| Jianshen Granule is used for early treatment of chronic renal failure which is composed of cornus,rehmanniae radix,Astragali radix and other eight herbs.In order to improve the curative effect and safety,the preparation process and quality control research,pilot process verification,preliminary stability test and pharmacodynamics evaluation of Jianshen Granules were carried out in this subject.With the indexes of dry extract yield and the content of morroniside,loganin and calycosin glucoside,with the variables of amount of water,extraction times and extraction time,the Box-Behnken Design of response surface methodology was employed to optimize the extraction process of Jianshen Granule,final extraction process of Jianshen Granule was: the amount of water was 8 times the total weight of herbs,extracting twice and1.5 hours for each time.The molding process of Jianshen Granule was optimized With the indexes of forming ability and dissolubility,final molding process was: the ratio of dry extract,dextrin and starch was 2:1:1,The wetting agent was85% ethanol.Thin layer chromatography(TLC)was applied to the qualitative identification of cornus,rehmanniae radix,astragali radix,salvia miltiorrhiza,angelica sinensis,ligusticum wallichii and bighead atractylodes rhizome.High performance liquid chromatography(HPLC)was applied to the quantitative determination of calycosin glucoside,morroniside and loganin.The results showed,the TLC method is special and repeatable,morroniside,loganin and calycosin glucoside were linear in the ranges of 0.035~0.702μg,0.117~2.340μg,0.011~0.220μg,respectively,and the recovery was 97.73%,99.28%,98.92%,respectively.The HPLC method was precise,stable,repeatable and accurate.Therefore,The qualitative and quantitative methods can be used for the quality control of Jianshen granules.Accelerated stability test was carried out under temperature(40±2)℃and RH(75±5)% condition for 6 months,and long-term stability test was carried out under temperature(25±2)℃ and RH(60±10)%condition for 6months,there was no significant change in each inspection item.It showed that Jianshen Granules was stable in the current 6 months,while the final stability requires further study.Using 5/6 nephrectomy to construct CKD rat model,the levels of Scr and BUN in the 5/6 nephrectomy model group and the sham group were determined 2 weeks after operation to test whether the model was successful.After the models succeed,we divided the experimental rats into model group,Uremic clearance granules group(UCG),Jianshen granule low-dose group(JS-L),Jianshen granule middle-dose group(JS-M),Jianshen granule high-dose group(JS-H).In addition,set blank group and sham operation group,8 rats each group.Drug delivery methods: UCG was given a gavage of 3.6g/kg/d premixing solution.JS-L,JS-M and JS-H was given a gavage of 0.96,1.92,3.84mg/g/d premixing solution.Model group,Sham group and model group were given an equal volume of distilled water.Gave medicine twice a day,and all groups continuously administrated for 8 weeks.During the administration period,the physiological state of the rats was observed and the body weight was recorded.Collected the serum through eyeground vein blood sampling every two weeks,and determined the levels of Scr,BUN,ALT,AST.Collected the 24 h urine at the fourth week,sixth week,and eighth week,determined the levels of the urinary protein(UPr)and measured the urine volume of the last week of administration.The results showed,Jianshen Granules can reduce serumcreatinine,urea nitrogen and 24 h urinary protein in CRF rats,thus protecting residual renal function and relieving renal failure symptoms.This product has no significant effect on liver function. |
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