| The antibacterial mechanism of florfenicol is working by inhibiting protein which was synthesized in ribosomes of bacterium. Florfenicol has a broad antibacterial spectrum and a stronger bactericidal effect which was used to treat the diseases caused by bacterium of pigs, cattle, aquaculture animal and Aquatic animals bacterial widely. However, currently, florfenicol has poor water soluble and its solution formulation should be dissolved in an organic solvent which reduce the bioavailability of florfenicol; And it has poor stability which leads to occur degradate easily and the efficacy will be disappeared. In this paper, by changing the antibacterial activity of florfenicol to study the stability and the change of degradation in acidic, neutral and alkaline solution; Finally, florfenicol was inclusioned with β-cyclodextrin and Preparated of β-cyclodextrin inclusion in order to improve the water solubility and stability of florfenicol.Common florfenicol contains two optical isomers, L-type and D-type; The type of florfenicol (1R,2S) L-body configuration has antibacterial activity; While the right-handed optical isomers configuration (IS,2R) has no activity and even possible to inhibit florfenicol itself activity to some extent. While in neutral liquid environment, the structure of florfenicol did not change over time, but its antibacterial activity was disappeared with the time ago. Thus, we speculated that florfenicol have changed its structure by right-handed florfenicol to left-handed after it was dissolved in the water, which leads to the antibacterial activity was disappeared but its structure has not changed.The florfenicol was dubbed to acidic, neutral and alkaline solution, the decomposition was detected by HPLC. The structural decomposition components of florfenicol was confirmed by LC-MS.The results showed that florfenicol is stable in acidic and neutral environment, while it is unstable in alkaline solution, and it content is changing with time.F ions was substituted by hydroxyl and generated thiamphenicol, amide bond was hydrolyzed, amino section generated florfenicol amine, and hydroxyl moiety generated dichloro acetaldehyde in alkaline environment. While dichloro aldehyde is unstable in alkaline solution, which will be converted to dichloroacetic acid and generated dichloroacetic acid sodium at the last. Thus, the dichloro acetaldehydean content was unstabled when it was showed in the liquid phase diagram. The content of thiamphenicol was increased at beginning, but the content was reduced later because the generated thiamphenicol contains an amide bond which is unstable and was turned to florfenicol amine and dichloro acetaldehyde finally in an alkaline environment.The best formulation and preparation process were selected through single factor and the orthogonal table L9(34)was screened to preparate florfenico1 -β- cyclodextrin inclusion complex.Florfenicol was dissolved in propylene glycol, and inclusion complex was prepared by saturated aqueous solution. The result of inclusion was detected by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Test Results showed that the dissolution of inclusion complex was significantly higher than florfenicol. The cumulative dissolution rate of inclusion complex reached 82.83% while the florfenicol was 12.43% at 45min and the water-soluble was improved 6.67 times. It suggested that cyclodextrin inclusion could improve the solubility of florfenicol and improve its bioavailability.With the Florfenicol instead of chloramphenicol was used widely and even abuse in veterinary clinic, the phenomenon of bacteria resistant to florfenicol was more serious, some common pathogens such as E. coli etc had very high resistance rates. The activity research of florfenicol combined with berberine to against E. coli. Joint sensitivity test, The MIC of florfenicol was 8ug/ml while berberine was 32ug/ml and the FIC index was 0.75; it indicated that florfenicol and berberine has an additive effect. The mechanism of combine berberine (BBR) with florfenicol may eliminate the resistance plasmid of berberine or may BBR increased the permeability of the bacterial cell membrane so that florfenicol was easy into E. Coli and reduced MIC values. However, this study is a preliminary test and the results were limited to the laboratory.To sum up:The degradation of florfenicol was studied preliminarily in this paper, which was proved that the degradation of florfenicol under different environmental conditions. Florfenicol with β-cyclodextrin inclued, its water-soluble greatly was increased which improved the the water-soluble of florfenicol effectively. Florfenicol combine with berberine can also provide a reference for improving the florfenicol resistance. These results provide a theoretical basis for in-depth exploration of florfenicol. |
