Clinical Efficacy And Safety Of Shenwu Yishen Tablets In Prevention And Treatment Of Chronic Kidney Disease(Stage 2?5)after Approved Marketing

Objective:To systematize the important literature on chronic renal failure in ancient and modern times,and summarize the new theory,new treatment and new prescription of chronic renal failure based on syndrome differentiation by Professor Wang Gang.To explore the connotation of "tonifying nephrology" as the core idea of Zou's nephrology and the systematic research results.Based on a large sample study,the efficacy of Shenwu Yishen Tablets,a newly approved new drug,in the treatment of chronic renal failure patients with different etiology and stages(CKD2?5)was studied,and the effect of Shenwu Yishen Tablets in improving clinical syndrome and protecting renal function as well as drug safety were observed.The optimal conditions for clinical use of Shenwu Yishen Tablets were proposed.The pharmacological mechanism of active components in Shenwu Yishen Tablet was futher analyzed from the perspective of network pharmacology.Methods:1.Using the method of literature research,we analyzed and sorted out the important traditional Chinese medicine literature related to chronic renal failure in ancient and modern times,and summarized Professor Wang Gang's new theory,new treatment and new prescription in the treatment of chronic renal failure based on syndrome differentiation through 13 years of learning records from teachers,literature sorting,interview and discussion,etc.2.Through the systematic study of the academic thought of Zou Yunxiang,Zou Yanqin and Wang Gang,three generations of experts in Zou's nephrology department,the connotation of Zou's core thought of"tonifying nephrology" and the systematic research results were excavated.3.Clinical study:744 patients with chronic renal failure(CKD stage 2?5)who were diagnosed and treated in our hospital from March 2013 to December 2018 were retrospectively collected as research subjects.Patients were divided into study group(routine treatment+Shenwu Yishen Tablet)and control group(routine treatment only)according to the treatment records of Shenwu Yishen Tablet.In the study group,on the basis of conventional treatment,Shenwu Yishen tablet was taken orally,3 times a day,4 tablets each time.Patients in the control group were treated with conventional therapy alone.Comparison ? The improvement of TCM syndrome before and after treatment in the two groups;? Laboratory indexes before and after treatment in 2 groups:serum creatinine(SCR),urea nitrogen(BUN),glomerular filtration rate(EGFR),endogenous creatinine clearance rate(CCR),hemoglobin(Hb),serum albumin(ALB);? Liver function,diarrhea and other adverse events were recorded before and after medication in 2 groups,and the safety of Shenwu Yishen Tablet was observed.4.From the perspective of network pharmacology,a network of medicinal materials-compounds-targets-diseases was constructed to analyze the pharmacological effects of active components of Shenwu Yishen Tablet on targets and their relationship with clinical diseases.Results:1.To summarize Professor Wang Gang's inheritance and development of Zou's core idea of "tonifying kidney yuan",and to create a new theory,new treatment and new prescriptions for treating chronic renal failure based on syndrome differentiation.(1)Disease name:Professor Wang Gang suggested that "kidney strain" should be taken as the basic disease name of chronic renal failure,together with the different main symptoms in each disease stage.According to the severity of the disease,the name of the disease can be divided into the order of primary and secondary,such as the occurrence of multiple primary diseases can be diagnosed at the same time.(2)Etiology and pathogenesis:Professor Wang Gang believes that the etiology and pathogenesis of chronic renal failure can be summarized as "nephron failure,turbidity and toxic retention".Nephron deficiency refers to the failure of both the true Yin and the true Yang of the kidney,and the retention of turbidities and toxins is the retention of all kinds of metabolic wastes caused by nephron failure.Nephron failure is the origin of the disease,and turbidity and toxic retention is the standard of the disease.These criteria influence each other and the manifestations are each other's severity,which are common throughout the pathogenesis of chronic renal failure.(3)Professor wang gang of put forward the guiding ideology of "this virtual is a key link,the standard is a yard,and both",identified the type is given priority to with the certificate of master card,give priority to with the card and card type,the main type of syndrome type and and can be as the pathogenesis of the dynamic change of each other and clamp,clinical can hold Jane yu complexity,and can know often change,on this basis,created the chronic renal failure type differentiation and the national standard,in use today.(4)Treatment method:Professor Wang Gang syndrome differentiation in the treatment of chronic renal failure of the general principle of "tonifying nephron,and collaterals to relieve turbidity ".Treatment drugs are mostly Ganping agent,so that Qi Qi is not stagnant,warm Yang is not dryness,nourishing Yin is not boring,slowly plan treatment,maintain the dynamic balance of kidney Yin and kidney Yang at a low level,Yin Ping Yang secret,in order to delay the progress of chronic renal failure effect.Create treatment based on syndrome differentiation+low and high retention enema,develop renal failure retention enema sac;In the 1980s,it was first reported that Chinese medicine+skin penetrant applied to acupoints to treat uremia.In the 1990s,systematic combination and multi-channel drug administration were used to delay the progression of chronic renal failure and improve the clinical efficacy.(5)development of new drugs,research on "tonifying nephron" mechanism:"tonifying nephron" representative drugs developed by Professor Wang Gang and Professor Zou Yanqin,national traditional Chinese medicine new drug "Huangzhiyishen Capsule" tonifying nephron,qingli and promoting blood circulation mechanism:May be through a stable internal environment,two-way regulating cell inner nucleotide TXA2 and PGI2 system balance,inhibit platelet aggregation,release,correcting high coagulation state,improve immune function,adjust the sex hormone metabolism,eliminate toxin,thus reduce glomerular pathological change,accelerate the dispel of immune complex deposition in situ,and protect the residual nephron,obtain good curative effect in patients with chronic kidney disease.2.Based on a large sample study,the clinical efficacy,safety and optimal conditions of use of Shenwu Yishen Tablets for the treatment of chronic renal failure after approval on the market were suggested.(1)Overall efficacy:Analysis of the total efficacy of the two groups after treatment showed that in the control group,29 cases(19.3%)were significantly effective,40 cases(26.7%)were effective,34 cases(22.7%)were stable,and 47 cases(31.3%)were ineffective,with a total effective rate of 68.7%.In the study group,184 cases(31%)were significantly effective,174 cases(29.3%)were effective,127 cases(21.4%)were stable,109 cases(18.4%)were ineffective,and the total effective rate was 81.6%.After treatment,there was significant statistical difference between the two groups(P<0.05),indicating that the total efficacy of Shenwu Yishen Tablet in the treatment of chronic renal failure stage 2?5 was better than conventional treatment.(2)Shenwu Yishen Tablet can effectively improve the clinical symptoms of patients with chronic renal failure.In TCM syndrome curative effect,the team the total effective rate was 85.4%,the control group was 74.7%,the team total effective rate is significantly higher than the control group(P<0.05),indicating that the cords wu yi kidney slices can obviously improve the patients with chronic renal failure CKD2?5 issue of nausea and vomiting,languid and lumbar debility,body weight and other traditional Chinese medicine syndrome,improve patient quality of life.(3)Clinical study results showed that Shenwu Yishen Tablet could reduce BUN,Scr,and increase GFR and CCR in patients with CKD stage 2-5.In addition,in each subgroup of CKD2-5 stage,compared with the control group,Shenwu Yishen Tablet group increased EGFR,CCR,decreased BUN,Scr,and the results were statistically significant(P<0.01).In the study group,the improvement of renal function level and staging effect of each subgroup of CKD2-5 patients after treatment were compared.Shenwu Yishen Tablet had the best effect on decreasing BUN,SCR,increasing GFR and CCR in CKD2 patients,followed by CKD3,CKD4,and CKD5.It was confirmed that Shenwu Yishen Tablet could improve renal function and delay the progression of chronic renal failure in CKD2?5 stage patients with deficiency of Qi and Yin.Early detection and early use of Shenwu Yishen Tablets has better therapeutic effect.(4)Improve serum albumin(ALB)effect:Clinical study results show that in CKD stage 3 subsamples,compared with the control group,the use of Shenwu Yishen Tablets patients with ALB level increased,indicating that Shenwu Yishen Tablets can improve the level of ALB,improve the nutritional status of patients with CKD.(5)safety observation:for the safety observation of Shenwu Yishen Tablets,mainly from the influence of Shenwu Yishen Tablets on liver function and the patient's diarrhea were analyzed.The results showed that there was no significant difference in liver function between the study group and the control group(P>0.05).5 cases of liver damage after Shenwu Yishen Tablets were investigated and analyzed.Among the 5 patients,2 had a history of liver,and the treatment of Shenwu Yishen Tablets and liver protection and enzyme reduction was discontinued.ALT and AST returned to normal.It is suggested that patients with previous liver history should pay attention to monitoring liver function when using Shenwu Yishen Tablets.(1)Shenwu Yishen Tablet can be used for chronic primary glomerular disease caused by chronic renal failure(CKD2?5 stage)in non-dialysis patients with Qi and Yin deficiency and dampness and turbidity syndrome,with obvious protection of renal function of patients,delay the progression of CKD effect;It also has the same effect of improving TCM syndromes and protecting renal function in non-dialysis patients with chronic renal failure caused by secondary diseases(CKD2?5 stage).It can also be taken clinically.? Shenwu Yishen Tablet can improve the symptoms of nausea,vomiting,lack of food,dry oropharynx,dry stool and so on in CKD2-5 patients.? Shenwu Yishen Tablet has the best effect on decreasing BUN,SCR,increasing GFR and CCR in CKD2 patients,and with the progression of CKD,the efficacy of CKD2?5 patients decreases successively.It is suggested that Shenwu Yishen Tablets should be taken at the early stage of chronic kidney disease in order to benefit patients as soon as possible.(4)Shenwu Yishen Tablet did not appear obvious liver function damage,but for CKD patients with previous liver history,attention should be paid to monitoring liver function.(5)After taking Shenwu Yishen Tablets,the number of stools in patients increased.If diarrhea symptoms occur,the dose can be reduced or suspended,and the dose can be reduced in patients with plain stools.3.To further analyze the pharmacological mechanism of the active components of Shenwu Yishen Tablet from network pharmacology.Pharmacology study through the network,and wu yi kidney slice of the effective compounds of triterpene and anthracene ketone compounds,these compounds have the anti-inflammatory,antibacterial,antiviral,hypoglycemic and lipid-lowering,fight ulcer,antitumor,oxygen free radicals,lower cholesterol,and increase the stomach power,protect liver,bravery,improve immune function,through the stool,such as the water swelling effect,they act in NOS3,mTOR,CETP,TNF alpha,ACE,MAO-B,ADRB2,KOR,DRD2,AchE,11 beta HSD1 and 5-LOX targets,It can treat and relieve glomerulonephritis related symptoms such as nausea,vomiting,insomnia,dry mouth and edema caused by hypertension,inflammatory diseases,dyslipidemia,obesity and so on.