The Study Of Sodium-Aescine Microemulsion Injection

Sodium-Aescine are triterpenoid saponins sodium salt extracted from the dry ripe fruit of Chinese medicine(TCM) horse chestnut, used to be made for intravenous injection powder by freeze drying. They have the functions of anti-inflammation, anti-exudation, increasing the vein tension, improving blood circulation, correcting of brain dysfunction and relieving cerebral edema. Microemulsion can parcel drugs to reduce the contaction with the blood vessel walls and have a tendency to inflammatory lesions at the same time, so it can improve drug action. This paper changes lyophilized powder to microemulsion injection and studies the quality standards of microemulsion injection and its efficacy evaluation in vivo and in vitro.In the first part of this paper, the physical and chemical properties of Sodium-Aescine, including characters and oil-water partition coefficients, were mainly studied. This product is white powder or crystalline powder, it is water soluble in neutral and alkaline conditions, and the liposolubility increases significantly under acid condition, so it is better for the distribution of sodium aescinate in oil phase.In the second part, the prescription and preparation process of Sodium-Aescine microemulsion injection were studied. The best oil phase, emulsifier, Km and preparation process were determined. The optimal formulation of microemulsion was determined through screening surfactants, cosurfactants and oil phases by using pseudo-ternary phase diagrams and measuring the size of the microemulsion. The optimum prescription was as follows:the surfactants were both lecithin and emulgator A (1:2), Km=3.75, the oil phase was medium chain triglycerides, the proportion of oil phase and emulsifying agent was1:1.5. The optimum temperature the oil phase joined was60-70℃, with aseptic filtration and pH at5-6.Preliminary evaluation in vitro such as appearance, size, electric potential, stability of the plasma and so on were carried out for Sodium-Aescine in the third part of this article. The results have shown that the sizes of microemulsion were less than 50nm (between20and40nm). Most of them were sphericall, stable within24h and neutral.In the fourth part, the quality standards of Sodium-Aescine microemulsion injection were studied, including the content and related substances. The escin A and escin B in a bottle of Sodium-Aescine microemulsion injection are drawed up preliminary2.5～4.5mg and2.0～3.5mg, respectively. Related substances was not more than20%by calculating with area normalization method and it was stricter compared with the original powder injection.In the fifth part, stability of Sodium-Aescine microemulsion injection were studied, including accelerated stability and long-term stability. Accelerated stability study results have shown that the isomers of Sodium-Aescine are prone to convert among them at40℃,30℃and25℃. At the same time, the particle sizes of microemulsion began to increase after3monthes at40℃, which showed that the preparation is very sensitive to temperature. The results of long-term stability for six months demonstrated that there were no significant changes both particle size and content wihtin6months.In the sixth part, safety of Sodium-Aescine microemulsion injection were studied by determined with Micelles stimulation to blood vessel. The experimental results have shown that Sodium-Aescine microemulsion injection and Sodium-Aescine powder-injection have both hemolysis and red blood cell condensation reaction, and vascular irritation reaction as well. The congestion phenomenon of Sodium-Aescine microemulsion injection was slightly weaker than that of Sodium-Aescine powder-injection, but there were no significant differences, which indicates there was still a risk by intravenous adminstration.In the seventh part pharmacodynamics of Sodium-Aescine microemulsion injection were evaluated, by inhibitory effect to ear swelling and antagonism to the increase of blood capillary permeability caused by dimethylbenzene. High and low dose groups of Sodium-Aescine powder-injection and Sodium-Aescine microemulsion injection all have obvious antagonistic effect to the increase of blood capillary permeability of the auricle of mice caused by dimethylbenzene, and antagonistic effect of Sodium-Aescine microemulsion injection was better.