Research On The Preparation Process And Quality Standard Of Tibetan Medicine Xiaoer Qingre Granules

Objective:The classic prescription of Tibetan medicine "Xiaoer Qingre Decoction" comes from the "Tibetan Medicine Supplement",which is used to treat pediatric cold and influenza.It is recorded in ancient books as a decolorization,which has some shortcomings such as large dosage,easy mildew,inconvenient carrying,inaccurate quantitative measurement,poor taste and poor compliance in children.On the basis of scientific control of the quality of medicinal materials,this topic uses modern medical technology to develop " Xiaoer Qingre Decoction " into orthopedic taste granule,investigate the extraction,concentration and particle forming process,and establish the quality control method of intermediates and finished products,so as to provide reference for the development of classic prescription products and mass production.Methods:1.On the basis of the research on the origin and producing regions of the Tibetan medicinal materials of Aconitum Naviculare,Bergeniae Rhizoma and Solms Laubachia,the quality of the seven medicinal materials in the prescription were examined,and the influence of electron accelerator irradiation on the sterilization effect and active ingredients of the two medicinal materials of Carthami Flos and Bergeniae Rhizoma were investigated.2.The effect of sugar on extraction was investigated with hydroxysafflor yellow A(HSYA)and kaempferol content as indicators;orthogonal test was designed to optimize the water extraction process with the yield of dry extract,the yield of ethyl acetate extract and the HSYA transfer rate as indicators;the concentration method and temperature were also investigated.3.The compatibility of raw and auxiliary materials was investigated;the types and amounts of fillers and adhesives were investigated with the particle forming rate,angle of repose,moisture absorption percentage and melting time as the inspection indexes;the flavor correction agent and aromatic agent were investigated by fuzzy mathematics comprehensive evaluation method;HSYA content,total flavonoid content and water content were used as indicators to investigate the drying mode,drying temperature and time of granules;and the hygroscopicity and critical relative humidity of the particles were also investigated.4.On the study of the quality standard,Carthami Flos,Bergeniae Rhizoma,Solms Laubachia and Licorice Extract in Xiaoer Qingre Granules were qualitatively identified by thin-layer chromatography(TLC);HSYA content was determined by high performance liquid chromatography(HPLC);the content of total flavonoids was determined by UV-Vis spectrophotometer;the particle size,solubility and content uniformity were determined according to the Chinese Pharmacopoeia 2020.Results:1.Through literature research and combined with the opinions of Tibetan medicine experts,it is determined that the origin of Aconitum Naviculare is the dry whole grass of the Ranunculaceae plant Aconitum naviculare(Bruhl.)Stapf,the origin of Bergeniae Rhizoma is the dry root and rhizome of the Saxifragaceae plant Bergenia purpurascens(Hook.f.et Thoms.)Engl.,and the origin of Solms Laubachia is the dry root and rhizome of the Cruciferae plant Pegaeophyton scapiflorum(Hook.f.et Thoms.)Marq.et Shaw.All the seven medicinal materials in the prescription meet the Chinese Pharmacopoeia 2020 or local relevant standards.There were no significant change in the properties of Carthami Flos and Bergeniae Rhizoma powder and water extract before and after irradiation.There were no obvious change in the microscopic characteristics,TLC and content of Carthami Flos and Bergeniae Rhizoma powder before and after irradiation(P>0.05).But there were significant difference in the content of water extracts of Carthami Flos and Bergeniae Rhizoma before and after irradiation(P<0.05).The number of bacterial colonies and the total number of mold and yeast colonies decreased significantly(P<0.05).When the irradiation dose reached 10 k Gy,the total number of bacteria,molds,yeasts and coliforms in the powder and water extract of Carthami Flos and Bergeniae Rhizoma meet the standards specified in the pharmacopoeia 2020.2.Sugar had no effect on extraction.The optimal water extraction process of Xiaoer Qingre Granules was to add 12 times of water for 3 times,0.5h each time.The optimum concentration process was 0.09 Mpa and reduced pressure concentration at 80℃ until the relative density of the thick extract reached 1.05～1.10(20℃).3.Dextrin and polyvinylpyrrolidone K30(PVP K30)were selected as filling agents,and sucralose and sweet orange essence were used as flavoring agents and fragrances.They were mixed with thick extract and cultured cow bezoar in vitro to make soft materials,granulated through 10 mesh sieve,dried under reduced pressure at 80℃ for 1h,whole grain,and divided in 6 g per bag.4.The ingredients of Carthami Flos,Bergeniae Rhizoma,Solms Laubachia and Licorice Extract in the granules can be qualitatively identified by TLC without negative interference;the content of HSYA was linear in the range of 7.77～194.18 μg/m L,the correlation coefficient was 1.0000,the average recovery rate was 99.99%,and the RSD was 2.12%(n=6).The content of total flavonoids determined by UV-Vis spectrophotometer was linear in the range of 0～46.16 μg/m L,the correlation coefficient was 0.9998,the average recovery rate was 96.61%,and the RSD was 1.50%(n=6).The particle size,water content,solubility and content uniformity all comply with the requirements of pharmacopoeia.Conclusion:The original medicinal materials of Carthami Flos and Bergeniae Rhizoma are suitable for electron accelerator irradiation sterilization,but the water extracts of Carthami Flos and Bergeniae Rhizoma are not suitable.The extraction,concentration and molding process of Xiaoer Qingre Granules are stable and feasible.And the draft quality standard can effectively control the quality of Xiaoer Qingre Granules.