氧化镁片在黄原胶基增稠剂中形成坚硬团块：一例临床病例揭示的物理化学危害

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中文摘要

背景： 吞咽困难，即吞咽障碍，在老年人中是严重关切的问题。虽然增稠剂对吞咽困难管理至关重要，但它们在药理学上并非惰性；其与口服药物的物理化学相互作用仍知之甚少，并可能造成机械性食管梗阻的医源性危害。方法：在一例原因不明的急性食管梗阻病例之后，本研究旨在识别异物，评估任何崩解失败在不同制剂和增稠剂中的可重复性，并检查会使此类危害持续未被解决的系统性障碍。该异物为一枚氧化镁（MgO）片，在恶性食管狭窄处造成梗阻。采用离体计算机断层扫描和化学分析对其进行分析。使用静态浸泡模型模拟食管淤滞。使用增稠剂（1.0-3.0%）和药用吞咽辅助凝胶（SA-J）比较四种MgO制剂（每组n=6）的崩解行为。此外，在日本九个地区进行了一项横断面市场调查，以评估将SA-J作为替代吞咽辅助剂临床采用的经济障碍。结果：异物被鉴定为未崩解、膨胀的MgO团块。体外实验证实了在所有测试制剂中观察到的一致现象：增稠剂在所有测试组合中完全抑制崩解，在2.0-3.0%浓度下使片剂重量增加约2.2倍并形成坚硬团块。相反，片剂在SA-J中约25秒内崩解。市场调查显示，SA-J每次给药的费用比增稠剂高约14.5倍（p<0.001）。结论：尽管基于单例病例，这些发现强调黄原胶基增稠水代表一种在当前临床实践中可能未被认识的物理化学危害。选择吞咽载体时应充分意识到黄原胶基增稠剂可阻止MgO片崩解。

英文摘要

Dysphagia, or difficulty swallowing, is a matter of serious concern among older adults. While thickening agents are essential for dysphagia management, they are not pharmacologically inert; their physicochemical interactions with oral medications remain poorly understood and can pose an iatrogenic hazard of mechanical esophageal obstruction. Following a case of acute esophageal obstruction of unknown origin, this study aimed to identify the foreign body, to assess the reproducibility of any disintegration failures across formulations and thickeners, and to examine the systemic barriers that would allow such a hazard to remain unaddressed. This foreign body, a magnesium oxide (MgO) tablet, caused obstruction in a malignant esophageal stricture. It was analyzed using ex vivo computed tomography and chemical analysis. A static immersion model was used to mimic esophageal stasis. The disintegration behaviors of four MgO formulations (n = 6 each) were compared using thickeners (1.0-3.0%) and a pharmaceutical swallowing aid jelly (SA-J). Furthermore, a cross-sectional market survey was conducted in nine regions in Japan to assess the economic barriers to the clinical adoption of SA-J as an alternative swallowing aid. The foreign body was identified as a non-disintegrated, swollen MgO mass. In vitro experiments confirmed a consistent phenomenon observed across all tested formulations: thickeners completely inhibited disintegration in every combination tested, increasing tablet weight by approximately 2.2-fold at concentrations of 2.0-3.0% and forming rigid masses. Conversely, the tablets disintegrated in SA-J in approximately 25 s. The market survey revealed that SA-J costs were approximately 14.5-fold higher per administration than thickeners (p < 0.001). Although based on a single case, these findings highlight that xanthan gum-based thickened water represents a physicochemical hazard that may remain unrecognized in current clinical practice. Choice of swallowing vehicle should be made with full awareness that xanthan gum-based thickeners can prevent the disintegration of MgO tablets.