Studies On The High Bioavailability Of Saponins Of Panax Notoginseng

In present study, pharmacokinetics and oral bioavailability of saponins of panaxnotoginseng (PNS) in rats were investigated firstly. Consequently, the permeation of PNS through small intestine was studied, and then the formulation with high bioavailability of PNS was prepared and evaluated. The contents mainly are: 1. development of analytical methods, investigation of physical and chemical properties and stabilities of main saponins from PNS. 2. pharmacokinetics of ginsenoside Rb1 and ginsenoside Rg1 from PNS in rats, and permeation of PNS through rat small intestine in vitro and in situ. 3. preparation and evaluation of PNS phytosome. 4. study and evaluation of intranasal drug delivery system of PNS.HPLC-UV method was used to determine the percentages of two of main active saponins in PNS, ginsenoside Rb1 and ginsenoside Rg1. Results indicated that the recovery were 97.95% for ginsenoside Rb1 and 108.73% for ginsenoside Rg1, relative standard deviation were 1.56% for ginsenoside Rb1 and 2.34% for ginsenoside Rg1, and content percentages were 30.62% and 32.20% for ginsenoside Rb1 and ginsenoside Rg1 in PNS, respectively. Octanol-water system was used to determine the apparent partition coefficients of ginsenoside Rb1 and Rg1 from PNS, and the effects of heat, light and pH on stability of ginsenoside Rb1 and Rg1 were studied. Results showed that the apparent partition coefficients were between 4 and 5 for both of ginsenoside Rb1 and Rg1. Both of them were sensitive to light, heat and acid condition, and were relatively stable in normal and alkalescence condition.HPLC method was established to analysis ginsenoside Rb1 and Rg1 in biological samples such as serum. Results showed that this method which was sensitive, effective and repeatable can meet the requirement to the biological samples. Then the pharmacokinetic features of ginsenoside Rb1 and Rg1 from PNS in rats were elucidated. The decline of ginsenoside Rb1 in serum could be described by a two-compartment model. The half-life of a phase was 29.40 min and that of phase was 18.57 h. Ginsenoside Rb1 was absorbed from the digestive tract and the absolutebioavailability via P.O. was 4.35%. The pharmacokinetics of Rg1 in rats also could be described by a two-compartment model. The half-lives of Rg1 were 22.20 min for aphase and 7.25 h for phase. Rg1 could be absorbed in the digestive tract and the oral bioavailability was 18.40%. Permeation of ginsenoside Rb1 and Rg1 via rat everted gut sacs and intestine in situ were investigated, and results showed that ginsenoside Rb1 and Rg1 were very sensitive to enzymes in intestine, and transport of PNS through intestine was not passive absorption.Phytosome of saponins can display better properties than saponins in many aspects such as enhancing absorption and increasing bioavailbility of drugs. In present investigation, phytosome of PNS was prepared and evaluated. Results indicated that the phytosome can reduce the mucosal toxicity markedly. However, the oral absorption of phytosome was lower than PNS. According to the study of tissue distribution, it is likely that this phytosome has the characteristic of sustained release.Nasal systemic drug delivery is a potentially valuable alternative to parenteral administration of polar molecules that are poorly absorbed from the digestive tract, such as polypeptides and water-soluble drugs, In present study, some freeze-drying powder and gel formulations were prepared to improve nasal absolute bioavailablity of PNS and further studies were performed to evaluate the local toxicity of formulations. Results indicated that the powder formulation containing MCC gave high bioavailability and low irritation, and the transnasal administration of PNS is feasible. At the same time, studies of tissue distribution showed that there is higher concentration of ginsenoside Rg1 in brain via intranasal administration than intravenous administration, indicating intranasal formulation maybe effective in treating brain diseases.