Study On The Feasibility Of The Compatibility Of Kudiezi Injection And Common Clinical Drugs

In recent years,the incidence rate of coronary heart disease and other myocardial ischemia diseases has increased year by year,which seriously threatens people's health.As a kind of traditional chinese medicine injection for promoting blood circulation and removing blood stasis,kudiezi injection was extracted and refined from Ixeris sonchifolia Hance,a compositae plant.It has been widely used in the prevention and treatment of myocardial ischemia,coronary heart disease,stroke,cerebral infarction and other diseases.In clinical use,kudiezi injection is often combined with different solvents and other drugs,but there are still two key problems in clinical compatibility.First,whether drug compatibility is feasible,whether there are incompatibilities between different drugs,whether it will cause adverse reactions.Second,whether drug compatibility will affect the stability of drugs and lead to the reduction of clinical efficacy.In view of the current key problems,this study carried out the feasibility study on the compatibility of kudiezi injection with commonly used clinical drugs from the perspective of chemical stability of drug compatibility in vitro and the efficacy of drug compatibility in vivo,in order to provide a reference for the safe and reasonable combination of drugs in clinical.The specific experimental contents and conclusions are as follows:(1)Study on the chemical stability of kudiezi injection compatible with common drugsBased on the guiding principle of drug stability test and the simulation of the commonly used clinical drug concentration of kudiezi injection,using 0.9% sodium chloride injection and 5% glucose injection as the solvent,the appearance,p H value,insoluble particles of kudiezi injection and two commonly used drugs(cefotiam hydrochloride for injection and ligustrazine hydrochloride injection)in the environment of 4 ?,room temperature and 30 ?were investigated change of absorbance and content of effective components.The results showed that after kudiezi injection was combined with the above two solvents and drugs,there was no turbidity in the solution,p H value,absorbance and content of effective components did not change significantly in the solution within 8 hours,and insoluble particles had obvious changes and exceeded the scope of pharmacopoeia.According to the results of various studies,when kudiezi injection was used in combination with cefotiam hydrochloride and ligustrazinehydrochloride injection in clinic,it was necessary to select the solvent and use it as soon as possible.It was found that the compatibility of kudiezi injection with 0.9% sodium chloride injection and ligustrazine hydrochloride injection was relatively stable,and the follow-up study could be carried out in vivo.(2)Study on the mechanism of kudiezi injection combined with ligustrazine hydrochloride to prevent myocardial ischemia based on metabonomicsIn this experiment,isoproterenol(ISO)was used to establish the myocardial ischemia model of rats and drugs were given.Through the comparison of biochemical indexes and pathological sections of the heart,it was found that the protective effect of kudiezi injection combined with ligustrazine hydrochloride on myocardial ischemia was more prominent.In addition,UPLC-Q-TOF/MS technology was used for non targeted metabonomics analysis.17 cardiac tissue markers and 16 plasma markers were screened through multivariate statistical analysis,which mainly regulate sphingolipid metabolism,glycerophosphingolipid metabolism,tryptophan metabolism,glutathione metabolism,linolenic acid metabolism,steroids biosynthesis and other pathways.The results of this study showed that kudiezi injection combined with ligustrazine hydrochloride can callback more metabolites,and the change multiple of metabolite level was large,which indicated that kudiezi injection combined with ligustrazine hydrochloride has obvious callback degree and outstanding effect on metabolites.This study reflected that the compatibility of kudiezi injection and ligustrazine hydrochloride could significantly enhance the protective effect on myocardial ischemia,and provided experimental basis for further exploring the protective mechanism of kudiezi injection on myocardial ischemia.(3)Study on the mechanism of kudiezi injection combined with ligustrazine hydrochloride to prevent myocardial ischemia based on network pharmacologyBased on the above research,the network pharmacology technology in this study was used to analyze the protective mechanism of kudiezi injection before and after compatibility with ligustrazine hydrochloride.The potential targets were predicted by the effective components and recalled myocardial ischemia metabolites,and the “component target disease” regulatory network was further integrated.The mechanism of “multi-component,multi-target and multi-path” was discussed by analyzing the related pathways of potentialtargets.In this study,110 target proteins which can regulate myocardial ischemia metabolism disorder were screened out.The drug compatibility can not only affect the common target FAAH and DRD2 of kudiezi injection and ligustrazine hydrochloride.At the same time,it can also act on the target proteins of kudiezi injection and ligustrazine hydrochloride,such as ACE,KCNK2,CCR1,etc.It was found that the combination of kudiezi injection and ligustrazine hydrochloride can act on more targets and pathways,such as calcium signaling pathway,neuroactive ligand receptor interaction pathway,cyclic adenosine monophosphate signaling pathway,etc.Its active components may improve myocardial ischemia by acting on key factors in the above signaling pathway.This study confirmed that kudiezi injection combined with ligustrazine hydrochloride can play a common role in the prevention of myocardial ischemia,can synergistically affect the level of metabolites,and had a more prominent protective effect on myocardial ischemia.