| Objective:The original recipe for Xuefu Zhuyu Decoction was stem from Qing Dynasty physician Wang Qingren’s Yilin Gaicuo,which composed of 11 traditional Chinese medicines,such as safflower,red paeony root,fructus aurantii,Angelica and Chuanxiong.It is a classic recipe for promoting blood circulation and removing blood stasis,and has the effects of promoting blood circulation and removing blood stasis,and promoting qi and relieving pain.It is used to treat the syndrome of blood stasis in the chest,chest pain,chronic headache,pain such as acupuncture with definite place,or persistent hiccups,or internal heat depression,palpitation,insomnia,impatience and irritability,hot flashes,dark lips or dark eyes,dark red tongue or bruises,astringent pulse or tight string[1].Xuefu Zhuyu Decoction is still widely used in clinical practice with its characteristics and advantages.In order to develop a patent medicine preparation that can maintain Medicinal substances and the curative effect of the original decoction for the convenience of patients,according to the relevant technical guidelines of pharmaceutical research of new Chinese medicines,carried out research on the preparation technology,quality standards and preliminary stability on overcome"decoction of medicines"defects of Xuefu Zhuyu granules.Methods and Results:1.Preparation process research（1）The determination of dosage form and process routeIn this experiment,according to the daily dosage of Xuefu Zhuyu Decoction and the extraction rate of extract,physical and chemical properties and taste,the dosage form was determined to be granule with large dosage and better stability,so as to retain the clinical efficacy of the decoction.According to the clinical experience of decoction application,combined with the properties of the active components of each crude drug in the compound and the preliminary experimental results,the process route was determined as the whole prescription medicinal materials were prepared by water decocting process,water decocting solution was concentrated,an appropriate amount of soluble starch was added,and granule was prepared by spray drying.（2）The establishment of HPLC methods for determination of index constituentsIn this experiment,the HPLC determination method of Hydroxysaffior Yellow A,Paeoniflorin,Naringin,Ferulic Acid from the Xuefu Zhuyu decoction were builded respectively.The results were that in the optimized chromatographic conditions,good separation of each components were gained,and the negative had no interference.The establishment of the content determination method provides the basis for multi-index component screening of compound decocting,concentrating and drying process.（3）Study on compound water decocting technologyIn this experiment,the comprehensive retention rate of hydroxyl safflower A,paeoniflorin,ferulic acid and naringin was used as the index to investigate the compound water decocting process.Orthogonal experimental method was used to optimize the extraction times,solvent dosage and extraction time.According to the experimental results,the water decocting process was determined as follows:Add 10 and 8 times of water to the whole prescription,respectively,and fry the herbs twice,each time for 1 hour.The experimental results show that the synthetic retention rate of the above indexes is more than60%and the solid yield is 40%under this process condition.The results are repeatable,suggesting that the extraction process route and parameters are suitable.（4）Study on thermal stability of compound drug solutionIn this experiment,the retention rates of hydroxyl safflower yellow pigment A,paeoniflorin,naringin and ferulic acid were used as indexes to investigate the stability of xuefu Zhuyu solution under different temperatures,so as to simulate the influence of different temperatures on the concentration process of compound solution.The results showed that the concentration temperature had little influence on the retention rate of paeoniflorin and naringin at different temperatures（50°C,60°C,70°C,80°C and 100°C）for 5 hours.The retention rate of hydroxyl safflower yellow pigment A and ferulic acid decreased during the heating process above 70℃.The higher the temperature was,the more obvious the retention rate was.The retention rate of each index component in decompression concentrate and flow extract was investigated to determine the concentration end point.The results showed that the loss of hydroxyl carthami yellow pigment A and ferulic acid was not significant when the concentration was reduced to0.3g/m L,and the loss of hydroxyl carthami A and ferulic acid was greater when the concentration was continued to 1.20.The endpoint of reduced pressure concentration had little effect on the retention of paeoniflorin and naringin.Combined with the performance of the production equipment and comprehensive consideration,the compound liquid was determined to be concentrated under reduced pressure（-0.06 MPa）at a concentration temperature below 70℃and to 0.3 g/m L of raw drug content.（5）Study on drying technology of compound drug solutionIn this experiment,the retention rates of hydroxyl safflower yellow pigment A,paeoniflorin,naringin and ferulic acid were used as indexes to investigate the effects of reduced pressure drying and spray drying on the index components.The results showed that compared with reduced pressure drying,spray drying was more beneficial to the retention of index components,and the spray drying process was determined to optimize the parameters of spray drying process.Results showed that compound liquid enrichment content to 0.3 g/m L,adding suitable amount of soluble starch by spray drying,air inlet temperature is 150℃,the outlet temperature of 80℃),each index component retention rate is higher,A hydroxy safflower yellow pigment was 75%,naringin,paeoniflorin and ferulic acid for more than 85%,show that the selection of drying process is feasible and reasonable.（6）Study on forming technologySince the product contains thermal instability components such as hydroxyl safflower yellow pigment A,dry pressing granulation method was selected.Taking the yield,solubility and appearance of the particles as indicators,the dry pressing granulation process was investigated,and the optimal granulation process was as follows:feeding speed was300 r·min-1,roll speed was 50 r·min-1,and roll pressure was 4.0 MPa.The particle size,hygroscopicity and fluidity were investigated,and the results showed that the particle size was 9%,the critical relative humidity was 66%,and the resting Angle was 38°.There is no loss of each index component in the forming process.（7）Study on Mid-experiment technologyIn this experiment,the retention rates of hydroxylsafflower yellow pigment A,paeoniflorin,ferulic acid and naringin were taken as indicators,and A pilot study was carried out according to the above optimized process parameters.The results showed that by decocting,concentrating,centrifugal and spray drying process,the indexes of naringin,paeoniflorin,hydroxyl safflower yellow pigment A and ferulic acid in the compound had higher extraction rates（78%,56%,58%and 69%,respectively）during decocting process.No obvious loss was observed in the subsequent process of decompression concentration and centrifugation.The retention rate of the above components in spray drying process was62%,46%,36%and 50%respectively.There is no loss of component in molding process.It shows that the technological parameters adopted are reasonable and feasible and suitable for mass production.The daily intake of naringin,paeoniflorin,hydroxyl safflower yellow pigment A and ferulic acid in xuefu Zhuyu granules obtained by this experiment was significantly better than that of other commercially available capsules,granules and oral liquid.The daily intake of naringin,paeoniflorin,hydroxyl safflower yellow pigment A and ferulic acid in Xuefu Zhuyu granules obtained by this experiment was significantly better than that of other commercially available capsules,granules and oral liquid.Similar to the daily intake of the above components in the decoction made from the same batch of sliced decoction pieces with the same raw dosage,overcome“decoction of medicines”defects of the listed similar preparations.2.Study on quality standardsIn this experiment,thin-layer identification methods of safflower,Red Paeony Root,Radix Angelicae Sinensis,Rhizoma Chuanxiong,Fructus Aurantii,Radix platycodonis,Radix Bupleuri and other medicinal materials in Xuefu Zhuyu granules were established respectively,and the content determination methodology of hydroxylsafflower yellow element A,paeoniflorin and naringin was investigated,and the minimum limit of product content was stipulated.The particle size,water content,solubility,loading difference and microbe of the three batches of samples were examined,which all met the relevant requirements under the Chinese Pharmacopoeia granule.3.Preliminary stability studyThis product is granules,use aluminum foil bag packaging,three batches of samples in（T=40℃±2℃,RH75%±5%）under the condition of preservation at 6 consecutive months and three batches of samples at room temperature natural（T=14～28℃,RH=40%～70%）conditions keep at 6 months,this product character,identification,content determination and moisture,particle size,loading difference,microbiology examination of the product were tested,and there was no significant change in each index during the testing period,indicating that Xuefu Zhuyu granules were stable within the inspection period.Conclusion:Taking the retention rate of multiple components as the index,this project screened and optimized the technological parameters of decoction,concentration,drying and molding of Xuefu Zhuyu granules.The retention rate of the above components was tracked in each process step of the pilot test.It shows that the optimized technological parameters are reasonable and the quality of the preparation is controllable.This study prepared xuefuzhuyu granules consistent with the dosage and usage of the original prescription in clinical decoction,and the daily intake of pharmacodynamic components was also similar to that of decoction.The above studies are beneficial to preserve the efficacy of Xuefu Zhuyu prescription,provide scientific basis for the production of Xuefu Zhuyu granules,and also provide reference for the development of new TCM compound drugs,classic TCM prescriptions or clinical experience formulations. |
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