Preparation And Quality Evaluation Of Compound Breviscapine Freeze-dried Powder Injection

Objectives:The aim of this topic was to study the method of separating high-purity ginsenoside Rgl and ginsenoside Rbl from notoginseng total saponins,and explore a new composition of breviscapine,ginsenoside Rgl and ginsenoside Rbl monomer for the treatment of stroke combined lyophilized powder injection,The compound freeze-dried powder injection was prepared,and the quality standard of the compound freeze-dried powder injection was established,and the preliminary quality stability of the compound freeze-dried powder injection was investigatedMethods:1.From the notoginseng total saponins,through the macroporous resin crude separation,solvent extraction,medium pressure preparative liquid phase purification,high pressure preparative liquid phase purification,silica gel normal phase column purification method,high purity Ginsenoside Rgl and ginsenoside Rbl was prepared.2.Six compound ratios were designed by uniform design method,and the pharmacodynamic screening of mice cerebral ischemia-reperfusion was performed to screen out a better compound ratio,and study on the Prescription Process of Preparation with the Matching Ratio.The optimum minimum amount of the cosolvent is determined by the solubility and the clarity of the solution after dissolution,and the alkali is selected by the solution color,the solution clarity,the pharmic content,and the change of the related substances in the solution over time after adding the different alkalis;Screening for resistance to the solution color,the solution clarity,the pharmic content,and related substances under 60? accelerated conditions by compound anti-oxidant sodium bisulfite,antioxidant L-cysteine hydrochloride and no antioxidant Oxygen agent;by studying the compound appearance,resolubility and solution clarity after adding cryoprotectant mannitol 0,3%,5%,7%,and the amount of cryophilized protective agent added was determined;By investigating the effects of activated carbon adsorption on the content of 0.005%,0.01%and 0.02%,the amount of activated carbon was determined by the adsorption of activated carbon;the eutectic point and the eutectic point were determined by electric resistance method,and the freeze-drying curve was optimize to determine its lyophilization process.3.The three batches of small samples were examined for their properties and chromatographic identification.The dissolution time,pH value,solution color,moisture,loading difference,Content and related substances were examined.The methodological study and method validation were carried out to establish the preliminary quality standards.4.Study the quality stability of compound breviscapine by influencing factors,accelerating investigation and long-term investigation.Results:1.The study found a more efficient method for separation and purification of ginsenoside Rg1 and ginsenoside Rb1 from total saponins of Panax notoginseng,and isolated ginsenoside Rgl and ginsenoside Rbl with more than 95%purity from total saponins of Panax notoginseng.2.The optimal ratio of breviscapine,saponin Rgl and ginsenoside Rbl was determined by pharmacodynamic screening,and the formulation process was studied with this ratio,and the cosolvent B was used as the cosolvent.breviscapine:B=150:58.5 as the best minimum amount of cosolvent,the concentration of the main drug solution is 90mg/ml,no antioxidant is added,no lyoprotectant is added,and the amount of activated carbon is 0.005%.Shake for 30 min and filter through a 0.22 ?m filter.The eutectic point of the compound was-23.7?,the eutectic point was-19.7?,the pre-freezing temperature was set to-35?during lyophilization,the temperature was maintained for 1.5 h,the temperature was raised to 30?,and the total freeze-drying time was 13 h.3.According to the 2015 edition of the Chinese Pharmacopoeia,its formulation traits,identification,and inspection items are in compliance with the regulations.The content determination method is reasonable and effective,and a preliminary draft quality standard has been established.4.Under the influence factors,acceleration and long-term conditions,the reconstitution time of the preparation was less than 40s,the solution was clear and transparent,the pH value was maintained between 7.00-7.50,and the content of the main drug was changed within±2%,and the stability of the preparation was good.Conclusion:The optimal ratio of the new compound breviscapine for the treatment of ischemic stroke was explored.The prescription process of the compound preparation was basically reasonable,the quality standard was controllable,and the preliminary stability test showed that the new preparation had good stability.