| Resveratrol(Res)is a polyphenol compound structure,also known as stilbene three phenol,widely with the nature,has a good ability to remove free radicals and antioxidant prevent gene mutation,antibacterial anti-inflammatory,regulate nerve,protect the liver,the prevention and treatment of cardiovascular disease,and even to the prevention and treatment of cancer.The study showed that resveratrol can at the start of a cancer cell growth,proliferation,development,the three main stages can inhibit or even reverse effect.This makes resveratrol,a natural green low toxicity of antitumor substances.But as a result of resveratrol,poorly soluble in water,which greatly reduces their bioavailability,limits the development and application of its products.This work mainly studied the one using the method of supercritical flow weight crystallization technology SAS to resveratrol superfine powder preparation process.Resveratrol for poorly soluble in water,the method in supercritical conditions,make its recrystallization,by adjusting the supercritical various factors,to control the development of resveratrol crystal nucleus,and thus reduce the resveratrol powder particle size,reduce the crystallinity,increase the specific surface area,improve the resveratrol solubility in water.So as to achieve the aim of improve bioavailability.This study first preparation technology for the orthogonal optimization.Preparation of samples,and then in the best possible conditions and their morphology,physical and chemical properties,purity,dissolution behavior,in vitro antioxidant,fruit flies in vivo antioxidant and pharmacokinetic.Research results are as follows:1.Using the orthogonal experiment for supercritical SAS of resveratrol superfine powder prepared by the process optimization,it is concluded that the best process conditions as follows:reaction temperature is 50?,the reaction pressure of 20 Mpa,resveratrol,the concentration of ethanol solution for 9 mg/mL,dosing rate of 1 mL/min.Preparation of resveratrol in the best possible conditions to the average particle size of nanometer powder 0.68?mą0.03?m.2.The morphology characteristics of superfine powder:after eye look carefully,we found that resveratrol powder is colorless crystalline powder,crystal needle bulky,powder density.The resveratrol superfine powder is colorless flocculent powder,powder loose,light,density is small.This also reflected from the side,resveratrol superfine powder particle size decreases,and the crystal degree reduced.Observed in the electron microscope,resveratrol powder microstructure is strip type columnar crystal structure,large complete crystal shape,particle size in a few hundred microns,and the microstructure of resveratrol,superfine powder to small thin sheet there is no clear crystal structure,uniform size distribution,particle size of about a few microns in general,or less.Thus resveratrol superfine powder than powder has smaller crystal shape and smaller particle size.3.From two aspects of chemical structure and physical structure research,the supercritical SAS of resveratrol superfine powder and powder prepared have been characterized.Chemical structure:infrared spectrum detection showed that resveratrol in the process of preparation,functional group no change.Molecular weight of the mass spectrum detection showed that resveratrol has not changed.Physical structure:X-ray diffraction test showed that resveratrol superfine powder,the powder,the crystallinity is greatly reduced.DSC test showed that resveratrol,weak in the second-stage superfine powder crystal structure.TGA test showed that resveratrol superfine powder is faster than by weightlessness,and its small particle size,large surface area surface energy,unstable.4.Purity:resveratrol superfine powder purity 99.2%ą 0.5(meanąSD),and resveratrol powder purity is 98.5%ą0.5(meanąSD).This shows that during the preparation of resveratrol in supercritical SAS,recrystallization,and the step and purification.5.Dissolution behavior:resveratrol powder and ultrafine powder of supersaturation solubility in water of 31.8 ?g/mL and 75.1 g/mL.The greater than in phosphate buffer pH 7.4 package and solubility of 66.2 ?g/mL and 29.6 g/mL.Resveratrol superfine powder of the greater than the saturation in the water is 2.4 times that of the second-stage in phosphate buffer pH 7.4,2.3 times that of powder.Resveratrol dissolution velocity experiment,hellebore alcohol superfine powder in water dissolved by 89.5%in less than 5 min,15 min or so almost completely dissolved.And at the time of the 5 min resveratrol powder dissolved only 72.6%,only 77.3%dissolved in 15 min,and flatten out,has reached its limit.This suggests that resveratrol superfine powder are faster than the second-stage dissolution rate.6.In vitro antioxidant:resveratrol remove DPPH free radicals in vitro experiments have shown that resveratrol IC50 alue concentration of superfine powder 7.75 ?g/mL,and IC50 alue concentration of resveratrol powder 14.55 ?g/mL.Resveratrol superfine powder of the ability of removing free radicals is by 1.9 times.This shows that with the decrease of the resveratrol particle size,its ability to remove free increase greatly.This is because with the decrease of the resveratrol particle size,resveratrol saturated solubility and dissolution rate of increase,resulting in the resveratrol superfine powder of the ability of removing free radicals than powder.7.fruit flies in vivo antioxidant:results show that the solution concentration is 2.5 mg/mL,the average life span and maximum life of resveratrol superfine powder flies are respectively 1.04 and 1.02 times,the second-stage is 1.20 and 1.08 times that of blank group;Solution concentration at 5 mg/mL,average life span and maximum life of resveratrol superfine powder flies are respectively 1.02 and 1.02 times,the second-stage is 1.35 and 1.21 times that of blank group;Solution concentration in 10 mg/mL,the average life span and maximum life of resveratrol superfine powder flies are respectively 1.02 and 1.02 times,the second-stage is 1.24 and 1.14 times that of blank group.This suggests that resveratrol can slow down the ageing process of fruit flies,prolong the service life of fruit flies,and in effect is better than that of the second-stage resveratrol superfine powder.8.pharmacokinetic analysis:resveratrol superfine powder and powder in rat in vivo bioavailability.Results the blood concentrations of resveratrol superfine powder during 15 min has reached the maximum peak 2.35 ?g/mL,at 30 min to reach 1.8 ?g/mL,then slowly fell to 0.01?g/mL in 8 hours.Resveratrol powder blood drug concentration,also reached the maximum peak when 15 min 1.95 ?g/mL,then slowly fell to 0.01 ?g/mL in 8 hours(including g/mL.And resveratrol superfine powder of the AUC value is 1.9 times of the second-stage.This shows that the bioavailability of resveratrol superfine powder powder is 1.9 times.After 3P87 software calculation,Ka values more resveratrol superfine powder,in effect time is long,long half-life,have sustained-release effect.Given all this,using the method of supercritical flow weight crystallization technology SAS to resveratrol superfine powder preparation technology,mature,reliable,preparation of resveratrol superfine powder,particle size is small,the saturation solubility,dissolution speed,good antioxidant effect and high bioavailability.This technology greatly improved the water soluble of resveratrol,and not to introduce impurities.Provides a new basis for resveratrol production. |
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