Preparation And Evaluation Of Freeze - Dried Powder Of Puerarin Derivatives

Puerarin (4’,7-dihydroxy-8-β-D-glucosylisoflavone), a C-glycoside, is present in large amount as the active component of Pueraria lobata (Wild.) Ohwi, a commonly used Chinese herbal medicine. Large numbers of studies show that puerarin may prevent cancer, act as an antioxidant, scavenge free radicals, lower serum cholesterol and have antithrombotic and antiallergic activities.However, widely clinical utilizations of puerarin have been suffering from its poor fat-solubility and water-solubility, low bioavailability and obvious side effects of injection for a long time (>10 days). Previous studies indicated that a low affinity between cell and glucose connecting to puerarin led to little absorption. In the present study, in order to modify these properties of puerarin mentioned above, a novel puerarin derivative (4’, 7-dihydroxy-8-β-D-tetraacetyl-glucosylisoflavone,4ac) was synthesized by acetylation. In comparison to puerarin,4ac was more fat-soluble and its bioavailability was improved. Furthermore, our pharmacological test demonstrated 4ac was effective on treating arrhythmia induced by chloroform, myocardial ischemia induced by hypophysin and hyperlipemia in rats. Hence,4ac has the potential to be developed into a new drug.According to its physico-chemical properties and clinical requirement, injection based on freeze-dried powder was chosen, and optimum processing conditions were established by screening of different preparative conditions and orthogonal design experiment.Results of differential scanning calorimeters (DSC), infrared (IR), scanning electron microscopy (SEM) etc showed that obvious interaction was not detected between 4ac and other compositions. The freeze-dry powder of 4ac was a solid dispersion and not a new compound, which implied that the preparative process was successful. The establishment of quality control standard, stability study and pharmacology study has provided further theoretical and practical support to the safety and efficacy of 4ac in freeze-dried powder form.