Study On The Preparation Technology And Quality Standard Of Jianpi Shugan Granules

ObjectiveNon-Alcoholic Fatty Liver Disease is commonly regarded as a fat metabolism disorder,and it is caused by metabolic imbalance which leads to excessive fat accumulation in livers.This common disease can lead to liver cancer and cirrhosis,so it has become one of the most health-threatening diseases in the world.Currently,there is no effective patent Chinese medicine to cure non-alcoholic fatty liver disease in the market.Therefore,a safe and effective patent Chinese medicine for the treatment of NAFLD has the good social value and economic benefit.Jianpishugan Granule is originated from a clinical prescription,which composed of Herba Gynostemmatis Pentaphylli,Silybi Fructus,Saliviae Miltiorrhizae Radix Et Rhizoma,Sinapis Semen,Cassiae Semen.Based on the theory of Chinese medicine,this study combined modern science and technique to optimize the extraction and purification processes,initially establish the appropriate quality standard,maximize the clinical efficacy and satisfy the market requirement.MethodsThe method mainly included the following parts:extraction and purification processes,forming processes,three batches of pilot-scale experiments and the establishment of quality standard.(1)Study on the extraction and purification process:water extraction and alcohol precipitation processes for Saliviae Miltiorrhizae Radix Et Rhizoma and other herbs were tested with orthogonal experiments and single factor tests,regarding the extraction rate of salcianolic acid B as the index;alcohol extraction process of Herba Gynostemmatis Pentaphylli,Curcumae Radix and Silybi Fructus were tested with orthogonal experiment and single factor test as well,regarding the extraction amount of the Gypenoside,Curcumin and Silybin as the evaluation index.(2)Granule was selected as the dosage form based on the pharmaceutical technology design and the characteristics of ingredients.This study determined the medicine auxiliary proportion according to process results and practical situations.The process parameters were determined by investigating moisture absorption rate,forming rate,soft material properties for granules.In addition,we also investigated the critical relative humidity of forming granule,which provide a reference for the humidity control of the preparation process.(3)Experiment of three batches of pilot-scale:According to the extraction,purification and forming processes,three batches pilot-scale samples were produced to furtherly investigate the stability and feasibility of the above processes.(4)Quality standard research:In order to develop appropriate quality standards,the HPLC,TLC methods were created to conduct the quantitative and qualitative researches for Jianpishugan Granule.Results(1)Results of the extraction and purification process:The optimum water extraction and alcohol precipitation process:The herbs were decocted with 8 times of water for 1h each time,totally 3 times.Then the filtrate was concentrated to a relative density of 1.11-1.15(60?).The alcohol was added to the concentrated liquid to 60%alcohol concentration.The optimum alcohol extraction processes:The herbs were decocted with 14 times of 70%alcohol for 1.5 h each time,totally 3 times.(2)Result of the forming process:Dextrin was selected as supplementary material,the ratio of extract powder and supplementary material was 2:1,95%alcohol was regarded as wetting agent.The environment critical relative humidity was controlled lower than 70%.Wet granulation was conducted to produce soft material.(3)Result of three batches of Pilot-scale experiments:Three batches of pilot-scale production data showed that extraction and purification processes and forming processes were stable and feasible.(4)Result of quality standard research:The TLC method for the identification of Herba Gynostemmatis Pentaphylli,Silybi Fructus,Saliviae Miltiorrhizae Radix Et Rhizoma,Sinapis Semen,Cassiae Semen,etc.has been established.The HPLC method was also built to measure the content of Ginsenoside Rbi and salvianolic acid B in Jianpishugan granule.The chromatographic conditions of Ginsenoside Rbi:Agilent Zorbax SB-C18 column(4.6 mm ×250 mm,5 ?m),isocratic elution with acetonitrile-water(30:70),column temperature was 25?,flow rate was 1.0 mL/min,drift tube temperature was 100?,flow rate of carrier gas was 2.7 L/min.The chromatographic conditions of salvianolic acid B:Agilent Zorbax SB-C18 column(4.6mm × 250mm,5?m),isocratic elution with acetonitrile-0.2%phosphoric(21:79),column temperature was 30?,flow rate was 1.0mL/min,detectiong wavelength was 286nm.ConclusionA stable and feasible preparation process of Jianpishugan granule is established by the research of extraction,purification and forming process,with producing qualified granules.The study set up the qualitative identification and quantitative determination through the relevant quality standards to guarantee that the formulation quality of Jianpishugan granule achieve the expected experimental objective.