Research On Dosage And Related Rules Of Heat-clearing Drugs Applied By Masters Of Traditional Chinese Medicine Based On Data Mining Technology

Objective:To explore the dosage and related rules of heat-clearing drugs applied by masters of traditional Chinese medicine（TCM）based on data mining technology so as to provide theoretical basis for application of heat-clearing drugs in safe,effective and rational ways,and to provide objective basis for amendment and perfection of medication dosing of heat-clearing drugs in new edition of Chinese Pharmacopoeia.Methods:The medical cases and medical notes published by masters of TCM were collected,and the data of prescriptions were selected by reasonable inclusion criteria and exclusion criteria.Afterwards,these data of prescriptions were performed standardized processing via data cleansing technology to construct "Database for Prescription of Masters of TCM"（DB-MTCM）.The prescriptions containing heat-clearing drugs from the database were extracted as data set by searching names of drugs.Based on SPSS23.0 software and Auxiliary Platform System Software for Traditional Chinese Medicinal Inheritance（Version 2.50）,the dosage rules of commonly used heat-clearing drugs,and indications and compatibility rules of representative drugs such as Zhimu,Huanglian,Jinyinhua,Shengdihuang and Digupi,were analyzed in multiple perspectives and multi-level analysis and using data mining method.Results:1.There were 31 commonly used heat-clearing drugs in the DB-MTCM,including Shigao,Zhimu,Lugen,Tianhuafen,Zhizi,Xiakucao,Juemingzi,Huangqin,Huanglian,Huangbai,Longdan,Jinyinhua,Lianqiao,Banlangen,Pugongying,Chonglou,Loulu,Tufuling,Yuxingcao,Shegan,Banzhilian,Baihuasheshecao,Shengdihuang,Xuanshen,Mudanpi,Chishao,Zicao,Shuiniujiao,Qinghao,Baiwei,Diguping,etc.,and their dosage all exceed the maximum recorded in the Chinese Pharmacopoeia.Among these prescriptions,the prescriptions with Chonglou and Loulu over the maximum of regulated dosage in Chinese Pharmacopoeia accounted for 97.14% and 94.44%,respectively.2.There were 526 kinds of diseases in total treated by frequently used heat-clearing drugs,among which cough,pain in stomach collaterals and vertigo induced by the wind ranked the top three.The frequently used heat-clearing drugs for treating cough included Huangqin,Yuxingcao,Jinyinhua,Lianqiao,Zhimu,etc.,Huanglian,Huangqin,Pugongying,Baihuasheshecao,and Chishao etc.,for treating pain in stomach collaterals,and Shengdihuang,Chishao,Huangqin,Xiakucao,and Juemingzi,etc.,for vertigo induced by the wind.3.Zhimu was frequently used in treating commonly occurring diseases including cough,insomnia,Bi syndrome induced by wind-dampness,and was usually compatible with heat-clearing and tonifying drugs.The therapeutic window in treating insomnia ranged from 6g to 30 g,and the core drug pairs and their most commonly used dosage ratios were Zhimu-Beishashen（a ratio of 1 to 1）,Zhimu-Maidong（a ratio of 5 to 6 or 1 to 1）,Zhimu-Huangqin（a ratio of 1 to 1）,Zhimu-Sangbaipi（a ratio of 1 to 1）.The therapeutic window in treating cough ranged from 6g to 15 g,and the core drug pairs and their most commonly used dosage ratios were Zhimu-Suanzaoren（a ratio of 1 to 3）,Zhimu-Chuanxiong（a ratio of 1 to 1）,Zhimu-Huanglian（a ratio of 5 to 3）.The therapeutic window in treating Bi syndrome induced by wind-dampness ranged from 6g to 20 g,and the core drug pairs and their most commonly used dosage ratios were Zhimu-Guizhi（a ratio of 2 to 1）,Zhimu-Gancao（a ratio of2 to 1）.4.Huanglian was frequently used in treating commonly occurring diseases including stomachache,insomnia,diarrhoea,and was usually compatible with heat-clearing and tonifying drugs.The therapeutic window in treating stomachache ranged from 1.5g to 15 g,and the core drug pairs and their most commonly used dosage ratios were Huanglian-Xiangfu（a ratio of 3to 10）,Huanglian-Wuzhuyu（a ratio of 2 to 1）,Huanglian-Gancao（a ratio of 1to 1）,Huanglian-Chenpi（a ratio of 3 to 10）.The therapeutic window in treating insomnia ranged from 1.6g to 15 g,and the core drug pairs and their most commonly used dosage ratios were Huanglian-Shengdihuang（a ratio of2 to 5）,Huanglian-Suanzaoren（a ratio of 1 to 3 or 1 to 2）,Huanglian-Banxia（a ratio of 1 to 2）,Huanglian-Baishao（a ratio of 3 to 5）,Huanglian-Fuling（a ratio of 2 to 3）.The therapeutic window in treating diarrhoea ranged from 2g to 15 g,and the core drug pairs and their most commonly used dosage ratios were Huanglian-Fuling（a ratio of 1 to 1）,Huanglian-Chenpi（a ratio of 1 to 1）,Huanglian-Muxiang（a ratio of 1 to 1）.5.Jinyinhua was frequently used in treating commonly occurring diseases including cough,pharyngeal tumefaction,seasonal disease,and was usually compatible with heat-clearing and tonifying drugs.The therapeutic window in treating cough ranged from 3g to 30 g,and the core drug pairs and their most commonly used dosage ratios were Jinyinhua-Lianqiao（a ratio of 1to 1）,Jinyinhua-Gancao（a ratio of 2 to 1）,Jinyinhua-Huangqin（a ratio of 1 to1）,Jinyinhua-Jiegeng（a ratio of 5 to 3）.The therapeutic window in treating pharyngeal tumefaction ranged from 10 g to 15 g,and the core drug pairs and their most commonly used dosage ratios were Jinyinhua-Gancao（a ratio of 10 to 3）,Jinyinhua-Lianqiao（a ratio of 1 to 1）.The therapeutic window in treating seasonal disease ranged from 9g to 30 g,and the core drug pairs and their most commonly used dosage ratios were Jinyinhua-Lianqiao（a ratio of 1 to 1）,Jinyinhua-Gancao（a ratio of 3 to 1）,Jinyinhua-Huangqin（a ratio of 5 to 3）.6.Shengdihuang was frequently used in treating commonly occurring diseases including severe palpilation,insomnia,apoplexy,and was usually compatible with heat-clearing and tonifying drugs.The therapeutic window in treating severe palpilation ranged from 6g to 80 g,and the core drug pairs and their most commonly used dosage ratios were Shengdihuang-Maidong（a ratio of 1 to 1）,Shengdihuang-Danshen（a ratio of 1 to 1）,Shengdihuang-Wuweizi（a ratio of 5 to 2）,Shengdihuang-Zhigancao（a ratio of 5 to 2）.The therapeutic window in treating insomnia ranged from 9g to 50 g,and the core drug pairs and their most commonly used dosage ratios were Shengdihuang-Danggui（a ratio of 1 to 1）,Shengdihuang-Suanzaoren（a ratio of 1 to 1）.The therapeutic window in treating apoplexy ranged from 6g to 30 g,and the core drug pairs and their most commonly used dosage ratios were Shengdihuang-Chishao（a ratio of 1 to 1 or 5 to 3）,Shengdihuang-Dilong（a ratio of 3 to 2）,Shengdihuang-Jiangcan（a ratio of 3 to 2）.7.Digupi was frequently used in treating commonly occurring diseases including consumptive thirst,and was usually compatible with heat-clearing and tonifying drugs.The therapeutic window in treating consumptive thirst ranged from 15 g to 30 g,and the core drug pairs and their most commonly used dosage ratios were Digupi-Mudanpi（a ratio of 4 to 3 or 2 to 1）,Digupi-Gouqizi（a ratio of 1 to 1）,Digupi-Shengdihuang（a ratio of 4 to 3）.Conclusion:1.Masters of TCM pay great attention to the medication dosing rules.Application of heat-clearing drugs has the characteristics of wide dose threshold and flexible dosage.They apply usual dosage and adjust them in treating diseases,and rarely use the dosage under minimum of Chinese Pharmacopoeia in the prescriptions.However,the dosage above the maximum of Chinese Pharmacopoeia in prescriptions frequently occurs.TCM masters greatly challenge the authority of Chinese Pharmacopoeia in dosage application of heat-clearing drugs.2.TCM masters usually combine heat-clearing drugs with heat-clearing and tonifying drugs,which reflect the laws of mutual reinforcement,synergetic effects,spleen and stomach protection,and consistence from the beginning to the end in combination of medicines.Zhimu,Huanglian,Jinyinhua,Shengdihuang and Digupi have differed therapeutic windows in treating different diseases.Thus,different therapeutic windows of drugs cause difference in efficacy,which implies a more complex dose-effect relationship.The above five drugs are capable of treating diseases in a wide range,and they should be in accordance with differed compatibility laws and dose ratios in treating diseases.3.The characteristics of TCM masters in application of heat-clearing drugs can be summarized as follows: being skillfully in syndrome differentiation,pulse classification of deficiency and excess,clearing away the heat when required;precise observation of the nature of the drugs,differentiation of strong or weak constitutions,moderate usage of cold-or cool-nature drugs;mastering pharmacology,each medicine treating in main diseases or having varied actions,usage of specialized drugs in treating special diseases.The formation of difficult and complicated diseases is not usually caused by a single factor,but by a set of factors.TCM theory holds that“strange diseases are usually caused by sputum,and patients with refractory or chronic diseases are prone to mingle with sputum and blood stasis”“those with chronic diseases usually present deficiency syndrome and blood stasis,and long-term pain invades into collaterals,thereby involving in the kidney”“ physicians of TCM should follow the principle of treatment from the bottom for those with inconsistency of illness in upper and lower body,and follow the principle of internal treatment for those with inconsistency of interior and exterior illness”,and “long-term disease without efficacy should be treated from middle energizer ”.The masters of TCM consider that treatment of difficult and complicated illness should comply with the above TCM concepts.When long-course treatment is not effective,it is necessary to dissipate phlegm,remove blood stasis,eliminate Bi syndrome,dredge collaterals,extinguish the wind and relieve convulsion,and insect drugs can be added to enhance the therapeutic effect at this phase.The treatment principles and laws summarized by them from clinical practice are of important values in theory and clinical application.Therefore,it is worthy of further research and study.