Study On The Preparation Technology And Evaluation Of Antipyretic Gel Paste In Children

Objective:The clinical experiential pediatrics antipyretic external prescription is developed into Xiaoertuire cataplasm based on the theory of traditional Chinese medical external treatment, expected to play double efficacy of both Chinese medical defervescence and physical cooling. The extraction technology of the prescription isoptimized while the release and transdermal absorption properties in vitro is investigated. Furthermore, the pharmacodynamics and the safety of Xiaoertuire cataplasm is evaluated. The research in this thesis will be helpful in developing more effective, safe and easily acceptableexternalChinesemedicine compound preparationfor exogenous fever in children.Methods:(1) Study on the extraction technology of Xiaoertuire Cataplasm:① By single factor and orthogonal test, the extraction technology of Bupleurum chinense DC. is optimized with the index of transfer rate of SSa, SSd and the content of volatile oil.②By single factor and orthogonal test, the extraction technology of Gardenia jasminoides Ellisis optimized with the index of transfer rate of GP.③ By single factor test, the extraction technology of Mentha haplocalyx Briq.is optimized with the content of volatile oil.(2) Study on the forming process of Xiaoertuire Cataplasm:① The order of excipients in the forming process is screened according to its properties and functions.② Screen the species of moisturizer with the index of cumulative water loss rate.③ By single factor test, the range of excipients is optimized with the index of comprehensive sensory score.④The composition of Cataplasm is optimized by D-optimal mixture design, taking the initial bonding strength, the endurance bonding strength, and the gel strength as the evaluating indicators.(3) Study on the release and transdermal absorption properties in vitro of Xiaoertuire Cataplasm:① Modified Franz diffusion cells are used to study the in vitro release of Xiaoertuire Cataplasm, with the indexs of Q24% of GP.② Screen the species of transdermal penetration enhancer with the index of Q24, Jss, ER. and modified Franz diffusion cells are used to study the in vitro transdermal absorption of Xiaoertuire Cataplasm.(4) Study on the pharmacodynamics of Xiaoertuire Cataplasm:The rat models are established by subcutaneous injection of dried yeast suspension to evaluate the pharmacodynamics of Xiaoertuire Cataplasm with the index of AT.(5) Study on the safety of Xiaoertuire Cataplasm:The skin irritation and anaphylaxis are observed to evaluate the safety of Xiaoertuire Cataplasm.Results:(1) The extraction technology of Xiaoertuire Cataplasm:①Bupleurum chinense DC is impregnated at the temperature of 40 ℃ with 8 volume water for 3 hour until the volume of distilled fluid is 2 times of weight of Bupleurum chinense DC. Then Bupleurum chinense DC andGardenia jasminoides Ellis are extracted 2 times with 10-fold of 80% alcohol,1 h for each time.②Mentha haplocalyx Briq.are extracted with 12-fold water for 2 h.(2) The forming process of Xiaoertuire Cataplasm:① The preparation of Xiaoertuire Cataplasm is as follows:Disperse NP700 and dihydroxyaluminum aminoacetate evenly in glycerinum as phase A. Dissolve PVP K90 and tartaric acid by water as phase B. Then add phase B and Xiaoertuire liquid extract into phase A. At last, spread the system on cloth until it becomes uniformity. The cataplasm is done when the crosslink structure is formed.②The matrix formulation of Xiaoertuire Cataplasm is as follows:NP700:9.00 g, dihydroxyaluminum aminoacetate:0.70 g, tartaric acid:0.80 g, glycerin:30.00 g, PVP K90: 5.00 g, water:30.50 g, and Xiaoertuire liquid extract:8 g.(3) The release and transdermal absorption properties in vitro of Xiaoertuire Cataplasm:① The Q24% of GP is (79.23±2.83)%in Xiaoertuire Cataplasm.And the in vitro release of GP is in accordance with the first order kinetics equation.②The azone-propylene glycolis chose as transdermal penetration enhancer with the percentage of 5. The Jss of GP is 6.93 μg·cm-2·h-1, the Q24 is 86.50 μg·cm-2. And the cumulative transdermal rate is (8.34±0.64)% in 24 h.(4) The pharmacodynamics evaluation of Xiaoertuire Cataplasm:Xiaoertuire Cataplasm provides an effective treatment for fever induced by dried yeast. The body temperature of rat models with fever return to normal five hours after drug delivery.(5) The safety evaluation of Xiaoertuire Cataplasm:No significant erythema or edema of guinea pig’s skin is observed under the applying of Xiaoertuire Cataplasm, proving that Xiaoertuire Cataplasm will not cause irritation or allergic reaction to skins.Conclusions:The Xiaoertuire Cataplasm developed in this thesis is stable and feasible in preparation processes, while it has been shown to be with high efficient drug release, effective treatment of fever, and good safety in experiments. This research would provide some reference to the pediatrics antipyretic treatment by Chinese medicine and the further development of Chinese medicine cataplasm.