| The liver is the main detoxification organ in the body.The incidence of drug-induced acute liver injury has gradually increased in recent years,and there are fewer Chinese and Western medicines for the treatment of drug-induced liver injury.In this paper,the traditional Chinese medicine preparation-Yinhuang oral liquid for the treatment of drug-induced acute liver injury was screened by orthogonal methodsFirstly,orthogonal methods were used to optimize drug-induced acute liver injury model.Taking the dose,poisoning route,blood collection time,and sex of the anima 1 as the test conditions,the male mice were intraperitoneally injected with 800 mg/kg APAP by orthogonal methods.After 28 hours,blood test can be used to produce the best rat drug-induced liver injury modelOn the basis of the above,the Chinese Herbal Medicine Jiedu Jiedu Granules were screened by orthogonal methods.After 12 h,24 h and 36 h of modeling,rats in each group were given medication at 20 g/kg three times,and blood was collected 48 h later.With pharmacodynamics as the evaluation index,Yinhuang oral liquid with capillaris:Astragalus membranaceus(2:1)was obtainedExplore the best boiling conditions for Yinhuang Oral Liquid.Taking soaking time,decoction time,boiling frequency and ratio of liquid to liquid,four factors were selected for each factor to perform orthogonal test.The Yinhuang oral liquid was soaked for 1 hour and the ratio of liquid to liquid was 1:10.Boil for 3 times,2 h each time for the best boiling conditions.At the same time,establish the quality inspection standard of Yinhuang oral liquid.The qualitative identification of Artemisia capillaris and Astragalus membranaceus in Yinhuang oral liquid was carried out by TLC.Quantitative detection of Artemisia capillaris was carried out by HPLC.The results showed that the chromatograms of the two Chinese herbal medicines and the reference medicines and standard products of Chinese medicines the concept is not clear!]Spots of the same color appeared at the corresponding positions of the chromatogram.No interference was observed in the negative control.The method was feasible,and the specificity and repeatability were good.The content of chlorogenic acid in capillaris was determined using HPLC.Chromatographic conditions were:C18 column(250 mm X 4.6 mm,5 u m):mobile phase:acetonitrile 0.05%phosphoric acid(10:90);detection wavelength was 327 nm;flow rate was 1 mL/min;column temperature was 40 C.The linear range was examined:y=66212 x-380186,R2=0.9994.Linear range:0.25 u g to 8 u g.The precision RSD was 1.89%,the stability was 1.07%,the repeatability was 1.19%,the sample recovery rate was 100.39%,and the RSD was 3.09%,all meeting the quality inspection requirements.The pharmacodynamic study of Yinhuang oral liquid on the animal level,the detection of blood biochemistry and the pathological observation of the liver tissue section were studied.The results showed that Yinhuang oral liquid had a good therapeutic effect on DILI at doses of 20 g/kg and 15 g/kg.To study the safety pharmacology of Yinhuang oral liquid,MC4000 mouse noninvasive blood pressure monitor and EMKA small animal noninvasive pulmonary function instrument were used to Detect the Effects of Yinhuang oral liquid on the cardiovascular and respiratory systems in mice.Meanwhile,mice were subjected to a hypnosis test with threshold and subliminal doses of pentobarbital sodium.Mouse autonomous activity and functional exercise tests were carried out to examine the effects of drugs on the nervous system.The results showed that Yinhuang oral liquid had no adverse effects on mice in the cardiovascular respiratory and nervous systems.The toxicological activity of Yinhuang oral liquid,including acute toxicity and Long-term toxicity tests)showed that the LD50 of Yinhuang oral liquid was more than 5000mg/kg,which means practically nontoxic.In long-term toxicity test,compared with the control group,there was no significant difference in each of the following parametersweight gain,water and feed intake,hematology,blood biochemical indices).No tissue lesions were observed in the tissue sections.For Yanhuang oral liquid target animal clinical trials and target animal safety pharmacological studies,the body surface area of the chicken was measured and calculated.For Yanhuang Oral Liquid Target Animal Clinical Trials and Target Animal Safety Pharmacology Study.The body surface area of the chicken was measured and calculated.Cuted the chicken skin completely,placed it on a scanner,and measured the surface area of the chicken skin using Photoshop.Calculated chicken's K value in Meeh-Ruhuer's formula based on chicken body weight and body surface area.Conclusion:The K value of the chicken in Meeh-Rubner's formula is 9.24±1.03,and the transfer factor of mg/kg-mg/m2 is 10.00±1.36.The relative ratio of surface area per unit mass is 0.30 ± 0.044.Finally,an acute drug-induced hepatic injury model was established in chickens.Enrofloxacin was given at 200 mg/kg,150 mg/kg,and 100 mg/kg for 5 days.Blood was collected on the sixth day for serum biochemical detection,and hepatic histopathology was examined.The results showed that enrofloxacin can lead to stable and e-ffective chicken DILI model.In summary,this study screened the traditional Chinese medicine prescription for the treatment of DILI.Yinhuang oral liquid,which is safe and effective,with controllable quality,and potential clinical application. |
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