The Research On Improving Solubility Of Dehydrosilybin By Phtosomes And Nanosuspension

Silymarin extracted from milk thistle is the main component of flavonoids.Silybin is one of silymarin which has the main medicinal activities.There are two isomorphic forms of silybin A and silybin B.The medicinal activities of the two substances are mainly reflected in the effects of protecting liver,eliminating free radicals in vivo,resisting reactive oxygen and inhibiting the proliferation of cancer cells.In addition,they also have the effects on regulating blood sugar and improving the level of fat metabolism in the body.However,its bioavailability was low owing to the poor solution.2,3-dehydrosilybin was obtained by removing a pair of hydrogen atoms at the 2,3 position and forming a double bond of carbon.It possessed the most of the medicinal activities of silybin and higher activity than silybin in free radical scavenging,antioxidation and anticancer changes.However,the poor solubility,low content in nature,and difficult to separate also hindered its application.Therefore,the preparation method of 2,3-dehydrosilybin was studied in this paper,and the solubility of it was improved by the method of phospholipid complex and nano-suspension.The inorganic base catalytic method was used to prepare 2,3-dehydrosilybin to avoid the introduction of high toxicity and polluting substances in this paper.The effects of different catalysts,reaction temperature,time and environment on the yield of silybin were investigated.The yield of the prepared product can reach 49.7%at the optimum process conditions that anhydrous K₂CO₃ was as catalyst,heating temperature was 63°C,the refluxing time was 1.5h and the pH was 12.6.In this paper,2,3-dehydrosilybin was prepared to submicron or nanometer-sized particles by the method connecting wet ball milling with nano-precipitation.Then,stable colloidal dispersion was formed in water by using surfactant and auxiliary agent.Finally,the nanometer suspension was obtained.The effects of different stabilizers,the concentration of dehydrosilybin,the content of surfactant,rotating speed of ball mill and treatment time on the particle size distribution were investigated.It was found that Poloxamer 188 used as stabilizer,the concentration of dehydrosilybin?15 mg/ml?,the content of Poloxamer?0.5%?,the rotation speed of ball mill?600 rpm?,and the rotation speed?300 rpm?was the optimal condition.In addition,on this condition that ethanol selected as solution medium,water used as the reverse solvent and the drop rate being 3 ml/min,the particle size distribution was fine?PDI=0.15;MPS=232 nm;Zeta potential=-45 mV?,and the dissolution rate and the degree of dissolution were increased by 1.12 times and 0.87 times than before treatment,respectively.what's more,it had good short-term stability.Stable phytosome was formed by electron transfer between soybean lecithin and dehydrosilybin.the effect of the selection of solvent,the ratio of drug to lipid,the heating temperature and the amount of solvent on combination rate and yield were investigated by single factor experiment.The yield of acetone was 85.2%and the bonding rate was 94.2%on this conditinon that acetone used as organic phase,the ratio of drug to lipid?1:1?,the heating temperature?40°C?,the amount of solvent?40 ml?.The characterization results of DHS-Phytosome Nanosuspension was MPS=405 nm,PDI=0.1,the solubility in water was increased by 5 times,and the fat-solubility was increased by nearly 2 times.