Preparation Process Of Compound Liquorice Capsule And Its Determination Of Active Components

Pulmonary fibrosis is a serious lung disease that can lead to progressive loss of lung function.Most patients have unknown etiology,also known as idiopathic pulmonary fibrosis IPF.The pathogenesis of the disease is complex and the fatality rate is high.The average life span after diagnosis is 2-3 years.It is called oncoid disease.Traditional western medicine uses glucocorticoids and immune preparations,which have great adverse reactions and poor therapeutic effect.In recent years,many new drugs have been developed in many countries,but there are not enough clinical trials,which increase the risk of patients and cost expensive treatment.The emergence of traditional Chinese medicine compound preparations has solved this problem to a certain extent,and provided new drugs with little side effects and reasonable price for patients with pulmonary fibrosis.On the basis of studying the ancient famous prescription Kushen Licorice Decoction and Angelica Fritillaria Sophora Decoction in the Synopsis of the?Golden Chamber?by Zhang Zhongjing of the Eastern Han Dynasty,this paper optimizes the traditional Chinese medicine prescription with Radix Glycyrrhizae Sophorae as the monarch medicine,In the pharmacological study of asthma treatment,it was found that the prescription had significant anti-pulmonary fibrosis effect,and the therapeutic effect on pulmonary fibrosis model mice was better than that of pifenidone.It has an important development Compound liquorice extract was obtained by extracting,separating,concentrating and freeze-drying the raw materials of the preparation.A method was established for the determination of many effective components in the extract,and the content of many effective components was determined.The forming process of the capsule was designed.At the same time,the content of each effective component after the capsule was determined,which laid a foundation for industrial production.This paper is divided into three parts.Part ? Determination of Matrine,Oxymatrine,Glycyrrhizin and Glycyrrhizic ate in Compound Licorice ExtractObjective: To establish a HPLC method for simultaneous determination of matrine,oxymatrine,glycyrrhizin and Ammonium Glycyrrhizinate in the extract ofintermediate of Compound Glycyrrhiza capsules.Method: The chromatographic conditions of matrine and Oxymatrine were Kromasil-NH2 column(250 mm x 4.6mm,5 ?m),mobile phase was acetonitrile-anhydrous ethanol-3% phosphoric acid(80:10:10 V/V/V),detection wavelength was 220 nm,the flow rate was 1.0 mL/min,and the column temperature was 30 ?.The chromatographic conditions of glycyrrhizin and ammonium glycyrrhizinate were as follows: Venusil ASB-C18column(4.6 x 250 mm,5?m)mobile phase was 0.05% phosphoric acid(A)-acetonitrile(B)gradient elution,the column temperature was 30?,the flow rate was1.0 ml/min,the detection wavelength was 237 nm.Result: Matrine was 10.28ug/mL ~ 308.4?g/mL(r=0.999 5),Oxymatrine had a good linear relationship with peak area in the range of 10.192 ug/mL~305.76 ?g/mL(r=0.999 5).The average recovery rate of matrine was 100.28%,RSD was 0.85%(n=6),the average recovery rate of oxymatrine was 99.53%,RSD was 0.98%(n=6).The linear relationship between glycyrrhizin and ammonium glycyrrhizinate was good in the concentration range of 10.026~302.88? g/mL and 100.44~602.64 ?g/mL.The average recovery of glycyrrhizin was 99.82%,RSD was 0.45%(n=6),and that of glycyrrhizic acid was99.51% and RSD was 0.55%(n=6).Conclusion: The method is accurate,stable and reproducible.It can be used for the quality control of the intermediate extract of Compound Glycyrrhiza Capsules.Part ? Study on preparation technology of compound licorice capsuleObjective: To determine the forming conditions of compound licorice capsules,and to determine the reasonable and effective compound preparation according to the determination results of extract content and forming conditions.Methods: With moisture absorption rate,angle of repose,bulk density and critical relative humidity as the evaluation indexes,suitable accessories were selected,the proportion of accessories was optimized,and the optimum forming conditions were determined.Result: The capsule forming technology showed that the freeze-dried powder and microcrystalline cellulose+microcrystalline silica gel ?volatile oil were blended at the ratio of 3:(0.5+0.5):0.9.Soft materials were prepared by adding 90% ethanol and granulated by 20 mesh drug sieve,low temperature drying at 40 ?,The angle of repose of granules was 28.28°,the bulk density was 0.412 g/ml,filling with capsuleNo.1 and the critical relative humidity was 58%.Conclusion: The preparation technology of compound licorice capsule is reasonable and feasible,and can be applied to industrialization.Pard ? Determination of matrine,oxymatrine,glycyrrhizin and Ammonium Glycyrrhizinate in Compound Glycyrrhiza capsules.Objective: To establish a preliminary method for the determination of effective components in Compound Glycyrrhiza Capsules and to provide basis for the formulation of quality standards.Method: The chromatographic conditions of matrine and Oxymatrine were Kromasil-NH2 column(250 mm x 4.6 mm,5?m),mobile phase was acetonitrile-anhydrous ethanol-3% phosphoric acid(80:10:10V/V/V),its detection wavelength was 220 nm,the column temperature was 30 C,and the flow rate was 1.0 mL/min.The chromatographic conditions of glycyrrhizin and ammonium glycyrrhizinate were as follows: the mobile phase of Venusil ASB-C18column(4.6 x 250 mm,5?m)was 0.05% gradient elution of phosphoric acid(A)-acetonitrile(B),the flow rate was 1.0 ml/min and the detection wavelength was 237nm;the column temperature was 30 C.Result: In the range of 10.28~308.4? g/mL for matrine and 10.192~305.76? g/mL for oxymatrine,the linear relationship is good.The average recovery of matrine is 99.73%,RSD is 1.05%(n=6),and the average recovery of oxymatrine is 99.73% RSD is 1.29%(n=6).The linear relationship between glycyrrhizin and ammonium glycyrrhizinate was good in the range of10.02~302.88? g/mL,100.44~602.64? g/mL.The average recovery of glycyrrhizin was 99.83%,RSD was 1.04%(n=6),and the average recovery of glycyrrhizic acid was 99.55% and RSD was 0.83%(n=6).Conclusion: The method is accurate,stable and reproducible,and can be used for the quality control of Compound Glycyrrhiza Capsules.