| Objective: Chinese medicine Venenum Bufonis as a model drug for the treatment of hepatitis ducklings intramuscular injection of new temperature-sensitive fo-rmulations, conducting research on its preparation, in vitro Release of gel pharmacodynamic components, quality standards, and the gel formulation stability and du-cklings duck hepatitis virus in vivo pharmacodynamics of a preliminary study.Methods: Pharmaceutical indicators results is an important index for the choice of Venenum Bufonis preparation process; Determine the detail technological parameter by orthogonal experiment, to prefer route preparation process parameters by multiple indicator; Chinese medicine Venenum Bufonis as a model drug, On the basis of scientific lit- eratures,the use of temperature-sensitive materials P407, P188, viscosity modifiers MC, HPMC, SA, PEG4000, etc., the composition of the formulation screening by gelation temperature(Tgel) and in vitro release rate.blank and drug-containing gel preparation by means of“cold Method”, Tgel of different prescription was determined by“magnetic bar method”. the release behaviors of thermosensitive gels were performed by dialysis bag-paddle,to measured and calculated the percentage of in vitro cumulative release of drugs through dialysis bag-paddle, rendering the cumulative release percentage of time curve. The data was fitted by zero-order release equation, first release equation, Higuchi equation to study mechanism of drug release. content determination of cinobufagin and resibufogenin in the new formulations were determined by HPLC,by comparating muscular injection in vivo efficacy of Temperature-sensitive toad venom injection 、Toad venom injection and Amantadine medicine powder injection to preliminary pharmacodynamic study of Temperature-sensitive toad venom injection.Result: the preferred route for preparation process of model drug Venenum Bufonis was refluxed for 3 times by ethanol Ethanol concentration of 90 percen-t,amount of solvent was 8,6,6, every extraction time was 1 h, then filtration an d combined filtrates, and the filtrate was concentrated by evaporated to 0.5 g cr ude drug / mL. The best prescription for temperature-sensitive formulations was Venenum Bufonis concentrate-P407-P188-HPMC-PEG4000(0.08ml:20:2:0.5:0.5). In this formulation, the formulation of the gelling temperature of about 38.8 ℃.In vitro release results showed that the temperature-sensitive gel gradually increase-d release of the active ingredient,in a total of 12 days to release the drug for more than 90%, indicating that the temperature-sensitive gel prepared a model d rug toad venom active ingredients obviously sustained release. Release modelfit the Higuchi equation. Through quantitative analysis to determine the total content of cinobufagin and resibufogenin was not less than 15 μg / ml. Body pharmacodynamic results show: toad venom injection survival rate was 74.3%, medicine amantadine p owder survival rate was 68.6%, Toad temperature-sensitive injection survival rate was 82.9%, the results was Pearsonx2 = 1.943, df = 2, P = 0.379(>0.05) by three groups chi-square test, three methods of treatment of Ducklings viral effe-ct is not significantly different, but in the actual experiment process, due to toad venom injection and amantadine powder injections more frequently, causing s-tress response duck, duck weight decreased, while the temperature-sensitive toad venom injection group and no associated symptoms.Conclusion: Above all in vivo experiments show that, Toad temperature-sensitive gel preparation suitable gelling temperature, uniform and stable formulation, quality control method is accurate, reproducible good; after temperature-sensi-tive gel by intramuscular injection, can significantly retard the active ingredient-s of traditional Chinese medicine Chansu release, improve the bioavailability of the drug, while its low toxicity, and toad venom temperature-sensitive gel to show a good prospect intramuscular injection, the preparation process is stable. |
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