Preliminary Study On Hydroxsafflower Yellow A Complex Nanoemulsion

Hydroxysafflor yellow A（HYA）is a chalcone drug derived from the dried tubular flower of the safflower of the genus Composita.It have many pharmacological activities,such as cardiovascular disease,anti-cancer,anti-inflammatory,and metabolic regulation.HYA has poor fat solubility and low bioavailability.Currently,only safflower injection is widely used in clinical,and oral application is greatly limited.In this paper,Hydroxysafflor yellow A complex nanoemulsion（HYACN）was prepared by titration method,and HPLC analysis method of HYA was established in vivo and in vitro,and the pharmacokinetic behavior and intestine absorption of HYACN were observed.HYACN could improve the oral bioavailability of HYA.The first part,prepares HYACN and establishes the method for determining the in vitro content of HYA in HYACN.Objective:To prepare HYACN,and establish a method for determination of HYA in HYACN.Method:Preparation of HYACN by titration;determination the content of HYA in HYACN by HPLC in vitro:HPLC analysis:COSMOSIL5C₁₈-MS-II column（250 mm×4.6 mm,5μm）,acetonitrile（A）-20mmol·L^-11 potassium dihydrogen phosphate solution（B,pH=3.5）was the mobile phase,gradient elution;detection wavelength 403 nm,flow rate was1.0 mL·m^-1,column temperature was 30°C,injection volume was20μL,repectively.Results:HYACN was yellow clear liquid with uniform dispersion.The content of HYA in HYACN was not interfered by other excipients in the preparation.The linear relationship between HYA peak area and concentration was good in the range of 1¹25μg·mL^-1.The linear regression equation was A=18910 C-12337,r=0.9997.The limit of detection was 12 ng·mL^-11 and the limit of quantification was 45 ng·mL^-1.The intraday and daytime precision was good,the relative standard deviation was in the range of 0.62%¹.32%;the recovery rate is in the range of 91%¹00%.Conclusion:The successful preparation of HYACN and the determination method of HYA in HYACN was reliable.The second part,pharmacokinetic studied of HYACN.Objective:To establish a method for determination of HYA in plasma,study the pharmacokinetic behavior of HYA and HYACN in SD rats.Methods:The reversed-phase HPLC method was used to determine HYA,and the pharmacokinetic parameters,bioavailability and bioequivalence of HYA and HYACN were investigated.Results:The AUC_{（0-72 h）}and C_maxax of HYACN were 9.99 times and 16.11 times than that of HYA,respectively.The bioavailability of HYA was increased about 10 times,HYACN and HYA were not equivalent.Conclusion:HYACN was better than HYA,the bioavailability of HYA was significantly improved.The third part,intestinal absorption studied of HYACN.Objective:To establish a HPLC method for determination of HYA in intestinal fluid,and study the absorption of HYACN and HYA in the duodenum,jejunum,ileum and colon in SD rats.Methods:A method for determination of HYA in intestinal absorption was established to evaluate the intestine absorption behavior of HYACN and HYA.Results:HYACN and HYA were mainly absorbed in the duodenum and ileum.The percentage of HYA absorption in the duodenum and ileum in HYACN were 79.41%and 79.02%,respectively,which were 48.71 and 11.19 times of HYA,respectively.Conclusion:HYACN significantly increased the intestinal absorption of HYA in rats.