Study On Preparation And Quality Standard Of Bupleurum Chinese Dispensing Granules

Traditional Chinese medicine（TCM）has been used to prevent and treat diseases in China for thousands of years.Nowadays,the dispensing granules break through the application form of TCM decoction pieces and have the advantages of decocting ignoring,direct preparation,hygiene and safety,and convenient carrying.So,it is increasingly recognized by the majority of patients.The Bupleurum Chinese dispensing granule is one kind of widely used dispensing granules.However,a number of investigations have revealed many problems with Bupleurum Chinese dispensing granule,such as different preparation techniques,the consistency of quality and efficacy of such granules and imperfections of the current national standard.In this paper,new methodology for Bupleurum Chinese dispensing granule quality standard was provided based on the modern pharmaceutical analysis techniques and the preparation technology of Bupleurum Chinese dispensing granule was optimized based on the pressurized hot water extraction technology.The main research works are as follows:1.Quality investigation of commercially Bupleurum Chinese dispensing granule:the quality of 30 batches of Bupleurum Chinese dispensing granule was evaluated according to the current national standard.The problems with the Bupleurum Chinese dispensing granule were found such as moisture absorption,poor solubility and poor consistency of quality,which indicated that the production process and parameters currently used by enterprises need to be improved.Furthermore,the current national standard can not evaluate the quality of Bupleurum Chinese dispensing granule comprehensively by using saikosonin a as the control parameter.2.Improvement of Bupleurum Chinese dispensing granule quality evaluation methods:the fingerprint of Bupleurum Chinese dispensing granules was established based on HPLC-ELSD method.16 common peaks were found and five common peaks,including saikosaponin c,saikosaponin f,saikosaponin a,saikosaponin b₂and saikosaponin b₁,were identified.And the similarities of Bupleurum Chinese dispensing granules were 0.886～0.997,which indicated the differences between different enterprises and batches based on the new evaluation method.One batch is not conformed to the proposed limits,which was found according to the new method but not detected with current standards.The contents of saikosaponin c,saikosaponin f,saikosaponin a,saikosaponin b₂and saikosaponin b₁were determinate by external standard method,and the total saponins of Bupleurum Chinese dispensing granule was4.47～11.65 mg/g.The difference of component content is obvious between different enterprises and batches,which cannot be found according to current standards.Furthermore,the new method of detecting adulteration of Bupleurum marginatum var.stenophyllum and Bupleurum bicaule in Bupleurum Chinese dispensing granule was established based on HPLC-MS/MS method,which using nepasaikosaponin K and prosapogenin D as the control parameters.However,the adulteration could not be identify according the current legal standard.3.Establishment of index parameters of Bupleurum Chinese standard decoction:the fingerprint of Bupleurum Chinese decoction pieces was established on the basis of HPLC-ELSD method.And 4 out of 24 common peaks were identified,including saikosaponin c,saikosaponin f,saikosaponin a,and saikosaponin d.The similarities of Bupleurum Chinese decoction pieces were higher than 0.97.The fingerprint of Bupleurum Chinese standard decoctions was also established on the basis of HPLC-ELSD method,and there are obvious differences of chemical constituents in fingerprints of Bupleurum Chinese decoction pieces and standard decoctions.The related parameters of Bupleurum Chinese standard decoctions were determined as:the permissible range of extract yield was 11.28%～20.94%,the similarity with control fingerprint of Bupleurum Chinese standard decoction can not lower than 0.85,and the permissible range of extract transfer rate was 25.52%～47.38%.4.Preparation of Bupleurum Chinese dispensing granule:Firstly,the active components of Bupleurum Chinese were extracted by pressurized hot water method.The effects of pressure,temperature,liquid-solid ratio and time on the extraction yield of total saponins were investigated,and the process was optimized by the response surface method.At the conditions of liquid-solid ratio 1:11.6,extraction time 38 min,extraction temperature 130℃,the yield of total saponins was 7.02%.And then,the fillers and adhesives was selected.The results showed that microcrystalline cellulose was suitable for the preparation of Bupleurum Chinese dispensing granules as filling agent,and the ratio of microcrystalline cellulose added to pressurized extract was as follows:Microcrystalline cellulose 1:1 and 90%ethanol was used as binder.Then,3batches of Bupleurum Chinese dispensing granules were prepared,and the quality,the stability and the dissolution were evaluated.The results showed that the quality of self-made Bupleurum Chinese dispensing granules was up to the current national standard,and the stability was better than the market Bupleurum Chinese dispensing granules.In conclusion,the established method can control the quality of Bupleurum Chinese dispensing granules.The pressurized hot water extraction technology can be used to extract total saponins from Bupleurum Chinese with advantage of high efficiency and low cost.Moreover,the dispensing granules,prepared with pressurized hot water extracts,present ideal stability,good application and development prospect.