| 1.Study on the forming process and quality standard of SZ52Neurodegenerative disease is one of the 10 major diseases that seriously threaten human health.Alzheimer’s disease is a typical neurodegenerative disease.On the basis of long-term clinical practice,academician Wang Yongyan pointed out that "obstruction of the brain" is the key link for the onset and aggravation of Alzheimer’s disease.The "SZ52"consist of 5 traditional Chinese medicines to treat Alzheimer’s disease.SZ52 is composed of pseudo-ginseng and two flavors of Gardenia.The previous pharmacological research of the group has confirmed that total saponins of geniposide and pseudo-ginseng in the SZ52 prescription are the main pharmacological components,and the cooperative units have been related to the production,and can directly provide the Gardenia jasminoides and the PNS Panax Notoginseng Saponins extracts.In this part,the film coating was prepared by SZ52 component.Through the preparation process,the optimum process was determined:starch and microcrystalline cellulose(1:1)as excipient,drug assisted ratio 1:0.7,85%ethanol as wetting agent and 14 mesh granulating screen.1%of magnesium stearate was mixed with the granuala to 0.75g to suppress heteromorphic tablets.The plain film was coated with the premixture of medicinal film coating(gastric solution)as coating material,the solvent was pure water,the concentration of coating liquid was 10%,the temperature of the coating bed was 50℃,the coating liquid speed was 20g/h,the weight increases 4%-5%,and the process of SZ52 film could be well formed from the particles,to the plain film and then to the film coating.In order to control the conditions of the production environment,ensure the fluidity of the particles and the stability of the tablets,and the critical relative humidity of the pellets used for the production of SZ52 tablets was 83.87%.The content determination method of Geniposide and PNS Panax Notoginseng Saponins in SZ52 tablets was studied.The linear equation of Geniposide was Y=7.1887X+0.7255,r=0.9999,and the linear range was 16.11μg/mL～171.84 μg/mL.The average recovery rate was 99%,RSD was 2.04%,and the fine density,repeatability and stability were all well investigated.The linear equation of Notoginsenoside R1 was Y=1.6718X+1.5183,r=0.9999,linear range was 37.07～296.59μg/mL,and the average additive recovery rate was 101.09%,RSD 1.27%.The linear equation of Ginsenoside Rg1 was Y=2.1858X+9.7116,r=0.9998,131.76～1054.10 μg/mL in the linear range,100.83%of the average return yield.The linear equation of Ginsenoside Re was Y=1.9272X-0.8652,r=0.9997,the linear range was 18.54～148.30 μg/mL,and the average recovery was 101.46%,RSD 0.90%.The linear equation of Ginsenoside Rb1 was Y=1.5569X+17.793,r=0.9996,the linear range was 138.78～1110.22 μg/mL,the average addition recovery rate was 100.63%,RSD 1.19%.The linear equation of the Ginsenoside Rd was Y=1.7195X+3.5815,r=0.9998,the average addition recovery rate was 99.62%.The density,repeatability and stability were all good.2.Determination of 9 residual solvents in macroporous resin of ginseng tablets.It was composed of eight flavors including Salvia miltiorrhiza,Astragalus membranaceus,Periploca sepium,etc.It has the function of promoting qi and activating blood circulation and warming yang for diuresis.It was used for the symptoms of qi deficiency and blood stasis and yang deficiency,and the chronic and moderate chronic congestive heart failure caused by coronary heart disease and pulmonary heart disease.The preparation techniques of the added ginseng tablets are:reflux extraction of alcohol solution or water extraction and alcohol precipitation,adsorption and separation of macroporous resin and alcohol solution elution in liquid,and concentration drying of eluent and water extracting alcohol to dry paste and supplementary materials to make tablets and coating.Two types of macroporous resin,AB-8 and D-101,were used for the separation and purification of the liquid.The unpolymerized monomers,crosslinker,pore forming agent,dispersant and preservative may not be completely removed in the process treatment,so it was strictly checked and controlled.In this experiment,the limit standard of residual solvents for macroporous resins was formulated for the possible residual n-hexane,benzene,dimethylbenzene,toluene,xylene(including parylene,xylene,o-xylene),styrene and octanol,and the determination of residual solvents for the 9 macroporous resins were studied.The standard addition sample method was used to measure the residual solvent of macroporous resin,which avoided the influence of the difference between the matrix effect and the sample pretreatment on the sample test.The chromatographic conditions were investigated,the chromatographic conditions of the curing column were selected to ensure the long-term stability of the column efficiency,and the sensitivity of the control and salt salting out method was used to improve the sensitivity of the octanol.The headspace conditions are investigated and determined by the sensitivity of the residual solvents to be measured.The headspace equilibrium temperature was 90℃,the quantitative ring temperature was 100℃,the transmwassion line temperature was 110℃,and the headspace was 50min.The linear relationship between the 9 residual solvents was investigated.The linear equation of n-hexane was Y=2.3776X-1.1276,r=0.9979,and the linear range was 0.626～6.26 μg/mL.The linear equation of benzene was Y=2.2261X+0.0011,r=0.9998,and the linear range was 0.0238～0.238 μg/mL.The linear equation of the positive-dimethyl was Y=0.9954X-0.1822,r=0.9951,and the linear range was 0.249～2.49 μg/mL.The linear equation of toluene was Y=2.0899X-0.005,r=0.9999,and xylene.The linear equation was Y=1.9333X+0.0088,r=0.9999,and the linear range was 0.254～2.54 μg/mL.The linear equation of p-xylene was Y=1.69X+0.0137,r=0.9999,and the linear range was 0.256～2.56 μg/mL.The linear equation of xylene was Y=1.69X+0.0137,r=0.9999,and the linear range was 0.267～2.67μg/mL.The linear equation of styrene was Y=1.69X+0.0137,r=0.9997,the linear range was 0.255～2.55 μg/mL.The linear equation of octanol was Y=0.2659X+0.0136,r=0.9975,and the linear range was 0.255～2.55 μg/mL.The accuracy of the 9 residual solvents was good. |
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