The Pharmaceutical Research Of The Qinzhu Tongjing Patch

Objective:To reform the Qinzhu Pill from its traditional preparation to Patch,which can be adhered on the skin to treat dysmenorrheal, and study on its extractive processing,technology of preparation, quality standards,release rate,in vitro percutaneous absorption and stability tests,etc,so as to establish the foundation for Qinzhu Tongjing Patch.Methods:1 Preliminary pharmacodynamics experiment:The isolated uteruses of small white mouse get by regular method as well as the BL-420 Biological Functional System were adopted to observe the effects of the extracts of the medicinal materials extracted by different extraction technologies.2 Study on the extraction technology:The contents ofwogonin and baicalin,which were regarded as the indexs of the chemical compositions extracted,were determined by NPLC.The content data determined were used to optimize the ethanol extraction process by orthogonal design experiment.In the experiment four influence factors such as the concentration of alcohol,the volume of solvent, the percolating speed and the time of soaking were considered and the L₉(3⁴) table was used.The amount of volatile oil extracted from atractylodes by distillation method was regarded as the index of chemical compositions extracted to optimize the extraction process of atractylodes by orthogonal design experiment.In the experiment three influence factors such as amount of water,soaking time and extraction time were considered and the L₉(3⁴) table was used.3 Study on the manufacturing technology:Base on the results of the literature consulting and experiment,the kinds and the use range of matrixes were determined for Qinzhu Patch and cataplasma respectively.The manufacturing technology for the patch was optimized by L₉(3⁴) orthogonal design by determinating the adhesion and scoring synthetically on some other aspects such as the smoothness,glossiness,uniformity,degree of softness,quantity of remains on skin and permeability of back lining of the patchs together as index.The procedure of the Qinzhu cataplasmata was optimized by L₉(3⁴) orthogonal design with the adhesion and scoring synthetically on some other aspects such as appearance,layer residue,spreading capability.4 The study on the quality standards for the preparation:The baikal skullcap root in the patch preparation were identified by TLC.The content of wogonin in the patch preparation was determined by HPLC.The chromatography conditions were that the Agilent ZORBAX SB-C18(4.6mm×250mm,5μm) column was used;that mobile phase was composed of methanol -0.1%phosphoric acid solution(58:42);the flow rate was 1mL·min^-1 with UV detection at 278nm and that the column temperature was 25℃.The adhesive ability and weight variation of the preparation were tested according to the method described for adhesive ointment in 2005 China pharmacopeia below the relative volumns of appendixâ… â… .5 The study of the release rate and the in vitro percutaneous absorption:Releasing installment and Franz permeating pull were used respectivelly to carry out the relative experiments.The content of wogonin of both released and percutaneous absorbed from Qinzhu Tongjing Patch and cataplasmata were determined by HPLC.6 The influencing factors test for the preparation:The Qinzhu Tongjing Patch was placed under high temperature and high humidity Environment.The influencing factors stable property was studied with the investigation items such as characteristics, identification,adhesive ability,the content of wogonin.Results:1 The preliminary pharmacodynamics tests had shown that co-extractive of the baikal skullcap root and atractylodes could reduce the contortion frequency caused by pituitrin,oxytocin or cloprostenol in model mouse.And the result of the test also showed that the extract has obvious inhibitory effect on the exciting shrinkage of isolated uterus in model mouse.2 The optimum ethanol extraction technology of both baikal skullcap root and atractylodes rhizome was that the medicinal materials were soaked with 70%alcohol,then was percolated with 15 times amount of 70%alcohol and the percolating speed was 15ml·min^-1·kg^-1.The optimium volatile oil extraction technology for atractylodes rhizome was that the coarse powder was soaked for 2 hours and then extracted with 6 times of water for 3 hours continuously.3 The optimum manufacturing technology for Qinzhu Tongjing Patch was that the patch was prepared by the melted method and the matrix was made 2 parts of PAANA,2 parts of glycerel monostearte, 0.25 parts of sodium lauryl sulfate,0.25 parts of microcrystalline cellulose and 1.125 parts of extractive.The optimum ingredients of the matrix of the cataplasmata were PAANA(1%):PVP K-30:gelatin: glycerol =4:4:3:4. 4 The quality standards for the preparation:The TLC identification method for baikal skullcap root in the patch preparation was simple and the spots on TLC pictures were clear. The determination had shown that the linear rang of the concengtration of wogonin was 0.0148μg～0.148μg(r=0.9999);that the precision test indicated that RSD was equal to 1.26%;that the stability test indicated that RSD was equal to 1.72%;that the repeatability test indicated that the average content of wogonin in the patch was 0.1060%and the RSD was 1.87%;that the average recovery was 96.7%and the RSD was 1.01%and the content of wogonin in 3 batch of patches were 4.8455mg per patch,4.8169mg per patch and 4.8268mg per patch respectively.The adhesive capability and the weight variation of the patch preparation were accord with the regulation.5 The released rate and the in vitro percutaneous rate tests had shown that the content of wogonin released from Qinzhu Tongjing Patch was 9.82%in 100 minutes in water,and the cumulative rate in vitro permeation(white rat) was 15.71%in 48 hours and that the content of wogonin released from Qinzhu Cataplasmata in water was 99.79%in 100 minutes in water and the cumulative in vitro permeation(white rat) rate was 17.92%in 48 hours.6 The influencing factors test had showed that all results of the samples did not change markedly contrast to that of the samples before the test at 40℃.During the high humidity experiment,the absorbing humidity rate of samples without package was above 5% under the environment of relative humidity of 90%±5%,while the sample with package did not change evidently.Conclusions: The developed Qinzhu Tongjing Patch possesses satisfactory adhesive property to skin,good stability and low water content in matrix.Many research have been done in many different aspects, such as the preliminary pharmacodynamics,extraction technology, manufacturing technology,quality standards of the preparation, test of released rate and the cumulative permeation rate,the influencing facters research.All of these reseaches lay a good foundation for the further development of traditional Chinese medicine Qinzhu Tongjing Patch.