| Venenum Bufonis, an important traditional Chinese medicine with a longapplication history, is the dried white secretion of Bufo bufo gargarizans Cantor or Bufomelanostictus Schneider. It is effective to remove toxic agents, subdue swelling, alleviatepain and induce resuscitation and is often used to treat many diseases, such as hardfuruncle, furunculosis, sore throat, sunstroke, asphyxia. Although Venenum Bufonisshowed better effects on the treatment of pig disease, such as fever and anorexia at Ka-eracupoint, as well as coughs and asthma at Dan-zhong acupoint, the crude implantationwas not only complicated for operation and accurate administration, but also did notmeet the hygeian requirements in veterinary clinic. Based on the theory of traditionalChinese veterinary medicine, the sustained-release injection of Venenum Bufonis (SIVB)which was a new type of acupoint sustained-release injection with the characteristic oflong effect and convenient operation was prepared with modern pharmacy technology.According to Chinese veterinary medicine management standard, its pharmacology andsafety was also evaluated in order to establish the foundation for the further clinicalapplication of SIVB.According to the Ministerial standard WS3-B-3354-98, Venenum BufonisInjection (2mg/ml crude Venenum Bufonis) was prepared by the enterpriseauthorized by GMP, then SIVB was prepared with adding Poloaxmer407throughcold dissolve method. Its formulation was optimized on the basis of the selection ofsuitable gelation temperature, then the memberless model was applied to study itsdrug release behavior in vitro, and the mouse auricle inflammation model was usedto confirm its long effect in vivo.The results showed that the optimal ratio ofPoloxamer407in SIVB was15.25%, resulting in the gelation temperature of30.2±0.3℃. SIVB was proved to have long action and its drug release in vitrofollowed the zero order kinetics with the release equation Q=3.989t+0.322 (r=0.999).The acute toxicity test, the sub-chronic toxicity test, the local stimulation testand the general allergy test were carried out to study the safety of SIVB and theresults suggested that SIVB has higher safety and can be used for acupoint injection.The results of acute toxicity test showed that the LD50of SIVB was not detected inthe test and its maximum tolerated dose was over25ml/kg body weight bysubcutaneous injection. The results of sub-chronic toxicity test showed that the ratshad good general condition, items of body weight, hematologic index, biochemicalindex and histology were all normal, the organ indexes of the heart, liver, lung andkidney were normal, but the spleen index was significantly improved after SIVBwere subcutaneously injected into the rats for continuous4weeks at2.5ml/kg bodyweight. The results of local stimulation test showed that there was congestion in theinjection sites with score1.5, indicating that SIVB had slight irritation and could beapplied in muscle injection. The results of general allergy test showed that SIVB didnot cause allergy reaction.SIVB significantly promoted the development of the immune organs, andenhanced the humoral and cellular immunity. ICR mouses were injected with SIVB(5ml/kg body weight, once every other days) at ear acupoint and the results showedthat the spleen index, splenocyte proliferation and ovalbumin specific antibody IgGwere significantly enhanced by SIVB and the effect was better than that of VenenumBufonis Injection at the same dose of crude Venenum Bufonis.In conclusion, SIVB prepared with the selected formulation and technology hadgood sustained-release properties and high safety, and It also could significantlyenhance the immune function higher than Venenum Bufonis Injection by ear acupointinjection. These results provided the evidences for the further clinical application ofSIVB. |
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