| Diarrhea is one of the most common diseases in piglets,which can cause problems such as stunted growth and death of piglets.Piglet diarrhea has caused huge economic losses to my country’s animal husbandry,and it is a great problem that the pig industry is concerned about.The research group’s previous research found that baicalin aluminum has a significant effect on the treatment of piglet diarrhea,and baicalin zinc has good antibacterial activity.Premix is a commonly used veterinary dosage form,suitable for group administration of pigs and chickens.Therefore,this project optimized the synthesis process of baicalin zinc,confirmed the structure of baicalin zinc,prepared premix of baicalin zinc for piglets through prescription screening and process research,and developed a draft quality standard of baicalin zinc premix.1.Synthesis and structure characterization of baicalin zinc.Based on the previous research of our group,the process optimization was carried out to react baicalin raw material with zinc salt to produce baicalin zinc,and the two drying methods（oven drying at 55℃or freeze-drying）of the product were investigated by comparison of solubility,drying weight loss and content determination.The results showed that the baicalin zinc obtained in both ways was almost insoluble in water,anhydrous ethanol,methanol and acetonitrile;the difference in drying weight loss results was small（drying:6.35%,freeze-drying:6.31%）;the baicalin content in freeze-dried baicalin zinc（61.95%）was lower than that in the drying condition（74.37%）,which may be due to the degradation of baicalin content caused by the long freeze-drying time,and freeze dryer was thought to be costly in production applications,so the drying method of oven drying was chosen.The synthesized product was structurally confirmed by UV,IR and atomic absorption spectroscopy,and it was presumed that baicalin zinc was a 1:1 complex of baicalin and zinc with a molecular weight of 685.2.Prescription screening and preparation process of baicalin zinc premix.The premix was prepared by adding appropriate amount of diluent and flow aid with baicalin zinc as the main active ingredient.The diluent was screened by drying weight loss,moisture absorption,fluidity and pH,and the flow aid was investigated by comparing the fluidity of adding different proportions of micronized silica gel,and finally anhydrous calcium hydrogen phosphate was determined as the diluent and 1%micronized silica gel as the flow aid.The preparation process of baicalin zinc premix was as follows:baicalin zinc,anhydrous calcium hydrogen phosphate and micronized silica gel were dried,crushed,passed through 100 mesh sieve,mixed in equal increments according to the ratio of baicalin zinc:anhydrous calcium hydrogen phosphate:micronized silica gel of 27:72:1,and packed in double-layer aluminum foil bags of 100 g each.3.Study on the quality standard of baicalin zinc premix.The identification and content determination of baicalin contained in baicalin zinc were carried out by high performance liquid chromatography.Baicalin zinc was dissolved by ultrasonication with acetonitrile-0.05%phosphoric acid solution（40:60）as diluent,The chromatographic conditions were as follows:a Diamonsil C18（5μm,150×4.6 mm）column was used;the mobile phase was acetonitrile-0.05%phosphoric acid（30:70）,the UV detection wavelength was 278 nm,the flow rate of 1.0 m L/min,the column temperature was 30℃,and the injection volume was 20μL.After methodological verification,the correlation coefficient was 0.9999 in the range of baicalin concentration of 10～200μg/m L.The results showed that the method had a good linear relationship.The linear equation was Y=76954X-24589,the average recovery rate was101.82%,the precision RSD value was 0.08%and the repeatability RSD value was0.97%,and the stability test results showed that the solution was stable within 24hours after preparation,which was in line with the"Guidelines for the Verification of Veterinary Drug Quality Standard Analysis Methods".Three batches of small samples were prepared and tested for the properties,identification,inspection items（loss on drying,uniformity of appearance）and content of the preparation in accordance with the inspection requirements of the premix of the Veterinary Pharmacopoeia of the People’s Republic of China（2020 edition）,Part I（Appendix）.The quality standard（draft）of baicalin zinc premix was formulated to provide a basis for the quality control of baicalin zinc premix.4.Stability study of baicalin zinc premix.In accordance with the Technical Guidelines for Stability Study of Veterinary Chemical Drugs and the proposed quality standard of baicalin zinc premix（draft）,factor,accelerated and long-term tests were conducted to examine the stability of the prepared baicalin zinc premix products.The results of the factor test showed that the appearance and content of baicalin zinc premix did not change significantly under the condition of 4500 Lx of light,indicating that the product was stable under strong light.Under the condition of high temperature60℃,the color of product appearance lightened slightly,and the content changed a lot,which decreased about 11.02%,indicating that the product needs to be stored at room temperature.Under the condition of high humidity（90%,75%）,the appearance and color of the product deepened,and the content did not change significantly.The indicators of each check item in the accelerated test results were in accordance with the requirements of premixes in the general rules for preparations of the Veterinary Pharmacopoeia of the People’s Republic of China（2020 edition）part I.There was no significant change in the appearance of the product and no significant decrease in the content,indicating that the product was stable under the accelerated test conditions and could be packed in aluminum foil bags with stable quality.The long-term test was conducted for 2 months and the stability of the product was good,and the study is still in progress.In conclusion,the premix of baicalin zinc developed in this experiment is reasonable in prescription,simple in preparation process and controllable in quality,which is expected to provide a new therapeutic drug for piglet diarrhea. |
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