The Methodological Research On Coupling Effect And Compatibility Law Of Prescription

The compound prescription is the main means for Chinese medicine treating diseases and main form of clinical medication of CM.More than two drugs of multi-drug being in combination with,according to a certain compatibility law is the essence of Prescription.The whole efficiency of Prescription comes into being by the interaction between drugs.Without this interaction,the whole efficiency neither is being formatted,nor explained.The characteristics of Prescription is using of multi-drug medication.Among the Prescription,the lesser has four or five elements,and the more have ten or twenty elements. So it is so big difficulties in experimental design on Prescription firstly.Secondly,the Prescription often involving with multi-objective comprehensive evaluation because of the multi-effect of Prescription.The paper constructed an evaluation pattern of Prescription whole efficacy suiting for the Prescription characteristics of multi-drug,multi-effect and multiple-objective evaluating,based on Uniform design combined with multi-objective optimization algorithm.The paper analyzes and confirms the hypothesis of "coupling up in Prescription" from the pharmacological point,and develops the evaluation software of coupling effect-whole efficacy in Prescription,based on windows operation system of program operation interface.The evaluation pattern can provide a new idea and method for research of Prescription,which is beneficial to deeply understand the action mechanism of Prescription.The coupling up in Prescription indicates that the drugs can interact,interplay and integrate into a whole efficacy,which is different from the effect of single medicine.The coupling effect due to the drug compatibility have three kinds of results or phenomenon, including synergistic effect,additive effect and antagonistic effect.(一)the types of coupling up in Prescription1 Seven different combination in drug1.1 Going aloneTwo drugs of combination action have no synergistic effect and antagonistic effect, named as additive effect(1+1=2).The going alone has similar properties to additive effect. In addition,additive effect has a special case of irrelevant effect,namely the principal drugs do not need to use combination therapy,being similar to the panax ginseng decoction in Prescription(1+0=1).1.2 Mutual reinforcementThe effect of mutual reinforcement embody synergistic effect(1+1＞2).The drugs of mutual reinforcement have a similar action mechanism and action direction and additive effect among efficacy.1.3 Mutual assistanceThe effect of mutual assistance embody synergistic effect also,(1+1＞2).1.4 Mutual restraint,Mutual detoxicationThe effect of mutual restraint and mutual detoxication embody that a drug can inhibit another drug's effect,which have an antagonistic effect,1+1＜2.1.5 Mutual inhibitionThe mutual inhibition is similar to mutual restraint and mutual detoxication,and embody that a drug can inhibit another drug's effect,which have a antagonistic effect of comprehensive effect,1+1＜2.1.6 Adverse of Chinese MedicineThe Adverse of Chinese Medicine reflect that drug combination is synergistic or additive effect,which the comprehensive therapeutic effect is "1+1＞2".Nothing but its coupling effect is not the therapeutic effects.2 Principal,Assistant,Complement,GuideThe theory of "Principal,Assistant,Complement,Guide" described the compatibility relationships among drugs,according to the master-slave position and real division of elements in Prescription.The coupling up in Prescription determinate the principle drug according to the importance of drug to the Prescription,and accordingly divide into synergistic drug, additive drug and antagonistic drug.Concretely speaking,it can summarize for five compatibility relationships(1)enlarge effect.(2)Synergism;(3)decreasing effect;(4) increase toxicity;(5)attenuated toxicity.The coupling effect in Prescription isn't constant,which change with dosage, diseases and dosage ratio.The research on the action and compatibility rule aims to explicit the influence factor.(二)To establish the evaluation software of coupling effect-whole efficacy in Prescription1 Uniform design to arrange the experiment combination1.1 Define the test purpose,choose the Prescription,determine the expectant experimental model,and determine the test indexes.1.2 Choose the factor.1.3 Determine the drug level.1.4 Choose uniform designs table,Arrangement the factor and level.1.5 To arrange the test according to the experimental project.2 Mathematical modeling2.1 The experimental data are fitted with and acquire the multiple regression equation by least square method.2.2 To analyze on coupling effect in Prescription according to the regression equationBased on the magnitude of regression coefficient of factor,it can see obviously X's influence value on Y,thus qualitatively discriminate the position and role in Prescription, and properly define the "principal,assistant,complement,and guide".①When the regression coefficient is positive value;there is a positive correlation between factors,the greater the value is,the more the more powerful effect of the factor;②When the regression coefficient is zero,there is not an influence on the test;③When the regression coefficient is negative value,there is a negative correlation between factors.As toβ_ijx_ix_j,it show that the interaction exist in x_i and x_j.Ifβ_ij＞0,the interaction existing in x_i and x_j is positive.Ifβ_ij＜0,the interaction existing in x_i and x_j is negative,ifβ_ij= 0,the interaction existing in x_i and x_j is additive action.3 Single objective optimizationTo calculate the optimum conditions according to regression analysis.4 The comprehensive evaluate on whole efficacy of PrescriptionThe paper evaluates the whole efficacy using the grid trial method.The aim is to acquire the optimum combination,meeting with the multi-objection optimal values. (三)Applications examples1,Software introductionThe software adopted the VC ++ and carried out the establishment of the evaluating patter n of whole efficacy of Prescription control system software which is based on the coupling effect of the P.the soft include a series of analysis method above-mentioned。It can run on the Chinese operation system based on Win95,Win NT or on this kind of the English operation system with plug-in Chinese work station.2,The application example of software(1)Prescription or Herbs Proportioning TestBy citing the article "Application of uniform-design method used to select best proportion of ingredients in Danxintong",the paper analyze the experimental data with the software and acquire the optimal proportion of ingredients in DXT,based on comprehensive thinking over two efficacy indexes.(2)The paper deals with the experimental data from Xiaochengqi Decoction and acquires the compatibility law of Xiaochengqi Decoction by the software.(四)Research on coupling effect and compatibility law of Yinqiao-SanYinqiao-san has ten kinds of elements.We analyze the coupling effect in Yinqiao-San and comprehensive evaluate the whole efficacy of antiviral and anti-inflammatory effect,by aid of the software and the evaluation platform,the models of influenza infected mice and mice ears edema model by dimethylbenzene.Via computer simulating optimization,the optimal proportion of ingredients in Yinqiao-San is acquired.(五)Innovation of the researchThe hypothesis of coupling effect in Prescription illustrate the interaction of Prescription by science and technology,which help to thoroughly understand the action mechanism and compatibility law,and bridge the gap between elucidating the compatibility law and science by experiment.The evaluating pattern,based on uniform design,system modeling and multi-objective optimization,produce an approach to the research of TCM and the exploration on the Prescription composition rules.The evaluating method can more embody the whole view of the system theory.