Research On The Improvement Of The Quality Standard Of Compound Dangshen Tablets And The Optimization Of Its Preparation Process

The compound codonopsis tablets is made of Chinese medicines such as Codonopsis pilosula,Salvia miltiorrhiza,Angelica sinensis,Jinguolan,and Beisha ginseng.It has the functions of promoting blood circulation and removing blood stasis,replenishing qi and so on.It is usually used as angina pectoris and chest tightness caused by myocardial ischemia.There are 5 enterprises that have obtained the approval documents,but none of them have been listed on the market.They have been entrusted by the Guilin Red Cross Enterprise to conduct research on the quality improvement of the compound party.Among the drugs required for determination in the Pharmacopoeia are tanshinones and salvianolic acids in Salvia miltiorrhiza,ferulic acid in Angelica,and Gulenbin in Golden Fruit.The determination of the quality standard content of the current compound Codonopsis tablets only requires the determination of the content of tanshinone IIA,while the other herbs are only identified as Codonopsis pilosula,Salvia miltiorrhiza,and Ginkgo biloba,but the active ingredients of other drugs are not determined.In view of the significant contribution of many other active ingredients of other drugs to the efficacy of the compound Codonopsis tablets,it is necessary to include their content in the quality standards.Codonopsis pilosula is the main drug of the compound,and its main active ingredient,ginsenoside,is also necessary to be included in the quality study.In view of the fact that the water extraction method provided by the Guilin Red Cross Society failed to detect tanshinone IIA,from the perspective of re-registration of pharmaceutical technology,the following studies were completed:1.Research on the improvement of quality standards:The determination of the content of the prescriptions of the main medicinal ginseng,the ginseng glucoside,the angelica sinensis,the salvianolic acid in the salvia miltiorrhiza Bunge and the ginsengin and the corresponding quality research method.All methods were stable and effective by methodological investigation.The results of the content determination showed that the content of ginsenoside,ferulic acid,salvianolic acid B and gulimpin in the compound Codonopsis tablets were:1109.34,234.26,57.448,134.10?g/piece?large piece 0.53 g?;The HPLC method was determined by measuring the content of four components in the compound ginseng tablets:HPLC column:Dalian Yilite Hypersil ODS2 column?150 mm×4.6 mm,5?m?;mobile phase:80%acetonitrile?mobile phase?A)-0.02%phosphoric acid solution?mobile phase B?;according to the method?0⁸min,9²2%A;8⁴0min,22³9%A;40⁴2min,39%⁹%A;42⁶0 Min,9%A?Gradient elution;flow rate:0.8 ml/min;detection wavelength:210 nm;column temperature?40±0.1?°C;injection volume:10?L.The results of the determination under the method showed that the contents of codonopsis,ferulic acid,salvianolic acid B and coulombiin in the compound Codonopsis tablets were 382.19,83.36,21238.1,240.69?g/g,respectively.Compound Codonopsis pilosula is a compound preparation.In order to ensure the quality of the preparation product and the stability of the drug effect,the fingerprint of the compound Codonopsis pilosula is studied.The chromatographic conditions are the same as the ones under the one method,and a batch of compound Codonopsis tablets is used as the standard.Five batches of samples were continuously fed under the same conditions and calculated by the similarity system.The similarity of the five batches of samples was above 0.90,and there were 10 common peaks.After calibration with the reference substance,three of the peaks were determined to be ginsenosides.Ferulic acid,salvianolic acid B,and salvianolic acid B have good peak shape and good resolution,so it is used as a control peak.The results of the final fingerprints show that the method is effective and stable,and is suitable for the quality research of compound Codonopsis tablets.2.Preparation of compound ginseng tablets:Based on the original quality index,determine the extraction parameters of tanshinone IIA.?1?According to the single factor experiment results,select the representative factors from five factors to test the concentration of ethanol.),extraction temperature?B?,ratio of material to liquid?C?and extraction time?D?as factors of investigation,the extraction amount of tanshinone IIA as a comprehensive index,this part designed a four-factor three-level experiment L₉?3⁴?orthogonal table It is concluded that the extraction conditions of tanshinone IIA are superior.It can be known from the experimental data of the orthogonal table,wherein the larger the R value?very poor?,the greater the influence of the factors it represents,and the amount of the tanshinone IIA can be extracted from the magnitude of the range in the orthogonal table.The influencing factors are ethanol concentration?A?>material to liquid ratio?C?>extraction temperature?B?>heating time?D?.The result is that the optimal condition for the extraction of tanshinone IIA from the compound ginseng tablets is 70%ethanol,the heating temperature is 50°C,the ratio of material to liquid is 1:20,and the heating time is 2 h;?2?the original preparation process is optimized to the new quality standard.The parameters of salvianolic acid B extraction were optimized for the benchmark.The results showed that the heating factors?D?>ethanol concentration?A?>liquid-liquid ratio?C?>extraction temperature?B?.It can be seen from the table that the superior conditions for the extraction of salvianolic acid B in the compound Codonopsis tablets are 50%ethanol,the heating temperature is 70°C,the ratio of material to liquid is1:20,and the heating time is 1 h.