Study On The Preparation Technology And Quality Standard Of Wenluotong External Granule

Objective:The WenLuoTong(WLT)prescription is a clinical experienced prescripti on used for preventing and treating Chemotherapy-induced peripheral neuropathy(CI PN)which consists of Epimedium,Geranium wilfordii,Cassia Twig and Carthamus tinctorius.The prescription has been used as medical therapy for many years,whi ch works by warming and activating meridian,promoting blood circulation to remo ve blood stasis.It has tremendous potentials to be developed into new Chinese Pat ent Medicine.This study involves extraction process,forming process and quality st andard development.Methods:(1)Study on extraction technology.Four extraction routes were designed by medicial position and function of the 4 Chinese Materia Medica in WLT priscription and physicochemical properties of main effective components The optimal extraction process route was evaluated by FAHP based calculation according extracted rate of Icariin(ICA)and Hydroxysafflor Yellow A(HSYA),conbined with pharmacodynamic test and ratio of extraction.(2)Study on optimizing extraction parameter:Therein,the optimal extraction parameter of Epimedium et al.was optimized by Orthogonal test which regarded the content of icariin and yield rate(impurity control)as indexes.Similarly,the optimal extraction parameter of Carthamus tinctorius was optimized by Single Factor Experiment and Orthogonal test which regarded the content of HSYA and yield rate(impurity control)as indexes.(3)Study on optimizing Fluid-bed granulation parameter:Therein,the optimal Single factor experiments were used to choose diluent by mixing dextrin,starch,sucrose and lactin with dried extract respectively for 96 h under certain moisture conditions.The optimal amount of dextrin,concentration of PVP-K30,the tempreture of inlet-air,into-fluid velocity were gained by comparing different levels using pelleting status,shaping rate and moisture content of granule.(4)Study on quality standards:Firstly,establish the qualitative identification standard for WLT particle by developing TLC method for Epimedium,Geranium wilfordii,Cassia Twig and Carthamus tinctorius.Secondly,that the particle size,moisture content,dissolubility,content uniformity,arsenic salt and heavy metal(refer to plumbum there)content is tested.Finaly,HPLC method and methodological evaluation for icariin and HSYA are developed respectively.Results:(1)The optimal extraction route is that Carthamus tinctorius is extracted by warm maceration,Epimedium et al.circulated reflux with water and alcohol precipitated.(2)Ultimately,Carthamus tinctorius extraction process is as follows:adding 15 times amount of water and immerses at 60℃ for 2 times.(2.5 h per extraction)Concentrate under reduced pressure(-0.08～0.09 MPa,60℃).Epimedium et al extraction process is as following:adding 18 times amount of water at the first time,adding 14 times amount of water at second time.(circulated reflux 2 h per extraction).Then filter,concentrate under reduced pressure(-0.08～0.09 MPa,80℃)to get a 1.05～1.10(60℃)relative density.Then add 95%alcohol to 70%Alcohol content,keep in cold storage.After 12 hours,filter,recover alcohol,concentrate,mixed with Carthamus tinctorius concentrated solution,continue to concentrate to a 1.15～1.20(60℃)relative density.(3)96 h Moisture absorption test showed that choose dextrin as diluent.Pelletize status showed that the optimal dosage rate=1:1.Choose 2.5%Polyvinylpyrrolidone(PVP-K30)as adhesive,which holds 6%percentage of total amount.The optimal Inlet air temperature is 80℃,the Into the fluid velocity is 120 r/min,the drying time is 4 h under 55℃.(4)The TLC results showed that there exists negative interference in thin layer chromatography of Geranium wilfordii.For other 3 medicinein in WLT priscription,spots are clear in every particular thin layer chromatography.Secondly,that the particle size,moisture content,dissolubility,content uniformity,arsenic salt and heavy metal(refer to plumbum there)content is tested,which met the demands for particle of Chinese pharmacopoeia(Version.2015).Finaly,HPLC method and methodological evaluation for icariin and HSYA are developed respectively.The consequences indicated that the peak area of icariin and the concentration of the sample had good linear relationship in 23.060μg/mL～307.472 μg/mL,and the regression equation was y=23852x-10338(r2=0.9999).Other items are also qualified.Also,the peak area of HSYA and the concentration of the sample had good linear relationship in 16.83 μg/mL～269.27 μg/mL,and the regression equation was y=32525x-205335(r2=0.9991).Other items are also qualified.In conclusion,all studies above indicated that the preparation technology of WLT partitle is reasonable and feasible,and the quality standards are scientific and can be useful for quality control for WLT external particle.