Devices for regenerative medicine

Abstract

The present invention provides a treatment device that can be used for treatment based on a treatment theory in which stress is applied to microvascular tissue to induce transient hypoxia as a trigger. A medical device comprising a hot air supplying means for supplying hot air to microvascular tissue in the olfactory region of the nasal cavity to impart thermal stress thereto.

Description

[Technical field]

[0001] The present invention relates to medical devices and treatment techniques. [Background technology]

[0002] Conventional regenerative medicine techniques mainly involve extracting culturable stem cells from the body, culturing and proliferating them, and then returning them to the body. However, in the last 10 years or so, researchers from the Japanese Society of Cerebral Circulation and Metabolism, the Biochemical Society, and other related research institutes have been reporting new research on stroke and cerebral infarction. As a result, it has become clear that neurogenesis also occurs in the adult brain.

[0003] In particular, it was discovered that neural stem cells that become neurons are expressed from pericytes (vascular pericytes) in the blood vessels of the brain during cerebral infarction. Furthermore, it has been reported that even if the blood flow to these blood vessels is non-lethally stopped for only about 5 minutes, neural stem cells that change into neurons appear from the pericytes of these blood vessels (expressing Nestin), and these are named ischemia-induced pluripotent stem cells (iSC cells) (see Non-Patent Documents 4-8, 20). This phenomenon is academically a type of hypoxia adaptation response (stress response), and when a small portion of the blood vessels of a cell is exposed to hypoxia for a short period of time, the expression of 800 genes, and in some cases more than 2000 genes, is regulated by the hypoxia stress response (see Non-Patent Documents 3 and 63).

[0004] In the conventional approach, regenerative medicine was attempted by culturing iSC cells and transplanting them into patients in an appropriate manner, but this has not yet been put to practical use due to the complexity of the process. In addition, a safe and appropriate method or mechanism for hypoxia in living tissue has not yet been discovered or invented. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 6323894 [Non-patent literature]

[0006] [Non-Patent Document 1] The True Nature of Active Oxygen, edited by Keiichiro Suzuki, Professor at Hyogo College of Medicine, February 16, 2014, published by Nap Co., Ltd., p22 [Non-Patent Document 2] Dynamics and control of cytokines by exercise, Katsuhiko Suzuki, 22nd Annual Meeting of the Japan Preventive Medicine System Association, Symposium 5, Symposium commemorating the launch of the Exercise Division, "Organ-related interactions with exercise and preventive medicine measures," Journal of the Japan Preventive Medicine System Association, Vol. 22, No. 1 [Non-Patent Document 3] Hypoxic stress and HIF Special feature: Stress response molecules: Elucidation of molecular mechanisms and understanding of pathology Minoru Kobayashi, Hiroshi Harada (Biochemistry, Vol. 85, No. 3, pp. 187-195, 2013) (Internet resource) [Non-Patent Document 4] Induction of pericyte-derived neural stem cells by transient cerebral ischemia / canalicular flow injury, (15 minutes of ischemia) Yoshihiro Hyakuta, Department of Dental Anesthesiology, Osaka Dental University, (Cerebral Circulation and Metabolism 28:347~351.2017) (Internet resource) [Non-Patent Document 5] Ischemic pericytes as pluripotent stem cells Professor Tomohiro Matsuyama, Department of Neural Regeneration, Institute of Advanced Medical Science, Hyogo College of Medicine, (Internet resource) [Non-Patent Document 6] Brain-derived ischemia-induced pluripotent stem cells, Takayuki Nakagomi, Institute of Advanced Medical Science, Hyogo College of Medicine, (Cerebral Circulation and Metabolism 26:203-206,2015) (Internet resource) [Non-Patent Document 7] Origin of pericytes and their involvement in brain tissue regeneration, Tomohiro Matsuyama, Takayuki Nakagomi, Department of Advanced Brain Therapy and Neuroregeneration, Institute of Advanced Medicine, Hyogo College of Medicine (Cerebral Circulation and Metabolism 30:71-75.2018) (Internet resource) [Non-Patent Document 8] Why does neurogenesis continue in the mammalian brain? "Mechanisms that realize neurogenesis and the functional significance of neurogenesis" by Imayoshi, Isamu, Division of Cell Growth Regulation, Institute for Virus Research, Kyoto University, (Internet resource) [Non-Patent Document 9] Role of NADPH oxidase in cerebral ischemia Hideyuki Yoshioka, Takashi Yagi, Yuichiro Fukumoto, Koji Hashimoto, Takuma Wakai, H. Pak, Chan, Hiroyuki Kiuchi Cerebral Circulation and Metabolism 187-192, 2012 [Non-Patent Document 10] Physiological Functions and Diseases of Stress Granules, Yuji Kubota, Kyoko Matsuzaki (Arimoto), Mutsuhiro Takekawa, Department of Molecular Signaling Regulation, Institute of Medical Science, University of Tokyo, Medical History Vol. 254 No. 5 2015.8.1 (Internet resource) [Non-Patent Document 11] Elucidation of the mechanism of stress defense and cancer progression by the formation of liquid-liquid phase-separated "stress granules", Professor Mutsuhiro Takekawa et al. Institute of Medical Science, University of Tokyo, May 9, 2023 [Non-Patent Document 12] Regulation of stress-induced apoptosis by stress granule formation and its disruption by reactive oxygen species, Mutsuhiro Takekawa, Department of Molecular Signaling, Institute of Medical Science, The University of Tokyo [Non-Patent Document 13] Mechanism of stress response signaling and cell fate control by stress granule formation Mutsuhiro Takekawa Department of Molecular Signaling, Institute of Environmental Medicine, Nagoya University [Non-Patent Document 14] The role of RNA granules as signal control centers, spatial control of signaling molecules by RNA granules, Ryosuke Sato, Kanako Hagiwara, Ayako Kita, Reiko Sugiura, Japanese Pharmacological Society, J. Pharmacol. J. 147, 340-345 (2016) [Non-Patent Document 15] Intrinsic neural regeneration mechanism in the brain, Kazunobu Sawamoto, Clinical Neurology, 49:830-833, 2009 [Non-Patent Document 16] Control mechanism of cell migration by the reactive oxygen generating enzyme NOX Yoshi Miyano and Akira Yamauchi Seikagaku Vol. 94, No. 1, pp112-117 (2022) [Non-Patent Document 17] Interleukin-1: From cell proliferation control to chronic inflammatory diseases, Kikuo Onozaki, Department of Host Defense, Graduate School of Pharmaceutical Sciences, Nagoya City University [Non-Patent Document 18] Toru Sasaki, Physiological Function of Active Oxygen - Increased Production of Active Oxygen When Increased Energy Metabolism is Released - Basic Aging Research 35(4);17-26, 2011 (Internet resource) [Non-Patent Document 19] Isotope measuring equipment for life sciences (5th series) Real-time bioradiography method Toru Sasaki, Akinori Iwamoto, Hisashi Tsuboi, Toru Kato, Saneyuki Kudo, Erito Kato, Yasuyoshi Watanabe Tokyo Metropolitan Institute of Gerontology Aging Genome Biomarker Research Team RADIOISOTPES, 55, 585-598 (2006) (Internet resource) [Non-Patent Document 20] AIST confirms that even in aged brains, external stimuli increase the production function of nerve cells, and increases the production of "Wnt3," a factor that regulates "aging" and "rejuvenation" in the brain, MIND SCIENCE, [2011 / 08 / 10] (Internet document) [Non-Patent Document 21] Elucidating the function of immune cells that support athletic endurance - Discovery of the unexpected beneficial metabolic effect of bad cytokine (IL-1) - Tohoku University Graduate School of Medicine and Engineering Press Release, May 22, 2018 (Internet material) [Non-Patent Document 22] RIKEN National Center of Neurology and Psychiatry Discovery of the initialization mechanism of the mitochondrial genome - How is mutated mitochondrial DNA "reset"? (April 28, 2016) (Internet resource) [Non-Patent Document 23] European Union Risk Assessment (Volume 38, 2003) Hydrogen Peroxide National Institute of Health Sciences Safety Information Department March 2012 (Internet resource) [Non-Patent Document 24] Biological effects of physical stress and its therapeutic application: considering the role of active oxygen Takashi Kondo, Department of Radiation Basic Medicine, Graduate School of Medicine and Pharmaceutical Sciences, Toyama University, Fukuoka Medical Journal, 106(9), pp.247-253, 2015-09-25, Fukuoka Medical Association [Non-Patent Document 25] The impact is greater than you might imagine! Temperature-dependent biological reactions, by Makoto Tominaga, Professor, Department of Cell Physiology, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences (Internet resource) [Non-Patent Document 26] Structure and Diverse Functions of TRP Channels Akihiro Numata, Daisuke Kasai, Shigenari Takahashi, Kenta Kato, Koji Uryu, Shinichiro Yamamoto, Takeshi Kaneko, Tatsuo Mamoto, Yasuo Mori, Biochemistry Vol. 81, No. 11, pp. 962-983, 2009 (Internet resource) [Non-Patent Document 27] All about the TRP Channel, Makoto Tominaga, Motohiro Nishida, Medical, Dental and Pharmaceutical Publishing Co., Ltd., July 20, 2020 [Non-Patent Document 28] Discovery of the mechanism of nerve regeneration after cerebral infarction - Neuronal function improved by promoting the migration of nerve cells -, Nagoya City University Graduate School of Medical Sciences, Professor Kazunobu Sawamoto, Associate Professor Naoko Kaneko, University of Valencia, Jichi Medical University, Press release dated December 13, 2018 (Internet material) [Non-Patent Document 29] Regulatory function of neuronal migration in the postnatal brain Masato Sawada, Kazunobu Sawamoto, Lecturer, Department of Regenerative Medicine, Graduate School of Medicine, Nagoya City University, Professor, Biochemistry, Vol. 91, No. 2, pp. 178-190 (2019) [Non-Patent Document 30] Cell cycle control of cardiomyocytes by oxygen metabolism and cardiac regeneration, Wataru Kimura, Ph.D., Team Leader, Cardiac Regeneration Research Team, RIKEN Center for Biosystems Dynamics Research, Seikagaku Vol. 90, No. 3, pp. 385-387 (2018) [Non-Patent Document 31] Control mechanism of stem cell maintenance and differentiation brought about by cooperation between nerves and blood vessels, Kenichi Mizutani, Professor, Stem Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Biochemistry, Vol. 89, No. 3, (2017) [Non-Patent Document 32] Phagocytosis of dead cells during myocardial infarction Michio Nakaya, Associate Professor, Department of Drug Safety, Graduate School of Pharmaceutical Sciences, Kyushu University Biochemistry, Vol. 90, No. 5, pp. 724-727 (2018) [Non-Patent Document 33] Rehabilitation dynamically changes brain circuits and restores function, Nagoya City University, Kyoto University Graduate School of Medicine, and Sponsor (Internet resource) [Non-Patent Document 34] Discovery of a new mechanism for memory transfer from the hippocampus to the cerebral cortex, RIKEN Brain Science Institute, RIKEN-MIT Center for Neural Circuit Genetics, Director Susumu Tonegawa, and seven others, April 7, 2017 (Internet document) [Non-Patent Document 35] Reprogramming technology will change regenerative medicine, Masaki Ieda, Lecturer at Keio University, Top Researchers, (Internet resource) [Non-Patent Document 36] Discovery of neural circuits for retrieving memories - Two local circuits in the hippocampus share the role of writing and retrieving memories - RIKEN, Brain Science Institute, RIKEN-MIT Center for Neural Circuit Genetics, Director, Susumu Tonegawa, and seven others, August 18, 2017 (Internet document) [Non-Patent Document 37] The Frontline of Olfactory Neuroscience, Weekly Medical Progress Vol. 253 No. 6 2015 5 / 9 pp. 481- 486, Masahiro Yamaguchi, Department of Cellular and Molecular Physiology, Graduate School of Medicine, The University of Tokyo, pp. 525-526 (Remote preconditioning Update) Ishiyaku Publishing Co., Ltd., [Non-Patent Document 38] Thymic involution and immunosenescence associated with early decline in thymic epithelial stem cell activity, Yoko Hamasaki, Nagahiro Minato, Kyoto University Graduate School of Medicine, Molecular and Cellular Informatics Experimental Medicine 5, 2017 Vol. 35 No. 8, Yodosha pp. 1309-1315, pp. 1325 [Non-Patent Document 39] Identification of vascular endothelial stem cells and the mechanism of angiogenesis and remodeling, Nobuyuki Takakura, Professor, Institute for Microbial Diseases, Osaka University Biochemistry, Vol. 92, No. 3, pp. 453-457 (2020) Ho-no-Abi-17, No. 1, January 2006, (Internet resource) [Non-Patent Document 40] Good Stress and Bad Stress, Director of the Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Japan Pharmacological Journal, 129, 76-79 (2007) (Internet resource) [Non-Patent Document 41] Exercise and Oxidative Stress: The Importance of a Balance between Active Oxygen and Antioxidant Defense, Shuji Oishi, National Hospital Organization Ibaraki East Hospital, IRYO Vol.69 No.7(317-324)2015 (Internet resource) [Non-Patent Document 42] Vascular endothelial cells responding to blood flow, Masako Miho, Department of Pathology, Nihon University School of Medicine, (Internet resource) [Non-Patent Document 43] Blood Rheology and Physiological Functions, Educational Lecture, 1st Lecture: Fundamentals of Hemodynamics and Blood Viscosity, Shinji Maeda, Department of Organ Physiology, Department of Integrated Life Sciences, Faculty of Medicine, Ehime University, 234, Nihon Seishi Vol.66, No.7.8 2004, (Internet resource) [Non-Patent Document 44] Cell therapy for cerebral infarction, Koichi Ohki, Department of Neurology, Keio University School of Medicine, (Cerebral Circulation and Metabolism 28:309-314, 2017) (Internet resource) [Non-Patent Document 45] Mechanical Stress and Blood Vessels, Joji Ando, ​​Department of Biomedical Engineering, Graduate School of Medicine, The University of Tokyo, Perspectives on Geriatrics (Japanese Journal of Geriatrics 2000;37:666-675) (Internet resource) [Non-Patent Document 46] A new perspective on kidney disease: hypoxia and epigeneticsMasaomi Minami, Imari Mimura, Tetsuhiro Tanaka, Department of Nephrology / Endocrinology, Graduate School of Medicine, The University of Tokyo, April 17, 2016, Journal of the Japanese Society of Internal Medicine, Vol. 105, No. 9, pp. 1723-1726 (Internet resource) [Non-Patent Document 47] Development of arrhythmia treatment using regenerative myocardium, Hiroyuki Nakanishi, Jong-Kook Lee, Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Endowed Chair of Cardiovascular Regenerative Medicine, Cardiovascular Disease and Regenerative Medicine, Heart Vol. 46 No. 12 (2014) (Internet resource) [Non-Patent Document 48] Prospects for biological pacemakers, Kumi Morikawa, Yasuaki Shirayoshi, Ichiro Kuru, Regenerative Medicine Division, Next Generation Advanced Medical Promotion Center, Tottori University Hospital, (Internet resource) [Non-Patent Document 49] Elucidation of the mechanism of mitochondrial control of sinoatrial node automaticity, Yukari Takeda, Tatsuya Matsuoka, Life Science Innovation Center (Internet resource) [Non-Patent Document 50] Current status of spinal nerve regeneration, Koichi Iwatsuki, Osaka University Department of Neurosurgery, Spinal Surgery VOL29 NO.1 April 2015 (Internet resource) [Non-Patent Document 51] Oxidative Stress Response and Cell Cycle Regulation in Cardiomyocytes, Wataru Kimura, University of Tsukuba, Center for Interdisciplinary Research in Life Sciences, Heart Vol. 47 No. 12 (2015) (Internet resource) [Non-Patent Document 52] Identification of proliferating cardiomyocytes in adult mammalian hearts - New possibilities for the treatment of myocardial infarction -, Assistant Professor Wataru Kimura, University of Tsukuba (2015) (Internet resource) [Non-Patent Document 53] Aging research initiative - Regeneration and rejuvenation of cardiac myocytes and nerve cells? Yoji Mitsui, Tokushima Bunri University, Basic Aging Research 35(3):45-46,2011 (Internet resource) [Non-Patent Document 54] Cardiac regeneration and differentiation switch using cells, Nanako Kawaguchi, Tokyo Women's Medical University International Institute of Integrated Medical Sciences, JWS Vol.13,14-22,2013 (Internet resource) [Non-Patent Document 55] Biological Effects and Therapeutic Applications of Ultrasound, T. Kondo, R. Ogawa, and Q. Cho, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Journal of the Acoustical Society of Japan, Vol. 73, No. 2 (2017), pp. 108-113, (Internet resource) [Non-Patent Document 56] World's first investigator-initiated clinical trial of ultrasound therapy for Alzheimer's disease, - Utilizing the self-repairing ability of dementia - Professor Hiroaki Shimokawa, Department of Cardiology, Tohoku University Graduate School of Medicine, Press Release, (Internet material) [Non-Patent Document 57] Ultrasound's angiogenic effect discovered - investigator-initiated clinical trial to be conducted - Professor Hiroaki Shimokawa, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, August 19, 2014, press release, (Internet resource) [Non-Patent Document 58] Superoxide dismutase activity and oxygen content in red blood cells of Japanese people (No significant difference in SOD activity, age, or gender was observed) Takeshi Saito, Keizo Ito, Masaaki Kurasaki, Kazuo Saito, Department of Environmental Medicine, Graduate School of Environmental Science, Hokkaido University, Jpn.J.Hyg., Vol. 37, No. 5, December 1982, (Internet resource) [Non-Patent Document 59] Factors controlling regeneration and differentiation of retinal neuronal cell death, Akinori Akaike, Toshiaki Kume, Yasuhiko Izumi, Fumitaka Osakada, Department of Drug Analysis, Graduate School of Pharmaceutical Sciences, Kyoto University, FoliaPharmacol.Jpn 135.142-145(2010)(Internet resource) [Non-Patent Document 60] Weekly Medical Newspaper, December 2, 2019, No. 3349, Igaku Shoin [Non-Patent Document 61] Measurement of in vivo oxygen dynamics using near-infrared spectroscopy, Hisao Iwane, Takafumi Hamaoka, Department of Hygiene and Public Health, Tokyo Medical University, Physical Fitness and Sports Science (1995) 44, 475-480 [Non-Patent Document 62] Study on the inhibitory effect of NADPH oxidase inhibitor (apocynin) (DPI, ML-171) on hepatocarcinogenesis, Shugo Suzuki, Director of Pathological Diagnosis, Nagoya City Eastern Medical Center, Satoshi Takahashi, Professor of Experimental Pathology, Graduate School of Medical Sciences, Nagoya City University (Internet resource) [Non-Patent Document 63] Weekly Medical Progress, 2022 / 10 / 29, All about cell death, its mechanism and its relationship to life phenomena and diseases, Ishiyaku Publishing Co., Ltd. [Non-Patent Document 64] Reactive oxygen signaling in microglial cell function: A new cell control mechanism via TRP channels, Takahito Miyake, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko, Graduate School of Pharmaceutical Sciences, Kyoto University, Department of Biofunctional Analysis, Pharmacology Journal 147.6-11, (2016) (Internet resource) [Non-Patent Document 65] Molecular biology of neutrophils' ability to produce reactive oxygen species and their activation mechanism, Akira Yumoto, Director of the Department of Hematology, Research Institute, International Medical Center of Japan, IRYO Vol.53 No.4(231~238)1999.4 (Internet resource) [Non-Patent Document 66] Control mechanism of cell migration by the reactive oxygen generating enzyme NOX, Yoshi Miyano, Akira Yamauchi, Department of Biochemistry, Kawasaki Medical School, Biochemistry Vol. 94, No. 1, pp112-117(2022) [Non-Patent Document 67] A new therapeutic target for Alzheimer's disease is the activation of neural regeneration in the hippocampus - Proposing a completely new mechanism regarding the onset of dementia and the essence of aging - Kobe Biomedical Industry Development Organization, November 30, 2023 [Non-Patent Document 68] Molecular Mechanism of Reactive Oxygen Production by Neutrophils, Yoshi Miyano, Minoru Tamura, Hideki Sumimoto, Kyushu University Medical Institute of Bioregulation, Division of Growth and Differentiation Regulation, Ehime University Faculty of Engineering Department of Applied Chemistry, Inflammation and Regeneration Vol.25 No2 MARCH 2005, Internet material [Non-Patent Document 69] Mechanosensor TRPV2 promotes neural circuit formation, Mitsushi Shibasaki, Department of Cellular Biochemistry, Graduate School of Human Health Sciences, University of Nagasaki, Progress of Medicine [Non-Patent Document 70] Thermosensitive TRP channels and epithelial barrier, Mizuho Kido, Reiko Yoshimoto, Department of Histology and Neuroanatomy, Faculty of Medicine, Saga University, Medical History [Non-Patent Document 71] Doctor's Squat, How to Eliminate Lack of Exercise in 30 Seconds, Kiyoshi Yoshihara, Ascom Co., Ltd. [Non-Patent Document 72] Vitamin C and hydrogen peroxide remove cancer cells. New function of low-concentration vitamin C discovered. Takumi Sato, Professor of Applied Biology, Tokyo University of Technology, Internet material. [Non-Patent Document 73] Windows IoT Enterprise is an Internet resource. [Non-Patent Document 74] How to use IoT technology in the medical field? Check out the benefits and precautions of its introduction, 2024 Sony Group, Online material [Non-Patent Document 75] Formation of signaling complexes centered on TRP channels and control of cell proliferation and death, Motohiro Nishida, Yuji Hara, Takashi Inoue, Yasuo Mori, Okazaki National Research Institutes, Institute of Integrated Bioscience, Kyushu University Graduate School of Medicine, Bioinformation Pharmacology, Pharmacological Journal of Japan, 121, 223-232 (2003) [Non-Patent Document 76] TRPC3-Nox2 Complex Formation and Its Application to the Treatment of Muscular Dystrophy, Kazuhiro Nishiyama, Research Fellow, Graduate School of Pharmacology, Kyushu University, Department of Drug Discovery and Development Research, Uehara Memorial Foundation for Biochemistry Research Reports, 35 (2021) [Non-Patent Document 77] Intracellular heat drives neural differentiation, University of Tokyo: Graduate School of Pharmaceutical Sciences, Osaka University: Institute for Protein Research, National Institute of Advanced Industrial Science and Technology: Biomedical Research Institute, Kyoto University: Graduate School of Life Sciences, May 10, 2024 Journal name Nature Communication Internet material [Non-Patent Document 78] A textbook for learning IoT through Python, Shoeisha Co., Ltd. VOST Co., Ltd. [Non-Patent Document 79] A Textbook for Understanding IoT Development, Daisuke Bando, Gijutsuhyoronsha Co., Ltd. Summary of the Invention [Problem to be solved by the invention]

[0007] By applying physical stress (heat stress) to a few centimeters of human microvascular tissue around olfactory cells, the dissolved oxygen in the blood flowing through the capillaries of the microvascular tissue is converted to O2 by the activation of the signaling complex between TRP channels and NADPH oxidase. ·-Hydrogen peroxide H2O2 is generated by the action of SOD via (superoxide), and this disproportionation reaction causes the environment in the capillary to become hypoxic. Furthermore, the expression of NOX4 further activates TRP channels and NADPH oxidase, which in turn causes the expression of hypoxic stress response HIF-1α, promoting biochemical changes in the area and causing some of the vascular pericytes to become neural stem cells, which can then be dedifferentiated into neurons, etc.

[0008] Specifically, by applying appropriate stress (heat) to microvascular tissue, neurogenesis is promoted through the production of hydrogen peroxide and hypoxia, and the concentration of hydrogen peroxide in the microvascular tissue during biochemical reactions is controlled using an appropriate method (appropriate mechanism). This process is expected to promote the initialization of the mitochondrial genome of neurogenesis cells and provide a new type of non-invasive neural metabolism aimed at repairing damaged or deteriorated tissues.

[0009] An object of the present invention is to provide an apparatus that can be used for treatment based on the above-mentioned treatment theory, which applies stress to microvascular tissue and induces transient hypoxia as a trigger. [Means for solving the problem]

[0010] The present invention that solves the above problems is as follows. [1] A medical device comprising a hot air supplying means for supplying hot air to microvascular tissue in the olfactory region of the nasal cavity to impart thermal stress.

[0011] [2] The medical device described in [1], wherein the hot air supply means is configured to supply hot air for a period of 1 to 30 minutes.

[0012] [3] A medical device as described in [1] or [2], comprising a hydrogen peroxide mist supply means for supplying a mist of hydrogen peroxide to microvascular tissue in the olfactory region of the nasal cavity.

[0013] [4] The medical device described in [2] or [3], wherein the hydrogen peroxide concentration of the hydrogen peroxide solution is 600 μM or less.

[0014] [5] The medical device according to any one of [2] to [4], wherein the hydrogen peroxide mist supply means is configured to supply the hydrogen peroxide mist for 60 minutes or less.

[0015] [6] The device described in any one of [2] to [5], wherein the hydrogen peroxide mist supplying means supplies a negatively charged hydrogen peroxide mist.

[0016] [7] The device described in any one of [1] to [6], configured to heat the nasal mucosa with the hot air and transiently heat the area around the internal olfactory area to within 39°C to 45°C through thermal conduction.

[0017] [8] The hot air supply means is A heated hot air supply unit; A flow path portion that configures a flow path of hot air supplied from the heated hot air supply portion; The medical device according to any one of [1] to [7], further comprising a nose attachment part provided at a distal end of the flow path part and adapted to be attached to the nose to supply warm air to the nasal cavity through the flow path part.

[0018] [9] The hot air supply means further includes a mist generating unit that generates a mist of water or hydrogen peroxide solution, The medical device according to [8], wherein the mist is supplied through the flow path together with the warm air supplied from the heated warm air supply unit.

[0019]

[10] A medical device comprising: a plurality of medical devices according to any one of [1] to [7]; and a server; A medical system, wherein the medical device is equipped with a communication unit for communicating information with other medical devices and the server.

[0020]

[11] The medical device includes an imaging means for imaging a state of a patient, The medical system according to

[10] , wherein the communication unit transmits images captured by the imaging unit to the server. Effect of the Invention

[0021] According to the present invention, treatment based on the above-mentioned treatment theory becomes possible. [Brief description of the drawings]

[0022] [Figure 1] Explain the secretion of cytokine IL-1 and metabolism due to neutrophil activation in exercising muscles, and the effects of hydrogen peroxide and cell division in the human body [Diagram 2] Analysis example of transient phenomenon caused by stress application to microvascular tissue (calculation diagram) Excerpt including internet data [Diagram 3] An example of the interaction between cytokines and neutrophils and vascular endothelial cells, excerpted from Non-Patent Document 71, an illustration of cytokines and neutrophils. Molecular phylogenetic tree of human TRP channels and explanation of temperature sensitivity, excerpted from Medical Progress Special Edition, All about TRP Channels. [Figure 4] An illustration of temperature-sensitive TRP channels and their activation temperature thresholds, excerpted from Medical Progress Special Edition: All About TRP Channels. [Diagram 5] Scheme of the components and functions of NADPH oxidase. From IRYOVol.53 No.4(231-238)1999.4 Molecular biological basis of neutrophils' ability to produce reactive oxygen species and their activation mechanism (Internet resource). [Figure 6] Table of oxygen metabolism during respiratory burst. From IRYOVol.53 No.4(231-238)1999.4 Molecular biological basis of neutrophils' ability to produce reactive oxygen species and their activation mechanism (Internet resource). [Figure 7] Diagram of NOX activation mechanism and epithelial cell migration, Biochemistry Vol. 94, No. 1 (2022) Control mechanism of cell migration by the reactive oxygen generating enzyme NOX (Internet resource). [Figure 8] A cross-section of the brain showing the relative positions of the nasal cavity, olfactory bulb, hypothalamus, and hippocampus, and predicting neurogenesis when heat stress is applied to the olfactory bulb and olfactory region (Internet resource). [Figure 9] Also, an explanatory diagram of the human head (Internet source). [Figure 10] The migration pattern of newborn neurons in mice is thought to be similar to that in humans. (RIKEN (Internet resource)) [Figure 11] Diagram of nerve and blood vessel wiring. Excerpt from Biochemistry, Vol. 8, No. 3, pp. 384-390 (2019) Control mechanism of stem cell maintenance and differentiation brought about by nerve and blood vessel cooperation (Internet resource). [Figure 12] Diagram of the progression of cerebrovascular pericyte stem cells in the brain. Excerpt from Cerebral Circulation and Metabolism, Vol. 30, No. 1 (Internet resource). [Figure 13] Mechanism of SG formation by RNA-binding protein Nrd1, excerpt from the Institute of Medical Science, University of Tokyo (Internet resource). [Figure 14] Diagram of the inhibition of caspases and cell death (apoptosis) by the formation of liquid-liquid phase separators called "stress granules," data from the Institute of Medical Science, University of Tokyo (Internet data). [Figure 15] An explanatory diagram of mitochondrial genome reprogramming in human cells by reactive oxygen species (ROS), from the RIKEN data (Internet resource). [Figure 16] An explanatory diagram of the relationship between oxygen environment and proliferation of cardiomyocytes. Document from the Center for Interdisciplinary Research in Life Sciences, University of Tsukuba (Internet document). [Figure 17] A conceptual diagram of a regenerative medical device that applies heat stress to the human body's nostrils and nasal cavity for a short period of time, followed by inhalation of a fine mist containing H2O2 to promote neurogenesis around the olfactory area, thereby initializing the mitochondrial genome and promoting highly active neurogenesis. [Figure 18] An example of blood flow distribution in each organ in the human body at rest, oxygen consumption, and oxygen concentration in biological tissues under physiological conditions. [Figure 19] Schematic diagram of the neurovascular unit and structural diagram of the blood-brain barrier, and in vitro reproduction of cerebral capillaries, excerpted from Japanese Journal of Pharmacology 143, 137-143 (2014). [Figure 20] FIG. 1 is a basic explanatory diagram of the mechanism of action and operation of the present invention. [Figure 21]Diagram of the molecular basis of TRPV2 activation mechanism and axonal elongation, excerpted from Medical Progress. [Figure 22] Diagram of epithelial cell function regulation via temperature-sensitive ion channels in the skin and mucous membranes (Excerpt from Medical Progress) [Figure 23] FIG. 1 is a diagram of a first embodiment of the present invention. [Figure 24] Network diagram of the first embodiment [Diagram 25] Figure of Example 2 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] In order to establish a treatment theory, the inventors needed to consider a method for hypoxia in the microvascular tissues (an area of ​​several centimeters) of the brain of living subjects. Specifically, they needed to discover and invent a method for blocking blood flow for a short period of time, or a method for achieving the same effect without blocking blood flow. To this end, they collected and analyzed epidemiological information and big data, and after repeated trial and error and clinical experiments, they discovered a method for creating a temporary state of hypoxia in a part of the brain's microvascular tissues while maintaining blood flow, and its mechanism of action.

[0024] When a specific stress (heat) is applied to microvascular tissue, a biochemical reaction occurs. Recent research has revealed that TRP channels respond to specific temperatures, chemicals, and mechanical stress. In addition, research papers in this field have also described that some TRP channels form complexes with NADPH oxidase. The safest and most controllable of these stresses is temperature, especially heat. Therefore, by targeting the olfactory cells and microvascular tissue of the olfactory region, which regenerate throughout life, and heating the olfactory region to 39°C to 45°C for one to several tens of minutes, TRP channels are activated, and at the same time, NADPH oxidase is activated on the surface of neutrophils and on the vascular endothelium (by the signal complex of TRP and NADPH oxidase). The action of this NADPH oxidase converts dissolved oxygen in the blood into active oxygen (O2·-), which is then converted into hydrogen peroxide by the action of blood SOD. (NOX4 directly converts O2 to H2O2 and appears and becomes active during initial hypoxia.) This dismutation reaction reduces the oxygen concentration in the blood, generating a transient hypoxic state. This hypoxia further activates TRP and NADPH oxidase, and activates the expression of the hypoxic stress response HIF-1α.

[0025] This reaction is a contact reaction, and NADPH oxidase does not act uniformly on neutrophils and microvascular endothelium. Therefore, the dissolved oxygen in the blood vessels in the region becomes less than a few tenths, and the HIF-1α stress response begins immediately, stress granules are generated, and cells are protected from apoptosis caused by activation of Casp3 / 7 due to transient hypoxia. Since stress granules do not have a membrane structure, they are resolved within a few minutes when stress is released. If this high-temperature hypoxic state continues for 15 minutes or more, apoptosis will be promoted, and the surrounding tissues are likely to die within 30 minutes. Therefore, the method of applying stress (temperature and time) must be strictly controlled. The temperature should be within 39°C to 45°C, and the time should be within 60 minutes, and more preferably about 1 minute to 30 minutes.

[0026] As a result of this reaction, some of the pericytes in the microvascular tissue become stem cells (express nestin) through the action of HIF-1α, dedifferentiate into nerve cells, and migrate along the capillaries. This action of NADPH oxidase has attracted attention as it is involved in the worsening of stroke. According to a paper by the RIKEN Institute, if the concentration of hydrogen peroxide in blood plasma (around cells) is controlled to around 100 μM, the mitochondrial genome is initialized during cell division, and heteroplasmy changes to homoplasmy during the M phase of cell division. Autophagy (mitophagy) is promoted by a low-oxygen environment, and mutant mtDNA in mtDNA is erased, leaving wild-type (healthy) mtDNA, improving the quality of the mitochondria in dedifferentiated neural stem cells.

[0027] According to European Union risk assessment materials, the plasma hydrogen peroxide concentrations in six male researchers aged 30-35 years ranged from 13 to 57 μM, and the tolerable concentration in plasma is 600 μM at 1 atmosphere (600 μM when water with a 100% oxygen concentration is converted to hydrogen peroxide).Therefore, it is possible to control the concentration to around 100 μM during the M phase of the above-mentioned biochemical reaction, but only around the olfactory area, by adding appropriate measures. (Without this additional step, reprogramming of the mitochondrial genome of neuroblastomas generated from stem cells does not occur, but mitophagy allows neuroblastomas to maintain age-appropriate mitochondrial activity.)

[0028] (Note) There is no medical practice of measuring H2O2 in blood. Therefore, it is thought that tests cannot be performed at ordinary hospitals. Although there is almost no epidemiological information, as described in Reference 22, in an environment where the concentration of H2O2 in the blood is about 100 μM in combination with the surrounding environment during the M phase of cell division, the mitochondrial genome of the dividing cancer cell is initialized when the cancer cell divides in the body, and the activated cancer cell (which has been given toughness) may metastasize. Such activated cancer cells may not be easily dealt with by the immune system. Cancer cells hypoxicize the surrounding area, and the hydrogen peroxide concentration (value) around the cancer cell is also high. It is recommended to keep the hydrogen peroxide concentration in the blood at at least 50 μM or less by taking antioxidants such as vitamin C orally so that the hydrogen peroxide concentration in the blood does not reach about 100 μM when this is added. Fortunately, antioxidants can be purchased cheaply, so they should be kept in mind on a daily basis. It is also expected that a simple and relatively inexpensive device for measuring blood hydrogen peroxide concentration, like a blood glucose test device, will be developed. (End of warning)

[0029] Regarding the migration of stem cells and neurogenesis cells, research by the RIKEN Institute shows that nerve cells move in a chain-like manner along blood vessels (see Figure 10). The pathways from the lateral ventricle of the brain to the olfactory area and from the olfactory area to the hippocampus are shown, and it is believed that the migration of nerve cells along these pathways contributes to the activation of hippocampal nerve cells that have lost their vitality.

[0030] According to non-patent literature 18 and 19, it takes about 60 minutes for cells to return to normal after exposure to hypoxia. In addition, stress granules are aggregates consisting of mRNA and RNA, and it is necessary to deepen our understanding of their functions. In addition, the convex shape of the characteristic curve of hydrogen peroxide concentration in Figure 2 can be seen as being due to the fact that NOX4 is expressed and activated in the initial hypoxia, and O2 is directly and efficiently converted to H2O2.

[0031] The hypoxic stress response occurs not only in the brain but also in other organs. Although organ metabolism is possible with optimal methods and control systems, the present invention acts within the range of the homeostatic system and is limited to a small area. Side effects may occur if the safe area of ​​action is exceeded. To expand the area, it is necessary to divide the area of ​​action into small areas including organ units and repeat the same operation at different times.

[0032] In this invention, in order to apply heat stress to the olfactory region with the goal of neurogenesis in the brain, a method was devised in which hot air (approximately 41°C to 47°C) is introduced into the nasal cavity from the nose using a closed nasal mask and then discharged from the open oral cavity. With this method, the temperature of the olfactory region is controlled within 39-45°C and heated for 1 to 30 minutes. Furthermore, for the purpose of initializing the mitochondrial genome, a device was used that simultaneously aspirates a mist (approximately microns) of hydrogen peroxide solution of 600μM or less from the nasal cavity using the same system for 60 minutes or less.

[0033] The most important factors in hypoxia are the TRP channels and NADPH oxidase in the vascular endothelium. In the metabolism caused by moderate exercise, the inflammatory cytokine IL-1 is secreted in the muscles, activating neutrophils and the vascular endothelium. The mechanical stress and temperature rise caused by exercise activate the TRP channels and NADPH oxidase (signal complex), converting some of the oxygen in the bloodstream into superoxide O2. ·-It is converted to hydrogen peroxide by the action of SOD enzyme in the blood (or the action of NOX4). This disproportionation reaction reduces the blood oxygen concentration, causing a hypoxic stress response. Furthermore, hypoxia activates TRP channels and NADPH oxidase, and when the concentration of hydrogen peroxide in the stressed area reaches about 100 μM, the mitochondrial genome is initialized during cell division, and the cells are metabolized into healthy and active cells. However, as shown in the example of oxygen concentration in biological tissues at rest in Figure 18, during exercise, there is a possibility that the mitochondrial genome will be initialized in major muscles when exercising appropriately, but other parts, especially the head and inside the brain, are in a relatively low-oxygen environment, and it is determined that the mitochondrial genome will not be initialized during the generation of new nerve cells as it is. (However, mitophagy allows for healthy activity appropriate to age) (H2O2 concentration in blood plus H2O2 concentration generated during hypoxic stress response HIF-1α, estimated 20-30 μM<100 μM)

[0034] If the exercise is excessive, the hydrogen peroxide concentration will increase, the mitochondrial genome will not be initialized, and apoptosis will occur due to the influence of stress granules from the active oxygen (other types of active oxygen may be generated). If a large amount of the antioxidant vitamin C is ingested during exercise, the hydrogen peroxide concentration will not reach approximately 100 μM, and the revitalizing effect of exercise cannot be expected to be very great. These have been reported academically. Comparing the brain neurogenesis of the present invention with exercise therapy, which does not occur naturally, it is estimated that the amount of neurogenesis cells in one session is several times that of healthy exercise therapy. Because it is non-invasive and can be easily performed repeatedly, it is believed that it is possible to generate tens to hundreds of times more high-quality neurogenesis cells in cumulative terms.

[0035] To determine the optimal intensity and duration of exercise therapy for each individual, it is ideal to measure the hydrogen peroxide levels in the muscles by blood sampling before and after the end of exercise. According to a temporal analysis of the biochemical response to stress applied to an area, when effective heat stress or mechanical stress is applied for about 30 seconds, hydrogen peroxide is generated, and the hydrogen peroxide level continues to rise even after 30 seconds, and then starts to decrease in about 30 minutes. If the hydrogen peroxide concentration can be maintained at around 100 μM during the M phase of the cell cycle by appropriately adjusting the amount and intensity of aerobic exercise based on this reaction, the mitochondrial genome of dividing cells will be initialized, and together with the production of other physiologically active substances, the activity of the cells through metabolism will be improved and the state of the cells' mitochondria will be rejuvenated.

[0036] Stress application to the nasal cavity around the olfactory cells can induce cell division in a short period of time, but assuming that the blood H2O2 concentration around the microvascular tissue is 20-40μM, the H2O2 concentration generated by application of heat stress to the olfactory area is at most 20-30μM, with a total of 40-70μM if the oxygen concentration in the surrounding area is 4-5%, and does not reach approximately 100μM during cell division. If measures are taken to increase the H2O2 in the blood, there is a risk that cancer cells may grow if they are present in the body, so a mechanism was adopted that is limited to the olfactory area of ​​the nasal cavity. That is, while simultaneously applying short-term heat stress, a closed nasal mask was used to inhale a micron-sized mist of hydrogen peroxide of 600μM or less from the nasal cavity in a controlled rhythm for up to 60 minutes, and a system was adopted in which the micro-mist containing H2O2 (or charged with negative ions) penetrates into the surrounding area through the mucus in the nasal mucosa, aiming to control the hydrogen peroxide concentration in the microvascular tissue around the olfactory area during the cell division phase to around 100μM.

[0037] The present invention has been completed based on the above findings. The following is a detailed description of an embodiment of the present invention. The present invention is composed of an auxiliary control unit controlled by a microcomputer, related devices, a power supply, etc. The stress application unit includes a heating and blowing unit that filters indoor air to generate warm air, and a fine mist supply unit of hydrogen peroxide linked to the heating and blowing unit uses hydrogen peroxide with a concentration of 120 μM to 200 μM from a built-in H2O2 container (tank), generates fine mist using a high-voltage nozzle spray device or ultrasonic atomizer, etc., and supplies the fine mist to the external supply port of the device using the conveying air from the heating and blowing unit. All operations are performed by a microcomputer and auxiliary peripheral devices inside the device. 120 μM hydrogen peroxide is supplied to the negative ion atomizer from a unitized 1 to 2 L container, and is replaced and replenished on a unit-by-unit basis as it is used.

[0038] The present invention encompasses two embodiments, both of which involve the activation of TRP channels and NADPH oxidase, activation of HIF-1α hypoxic adaptation response and stress granules, and promotion of mitochondrial genome reprogramming.

[0039] The first form is a method of applying appropriate heat stress to the olfactory area of ​​regenerating olfactory cells in order to promote regeneration of brain function and neurogenesis. As shown in Figures 17 and 23, warm air of about 41°C to 47°C is introduced into the nasal cavity for 1 to 30 minutes using a closed nasal mask and discharged from the open oral cavity. With this method, heat is transferred from the warm air through the nasal mucosa, and the temperature around the olfactory area is heated to 39°C to 45°C for a short period of time, causing a biochemical reaction. The amount of heat transferred varies depending on the amount of heat injected into the nasal cavity and the flow rate. Prior to treatment, a specialist such as an otolaryngologist uses an endoscope to confirm that there are no signs of tumors or cancer along the path from the nasal cavity to the pharynx to the oral cavity shown in Figure 9. (If there is a problem, the present invention will be provided after treatment.) Furthermore, at the same time as applying this heat stress, fine mist of H2O2 is aspirated using the same system to measure the penetration from the skin surface of the olfactory area of ​​the nasal mucosa, and the hydrogen peroxide concentration around the olfactory area approaches approximately 100 μM. The concentration of hydrogen peroxide used at this time is 120 to 180 μM, and the initial setting is 120 μM hydrogen peroxide.

[0040] [Table 1]

[0041] [Table 2] EXAMPLES

[0042] <Example 1> FIG. 23 is an image explanatory diagram of the first embodiment of the present invention. First, the user is examined by an otolaryngologist or other specialist in advance to check for the possibility of cancer or other problems in the passage from the nasal cavity to the airway, and to confirm that there are no problems. This device is roughly divided into two parts. It is made up of a Windows computer (here a laptop) that performs overall control of the device, various interface boards controlled by this computer, various instruments, the regenerative medicine device itself which has a built-in power supply unit, etc., and cables (LAN, USB, etc.) that connect them. The basic operation is to inject a fine mist of hydrogen peroxide and heated air into the nose through a closed nasal mask, then open the mouth to expel the air from the mouth. Breathing is done through the mouth during treatment.

[0043] The laptop has IoT-related software installed and is connected to the Internet (equipped with 4G and 5Gn LTE mobile communication systems as needed). First, regarding the operation and function of the device, reference number 1 in Figure 23 is a closed nose mask that is used by placing it tightly against the nose. It can be fixed from the back of the head with a band. Reference number 2 is a tube for the passage of heated hot air and fine mist of hydrogen peroxide connected to 1, reference numbers 3 and 4 are relay connection points, reference number 5 is a two-way switching valve for this fluid (heated hot air) and an electromagnetic switching valve with a built-in precision temperature sensor. The temperature sensor signal is sent to a computer, and the switching of the electromagnetic valve is controlled by the computer. Reference number 8 is an artificial nasal cavity that imitates the nasal cavity, which is used when the heated hot air is not guided to the nasal cavity, and is either discharged indoors or connected to reference numbers 9a or 9b in the flow path to evaluate the characteristics of the time-series temperature change caused by the contact of heated hot air with the nasal mucosa and the penetration characteristics of hydrogen peroxide mist into the nasal mucosa. Each sample is analyzed and evaluated in a test of about 10 minutes, and the temperature setting, the quantity and quality of the hydrogen peroxide mist, and the spray pattern are evaluated and used for computer settings.

[0044] The other is that if the temperature sensor 7 detects that the temperature exceeds the set upper limit for some reason during actual treatment, the solenoid valve is switched under computer control, the heated air is released into the room, and the computer lowers the set temperature of the precision heating device 17 by an appropriate temperature (usually 2°C), and when the temperature sensor 7 drops to a safe value, the solenoid switching valve 5 again directs the heated air toward the nasal cavity, and treatment continues (it runs for the set time and then stops at the computer's command). Reference number 11 denotes a hydrogen peroxide container which stores 1 to 2 liters of approximately 150 μM hydrogen peroxide. This hydrogen peroxide is sent to an electrostatic atomizer 12, where the fine mist is negatively ionized and pushed into the passage (tube) 6 by heated air 16. The inner surface of the flow path tube is coated with an insulator or made of an insulating material. When the negatively ionized hydrogen peroxide mist is introduced into the nasal cavity, it is easily adsorbed by the surface of the nasal mucosa (conductor).

[0045] Regarding computer software and networks, Windows IoT Enterprise is a representative example, but the system of this application does not require 1msec real-time control, and a delay of about 1 second does not cause any control problems. However, the multi-language and rich applications that Windows has are useful. This system was configured by installing a dedicated app and equipping related IoT devices. Reference number 23 is the main body of the regenerative medicine device, which contains all elements other than the computer and has opening and closing plates (screw fastening) for maintenance reference numbers 21 and 22. The power is turned on in the outlet 19, the computer is placed in the installation area, and the power cable, LAN cable, and USB cable are connected to reference number 18. Next, the medical staff turns on the power switch reference number 23 and the computer to go into standby. A startup message appears on the computer screen, and when the medical staff enters the set password, all startup begins. A start-up video starts in the specified language on the touch panel, and a video on how to handle the regenerative medicine device and how to deal with patients is played. Next, the medical staff and the patient's IDs (identification code numbers) are entered. Next, the device's core settings appear, displaying options for how long the hot air should last and what temperature it should be.

[0046] After selecting the items and explaining to the patient and putting on a nasal mask, the patient presses the start button on the computer work screen. After that, the treatment is completed after the selected time (usually 20 to 30 minutes) according to the predetermined sequence. If the patient agrees, a short video recording is automatically performed using a high-performance web camera (tracking function). (The interview, the state during and after treatment, and the patient's detailed facial expression) These are recorded on the computer and, with the consent of the medical staff and the patient, are automatically sent via the Internet to a server in a separately installed information center. By observing for one week to four weeks, the changes in the pathological condition over time in response to this regenerative treatment for various neurological diseases are read from the changes in the patient's images, and the data from each base is aggregated and subjected to AI statistical processing, and the information is fed back to each base, contributing to the rapid development of treatment technology. There are two types of temperature settings: a temperature for dedifferentiating neural stem cells from pericytes in the olfactory part of the nasal cavity and a temperature for stably maintaining the effect (usually 1 to 2 degrees Celsius lower), which are automatically adjusted according to the elapsed time. Although it is not shown in the drawing, the recommended indoor temperature is 20℃, but if it exceeds 25℃, the computer screen will display a message saying that the room temperature needs to be adjusted, and the system is programmed to prevent patient treatment. In the event of an abnormality, a warning message will be displayed on the screen and a voice will be played. Although not shown, data from the attached sensors is recorded in the main unit and automatically transmitted to the information center server as necessary. Furthermore, as long as a patient has a valid ID, they can continue their previous treatment at another facility, but as each patient is provided with a single sealed nasal mask and they are not shared, they must bring their own sealed nasal mask, numbered 1. Furthermore, we use mass-produced (commercially available) sealed nasal masks, but for patients for whom the masks simply do not fit, we can use the 3D scanner at the top of Figure 23 to create a model of the patient's nose and modify the commercially available mask to fit the shape.

[0047] As for the crucial temperature setting of the heated air, the initial setting (one week after the start of treatment) is a nasal surface temperature of 42°C to 43°C, a heated air temperature of 44°C, and a time of about one minute, after which the maintenance temperature for dedifferentiation of stem cells is a nasal surface temperature of 39°C or higher, a heated air temperature of 41°C, and the initial setting for the total suction time in the nasal cavity is 20 to 30 minutes. After one week or six treatments, the progress is analyzed and the settings are reset. In addition, the computers have internet connectivity, so it is possible to exchange information with each other outside of patient treatment hours by using the email addresses of the user list sent from the information center (this can also be done using smartphones).

[0048] <Example 2> Figure 24 shows the second embodiment of the present invention. This is a small and simple regenerative medicine device, and all operations are set manually except for sequence control for sequential operation. The simple regenerative medicine device can be operated by turning on the power and main switch. The adjustable blower takes in air from the room and sends it through an air filter, and the heater (adjustable) heats the air to the set temperature, and the ultrasonic humidifier passes through an ultrasonic atomizer containing hydrogen peroxide water with a concentration of 120 μM to 150 μM, not water, and the heated fine mist is added to the hot air and sent through a temperature sensor to a closed nose mask. The equipment shown is built into the device. The operation switch on the top allows you to adjust the amount and temperature of the hot air, the output of the ultrasonic atomizer, and the ONN-OFF time timing of the intermittent control. When the switch to operate is turned on, the blower, heater, and ultrasonic atomizer are started in a delayed sequence, and when an instruction to stop is given, they are stopped in the reverse order. The thermometer has a digital display, and when the optimal temperature (target temperature) is reached, an alarm sound and a green indicator light will notify you. If the set upper limit is exceeded, the device is programmed to sound a buzzer and light up a red indicator light to notify the user. There is a slight delay between when the device is turned on and the warm air reaches the appropriate temperature. Fluctuations in each element can also cause fluctuations in the temperature of the warm air. The user (patient, medical staff) waits until the green light comes on and then connects the sealed nasal mask to the connector to begin treatment. After the set time has elapsed, an end sound will sound and the device will automatically stop. This takes approximately 30 minutes. During the latter half of startup, the temperature of the heated warm air is set to target a nasal temperature of 39°C to 40°C. As a medical device, the simplified regenerative medical device is managed medically under the instructions of medical staff (doctors). [Industrial Applicability]

[0049] This invention brings revolutionary changes to regenerative medicine, and will replace regenerative medicine using stem cell culture transplantation in the development and treatment of brain function. It can provide new and essential treatment opportunities for many neuropsychiatric disorders, including developmental disorders such as dementia and attention deficit hyperactivity disorder. Furthermore, by sharing information between each base, it is expected that global expansion without region restrictions and improvement of adaptability to changes over time for rapid treatment of patients with various neurological diseases can be achieved. [Explanation of symbols]

[0050] 1 Closed nose mask (with head strap) 2. Hot air (tube) passage to the sealed nasal mask 3. Tube connection 4 Connection with solenoid distribution valve 5 Built-in temperature sensor, 2-way solenoid valve, 5 is always on, 8-way, 4-way during treatment 6. Hot air passage (tube) containing negatively ionized hydrogen peroxide mist 7 Precision Temperature Sensor 8 Passage (tube) from the switching valve to the outside 9a Hydrogen peroxide micro-mist evaluation device, for evaluating the quantity and quality of micro-mist by simulating an artificial nasal cavity 9b. Apparatus for evaluating thermal conduction from the nasal surface of heated air, for evaluating thermal conduction from the mucous membrane surface by simulating an artificial nasal cavity 10. Adjustment discharge path (tube) from solenoid distribution valve to indoors 11 Container of hydrogen peroxide (120 μM), 1 L to 2 L 12 Hydrogen peroxide electrostatic atomizer 13 Variable speed blower, air supply 14 Precision heating equipment, 15 Passage from air supply to heater 16 Passage to the electrostatic atomizer 17 Handle for carrying the regenerative medical device 18 The interface between the device and the computer includes a LAN, USB, and a terminal for powering the computer. 19 Equipment and system power outlets (room outlets and cable connections) 20 Carry for transporting the device (with stopper) 21.22 Internal maintenance cover (screwed) 23 Regenerative medical device body, with interface boards between the computer and the device installed inside

Claims

1. A hot air supplying means for supplying hot air to the microvascular tissue in the olfactory region of the nasal cavity to impart thermal stress; A hydrogen peroxide mist supplying means for supplying a mist of hydrogen peroxide to microvascular tissue in the olfactory region of the nasal cavity; A medical device comprising:

2. 2. The medical device according to claim 1, wherein the hot air supplying means supplies hot air for a period of time ranging from 1 minute to 30 minutes.

3. The medical device according to claim 1 , wherein the hydrogen peroxide solution has a hydrogen peroxide concentration of 600 μM or less.

4. 2. The medical device according to claim 1, wherein the hydrogen peroxide mist supply means is configured to supply the hydrogen peroxide mist for a period of 60 minutes or less.

5. 2. The apparatus of claim 1, wherein the hydrogen peroxide mist supply means supplies a negatively charged hydrogen peroxide mist.

6. The device according to claim 1 , configured to heat the nasal mucosa with the hot air and to transiently heat the area around the internal olfactory area to within 39° C. to 45° C. by thermal conduction.

7. The hot air supply means is A heated hot air supply unit; A flow path portion that configures a flow path of hot air supplied from the heated hot air supply portion; The medical device according to any one of claims 1 to 6, further comprising a nose attachment portion provided at a distal end of the flow path portion and attached to the nose to send warm air to the nasal cavity through the flow path portion.

8. The hot air supply means further includes a mist generating unit that generates a mist of hydrogen peroxide solution, The medical device according to claim 7 , wherein the hot air supply means and the hydrogen peroxide mist supply means are configured to supply the hydrogen peroxide mist through the flow path together with the hot air supplied from the heated hot air supply unit.

9. A system comprising: a plurality of medical devices according to any one of claims 1 to 6; and a server; A medical system, wherein the medical device is equipped with a communication unit for communicating information with other medical devices and the server.

10. The medical device includes an imaging means for imaging a state of a patient, The medical system according to claim 9 , wherein the communication unit transmits the image captured by the imaging unit to the server.

Images