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桂枝芍药生姜的剂量功效关系比较研究

Comparative Study on the Dose-effect Relationship in Guizhi,Shaoyao and Shengjiang

【作者】 李宇铭

【导师】 姜良铎;

【作者基本信息】 北京中医药大学 , 中医内科学, 2012, 博士

【副题名】经方原方剂量应用临床体会

【摘要】 目的以近新考证的药量折算方法,将《伤寒论》、《金匮要略》和《温病条辨》的全部方剂换算成现代剂量,透过多种剂量比较,总结桂枝、芍药与生姜三味药的“剂量功效关系”,并探讨张仲景与吴鞠通在用药剂量上的承传关系;分析导师姜良铎教授在运用上述三味药的“剂量功效关系”,并与张仲景和吴鞠通的剂量理论作古今比较。研究方法本研究先将《伤寒论》、《金匮要略》与《温病条辨》全书的方剂折算为“克”(g)。经方药物的用量,以一两兑换15.625g的方法换算;《温病条辨》药物的用量,则按一两兑换37.3g换算。根据煎服法不同,计算出折算量、一天量与一次量等三种剂量。将以上数据输入电脑数据库,制成多个列表进行文献比较分析。提出“文献量”的概念,指药物在文献中分析得出的理论用量。文献量是以方剂中的“一次量”作为剂量比较的基础,用于揭示药物的剂量比例关系,使古今方药放在同一用量层次平台作比较,有助理解如何将古方在今天应用。导师姜良铎教授的剂量研究,透过分析近六年病案数据库的处方纪录,以得出剂层次与范围;并且透过近两年门诊病历复诊病案加减法的用药,分析剂量与功效的关系。结果第一章:桂枝研究张仲景运用桂枝,从最大量62.5g到最小量1.3g,剂量相差48倍,药量变化甚广桂枝具有6种剂量功效层次,并总结出桂枝的剂量功效关系表,以及桂枝与8种药物的“绝对剂量”配伍比例关系。吴鞠通运用桂枝,从最大量的12.4g到最小用量0.9g,之间相差约14倍,虽然与现代常用量3-10g较为接近,但用药变化差距更广。桂枝具有5种剂量功效层次,并总结出桂枝的剂量功效关系表。张仲景与吴鞠通运用桂枝的比较。两者皆具有多层次的“剂量功效关系”,且具有类似特点,包括量大则病位趋于表、或用在重证;中量则病位在中,用在宣通中焦阳气;小量则多用在助药配伍。然同中有异,两者在大、中、小量层次具体用量不同,吴氏用量总体相对较轻,而在用量较轻的剂量功效关系上,两者则有明显差异。姜良铎教授运用桂枝,占所有门诊处方中21.9%,剂量范围在6-30g,相比现代桂枝常用量3-10g的用法,剂量起点较高,用量范围更广。其中包含了8种剂量层次,总结出姜教授运用桂枝的剂量与主治病证特点关系表。姜良铎教授与张吴二氏比较。张仲景在运用桂枝一般在5.2-20.8g的剂量范围,这与姜良铎教授运用桂枝习惯较为接近,而姜教授使用桂枝30g的机会似乎更为频繁;吴鞠通在运用桂枝一般在3.7-12.4g的剂量范围,此一范围相对较窄,总体剂量使用颇轻。第二章:生姜研究张仲景运用生姜,从最大用量62.5g到最小量1.6-3.9g、或5.2g,剂量跨度相差39倍或12倍,药量变化甚广。生姜具有7种剂量功效层次,并总结出生姜的剂量功效关系表,以及总结生姜与7种药物的“绝对剂量”配伍比例关系。以桂枝与生姜进行比较,生姜用量总体较大,反映生姜力量较弱。吴鞠通运用生姜,从最大用量9.3g到最小量1.3g,与现代生姜常用量3-10g接近。生姜具有3种剂量功效层次,并总结出生姜的剂量功效关系表。张仲景与吴鞠通运用生姜的比较。两者均具有多层次的剂量功效关系,部份剂量层次之间功效相同,而只是在于病情轻重的不同;两者皆甚少运用生姜作为“君药”,大多用作为臣佐配伍。在剂量的层次数量上,两者差别较大,吴鞠通剂量层次较少,反映张仲景运用生姜较为灵活多变。姜良铎教授运用生姜,占所有门诊处方中5.3%,剂量范围在3-10g,与现代常用量基本一致。其中包括了3种剂量层次,无论在初诊抑或复诊应用生姜,皆以9-10g生姜最为常用,且大部分情况下均配伍大枣使用。总结出姜教授运用桂枝的剂量与主治病证特点关系表。姜良铎教授与张吴二氏比较。张仲景运用生姜一般在10.4-62.5g的剂量范围,剂量规度甚广,其中以15.6g为较常用的剂量,较姜教授对生姜的常用量接近而剂量更重;张仲景使用生姜剂量较为明确,全部方剂使用“斤两”为单位,而姜教授则较多使用“片”作为单位。吴鞠通运用生姜的剂量范围一般在3.7-9.3g,与姜教授的用量基本相同;吴鞠通运用生姜剂量分布较为零散,较为常用3.7g,相较姜教授则最为集中运用9-10g剂量。吴鞠通运用生姜亦多用“片”作为单位,这与姜教授运用生姜的剂量用法十分相近。第三章:芍药研究据考证张仲景所用芍药当为“赤芍”,并无补益之功,其功效在于通降营血。由此重新理解桂枝汤的方义,则桂枝在于宣通上焦营卫之气,而芍药则在通降中下二焦而营气,两者一升一降、一阳一阴,皆在于通行营卫。以此角度对多首经方作重新解释。张仲景运用芍药,从最大量31.3g到最小量的1.3g,其中相差相差24倍,药量变化甚厂。芍药具有5种剂量功效层次,并总结出芍药的剂量功效关系表,以及芍药与6种药物的“绝对剂量”配伍比例关系张仲景运用芍药与桂枝、生姜作比较,三者均具有多层次的“剂量与功效关系’均是在15.6g剂量层次较为常用。三者相异之处较多,如剂量跨度距离不同,总体运用生姜剂量偏大,一般运用芍药剂量范围比桂枝要大,只在特殊情况下桂枝剂量甚重,而芍药则无此一特殊情况。三药的“剂量功效关系”层次情况有别,芍药虽然有不同剂量层次,但是各种剂量的功效也是基本相同,而只在于通降营气的强弱之别;生姜则在某些层次之间的区分并不明确,桂枝则相对每一个层次的功效差异较为明确。三药在能否成为“君药”的问题上,桂枝较多机会成为君药,芍药则较少,而生姜则甚少。吴鞠通应用芍药,吴氏认为古之芍药当为“白芍”,具有三方面功效:补阴、敛阴;去恶血而生新血;补脾。但吴氏对于芍药味苦的认识有所矛盾,一方面认为白芍能上行,但又认为芍药能下行通降。吴鞠通运用芍药,从最大量9.3g到最小量1.2g,之间相差约8倍,比现代白芍的常用量6-15g更轻。芍药具有4种剂量功效层次,并总结出芍药的剂量功效关系表。张仲景与吴鞠通运用芍药的比较。两者均具有多层次的“剂量功效关系”,而且剂量功效层次界限不清晰,即是不同剂量层次但功效基本相同。由于两者所选用的芍药不同,导致两者的功效差异较大。姜良铎教授运用芍药,占所有门诊处方中75.4%,其中97.8%为“赤白芍同用”只有0.7%单用赤芍、1.5%单用白芍。姜教授运用芍药,剂量范围在6-30g,但由于大部分情况下均是赤白芍同用,亦即运用芍药剂量在12-60g的范围,比现代一般认为的常用量要大得多,但在97.9%的处方中,均使用赤白芍各12g的剂量,实际上芍药的剂量范围较为狭窄。总结出姜教授运用芍药的剂量与主治病证特点关系表。姜良铎教授与张吴二氏比较。张仲景运用芍药,一般在10.4-30.3g剂量范围,其中更以15.6g的方剂出现最为频密,这与姜教授一般运用芍药在12-15g亦较为接近。至于吴鞠通应用芍药的剂量范围在1.2-9.3g,总体剂量范围比姜教授用药更轻。但是,由于三者所用的芍药不同,因此难以直接进行比较。结论本论文总结了张仲景与吴鞠通在运用桂枝、生姜、芍药三药的理论,指出二人的在运用三种药物的多层次“剂量功效关系”,并发现吴鞠通在张仲景的用药基础上有继承而发展。另外亦总结出姜良铎教授运用三药的剂量层次与范围,以及剂量与主治病证关系,姜教授用药与张吴二氏同中有异,且未发现明确多层次的剂量功效关系。另外,本论文附上一相关研究课题:(见后页)目的尝试证明经方原方以及原方剂量,能够运用于现代临床。研究方法以汉代一两等于15g的折算方法,于现代临床运用经方的原方以及原方剂量,总结250例亲身诊治病案的临床体会。结果在治验的病案之中,在2剂药内治愈的病例占六成,而5剂药内治愈的约占九成,需要用上7剂药以上的只占少数;另外,2剂内主诉减半的病例占八成,而3剂内能够使主诉减半的病例更占九成多。体会由此临床实践,初步验证了经方原方能够应用在当今临床,具有“一剂知、两剂已”的速效,临床运用经方并非必须“灵活加减”,亦体会经方并非不能长期服用,原方剂量拉伸距离甚广,经方煎服法方便患者,翻煎破坏方剂配伍关系,使用经方必须注意药物质量,打破药典“常用量”的局限,使用“原方”必须重视“原意’

【Abstract】 ObjectiveBy using the latest research on dosage conversation method, all the formulas and medicinal in Treatise on Cold Damage Disease, Synopsis of Prescription of the Golden Chamber and Systematized Identification of Warm Diseases were converted into modern dosage. Through several dosage comparisons, it summarized the "dose-effect relationship" of 3 medicines: Guizhi, Shengjiang and Shaoyao, and also discussed on the inheritance relationship between Zhang Zhong-jing(abbr ZZJ) and Wu Ju-tong(abbr WJT). Moreover, the analysis of the "dose-effect relationship" of above 3 medicines used by mentor Prof. Jiang Liang-duo(abbr JLD) and comparison between Zhang Zhong-jing and Wu Ju-tong for the dosage theory from ancient to modern were presented.Research MethodsIn this study, firstly it converted all the formulas and medicinal in Treatise on Cold Damage Disease, Synopsis of Prescription of the Golden Chamber and Systematized Identification of Warm Diseases into grams(g). For the medicine in classical formula,1 tael (Liang) is converted to 15.625g. For medicine in "Systematized Identification of Warm Diseases",1 tael (Liang) is converted to 37.3g. According to different Decoction and Medication methods, there are 3 types of dosage calculations which are:Converted dosage, One day dosage and Once intake dose. Above data is required to input into computer database, and make multiple lists for literature comparison analysis.The concept of Literature dose refers to the theoretical dose of medicine obtained from literature. Literature dosage adopted "Once intake dose" of formulas and medicinal for the basis of comparison. To reveal the dose ratio relationship between medicines, the ancient and modern prescriptions were compared on the same dose level platform to help understanding on how to use ancient prescriptions nowadays. For the dose study on Mentor JLD, the past six years prescription medical records in the database were analyzed in order to obtain the dose level and range. The dose-effect relationship was analyzed through the past two years outpatient follow-up medical records on the medicine addition and subtraction.ResultChapter 1:Guizhi Research ZZJ used Guizhi, from maximum dose 62.5g to minimum dose 1.3g, with 48 times difference and the dose range was very wide. Guizhi had 6 dose-effect levels, and it concluded the table of dose-effect relationship of Guizhi, as well as the "absolute dose" compatibility ratio relationship of Guizhi with 8 kinds of medicines. WJT used Guizhi, from maximum dose of 12.4g to minimum dose of 0.9g, with 14 times difference. Although it was relatively closer to modern usual dose 3-10g, the dosage gap was wider. Guizhi had 5 dose-effect levels and concluded the table of dose-effect relationship of Guizhi.The use of Guizhi between ZZJ and WJT were compared and both of them had multi-level dose-effect relationship with similar characteristics. For instance, for the location of disease tends to exterior in high dose, or using in serious situation. The location of disease tends to middle in middle dosage, using for diffuse and free the yang qi in middle energizer. It assists medicine in combination in low dose. But there were differences in specific dose at high, middle and low levels. WJT was relatively light in dose, and also in the dose-effect relationship of low dose level, there were significant differences between them.JLD used Guizhi, accounting for 21.9% of all outpatient prescriptions, in a 6-30g dose range, compared to the 3-10g modern usual dose of Guizhi. The starting point was higher and dose range was wider. With 8 dose levels, summerized the table of dose and disease treatment characteristics relationship of Guizhi by usage of JLD.JLD with ZZJ and WJT were compared. ZZJ used Guizhi generally in 5.2-20.8g dose range. It similar as the habit of JLD, but seems that JLD used 30g Guizhi more frequently whereas WJT used Guizhi generally in 3.7-12.4g dose range. This range was relatively narrow and the overall dose was quite light.Chapter 2:Shengjiang ResearchZZJ used Shengjiang, from maximum dose 62.5g to minimum dose 1.6-3.9g, or 5.2g, with 39 times or 12 times differences and dose range was very wide. Shengjiang had 7 dose-effect levels, and concluded the table of dose-effect relationship of Shengjiang, as well as the "absolute dose" compatibility ratio relationship of Guizhi with 7 kinds of medicines. When Guizhi was compared with Shengjiang, dose of Shengjiang was relatively higher which incidated Shengjiang was weak in effect. WJT used Shengjiang from maximum dose 9.3g to minimum dose 1.3g, was closer to modern usual dose 3-10g. Shengjiang had 3 dose-effect levels, and summarized the table of dose-effect relationship of Shengjiang.The use of Shengjiang between ZZJ and WJT was compared. Both of them had multi-level dose-effect relationship and some of the dose level got the same effect, with varying severity. Both of then seldom used Shengjiang as sovereign medicinal, mostly used as minister or assistant combination. There were great differences on the dose level. WJT had lesser dose level, showing that ZZJ was more flexible and variable in using Shengjiang.JLD used Shengjiang, accounting for 5.3% of all outpatient prescriptions, in a 3-10g dose range, it is basically the same as modern usual dose, including 3 dose levels. For both first visit or follow up patients,9-10g was the commonly used dose, combined with Dazao in most situations. The table of dose and disease treatment characteristics relationship of Shengjiang by usage of JLD was concluded.JLD with ZZJ and WJT were compared. ZZJ used Shengjiang generally in 10.4-62.5g dose range and the dose range was very wide, but 15.6g was the common dose and it was closer to JLD but with higher dose. ZLD used Shengjiang which was more clear in dose, because all of prescriptions used Jin and Liang as unit, while JLD usually used pieces as unit. WJT used Shengjiang generally in 3.7-9.3g dose range, basically the same as JLD. The dose of Shengjiang used by WJT was in a variety of distribution, it was relatively common use in 3.7g, but JLD was more centralized in 9-10g. WJT also frequently used pieces as unit, similar to JLD.Chapter 3:Shaoyao researchAccording to textual research, Shaoyao used by ZZJ was "Chishao". which has no function of tonifying and replenishing, but free and downbearing the nutrient and blood. Therefore this is a new understanding of Guizhi decoction. Guizhi aims to diffuse and free the yang qi in upper energizer, Shaoyao frees and downbears the nutrient and blood in middle and lower energizer. They together function in upward and downward, yang and yin, both aims to free nutrient qi and defense qi. From this angle, it re-explained several Classical formula.ZZJ used Shaoyao, from maximum dose 31.3g to minimum dose 1.3g, with 24 times difference and dose range was very wide. Guizhi had 5 dose-effect levels, and concluded the table of dose-effect relationship of Guizhi, as well as the "absolute dose" compatibility ratio relationship of Guizhi with 6 kinds of medicines.Shaoyao, Guizhi and Shengjiang used by ZZJ were compared. All of them had multi-level dose-effect relationship, and 15.6g dose level was more commonly used, but there were many differences, such as different dose range, high overall dose of Shengjiang and generally the dose range of Shaoyao was higher than Guizhi, but for some specific situations, Guizhi could be even higher, but Shaoyao did not have this exceptional case. The "dose-effect relationship" of 3 medicines was different. Although Shaoyao had several dose levels, the effect of every level was almost the same. The only difference lies in the power of freeing and downbearing nutrient qi. Some dose level of Shengjiang was indistinguishable in effect, while Guizhi was clearer in every dose level. In terms of "sovereign medicinal", Guizhi got highest chance, lesser chance in Shaoyao,and seldom in Shengjiang.WJT used Shaoyao. He thought that the ancient Shaoyao was "Baishao", it got the effects of tonifying yin and constraining yin, removing malign blood and promoting regeneration blood, and tonifying the spleen. WJT was inconsistent in the understanding of Bitter taste in Shaoyao, not only believed that Baishao could upward bearing, but also think that Shaoyao could free and downward bearing. WJT mainly used Baishao from maximum dose 9.3g to minimum dose 1.2g with 8 times difference and dose was relatively lighter than Baishao modern usual dose 6-15g. Shaoyao had 4 dose-effect levels, and summerized the table of dose-effect relationship of Shaoyao.The use of Shaoyao between ZZJ and WJT was compared. Both of them had multi-level dose-effect relationship, and also indistinguishable in the dose-effect level, that is different dose level but with similar function. Since they used different Shaoyao, as a result their function had great difference.JLD used Shaoyao, accounting for 75.4% of all outpatient prescriptions,97.8% of them were "Chishao and Baishao used together", only 0.7% used Chishao solely, and 1.5% Baishao solely. JLD used Shaoyao in 6-30g dose range, but since most of situations were "Chishao and Baishao used together", that means Shaoyao dose level was 12-60g range, it was much higher than the modern common dose, but 97.9% prescriptions were using "Chishao and Baishao" both 12g, the actual dose range of Shaoyao was narrow. In the follow up addition and subtraction of medicine, JLD seldom used Shaoyao, it means most of the first visit case already prescript Shaoyao, so, it was not necessary to add in follow up, but also reflect the dose range of Shaoyao is relatively centralized and no need to change dose in follow up. The table of dose and disease treatment characteristics relationship of Shaoyao by usage of JLD is concluded.JLD with ZZJ and WJT was compared. ZZJ used Shaoyao generally in 10.4-30.3g dose range, and more commonly used in 15.6g. It was similar as 12-15g common dose in Proj JLD. WJT using Shaoyao gererally in 1.2-9.3g, the overall dose range was lighter than JLD. However, since 3 people used different Shaoyao, it was difficult to compare it equally. By comparing on the dose level, the dose level of Shaoyao used by ZZJ was more disguisable and overall dose in Shaoyao could be higher than JLD (it depends on superimposing the dose of Chishao and Baishao or not). JLD and WJT used Shaoyao were similar but with some differences. WJT got 4 different dose levels, but the dose of each level was not clear and 3 dose levels which cannot be discovered clear common function. JLD also not clear in every dose-effect level, whereas JLD not only used Shaoyao in Yin deficiency or static blood syndrome, but also used in harmonized the nutrient and defense, nourish and move blood, emolliate the liver and relieve pain. ConclusionThis thesis concluded the theory of using Guizhi, Shengjiang and Shaoyao by ZZJ and WJT which indicated both of them had multi-level dose-effect relationship and discovered that WJT based on the theory of ZZJ and its development. Also, it concluded the dose level and range of 3 medicines by JLD, as well as the dose and disease treatment characteristics relationship. JLD was similar as ZZJ and WJT but with some differences and there was no clear multi-level dose-effect relationship discovered.In addition, this thesis is accompanied by a relevant research topic:Clinical Experience with Classical Formula by Original Formula Dosage ApplicationObjectiveTo proof that the original formula and original dosage of Classical formula could be used in modern clinical practice.Research methodConverted 1 tael (Liang) in Han Dynasty equals to 15g and using original formula and original dosage of classical formula in nowadays clinical practice,250 cases firsthand clinical experiences are concluded.ResultsIn those cured clinical cases,60% was cured within 2 packs dosage, and 90% was cured with 5 packs dosage, only few cases was cured by more than 7 packs dosage. Moreover,80% cases could reduce the chief complaint by half within 2 pack dosage, and more than 90% cases could reduce the chief complaint by half within 3 pack dosage.ExperienceFrom this clinical practice, it preliminarily proofed that the original dosage of classical formula can be used nowadays. It has instant effect of "therapeutic effect by one pack dosage, and cured by two pack dosage", when using classical formula in clinical which did not require "modification flexibly ". In addition, it shows that the classical formula can still be long term used, the range of original dosage is very wide, the decoction and medication method of Classical formula is convenience to patient, the re-boiling method ruining the compatibility relationship between medicines, using classical formula should pay attention to quality of medicine, breakthrough the limits of "common dose" in pharmacopeia, using "original dosage"; must pay attention to "original theory".

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