Studies On Coenzyme Q₁₀ Intravenous Nanoemulsion

As biochemical drugs, CoQ₁₀ is lipophilic medicine and it coexists with vitamin. Itexists in animal body and the concentration of CoQ₁₀ in hominine heart, liver andpancreas are higher. Total concentration is 0.5¹.5g. CoQ₁₀ is endogenesis compound andit has lots of pharmacological active. It can active cellular breath and metabolization. Atthe same time it is very important antioxidant。Studies on epidemiology indicate that theconcentration of CoQ₁₀ of human being is beginning to descend gradually when we 20years old. Complement of CoQ₁₀ can make CHF patients, damnification of lymphocytemembrane lighten. The heart function is improve in evidence. This article has studied onCoQ₁₀ focusing on its therapy about CHF.At present, there are injection, tablet, capsule and lipid on sale. The price of CoQ₁₀ istoo high and it is hardly dissoluble, but it can dissolve in ethanol and oil, We test themelting point, apparent oil/water distribute coefficient (P) and examine the stabilitiesunder the high temperature and strong light, therefore this article choose the intravenousnanoemulsion to be the dosage form of CoQ₁₀. At first common lipid emulsion is blank, itcan offer nutrition for patients who have been operated just now. With pharmacydeveloping, the lipid emulsion became a new carrier of indiscerptible dugs. It not onlycan improve stability, but can avoid bring more organic impregnant. At the same timeconcentration of medicine in out-water-phase is very low, it can reduce possibility ofphlebitis. In addition intravenous emulsion has strong target ability. It can arrive at theRES of liver, kidney, spleen, lung, heart and marrow. So concentrationg of other tissuesare lower correspondingly.Refined egg phospholipid and importation F-68 were chose as emulsifiers , the bestproportion and total dosage were decided when the judgemental criterion was interfacialtension using single factor method. We also decided dosage of oleic acid Na. Therefore,we frame the recipe of CoQ10 intravenous nanoemulsion(1.25mg/ml).Conventionalintravenous emulsion was prepared with ultrasonic, high speed mix round machine,colloid milling etc. We use the more advanced nano-machine to prepare the intravenousemulsion and make the particle size of emulsion is about 200nm. During this course, weinspect the particle size distribution and zeta-potential to choose the best technics:original emulsion is under ultrasonic for 5min,70℃then we use secondary P 1000barand first P 100bar ,3times.Finally,adjust pH to 8.0 and sterilizing for 30min under 115℃. Establish quality evaluation and content determination method of CoQ10nanoemulsion by ultraviolet and HPLC to test the physico-chemical stabilities. One isphysical stability, it is about rheology character, viscidity value is 5.58 mpa.s, it willaffect the expedite character, when we inject. So we use the CoQ10 intravenousnanoemulsion mixed with physiological saline and glucose injection with the samevolume. Viscidity values are reduce to 1.07 mpa.s and 1.51 mpa.s respectively. The otheris chemic stability, we use HPLC to test the concentrationg changes under hightemperature, strong light and accelerated test. At the same time we screen out the bestextraction method of CoQ10 from emulsion.According to Arrhenins formula, we calculate the t0.9 is 724 days(1.98years). Establish quality evaluation and content determination method of CoQ10 of ratblood plasma, The CoQ10 nanoemulsion release kinetics of rats is complied with thesecend order model according to results of 3p97. CoQ10 intravenous nanoemulsionpharmacokinetics equation of rats :C=57.17e-0.0696t + 437.92e-0.0267t. T1/2a =9.956min,T1/2b=25.960min, K10=0.0287, K12=0.0290min, K21=0.0650, MRT=30.56,AUC(0-t)=17222.08, AUC(0-&)=18236.82, AUMC=535151.3 and according to results ofStat. quadrature : AUC(0-t)=14686.47,AUC(0-&)=15360.0,AUMC=516033, Ke=0.0261,...