Compound Yuanhuzhitong Plaster Preparations

Objective:To develope a type of patch preparation for Fufang Yuanhu Zhitong patch,which is not only have a nice stability and a good adhesion to skin,but also low in water content.This preparation would be studied systematicly on its extraction technology,manufacturing technology, quality standards,release rate,vitro percutaneous absorption, preliminary stable property and preliminary experiment on pharmacodynamics.Methods:1 The research of the extraction technology:The content of tetrahydropalmatine in the monarch Rhizoma Corydalis,which was regarded as one of the indexs of the chemical compositions extracted,was determined by HPLC.The content data determined were used to optimize the ethanol extraction process of both Rhizoma Corydalis and Radix Angelicae Dahuricae by orthogonal design experiment.In the experiment four influence factors such as ethanol density,amount of ethanol,time for extraction and number of times for extraction were considered and the L₉(3⁴) table was used,and the craft of purifying the samples with neutral aluminum oxide column was inspected.The amount of volatile oil extracted from Fructus hmomi Rotundus by distillation method was regarded as the index of chemical compositions extracted to optimize the extraction process of Fructus Amomi Rotundus by or thogonal 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.2 The study on the manufacturing technology:Base on the results of the literature consulting and Pre-experiment,the kinds and the use range of matrixes were determined for Fufang Yuanhu Zhitong Patch and cataplasma respectively.The manufacturing technology for the patch was optimized by L₁₈(3⁷)orthogonal design by determinating the adhesion and scoring synthetically on some other aspects such as the smoothness,glossiness, degree of softness,uniformity,quantity of remains on skin and permeability of back lining of the patchs together as index.The procedure of the Fufang Yuanhu Zhitong cataplasmata was optimized by L⁹(3⁴) orthogonal design with the adhesive ability,spreading ability,appearance and layer residue as indexes.3 The study of the release rate and the vitro percutaneous absorption: Releasing installment and Franz permeating pull were used respectivelly to carry out the relative experiments.The content of tetrahydropalmatine of both released and percutaneous absorbed from Fufang Yuanhu Zhitong Patch and cataplasmata were determined by HPLC.4 The study on the quality standards:The Rhizoma Corydalis,Radix Angelicae Dahuricae and Fructus Amomi Rotundus in the patch preparation were identified by TLC.The content of tetrahydropalmatine 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 compond of methanol-0.1%phosphoric acid solution(adjust the pH to 6.0 with triethylamine)(64:36);the flow rate was 0.8mL.min^-1; with UV detection at 280nm and that the column temperature was 35℃.The adhesive ability and weight variation of the preparation were tested according to the method described for adhesive ointment in 2005 derision pharmacopeia below the ralative volumns of appendixâ… â… .5 The study on the preliminary stable property:The Fufang Yuanhu Zhitong Patch was placed under the conditions of 37℃and relative humidity of 75%for 3 months.The preliminary stable property was studied with the investigation items such as characteristics,identification and the content of extraction,adhesive ability,the content of tetrahydropalmatine. 6 The study of the preliminary pharmacodynamics:The analgesic effect of Fufang Yuanhu Zhitong Patch for dysmenorrhea was evaluated by ip oxytocin or cloprostenol to cause dysmenorrhea and incur contortion on rats as test model.Results:1 The optimum ethanol extraction technology of both Rhizoma Corydalis and Radix Angelicae Dahuricae was as follows:The medicinal materials was extracted for 3 times with 3 times amount of 75%ethanol and for 1.5 hours per time.The transfer rate of tetrahydropalmatine in the medical material was 82.7%.The craft of using alumina column to purify the samples is better than that of ether extraction in the process of assaying.The optimium volatile oil extraction technology for Fructus Amomi Rotundus was as follows:The coarse powder was soaked for 2 hours and then extracted with 10 times of water for 4 hours continuously.The rate of oil extracted was 5.23%.2 The optimum manufacturing technology for Fufang Yuanhu Zhitong Patch was that the patch was prepared by the melted method and the matrix was made of paraffin wax lg,stearic acid 8g,triethanolamine 3g,gelatin 2g,PAA(S)(70%)1.5g,glycerol 0.5g,sodium dodecyl sulphate(SDS)0.1g and extractive 3.2g.The optimum ingredients of the matrix of the cataplasmatawere gelatin:PAA(S)(70%):PVP K-30:glycerol =3:4:2:1.3 The released rate and the vitro percutaneous absorption:the content of tetrahydropalmatine released from Fufang Yuanhu Zhitong Patch in water was 24.28%and the cumulative vitro permeation(mouse)rate within 48 hours was 34.78%;the content of tetrahydropalmatine released from Fufang Yuanhu Zhitong Cataplasmata in water was 82.63%,and the cumulative vitro permeation(mouse)rate within 48 hours was 40.95%.4 The quality standards:The TLC identification methods for each medical material in the patch preparation were simple,and the spots on TLC pictures were clear.Study on determination had shown that the linear rang of the concengtration of tetrahydropalmatine was 0.1148μg～1.148μg(r=0.9999);that the precision test indicated that RSD was equal to 0.495%;that the repeatition test indicated that the average content of tetrahydropalmatine in the patch was 0.04431mg per patch and the RSD was 2.45%;that the average recovery was 97.995%and the RSD was 2.89%and that he content of tetrahydropalmatine in 3 batch of patches were 0.443mg per patch,0.378mg per patch and 0.381mg per patch respectively.The adhesive ability and the weight variation of the patch preparation were accord with the regulation.5 The accelerated preliminary stable property:all the detection indexes examined unchanged evidently.6 The preliminary pharmacodynamics:Fufang Yuanhu Zhitong Patch could reduce the contortion frequency caused by oxytocin or cloprostenol in model rats.And the result of the test also showed that the patch is more effective in therapying dysmenorrhea than the dosage form of Yuanhu Zhitong Tablet.Conclusions:The Fufang Yuanhu Zhitong Patch possesses good stability,super adhesive property to skin,and low water content in matrix.Many research have been done in many different aspects,such as extraction technology, manufacturing technology,quality standards of the preparation,test of released rate and the cumulative permeation rate,the accelerated preliminary stable property,and the preliminary pharmacodynamics.All of these reseaches lay a good foundation for the further development of new traditional Chinese medicine Fufang Yuanhu Zhitong Patch.