Research and development

This section introduces the research and development of our company.


Overview of research and development

According to recent study results of gaseous molecules, various physiologic activities have been seen of gaseous molecules of nitric oxide, carbon monoxide, hydrogen sulfide and hydrogen within a living body. Ever since Osawa et al. reported in Nature Medicine (Ohsawa I, Ishikawa M, Takahashi K, et al : Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med, 2007, 13: 688-694) that hydrogen gas eliminates the hydroxyl radical with the strongest oxidizing power even in reactive oxygen species, research on molecular hydrogen has expanded exponentially.
 It is understood from recent study results that molecular hydrogen demonstrates not only an antioxidant effect, but also an anti-inflammatory effect, an antiallergic action, an anti-apoptotic action, a lipid hypermetabolic action, etc., and approximately 740 original theses on animal tests and clinical studies of the effects of molecular hydrogen have been reported until now.
 MiZ has foreseen the possibilities of medical use of molecular hydrogen for the past twenty years, drawn a conclusion that molecular hydrogen will provide a paradigm shift in medicine of the 21st Century, and researched and developed based on a main theme of pursuing ideal technology regarding a hydrogen administration method for clinical application to humans.
 Technologies regarding hydrogen administering methods developed by MiZ until now are (1) method of administering dissolved hydrogen orally, (2) method of adding hydrogen to a liquid drug and administering it by injection, intravenous drip, or the like, and (3) method of administering hydrogen gas as an exhaust gas. We believe that these technologies can inevitably contribute to medicine of the 21st Century.

Primary patents


(Number of domestic registered patents:25, Number of foreign registered patents: 59)

List of Academic Papers

As of November 13, 2023

No. Type of articles Authors Title Published Journal
1 Case reports Hirano S, Ichikawa Y, Sato B, Takefuji Y, Satoh F. Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using the hydrogen gas: a case report in four patients Med Gas Res, 14: 84-86, 2024.
2 Review Hirano S, Ichikawa Y, Sato B, Takefuji Y, Satoh F Clinical use and treatment mechanism of molecular hydrogen in the treatment of various kidney disease including diabetic kidney disease Biomedicines, 11: 2817, 2023.
3 Review Ichikawa Y, Yamamoto H, Hirano S, Sato B, Takefuji Y, Satoh F. The overlooked benefits of hydrogen-producing bacteria Med Gas Res, 13; 108-111, 2023.
4 Review Ichikawa Y, Hirano S, Sato B, Yamamoto H, Takefuji Y, Satoh F. Guidelines for selecting safe hydrogen gas inhalers based on hydrogen explosion accidents Med Gas Res, 13; 43-48, 2023.
5 Review Hirano S, Ichikawa Y, Sato B, Takefuji Y, Satoh F. The conventional drug acts as a “rifle gun” while hydrogen as a “machine gun” Med Gas Res, 13; 89-91, 2023.
6 Original paper Okada M, Ogawa H, Takagi T, Nishihara E, Yoshida T, Hyodo J, Shinomori Y, Honda N, Fujiwara T, Teraoka M, Yamada H, Hirano S, Hato N. A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss Front Neurosci, 16, 1024634, 2022.
7 Review Hirano S, Ichikawa Y, Sato B, Takefuji Y, Satoh F. Molecular hydrogen as a medical gas for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): possible efficacy based on a literature review Front Neurol. 13: 841310, 2022.  
8 Review Hirano S, Yamamoto H, Ichikawa Y, Sato B, Takefuji Y, Satoh F. Molecular hydrogen as a novel antitumor agent: possible mechanism underlying gene expression Int J Mol Sci, 22: 8724, 2021.
9 Review Yamamoto H, Ichikawa Y, Hirano S, Sato B, Takefuji Y, Satoh F. Molecular hydrogen as a novel protective agent against pre-symptomatic diseases Int J Mol Sci, 22: 7211, 2021.
10 Original paper Hirano S, Aoki Y, Li XK, Ichimaru N, Takahara S, Takefuji Y. Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study Med Gas Res, 11: 104-109, 2021.
11 Review Hirano S, Ichikawa Y, Sato B, Yamamoto H, Takefuji Y, Satoh F. Molecular hydrogen as a potential clinically applicable radioprotective agent Int J Mol Sci, 22: 4566, 2021. 
12 Review Hirano S, Ichikawa Y, Sato B, Yamamoto H, Takefuji Y, Satoh F. Potential therapeutic applications of hydrogen in chronic inflammatory diseases: possible inhibiting role on mitochondrial stress Int J Mol Sci, 22: 2549, 2021.
13 Original paper Matsuura H, Matsumoto H, Okuzaki D, Shimizu K, Ogura H, Ebihara T, Matsubara T, Hirano S, Shimazu T. Hydrogen gas therapy attenuate inflammatory pathway signaling in septic mice J Surg Res, 236: 63-70, 2021
14 Original paper Li S, Takahara T, Que W, Fujino M, Guo WZ, Hirano S, Ye LP, Li XK. Hydrogen-rich water protects liver injury in nonalcoholic steatohepatitis though HO-1 enhancement via IL-10 and Sirt 1 signaling Am J Physiol Gastrointest Liver Physiol, 320: G450-463, 2021.
15 Original paper Kayawake H, Chen-Yoshikawa TF, Saito M, Yamagishi H, Yoshizawa A, Hirano S, Kurokawa R, Date H. Protective effects of a hydrogen-rich preservation solution in a canine lung transplantation model Ann Thorac Surg, 111: 246-252, 2021.
16 Original paper Hori A, Sobue S, Kurokawa R, Hirano S, Ichihara M, Hotta N. Two-week continuous supplementation of hydrogen-rich water increases peak oxygen uptake during an incremental cycling exercise test in healthy humans Med Gas Res, 10: 163-169, 2020.  
17 Review Hirano S, Ichikawa Y, Sato B, Satoh F, Takefuji Y. Hydrogen is promising for medical applications Clean Technol, 2: 529-541, 2020.
18 Review Ichikawa Y, Satoh B, Hirano S, Kurokawa R, Takefuji Y, Satoh F. Proposal of next-generation medical care “Mega-hydrogen Therapy” Med Gas Res, 10: 140-141, 2020.
19 Review Hirano S, Ichikawa Y, Kurokawa R, Takefuji Y, Satoh F. “Philosophical molecule”, hydrogen may overcome senescence and intractable diseases Med Gas Res, 10: 47-49, 2020.
20 Original paper Wang P, Zhao P, Chen Z, Wu G, Fujino M, Zhang C, Zhou W, Zhao M, Hirano S, Li XK, Zhao L. Hydrogen gas attenuates hypoxic-ischemic brain injury via regulation of the MAPK/HO-1/PGC-α pathway in neonatal rats Oxid Med Cell Longev. 2020:  Article ID 6978784, 2020.
21 Original paper Saito M, Chen-Yoshikawa TF, Takahashi M, Kayawake H, Yokoyama Y, Kurokawa R, Hirano S, Date H. Protective effects of hydrogen-rich solution during cold ischemia in rat lung transplantation J Thorac Cardiovasc Surg, 159: 2110-2118, 2020.
22 Original paper Korovljev D, Trivic T, Stajer V, Drid P, Sato B, Ostojic, S. Short-term H2 inhalation improves cognitive function in older women: a pilot study Int J Gerontol, 14: 149-150, 2020
23 Review Kurokawa R, Hirano S, Ichikawa Y, Matsuo G, Takefuji Y. Preventing explosions of hydrogen gas inhalers Med Gas Res, 9: 160-162, 2019.
24 Original paper Ozeki N, Yamawaki-Ogata A, Narita Y, Mii S, Ushida K, Ito M, Hirano S, Kurokawa R, Ohno K, Usui A. Hydrogen water alleviates obliterative airway disease in mice

Gen Thoracic Cardiovasc Surg, 68: 158-163, 2019.
25 Original paper Wu G, Chen Z, Wang P, Zhao M, Fujino M, Zhang C, Zhou W, Hirano S, Li XK, Zhao L. Hydrogen inhalation protects hypoxic-ischemia brain damage by attenuating inflammation and apoptosis in neonatal rats Exp Biol Med (Maywood), 244: 1017-1027, 2019.
26 Original paper Sakai T, Kurokawa R, Hirano S, Imai J. Hydrogen indirectly suppresses increase of hydrogen peroxide in cytoplasmic・OH-induced cells and suppresses cellular senescence Int J Mol Sci, 20, 456, 2019.
27 Original paper Yamamoto S, Torisu S, Amiya R, Kurokawa R, Hirano S, Ong BHE, Sonoda H, Kaneko Y, Mizutani S, Ikeda M, Naganobu K. Inhibitory effects of hydrogen gas inhalation to isoflurane-induced oxidative stress in healthy dogs J Comparative Integrative Med, 26: 5-12, 2019.

28 Original paper Li S, Fujino M, Ichimaru N, Kurokawa R, Hirano S, Mou L, Takahara S, Takahara T, Li XK. Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression Sci Rep, 8: 14019, 2018.
29 Original paper Ikeda M, Shimizu K, Ogura H, Kurakawa T, Umemoto E, Motooka D, Nakamura S, Ichmaru N, Takeda K, Tkakahara S, Hirano S, Shimazu T. Hydrogen-rich saline regulates intestinal barrier dysfunction, dysbiosis and bacterial translocation in a murine model of sepsis Shock, 50: 640-647, 2018.
30 Original paper Suzuki Y, Sato T, Sugimoto M, Baskoro H, Karasutani K, Mitsui A, Nurwidya F, Arano N, Y. Kodama Y, Hirano S, Ishigami A, Seyama K, Takahashi K. Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice Biochem Biophys Res Commun, 492: 74-81, 2017.
31 Original paper Kurokawa R, Seo T, Sato B, Hirano S, Sato F. Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation Med Gas Res, 5: 13, 2015.
32 Case reports Ishibashi T, Ichikawa M, Sato B, Shibata S, Hara Y, Naritomi Y, Okazaki K, Nakashima Y, Iwamoto Y, Koyanagi S, Hara H, Nagao T. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases Mol Med Rep. 12: 2757-2764, 2015
33 Original paper Shigeta T, Sakamoto S, Li XK, Cai S, Liu C, Kurokawa R, Nakazawa A, Kasahara M, Uemoto S. Luminal injection of hydrogen-rich solution attenuates intestinal ischemia-reperfusion injury in rats Transplantation.; 99: 500-507, 2015
34 Original paper Liu C, Kurokawa R, Fujino M, Hirano S, Sato B, Li XK. Estimation of the concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes Sci Rep, 4: 5485, 2014.
35 Original paper Yamada T, Uchida K, Onuma K, Kuzuno J, Ujihira M, Inoue G, Sato BKurokawa R, Sakai R, Takaso M. Hydrogen supplementation of preservation solution improves viability of osteochondral grafts Scientific World Journal. 2014; 2109876, 2014.
36 Original paper Sakai T, Sato B, Hara K, Hara Y, Naritomi Y, Koyanagi S, Hara H, Nagao T, Ishibashi T. Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function Vasc Health Risk Manag. 10:591-597, 2014.
37 Original paper Ishibashi T, Sato B, Shibata S, Sakai T, Hara Y, Naritomi Y, Koyanagi S, Hara H, Nagao T. Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study Int Immunopharmacol. 21:468-73, 2014.
39 Original paper Terawaki H, Hayashi Y, Zhu WJ, Matsuyama Y, Terada T, Kabayama S, Watanabe T, Era S, Sato B, Nakayama M. Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients: a novel approach to suppress oxidative stress in the peritoneal cavity Med Gas Res, 3:14, 2013
40 Original paper Seo T, Kurokawa R, Sato B. A convenient method for determining the concentration of hydrogen in water: use of methylene blue with colloidal platinum Med Gas Res. 2:1, 2012.
41 Original paper Ishibashi T, Sato B, Rikitake M, Seo TKurokawa R, Hara Y, Naritomi Y, Hara H, Nagao T, Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis an open-label pilot study Med Gas Res, 2: 27, 2012.
42 Original paper Abe T, Li XK, Yazawa K, Hatayama N, Xie L, Sato B, Kakuta Y, Tsutahara K, Okumi M, Tsuda H, Kaimori JY, Isaka Y, Natori M, Takahara S, Nonomura N. Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury   Transplantation, 94:14-21, 2012
43 Original paper Nakai Y, Sato B, Ushiama S, Okada S, Abe K, Arai S. Hepatic oxidoreduction-related genes are upregulated by administration of hydrogen-saturated drinking water Biosci Biotechnol Biochem. 75: 774-776, 2011.
44 Original paper Yanagihara TArai KMiyamae KSato BShudo TYamada MAoyama M. Electrolyzed hydrogen-saturated water for drinking use elicits an antioxidative effect: a feeding test with rats Biosci Biotechnol Biochem. 69:1985-1987, 2005.