Study On Preparation Technology Of Tongfengqing Plaster And Its Percutaneous Penetration In Vitro

This subject comes from the Scientific Research Fund Project of Education Department of Yunnan Province"Tongfengqing Babu preparations research"（No.2015Y318）,which aimed to combine with the characteristics of transdermal drug delivery,reform the prescription of traditional Chinese medicine“Tongfengqing Lotion”into a gel paster and an experimental study on the preparation technology and the quality control method of Tongfengqing Plaster were conducted systematically,then the percutaneous penetration in vitro was investigated.The content of matrine and oxymatrine in Tongfengqing Plaster was determined by HPLC and the quality control method was established.This paper provide experimental basis and technical support for improving the dosage form and enhancing the curative effect,and lay the foundation for clinical application of TongFengqing Plaster.1 Study on preparation processWater extraction technology:The contents of matrine and oxymatrine in water extract were taken as indexes,the amount of water,extraction time and extraction times of the water extraction technology were investigated,and orthogonal test was used to optimize the extraction conditions.Result showed the optimum conditions for water extraction were as follows:10 timesof water,decocting 1 times,and 90minutes for each times.Alcohol precipitation technology:The contents of matrine and oxymatrine was taken as indexes.Orthogonal test was used to investigate the extraction parameters,including density of the extract,alcohol concentration and alcohol precipitation time,and optimize the conditions of water extraction.Result showed the optimum conditions of alcohol precipitation were as follows:the density of water extract was1.20,the concentration of alcohol was 70%,and the static timeof precipitation was 24hours.The preparation process:Based on the pre-experiment,the initial viscosity and sensory evaluation scores were taken as the indexes,the substrate ratio of Tongfengqing Plaster were optimized by orthogonal test method to determine th e optimal preparation conditions.The optimal medium was:PVPK30:CMC-Na:Carbomer934:Dihydroxyaluminum Aminoacetate:NP700:Kaolin:Glycerol=1.5:1.5:0.1:0.1:1:0.8:2,and the content of extract was 40.5%.2 Research on quality control methodTLC qualitative study:the TLC method was used to identify the 3 kinds of medicinal material,Radix Sophorae,Rhizoma Polygoni Cuspidati and Cortex Phellodendri,in Tongfengqing Plaster.The result showed that in the chromatogram of the tested products,the spots of the same color were found in the corresponding positions of the control herbs or the reference substance,while the negative control was not interfered in the corresponding positions.Study on the determination of the content of matrine and oxymatrine:The content of matrine and oxymatrine in Tongfengqing Plaster werdetermined by HPLC method.Amino bonded silica was used as filler,the mobile phase was acetonitrile-anhydrous ethanol-2%phosphoric acid（75:12.5:12.5,v/v）with 1.0ml·min^-11 of flow rate and 220nm of the detection wavelength,the sample volume was10μl,the column temperature was 30℃.The results show that the method was reasonable and feasible and had good reproducibility.It can be used in the quality control of Tongfengqing Plaster.3 Study on transdermal permeation in vitroThe Franz diffusion pool method was used to detect the permeability and release of matrine and oxymatrine by HPLC method,and the cumulative permeability of the total alkaloid of Radix Sophorae was expressed by the sum of the cumulative permeability of the two.The results showed that matrine and oxymatrine in Tongfengqing Plaster prepared by the optimum preparation process could penetrate the skin of mice,and the average cumulative permeability of 12h(Q₁₂,mg.cm^-2)was0.7660,and the average cumulative permeability of 8h(Q₈,mg.cm^-2)was 0.7471,and the average transdermal rate of 8h(J_ss,mg.cm^-2.h^-1)was 0.3480.After adding azone,the average cumulative permeability of 12h(Q₁₂,mg.cm^-2)was 0.8106,and the average cumulative permeability of 8h(Q₈,mg.cm^-2)was 0.7904,and the average transdermal rate of 8h(J_ss,mg.cm^-2.h^-1)was 0.3498,and the enhancement ratio（ER）of 8h was 1.005.By t test,the cumulative permeability of matrine and oxymatrine in azone paste group was significantly higher than that of matrine and oxymatrine（p<0.05）in the addition of Azone paste group at 0.5h,1h and 4h.It is suggested that azone can accelerate the percutaneous penetration of the main components.It shows that the optimized preparation process of matrine and oxymatrine can penetrate the skin of mice,and the addition of 5%azone can obviously improve the transdermal permeation of the total alkaloid of Sophora flavescens,and the gel plaster is well made.It can be used for the next Tongfengqing Lotion agent to be changed into gel paste and provide some technical support in clinical practice.