Research On Preparation Technology And Quality Standard Of XianQian Granules

Objective:Xianqian decoction is a clinical experience prescription for treating acute superficial thrombophlebitis of lower extremity used in Shanghai Integrated Traditional Chinese and Western medicine hospital.The prescription consists of six herbs including Agrimonia pilosa and Rubia cordifolia,etc.This project intends to develop Xianqian granules（XQG）based on the principles from"Guidelines for Research on New Chinese Medicines"by studing its preparation technology and establish a reasonable preparation quality standard,in order to provide a scientific basis for the clinical efficacy and safety of medicine porducts.Methods:Taking paeoniflorin transfer rate and extract rate as evaluation indexes,the extraction process parameters of Xianqian decoction were determined on the basis of single factor test and orthogonal test.Compare the effects of alcohol precipitation method,centrifugal method and flocculation method on the transfer rate of paeoniflorin and the yield of ointment,determine the purification method of XQG,and investigate the relevant parameters of the purification process.Using dry powder properties,paeoniflorin transfer rate,yield,water content,etc.as evaluation indicators,compare the effects of drying methods on extract powder,and determine the drying process.In the process of granule preparation,the soft material condition,granulation difficulty,granule forming rate,melting ability,etc.are used as evaluation indicators to investigate the granulation method,the types of excipients,the amount of excipients,the concentration and amount of wetting agent,etc.,to determine the formulation forming process.On this basis,a pilot scale-up study was carried out to further optimize the process parameters.Thin layer chromatography（TLC）was used to identify Radix rubiae,radix paeoniae rubra,cortex moutan and Panax notoginseng in XQG.The sample size,plate type,chromatographic temperature and humidity were investigated to establish TLC identification method.HPLC was used to determine the content of hydroxy-lizarin and paeoniflorin in XQG.The linear relationship,precision,specificity,repeatability and recovery rate were investigated.The HPLC fingerprint of XQG was established by HPLC.Results:The preparation process of XQG was as follows:except Panax notoginseng,five herbs were decocted together,soaked in 10 times of water for 30 min,decocted three times,1.0 h each time.The filtrate was concentrated at 60℃to 1.135～1.140（60℃）.Add 95%ethanol and adjust the alcohol content to 60%.After 12 h at 4℃,the filtrate was filtered and concentrated at 55℃to a relative density of 1.280～1.310（60℃）,and then dried in vacuum at 60℃to obtain dry extract.Smash Panax notoginseng and dry extract,pass through 120 mesh sieve.Add 45%of the total amount of particles（dextrin:sugar:4:1）,mix well,use 75%ethanol as wetting agent,make soft material,extrude and granulate,vacuum dry at 70℃,package the whole particles in different doses（10 g/bag）.The particle size of the pilot productwas 3.55%,the moisture content was 5.17%,the difference of loading capacity and solubility were in line with the relevant provisions of the 2015 edition of the Chinese Pharmacopoeia.The TLC identification method of Rubia cordifolia,radix paeoniae rubra,cortex moutan and Panax notoginseng was established.The spots were clear and the negative samples had no interference.HPLC was used to determine the contents of Hydroxylizarin and Paeoniflorin,which were 1.44 mg/bag and 117.9 mg/bag;and the fingerprint of XQG was established,which identified paeoniflorin,paeoniflorin,Notoginsenoside R₁,Ginsenoside Rg₁,ginsenoside Rb₁ and rubicin,providing data support for further improving the quality standard of XQG and the stability between batches.Conclusion:The preparation technology of XQG was obtained and its quality standard draft was established in this thesis,which will improve the effectiveness and quality controllability of Xianqianfang and lay a foundation for its further development and new Chinese medicine.