Re-evaluation Study On Preparation Process And Quality Standards Of Ginseng Polysaccharide Injection

As a sterile aqueous solution of ginseng polysaccharides,Ginseng Polysaccharide injection was used as a adjuvant of tumor radiotherapy and chemotherapy on the clinical.It has a good effect in enhancing the patient's immunity,improving their life quality,and reducing the side effects of cancer radiotherapy and chemotherapy.Due to the limitations of historical conditions,there are many defects of this variety,mainly as rough preparation process,low quality standards,the lack of pre-clinical safety and efficacy studies and others.Subject to the legislation of re-evaluation on traditional Chinese medicine injection published by SFDA in 2009,and based on the original standards of Ginseng Polysaccharide injection,this study was carried out to re-evaluation the production process and quality standards of Ginseng Polysaccharide injection,and have a preliminary study of it's safety and pharmacodynamic.To provide a scientific basis for producing a Ginseng Polysaccharide injection with stable production process,quality,safety and effective.The main contents and results of the papers are as follows:1.Studies on optimizing of the extraction and purification technology of Ginseng Polysaccharide injection intermediatesOn the basis of the original process route,through the single factor and orthogonal experiments,optimized the original process.The optimized production process of Ginseng Polysaccharide injection intermediates was:use 75%ethanol to extract Panax ginseng dregs by refluxing of 2 times,each time for 2 hours,the solid-liquid ratio is 1:12.Then adding 12 times amount of water in the residue,extract it for 3 times at the temperature of 100?,each time for 2 hours.Concentrated the extraction solution for 4 times,then decolored by 0.3%activated carbon for 30 minutes.Using the JK008 cation exchange resin to remove protein of the polysaccharide extract under the condition of the proportion of the crude drug and drying resin was 1:1,high diameter ratio was 1:7and elution agent was 3BV.Concentrated the purified solution to a relative density of 1.1(50 ?),added ethanol to a content of 30%,centrifugation to remove precipitated.The supernatant continue to add alcohol to the alcohol content of 80%.Using ethanol and acetone to wash the precipitation twice respectively,vacuum drying,finally can get ginseng polysaccharide about 1000g.The experiments show that the process is simple and feasible,and shorten the production cycle,cost savings of the original process.It is suitable for large-scale production,and laid the foundation to give full play of ginseng herbs and ginseng polysaccharide injection efficacy 2.Studies on molding process of Ginseng Polysaccharide injectionThe molding process of Ginseng Polysaccharide injection was:Dissolved ginseng polysaccharide by adding 100 times amount of water for injection,adjusting the pH to 5.5?6.6.Heated to boiling for 15?20min to make fully dissolved.Refrigerated at 4? for 24h,then remove insoluble matter.Filtered using 0.22um millipore,then use the 500KD plate membrane ultrafiltration to remove macromolecular polysaccharide,add 0.3%activated carbon to adsorb pyrogen,decarburization.Filtered using 0.22um millipore again.,potting,115? sterilization 30min,leak detection,molding.3.Studies on preliminary safety and pharmacodynamics of Ginseng Polysaccharide injection.Have a preliminary evaluation of the safety of ginseng polysaccharide injection.The results showed that Ginseng Polysaccharide injection has no abnormal toxicityand active allergic.The acute toxicity found that in the the dose 1.56g/kg case(equivalent to 500 times the clinical dose),all indicators are normal of the mice,no mortality,indicating that ginseng polysaccharide injection was good in safety.The efficacy results showed that ginseng polysaccharide injection can improve the phagocytosis function of reticuloendothelial system and macrophage,and the hemolysin antibody production response of immunsuppiessive mice.It can also inhibit the reduction in white blood cells,bone marrow suppression and liver injury caused by Cyclophosphamide,and improve the anti-tumor effect of cyclophosphamide 4.Studies on complete upgrade the quality standards of ntermediates and formulations of ginseng polysaccharide injectionOn the basis of has a stability production process,this subject established quality standards of ntermediates and formulations of ginseng polysaccharide injection.The main contents include Characters,identification,check items,content,infrared spectra,molecular weight distribution and monosaccharide composition.The quality standards of ntermediates was:the-COOH and D-glucopyranose ring should be included in the absorption peak of the infrared absorption;the acidic sugar content is between 32%to 50%,total sugar content is not less than 90%;weight average molecular weight above 50,0000Dal can not exceed 25%,weight average molecular weight of 1,0000Dal?20,0000Dal should not less than 70%;Monosaccharide composition should contain rhamnose,arabinose,glucose,galactose,glucuronic acid and galacturonic acid.The quality standards of formulations was:Each ginseng polysaccharide injection containing polysaccharide of not less than 6.0mg;weight average molecular weight above 40,0000Dal can not exceed 8%,weight average molecular weight of 1,0000Dal-20,0000Dal should not less than 85%;Monosaccharide composition should contain rhamnose,arabinose,glucose,galactose,glucuronic acid and galacturonic acid.5.Studies on stabilityReference to the established quality standards,this study carried out preliminary stability study of three batches of ginseng polysaccharide injection.The results showed that the preparations is stabilize in three months.