Preparation And Study Of Pueraria Total Flavonoids In Gastrointestinal Adhesion Floating

Oral administration is the most secure and convenient mode of administration, but the water-soluble and fat-soluble of Pueraria Total Flavonoids were not good, so its oral bioavailability is not high. Based on the study of detection mothod, solubility、 apparent oil-water partition coefficients and intestinal absorption kinetics and absorption mechanism in the early, the experiment studied the Caco-2permeability membrane of Pueraria total flavones. Due to the fat-solubility of PTF is weak but the absorption characteristics in the upper stomach and intestinal is better, using different means of preparation, to release and penetration enhancing drugs from fat-soluble, membrane permeability or extend the residence time in body, to improve oral bioavailability, providing an important reference for the design and preparation of Pueraria total flavones’high oral bioavaiability formulations.This paper studies the basic physical and chemical properties of Pueraria total flavoness; studies its absorption characteristics through caco-2cell permeability membrane absorption; prepared the phospholipid complex from Pueraria total flavones as raw materials and soy lecithin as matrix, according to the composite rate and apparent coefficient of water partition, prepared different prescriptions of Pueraria total flavones phospholipid by orthogonal design; Combined Carbopol934P and HPMC K15M as a combination of adhesive material, the octadecanol the density float type floating material and sodium bicarbonate, as the gas production materials of type floating material, according to the indicators of adhesion, floating, cell permeable membrane absorption performance, prepared different prescription of Pueraria total flavones gastrointestinal floating bioadhesive agents by orthogonal design, and exploring the oral bioavailability of the agents through in vivo studies.Firstly, using the high performance liquid chromatography and ultraviolet spectrophotometry to investigate the solubility in water of Pueraria total flavones and puerarin, and the value changes of apparent oil-water partition coefficient Papp and log Papp with pH of puerarin, and found their good solubility in water and the solubility increased with the increase of pH, which may be related to the structure of Flavone. The main active ingredient is isoflavones in Pueraria total flavones, there’re phenolic hydroxyl group in Flavone, as the pH increases, the solubility increases. The apparent oil-water partition coefficient of puerarin decreased with increasing pH, and its logPapp are less than zero in each of physiological pH values, indicating that its polarity is wide, lipophilic is weak, and transparent membrane absorption is difficulties, it came to be one of the reasons of poorly absorbing in gastrointestinal tract. For the absorption in the upper stomach and intestinal is better, the fat solubility can be improved by means of formulations, so as to promote absorption.Secondly, using caco-2cell model to simulate evaluation of absorption mechanism of Pueraria Flavone in vivo, found puerarin in Pueraria Flavone has passive diffusion mechanisms involved during permeable membrane absorption process, showing the dependence of time and concentration, and also affected by the proton gradient, proton gradient at AP side (Top side) can significantly promote the absorption of the puerarin in Pueraria Fotal Flavone. This may be related to the structure of Flavone. Flavone has phenolic hydroxyl group, it absorbed preferably under acidic conditions. It can be speculated that Flavone have a better absorption and a longer absorption period in the stomach and intestinal segments, so it can extend the residence time of Pueraria Flavone in the gastrointestinal tract with the preparation of the floating-adhesion preparations.In this experiment, regarding the composite rate and apparent oil-water partition coefficient as indicators, screening and optimizing prescription by single factor and orthogonal design, with the use of phospholipid complex consists total Flavone and soy lecithin, there are some improvement in fat-soluble of drugs, but not obvious.In this study, using single factor and orthogonal design to adhesion, screening and optimizing prescription by floating absorption performance and cell permeable membrane in Caco-2as indicators, combining Carbopol934P and HPMC K15M as a combination of adhesive material, the octadecanol and sodium bicarbonate as the density float type floating material, prepared different prescriptions Pueraria total flavones gastrointestinal bioadhesive floating multi-unit preparations.In this paper, take Pueraria total flavones floating bioadhesive formulations as test preparation, the raw materials as the reference drug, inspected the bioavailability of formulation in vivo in SD rats, determined plasma concentration-time curve and relative bioavailability of puerarin in rat plasma, The results showed the relative bioavailability was179.4%between test preparation and reference drug. It come out to be that by combining Carbopol934P and HPMC K15M as a combination of adhesive material, the octadecanol and sodium bicarbonate as the density floating material, the gastrointestinal floating bio-adhesive formulations can increase the oral bioavailability of pueraria total flavoness. The study does make sense.