Ishihara Shinsuke, Labuta Jan, Hill Jonathan P, Nakanishi Takashi, Kakinohana Manabu, Iyi Nobuo
Research Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Ibaraki, Japan.
NMR Spectroscopy Group, Institute of Organic Chemistry and Biochemistry (IOCB), Czech Academy of Sciences (CAS), Prague, Czech Republic.
Sci Technol Adv Mater. 2025 Apr 10;26(1):2474788. doi: 10.1080/14686996.2025.2474788. eCollection 2025.
Inhaled nitric oxide (iNO) is a powerful therapy for the treatment of various cardiopulmonary and respiratory diseases. However, access to iNO therapy is often limited by the necessity of cumbersome gas tanks and/or elaborate gas blending apparatus. Here, we report a lightweight, inexpensive, and maintenance-free tablet that autonomously generates a therapeutic quantity of NO in air. The tablet is composed of a thimble filter paper containing a powdery mixture of nitrite (NO )-type layered double hydroxide (NLDH) and ascorbic acid loaded on silica gel (AASiO). NLDH by itself generates trace amounts of NO in the air due to the left-shifting of the protonation equilibrium of NO by aerial CO and HO (2[NO ] + CO + HO 2HNO↑ + [CO ]), which is followed by disproportionation of 2HNO to NO, NO and HO. In contrast, it was found that the protonation equilibrium can be shifted to the right side when volatile acid products (HNO and NO) are readily converted to neutral NO over the AASiO reductant. Based on this, even a single tablet (containing 0.30 g NLDH and 0.90 g AASiO) generates 5 ~ 20 ppm NO at 0.5 L/min for 24 h, which is sufficient to be useful for the relief of severe hypoxia caused by persistent pulmonary hypertension of the newborn (PPHN). Moreover, the tablet can be activated by exhaled breath for high-dose iNO therapy (80 ~ 180 ppm for several hours), revealing its potential utility for treating viral pneumonia. The NO tablet can be stored stably over long periods at ambient temperature in a gas barrier bag and has the potential to break the logistical, financial, and operational barriers that have long existed for the widespread implementation of iNO therapy.
吸入一氧化氮（iNO）是治疗各种心肺和呼吸系统疾病的有效疗法。然而，iNO疗法的应用常常受到笨重的气罐和/或复杂的气体混合装置的限制。在此，我们报告了一种轻便、廉价且无需维护的片剂，它能在空气中自主产生治疗剂量的一氧化氮。该片剂由一个顶针状滤纸组成，滤纸上装有负载在硅胶上的亚硝酸盐（NO₂⁻）型层状双氢氧化物（NLDH）和抗坏血酸的粉末混合物（AASiO）。由于空气中的CO₂和H₂O使NO₂⁻的质子化平衡左移（2[NO₂⁻] + CO₂ + H₂O ⇌ 2HNO₂↑ + [CO₃²⁻]），NLDH自身会在空气中产生微量的NO，随后2HNO₂歧化为NO、NO₂和H₂O。相反，研究发现，当挥发性酸产物（HNO₂和NO）在AASiO还原剂上容易转化为中性的NO时，质子化平衡会右移。基于此，即使是单片剂（含有0.30 g NLDH和0.90 g AASiO）在0.5 L/min的流速下24小时也能产生5至20 ppm的NO，这足以用于缓解新生儿持续性肺动脉高压（PPHN）引起的严重缺氧。此外，该片剂可通过呼气激活以进行高剂量iNO治疗（数小时内80至180 ppm），显示出其在治疗病毒性肺炎方面的潜在用途。这种NO片剂在室温下可在阻气袋中长时间稳定储存，并且有可能打破长期以来iNO疗法广泛应用所存在的物流、资金和操作障碍。
