基于医案统计分析的六味地黄丸（汤）及其类方证治分类研究
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摘要
目的:六味地黄丸(汤),原名地黄丸(汤),出于宋·钱仲阳《小儿药证直决》,由汉·张仲景《金匮要略》所载“崔氏八味丸”化裁而来。作为补阴剂的代表方之一,因其立法巧妙、适用病症广泛,成为近代方药研究的重点,相关研究的数量之多、范围之广,实居诸补阴方剂之首。由于历史条件有限,以往的相关研究多侧重于相对简单的临床经验总结和方药药理实验研究。对于六味地黄丸(汤)类方主治范围的多样性,却有许多基本问题未正面回答,即六味地黄丸类方在诸多疑难杂症中的广泛应用和卓越疗效,究竟是依据中医怎样的治疗机制与发病机理;面对六味地黄丸立方后近千年的临床经验积累,如何从理论高度去认识、总结六味地黄丸及其类方方证的灵活辨治和应用范围;现行的研究方法是否能够满足和指导临床应用以开拓新的主治领域。本研究针对上述问题,开展了对六味地黄丸(汤)及其类方证治分类研究,对古今医家所积累的丰富临床经验,利用现代统计分析方法,从理论高度,根据辨证论治的要求,加以系统梳理与总结。
方法:依照中医研究必须将经典理论与临床实践紧密结合的原则,充分利用古今研究资料丰富和临床取效病例广泛的优势,以经典证治为起点,方证分类问题为线索,古今文献为依据,临床疗效为准绳,证治规律为主导,从六味地黄丸及其类方的相关医案角度切入,对六味地黄丸及其类方丰富的证治经验,从病位、证候表现、病因病机、组方配伍药物等方面进行频数、因子、聚类等统计分析。根据统计的大致趋势,结合传统中医理论,划定本类方剂的证治分类和主次关系,最后将临床证治分类结果与相关文献理论相互印证。在深入分析六味地黄丸及其类方的广泛应用基础上,对六味地黄丸及其类方繁杂多样的证治类型加以广泛沟通和系统归类。
结果:通过对所集629个医案证候表现、全部药物及加用药物的频数、聚类、因子等数理统计分析,将统计学原理与中医理论结合,得到
结果如下,
1.六味地黄丸(汤)及其类方方证可分为7个聚类组,分别为肝肾阴虚类;肾阴亏虚类;阳虚水泛类;气阴两虚,津液受伤类;肺肾阴虚类;心脾肾阳虚类;虚热内盛类。本类方证共提取11个公因子,结合中医理论合并为6个公因子组,按照其累计贡献率排序,依次为肾阴亏虚类、肝肾不和、肾阳气亏虚、肺肾不足、心肾不交、脾肾亏虚。
2.六味地黄丸(汤)及其类方用药的药性特点为寒性药、温性药和平性药最多(占累计频次的95.50%);热性药和凉性药较少(占累计频次的4.50%)。归经特点为五脏的累计频次最多(占累计频次的93.38%,其中肾出现频次最多,占累计频次的35.30%,肝次之,占累计频次的18.34%,心、脾再次之,分别占累计频次的15.12%和14.66%,肺较少,占累计频次的9.97%),同属六腑的膀胱、胃、胆最少(占全部累计频次的6.62%,其中膀胱相对最多,为4.18%)。
3.六味地黄丸(汤)及其类方加用药物治则可分为12个聚类组,分别为清热养阴,滋水涵木类;养阴清热,敛肺生津类;滋补肝肾,养阴明目类;补肾固精,收涩止遗类;补益肝肾,强筋健骨类;补助肾阳,填精益髓类;温阳化气,利水消肿类;补益元气类;理气行滞类;涩精止遗,镇惊安神类;养心安神类;交通心肾类。加用药物共提取11个公因子,结合中医理论合并为6个公因子组,按照其累计贡献率排序,依次为滋补肾阴,涩精止遗组、补益肝肾组、温补肾阳,利水通淋组、清心安神组、补益脾肾组、滋补肺肾组。
结论:通过对地黄丸及其类方的相关证治经验的综述和数理统计结果分析,得到如下结论。
1.地黄丸及其类方方证的病因为先天不足、后天失养、年高体虚、久病伤正、情志内伤、劳逸失度;
2.地黄丸类方方证的证治分类框架,包括辨证分类及辨证要点、论治分类及论治要点。
3.地黄丸及其类方适应症具有多元性、地黄丸“滋阴补肾”法有兼容性、肾气丸类方证在本研究中属六味地黄丸类方的组成部分、地黄丸类方应以六味地黄丸为核心;
4.地黄丸类方方剂选药的药性特点为多用寒、温、平,配用凉热,药味特点为重用甘味,淡,苦,酸涩咸并举,佐以辛味,地黄丸类方方证的病位规律为多见五脏,以肾为本,肝次之,兼有心脾,少有肺;少见六腑,偶有膀胱、胃,少有余腑。
Object: Liuwei Dihuang Pill, alternate name Dihuang Pill, comes from key to Therapeutics of Children’s Diseases whose author is Qian Yi in song dynasty, and it’s modification of prescription is from eight tastes pill from surname cui in synopsis of prescriptions of golden chamber in the Han Dynasty. And then, It becomes the focal point of the Study of Prescription and Herbs in contemporary times as one of the representative prescriptions for invigorating yin because of ingenious principles of treatment and extensive indications. Liuwei Dihuang Pill can be also known as the head of prescription for invigorating yin due to greatness of quantity and extent on relevant researches. Previous relevant researches emphasizes on simply clinical empirical summary and the study of pharmacological experiments owing to the limitation of historical conditions. As a result, lots of basic problems such as the diversified range of indications of Liuwei Dihuang Pill havn’t be given affirmative replication, for example, what are the therapeutic mechanism and pathogenesis of Liuwei Dihuang Pill and its associated prescriptions which have the wide applications and eminent effects on treating intractable diseases, and how to know Liuwei Dihuang Pill and its associated prescriptions from the standing of theory and control the flexible differentiation and extensive application of Liuwei Dihuang Pill, as to this, whether or not current theories can generalize the numerous and complicated clinical experiences, and alone can it be clinical and dialectical guides by opening up the new field of curing. Subject this to issue the above, launch to light root of Liuwei Dihuang Pill and add and subtract square manage system of law study, attempt to clear up and summarize systematically its abundant clinical experience that the many doctors accumulate at all times, from the standing of theory, according to the dialectical theory.
Method: Subject to the principle that combine classical theory with clinical practice, fully take advantage of the abundant researching documents and extensive clinical cases etc. At all time, regard treating in classical symptoms as the starting point, regard the classification of ZHENG-oriented as the clue, regard the ancient and modern documents as the basis, regard clinical effect as the criterion, regard diagnosis and treatment regularity as leading guidance, ancient and modern medical cases on applying Liuwei Dihuang Pill as the point of penetration, make frequency analysis, factor analysis and cluster analysis from location of diseases, clinical manifestations, etiology and pathogenesis and derivative medicines from abundant experiences on treating of Liuwei Dihuang Pill in ancient and modern times, then according to the trend roughly of statistics, delimit primary and secondary of type of differentiation, finally manage the mutual confirm of the practical clinical and documentary theory, on the basis of analyzing in depth the Liuwei Dihuang Pill and use extensive physiological mechanism, extensively communicate miscellaneous various types of differentiation and sort out systematically extensively to clinical experience in theory.
Results: We obtain the following results by mathematical statistics analysis of 629 clinical cases.
1.ZHENG-oriented of Liuwei Dihuang Pill and its associated prescriptions should be divided into 7 cluster groups: liver-kidney yin deficiency; kidney yin deficiency; edema due to yang deficiency; deficiency of both qi and yin, body fluid consumption; lung-kidney yin deficiency; heart-spleen -kidney yang deficiency; asthenia excess Heart in interior. The ZHENG-oriented could be extracted 11 common factors into 6 common factors according to accumulative contribution rate: kidney yin deficiency, incoordination between liver and kidney, kidney yang and qi deficiency, lung-kidney deficiency, disharmony of the heart and kidney, spleen-kidney deficiency.
2. The characteristics of herbal nature of Liuwei Dihuang Pill and its associated prescriptions are as follows: herb of cold property, warm property and constant property accounted for a very large proportion ( 95.50% ); herb of hot property and cool property accounted for a small proportion (4.50%). The characteristics of herbal channel tropism are as follows: five viscera accounted for a very large proportion(totally 93.38%, Kidney-35.30%;Liver-18.34%; Heart-15.12%; Spleen-14.66%, Lung-9.97%); six hollow viscera accounted for a small proportion(totally6.62%, bladder-4.18% which is the biggest proportion of six hollow viscera).
3. The principles of treatment of Liuwei Dihuang Pill and its associated prescriptions should be divided into 12 cluster groups: clearing away heat and nourishing yin, nourishing kidney and liver; nourishing yin and generating body fluid, astringing lung and checking diarrhea; nourishing liver and kidney, nourishing yin and improving eyesight; reinforcing kidney to strengthen essence and arresting discharge; nourishing liver and kidney and strengthening the tendons and bones; nourishing kidney yang and filling essence; warming yang to fluidizing qi and induce diuresis to alleviate edema; nourishing primordial qi; regulating qi and stagnation of qi; arresting seminal emission, tranquilizing and relieving uneasiness; hyperactivity nourishing heart to calm mind; coordinating heart-kidney. The derivative herb could be extracted 6 common factors according to accumulative contribution rate: nourishing kidney yin and arresting seminal emission; nourishing liver and kidney; nourishing kidney yang and relieving stranguria by diuresis; relieving heart and relieving uneasiness; nourishing spleen and kidney; nourishing lung and kidney.
Conclusion: Through the summary and mathematical statistics analysis, we obtain the following conclusions.
1. The etiological factors of ZHENG-oriented on Dihuang Pill and its associated prescriptions are as follows: congenital deficiencies, acquired missing nourish, oldness to deficiency, chronic disease to deficiency, emotion transfer to damage, overload and exertion.
2. The frame of syndrome differentiation and treatment of Dihuang Pill and its associated prescriptions includes the differentiation for syndrome classification, differentiation for treatment classification and critical medication usage.
3.The characteristics of indications have great variety; and the method of nourishing the kidney-yin has good-compatibility; Kidney-Qi Pill and its associated prescriptions are parts of Liuwei Dihuang Pill and its associated prescriptions; Dihuang Pill is the central status among Liuwei Dihuang Pill and its associated prescriptions.
4.The characteristic of herbal nature of Dihuang Pill and its associated prescriptions mainly includes multiple herb of cold property, warm property and constant property with herb of hot property and cool property. And the characteristic of taste of herb is as follows:excessive sweetish taste in combination with mild, bitter, sour,harsh,saline taste and pungent herbs;The regularity of locations: five viscera is common, kidney is as oriented followed by liver, both heart and spleen are included with lung as well as rare six hollow organs, frequent bladder and stomach.
方法:依照中医研究必须将经典理论与临床实践紧密结合的原则,充分利用古今研究资料丰富和临床取效病例广泛的优势,以经典证治为起点,方证分类问题为线索,古今文献为依据,临床疗效为准绳,证治规律为主导,从六味地黄丸及其类方的相关医案角度切入,对六味地黄丸及其类方丰富的证治经验,从病位、证候表现、病因病机、组方配伍药物等方面进行频数、因子、聚类等统计分析。根据统计的大致趋势,结合传统中医理论,划定本类方剂的证治分类和主次关系,最后将临床证治分类结果与相关文献理论相互印证。在深入分析六味地黄丸及其类方的广泛应用基础上,对六味地黄丸及其类方繁杂多样的证治类型加以广泛沟通和系统归类。
结果:通过对所集629个医案证候表现、全部药物及加用药物的频数、聚类、因子等数理统计分析,将统计学原理与中医理论结合,得到
结果如下,
1.六味地黄丸(汤)及其类方方证可分为7个聚类组,分别为肝肾阴虚类;肾阴亏虚类;阳虚水泛类;气阴两虚,津液受伤类;肺肾阴虚类;心脾肾阳虚类;虚热内盛类。本类方证共提取11个公因子,结合中医理论合并为6个公因子组,按照其累计贡献率排序,依次为肾阴亏虚类、肝肾不和、肾阳气亏虚、肺肾不足、心肾不交、脾肾亏虚。
2.六味地黄丸(汤)及其类方用药的药性特点为寒性药、温性药和平性药最多(占累计频次的95.50%);热性药和凉性药较少(占累计频次的4.50%)。归经特点为五脏的累计频次最多(占累计频次的93.38%,其中肾出现频次最多,占累计频次的35.30%,肝次之,占累计频次的18.34%,心、脾再次之,分别占累计频次的15.12%和14.66%,肺较少,占累计频次的9.97%),同属六腑的膀胱、胃、胆最少(占全部累计频次的6.62%,其中膀胱相对最多,为4.18%)。
3.六味地黄丸(汤)及其类方加用药物治则可分为12个聚类组,分别为清热养阴,滋水涵木类;养阴清热,敛肺生津类;滋补肝肾,养阴明目类;补肾固精,收涩止遗类;补益肝肾,强筋健骨类;补助肾阳,填精益髓类;温阳化气,利水消肿类;补益元气类;理气行滞类;涩精止遗,镇惊安神类;养心安神类;交通心肾类。加用药物共提取11个公因子,结合中医理论合并为6个公因子组,按照其累计贡献率排序,依次为滋补肾阴,涩精止遗组、补益肝肾组、温补肾阳,利水通淋组、清心安神组、补益脾肾组、滋补肺肾组。
结论:通过对地黄丸及其类方的相关证治经验的综述和数理统计结果分析,得到如下结论。
1.地黄丸及其类方方证的病因为先天不足、后天失养、年高体虚、久病伤正、情志内伤、劳逸失度;
2.地黄丸类方方证的证治分类框架,包括辨证分类及辨证要点、论治分类及论治要点。
3.地黄丸及其类方适应症具有多元性、地黄丸“滋阴补肾”法有兼容性、肾气丸类方证在本研究中属六味地黄丸类方的组成部分、地黄丸类方应以六味地黄丸为核心;
4.地黄丸类方方剂选药的药性特点为多用寒、温、平,配用凉热,药味特点为重用甘味,淡,苦,酸涩咸并举,佐以辛味,地黄丸类方方证的病位规律为多见五脏,以肾为本,肝次之,兼有心脾,少有肺;少见六腑,偶有膀胱、胃,少有余腑。
Object: Liuwei Dihuang Pill, alternate name Dihuang Pill, comes from key to Therapeutics of Children’s Diseases whose author is Qian Yi in song dynasty, and it’s modification of prescription is from eight tastes pill from surname cui in synopsis of prescriptions of golden chamber in the Han Dynasty. And then, It becomes the focal point of the Study of Prescription and Herbs in contemporary times as one of the representative prescriptions for invigorating yin because of ingenious principles of treatment and extensive indications. Liuwei Dihuang Pill can be also known as the head of prescription for invigorating yin due to greatness of quantity and extent on relevant researches. Previous relevant researches emphasizes on simply clinical empirical summary and the study of pharmacological experiments owing to the limitation of historical conditions. As a result, lots of basic problems such as the diversified range of indications of Liuwei Dihuang Pill havn’t be given affirmative replication, for example, what are the therapeutic mechanism and pathogenesis of Liuwei Dihuang Pill and its associated prescriptions which have the wide applications and eminent effects on treating intractable diseases, and how to know Liuwei Dihuang Pill and its associated prescriptions from the standing of theory and control the flexible differentiation and extensive application of Liuwei Dihuang Pill, as to this, whether or not current theories can generalize the numerous and complicated clinical experiences, and alone can it be clinical and dialectical guides by opening up the new field of curing. Subject this to issue the above, launch to light root of Liuwei Dihuang Pill and add and subtract square manage system of law study, attempt to clear up and summarize systematically its abundant clinical experience that the many doctors accumulate at all times, from the standing of theory, according to the dialectical theory.
Method: Subject to the principle that combine classical theory with clinical practice, fully take advantage of the abundant researching documents and extensive clinical cases etc. At all time, regard treating in classical symptoms as the starting point, regard the classification of ZHENG-oriented as the clue, regard the ancient and modern documents as the basis, regard clinical effect as the criterion, regard diagnosis and treatment regularity as leading guidance, ancient and modern medical cases on applying Liuwei Dihuang Pill as the point of penetration, make frequency analysis, factor analysis and cluster analysis from location of diseases, clinical manifestations, etiology and pathogenesis and derivative medicines from abundant experiences on treating of Liuwei Dihuang Pill in ancient and modern times, then according to the trend roughly of statistics, delimit primary and secondary of type of differentiation, finally manage the mutual confirm of the practical clinical and documentary theory, on the basis of analyzing in depth the Liuwei Dihuang Pill and use extensive physiological mechanism, extensively communicate miscellaneous various types of differentiation and sort out systematically extensively to clinical experience in theory.
Results: We obtain the following results by mathematical statistics analysis of 629 clinical cases.
1.ZHENG-oriented of Liuwei Dihuang Pill and its associated prescriptions should be divided into 7 cluster groups: liver-kidney yin deficiency; kidney yin deficiency; edema due to yang deficiency; deficiency of both qi and yin, body fluid consumption; lung-kidney yin deficiency; heart-spleen -kidney yang deficiency; asthenia excess Heart in interior. The ZHENG-oriented could be extracted 11 common factors into 6 common factors according to accumulative contribution rate: kidney yin deficiency, incoordination between liver and kidney, kidney yang and qi deficiency, lung-kidney deficiency, disharmony of the heart and kidney, spleen-kidney deficiency.
2. The characteristics of herbal nature of Liuwei Dihuang Pill and its associated prescriptions are as follows: herb of cold property, warm property and constant property accounted for a very large proportion ( 95.50% ); herb of hot property and cool property accounted for a small proportion (4.50%). The characteristics of herbal channel tropism are as follows: five viscera accounted for a very large proportion(totally 93.38%, Kidney-35.30%;Liver-18.34%; Heart-15.12%; Spleen-14.66%, Lung-9.97%); six hollow viscera accounted for a small proportion(totally6.62%, bladder-4.18% which is the biggest proportion of six hollow viscera).
3. The principles of treatment of Liuwei Dihuang Pill and its associated prescriptions should be divided into 12 cluster groups: clearing away heat and nourishing yin, nourishing kidney and liver; nourishing yin and generating body fluid, astringing lung and checking diarrhea; nourishing liver and kidney, nourishing yin and improving eyesight; reinforcing kidney to strengthen essence and arresting discharge; nourishing liver and kidney and strengthening the tendons and bones; nourishing kidney yang and filling essence; warming yang to fluidizing qi and induce diuresis to alleviate edema; nourishing primordial qi; regulating qi and stagnation of qi; arresting seminal emission, tranquilizing and relieving uneasiness; hyperactivity nourishing heart to calm mind; coordinating heart-kidney. The derivative herb could be extracted 6 common factors according to accumulative contribution rate: nourishing kidney yin and arresting seminal emission; nourishing liver and kidney; nourishing kidney yang and relieving stranguria by diuresis; relieving heart and relieving uneasiness; nourishing spleen and kidney; nourishing lung and kidney.
Conclusion: Through the summary and mathematical statistics analysis, we obtain the following conclusions.
1. The etiological factors of ZHENG-oriented on Dihuang Pill and its associated prescriptions are as follows: congenital deficiencies, acquired missing nourish, oldness to deficiency, chronic disease to deficiency, emotion transfer to damage, overload and exertion.
2. The frame of syndrome differentiation and treatment of Dihuang Pill and its associated prescriptions includes the differentiation for syndrome classification, differentiation for treatment classification and critical medication usage.
3.The characteristics of indications have great variety; and the method of nourishing the kidney-yin has good-compatibility; Kidney-Qi Pill and its associated prescriptions are parts of Liuwei Dihuang Pill and its associated prescriptions; Dihuang Pill is the central status among Liuwei Dihuang Pill and its associated prescriptions.
4.The characteristic of herbal nature of Dihuang Pill and its associated prescriptions mainly includes multiple herb of cold property, warm property and constant property with herb of hot property and cool property. And the characteristic of taste of herb is as follows:excessive sweetish taste in combination with mild, bitter, sour,harsh,saline taste and pungent herbs;The regularity of locations: five viscera is common, kidney is as oriented followed by liver, both heart and spleen are included with lung as well as rare six hollow organs, frequent bladder and stomach.
引文
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