Establishment Of Self-emulsifying Drug Delivery System Of Effective Part Of Jiao Tai Pill And Study On Its Antidepressant Effect

Objective Self-emulsifying drug release system for the effective part of Jiaotai Pills was established.The optimal formulation was prepared by Jiaotai Pill effective oral nanoemulsion(JPEON).The physical and chemical properties such as particle size,stability,and in vitro release were investigated.To investigate the antidepressant effect of JPEON,to provide a new dosage form for the development and application of the traditional Chinese herbal medicine group Jiaotai Pill,and initially explain its antidepressant mechanism.Method Coptis alkaloids were extracted by dilute acid precipitation method,the content of berberine is used as an indicator.Based on single factor,the optimum extraction technology of Coptis alkaloids was screened by orthogonal experimental design.Through the pseudo-ternary phase diagram,the effective interval self-emulsifying drug delivery system of Jiaotai Pill was determined.The Box-Behnken method was used to optimize the self-emulsifying drug delivery system of Jiaotai Pill,and the optimal formulation was confirmed and tested.Orthogonal experimental design was used to screen the best preparation technology of JPEON colostrum,and the repeatability,stability,recovery rate,entrapment efficiency,and in vitro release of JPEON were investigated.The rats were randomly divided into normal group,model group,positive group,JPEON high,medium and low dose group,8 rats in each group,except for the normal group,the chronic stress was used to prepare rat depression model.Rats were given JPEON and positive drugs by gavage 42 days later.After 14 days,the animals were subjected to behavioral inspection and sugar consumption test,and the activities of 5-HT,NE and DA in the whole brain were determined.Result The average content of alkaloids extracted by the optimal prescription was(84.03±0.38)%.The particle size of oral nanoemulsion was(34.05±2.49)nm in effective part of Jiaotai Pill by Box-Behnken method,the Zeta potential was(23.87±1.20)mV,and the emulsification time was(8.96±0.11)s.After orthogonal test,the particle size of JPEON was(100.67±2.46)nm.At 120 min,the cumulative release rate of Coptis alkaloids reached 91.42 %,and the cumulative release rate of cinnamaldehyde reached 90.35 %.The body weight of rats in the model group increased slowly,behavioral inspection and sugar consumption were significantly decreased,and the contents of 5-HT,NE and DA in the brain were significantly decreased(P<0.01).Compared with the model group,the body weight,behavioral inspection and sugar consumption of rats increased significantly after oral administration of nanoemulsion and fluoxetine hydrochloride at different doses of Jiaotai Pill(P<0.01).JPEON high-dose group was slightly higher than that of the positive group,but there was no significant difference(P=0.836,P=0.505).JPEON high-dose group on DA activity was slightly higher than that of positive group,but there was no significant difference(P=0.772).The antidepressant effect of JPEON high-dose group dosage group and the positive group was the most significant.Conclusion The content of Coptidis alkaloids extracted by dilute acid salting-out method was higher.The particle size of self-emulsifying drug delivery system by Box-Behnken method was better,the Zeta potential was larger and the emulsification time was shorter,JPEON rate is higher,good stability,can form a self-emulsifying drug delivery system.In vivo animal experiments show that JPEON can improve behavioral activities and sugar consumption in rats,has a certain resistance to chronic stress-induced depression.