Tanaka Izumi, Ishihara Hiroshi, Yakumaru Haruko, Tanaka Mika, Yokochi Kazuko, Tajima Katsushi, Akashi Makoto
Internal Decorporation Research Team, Research Program for Radiation Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences.
Biol Pharm Bull. 2016;39(3):353-60. doi: 10.1248/bpb.b15-00728. Epub 2015 Dec 25.
Radiocesium nuclides, used as a gamma ray source in various types of industrial equipments and found in nuclear waste, are strictly controlled to avoid their leakage into the environment. When large amounts of radiocesium are accidentally incorporated into the human body, decorporation therapy should be considered. Although standard decorporation methods have been studied since the 1960s and were established in the 1970s with the drug Radiogardase(®) (a Prussian blue preparation), application of recent advances in pharmacokinetics and ethical standards could improve these methods. Here we designed a modern dosage form of hydrogel containing cesium-absorbents to alleviate intestinal mucosa irritation due to the cesium-binding capacity of the absorbents. The effectiveness of the dosage form on fecal excretion was confirmed by quantitative mouse experiments. The total cesium excretion rate of the crystal form (1.37±0.09) was improved by the hydrogel form (1.52±0.10) at the same dose of Prussian blue, with a longer gastrointestinal tract transit time. Using a mouse model, we compared the effects of several drugs on fecal and urinary excretion of internal cesium, without the use of absorbents. Only phenylephrine hydrochloride significantly enhanced cesium excretion (excretion rate of 1.17±0.08) via the urinary pathway, whereas none of the diuretic drugs tested had this effect. These findings indicate that modifying the dosage form of cesium absorbents is important for the decorporation of internal radiocesium contamination.
放射性铯核素被用作各类工业设备中的伽马射线源,且存在于核废料中,因此受到严格管控,以避免其泄漏到环境中。当大量放射性铯意外进入人体时,应考虑采用促排疗法。尽管自20世纪60年代起就开始研究标准促排方法,并在20世纪70年代随着Radiogardase(®)(一种普鲁士蓝制剂)药物的出现而确立,但应用近期在药代动力学和伦理标准方面的进展可能会改进这些方法。在此,我们设计了一种含有铯吸附剂的水凝胶现代剂型,以减轻由于吸附剂的铯结合能力而导致的肠黏膜刺激。通过定量小鼠实验证实了该剂型对粪便排泄的有效性。在相同剂量的普鲁士蓝下,水凝胶剂型(1.52±0.10)在胃肠道转运时间更长的情况下,提高了晶体剂型(1.37±0.09)的总铯排泄率。我们使用小鼠模型,比较了几种药物在不使用吸附剂的情况下对体内铯粪便和尿液排泄的影响。只有盐酸去氧肾上腺素显著增强了铯通过尿液途径的排泄(排泄率为1.17±0.08),而所测试的利尿药物均无此效果。这些发现表明,改变铯吸附剂的剂型对于体内放射性铯污染的促排至关重要。