛；与气阴两虚有关的四个症状组合为盗汗+发热+咳嗽+气喘等。对补益方主治疾病与主要证候类型的关联性分析显示,虚劳与气虚、气血两虚、肾气虚、肾虚；腰痛与肾虚、阳虚、肾气虚；遗精与气虚、肾虚、阴虚、肾阳虚、气血两虚；咳嗽与气虚、阴虚；阳痿与肾阳虚、气虚；月经不调/不孕与气血两虚；腹泻与肾阳虚、脾虚；发热与血虚、气虚；腹痛/痘疮与气血两虚；耳聋与肾虚等密切相关。与肾虚有关的病症有遗精病-遗精(滑精,梦遗),伴有疲乏、盗汗、耳鸣、腰酸；腰痛病-腰痛、腰酸,伴有膝酸、膝痛、盗汗、遗精；盗汗病-盗汗,腰酸,遗精；与脾虚有关的病症有腹泻病-腹泻,呕吐,食欲不振；与肺虚有关的病症有咳嗽病-咳嗽,咳痰,气喘。还有发热病-发热,口中生疮,舌疮；浮肿病-浮肿,咳嗽,气喘等。显示了虚损病证中某些病症的组合规律。对证候与症状的关联分析获得有关阴虚、肾阴虚及脾胃两虚证的关联症群,如肾阴虚的盗汗、耳鸣、腰酸/腰痛、遗精、眩晕,膝酸/膝痛；脾胃两虚证的恶心,呕吐,食欲不振和呕吐,食欲不振,四肢无力,此与目前所认识到的辨证内容具有很好的一致性。
(3)病症与方药的关联性分析显示,治疗气虚、血虚、肾虚病症的关联药味药物多分别出自于四君子汤、四物汤、六味地黄丸等。对疾病-证候-症状-药味/药对/药团的分析中发现其关联规律主要有咳嗽病-气虚证-咳嗽症-人参→人参十白术→人参+白术十五味子,阳痿病-肾阳虚证-阳痿症-附子→附子+熟地黄→附子+熟地黄+肉桂等。
(4)补益方的断代考察表明,汉、晋、北齐补益方数量较低,宋代补益剂取得快速发展,金代进入低谷,元明又逐渐恢复增长,清代时补益剂增长至高峰。对历代补益方中部分药味配伍及其用量考察显示,补益方的常用药味在8味左右,其全方单服剂量在60～120克。提示临证补益处方不宜药味过多或剂量过大,疗效关键在于据证配伍,切中病机。
结论：补益方是以补益药为主,配伍其他多类药的一类方剂,其多以经典补益古方及其药味为核心药味,尤以补气与补血药的配伍为核心；补益方的主治涉及多科疾病,并偏重气血阴阳之虚损证。补益方所主病证中的病-证或证-症具有一定对应关系,而补益方药与病证症之间也存在一定的对应或组合规律。
本文在对中医历代补益方文献搜集和建库的基础上,运用数据挖掘技术,从多个维度对补益方的药-组-效-证的规律进行了探查,初步获得了补益方剂的应用范围、配伍用药特征、剂型与用法的经验、基于气血阴阳或五脏虚证的组方结构、以药物功效为基础的补益方类别、病证症与方药关联等规律。本研究结果丰富了目前方剂学中有关补益方内容；经标准化文本处理所建立的历代补益方数据库为中医药信息化研究提供了一定的基础；数据挖掘的结果也可为中医临床、教学和科研提供一定的参考。
"Relationship between formulas and syndromes" is an important proposition in the formula subject, and is also the logic regularities that the formulas literature studies should follow in the researches. The entry points of this topic are from ancient tonifying formulas, and the information sources are from the Dictionary of Formulas. With frequency analysis, association regularities, fuzzy clustering and comparative analysis, and research their materia medicas, formulas, functions, syndromes to1738tonifying formulas collected.
Methods:Establish the standards to filter out the tonifying formulas; and24information points (formula number, formula name, formula sources, dynasty, synonyms (source), pharmaceutical composition, dosage, usage, special frying method, special regimens, medication time, the dosage, the indicat ions, the syndrome, the symptoms, function, preparations, subtraction, taboo, notes, pro forma, square on the excerpted, clinical example, modern research. Refer to TCM clinical diagnosis term, Differential Diagnosis of Syndromes Learning, Learning the Differential Diagnosis of Clinical Symptoms, Concise Dictionary of TCM Syndrome, Chinese Herbal Medicine, Pharmacy, Chinese Dictionary, Chinese alias Dictionary, ancient and modern metrology standard tools such as books, and establish the standards of the diseases, the syndromes name, the symptoms name, the formulas functions, materia medica name, materia medica natures, materia medica efficacy, classification, etc. and according to the standard deal with their key information, and establish a database of ancient tonifying formulas, and using frequent item sets, association regularities, clustering analysis techniques relevant information in the database to analyze them totally and carefully. Also refer to the China Medical Books Summary, Song Medical Before Test, Test Medical Books, etc., and research the different characteristics of the tonifying formulas from the perspective of the origin and development of agent era.
Results:(1) The analysis shows that the tonic materia medica usage accounted for56.75%in the tonifying formulas, the order among them is that tonifying qi materia medica> tonifying blood materia medica> tonifying yang materia medica> tonifying yin materia medica. It also involves other non-tonifying formula more than10categories; High-frequency spectrum of tonifying formulas mainly related to the materia medica of classic Sijunzitang, Siwutang, Liuweidihuangwan. Commonly usage of materia medica couple, materia medica group, materia medica regiment come from2to5materia medicas of the above formula. Structural analysis of the most common materia medicas is tonifying qi, blood, yang, yin, and qi and blood compatibility. Tonifying internal five zang organs/yang and qi formulas is based on the main materia medicas of tonifying qi, yang, compatible blood, yin ones; Replenishing the internal five zang organs/yin and blood formulas is based on the main materia medicas of replenishing blood, yin, compatible qi, yang ones. Tonifying both qi and blood formulas are no fundamental differences from the tonifying qi formulas and replenishing blood formulas on the compatibility, and the differences only in the qi, blood focused; Governance structure of yin and yang deficiency of both formulas to yang, blood-based, Similarly with some qi deficiency, qi and blood deficiency, yang deficiency group isotropic. Analysis syndrome and group structure of the display side, Same syndromes may correspond to different set of square structure, the same set of square structure can correspond to different syndromes. Tonifying formulas function analysis showed that the function encompasses the tonic one and non-tonic one, The former is mainly including tonifying qi, blood, yin, yang and so on, or spleen, kidney, liver, lungs, etc., Make up the heart due to the frequency of low efficacy without the analysis shows that it can be used as a complementary nerves involved; The latter mainly involves Huoxuezhitong, induce diuresis and drain dampess, astringent fine just left, temperature of the Han Tan, uneasiness of mind, blood circulation to regulate menstruation, astringent intestinal diarrhea, regulate qi, divergent cold, astringent the lung to stop cough. From the perspective of yin and yang, qi and blood of internal five zang organs classified display, The main tonifying fomulas have five types:liver and kidney tonifying one, tonifying qi and replenishing blood one, spleen and lung tonifying one, lung and kidney tonifying one, nourishing and regulating ying-blood. Dosage and usage analysis showed that Tonic soups and party pills use frequencies up to80.61%, The use of dispersants is also certain proportion, before taking more than hollow or food. One of the pills, powders commonly used in wine, salt soup, rice drink delivery service.
(2) Analysis showed tonic agents attending object, The main tonifying formulas for internal diseases, in addition, commonly used in andrology, gynecology, pediatrics, surgery, ophthalmology and many other subjects. In the main deficiency syndrome kidney and heart deficiency syndrome of the internal organs are more common. The former involves the yin and yang, qi, refined loss. The latter relates to blood deficiency and qi, yin, yang, qi and blood deficiency mainly involves the spleen and stomach, lungs, kidneys. The blood deficiency involving the heart, liver, yin deficiency mainly related to kidney, liver and kidneys, heart and kidney, yang deficiency mainly related to the spleen(stomach)、kidney, yin and yang deficiency are mainly related to the kidney. The main symptoms of tonifying formulas include wasting syndrome (fatigue, loss of appetite, weight loss, etc.), related disorders (low back pain, fever, cough, etc.), and non-deficiency syndrome(vomiting, rapid pulse, etc.) categories. A combination of these symptoms two to four symptoms to some extent reflects the syndrome-correlation, such as the spleen and stomach qi deficiency symptoms related to a combination of two fatigue+loss of appetite, short of breathe, weight loss; Kidney-related symptoms with a combination of three of vertigo+tinnitus+knee soreness, backache, lumbago; qi and yin Deficiency symptoms associated with four combinations of cough, night sweats, fever or asthma. Indications for tonifying formulas diseases and syndromes correlation analysis shows consumption and qi, qi and blood, kidney qi, kidney deficiency; Back pain and kidney, yang, kidney qi deficiency; Emission and qi, kidney, yin, kidney yang, qi ang blood deficiency; Cough and Qi, yin deficiency; Impotence and kidney yang, qi deficiency; Irregular menstruation/infertility with qi and blood deficiency; Diarrhea and kidney yang, spleen deficiency; Fever and blood, qi deficiency; Abdominal pain/pox sores with qi and blood deficiency; Closely related, deafness and kidney deficiency. And kidney deficiency-related diseases and symptoms have semen disease emission (spermatorrhea, nocturnal emissions), accompanied by fatigue, sweating, tinnitus, backache:Lumbago disease-backache, back soreness, accompanied by knee soreness, knee pain, night sweats, nocturnal emission; Night sweats disease-sweats, back soreness, nocturnal emission; And spleen-related diseases have diarrhea, vomiting, loss of appetite; And lung deficiency-related diseases have a cough, sputum, wheezing. There fever diseases have fever, mouth sores, sore tongue; Edema diseases have edema, cough, asthma. It shows a combination of law between diseases and syndromes in certain conditions. Symptoms of syndrome associated with the analysis of access to relevant deficiency of yin, kidney yin, spleen and stomach. Such as deficiency of kidney yin related sweating, tinnitus, backache/back soreness, nocturnal emission, dizziness, knee soreness/knee pain; Deficiency of both the spleen and stomach related nausea, vomiting, loss of appetite and vomiting, loss of appetite, weakness, Recognizing this and the current dialectic content with good consistency.
(3) Correlation analysis of disease, syndrome, or symptoms and formulas showed the materia medica associated with treatment of deficiency of qi, blood, kidney disease, syndrome, or symptoms come from Si junzi tang, Siwutang, Liuweidihuangwan. Analysis of disease syndrome-symptoms-materia medica/materia medica couple/materia medica group/materia medica regiment found its associated regularities mainly cough-qi deficiency syndrome-cough symptom-Ginseng→Ginseng+Atractylodes→Atractylodes+Ginseng+Schisandra, Impotence disease-deficiency syndrome-impotence-Aconite→Aconite+Rehmannia→aconite+Rehmannia+cinnamon.
(4) Dating study of tonifying formulas showed the amount of tonifying formulas using in the Han, Jin, Northern Qi Dynasty is less. In the Song Dynasty the tonifying formulas using achieved rapid development, Jin into the bottom, Yuan and Ming gradually return to growth. In the Qing Dynasty the tonifying formulas using grew to new heights. Materia medica on the part of the ancient tonifying formulas and the amount of compatibility study shows that the materia medica of common tonifying formula is concerned to8ones, Its wholly-side single-serving doses of60to120grams. Tip clinical taste neither too much nor tonifying formulas overdose, according to the key lies in the efficacy card compatibility, fight the pathogenesis.
Conclusion:Tonifying formulas are based on tonifying materia medica and multi-compatibility of other non-tonic one. The core materia medica of tonifying formulas mostly come from classical ancient tonifying formulas, especially qi and blood compatibility of the drug at the key; Tonifying formulas involved multidisciplinary disease, and the emphasis of yin, yang, qi and blood deficiency syndrome. The disease and syndrome or syndrome and symptom in the indications of tonifying formulas has a certain correspondence relationship, and also has the same certain correspondence or combination regularity between the tonifying formulas and syndrome or symptom of the disease.
Based on the tonifying formulas of ancient Chinese medicine literature collection and building a database on using data mining techniques from multiple dimensions on the side of the drug-group
effect-syndrome the law permits were exploratory. Initially gained experience tonic prescription range of applications, compatibility characteristics medication, dosage and usage experience, the regularities about the formulas structure based on qi, blood and yin, yang or five zang organs deficiency syndrome, the categories of tonifying formulas based on materia medica function, the correspondence relationship between disease, syndrome, symptoms and formulas, materia medica.
The results of this study enriches the current formulas concerning tonifying formulas content; Normalized text processing side created a database for the tonifies of ancient Chinese medicine research information provided a foundation; Data mining can also be the result of clinical medicine, teaching and research to provide a reference.
引文
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