Studies On The Nano-preparation Of Puerarin

Cardiovascular disease is one disease that heavily threatens human health. After long-term clinical application, flavone compounds have showed considerate efficacy and safety in the treatment of cardiovascular disease.In this project, Puerarin was chosen as model drug and stearic acid as carrier. Puerarin-solid nanoparticle (PUE-SLN) was produced in order to enhance the bioavailability of Puerarin. The production technique and formulation of PUE-SLN were systematically studied. Its in vitro release and pharmacokinetic profile in rat were also investigated.The method of solvent injection was employed to produce PUE-SLN. On the basis of the stability of PUE solution under different techniques and environments, particle size and distribution, entrapment efficiency and drug loading were employed as main indexes to examine the influences of various lipids, concentration of Poloxamer 188, drug amount, ratio of oil to water as well as the amount of lecithin on the quality of produced PUE-SLN. Consequently, drug amount, concentration of Poloxamer 188 and amount of lecithin were chosen as main parameters to modify the formulation of PUE-SLN by orthogonal design. Quality evaluation was carried out to test the PUE-SLN under the optimum formulation and the mean particle size was 120.33±7.37nm, entrapment efficiency was 90.33±0.87%and the drug loading was 5.65±0.06%. The result proved that this formulation was repeatable and stable. In the experiment of in vitro release, PUE-SLN showed similar release pharmacokinetics in degasified purified water, 0.1N HC1 and pH 6.8 phosphate buffer. The release profiles of PUE-SLN in these three media all comply with the biexponential equation and exhibited the characteristic of sustained release. In the pharmacokinetic study of PUE-SLN in rat, a HPLC method was established to determine the concentration of PUE in rat plasma after intestinal loops administration of PUE solution and PUE-SLN. DAS procedure was used to process the determined results to get the pharmacokinetic parameters as well as the optimum compartment model. The result showed the pharmacokinetic profiles of PUE solution and PUE-SLN both fit to the two compartment model. By statistical test for the main parameters, PUE-SLN had prolonged elimination half life time as well as enhanced AUC by contrary with PUE solution, which meant the preparation of solid lipid nanoparticle could enhance the bioavailability of PUE and prolong its circulation time in vivo.On the whole, this project established a simple and reliable method to produce PUE-SLN using stearic acid as cartier material; after formulation, PUE-SLN showed enhanced bioavailability and different pharmacokinetic profile with its water solution as the reference. As a result, the purpose of this project was basically achieved and a new approach was proposed for the development of Purarin preparation.There was no report about the Puerarin preparation by solid lipid nanoparticle in the literature. The result of this project provided a promising method for the treatment of cardiovascular disease by natural compounds.