Study On The Preparation Of The Liposome Of The Toatal Ginsenoside Of Ginseng Stems And Leaves (L-GSLS) And Pharmacokinetics In Rats

Total Ginsenoside of Ginseng stems and leaves(GSLS)is the total saponins of Panax ginseng plant.In 2015,the GSLS was included in the Chinese Pharmacopoeia as one of the extracts of traditional Chinese Medicine.The main active components of ginsenosides in GSLS were ginsenoside Rg1,Re,Rf,Rb1,Rg2,Rc,Rb2,Rb3,Rd and so on.Ginsenoside had a variety of pharmacological activities,such as the protection of myocardial cells,protecting the central nervous system,improving immunity,anti-tumor,antioxidant and anti-aging effect.However,ginsenoside had poor permeability and low bioavailability,which was an effective way to improve bioavailability.This paper selects ginseng saponin as the research object,study the detection of GSLS,optimization of preparation technology of liposome of GSLS and the studying on pharmacokinetics of GSLS.The main research contents were as follows:(1)Preparation and optimization of preparation technology of GSLSEstablish the RP-HPLC determination of nine kinds of saponins monomers(Rg1,Re,Rf,Rb1,Rg2,Rc,Rb2,Rb3,Rd)in the GSLS.There was a good relationship between the nine kinds of saponins monomers in the range of 2~200 μg·mL-1.Intra day and Inner day precision were less than 5%.The recovery was 98.39~101.65%.Compared with the traditional methods,the method had a wide linear range and was suitable for the accurate detection.The preparation of the liposome of the GSLS was optimized using Box-Behnken experimental design(BBD)and response surface methodology.Based on single factor tests,the effects of the mass ratio of phospholipids to drug,phospholipids/cholesterol ratio and PH balue of PBS buffer solution were studied using BBD method.The result showed that the preparation of the liposome of the GSLS based on the analysis were: the mass ratio of phospholipids to drug was 8.01:1,phospholipids/cholesterol ratio was 15.07:1,PH balue of PBS buffer solution was 7.44,which was close to the theoretical entrapment efficiency 89.17%.The optimal preparation of the liposome of the GSLS were determined and the advantages included low cost,less energy consumption,short time high entrapment efficiency and so on.(2)Study on pharmacokinetics of L-GSLSTo investigate the difference of plasma concentration an pharmacokinetic parameters between liposome and aqueous solution of GSLS in rats through the duodenum and vein.After different time points of giving ginsenosides,the blood was taken from the femoral vein.The main method was the inestigation of the serum concentration of 9 main ginsenoside monomers Rg1,Re,Rf,Rb1,Rg2,Rc,Rb2,Rb3,Rd in different time points after giving aqueous solution and liposome of GSLS were determined by HLPC.The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters.The results from the experiment showed that by two kinds of administration of duodenum and vein,the pharmacokinetic parameters of two formulations were compared with each other.The pharmacokinetic of liposome is significantly different from that of aqueous solution,which could not only remain the drug for a longer time in vivo,but also reduce the elimination rate and increase the treatment efficacy.Compared with the traditional dosage forms,the GSLS can improve the sustained release of the drug,which is of great significance for the research and development of new dosage forms of ginsenosides in the future.