去甲斑蝥素缓释制剂毒性与疗效的实验研究
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Experimental study on toxic and curative effects of sustained-release preparation of norcantharidin
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    摘要:

    目的:初步探讨去甲斑蝥素缓释制剂的减毒增效作用。方法:选择泊洛沙姆407作为去甲斑蝥素局部用药的载体,将去甲斑蝥素制成缓释剂型,在初步证实该制剂兔肝内注射后确能缓慢释放的前提下,比较不同剂型的去甲斑蝥素的毒性及对荷W256肿瘤大鼠的抗肿瘤效果。结果:(1)去甲斑蝥素缓释制剂肝内注射后在局部至少能停留4 h;(2)去甲斑蝥素缓释制剂的毒性明显低于单纯去甲斑蝥素;(3)去甲斑蝥素缓释剂型治疗组大鼠肿瘤生长受到显著抑制,肿瘤组织坏死广泛,治疗后平均生存期延长(与单纯去甲斑蝥素组相比,P<0.05),综合疗效优于单纯去甲斑蝥素组。结论:去甲斑蝥素缓释制剂肝内局部注射能够通过延缓去甲斑蝥素的释放速度,增加其与肿瘤细胞直接作用的时间等途径达到减毒增效的目的。

    Abstract:

    Objective::To study the toxic and pharmocodynamic effects of sustained release preparation of norcantharidin (NCTD). Methods: Poloxamer 407 (P407) gel was used as a sustained-release vehicle for topical administration of NCTD. The toxicity of different preparations of NCTD in mice were observed. The antitumor effects of NCTD or NCTD and P407 (NCTD/P407) on SD rats implanted with W256 carcinoma were also studied. Results: (1) The sustained release preparation of norcantharidin in Poloxamer 407 (NCTD/P407) might stay in the liver at least for 4 h after injection. (2) The toxicity of the sustained release preparation of NCTD in P407 gel was lower than that of free NCTD. (3) There were significant slower tumor growth, more extensive tumor necrosis and longer survival in SD rats treated with NCTD/P407 than those treated with free NCTD. Conclusion: The NCTD in P407 gel is less toxic and have more tumoricidal effects than the equivulent dose of free NCTD, mainly because NCTD in P407 may stay in the injecting location and act with the tumor cells for a longer time.

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