Preparation And Characterization Reaseach Of Several Coenzyme Q₁₀ Nano-formulations

Coenzyme Q10(CoQ10)is a benzoquinone compound which can be produced by plant or the human body.As a component of the electron transport chain in the cell,coenzyme Q10 plays a key role in energy metabolism.Moreover,it is only lipophilic antioxidant in human body which is widely distributed in human cell membrane,and is very important to delay aging and improve immunity.However,coenzyme Q10 in the body would probably reduce because of gene mutation,aging,cancer or using drug.In this case,supplementation of the exogenous coenzyme Q10 is very necessary.In clinical practice,coenzyme Q10 is a medicine of curing heart disease,diabetes,Parkinson's disease or other diseases.Coenzyme Q10 is insoluble in water and its oral bioavailability is poor.Furthermore,it is unstable and likely to be oxidized in the air and be decomposed in the sunshine because molecular structure of coenzyme Q10 contains unsaturated double bonds.In addition,heat or encountering metal ions would accelerate the decomposition.These factors can result in decrease of coenzyme Q10 content in products.These properties greatly limit its application.Nano-drug delivery system can improve solubility and bioavailability of coenzyme Q10,and can prevent effective the destruction of drug structure.In this paper,we will conduct relevant reseach on coenzyme Q10 nano-transmission system to solve these issues above.The major contents are as follows:1.In order to improve hydrophilia of coenzyme Q10,coenzyme Q10 micro-particles were prepared by anti-solvent crystallization method.We investigated influences of the drug solution concentration,system temperature,stirring speed and stirring time,etc.on micro-particle size.Finally get optimum conditions of micro-particles preparation:drug concentration 50mg/ml;solvent and anti-solvent volume ratio 1:6;the system temperature 4?;stirring speed 4000r/min;stirring time 10min.In this process condition,microparticles of average diameter 1.84?m were obatained.Properties of products were characterized using X-ray diffraction(XRD),infrared spectroscopy(FT-IR),differential scanning calorimetry analysis(DSC),etc.The results show that chemical structure of coenzyme Q10 micro-particle has not changed,but the melting point and intensity of diffraction peak decreased.2.Solution method combined with high-pressure homogenization was used to prepare coenzyme Q10-y-cyclodextrin inclusion complex.Encapsulation efficiency and mean particle size of the drug inclusion complexes as indicators to examine the quality of products.Single-factor test was performed to select the appropriate factors and levels.On this basis,we optimize the preparation process of the inclusion using response surface method and the optimal results are as follows:the quality ratio of y-cyclodextrin and drug 7.76:1,the ultrasonic temperature of 40?,ultrasonic time 28.33min,and homogeneous pressure of 40MPa.Under such conditons,we obtained the drug inclusion complex of average encapsulation efficiency of 48.39%,and average particle size of 334nm.The saturation solubility of complex product increased about 4.8times compared to raw material.In vivo pharmacokinetic studies in rats showed that AUC values of raw materials and the inclusion compound products were 19.58?g/h/ml and 28.90?g h·ml-1 when oral doses was 40mg/kg,and bioavailability was effectively enhanced.3.Emulsion and vacuum evaporation combined with high pressure homogenization method was used to prepare coenzyme Q10 precursor nanoliposomes.Encapsulation efficiency and mean particle size of the drug inclusion complexes as indicators to examine the quality of products.Orthogonal experimental was performed for optimizing preparation process and formulations of precursor nanoliposomes,the results are as follows:the quality ratio of soybean lecithin and cholesterol 4:1,usage amount of soybean lecithin 100mg?mass ratio of soybean lecithin and drug 10:1,volume ratio of the organic phase and aqueous phase 1:6,high pressure homogenization pressure 60MPa,vacuum evaporation temperature 45?,the initial emulsification time 5min.Under such conditons,we obtained precursor liposome that its reconstruction solution's average particle size was 241nm,and encapsulation efficiency was 67.31%.Through comparing experiments,trehalose was chosed as appropriate lyoprotectant,and its dosage was 1:2(mass ratio of lecithin and trehalose).Prepared precursor nanoliposome has good stability.There were no significant changes of the average particle size and encapsulation efficiency after 90 days of storage.4.To investigate the O/W submicron emulsion injection formulation,and investigate its pharmacokinetics in the rat.Pseudo-ternary phase diagrams were established using the water titration method.The effects of different surfactants,cosurfactants and Km values on the phase diagram were investigated,and the prescription of submicron emulsion formulation was optimized.Stability of coenzyme Q10 submicron emulsion was evaluated,and the pharmacokinetics in the rat after intravenous injection was study.We found coenzyme Q10 submicron emulsion consisting of Poloxamer188/Lipoid S100/ethanol/PEG400/water have the lower viscosity,the smaller size and the higher encapsulation efficiency.An obvious sustained-release effect of coenzyme Q10 submicron emulsion was observed after IV injection in the pharmacokinetics experiment,and mean residence time is 6.55h.The optimized coenzyme Q10 submicron emulsion consumes smaller quantities of auxiliary materials and shows good stability.Moreover,it is easy to manufacture and convenient for clinical usage.