Study On Preparation Process And Pharmacodynamics Of Shenshuaining Dispersible Tablets, A Traditional Chinese Medicine

Chronic renal failure (CRF) is a common result of standing development of all kinds of primary or subsequent kidney disease and is one of the most familiar and refractory disease in clinic, which endanger badly people's health and life. Now the treatment of the CRF in western medicine mainly included expectant treatment such as decompress step down, diuresis, redressing acid-base equilibrium, anti-infection; hemodialysis, peritoneal dialysis, renal transplantation and so on. But expectant treatment can't remove the root cause of CRF and offen stopped by big side reaction of western medicine, dissatisfaction on curative effect or sufferer can't insist taking medicine. Treatment of dialysis has side reaction in different disgree and can't remedy pathology injure of kidney tissure. And the renal transplantation is limitted by lacking kidney source, reject rection and costly fee. So how to treat and prevent the CRF effectively is becoming a common concerned problem among the international medical researchers. CRF belongs to the domain of the"Dropsy", "Lingzheng", "Guange", "Longbi"and so on in TCM. TCM has a positivity therapy effect in treating and preventing CRF and has little side reaction, which brought out widely applying foreground. But some traditional TCM formulation is not convenient in carrying and taking, which limitts its using in clinic. Shenshuaining is a pure TCM in treating CRF in clinic. It can effectively bring down blood urea nitrogen (BUN) and creatinine, postpone the processing of CRF and has a posistive curative effect in treating early and metaphase CRF. But now the Shenshuaining orally preparation selling in the market need big dose. So we modificated the formulation of Shenshuaining and manufactured the Shenshuaining dispersible tablets and carried on the study of mainly pharmacodynamics in order to increase its curative effect, reduce oral dose, make formulation multiplicity. So that it can take more better effect in treating CRF in clinic.The details were as follows:Chart I Pharmacal study on Shenshuaining dispersible tabletsObjective: To convert Shenshuaining capsule into Shenshuaining dispersible tablets, a new fomulation of quick result and instant, precondition that its craft was not changed.Methods: (1) We selected all sorts of supplementary materials with the standard of their different time limit of disintegration and took microcrystalline cellulose (MCC) , cross-linked polyvinyl pyrrolidone (PVPP) and so on as supplementary materials of Shenshuaining disperisble tablets in the end.(2) We select the dosage of above supplementary materials of disperisble tablets by the method of orthogonal design with the standard of limit time of disintegration too.(3) We make certain content of the extractive powder and supplementary materials and crude drug of every tablet based on content of supplementary materials in Shenshuaining disperisble tablets.(4) We prepare the dispersible tablets with the method of directly pressing powder into tablets and detected their disperisble evenness degree. Results: (1) The craft route of the Shenshuaining dispersible tablets was as follows. Among the ten traditional Chinese medicinal materials in the prescription, we took 200g rhubarb and smashed them into tiny powder. Another 200g rhubarb were macerateed 24 hours with 70% alcohol, diacolation slowly, gathered percolate and concentrated into thick extractive (relative density is 1.10, 80℃) according to the diacolation method of CHP (2005) . The remnant nine traditional Chinese medicinal materials including heterophylly falsestarwort root cook with water three times, the first cooking time was 3 hours, the next was 2 hours and the last was 1 hours. Then the liquor was filtrated, merged and concentrated into sufficit quantum (1:1) with method of decompression. Added the alclhol and made their cotent arrived at 60%, mixed adequately, laised quietly for 72 hours, filtrated and concentrated into thick extractive(relative density is 1.12, 80℃) with method of decompression. We mixed them with rhubarb extractive and powder equably, dried and smashed them into tiny powder(passed through 100 mesh bolt) .Then we added 10% MCC, 20% PVPP and 1% Gum Arabic into them, mixed adequately and equably and pressed into tablets directly, which was the shengshuaining dispersible tablets. Every tablet weights 0.5g.(2) The dispersible tablets were prepared with tradional Chinese medicine and selected supplementary materials. Their disperisble evenness degree was that they desintegrated in 180 seconds and their disperisble homogeneity indicated that they could pass through bolt of two type and reached the demand of CHP (2005) .Conclusions: The recipe of Shenshuaining dispersible tablet was reasonable and its prepared craft was simple and credible.Chart II Pharmacodynamics study of the ShenShuaiNing Dispersible tablets in treating Chronic Renal Failure rats induced by Adenine Objective: To explore the effect of the Shenshuaining dispersible tablets in treating chronic renal failure (CRF) rats and provide the laboratorial evidence for its formulation innovation and clinic application.Methods: Seventy-two Sprague-Dawley rats were randomly divided into 6 groups: normal control group, model control group, Niaoduqing group, Shenshuaining dispersible tablets group (high, middle and low dose) . From two group to six group, we prepared model of CRF by feeding the rats with feed containing 0.5% adenine. All rats were treated with corresponding drugs for 7 weeks. During and after the treatment, the general state, blood and uric glucose levels of the rats in every group were observed. After treated in the last time, we hocused all the rats with 10% chloral hydrate, collected the blood via ventral artery. Some blood was anticoagulated with ethylenediamine tetraacetic acid (EDTA) and was detected blood routine examination. The other blood was gathered the serum by centrifuge and detected serum creatinine (Scr), Blood urea nitrogen (BUN), albumin (ALB), potassium (K⁺), natrium (Na⁺), calsium (Ca²⁺), phosphor (P), nitric oxide (NO), total nitric oxide synthase (T-NOS), inducing nitric oxide synthase (iNOS), configuration nitric oxide synthase (cNOS), total superoxide dismutase (T-SOD), Cu/Zn-SOD and malonaldehyde (MDA) levels. And we took out the kidney of the rats, observed the size and volume of them and measured the kidney weight and relative kidney weight. Then we scissored about 100mg left kidney tissue, homogenated and detected NO, T-NOS, iNOS, cNOS, T-SOD, CuZn-SOD and MDA in the kidney tissue. And we took out the right kidney, colorated with method of hematoxylin and eosin (HE) and investigated the renal pathological changes by optical microscope.Results: Compared with normal rats, model group rats' gerneral status was badder and their body weight reduced. The levels of BUN, Scr, K⁺, Na⁺, P in the blood rise in the model group rats. While the levels of ALB, Ca²⁺, RBC, HGB and HCT failed in those rats. In those rats' blood and kidney tissue, the levels of NO, T-NOS, cNOS, T-SOD, Cu/Zn-SOD failed and the levels of iNOS and MDA rise. And their kidney weight and relative kidney weight increased distinctly and came forth renal pathological lesions. Compared with rats in model group, the rats' gerneral status and weight was ameliorated markedly in Shenshuaining dispersible tablets group. And the levels of BUN, Scr, K⁺, Na⁺, P in those rats failed, the levels of ALB, Ca²⁺, RBC, HGB and HCT increased. In those rats' blood and kidney tissue, the levels of NO, T-NOS, cNOS, T-SOD, Cu/Zn-SOD rise and the levels of iNOS and MDA failed. And their kidney weight and relative kidney weight decreased distinctly and renal pathological lesions was ameliorated markedly. Treatment with Niaoduqing could ameliorateabove indexes too.Conclusions: Shenshuaining dispersible tablets could effectively ameliorate renal function, adject the turbulence of electrolyte, correct anemia, mitigate the renal pathological lesion and prevent and treat the CRF. The mechanism might be related to improving body's antioxidation effect, reducing damnification of free radical and increasing synthesis of cNOS and NO, which could protect the kidney.