The Difference Of Plasma Concentration Of Different Dosage Forms Of Curcumin In Rats And Its Effect On SOD Activity

BACKGROUND:Curcumin is a curcuminoid compound extracted from turmeric and was used to cure diseases thousands of years ago in ancient India and Chinese traditional medicine.Modern Chinese doctors believe that turmeric can break through and relieve pain.Modern medical research find that it has many functions in Western medicine,such as anti-oxidation,anti-inflammatory,free radical scavenging,and antibacterial.In view of its physicochemical properties,curcumin is soluble in organic solvents such as ethanol,alkali,acetic acid,acetone and chloroform,insoluble in water and slightly soluble in benzene and ether.However,because curcumin is poorly soluble in water and hardly soluble in water,it is especially limited in clinical application.After the drug enters the body,the metabolism is faster and the degree of utilization is low,and it is difficult to be absorbed.In the current reports,in order to enhance curcumin efficacy,it has been transformed into a variety of different formulations,such as:phospholipid complexes,nano-body,solid dispersants,etc.,through the author's previous literature review experimental results show that The modification of the preparation has a certain effect on improving its bioavailability and extending the half-life.However,the current various forms have not been widely used in clinical practice,and they have certain practical problems,such as poor stability,easy leakage,high cost,and difficulty in controlling the dosage.Therefore,it is particularly important to find a new dosage form that has a good and stable curative effect and that can be widely used in clinical curcumin formulations.AIM:In this experiment,through the combination of improved pharmaceutical dosage forms with the Materials Science Academy of Beijing University of Chemical Technology,after different doses of curcumin were given to SD rats,the plasma concentrations of curcumin in SD rats were measured to verify the effect of the curcumin dosage form on blood drug concentration.After the activity of SOD was determined,the curative effect of the curcumin dosage form on the antioxidative effect was understood.METHODS:?Preparation of drugs:take a certain amount of hydroxypropyl beta cyclodextrin,add 15%wt of sodium hydroxide,then add 5 times the excess of epichlorohydrin,reaction,dialysis,lyophilization to obtain cyclodextrin.The cyclodextrin and curcumin were added in a 40%ethanol solution at a certain ratio,and the ethanol was stirred in an oil bath at 50? to remove the ethanol on a rotary evaporator.The mixture was filtered and freeze-dried to obtain a curcumin cyclodextrin package.?Experiment 1:24 SD rats were selected and their body weights of about 200 g were randomly divided into 3 groups of 8 in each group.Group A curcumin was dissolved in 0.1%DMSO by intraperitoneal injection;group B curcumin inclusion complex was dissolved in 0.1%DMSO by intraperitoneal injection;group C curcumin inclusion complex was dissolved in 0.9%physiological saline by intraperitoneal injection.The dose was 20 mg/kg.Immediately after administration,blood was collected from the fundus venous plexus at 3,10,25,60,and 120 minutes.After the blood was taken,it was stored at and 4?centrifuged at 3000 rpm.min"1 for 15 minutes.After centrifugation,the upper layer plasma was collected and the label was stored frozen.Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to detect the plasma concentrations of different formulations of curcumin.?Experiment 2:32 SD rats weighing approximately 200g were randomly divided into 4 groups of 8 in each group.The A' group was a blank control group,an equal dose of physiological saline was injected intraperitoneally;B' group curcumin was dissolved in 0.1%DMSO intraperitoneally;C' group curcumin clathrate dissolved in 0.1%DMSO intraperitoneally;D' group curcumin inclusion compound was dissolved in physiological saline by intraperitoneal injection.The dose was 20mg/kg,blood was taken 60 minutes after administration,and SOD activity was measured to detect changes in the antioxidant index of different formulations of curcumin.?Data were analyzed by mass spectrometry using Waters MassLynx software.In addition,DAS 3.0 was used to establish an atrioventricular model and the plasma concentration of curcumin in rats plasma was determined to be the Peak concentration,the area under the cure,the elimination half-life,and the mean retention time.Some data were analyzed using SAS and SPSSsoftware.RESULTS:?Experiment 1:The linear relationship of curcumin concentration in the range of 12.5-1000 ng/mL was good(r2= 0.997);the lower limit of quantitation was 12.5 ng/mL.After rats were intraperitoneally injected with curcumin +0.1%DMSO solution,curcumin inclusion compound+0.1%DMSO solution,and curcumin inclusion compound + 0.9%physiological saline,the metabolic process of curcumin in rats complied with the one-compartment model,and theCmax was obtainedwere 6.13ng/ml,149.65ng/ml,and147.75ng/ml,respectively;t1/2 was 0.122h,0.736h,0.640h,respectively;AUC(O-t)were 4.120h*ng/ml,167.712h*ng/ml and 153.751h*ng/ml,respectively.MRT was 0.177h,1.062h,and 0.924h,respectively.?Experiment 2:The average value of SOD activity in the blank control group was 59.67,the average SOD activity in the curcumin ? 0.1%DMSO group was 106.67,the average SOD activity in the curcumin inclusion compound ? 0.1%DMSO group was 308.33,and the curcumin inclusion compound the average value of SOD activity in the physiologicalsaline group was 329.00.The activity of SOD in the drug group increased,and the SOD activity in the curcumin inclusion compound group increased more significantly.There was no significant difference between the two groups after statistical pairing design analysis.CONCLUSION:The plasma concentration of curcumin inclusion complex group was significantly better than that of ordinary curcumin group.Compared with the blank group,the SOD activity was increased,suggesting that curcumin cyclodextrin inclusion complexes are effective for transformation.Curcumin cyclodextrin inclusion compound can increase curcumin solubility and blood drug concentration,and can enhance the SOD activity.