| Ischemic stroke (AIS), one of the three diseases which is a serious threat to human health still lacks ideal treatment. And its high mortality makes it become a worldwide medical problem. This subject of brain spiritual microemulsion is composed by notoginseng, musk, Chuanxiong, Shichangpu, borneol, peppermint oil and so on. Based on the existed optimized preparation of brain spiritual microemulsion, the paper focused on pharmacokinetic study of brain spiritual microemulsion.First this research prepared the brain spiritual microemulsion according to the optimized methods and assayed the concentration of major components in brain spiritual microemulsion. The concentration of Chuanxiong ferulic acid, the active ingredients of Panax ginsenosides Rg1 and Rb1 were detected by HPLC. The results shown that brain spiritual microemulsion contained 149.56μg/ml ferulic acid, 8.48mg/ml ginsenoside Rg1 and 6.63mg/ml ginsenoside Rb1. The type of brain spiritual microemulsion, pH, particle size and stability were also studied. And it found that the brain clear microemulsion was belonged to O / W microemulsion, pH value was between 5.5 and 6.5, particle size was 100nm or less, and no stratification happened after centrifuge with still transparent clear brown microemulsion and the drug containment did not significantly reduced.In order to investigate the drug distribution, the pharmacokinetics of brain spiritual microemulsion was studied. This paper not only selected an appropriate protein precipitation method to deal with the biological samples for the pre-treatment, but also established a method to determine the concentration of ginsenoside Rg1 in rats and ginsenoside Rb1. The SD rats were divided into two groups: one group was taken by intranasal administration and the other group was taken by intragastric administration. After 0, 2, 5, 10, 15, 30, 60, 90, 120, 180, 240, 360, 480, 720 min, took out blood, brain, heart, liver, lung and kidney quickly and pre-treated them for HPLC. The ginsenoside Rg1 and Rb1 concentration - time curve of plasma and various tissues obtained at different times and different delivery modes were obtained. The results showed that the drug concentrations under nasal administration were higher than oral administration. Particularly the ginsenoside Rb1 was even could not be measured. And under the intranasal administration the ginsenoside Rg1 achieved the peak concentration with 16.65±1.63μg/ml in only 5min, while under the intragastric administration the ginsenoside Rg1 achieved the peak concentration with 11.29±1.09μg/ml in 60min. The peak concentration and time of ginsenoside Rb1 under intranasal administration was 3.03±0.46μg/ml and 15min, respectively, but it could not be detected after intragastric administration. These showed that intranasal administration can avoid the blood-brain barrier and improve the absorption of drugs in body.The concentration - time curves of ginsenoside Rg1 and Rb1 were fitted by DAS1.0 to get the pharmacokinetic parameters. The results indicated that all the pharmacokinetic parameters of tissues and blood are met the two-compartment model with the weight factor of 1/C2. Between the intranasal and intragastric administration in rats, the Tmax were 5 and 60 min; the Cmax were 16.65 and 11.29μg/ml; the AUCo-∞were 592.91 and 101.70 (μg ? h ? ml-1); the MRT o-∞were 17.12 and 12.86h, respectively.
|
PDF Full Text Request