Pharmaceutical And Preliminary Pharmacokinetics Research On Antipyretic Suppository

The Antipyretic Suppository consists of Bubalus bubalis Linnaeus,Bupleurum chinense,Notopterygium incisum Ting and other herbs.This prescription has a good effect in treating infantile fever.In order to solve Children’s medication difficulties,modern extraction,purification techniques were adopted to change the traditional dosage forms and route of this administration and preparation it to suppository.The literature research,extraction technology research,preparation technology research,.quality standards,stability studies and pharmacokinetic study were contained of this paper to design the prescription,provide scientific basis for it’s futuer development and utilization.1 The literature researchLiterature research summarizes the pathogenesis of infantile fever and the treatment of traditional Chinese medicine,explain the purpose and basis of the study.At the same time,we sum up the physical and chemical properties and pharmacological action of the Suppository in the prescription,in order to lay a solid foundation for the philosophy of design.2 Preparation technology research(1)With yield of water extract and contents of nitrogen as the evaluating index,orthogonal experiment was adopted to investigate the amount of water,times on extraction process and extraction time.The optimum preparation extraction conditions were added 14 times of water,extraction of 3 times and 8.0 h each time.(2)With the amount of volatile oil as the evaluating index,orthogonal design was used to optimize Crushing strength,water ratio,extraction time,soaking time which influenced the results of extraction.The optimum conditions were as follows:soak medicinal materials for 1h directly,add 10 times water and extract 5 h.(3)With composite score of contens of sailkosaponins,Isoimperatorin,obacunone and fraxinellone as index,rthogonal experient was adopted to investigate the effects of the amount of ethanol,ethanol concentration,times on extraction process and extraction time of Antipyretic Suppository.The optimum preparation extraction conditions for medicine residues were added 8 times of the amount of 80%ethanol,extraction of 3 times and 1.0 h each time.(4)With the index of each composition containing as indexes,screening the rationality of(5)the reduced pressure concentration and atmospheric concentrations,the ideal concentration is stress concentration when the temperature was 75℃.(6)With characteristic components and the rate of impurity as comprehensive evaluation indexes,three factors(relative density of extract,the amount of extraction solvent and extraction times)that influenced the results of purification experiment was studied and explored by uniform design method.The optimum purification conditions were as follows:keep the relative density of the extract is 1.18(60℃),added 1 times the amount of water saturation n-butyl and extracted 5 times.(7)With the index of each composition containing as comprehensive indexes,enrichment process was evaluated.The optimum purification conditions were:add 0.5 times the volume of water in the solution of n-butyl alcohol,then stress concentration and recovery of n-butyl alcohol when the temperature was 75℃.With characteristic components and the water content,single factor experiment was adopted to investigate time,temperature and the relative density of concrete,The optimum drying process conditions were:extract relative density was 1.25(60℃),drying for 24 hours when the temperature was 75℃.3 Moulding techniques researchWith composite score of external appearance and the vitro release,rthogonal experiment was adopted to investigate the formulation of Antipyretic Suppository.The optimum technology of the Antipyretic Suppository was as follows:the ratio of Powder to substrate is 1:4,the content of polysorhate-80 is 1.5%,the ratio of Lanolin to mixed fatty acid ester is 1:10,the bath temperature at 50℃ and the stripping time is 15 min.4 Quality standards researchIn order to make the quality of Antipyretic Suppository controllable,the quantitativa and qualitative inspection were carried out of the three batch of product.TLC was used in qualitative study and finally we established the qualitative methods.Then UV and HPLC methods was used for the determination of the content of obacunone,fraxinellone,saikosaponins and Isoimperatorin,content determination method were established and developed the quality standard.5 Stability researchWith reference to the quality standards that established by this study,preliminary stability of 3 batches of samples of Antipyretic Suppository was evaluated.the results shows that compound suppository fever is basically stable under the condition of simulated clinical use packaging.6 Preliminary Pharmacokinetics researchIn order to study pharmacokinetics characteristics by different ways of administration,the rabbits was given Antipyretic Suppository by rectum and oral administration,then sampling their blood regularly,LC-MS was adopted to determining the content of components in blood plasma.According to preliminary results,Saikosaponin a and Isoimperatorin were selected as the testing indexes,then we calculating the pharmacokinetic parameters of related on the basis of blood drug concentration.The result shows that the pharmacokinetic characteristics of compound Antipyretic Suppository for rectal administration group than oral administration set peak time is short,and has higher maximum plasma concentration.