Preparation Of Rutin Conjugate And Its Pharmacodynamics

Rutin?RT?is a flavonoid extracted from plants and has anti-inflammatory,anti-oxidant,anti-bacterial,anti-cancer and blood pressure lowering effects.However,due to its poor water solubility and low oral bioavailability,its clinical application is highly limited.In order to improve its clinical application.This experiment modified the RT with hyaluronic acid?HA?to improve its water solubility greatly.Moreover,the anti-inflammatory,anti-bacterial and anti-oxidation effects of the modified RT were improved to a certain degree.The article mainly carried out the following work:1 Rutin was extracted and separated by alkali extraction and acid precipitation.Conditions:The extraction solvent is alkaline water,the ratio of material to liquid is 1:10,the extraction temperature is 60°C,the extraction time is 30 min,and the extraction times are 3 times.¹H-NMR,FT-IR and UV were used to prove that the target product is rutin.2 HA-RT,a water-soluble compound with a solubility of 850 mg/mL,was obtained by modification of RT with HA?the grafting rate of RT on HA was 50%?.It was characterized by ¹H-NMR,FT-IR and UV.Haemolysis test,stability test and cytotoxicity test showed that HA-RT had good biological safety.3 In vitro,the effects of RT,HA-RT and DXMS on inflammatory factors?TNF-?,IL-1?,NO?in LPS-induced RAW 264.7 macrophage inflammation model were measured by ELISA kit.In vivo,the effects of RT and HA-RT on xylene-induced inflammation in mice were measured by auricle swelling method.The results showed that the levels of inflammatory factors?TNF-?,IL-1?,NO?in the HA-RT group were lower than those in the RT group.At the same molar concentration,the anti-inflammatory abilities of RT,HA-RT and DXMS were DXMS>HA-RT>RT.The ear swelling rate of auricle in the HA-RT group was lower than that in RT group,indicating that the anti-inflammatory effect of HA-RT was better than that of RT?the rutin content in HA-RT was the same as that of rutin monomer?.4 Minimum inhibitory concentration?MIC?and minimum bactericidal concentration?MBC?of RT and HA-RT against Escherichia coli.Staphylococcus aureus and Candida albicans were measured by test tube method.The results showed that the MIC and MBC of HA-RT?the solvent is sterilized water,the rutin content in HA-RT was the same as that of rutin monomer?were 0.08 mg/mL and 0.11 mg/mL for Escherichia coli,0.11 mg/mL and 0.13 mg/mL for Staphylococcus aureus,0.07 mg/mL and 0.09 mg/mL for Candida albicans.And the MIC?0.4 mg/mL?and MBC?0.8 mg/mL?of RT?solvent 20%ethanol?group were higher than those of the HA-RT group,indicating that the antimicrobial effect of HA-RT was better than that of the RT group.5 Scavenging DPPH radical method,ABTS⁺radical method and superoxide anion radical(O^2-)method were used to measure the antioxidant ability of RT,HA-RT and Vc.The results showed that after the concentration reached a certain level,the scavenging rates of DPPH free radicals,ABTS⁺free radicals and O^2-free radicals by Vc and HA-RT were almost equal to 100%.However,the clearance rate of O^2-radical by HA-RT was higher than RT at each concentration,indicating that HA-RT has stronger antioxidant capacity.In conclusion,the preparation of HA-RT has achieved the original research purpose,greatly improving the water solubility of RT,and making it have a good development,production and application prospects in anti-inflammatory,anti-bacterial,anti-oxidation and other applications...