Study On Preparation Technology And Drug Release Kinetics Of SQ Intrauterine Sustained-release Drug Rods

Objective:To reserch a gynecological external preparation named“SQ Intrauterine Sustained-release Drug Rods”to prevent and treat the bleeding side reaction induced by IUD,study on its extraction and purification process,preparation process,and drug release kinetics,in order to lay a foundation for its comprehensive development.Methods:1.Take the content of mollugin and purpurin as the evaluation indexs to optimize extract process of Rubiae Radix et Rhizoma by using orthogonal test.Take the content of mollugin and purpurin as the evaluation indexs to optimize macroporous resin purification process of Rubiae Radix et Rhizoma by using single factor test and orthogonal test.2.Through in vitro coagulation test in rats,optimize the main drugs proportion of SQ intrauterine sustained-release drug rods.Optimize the plasticizing,mixing and vulcanization parameters of SQ intrauterine sustained-release drug rods by using single factor test,orthogonal test and the central composite design-response surface methodology.Determine the prescription composition and preparation process of SQ intrauterine sustained-release drug rods.3.To establish a HPLC method for determinating the content of notoginsenoside R₁,ginsenoside Rb₁,ginsenoside Rg₁,mollugin and purpurin in the SQ intrauterine sustained-release drug rods.Determination the cumulative release percentage of SQ intrauterine sustained-release drug rods in simulated uterine cavity fluid and rats by HPLC.Fit the drug release process in vitro and in vivo by using Zero-order kinetics equation,first-order kinetics equation and Higuchi equation.And carry out the preliminary drug release kinetics study.Result:1.The optimum extract process of Rubiae Radix et Rhizoma was as follows:used 0.2mol/L hydrochloric acid ethanol solution as solvent,the material-liquid ratio was1:8,carried out twice reflux extraction,each time 1.5h.The optimum macroporous resin purification process of Rubiae Radix et Rhizoma was as follows:Taken 0.5g/ml?equivalent to the original medicinal material?Rubiae Radix et Rhizoma extract solution,passed through AB-8 macroporous resin column?diameter to height ratio 1:8?at a speed of 1.5ml/min,sample volume is 4BV,washed with 3BV to remove impurities,then eluted with 8BV 95%ethanol at an elution speed of 1.5ml/min,and collected eluent.2.The best main drugs proportion of SQ intrauterine sustained-release drug rods was panax notoginseng saponin raw material medicine:Rubiae Radix et Rhizoma purified product=3:1.The best plastication process for medical silicone rubber was roll distance0.2cm,front roll temperature 55?60?,rear roll temperature 50?55?,speed ratio 1:1.25and plastication time 10min.The optimum mixing process was plasticizing silicone rubber:main drug=1:1,roll distance 0.2cm,front roll temperature 56-61?,rear roll temperature51-56?,speed ratio 1:1.25 and mixing time 19min.The best vulcanization process was90?and 70min.3.A scientific and accurate methond for determinating the content of SQ intrauterine sustained-release drug rods by HPLC was established.The drug release process of SQ intrauterine sustained-release drug rods in simulated uterine cavity fluid and rats both conforms to Higuchi equation.The drug release rate was faster in the initial stage of drug release,and then decreased and stabilized gradually with the prolongation of time.It had a good sustained release effect.Conclusion:The extraction and purification process of Rubiae Radix et Rhizoma is reasonable and feasible.The preparation technology of SQ intrauterine sustained-release rod is stable and reliable,and its content determination method is scientific and accurate.The finished product has good sustained-release effect.It is a preparation worthy of further study to prevent and treat bleeding side reaction induced by IUD.