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胃脘痛有效方药的筛选与评价
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摘要
胃脘痛,是一种古今常见的内科病证。中医治疗胃脘痛历史悠久,经验丰富,方法独特,疗效肯定,且自成体系。但同时也存在一些问题:如病证名称的混乱、病证内涵与外延的不确定,积累的古今文献虽然数量很多,但内容分散,所记载的胃脘痛治疗方药也是良莠参半,辨证与选方用药均缺少一定的规范性,使得临床疗效的稳定性差,或然性大等,影响了医界与患者对中医药治疗胃痛证的信任度,故有必要进行比较系统的研究。开展胃脘痛有效方药筛选与评价研究,可以挖掘胃脘痛有效方药,建立胃脘痛有效方药的筛选平台和评价体系,推进胃脘痛临床新药的开发进程,并促进对胃脘痛病因病机的研究。
     研究内容:分为胃脘痛文献的系统整理、胃脘痛方药的筛选、胃脘痛方药有效性的评价三个部分。
     研究方法:在文献调查、按类统计的基础上,利用频次分析方法进行筛选,并结合循证医学原理,以临床效验为依据,进行方药有效性的评价。
     研究结果:以胃脘痛相关病名为线索,进行相关方药的搜集。共收集中药75味,分别出自25种医籍;方剂263首,分别出自115种医籍;医案354则,分别出自55种医籍。
     在初步搜集的75味中药中,明确记载治疗胃脘痛的有45味,根据对其所出现的本草文献频次和方剂文献频次之和的统计,将超过6次的19味药物,逐一进行分析,19味药物分别是草豆蔻、荔枝核、蜗蠃、丁香油(露)、白术、白芍药、高良姜、吴茱萸、石膏、韭、延胡索、当归、川芎、白豆蔻、桂丁(肉桂子)、姜黄、藿香、麻黄、蒲黄。有的药物用于治疗胃脘痛的历史较久,被不同的医家、不同朝代反复引用,如草豆蔻;有的药物用于治疗胃脘痛的历史较久,历代引用文献较多,但使用该药进行配伍的方剂很少,提示本药以单味药使用为主,如荔枝核;有的药物历代引用文献较多,但由于含这类药物成分的西药的广泛使用(方便价廉),本药现代已基本不使用了,如蜗蠃;有些药物在本草文献中只出现1次,但在方剂文献中有较多首方剂组成含有该药,基本可以判断该药也是一味治疗胃脘痛的有效药物,如当归、川芎。
     通过对胃脘痛方组成药物的统计分析,发现263首胃脘痛方共使用药物261味,合计2251方次,平均每药出现8.6245方次。以平均方次8.6245最接近的整数9,作为胃脘痛重点药的标准,共收录到61种药味,占总药味数(261)的23.37%;这61种药味共出现1705方次,占药味总方次(2251)的75.74%。出现频次最高的药物是陈皮108,其次是甘草87、木香81、香附71、半夏55、厚朴53、砂仁52、茯苓51、延胡索46方次等,这些药除甘草外,大多为理气化痰燥湿药,其中含有二陈汤的全部配方成分,说明古今成方用二陈汤治疗胃痛的几率较高。
     胃脘痛有效方剂的筛选主要通过三个途径,一是从《中医方剂大辞典》等方剂文献中查检古今成方;二是从古今医案文献中查检胃脘痛案例;三是通过现代临床期刊报道进行查检。
     共检到符合收方标准的胃脘痛成方263首,胃脘痛医案文献涉方73首,现代临床期刊文献共涉方(传统成方)81首。
     将三类方剂进行比对,选出在两类文献中均出现的方剂作为重点方,共25首。25首重点方剂有以下几个特征:①小方居多,25方中就有5首是由2味药组成的方剂,其余也大多为4~5味的小方。②25方分属10个功效类别,每类平均2.5方,提示功效作用分散,临床胃痛证型广泛。③10类功效中包含了补虚与泻实两大类,补虚包含了补气、补血、养阴和温阳四法;泻实中则包含了调气、活血、化痰、祛湿、泻火和散寒六法,提示这些方法可能概括了治疗胃脘痛的基本大法,这些方剂也可能为治疗胃脘痛的基本方。其中有7首方剂在三类文献中均涉及,是重点方中的重点,分别是二陈汤、失笑散、金铃子散、理中汤、越鞠丸、平胃散、吴茱萸汤。
     二陈汤是一首化痰基本方,经过加味,一直被不同时代的医家用于治疗痰湿胃痛,兼有呕吐者效果更显著;失笑散古代多用于治疗妇人产后小腹痛,《女科切要》明确指出用于治疗“胃脘痛”,临床用于治疗“气滞血瘀”引起胃脘痛;金铃子散从明代《袖珍方》起,用于治疗热厥心痛,临床治疗肝气郁滞,气郁化火而致的胃脘痛;理中汤出自《伤寒论》,是温中散寒的基本方,可治疗脾胃虚寒性胃脘痛;越鞠丸为朱丹溪所创,原方用于解诸郁,治疗胃脘痛时常适当加味使用;平胃散出自《太平惠民和剂局方》,治疗湿滞胃痛;吴茱萸汤首见于《伤寒论》,治疗中虚寒凝之胃脘痛。
     结论与讨论:
     1.草豆蔻、荔枝核、蜗蠃、丁香油(露)、白术、白芍药、高良姜、吴茱萸、石膏、韭、延胡索、当归、川芎、白豆蔻、桂丁(肉桂子)、姜黄、藿香、麻黄和蒲黄等19种药物使用频次较高,为治疗胃脘痛的有效药物。结合方剂分析,则甘草、木香、香附、半夏、厚朴、砂仁、茯苓、延胡索为常用有效药。而二陈汤、失笑散、金铃子散、理中汤、越鞠丸、平胃散、吴茱萸汤等7首方剂为有效复方。
     2.治疗胃脘痛的单味药的频次与复方组成中频次的差异,恰好说明了某些药物需要通过配伍才能发挥药效;而另一些药物可能为治疗胃脘痛的有效单方,这两类有效药物均值得重视。
     3.对相关药物和方剂的分析表明,有效方药往往集中在理气活血、行气解郁、化痰燥湿、温中散寒等功效类型,说明胃脘痛的证候类型也以气滞血瘀、肝气郁滞、痰湿阻滞、阳虚寒凝为多见。
Stomachache is a very commonly seen disease in internal medicine. TCM remedy for the stomach pain has a long history, rich experience, unique methodology, positive curative effect and forms a distinctive system. But at the same time, there exists some problems, e.g. the chaos of different names being used for this disorder; the uncertainty of the name's denotations and connotations. Large as the amount of the classic and modern literature is, their contents are dispersive and recorded formulae of different levels for stomach pain therapy are intermingled; syndrome differentiation and choices of prescriptions are poorly normalized. As a result the clinical effect is unstable and opportunistic, which affects the doctors' and the patients' confidence in the using of TCM therapy for the stomach pain. Hence a systemic research is necessary. Through screening and evaluation, we can discover effective herbs and formulae for stomachache and preliminarily set up a screening and evaluation system. In this way the research and development of new medicine for stomachache can be promoted, meanwhile the understanding of etiology and pathogenesis of stomachache can be improved.
     Research contents: It can be divided into three parts: systemic collection of literature relating to stomachache, screening of formulae and herbs used in the treatment of stomachache, evaluation of the effectiveness of formulae and herbs being selected.
     Research method: Based on literature review and group statistic results, screening is carried out by using frequency analysis. Combining principles of evidence-based medicine and on the basis of clinical therapeutic result, the efficacy of herbs and formulae is evaluated.
     Research result: 75 herbs have been collected through searching of related formulae and these herbs are from 25 medical books separately. 263 prescriptions are found in 115 medical literatures, together with 354 medical notes from 55 medical books separately.
     Among 75 herbs collected in the preliminary search, 45 herbs are explicitly recorded for the treatment of stomachache. Based on the statistics of literature review, 19 herbs had been listed over six times and they are analyzed separately. The 19 drags are Caodoukou, Lizhihe, Guoluo, Dingxiang Oil(Dew), Baizhu, Baishaoyao, Gaoliangjiang, Wuzhuyu, Shigao, Jiu, Yanhusuo, Danggui, Chuangxiong, Baidoukou, Guiding(Rouguizi), Jianghuang, Huoxiang, Mahuang, Puhuang. Some herbs have been used to treat stomachache for a long time and were cited by many medical workers in different dynasties, like Caodoukou. Some herbs have been used for a long time and were cited considerably by previous literatures, but it was mainly used alone only with a few compatible application, like Lizhihe. Some drags were cited in many previous literatures, but they are out of use nowadays since western medicine which contains useful components of these drags have been widely used because of the administration convenience and low price, like Guoluo. Some drags only appeared once in the literature of Materia Medica, but they were used in many formulae in the literature related to formulae. So basically we can tell they are also effective in the treatment of stomachache, like Danggui and Chuanxiong.
     Through statistical analysis of herbs and formulae for stomachache, I find 261 dragshave been used in 263 formulae, with the total number of 2251 times. Each drag appeared 8.6245 times, so the closest interger 9 is being used as the criterion for the selection of key drags and 61 drags have been selected (which accounts for 23.37% of the total number of drags). These 61 drags appeared 1705 times, which amounts for 75.74% of the total number (2251). Chenpi appears with the highest frequency (108 times) and the next is Gancao (appeared 87 times), Muxiang (81 times), Xiangfu (71 times), Banxia(55 times), Houpu (53 times), Saren (52 times), Fulin(51 times), Yanhusuo(46 times) etc. Except for Gancao, most of these drags belong to one type of medicine with the function of regulating qi, resolving phlegm and dampness. The complete formula of Ercheng Tang (Decoction) is included, which explains why Ercheng Tang(Decoction)is frequently used for the treatment of stomachache from ancient to present.
     Effective formulae for stomachache are selected in three ways. First, search in Prescription Dictionary of Traditional Chinese Medicine for famous compound formulae from ancient to present. Second, search in medical record literature from ancient to present for cases of stomachache. Third, search through the up-to-date clinical reports appeared in periodicals.
     Based on the set criteria, 263 formulae were found, together with 73 formulae from the literature of medical record and 81 formulae (traditional formulae) from up-to-date clinical reports.
     After comparing formulae selected in the three ways, 25 prescriptions are chosen as key formulae as they appeared in more than one literature source mentioned above. These 25 key formulae have the following characteristics:①Minor prescriptions constitute the majority of these key formulae. Among the 25 formulae, 5 are made of only two kinds of Chinese Medicine and most of the rest are made of 4 to 5 minor formulae.②These 25 formulae belong to 10 functional categories, with 2.5 for each category. This indicates that this type of formula functions in many different ways and the clinical pattern of stomachache is widely spread.③The 10 functional categories can be divided into two kinds, tonifying and reducing. The tonifying method contains four ways: to tonify qi, tonify blood, nourish yin and warm yang. The reducing method contains six ways: to regulate qi, activate blood, resolve phlegm, resolve dampness, purge fire and dispel coldness. These methods possibly summarize the principles of treating epigastric pain and also these formulae could serve as the fundamental ones for the treatment of stomachache. Seven formulae - Erchen Decoction, Shixiao Powder, Jinlingzi Powder, Lizhong Decoction, Yueju Bolus, Pinwei Powder and Wu Zhuyu Decoction- are all referred in three kinds of literatures, which shows the great importance of them.
     Erchen Decoction, a basic formula for dissipating phlegm, has been modified and used by doctors of different times for treating stomachache which is caused by phlegm and dampness all the while. It works significantly well for patients with symptom of vomiting. Shixiao Powder (Powder for Dissipating Blood Stasis) was used for treating puerperal pain of lower abdomen in ancient times. Nvkeqieyao (Essentials in gynecology department) specifically indicates that Shixiao Powder can be used for the treatment of "Weiwantong"(stomachache). Meanwhile it is used in clinic for stomachache caused by qi stagnation and blood stasis. In Ming Dynasty, Jinlingzi Powder was first recorded in Xiuzhengfang (Formulae in pocket edition) for the treatment of chest pain, which is caused by pyretic syncope. In clinic Jinglingzi Powder is used to treat stomachache caused by stagnation of liver-qi transforming into fire. Lizhong Decoction (Decoction for Regulating Middle Energizer), recorded in Treatise on Febrile Diseases Caused by Cold (Shanghanlun), is a basic formula in regulating qi and eliminating cold, so it is effective in treating stomachache (deficiency cold of the spleen and stomach pattern). Yueju Pills was invented by Zhu Danxi to treat varies types of depression and it could be modified to treat stomachache. Pinwei Powder, which is from Taipinhuiminhejijufang (formulae edited officially in Ming dynasty), is used for stomachache caused by dampness. Wuzhuyu Decoction was first presented in Treatise on Febrile Diseases Caused by Cold (Shanghanlun) and proved its efficiency in treating stomachache of middle deficiency and cold congealing pattern.
     Conclusion and Discussion:
     1. 19 herbs are frequently used, and they are Caodoukou, Lizhihe, Guoluo, DingxiangOil(Dew), Baizhu,Baishaoyao, Gaoliangjiang, Wuzhuyu, Shigao, Jiu, Yanhusuo, Danggui, Chuangxiong, Baidoukou, Guiding(Rouguizi), Jianghuang, Huoxiang, Mahuang, Puhuang etc. These herbs serve as the effective medicine for treating stomachache. Combined with the formulae analysis, Gancao, Muxiang, Xiangfu, Banxia, Houpo, Sharen, Fulin, and Yanhusuo have been identified to be effective too. Seven formulae, including Erchen Decoction, Shixiao Powder, Jinlingzi Powder, Lizhong Decoction, Yueju Pills, Pinwei Powder, Wuzhuyu Decoction, are found to be effective compound formulae.
     2. The difference of herb-used-frequency proves the fact that some herbs can achieve therapeutic effect only through combination; while some other herbs can be used alone. These two kinds of herbs are worth noticing.
     3. Based on the function of effective herbs and formulae, most effective formulae have functions of regulating qi, quickening blood circulation, resolving phlegm and drying dampness, warming middle jiao while dispelling coldness. This findings go with the most commonly seen clinical patterns of stomachache, which are qi stagnation and blood stasis pattern, liver qi depression pattern, phlegm-dampness obstruction pattern and cold congealing due to yang deficiency pattern.
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