The Compatible Stability Of Breviscapine Powder Injection With Raceanisodamine Hydrochloride Injection And The Pharmacokinetics Effect Of Its Associated For Scutellarin In Rats

Objective: The article main investigates on the stabilities of breviscapine. Firstly, itresearches the powder injection of the0.9%sodium chloride injection (0.9%NS),5%glucose injection (5%GS),10%glucose injection (10%GS), glucose and sodiumchloride injection (GNS) and sodium lactate ringer’s injection (SLR). And theninvestigating the compatible stability of breviscapine powder injection mixed withraceanisodamine hydrochloride injection in vivo and in vitro. Finally, it investigates theeffect of the mixed medicine in rats in order to provide the basis for safe, effective andrational drugs’ using in the clinic.Method:(1) The clinical medication was simulated by mixing breviscapine forinjection with5kinds of the clinical common solvents. The samples of the mixtureswhich were prepared for the clinical dose of0.2mg/ml were recorded in0~24hours at25℃or0~48hours at4℃temperature to study the change of its appearance，pHvalues, absorbance, insoluble particle and HPLC chromatograms and contents.(2)Simulating the clinical medication, the solution by0.9%NS as the solvent which wasmixed with breviscapine and raceanisodamine hydrochloride injection were recorded at0~24hours at25℃or0~48hours at4℃temperature to study the change of itsappearance，pH values, absorbance, insoluble particle and HPLC chromatograms andcontents.(3) The rats were randomly divided into breviscapine group and mixture group.Injecting the tail vein with breviscapine firstly and then injecting with raceanisodaminehydrochloride， the plasma concentrations were tested at different time as every5,10,15,30,45,60,90,120,180minutes.The compartment model and pharmacokineticparameters were calculated with two groups and then compared the two groups fittedwith Practical Pharmacokinetic Program-Version (DAS2.1.1).Result:(1) After mixing the injection of breviscapine with5kinds of the clinicalcommon solvents, the appearance, pH values, absorbance, HPLC chromatograms and contents of the mixtures in24hours at25℃or48hours at4℃temperature showed noobviously change. There was in lined with the relevant regulation in ChinesePharmacopoeia in terms of insoluble particles when the breviscapine mixed with0.9%NS or5%GS at0~24hours at25℃or0~48hours at4℃temperature,but theincrease of insoluble particles was beyond the relevant regulation in ChinesePharmacopoeia with in0h at0~24hours in25℃or0~48hours in4℃temperatureafter mixing the breviscapine for10%GS, GNS and SLR.(2) It showed nothingdifference on the appearances, pH values, absorbance, insoluble particle and HPLCchromatograms and contents of the mixtures of breviscapine and raceanisodaminehydrochloride injection.While comparing with the breviscapine in0.9%NS, thecontents of mixture were decreased10%.(3) No matter the mean serum concentrationsof Scutellarin after iv breviscapine or the mixed drugs in rats were both fitted to atwo-compartment model with a weight of1/C2. And the main pharmacokineticparameters of Scutellarin in two groups were showed respectively as following:t1/2α=3.855±0.258min，t1/2β=44.048±10.837min，AUC(0-t)=454.574±54.967mg·min-1·kg-1，AUC(0-∞)=639.902±83.743mg·min-1·kg-1，Vc=0.425±0.193L·kg-1，CL=0.032±0.005L·min-1·kg-1.t1/2α=2.440±0.387，t1/2β=60.428±13.695min，AUC(0-t)=597.619±64.907mg·min-1·kg-1, AUC(0-∞)=965.45±127.965mg·min-1·kg-1， Vc=0.171±0.05L·kg-1,CL=0.021±0.002L·min-1·kg-1。Conclusion: Breviscapine for injection is stable in0.9%sodium chloride injection or5%glucose injection with24hours in room temperature and48hours in coldpreservation. Breviscapine for injection was not suit for combining withraceanisodamine hydrochloride injection directly. Raceanisodamine hydrochlorideinjection can accelerate the distribution and slow down the elimination of scutellarinobviously in rats. The experiments proved that the raceanisodamine hydrochlorideinjection may strengthen the effective of Pharmacodynamics of breviscapine.