| Nowadays, the most dangerous killer of harming the health of the humans is the cerebrovascular disease. The number of the death which is leaded by cerebrovascular disease is 300million every year in our country,. In other words, one person will die in every second, so the cerebrovascular disease is the most dangerous disease in the world. The latest medical data suggests that the appearance of this disease is arising and becoming youthful year by year. There are three features of this disease: high disease rate,high death rate and high mutilation. The patient of cerebrovascular disease should be administered repeatedly and persistently.Ginkgo bilobal Extract (GbE) is one of the most effective drugs to cerebrovascular disease, because its curative effect is definite and the side effect is low. The active component of GbE contains two parts: water soluble component which are flavonoid glycosides ,and lipid soluble component which are ginkgolides and bilobalides. Fortunately, the structure of noisome contain hydrophilic area and lipophilic area. So we can prepare the noisome of GbE in order to encapsulate different kinds of active components, which can help GbE transporting to the brain and protect the brain.High efficiency liquid chromatography was applied to determine the content of flavonoid glycosides, ginkgolides and bilobalides in the Ginkgo bilobal Extract niosomes (GbEN). We adopted ultracentrifugation in order to separate niosomes and free drugs and applied the method to determine the embedding ratio(ER). We also determined the saturate solubility of flavonoid glycosides, in different solution such as phosphate buffer saline, acidum aceticum buffer and acidum hydrochloricum solution. At the same time, we established the way of vitro-release of GbEN. The methodology result suggested that RP-HPLC method had high sensitivity and degree of confidence and it can use for detecting flavonoid glycosides, ginkgolides and bilobalides.Based on the results of traditional techniques and pre-experiment,we selected the modified film dispersion-homogeneization method to prepare GbEN. According to the single factor experiments and orthogonal experiment and use particle distribution ,ER and DL as test index, we decided the best condition of technology: surfactant: cholesterol molar ratio=1:0.5, HLB=11, GbE: carrier=15:100,hydration temperature=80℃. According to the best condition of technology we also prepared 3 groups of sample, and determined the mean diameter=141nm, ER=50.11%, DL=18.79%. Used freeze drying method for GbEN preparing freeze drying powder in order to raise the stability of GbEN and to easy to administration, storage and transportation. Filtrated the kind and the dosage of freeze drying protectant, used particle appearance, color, distribution , angle of repose and ER as test index, at last assured mannitol as the best one and decided the dosage(GbEN﹕mannitol =10mL﹕0.6g).We investigated the quality evaluation of GbEN. Observed the character, determined the particle distribution by Laser diffraction particle size analyzer, and observed the shape by microscope. The result of stability revealed that the character and ER of GbEN freeze drying powder hardly changed under two temperature such as 4-8℃and 25±2℃after 3 months. We determined the content of flavonoid glycosides, ginkgolides and bilobalides in the 3 groups of GbEN by HPLC-dialysis method. Also we studied the release of GbEN at different time in different medium. The result suggest that the release of GbEN is better in PBS(pH6.8)than acidum aceticum buffer and acidum hydrochloricum solution, because its accumulation release rate is more than 80% in 12h. However, its accumulation release rate is only 20% in 48h.Take GbE tablet for reference formulation, the body distribution of GbEN after oral administration in rats was investigated. Established RP-HPLC method to determine the content of flavonoid glycosides in rats'blood and tissues . The methodology result suggested that RP-HPLC method had high sensitivity and degree of confidence. The result of body distribution suggested that compared with GbE tablet ,the content of drug in rats'liver and spleen was degrade after oral administration. However, the content was increased in rats'heart, lung, kidney and brain, especially in brain. It can be inferred that GbEN has the ability to help drugs transport to the brain and avoid the phagocytosis by the endothelial system of liver and spleen so that it can prolong the resistance time of drugs in vivo.The model of experimental hyperlipoproteinemia rats has established successfully. compared with GbE tablet, the effect of hemorrheology after oral administration in rats was investigated. Results demonstrated that GbEN can decrease the raised content of TC, TG, LDL-c and the value of AI and LDL-C/HDL-C and can rise HDL-C meanwhile, which means that GbEN has the capability to improve the disorder of blood-fat metabolism of hyperlipoproteinemia rats. It also can decrease the viscosity of whole blood and plasma of hyperlipoproteinemia rats.In a word, we can select niosomes as the carrier of GbE to take the place of traditional formulation, because they can encapsulate not only the water solubility but also the liposoluble constituent. They might assist GbE pass through blood brain barrier. Therefore, niosomes can used as targeting preparation in the future.
|
PDF Full Text Request