| Objective:In the pre-clinical research on the basis of the six categories in accordance with traditional Chinese medicine and new drugs and "Chinese medicine,natural medicine technology research guidelines," the relevant technical requirements,to carry out Sanhuangyishen particles preparation process,quality standards and initial stability,and preparation Preliminary pharmacodynamics research,for the final development into a safe and effective,taking a convenient treatment of chronic kidney disease,a new preparation of traditional Chinese medicine to lay the foundation.Methods:1.Study on preparation(1)Process route selection Using the model of chronic renal failure(CFR)rats,combined with the results of literature review,screening the preparation process of Sanhuangyishen granule.(2)Study on Extraction TechnologyThe extraction process of volatile oil from cinnamon was optimized by the single factor comparison method.The extraction efficiency of rhubarb and Salviae was optimized by the single factor experiment and orthogonal design with the extraction rate of solid,combined with anthraquinone and tanshinone ⅡA.The rate of water extraction process.was determined by factor experiment and orthogonal design with the total mass of solid,the content of astragaloside and calycosin-7-glucoside.(3)Concentration and drying processThe method of recovering atmospheric concentration and vacuum drying process,liquid thicknessof vacuum drying of its extract are as follows,taking the retention rate of anthraquinone and tanshinone IIA as an index.The retention method of stragaloside and calycosin-7-glucoside was used as an index,and the method of atmospheric concentration,vacuum concentration and spray drying process are preferred.(4)Study on forming technology of preparationsThe physical properties of the extract were evaluated by measuring the moisture absorption rate,the critical relative humidity and the powder properties of the extract;The weight gain percentage,the melting rate and the forming rate of the material are the indexes,preferably the type of filler.The dry granulation process conditions were selected by particle yieldas.With the critical relative humidity of the particles as an index,to determine the environmental humidity requirements during formulation molding.The particle moisture absorption rate is an index,and the type of the packaging material of the drug is preferable.(5)According to the small test of the preferred process parameters,to carry out three batches of pilot test.2.Study on quality standard and stabilityThe medicinal such as astragalus,rhubarb,salvia and cinnamon related Sanhuangyishen granule was analyzed by TLC;the content of tanshinone ⅡA and astragaloside methodological studywas deteminated by HPLC;with the requirements "Chinese pharmacopoeia" 2015 version Ⅳ general 1014,to establish the preparation standard of the traits,water,particle size.3.Preliminary pharmacodynamics studyThe effect of Sanhuangyishen granule on the model of chronic renal failure rats was studied by using BUN and Cr.Results:1.Study on preparation(1)The preferred process route as:Cinnamon was extracted of volatile oil,rhubarb and salvia were extracted with ethanol reflux,the rest of herbal with water as solvent,the two were concentration,drying,molding,made into granule;(2)The optimum process for extracting volatile oil from cinnamon:8 times the water,distilled extraction 6h,the oil extraction rate of 0.92%(3)The preferred extraction process of rhubarb and salvia:rhubarb and salvia extraction 2 times,each plus 8 times the volume of 80%ethanol,reflux extraction 2 h,with the extraction rate of tanshinone ⅡA and combined anthraquinone 47.65%and 54.63%;the vacuum concentration(-0.08MPa,55~65℃)was optimized,with the retention rate of tanshinone ⅡA and combined anthraquinone 86.30%and 84.30%;optimized drying method was vacuum drying process(-0.08MPa,50~80℃),with the thickness less than 0.7cm.the retention rate of tanshinone ⅡA and combined anthraquinone 72.08%and 69.12%.(4)The preferred extraction process of the rest:the rest of herbal elataadded boiling 2 times,plus 10 times the amount of water,extraction 2 h,with the extraction rate of astragaloside and calycosin-7-glucoside 56.03%and 68.18%;the vacuum concentration(-0.08MPa,55~75℃)was optimized with the retention rate of astragaloside and calycosin-7-glucoside 85.92%and 78.40%;spray drying process(inlet air temperature 175±5℃,outlet air temperature 85±5℃)was optimized,with relative density of concentrated soluid 1.06~1.10(60℃),and the retention rate of astragaloside and calycosin-7-glucoside were 83.91%and 77.64%.(5)The moisture absorption rate of the extract was 22.61%,with the critical relative humidity 58%,the tap density 0.73 g · mL-1,the bulk density 0.68 g · ML-1;molding process identified as:maltodextrin as filler,adopted dry granulating method with material moisture between 3.0 to 5.0%was best;the moisture absorption rate was 13.81%,the critical relative humidity was 61%,the bulk density was 0.78 g · mL-1,and the tap density was 0.85 g · mL-1.The PET/AL/PE composite membrane was selected for encapsulation.After three batches of pilot test,it was proved that the preparation process was reasonable and feasible,with the transfer rate of astragaloside 66.12%~66.64%and tanshinone ⅡIA 32.02%~32.23%.2.Preliminary study on pharmacodynamicsThe effect of Sanhuangyishen granule on the BUN and Cr values of chronicrenalfailure rats was significantly reduced.3.Study on quality standard and stabilityThe method of TLC identification of Salviae,Astragalus,Rhubarb and Cinnamon and the content determination of astragaloside and tanshinone ⅡA by HPLC showed that the method was stable and no interference.Accorded to the requirements of "Chinese pharmacopoeia" 2015 versionⅣ general 1014,preparation of the particle size,moisture,traits,loading differences,melting,microbiological examination of the final products.After 6 months of room temperature stability test and accelerated stability test results show that the goods in the market under the conditions of packaging stability,the validity of the initial identified as 2 years.Conclusion:The preparation technology of Sanhuang Yishen Granule is effective,stable,feasible,reasonable and quality controllable,achieving the expected research purpose.It provides a reliable experimental basis for the clinical trial research and industrial production in the next step. |
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