| Coenzyme Q10(CoQ10),also known as ubidecarenone 50,is a kind of natural lipophilic chemicals.As an important intermediate in the electron transport system of mitochondria,it acts as a redox component of transmembrane electron transport system in mitochondria respiratory chain as well as a stabilizer on cell membrane.CoQ10 can also be used as an effective antioxidant and scavenger.At present,most of the researches on CoQ10's antioxidant activities are mainly focused on the relationship between CoQ10 and oxidative stress related diseases,such as cardiovascular disease,neurodegenerative diseases and photoaging and cancer.Despite its nutritional and drug benefits,CoQ10 is a liposoluble substance with poor water solubility and low bioavailability after oral administration,which limits its application.Therefore,the use of preparation methods to effectively improve the human bioavailability of CoQ10 has become a hot spot in recent years.This study was mainly prepared by chemical synthesis of folic acid dextran couplet,CoQ10 nanopreparation was prepared by high pressure homogenization method.A total of 4 factors that were the mass ratio of surfactants and CoQ10,the number of cycles,homogeneous pressure,the mass ratio of CoQ10 and folic acid dextran couplet were studied the effect on the mean particle size by single factor experiment method.On the basis of single factor experiment,orthogonal test was used to test the optimization of mean particle size,the optimum condition was obtained,and the CoQ10 nanopreparation physicochemical properties,preparations dissolution rate in vitro,bioavailability in vivo of rats,fluorescence imaging were studied.The results of the study are as follows:1.Folic acid dextran couplet was prepared by chemical synthesis method.by Fourier transform infrared spectroscopy(FITR)reaction after verification of dextran hydroxyl bending vibration peak at 1664.6 cm-1 disappeared,absorption peaks in the IR spectra of folate dextran at 1716.6 cm-1 in the carbonyl bond generation,that is folic acid dextran couplet,folic acid coupling degree is 14.125%.2.The single factor experiment on CoQ10 nanopreparation process was optimized,the optimum process conditions were as follows:the mass ratio of stabilizer and CoQ10 was 0.4:1,the mass ratio of CoQ10 and folic acid dextran couplet was 1:12,the cycle times were 6 time and homogenization pressure was 800 bar,.3.The orthogonal experimenton was based on single factor optimization,the optimum process conditions were as follows:the mass ratio of stabilizer and CoQ10 was 0.4:1,the mass ratio of CoQ10 and folic acid dextran couplet was 1:18,the number of cycles was 6 cycles and homogenization pressure was 800 bar.4.The results of CoQ10 nanopreparation physicochemical properties showed that the images of scanning electron microscopy(SEM)showed that the CoQ10 raw material physical mixture were dispersed,irregular crystal plate,and the particle size of CoQ10 nanopreparation decreased,a ball shaped.FI-TR showed that the three infrared absorption peaks were basically the same,indicating that functional groups or chemical structures were basically unchanged.But it can be seen from the result that CoQ10 nanopreparation had an absorption peak at 3375 cm-1.The absorption peak for the expansion vibration of intermolecular hydrogen bond O-H should be caused by nanoscale,and the particle size of nanoscale preparation was smaller,which leads to the increase of the intermolecular force,van der waal forces,and the hydrogen bond force was obvious.The results of X-ray diffraction(XRD)and differential scanning calorimetry(DSC)showed that the crystallinity of the CoQ10 nanopreparation decreased,and basically changed into amorphous structure.Stability experiment showed that CoQ10 nanopreparation,with preparing into lyophilized powders,possesses a long-term stability.5.The dissolution rate experiment in vitro results showed that the dissolution rate of CoQ10 nanopreparation was higher than that of the raw material,and the dissolution rate of nano preparation reached 77.5%at 60 min,while the raw material was only 21.3%and the nanopreparation was 3.64 times the raw material.The results showed that the CoQ10 nanopreparation can significantly improve the drug dissolution,mainly due to the reduction of the particle size of nanopreparation,which increased the specific surface area,thereby increasing the drug's dissolution rate.6.The pharmacokinetics results of CoQ10 nanopreparation showed that CoQ10 nanopreparation could significantly increase the oral bioavailability of CoQ10.The drug-time curve of CoQ10 showed that the plasma concentration at each time point was higher than that of the raw material.According to the pharmacokinetic parameters,the content of plasma CoQ10 in plasma was very low after oral administration,the drug slowly absorbed about 4 hours to reach Tmax and the CoQ10 nanopreparation was absorbed in about 2 hours.By observing the Cmax and AUC of the raw material and CoQ10 nanopreparation,the plasma CoQ10 content after oral administration was very low.It was found that the Cmax and AUC of the CoQ10 nanopreparation increased significantly,and the Cmax and AUC values were 0.82 ?g/mL and 10.94 mg/L-h,respectively.The Cmax and AUC of the nanopreparation were found to be significantly increased at 2.25 ?g/mL and 25.98 mg/L·h,indicating that the reduction in particle size can significantly increase the oral bioavailability of CoQ10.In summary,the CoQ10 nanopreparation studied in this paper were prepared by high-pressure homogenization and optimized by single-factor and orthogonal experiments.The average particle size was small,the crystallization degree was low,basically in the amorphous state.The dissolution rate in vitro increased,and significantly improved the bioavailability of CoQ10 in rats,so as to better exert their pharmacological effects. |
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