Study On The Solid Dispersion Of Extract Of Resina Dragoins And Its Bioavailability

Exact of resina draconis,the effective part of resina draconis,which contains flavonoids,stilbene,steroids,saponins and other ingredients and is insoluble in water,can inhibite platelet aggregation induced by ADP and PAF in vitro,protect focal cerebral ischemia and ruduce the water content of the ischemia rat brain without significant side effects.In the experiments,we aimed at using solid dispersion technology to improve its water-solubility and evaluating the relative bioavailability of exact of resina draconis and its solid dispersion in rats.During the research,we have completed its separation,investigated the activity of the components,and have established measuring methods of five components and its external digestion.We have studied the preparation of its solid dispersion and evaluated its relative bioavailability in rats through the study of its pharmacodynamics.1.Studied on the components of the exact of resina dracoins:we took the methods of silica gel chromatography,Sephadex LH-20 chromatography,ODS chromatography and recrystallization to separate the exact of resina dracoins and have obtioned seven components.They were Loureirin A,Loureirin B,7,4'-dihydroxy flavone,compesterol,pterostilbene,apiolin and resveratrol.We took qualitative study of the exact of resina dracoins using the technique of Q-TOF-MS and have deduced another ten components.We have identified the seventeen compositions in the total ion spectrum and UV spectrum.We found Loureirin A,Loureirin B,7,4'-dihydroxy flavone,pterostilbene and resveratrol highly existed in the exact of resina dracoins.So we took them as detective targets to make the following studies.We investigated the inhibition role of the isolated compounds on the ADP-induced platelet aggregation in vitro and its protective role on hypoxic brain celles.The results showed that resveratrol and loureirin B could inhibited ADP-induced platelet aggregation in vitro in a certain dose-dependent way and other componts' effect were insignificant.Loureirin A,Loureirin B and 7,4'-dihydroxy flavone coule protect the hypoxic brain celles and other componts' effect were insignificant.2.Studies on the preparation of solid dispersion of the exact of resina dracoins:First,we have set up the detective method of Loureirin A,Loureirin B,7,4'-dihydroxy flavone,pterostilbene and resveratrol in the exact of resina dracoins.Through the foundation of methodology,we have proved the stability of this method and have decided to use it to detective the five components.Second,using the cumulative dissolution of loureirin A,loureirin B,7,4 '-dihydroxyflavone,pterostilbene and resveratrol as evaluation index,we investigated the dissolution condition of extract of resina draconis in vitro:Detect following as the method of Chinese Pharmacopeia,take 0.20 mol·L-1 lauryl sodium sulfate as degestive medium,the volume was 100 ml,the temperature was 37 ?±0.5? and the speed was 100 r·min-1.Counting the time as put the drug into the medium,and taking samples of 2 mL at 6,10,15,30,45 min.Filtrate the samples using 0.45 ?m filtrate membrane and add the same volume of medium everytime you take the sample.Third,the study of making solid dispersion of the exact of resina dracoins:Take Loureirin A,Loureirin B,7,4'-dihydroxy flavone,pterostilbene and resveratrol as detective targets and through the experiment of studing single factors,we have ensured the preperation of solid dispersion:Accurately weigh drug and PVP-K30 as the ratio of 1:3(12g),put them into conical flask,add 80%ethanol of 150 ml,utrasound at 45 min to make them completely mixing,use rotary evaporator to recover the solvent,take them out and put in vacuum drying oven at four hours,porphyrizing and make them through griddle of 40 section.We investigated the solubility of the exact of resina dracoins and its solid dispersion and discover in the solid dispersion the solubility of five components all increased.Through IR and DSC,we inverstigated the aniseikonia of the solid dispersion.The result of IR indicate that in the process there was no chemical reaction.The result of DSC indicate that the exact of resina dracoins existed in the form of microcrystal in PVP-K30.We investigated characters,moisture,dissolution of three batchs of solid dispersion and finded no obvious discrepancy,it indicated that the preparation of solid dispersion was practicable.3.Study on the relative bioavailability of solid dispersion in rats:we have set up the detective method of Loureirin A,Loureirin B,7,4'-dihydroxy flavone,pterostilbene and resveratrol in black plasma and have founded the methodology.The results of showed that there was inprovement in the absorb of solid dispersion of the exact of resina dracoins.Their relative bioavailability were 154.3%,164.3%,127.2%,178.3%,130.5%.