组织类型等离子素激活剂分子变体和脱糖化形式的肌肉内注射后增加和持续的血度
B E Sobel1, S J Sarnoff, D A Nachowiak
1Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
Circulation
|April 1, 1990
概括
有较长半衰期的转基因组织类型等离子体激活剂 (t-PA) 变种在肌内注射后达到更高,持续的等离子体度. 这提高了使用更少材料的血栓溶解的治疗潜力.
科学领域:
- 生物化学 生化学
- 药理学 药理学是指药理学的学科.
- 生物技术是生物技术.
背景情况:
- 以前试图用肌内组织类型等离子体激活剂 (t-PA) 诱导冠状动脉血栓溶解需要大剂量,但未能维持治疗性血度.
- 已确定增强吸收的药物,但不足以克服野生类型t-PA的局限性.
研究的目的:
- 调查基因工程或化学修改t-PA以延长其半衰期是否可以达到更有利的血度.
- 测试这样的假设,即增加吸收-清除比率会提高治疗疗效.
主要方法:
- 创建了四种基因工程t-PA变体和一种酶去糖化变体.
- 药物动力学研究包括在子中进行注射,以确定半衰期.
- 在子和狗体内注射吸收增强剂,以评估与野生类型t-PA相比的血度概况.
主要成果:
- 所有修改的t-PA变体在静脉注射后在循环中表现出延长的半衰期.
- 改性t-PA变体的肌肉内注射导致血度明显更高,持续更长时间.
- 这些升高的水平在没有诱导全身解液状态的情况下实现,与野生类型t-PA.不同.
结论:
- 具有延长半衰期的t-PA分子变异使得在肌肉内注射与吸收增强剂后,可提高和维持血度.
- 这种方法使得用少量的t-PA.实现治疗性血液水平变得更加可行.
- 修改的t-PA变体代表了改善血栓解压疗法的有希望的策略.
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