New Dogskin Plaster Pharmacy

Objective:To transform the traditional black Goupi plaster to the new dosage form of Goupi patch.Study onThe possibility of replacing Radix aconiti praeparata and Radix aconite kusnezoffii praeparata with Radix aconiti and Radix aconiti kusnezoffi,the extraction technology,the manufacturing technology,the quality standards and preliminary stable property,the release rate and the percutaneous absorption for Goupi Patch would be researched to thar the foundation for the twice development of the Goupi plaster would be established.Methods:1,The research on the extraction technology:①The mount of extracts and content of whole alkaloid extracted were regarded as the index observed to optimize the technology of ethanol percolation extraction for Radix aconiti and Radix aconiti kusnezoffi,in which four influence factors such as ethanol density,amount of ethanol, time for soakage and percolation speed were considered and the L₉(3⁴)table was used. The mount of extracts and content of whole alkaloid extracted were regarded as the index observed to optimize the technology of ethanol circumfluence extraction for Radix aconiti and Radix aconiti kusnezoffi,in which 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.②The mount of extracts and content of whole alkaloid extracted were regarded as the index observed to optimize the technology of ethanol percolation extraction for the medicinal materials in prescription of Goupi patch,in which four influence factors such as ethanol density, amount of ethanol,time for soakage and percolation speed were considered and the L₉(3⁴)table was used.③The volume of volatile oil extracted by distillation method was regarded as the index observed to optimize the extraction process of the volatile oil for the medicinal materials such as Rhizome et radix notopterygii,Radix saposhnikoviae ect in prescription of Goupi patch,in which three influence factors such as time of soakage,amount of water and time of extraction were considered and the L₉(3⁴)table was used.2,The study of the manufacturing technology for Goupi Patch and cataplasmata: According to the preliminary test,the matrixes and the range of their dosages were selected to optimize manufacturing technology for Goupi Patch by L₁₆(4⁵)orthogonal design,in which the adhesion strength,degree of softness were regared as indexes and optimized the procedures of the cataplasmata by L₉(3⁴)orthogonal design,in which the adhesive ability and appearance were regared as indexes.3,The study of the quality standards and preliminary stable property:Radix aconiti,Radix aconite kusnezoffii,Radix et rhizome rhei,Rhizoma atractylodis,Caulis sinomenii,Herba ephedrae,Radix angelicae sinensis,Rhizoma chuanxiong,Radix Paeoniae rubra,libanotus in the patch preparation were identified by TLC.The content of whole alkaloid was determinated by acid-base titration and the content of estertype alkaloid was determinated by UV.The content of ephedrine hydrochloride in Goupi Patch was determined by HPLC.The chromatography conditions were that ZORBAX TC-C18(4.6mm×250mm,5μm)column was used,that mobile phase was composed of methanol-1%phosphoric acid(5:95),that flow rate was 1ml·min^-1,with UV detection at 207nm and that the column temperature was 25℃.The extraction,adhesive ability,heat resisting property and weight variation were determined.The preliminary stable property was studied with the investigation items such as characteristics,identification and the content of ephedrine hydrochloride4,The study of the release rate and the percutaneous absorption:The experiments on the released rate and the percutaneous absorption were done by the equipment of release and percutaneous absorption.The contents of ephedrine hydrochloride released and percutaneous absorbed from Goupi Patch were determined by HPLC.Results:1,The optimum extraction technologies were as follows:①The optimum technology of ethanol percolation extraction for Radix aconiti and Radix aconite kusnezoffi was that the medicinal materials was soaked with 55%alcohol for 36h, then were percolated with 12 times amount of 55%alcohol,and the percolate speed was 0.9ml/min.The optimum technology of ethanol reflux extraction for Radix aconiti and Radix aconiti kusnezoffi was that the medicinal materials was extracted 3 times with 6-fold of 85%alcohol,2 hour for the first time and then 1 hour next two times.The percolation method was better than the reflux method.②The optimum technology of ethanol percolation extraction for the medicinal materials in prescription of Goupi patch was that the medicinal materials was soaked with 55% alcohol for 24h,and then were percolated with 12 times amount of 55%alcohol and the percolate speed was 3ml/min.③The optimum technology of volatile oil extraction was that the medicinal materials were extracted for 6 hours with 10 times amount of water,no soaking.2,The optimum manufacturing technology for Goupi pacth was as follows:with extracts 2g,sodium dodecylsulfate(SDS)0.1g,glyceryl monostearate 2g,paraffin wax 1g,PANA 41g,glycerol 2g,gelatin 2g,vaseline 2g,the patch was prepared by melted method.The optimum ingredients of the matrix of the Goupi cataplasmata were: gelatin:CMCNa:PANA:D-glucitol:glycerol:PEG400:extractum=0.6:0.3: 1:2:4:0.4:1。3,The research of the quality standards:①The identification methods of the Radix aconiti,Radix aconite kusnezoffii,Radix et rhizome rhei,Rhizoma atractylodis, Caulis sinomenii,Herba ephedrae,Radix angelicae sinensis,Rhizoma chuanxiong, Radix Paeoniae rubra,libanotus in the patch preparation by TLC were simple,the spots on the TLC picture were clear.The average content of the whole alkaloid was 1.192%;The average content of the ester-type alkaloid was 0.02%,Study on the determination of ephedrine hydrochloride had shown that the liner rang was 0.04μg～0.4μg(r=0.9999),the precision(RSD)was 1.87%.The average recovery was 97.9% with RSD 1.38%,and the average content of the ephedrine hydrochloride was 0.0149%with RSD 1.68%.Study on the determination of dryobalanops camphor had shown that the liner rang was 1.0228μg～10.228μg(r=0.9995),the precision(RSD) was 1.638%.The average recovery was 96.9%with RSD 1.88%,and the average content of the dryobalanops camphor was 0.2982%with RSD 0.69%.Study on the determination of camphor had shown that the liner rang was 0.483μg～4.83μg (r=0.9993),the precision(RSD)was 1.629%.The average recovery was 96.5%with RSD 0.78%,and the average content of the camphor was 1.095%with RSD 0.90%. The content of the extraction,the adhesive ability,the heat resisting property and the weight variation of the patch preparation were right to the regulation.②Consequence of the preliminary stable property:There is no marked change with all detect item.4,The release rate of the ephedrine hydrochloride from Goupi patch in the water was 22.31%in 180 minutes and the cumulative permeation rate within 36 hours was 19.11%respectively.Conclusions:The new Goupi patch has more excellence than Goupi plaster.Such as,the compounds extracted are much more with optimum process;it is easy to adhere on skin and to remove from skin;it has good compatibility;the compounds in it are easy to be released and to permeation into skin;there is no lead in it and it has no skin sensitization;the condition that there was no TLC or determination for Goupi plaster is changed.Meanwhile,with Radix aconiti praeparata and Radix aconite kusnezoffii praeparata to substitute Radix aconiti and Radix aconiti kusnezoffi,the new preparation is more efficacious and safe.It is a firm foundation for the deep development of Goupi plaster.