| The tylosin is one of macrolide antibiotics that are used specially for animals,which has goodantibacterial activity on Gram-positive bacteria, Gram-negative bacteria and mycoplasma, so it'swidely used in livestock cultivation. It can be administered via i.v, i.m and oral. It distributeswidely in vivo after absorption, and the drug concentration of injection is 2～3 times than oraladministration. Because of the shorter elimination half life and extensive distribution, it's necessaryto make the tylosin into targeting sustained-release praeparatum. The purpose of the study is toprepare tylosin tartrate gelatin microspheres to extend the action time of tylosin in vivo, andinvestigate it's pharmacokinetics characteristic in vivo by the method of high efficiency liquidchromatography. The research provide theoretical basis for further enhancement of the preparationtechnology and the drug's clinic therapeutic efficacy.tylosin tartrate gelatin microspheres (TT-GMS) is prepared by the emulsification-chemicalcrosslinking method. We optimize preparation technology by single factor investigation andorthogonal design test. We detect efficiency of the microspheres by determining the size anddistribution of particle diameter, superficial appearance, fluidity, property of electricity, immersionexpansion coefficient, contents and so on. The result indicate that the mean diameter of TT-GMS is14.52μm, and 76.74 percent of microspheres' particle diameter distribute between 5 and 20μm. Theshape is round, the distribution is uniformity, the character is stable, the dispersion is fine. The drugload is 43.40 percent, the encapsulation efficiency is 87.76 percent, the consequence is well.TT-GMS in blood plasma is detected by high efficiency liquid chromatography. The mobilephase is the mix of natrium perchloricum(2mol/L, ph: 2.5±0.1): acetonitrile(60:40, V/V). Bloodplasma sample is treated by methanol, and we get 4 composition summit. The abruption of everycomposition summit is fine, the dopant summit has no effect. The density of tylosin is 0.05～10.0μg·mL-1, and the linear correlation is well. The coefficient correlation is 0.9969. The averagerecovery is 94.6 percent. The RSD is 4.65 percent. The relative standard deviation were 5.03 in aday, and 5.32 % between days. The result indicate that the reproducibility and the precision is fine,and the method can be used for qualitation and quantititative analysis.Gelatin microsopheres group and control group are established, pharmacokinetics characteristic of microspheres in rabbit is detected by high effeciency liquid chromatography after theintravenous injection. The result of the present study suggest that: pharmacokinetics characteristicof TT-GMS in vivo was fit two compartm, pharmacokinetics equations: C1=9.8456e-4.4489t+0.5670e-0.1828t. AUC 5.3152mg/L·h, distribution half-life time 0.1558h, elimination half life 3.7915h,Cmax 10.4125mg·kg-1, Tcp 22.0910h after administration.Pharmacokinetics characteristic ofTT-GMS in vivo was fit three compartm, pharmacokinetics equations: C1=1.4572e-3.9950t+0.4621e-0.2629t+0.1526e-0.0407t. AUC 19.8090mg/L·h, distribution half-life time 2.4307h, eliminationhalf life 15.7202h, Cmax 6.9845 mg·kg-1, Tcp 96.9400h after administration. Compared withcontrol group, elimination half life prolong 11.92861 h, take mycoplasma bacteriostasis for example,the maintenance time of effective concentration can prolong 28h, AUC increase 14.4938 mg/L·h.Comparison pharrnacokinetics of two sets of praeparatum indicate that it can achieve delayedrelease and prolonged action. |
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