Study On Dosage Form Reform Of Gutongyu Ointments

Objective:To reform Gutongyu vaseline ointment dosage,systematical research would be carried out and the reseach content include: extraction technology,preparation technology,quality criteria, preliminary pharmacodynamics and ex-vivo skin permeation absorption.One kind of Gutongyu cataplasma,which demand that its physical properties is stable,adhesion to skin is good,amount of remaining on the polyethylene membrane is small,application is comfortable and manufacture is simple,was attempted to develop. All work would lay the groundwork for the further development of Gutongyu vaseline ointment dosage.Methods:1 The extraction technology research:â‘ The amount of extract and content of imperatorin extracted were regarded as the evaluating index,and orthogonal design experiment was used to optimize the ethanol percolation extraction technology of Herba Lycopi and Radix Angeiicae Dahuricae,in which table L₉(3⁴) was used and the concentration of alcohol,the volume of solvent,the percolating speed and the time of soaking were selected as affected factors.â‘¡The amount of volatile oil extracted by distillation method was regarded as the index to optimize the extraction technology of the volatile oil for Flos Caryophylli,Pericarpium Zanthoxyli and Kadsura Root-bark by L₉(3⁴) orthogonal design experiment,in which four influence factors such as amount of water,soaking time, particle size and extraction time were selected.2 The preparation technology research:base on the results of both the kinds and the dosages range of excipients,which were determined in preliminary test,prelimilary adhesion and amount remained on the polyethylene membrane were selected as the evaluating index to optimize the proportion of the matrixes of two kinds of cataplasma by L₁₆(4⁵) and L₁₈(3⁷) orthogonal design experiments,in which two methods of Crosslinking and non-Crosslinking were used.Besides,two kinds of cataplasma were compared in the ways of adhesion,degree of comfort and stability etc.3 The quality standard research:The Kadsura Root-bark,Herba Lycopi and Radix Angeiicae Dahuricae in the Gutongyu cataplasma were identified by TLC.According to relative regulation in China Pharmacopoeia,amount of extract,adhesive ability,weight difference,bestows on the shape and heat resisting property were detected.The content of imperatorin in the Gutongyu cataplasma was detected by HPLC,in which the chromatography conditions were that the Agilent ZORBAX SB-C18(4.6mm×250mm,5μm) column was used,that the mobile phase was composed of methanol-water(55:45),that the flow rate was 1.0mL·min^-1,that the wavelength of detection was 300 nanometer and the column temperature was 30℃.4 the ex-vivo skin permeation rate research:modified Franz permeating pool was used to carry out the experiment upon the Mus musculus albus,in which 70%ethanol and physiological saline were chosen as accepting medium respectively.The content of imperatorin was detected by HPLC and the cumulative ex-vivo skin permeation rates of imperatorin were calculated.The ex-vivo permeation effects of two accepting mediums were compared.5 The preliminary pharmacodynamics research:abnormality of haemodynamics right lower extremity of rabbit was caused by hypodesising right lateral thigh veins and inferior gluteal veins, and then the analogue of Right knee osteoarthritis was formed. Intraosseous pressure and index of hemorheology such as whole blood viscosity,plasma viscosity,volume packed cells ect.were chosen and detected as the evaluating index.Results:1 The optimum technology of ethanol percolation extraction for Herba Lycopi and Radix Angeiicae Dahuricae was that the powder of medicinal materials was soaked with 90%alcohol for 12h,then was percolated with 20 times amount of 90%alcohol and the percolating speed was 7ml·min^-1·kg^-1.The optimium extraction technology of volatile oil for Flos Caryophylli,Pericarpium Zanthoxyli and Kadsura Root-barkwas that the thirty screen mesh powder of medicinal materials was extracted with 8 times of water for 5 hours continuously by distillation method.The rate of volatile oil extracted was 5.15%.2 The optimum preparation technology for Gutongyu non-Crosslinking cataplasma was that the proportion of the matrix was that CMC-Na:Gelatin:PAAS:PVPK-30:D-sorbierite:Glycerine: PEG-400:Azone was equal to 2:2:0.3:2:1.5:5:1:0.73,and the extract accounted for 25%.The optimum preparation technology for Gutongyu Crosslinking cataplasma was that the proportion of the matrix was that PAAS:Glycerin:Citric acid:Aluminum hydroxide:Azone was equal to 1.25:4:0.26:0.12:0.28,and the extract accounted for 20%.Research,by contrast,had shown that adhersion of Crosslinking cataplasma was strong,its physical properties was stable and application was comfortable,but those of non-crosslinking cataplasma were just general.3 The TLC methods of Kadsura Root-bark,Herba Lycopi and Radix Angeiicae Dahuricae in the crosslinking cataplasma was simple and the spots on the TLC pictures were clear and the negative contrast was not disturbed.The amount of extract,preliminary adhesion and weight difference,bestows on the shape and heat resisting property of crosslinking cataplasma were accord with the regulation of China Pharmacopoeia.The detection of imperatorin had shown that the linear rang of its concentration was 0.0406μg～0.406μg(r=0.9999),that the precision(RSD) was 1.11%,that the reproducibility experiment indicated that the average content of imperatorin in the cataplasma was 0.3888mg per patch and the RSD was 1.17%,that the average recovery was 99.96%and the RSD was 2.77%.The content of imperatorin in three batches of cataplasma were 1.438mg,1.408mg and 1.446mg per patch respectively.4 the ex-vivo skin permeation rate research had shown that the cumulative permeation rate of non-crosslinking and crosslinking cataplasma within 48 hours was 5.54%and 3.96%respectively when physiologic saline was chosen as accepting medium and the cumulative permeation rate of crosslinking cataplasma was higher than that of non-crosslinking cataplasma.Besides the skin cumulative permeation rate of crosslinking cataplasma was 70.06%,which was lower than 83.71%of non-crosslinking cataplasma,When 70%ethanol was chosen as accepting medium.5 The preliminary pharmacodynamics experiment had shown that Gutongyu cataplasma could reduce intraosseous pressure and amended the error state of marrow hemorheology when the intraosseous pressure was high.The pharmacodynamics of Gutongyu cataplasma is almost as same as Tongluoqutong plaster.Conclusions:Gutongyu crosslinking cataplasma,which had been developed,was that its physical properties was stable,adhesion to skin was good, amount of remaining on the polyethylene membrane was small,skin permeation rate was high,application was comfortable and preparation method was simple.Through the research on extraction technology,preparation technology,quality standards,ex-vivo skin permeation rate,a good foundation had been laid for the further development of Gutongyu cataplasma.