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Abstract:Objective To investigate the release rate and pharmacodynamics in vitro of of vincristine sulfate liposomes. Methods Vincristine sulfate liposomes was prepared by pH gradient method. The release rate was measured by dialysis method. Pharmacodynamics of vincristine sulfate liposomes was evaluated by its antitumor efficacy. Results The release rate of vincristine sulfate liposomes in vitro was fitted to zero?order model. After modification with long?circulating adjuvant, the release rate of vincristine sulfate liposomes decreased and antitumor efficacy increased obviously. Conclusion Long?circulating vincristine sulfate liposomes decrease release rate and increase curative effect.
Key words:vincristine sulfate; liposome; long?circulating liposome; release rate; pharmacodynamics
硫酸长春新碱(vincristine, VCR)为长春花生物碱类抗肿瘤药物,对白血?⒘馨土鼍哂邢灾?钚浴A俅灿τ玫牧蛩岢ご盒录钗?⑸浼粒?嬖谧乓┪锇胨テ诙獭⒋?豢臁⑸窬?低澈臀赋Φ蓝拘郧康热钡恪S醒芯勘砻鳎??侍遄魑?怪琢鲆┪镌靥蹇梢愿纳埔┪锢砘?灾省⑻岣吡菩А⒔档拖低澈吞囟ú课唬ㄈ缧脑唷⑸觯┑亩靖弊饔茫?]。Peter MK等人的研究也表明,硫酸长春新碱制成脂质体能改善药物体内行为、提高疗效、降低毒副作用[2]。因此,抗肿瘤药物与脂质体结合的处方设计越来越受到关注。
本文采用主动载药法中的pH梯度法,以氢化大豆卵磷脂/胆固醇(HSPC/Chol)为脂质体膜制备硫酸长春新碱脂质体。考察硫酸长春新碱脂质体的释放度和抗小鼠S180肿瘤抑瘤率,同时考察长循环辅料聚乙二醇单甲醚2000胆固醇琥珀酸酯(CHSPEG2000)对释放度和抑瘤率的影响,以期为该药临床应用提供更好的给药剂型。
1 实验材料
1.1 试药
硫酸长春新碱(广州环叶制药有限公司),硫酸长春新碱对照品(中国药品生物制品鉴定所),氢化大豆卵磷脂(HSPC,德国),胆固醇(Chol,药用,温州市瓯海食品生化厂),CHSPEG2000 (聚乙二醇单甲醚2000胆固醇琥珀酸酯,自制),阳离子树脂(上海树脂厂),其他试剂均为分析纯。
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