Study On The Mechanism Of Synergistic Compatibility Of Berbamine-berberine Hydrochloride Based On Absorption

Diabetic retinopathy（DR）is one of the most serious diabetic microangiopathy.At present,DR has become an important factor leading to blindness in diabetic patients..Therefore,in order to solve the serious and difficult diseases which plagued people’s health and improve the people’s quality of life,it is necessary to develop drug research on early prevention and control of DR.The pre-class study found that Tibetan Medicine Berberis Cortex,which the main component is berberine hydrochloride and berbamine hydrochloride,has obvious preventive and therapeutic effects on retinopathy of db/db mice,which can reduce the level of hyperglycemia in spontaneous DR mice and improve retinal vascular damage and prevent the birth of neovascularization.Berberine hydrochloride could significantly reduce the blood sugar level of diabetic rats,and there was no significant difference between berberine and berbamine added with half quantity of berberine,suggesting that the two may have the effect of synergism.Berberine hydrochloride has poor bioavailability because berberine hydrochloride may be the substrate of P-gp protein in the body.It is transported from the intestinal cell to the intestinal cell by P-gp protein.This series causes the decrease of the blood drug concentration of berberine,which leads to the decrease of oral bioavailability.Berbamine hydrochloride,similar to verapamil,is a natural source of calcium channel inhibitors,which can inhibit the expression and function of P-gp.And berbamine hydrochloride has the effect of sensitizing,promoting the absorption of drugs and improving the bioavailability of drugs.We can change the effective ratio of berberine hydrochloride and berbamine hydrochloride in order to promoting the absorption in the intestine and the oral bioavailability of berberine hydrochloride,which can play a better role in the treatment of DR.Objective:1.The binding rate of berberine hydrochloride and berbamine hydrochloride to bovine serum albumin was studied,and the relationship between concentration and protein binding rate was found.2.The vitro intestinal absorption characteristics of berberine hydrochloride in the groups of berberine hydrochloride,berbamine hydrochloride and its compatibility group in the normal environment and high calcium environment was studied by rat everted gut sacs.Method:1.Single factor test and equilibrium dialysis and HPLC were used to determine the binding rate of berberine hydrochloride,berbamine hydrochloride and bovine serum albumin.2.The absorption of berberine hydrochloride and berbamine hydrochloride in different groups in the normal environment and high calcium environment was studied with the model of intestinal vesicle of rat enteric valgus and HPLC.Result:1.In the study of the binding rate of berberine hydrochloride,berbamine hydrochloride in bovine serum albumin,when the drug concentration of berberine hydrochloride is 10⁸0μg·mL^-1,the binding rate is between 23.54%and 30.50%,which is the medium and low degree.When the drug concentration of berbamine hydrochloride is 10¹40μg·mL^-1,the binding rate is between 48.94%and 61.61%,which is the low degree.2.The results of drug absorption of berberine hydrochloride,berbamine hydrochloride and its compatibility group in the normal environment and high calcium environment showed that compared with the berberine hydrochloride group under normal conditions,the absorption of berberine hydrochloride in its compatibility group in the normal and high calcium environment increased in varying degrees and this shows that berbamine hydrochloride has a similar effect to verapamil and can promote the absorption of berberine hydrochloride in the intestine,which may be related to the inhibitory effect of berbamine hydrochloride on P-gp.The absorption rate of berberine hydrochloride in the high calcium group was greater than that in the normal group,indicating that the promoting effect of berbamine hydrochloride may be more obvious in the high calcium environment（the pathological state）,and the promoting effect may be related to the concentration of berbamine hydrochloride.Conclusion:When berbamine hydrochloride is combined with berberine hydrochloride,it can promote the absorption in the intestine and the oral bioavailability of berberine hydrochloride,which may be related to the inhibitory effect of berbamine hydrochloride on P-gp.The promoting effect of berbamine hydrochloride may be more obvious in the high calcium environment（the pathological state）,and the promoting effect may be related to the concentration of berbamine hydrochloride.