| Iron and cobalt are essential trace elements in the biological organism,which are closely related to the health of human and animal,directly or indirectly involved in the process of the metabolism of life activities.At present,the trace element injection of animal has the disadvantages of operation trouble,stress,and not suitable for large-scale,intensive farming use and so on.Oral dosage forms have a great quantity of medicine,frequent drug administration,poor absorption effect,and its safety and bioavailability are affected.In order to improve the bioavailability of two kinds of trace elements of iron and cobalt,the deficiency of the use of injection and oral preparation in the market is improved.The study by emulsion solvent evaporation method,the selection of acrylic resin II as capsule material,liquid paraffin as continuous phase,the preparation of iron-cobalt composite microcapsules.The characteristics of iron-cobalt composite microcapsules(appearance,particle size,drug loading,encapsulation efficiency,in vitro release rate,pharmacokinetics)and the effect of anti-anemia were measured.Its research contents are as follows:(1)Design the single factor experiment and response surface experimental design and optimization to optimize the prescription and preparation of microcapsules,the optimum prescription and process for Iron citrate dosage 0.48 g,liquid paraffin 80 mL,talcum powder 0.32g,Span-80 1.8 mL,Twain-80 0.2 mL.The surface of the prepared microcapsules was smooth and round,and the size distribution was even,with the average particle size of 180±9.45?m.In order to determine the encapsulation efficiency and drug loading of iron-cobalt composite microcapsules,the determination method(flame atomic spectrometric method)of iron and cobalt content was established.The average drug loading rate of iron-cobalt composite microcapsules was 45.32%,and the encapsulation efficiency was 90.61%.(2)To compare the pharmacokinetics of iron and cobalt in healthy rabbits by using iron-cobalt composite microcapsules and compound trace elements of animal and poultry.The plasma iron and cobalt concentrations were determined by flame atomic absorption spectrometry.The pharmacokinetic parameters were analyzed by DAS 2.0 and the data were analyzed with SPSS 19.The main pharmacokinetic parameters of iron in iron-cobalt composite microcapsules were obtained.Absorption half-time of T1/2Ka=(0.86 ± 0.14)h,drug distribution half-time T1/2?=(1.26± 0.23)h,Medicine under the curve of AUC(0-?)=(108.19+14.42)mg/L h.Iron-cobalt composite microcapsules group fitting equation of C =291.498e-0.564t+203.789e-0.361t-495.287e1.076t.The main pharmacokinetic parameters of cobalt in iron-cobalt composite microcapsules were obtained:absorption half-time T1/2Ka=(1.29±0.59)h;drug distribution half-time T1/2?=(1.99±0.72)h,drug curve AUC(0-?)(115.22±53.20)mg/L h.Iron-cobalt composite microcapsules group fitting equation of C=69.555e-0.375t+46.132e-0.196t-115.687e0.608t.The results show that iron-cobalt composite microcapsules of pharmacokinetic behavior is consistent with the two compartment model,cobalt iron trace elements after microencapsulation,slow absorption rate,eliminate slow rate,prolong action time and bioavailability are significantly improved.(3)The mice fed on low iron diet method to establish a mouse model of iron deficiency anemia,then the mice model of iron deficiency anemia intragastric administration of low,medium and high dose(0.08 g/kg weight,0.12g/kg body weight,0.16 g/kg weight),iron-cobalt composite microcapsules and to observe the changes of each group mouse red blood cell parameters and iron metabolism indices.Found that the mice were fed for 4 weeks,mice in the low dosage group of red blood cell parameters and iron metabolism indices were significantly lower than those in the normal level.The middle dose group anemia red blood cells parameters,iron metabolism return to normal levels.The high dose group of red blood cell parameters and iron metabolism refers to the standard is significantly higher than the normal level.Conclusion:The successful preparation of iron-cobalt composite microcapsules,the preparation method is simple,reliable,quality control.Drug quality assessment,in vitro release test and pharmacokinetics test showed that,iron cobalt composite microcapsules with enteric coated and slow release,increase the stability characteristics of and has a good application prospect.The test for treatment of mice with iron deficiency anemia,adding equivalent to dietary dose(0.12 g/kg body weight)of iron-cobalt composite microcapsules for 4 weeks can recovery red blood cell parameter value,index of nutritional iron status and did not cause other adverse reactions occur. |
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