Preparation And Pharmacodynamic Study Of Compound Glycyrrhiza Flavonoids Cream

Objectives:The formulation of compound glycyrrhiza flavonoids cream was optimized to establish the best technology and quality control parameters. Glycyrrhiza flavonoids and ferulic acid were examined and high performance liquid chromatography was applied to determine ferulic acid. In addition, the mechanism of cream in the treatment of melasma was verified.Methods:The simplex reflected right angle method was used to study stretch and stability of cream and optimize amount of Myrj 52-glycerol monostearate and dimethyl silicone. Glycyrrhiza flavonoids and ferulic acid were analyzed by UV and ferulic acid was determined by high performance liquid chromatography. The quantification of ferulic acid was determined by HPLC at the wavelength of 320 nm using a Kromasil C18 (4.6 mm×150 mm,5μm) analytical column. The mobile phase, pumped at 1 ml/min, was a mixture of acetonitrile and 0.3% acetic acid (25:75, v/v). Chloasma mice models were produced by injecting progesterone into hind leg muscle of mice. The content of tyrosine in blood, liver and local skin, the activity of superoxide dismutase (SOD) in blood and liver and the content of MDA and lipofuscin in skin were determined and analyzed by contrast.Results:The optimized formulation was the amount of Myrj 52-glycerol monostearate (3:2) as 9.0% and dimethyl silicone as 2.5%. According to the best formula, the results of quality inspection showed that the cream was stable and the feature of extensibility was consist with semi-fluid cream. The absorption peak shape of licorice flavonoids and glycyrrhizin was similar,however,characteristic peak was different after reacting with alkali.Ferulic acid and reference substance had similar characteristics peak shape with the maximum absorption peak of 320 nm. The content of determination results showed that peak area and concentration of ferulic acid had a good linear relationship from 2.26μg/ml to 36.16μg/ml, r=0.9998.The average recovery was 97.50% and the RSD was 1.73%(n=6).Compared with model group, the middle and high dose groups of compound glycyrrhiza flavonoids cream can increase the activity of SOD in mice blood and liver and decrease the content of MDA in skin and serum, which make the content of tyrosine decrease significantly in liver, skin tissue and blood. It had significant differences (P<0.01). The low, middle and high dose groups of compound glycyrrhiza flavonoids cream can all decrease lipofuscin content in the skin significantly and had significant differences (P<0.01) compared with model group.Conclusions:The experimental design with simplex reflected right angle method had many virtues, such as fast optimization, simple computation, and high precision and can optimize reasonable formula with stable quality. The quality control and determination of compound glycyrrhiza flavonoids cream were established. The results indicated that compound glycyrrhiza flavonoids cream had significant therapeutic effect for melasma animal models,which was related to reducing the content of tyrosine, MDA, lipofuscin and increasing the activity of SOD.