Study On Blumea Balsamifera Formula Granules And Establishment Of Quality Standard

Objective:According to the theory of traditional Chinese medicine and combined with modern pharmaceutical technology,Blumea balsamifera decoction was developed into the formula granule.The molding process of the granule was studied,and quality evaluation system was established,the quality stability was investigated,and the hemostatic test was conducted,so as to provide references for the rational development and clinical application of Blumea balsamifera formula granules.Methods:1.The preparation processTo establish a method for the determination of protocatechuic acid in the extract of Blumea balsamifera.In the extraction process,the total content of protocatechuic acid was taken as the index,and the extraction times,extraction time and solid-liquid ratio were taken as the investigation factors.The extraction process was optimized by the orthogonal test method,and the extraction process was determined after the verification test.According to the decoction method of clinical decoction,the standard decoction of Blumea balsamifera was prepared.In drying process,the appearance of materials after drying is taken as the index to investigate the parameters of spray drying process,such as inlet air temperature,relative density of liquid and material flow rate,so as to optimize the spray drying process.Study on the molding process.Dry powder obtained after spray drying was used as raw material.Granulation was carried out by dry method.The preparation process verification test was carried out according to the determined processing standards.Three batches of particles were prepared and the quality was checked.2.Scale up pilot production,carry out 3 batches of scale up pilot production according to the determined best process,and conduct quality inspection.3.Establishment of quality evaluation system for Blumea balsamifera formula granulesWith reference to the relevant methods of Chinese pharmacopoeia,quality evaluation was carried out on the properties,particle size,moisture content,solubility and volume difference of enaxanax formulation granules,and TLC identification method was studied.The established TLC identification method was good.In the corresponding position with the control product and the control medicinal material,3 batches of test products showed clear spots with the same color,moderate R_f value,and no interference with the negative control.HPLC method was used to establish the content determination method and fingerprint of the Blumea balsamifera formula granules.4.Quality stability investigation,influence factor test,accelerated test and long-term test were carried out on the Blumea balsamifera to predict its expiry date.5.The hemostatic effects of Blumea balsamifera standard decoction and Blumea balsamifera formula granules were compared with coagulation time and hemostatic time.Results:1.The research results of preparation technologyFinally,the optimized extraction process is 14 times the amount of water.The extraction time is 30 min and the extraction time is 3 times.Molding process:the auxiliary material is soluble starch,the dosage is 0.8times of spray dry powder;The technical parameters of dry pelleting:roller pressure is 125bar,roller speed is 18.8 rpm,feeding speed is 2.8 rpm and roller distance is 1.8mm.The processing standard of Blumea balsamifera formula granules was determined,and three batches of granule were obtained through the preparation process verification test.The results of particle size,moisture content and solubility were all in line with the relevant provisions of granule in the 2015edition of Chinese pharmacopoeia.2.In the large-scale pilot production,the results of particle size,water content and solubility of the three batches of granulates were all in line with the relevant provisions of the granule of the 2015 edition of Chinese pharmacopoeia.3.The results of establishment of quality evaluation system for Blumea balsamifera formula granulesThe traits,particle size,moisture content,solubility and volume difference of granules all conform to the relevant provisions of appendix 0104 of the four parts of Chinese pharmacopoeia in 2015.TLC identification method established is good,in the corresponding position with the control,control drugs,3 batches of test products show the same color clear spots,R_f value moderate,negative control without interference.A HPLC method for the determination of protocatechuic acid in Blumea balsamifera formula granules was established.The concentration of protocatechuic acid within the range of 18.320⁷32.80?g/ml showed a good linear relationship with the peak area,and the standard curve equation was Y=74866X-46424,R=0.9998.The peak area RSD of the precision test was 1.09%（n=6）,the peak area RSD of the repeatability test was 0.68%（n=6）,and the content RSD was 0.66%（n=6）.The peak area RSD value of stability tes t was2.92%（n=6）,and the RSD value of protocatechuic acid content was 2.81%（n=6）.The average recovery was 98.40%and the RSD was 1.12%（n=6）.HPLC fingerprint method was established for Blumea balsamifera formula granules.Thechromatographic column was Zorbax SB-C₁₈（4.6×250mm,5?m）,the detection wavelength was 280 nm,column temperature was30℃,the flow rate was 1.0 ml/min,sample quantity was 10μl,with acetonitrile（A）-0.1%phosphoric acid water（B）as mobile phase in gradient elution.The fingerprints of the 15 batches of particles identified 12 common peaks and identified 5 chromatographic peaks,namely protocatechuic acid,protocatechuic aldehyde,chlorogenic acid,caffeic acid and rutin.4.After 6 consecutive months of quality stability investigation,there was no significant change in the particle size,water content,solubility,protocatechuic acid content and other indexes of the three batches of formula granules.5.Study on hemostatic effect of Blumea balsamifera formula granules and its standard decoction can shorten the bleeding time and coagulation time of mice and have the effect of hemostasis.Conclusion:The processing parameters of the Blumea balsamifera formula granule are explicit,the process is stable and feasible,and it is suitable for industrial production.The established quality evalution system can accurately detect and analyze the Blumea balsamifera formula granules qualitatively and quantitatively,and can effectively control the quality of the preparation.The formula granules and their standard decoction have the hemostatic effect,and their hemostatic effect has no obvious difference.