Studies On Preparation, Quality Standards And Pharmacokinetics Of Isoflavone Aglycones Dripping Pills

Isoflavone is a class of secondary metabolites formed in the plant growth process with high levels in soybean, including nine kinds of isoflavone glycosides and three kinds of ligands corresponding glycosides. And the highest biological activity is free aglycone.In modern medicine, the similar estrogen of isoflavone aglycones has the function effect, such as, anti-Alzheimer's disease, antioxidant, protecting neurons and cardiovascular disease, relieving the indisposion symptom of female climacteric state. It has the high value of studying and development. But, the indissolvable in water and low bioavailability of isoflavone aglycones brings some difficult for clinical application.In this study, an effective oral isoflavone aglycones dripping pills was prepared with isoflavone aglycones as raw material, PEG6000 as carrier, tween-80 as accessory by solid dispersion technology according to the "Chinese Pharmacopoeia" (2005 edition) . Carries` wettability and restrain crystallinity assured drug`s quickly dissolution, also increased the bioavailability and the therapeutic effect of the drug. Ioflavone aglycones dripping pills research provide the foundation for new drugs against Alzheimer's research and development to further.1.ObjectiveTo extract and purify the isoflavone aglycones as raw material,ensure the optimum preparation process of the isoflavone aglycones dripping pills. Quality standards, stability, and pharmacokinetic studies of isoflavone aglycones dripping pills was studied to provide the scientific basis and application.for future production. 2.Methods2.1 Extracted isoflavones from soybean meal, and then isoflavones have been transformed into aglycone glycosides with acid hydrolysis and refined with extraction.2.2 To determined the various conditions of preparation process with single factor experiment.2.3 According to the requirements of the "Chinese Pharmacopoeia", 2005 edition, the formulation was optimized on the basis of orthogonal design by assessing mean variance of weight, dissolution time and criterion of hardness; the content of isoflavone aglycones dripping pills was determinated with HPLC.2.4 Appearance quality, amounts range of extracts, weight variation and dissolution time of isoflavone aglycones dripping pills was studied with high temperature, strong light, high humidity and accelerate test.2.5 Plasma concentration, Half-time (t1/2), Time to peak (Tmax), Peak concentration (Cmax) and other kinetic parameters was determined after fed rats with isoflavone aglycones dripping pills by gavage.3.Results3.1 Extraction technology of isoflavone aglycones: The contents of three activity aglycones are 70.98%,Genistein,Daidzein and Glycitein were 46.59%, 21.215 % and 3.175%.3.2 Preparation technique of isoflavone aglycones dripping pills: The optimum dripping condition was as follows: the condensing agent was dimethyl silicone oil and the temperature was 10℃,the temperature of physic liquor was 80℃,dripping distance was 6cm,diameter and outer diameter of the dropper was 2.0/3.2mm and dripping speed was 15 drops per minute. the optimum formulation was aglycones:PEG6000:tween-80=2:4:1.3.3 Determination of isoflavone aglycones dripping pills: The content of genistein,daidzein and glycitein were 13.32%,6.00% and 0.89%.weight and dissolution time of dripping pills were 25.03mg and 5.0min.3.4 Stability study of isoflavone aglycones dripping pills: At high temperature and strong light conditions, the appearance quality, dissolution time and content of isoflavone aglycones dripping pills remains stable; At high humidity conditions, isoflavone aglycones dripping pills absorbed easier, weight increased, dissolution time and content decreased; At accelerate test conditions,the results was the same with high temperature and strong light conditions.3.5 Pharmacokinetic study of isoflavone aglycones dripping pills: there is a certain degree absorption of isoflavone aglycones in rats, plasma concentration increased rapidly within 15min after oral administration, Tmax=18.03min, Cmax=0.89μg·mL-1, elimination half-life t1/2α= 39.69min, Absorption half-life t1/2β= 3.65min, Plasma concentration - time area under the curve AUC=46.30μg/mL·min,isoflavone aglycones remove to the basement level after 150min.4.Conclusion4.1 The preparing technique of isoflavone aglycones from Soybean meal is stable and can be controlled.4.2 The optimum preparation method of isoflavone aglycones dripping pills is stable and finished product rate is high.4.3 The determination method of isoflavone aglycones dripping pills is feasible and specific.4.4 The formulation of isoflavone aglycones dripping pills is stable and meet the requirements of design.4.5 Isoflavone aglycones in rats were rapidly absorbed into the blood, with high plasma concentration and degree of absorption.