经方50味药物在明代13位医家中的用量规律研究

【作者】 宋佳；

【导师】 傅延龄；

【作者基本信息】 北京中医药大学 ， 中医临床基础， 2011， 博士

【摘要】 《伤寒杂病论》作为方书之祖,医方之经,创造性的将理-法-方-药-量融为一体,迄今学人犹奉为圭臬,其方亦被尊为“经方”而广泛流传,而以经方常用药物为研究对象进行方药剂量理论及剂量演变轨迹的研究是推进中药量-效关系研究的重要途径。然而,要研究经方的方药剂量规律,首先需要回答的就是经方的本源剂量究竟是多少。自上世纪八十年代根据“光和大司农铜权”考证得出东汉1两=15.625克的结果公布于世之后,中医界再次掀起对经方本源剂量的考证之风,各种考证方法、考证结论如雨后春笋,纷纷涌现,短期内很难达成一致观点。而现行国家药典与《中药学》教材中规定的中药剂量范围又与明代李时珍提出的“古一两今用一钱”之折算标准有着莫大关联。因此立足于明代,研究经方常用药物在明代医家中的常用剂量范围；探讨经方本源剂量在自东汉至明代这一千余年的时间内发生了怎样的演变,是何导致；揭示李时珍提出的折算标准的来龙去脉；进而总结明代医家在临床用药剂量方面的规律与特点,以及相关的临床剂量控制策略,将是本论文的研究目的与研究方向。1研究目的(1)筛选出《伤寒杂病论》中50味常用中药,根据现存明代医籍分别统计出这50味中药在明代医家中的剂量使用情况,包括常用剂量范围、平均剂量、最常用剂量值、剂量分布区间等。(2)按目前中医界对《伤寒杂病论》本源剂量认可最为广泛的观点仲景方1两≈13.92克折算出该50味药在经方中的剂量范围,并与统计得出的明代医家常用剂量范围相对比,验证明代医家对仲景方的折算比例与李时珍所述“古之一两,今用一钱”之比例是否一致,如果一致,试图探讨经方剂量至明代出现如此落差的原因；若不一致,试图找出明代医家运用经方时使用最为普遍的折算比例,并分析该比例缘何而来。(3)同时将统计得出的明代医家运用经方50种药物的常用剂量范围,与现行国家药典(2010年版)、《中药学》教材(“十一五”国家级规划教材)中规定的剂量范围相比较,总结明代医家与当代中医生临床用药剂量之间的差异,为未来制定合理、安全、科学、有效的中药剂量范围提供一定的参考。(4)通过对明代医家用药剂量的研究,总结古代医家医著中所涉及的影响方药剂量及量效关系的相关因素,如患者体质差异、气候因素、地域因素、药材炮制、用药剂型、哲学文化等,并从方药服法、剂型、病证类型、服药反应等方面深入挖掘古代医家临证施量的控制策略。2研究对象以本课题组筛选出的50种经方常用中药为研究对象,以13本明代医著为研究内容,统计得出该50味常用中药在明代13本医著中的平均剂量、最常用剂量、常用剂量范围以及剂量分布区间。所要研究的13本明代医著如下：《石山医案》(汪机)、《孙一奎医案》(孙一奎)、《里中医案》(李中梓)、《先醒斋医学广笔记》(以下简称《广笔记》缪希雍)、《医验大成》(秦昌遇)、《奇效医述》(聂尚恒)、《景岳全书·古方八阵》(张景岳)、《医学正传》(虞抟)、《明医杂著》(王纶)、《内科摘要》(薛己)、《寿世保元》(龚廷贤)、《瘟疫论》(吴又可)、《古今医统大全·伤寒门》(徐春甫)。3研究方法本研究采用EXCEL表格数据处理功能及基本统计学方法(百分位数、方差、标准差、离散度、相关性、算术平均数等概念)来处理所要研究的50味常用中药的出现频次、最常用剂量(出现频次最高的剂量值)、平均剂量、常用剂量范围以及剂量分布区间(最小剂量与最大剂量之间的值域范围)等。其中常用剂量范围采用统计学百分位数PX=L+i/fx[n.X%-∑fL]的计算方法,用[P10～P90]之间的数值范围来描述。4研究结果本论文的研究结果部分将对50味药总论与单味药各论分别进行探讨,以做到点面结合,纵横相参,既对50味药在明代及仲景时代的剂量情况有整体的把握,又对单味药在明代不同医家中的剂量分布情况有直观的理解。所得主要结论有以下几点：(1)50味常用药物在《伤寒杂病论》中的用药剂量无论从最常用剂量、平均剂量、常用剂量范围,还是剂量分布区间,均要显著超过明代以及现代。以最常用剂量值为例,50味药物中有23味在明代的最常用剂量尚不足其在《伤寒杂病论》中最常用剂量的1/10。(2)明代医家用药剂量多分布在仲景本源剂量1/10～1/3的范围内,李时珍提出的“古一两今用一钱”的折算标准相当于只取仲景原方剂量的1/3,根据本论文的研究结果,这一折算比例在当时算是用量偏大者。(3)现行国家药典及《中药学》教材中规定的中药剂量范围与明代相比较为接近,除大黄、石膏、黄芪、滑石、牡蛎等药两者上限值相差较大,差值可达10余克以外,大部分药物两个范围的重合区域均较大。5分析探讨基于本论文研究部分所得结果可以看出,经方本源剂量发展至明代出现了明显的下降,而在自明至今近600年的时间内剂量变化似乎并不大,因此,寻找迷失的经方本源剂量,揭开经方本源剂量下降之秘,成为本论文下篇分析探讨部分的重点。(1)在“寻找迷失的经方本源剂量”一节,分别从文物考古学、文献考据学,以及“药升”、“药秤”、“黄金小秤”否定说角度浅证并支持经方本源剂量即为吴承洛先生提出的1两≈13.92克之说。(2)在“破解经方剂量下降之谜”一节,指出自汉至明,经方本源剂量存在着明显的“左移”现象,即剂量下降趋势。并分别从宋代推行散剂之追本溯源；宋代盛行煮散之得失探讨,主要是导致汤药服法从仲景时代的“一剂三服”发展至明清时期的“一剂一服”；李时珍“古之一两今用一钱”之对错分析；气候-地域-体质三链效应对临床用药剂量的影响；哲学-文化-用药心理学的内在影响等五方面探讨了每个因素对经方本源剂量之下降可能造成的影响。(3)在“从明代医家用药探讨临床剂量控制策略”一节,提出方药用量的“右墙”假说,即任何一首方剂,一味中药,对应每一位患者都存在着一个极限剂量值,即“右墙”剂量。而同一首方剂,同一味中药,对不同的患者而病证而言,其“右墙”剂量亦有所不同。在临床中,“右墙”剂量以左的剂量区间均属有效剂量区间,即治疗窗。然而最佳剂量范围却只有较窄的一段区域,如何找出方药的“右墙”剂量并确定其最佳剂量范围应为今后量-效关系研究的重点。(4)由于中药的阈剂量普遍较低而治疗窗普遍较宽,使得中药的临床用量千差万别,剂量变化十分灵活。本论文通过对明代13位医家的临床用药特色进行研究,并与其他朝代的医书互相联系参照,总结了古代医家在临证施量方面的两条常用控制策略：一为试探性给药法,常用于药性峻猛,气味辛烈,或有较大毒副作用的方药；一为阶梯式给药法,又分为阶梯式增量给药法与阶梯式增时给药法,常用于病程缠绵,需药力逐渐累积以获效,或轻剂缓图,以求祛邪而不伤正之病证。许多古人常用的剂量调控方法随着中医药的标准化与规范化正面临着逐渐被遗弃的处境,而进一步挖掘古代医家的临床用量控制策略将是开启方药剂量理论宝库的重要钥匙。更多还原

【Abstract】 The Chinese medical science has a distant source and a long stream.The traditional Chinese medicine (TCM) theories based on Yin Yang and five elements theory are broad and profound, that has successfully guided clinical treatments for thousands of years.The academic succession of TCM theories has continued for a long time, and never been broken off. However, compared to the integrated principles system of TCM prescription and treatments,the Chinese medical dosage theories have not been summarized and systemized. This makes the TCM dosage-effect relationship studies fall behind of the western medicine. Too many influencing factors which are mutually related and interplayed make the TCM dosage-effect relationship studies face tremendous difficult problems and great challenges, that has become the restriction of the innovation of TCM theories.Shanghan Zabing Lun (Treatise on Cold Pathogenic and Other Diseases) written by Zhang Zhong-jing with strict formulation and precise prescription was looked upon as the progenitor of prescription books and was called "classical prescriptions" best-known by afterworld. The study on dosage rules of commonly used herbal drugs in classical prescriptions is very important to study on TCM dosage-effect relationship theories. However, the first question needed to answer is that what the original dosage of classical prescription is. Since the conclusion "one Liang in Donghan dynasty approximated 15.625 gram in the present age" according to the " Guanghe Da Sinong Cuprum Counterweight" was promulgated in the eighties last century, a new upsurge of the textual research has emerged. All kinds of research methods and research conclusions are teeming one after another which can’t be obtained consistency in a short time.For the dosage ranges of many herb drugs in national pharmacopoeia and Chinese Pharmacy textbooks are closely related to "one Liang in Donghan dynasty approximated one Qian in Ming dynasty" put forward by Li Shi-zhen. Therefore, the main objective of this dissertation is to find the dosage ringes of the commonly used Chinese drugs in classical prescription in Ming dynasty, to find the evolution of dosage of commonly used herbs in classical prescription from Donghan Dynasty to Ming Dynasty, to summarize the characteristics and features and control strategies of Chinese medication usage in clinical practice by doctors in Ming dynasty.1 Objective(1)Choosing fifty commonly used Chinese drugs in Shanghan Zabing Lun (Treatise on Cold Pathogenic and Other Diseases), studying the clinical dosage rules and features of doctors’ using Chinese medicine in Ming dynasty, including common dosage range, average dosage, the most frequently used dosage, and the distribution extent from the minimum to the maximal dosage.(2) Calculating the dosage ranges of 50 commonly used Chinese drugs in Shanghan Zabing Lun (Treatise on Cold Pathogenic and Other Diseases) according to the conclusion that one Liang in Donghan dynasty approximated 13.92 g, studying the comparison with the dosage range in Ming dynasty, in order to prove that whether the dosage conver standard is close to "one Liang in Donghan dynasty approximated one Qian in Ming dynasty" proposed by Li Shi-zhen, and explaining the reason for the great drop height of common dosage range from Donghan dynasty to Ming dynasty.(3) Calculating the common dosage ranges of 50 frequently used Chinese drugs, in comparison to the dosage ranges in national pharmacopoeia and Chinese Pharmacy textbooks, summarizing the differences between the doctors’using Chinese drugs in Ming dynasty and contemporary time, in order to provide some reference for regulating safe, scientific, reasonable, effectual dosage ranges.(4) Summarizing the influencing factors of dosage-effect relationship, such as physical constitution of patients, climatic condition, geographical regions, herbs processing, preparation form, philosophy and culture, and so on, through the study on the dosage characteristics of the doctors in Ming dynasty, excavating the clinical dosage control strategies of the doctors in ancient China.2 ContentsThe fifty frequently used Chinese drugs chosen by studying team are the research objects, while the research contents are thirteen books published in Ming dynasty. The dosage features of the fifty Chinese drugs will be studied, including the average dosage, the common dosage range, the most frequently used dosage, and the distribution extent from the minimum to the maximal dosage. The thirteen books will be studied is listed as follows:Shi Shan Yi An (by Wang Ji), Sun Yi-kui Yi An (by Sun Yi-kui), Li Zhong Yi An (by Li Zhong-zi), Xianxingzhai Yixue Guang Biji (by Miu Xi-yong), Yi Yon Da Cheng (by Qin Chang-yu), Qi Xiao Yi Shu (by Nie Shang-heng), Jing-yue Quan Shu (by Zhang Jing-yue), Yi Xue Zheng Zhuan (by Yu Tuan), Ming Yi Za Zhu (by Wang Lun), Nei Ke Zhai Yao (by Xue Ji), Shou Shi Bao Yuan (by Gong Ting-xian), Wen Yi Lun (by Wu You-ke), Gu Jin Yi Tong Da Quan (by Xu Chun-fu).3 MethodThrough the Excel table processing function and basic statistical methods including, standard deviation, variance, dispersion, arithmetic mean and so on, obtain the occurrence frequency, the common dosage range, the average dosage, the most frequently used dosage, and the distribution extent from the minimum to the maximal dosage of the fifty Chinese drugs. The common dosage range is calculated by percentile method PX=L+i/fx[n.X%-∑fL], which is described by the range of[P10-P90]. 4 ResultsThe results of the study will be discussed separated into two parts, one is the general discussion about the fifty herb drugs, the other is individual exposition about thirty-two herb drugs of the fifty. The main results are stated as follows:(1)The common dosage range, the average dosage, the most frequently used dosage, and the distribution extent from the minimum to the maximal dosage of the fifty Chinese drugs in Shanghan Zabing Lun (Treatise on Cold Pathogenic and Other Diseases) are all higher than that in Ming dynasty and contemporary time. Taking the most frequently used dosage for example, the dosage of twenty-three herb drugs of fifty in Ming dynasty is lower than ten percent of the dosage in Donghan dynasty.(2) The dosage of common Chinese drugs in Ming dynasty is mainly distributed in from one tenth to one third of the dosage of common Chinese drugs in Zhong-jing ages."One Liang in Donghan dynasty approximated one Qian in Ming dynasty" proposed by Li Shi-zhen is equivalent to one third of dosage of Chinese drugs in Zhong-jing’s prescription, and this dosage convert standard is on the high side in Ming dynasty.(3) The dosage ranges of the fifty commonly used Chinese drugs in national pharmacopoeia and Chinese Pharmacy textbooks are close to the dosage ranges of these drugs in Ming dynasty. Except Chinese rhubarb, plaster stone, astragalus, talc, oyster etc. the dosage of the other Chinese drugs in fifty in Ming dynasty is at close range of that in national pharmacopoeia and Chinese Pharmacy textbooks.5 Analysis & DiscussionThe conclusion can be obtained that the original dosage of classical prescription has declined a lot from Donghan dynasty to Ming dynasty through the results of the study. But the dosage of common Chinese drugs did not change much from Ming dynasty to now. Therefore, the emphasis in this part is to search the original dosage of classical prescription and unveil the decline of original dosage of classical prescription.(1) In the chapter "Searching Lost Original Dosage of Classical Prescription", prove and support the conclusion "one Liang in Donghan dynasty approximated 13.92g" put forward by professor Wu Cheng-luo, through the negation to "herbs weighing scale", "herbs measuring cup" and "gold weighing scale".(2) In the chapter "Unveil The Decline of Original Dosage of Classical Prescription", the dosage of classical prescription declined so significantly, that is called "left shift" also. Analyse how these influencing factors act upon the dosage of classical prescription, such as powders prevailing in Song dynasty, powders prevailing making the taking medicine methods convert from "one dose taken for three times" to "one dose taken for one time", the influence of "One Liang in Donghan dynasty approximated one Qian in Ming dynasty" proposed by Li Shi-zhen, the influence of climate-area-constitution effect, and philosophy-culture-drug usage psychology, and so on.(3) In the chapter "The Study on The Dosage Control Strategies in Ming Dynasty", the "Right Wall" dosage hypothesis is proposed, that means that every herb drug, every prescription has a dose limit (maximal dosage), also called "Right Wall" dosage. For different patient or different disease, the "Right Wall" dosage of one Chinese drug is different too.The dose area in the left of the "Right Wall" dosage can be effective in clinical practice, but the most effective dosage range is very narrow. Therefore finding the "Right Wall" dosage of one prescription or one Chinese drug will be the main aim of the dosage-effect relationship research for the future.(4) Because of the lower threshold dosage and the wider treatment window, the doses of Chinese drugs are various in TCM clinical practice and can be changed flexiblely. Two frequently used dosage control strategies in clinical practice are summarized by studying the thirteen doctors’clinical drugs usage experiences in Ming dynasty. One is exploratory method for taking Chinese drugs, which is often for that the nature of herbs or prescriptions is impetuous, fierce or venenous.The other is laddered method for taking medicine, which includes laddered increasing dose method and laddered increasing time method for taking Chinese drugs.The laddered method for taking Chinese drugs is often for that the course of the disease is long and the efficacy of the medicine should be accumulated to eliminate pathogenic factors. It is a pity that many methods doctors in ancient China used frequently in clinical practice have been discarded nowadays with the traditional Chinese medical standardization. Thoroughly excavating the dosage control strategies in ancient medical books will be the most important key to open up the treasure house of TCM dosage theories.更多还原