CA2821870A1 - Method to use a stable foam composed of bubbles of various food/supplement/cosmetic/pharmaceutical substances to increase the bio-availability of otherwise inert molecular hydrogen gas for medically useful health maintenance, health promotion, anti-aging and generalized disease process interference purposes in biological living systems in a manner which... - Google Patents

Method to use a stable foam composed of bubbles of various food/supplement/cosmetic/pharmaceutical substances to increase the bio-availability of otherwise inert molecular hydrogen gas for medically useful health maintenance, health promotion, anti-aging and generalized disease process interference purposes in biological living systems in a manner which... Download PDF

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CA2821870A1
CA2821870A1 CA2821870A CA2821870A CA2821870A1 CA 2821870 A1 CA2821870 A1 CA 2821870A1 CA 2821870 A CA2821870 A CA 2821870A CA 2821870 A CA2821870 A CA 2821870A CA 2821870 A1 CA2821870 A1 CA 2821870A1
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molecular hydrogen
hydrogen
gas
aging
tissues
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Morris Folke Johnson
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/20Inorganic substances, e.g. oligoelements
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/50Feeding-stuffs specially adapted for particular animals for rodents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04Dispersions; Emulsions
    • A61K8/046Aerosols; Foams
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/005Preparations for sensitive skin

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Inorganic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Food Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Husbandry (AREA)
  • Dispersion Chemistry (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

This invention embodies a method to increase bioavailabilty of molecular hydrogen to both external and internal tissue surfaces including but not limited to epidermis external (e.g. skin) and epidermis internal (e.g. intraocular, vulvar, vaginal and internal reproductive structures, mouth, throat, esophegus , stomach , duodenum and colon).
secondary bioavailablity via extended assimilation e.g. via the lung as a result of slow release of hydrogen from bubbles in the stomach which are aspirated into the lung is a derivative of the primary use of this invention and therefore an aspect of it.
Another embodiment is the use of this invention to make molecular hydrogen available in a delivery medium which does not carry with it the regulatory impediments and insurance and safety of use liabilities as found in the state of the art which is free molecular hydrogen in uncompressed free gas or hyperbaric compressed gas state.
The state of the art is also restricted by the homeopathic concentrations available in "hydrogen water" or a limited use as an "in situ" derivative of lactulose within the bowel. This invention provides a solution to these problems.

Description

FIELD OF THE INVENTION
The invention relates to methods to make hydrogen gas commercially mass marketable for health management applications as described in but not limited to the reference papers cited within this invention filing without the absolute necessity to be provided in the form of a highly regulated pharmaceutical substrate, but namely as less regulated more broadly and cost effectively available food, nutraceutical and cosmeceutical , supplement, or medical foods. In these later formats the invention can be studied and progressively clinically elaborated upon for product specific medicinal efficaciousness. This can be further defined and elucidated during the commercial marketing phase instead of the pre-market phase. This makes molecular hydrogen gas medical technology more economically accessible by most consumers and scalable to market. This invention does also capture utilization of the same molecular hydrogen microbubbles as pharmaceutical agents when this is practical, based on the health studies which are optimally initially done on non pharmaceutical embodiments.
This invention is intended to be delivered as a whipped foam composed of one of many substances which have been whipped or sonicated into a stable foam containing molecular hydrogen as the gas component of a food, nutraceutical, food supplement, dietary supplement, natural health product, cosmetic or animal feed or pharmaceutical (or the equivalent class in any country this patent is registered in) .
This invention is intended to address Anti -aging applications derived from the improved bio availability of molecular hydrogen namely for developing and maintaining, youthful body function and general good health or enhanced health and wellness; as well as supporting biological processes reducing the rate of aging as manifested by cellular, organ system and whole body dysfunction namely the 8 root causes of aging 1-junk inside cells, 2 junk outside cells , 3-too few cells, 4-too many cells, 5-chromasome mutations, 6-mitochondrial mutations, 7-protein crosslinks, 8 Regulatory mutations (centriole and chromatin) ; as well as degenerative metabolic pathways namely inflammation, oxidative stress, metabolic syndromes and derivative pathology and intra phagocytic metagenomic microbiota pathology all of which singly or in combination eventually become evident as but are not limited to cataract, osteoporosis, type 2 diabetes, hypertension ,inflammatory connective, tissue diseases and inflammation of the joints, subclinical inflammatory metabolic syndrome, cancer; autoimmune diseases namely; crohns disease, multiple sclerosis, rheumatoid arthritis; cardiovascular diseases and neurological disorders, namely Alzheimer's, epilepsy, . stroke, motor neuron disease, parkinson's disease, dementia and such other applications as are described in the claims and rooted in referenced peer reviewed journal papers (7) BACKGROUND OF THE INVENTION:
Hydrogen gas has been shown to manifest medicinal properties to mammalian systems including humans since 1976. (citation 1- Hyperbaric Hydrogen, Fife Dole), list other citations here) Hyperbaric methods demonstrate some intriguing preliminary anticancer effects and a preliminary hypothesis for such action Hyperbaric uses as part of diving mixtures have proven that hydrogen gas is safe for consumption by mammals including humans.
This patent seeks to improve the state of the art namely with respect to liability issues and lack of patent protection which have been impediments to further research and commercialization of consumer goods which increase bioavailability of molecular hydrogen..
In the last decade a large amount of research detailing the medicinal aspects and theories as to the mode of action have been elucidated, however there have been only 5 methods for making hydrogen gas bioavailable namely:
1.- making hydrogen bioavailable by adding hydrogen to water....this method although with clinical benefits utilized only homeopathic levels as hydrogen cannot dissolve in liquids such as water at concentrations in excess of 4-6ppm. Those skilled in the art will recognize that homeopathic levels of hydrogen in liquids while not without efficacy is limited in its capacity to introduce optimal hydrogen levels to most tissues.
2.- via a method which utilizes lactulose which gut microbiome organisms utilize to create hydrogen gas in the bowel yields concentrations of pure gas. Clinical evidence however appears to indicate that hydrogen gas created by lactulose is not bioavailable to any greater degree than "hydrogen water" because it is produced and made bioavailable almost exclusively in the colon. Those skilled in the art will recognize that hydrogen gas in the colon is not of any application to be absorbed by other body tissues external and internal.
3. via introduction of high pressure hydrogen via a modified breathing mixture in a hyperbaric chamber. Those skilled in the art will recognize that hydrogen gas when delivered in a hyperbaric chamber at 8 atmospheres requires extremely expensive facilities staffed by highly skilled and specially trained research personnel and a specially trained physician.
4. via delivery into a face mask which dispenses a diving breathing gas mixture Those skilled in the art will recognize that open water with a surface of sufficient size to dissapate the exhausted gas into the atmosphere at a concentration below the critical levels which supports combustion and explosion.
5. via breathing hydrogen gas by inhaling the gas via a dispensing hose or through a mask where it combines with a breathable air mixture. Those skilled in the art will recognize that special breathing air mixtures , regulators, compressed gas tanks, a contract to procure medical grade breathing gas, and sufficient open air to disperse the gas breathed out below the critical level which supports combustion and explosion.
SUMMARY OF THE INVENTION
According to the one aspect of the invention there is provided a novel mode of introduction of molecular hydrogen to biological systems which by incorporating molecular hydrogen into a stable foam/gel allows slow and continuous release of molecular hydrogen gas both to fluids and into direct contact with biological structures which transfer molecular hydrogen to tissues, organ systems and initiate a series of biochemical events which enable molecular hydrogen to exert beneficial health management and support properties to living cells, tissues, organs and entire organisms.
According to the second aspect of the invention there is provided a method which deregulates and de-risks scalable economical commercial availability of molecular hydrogen to mass market consumers.
Another aspect is where hydrogen is regulated as an inert gas which is usually considered insoluble in body fluids and tissues but when the invention is applied the molecular hydrogen is incorporated into biological systems and can exhibit the functionality described in the journal citations cited at the end of this patent document.
Description of the preferred embodiments unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned hereunder are incorporated herein by reference.

REFERENCES:
1. Penghui Shi, Wancang Sun and Pengzhong Shi et al. Medical Gas Research 2012, 2:17 http://wwvv.medicalgasresearch.com/content/2/1/17 A hypothesis on chemical mechanism of the effect of hydrogen 2. Xiao Chen, Xiao Zhai, Zhimin Kang and Xuejun Sun et al. , Medical Gas Research 2012, 2:3 http://www.medicalgasresearch.com/content/2/1/3, Lactulose: an effective preventive and therapeutic option for ischemic stroke by production of hydrogen 3. Brandon J Dixon, Jiping Tang and John H Zhang et al., Medical Gas Research 2013, 3:10, http://www.medicalgasresearch.com/content/3/1/10, The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance 4. Shigeo Ohta, Current Pharmaceutical Design, 2011, 17, 2241-2252 2241 1381-6128/11 $58.00+.00 2011 Bentham Science Publishers Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications, 5. Kinji Ohno,1 Mikako Ito,1 Masatoshi Ichihara,2 andMasafumi Ito3 1Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicineõ 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan 2Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501, Japan 3Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan Correspondence should be addressed to Kinji Ohno, ohnok@med.nagoya-u.ac.jp Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity, Volume 2012, Article ID 353152, 11 pages doi:10.1155/2012/353152, Review Article, Molecular Hydrogen as an Emerging TherapeuticMedical Gas for Neurodegenerative and Other Diseases
6. Shigeo Ohta, Depi.irtnicia of Biochemistry and Cell Biology, Institute of De\ elopment iind Aging Sciences', Graduate School of Medicine, Nippon Nlodical µcllool. 1-396, Komigi-machi, Nakahara-ku, Kawasaki-cit, Kanagawa-prof. 211-8's-11 Japan Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1820, Issue 5, May 2012, Pages 586-594, Biochemistry of Mitochondria, Life and Intervention 2010, Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases
7. Haruhisa Kawasaki a,b, Jianjun Guan d, Kenichi Tamama a,b,c,*

a Department of Pathology, The Ohio State University, Columbus, OH 43210, United States b Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
43210, United States c Center for Stem Cell and Regenerative Medicine, The Ohio State University, Columbus, OH 43210, United States d Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210, United States, Biochemical and Biophysical Research Communications 397 (2010) 608-613 Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials
8. Hirohisa Onol , Yoji Nishijima, Naoto Adachi, Shigekuni Tachibana, Shiroh Chitoku, Shigeo Mukaiharaõ Masaki Salcamoto, Yohei Kudo, Jun Nakazawa, Kumi Kaneko and Hiroshi Nawashiro Ono et al. Medical Gas Research 2011, 1:12 http://www.medicalgasresearch.com/content/1/1/12 Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study
9. Kosuke Aoki, Atsunori Nakao, Takako Adachi, Yasushi Matsui and Shumpei Miyakawa , Medical Gas Research 2012, 2:12 http://www.medicalgasresearch.com/content/2/1/12, Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes
10. Michael P. Schoenfeld a, Rafat R. Ansari b, June F. Zakrajsek b, Timothy R. Billiar c, Yoshiya Toyoda d, David A. Wink e, Atsunori Nakao c,d, a The National Aeronautics and Space Administration (NASA), Propulsion Research and Technology Branch NASA Marshall Space Flight Center, Huntsville, AL, USA
b Bioscience and Technology Branch, NASA John H. Glenn Research Center at Lewis Field, Cleveland, OH, USA
c Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
d Thomas E Starzl Transplantation Institute, Heart, Lung, and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
e Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Medical Hypotheses 76 (2011) 117-118 Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight
11. Ki-Mun Kang1, Young-Nam Kang1, Ihil-Bong Choi1,2, Yeunhwa Gu2,3, Tomohiro Kawamura4, Yoshiya Toyoda4 and Atsunori Nakao4,5*, Kang et al.
Medical Gas Research 2011, 1:11 http://www.medicalgasresearch.com/content/1/1/11Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors
12. M. Hirscher*, B. Panella, Max-Planck-Institut fur Metallforschung, Heisenbergstr. 3, D-70569 Stuttgart, Germany Journal of Alloys and Compounds 404-406 (2005) 399-401 Nanostructures with high surface area for hydrogen storage
13. Mikako Ito, Masaaki Hirayama, Kazuaki Yamai, Sae Goto, Masafumi Ito, Masatoshi Ichihara and Kinji Ohno Medical Gas Research 2012, 2:15 http://www.medicalgasresearch.com/content/2/1/15 Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson's disease in rats
14. Biomarker Insights 2009:4 27-32 Akito Shimouchi, 5-7-1, Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Email: ashimouc@res.ncvc.go.jp Akito Shimouchi1, Kazutoshi Nose1, Makoto Yamaguchi2, Hiroshi Ishiguro2 and Takaharu Kondo2 1Department of Etiology and Pathogenesis, National Cardiovascular Center Research Institute, Japan.
2Research Center of Health, Physical Fitness and Sports, Nagoya University, Japan.
Breath Hydrogen Produced by Ingestion of Commercial Hydrogen Water and Milk
15. Journal of Inflammation 2012, 9:2 http://www.journal-inflammation.com/content/9/1/2 Zheng Xu, Jiangrui Zhou, Jianmei Cai, Zhen Zhu, Xuejun Sun and Chunlei Jiang*
Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema
16. Nephrol Dial Transplant (2010) 25: 3026-3033 doi: 10.1093/ndt/gfql 96 Advance Access publication 12 April 2010 Original Articles Masaaki Nakayama1,2, Hirofumi Nakano3, Hiromi Hamada4, Noritomo Itami4, Ryoichi Nakazawa5 and Sadayoshi Ito1,2,6 1Tohoku University Hospital, Department of Blood Purification (Sendai), 2Tohoku University, United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science (Sendai), 3Kashima Hospital (Iwaki), 4Nikko Memorial Hospital (Muroran), 5Tokatsu Clinic Hospital (Matsudo) and 6Tohoku University Graduate School of Medicine, Division of Nephrology, Endocrinology and Vascular Medicine (Sendai) Correspondence and offprint requests to: Masaaki Nakayama; E-mail:
mnakayama@mail.tains.tohoku.ac.jp A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial
17. Hindawi Publishing Corporation, Oxidative Medicine and Cellular Longevity Volume 2012, Article ID 353152, 11 pages, doi:10.1155/2012/353152, Review Article Kinji Ohno,1 Mikako Ito,1 Masatoshi Ichihara,2 andMasafumi Ito3 1Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan 2Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501, Japan 3Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan Correspondence should be addressed to Kinji Ohno, ohnok@med.nagoya-u.ac.jp Molecular Hydrogen as an Emerging TherapeuticMedical Gas for Neurodegenerative and Other Diseases
18. Gut, 1970, 11, 1043-1048 Progress report, Lactulose
19. Medical Hypotheses 76 (2011) 325-327 Xiao Chen a, Qiao Zuo a, Yuedong Hai b, Xue Jun Sun c,ir a Graduates Management Unit, Second Military Medical University, Shanghai 200433, PR China b Changzheng Hospital, Second Military Medical University, Shanghai 200433, PR

China c Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China Lactulose: An indirect antioxidant ameliorating inflammatory bowel disease by increasing hydrogen production
20. Hashimoto et al. Medical Gas Research 2011, 1:26 http://www.medicalgasresearch.com/content/1/1/26 Michio Hashimoto1*, Masanori Katakura1, Toru Nabika2, Yoko Tanabe1, Shahdat Hossain1,3, Satoru Tsuchikura4 and Osamu Shido1 Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model
21. Yun Wang1t, Lei Jing1t, Xiao-Min Zhao1*, Ji-Ju Han1, Zuo-Li Xia1, Shu-Cun Qin1, Ya-Ping Wu2,3t, Xue-Jun Sun4*
Respiratory Research 2011, 12:26 http://respiratory-research.com/content/12/1/26 Protective effects of hydrogen-rich saline on monocrotaline-induced pulmonary hypertension in a rat model
22. J. Clin. Biochem. Nutr., 46, 140-149, March 2010 Atsunori Nakao1,*, Yoshiya Toyoda1, Prachi Sharma2, Malkanthi Evans2 and Najla Guthrie2 1Heart, Lung and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213, USA
2KGK Synergize, Inc., London, ON, postal code, Canada, N6A 5R8 E ffectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome¨An Open Label Pilot Study
23. Hanaoka et al. Medical Gas Research 2011, 1:18 http://www.medicalgasresearch.com/content/1/1/18 (4 August 2011) Teruyasu Hanaoka1,2, Naomi Kamimura1, Takashi Yokota1, Shinro Takai2 and Shigeo Ohta2*
Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide
24. Ito et al. Medical Gas Research 2011, 1:24 http://www.medicalgasresearch.com/content/1/1/24 Mikako Itolt, Tohru lb'2t, Ko Sahashi3, Masashi Ichihara4, Masafumi Ito5 and Kinji Ohno1*
Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogenenriched water for mitochondria! and inflammatory myopathies
25. Seo et al. Medical Gas Research 2012, 2:1 http://www.medicalgasresearch.com/content/2/1/1 Tomoki Seo, Ryosuke Kurokawa and Bunpei Sato*
A convenient method for determining the concentration of hydrogen in water:
use of methylene blue with colloidal platinum
26. Cancer Chemother Pharmacol (2009) 64:753-761 DOT 10.1007/s00280-008-0924-2 Naomi Nakashima-Kamimura = Takashi Mori =
Ikuroh Ohsawa = Sadamitsu Asoh = Shigeo Ohta Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice
27. Hindawi Publishing Corporation, Journal of Biomedicine and Biotechnology Volume 2011, Article ID 305086, 7 pages doi:10.1155/2011/305086 Shulin Liu,1 Kan Liu,1 Qiang Sun,1 Wenwu Liu,1 Weigang Xu,1 Petar Denoble,2 Hengyi Tao,1 and Xuejun Sunl 1Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China 2Divers Alert Network, Center for Hyperbaric Medicine and Environmental Physiology, Duke University, Durham, NC 27710, USA
Correspondence should be addressed to Hengyi Tao, taohengyi@hotmail.com and Xuejun Sun, sunxjk@hotmail.com Consumption of HydrogenWater Reduces Paraquat-Induced Acute Lung Injury in Rats =

tr
28. C.R. Acad. Sci. Paris, Sciences de la vie! Life Sciences 324 (2001) 719-2001 Academie des sciences/Editions scientifiques et medicales Elsevier SAS.
Tous droits reserves Bouchra Ghariba, Stephane Hannaa, Ould M.S. Abdallahia, Hubert Lepidib, Bernard Gardettec, Max De Reggia*
a U399 Inserm, universite de la Mediterranee, 27, boulevard Jean-Moulin, 13005 Marseille, France b Laboratoire d'histologie, universite de la Mediterranee, 27, boulevard Jean-Moulin, 13005 Marseille, France c Comex SA, 36, boulevard des oceans,13009 Marseille, France Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation
29. Kyoto JAACT 2006 proceedings Z. GADEK1, T. HAMASAKI2 and S. SHIRAHATA2 1 Center for Holistic Medicine and Naturopathy.57392 Nordenau, Germany 2 Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan "NORDENAU PHENOMENON" - APPLICATION OF NATURAL
REDUCED WATER TO THERAPY.
FOLLOW UP STUDY UPON 411 DIABETES PATIENTS.
30. JY Zhang, et al., www.hepato-gastroenterology.org DOI 10.5754/hge11883 2012; 59(116): Ahead of print.
Jing-Yao Zhang, Chang Liu, Lei Zhou, Kai Qu, Ruitao Wang, Ming-hui Tai, Ji-chao Wei Lei Lei, Qi Fei Wu and Zhi-xin Wang Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiao tong University, Xi'an, China Corresponding author: Chang Liu, MD, PHD, Department of Hepatobiliary Surgery, the First Affiliated Hospital, School of Medicine, Xi'an Jiao tong University, Xi'an, 710061, China; E-mail:
bfzs 1 23sina com A Review of Hydrogen as a New Medical Therapy
31. British Journal of Cancer (2003) 89, 1395¨ 1399 & 2003 Cancer Research UK All rights reserved 0007 ¨ 0920/03 $25.00 www.bjcancer.com G Orive1, SJ Reshkin2, S Harguindey3 and JL Pedraz*,1 1Faculty of Pharmacy, Department of Pharmacy and Pharmaceutical Technology, University of the Basque Country, C Paseo de la Universidad no. 7, 01006 Vitoria, Spain; 2Department of General and Environmental Physiology, University of Bari, Via Amendola 165/A, 70126 Bari, Italy; 3Centro Me'dico La Salud - C Independencia 13, 01005 Vitoria, Spain Hydrogen ion dynamics and the Nap/HI ) exchanger in cancer angiogenesis and antiangiogenesis
32. Malcolm Dole, F. Ray Wilson, William P. Fife Source: Science, New Series, Vol. 190, No.
4210 (Oct. 10, 1975), pp. 152-154 Published by: American Association for the Advancement of Science Stable URL: http://www.jstor.org/stable/1740947 Hyperbaric Hydrogen Therapy: A Possible Treatment for Cancer
33. Aix-Marseille II- Universite de la Mediterranee, Faculte de Medecine - La Timone, Ecole Doctorale des Sciences de la Vie et de la Sante THESE En vue d'obtenir le grade de DOCTEUR DE L'UNIVERSITE DE LA
MEDITERRANEE, Specialite : Oncologie, Pharmacologie et Thera peutiques Presentee et soutenue publiquement le 23 avril 2002 par HADIA BENSALEM
= INSERM U399 lmmunologie et Genetique des Maladies Parasitaires Faculte de Medecine ¨ La Timone, Marseille = COMEX SA. Marseille Implication des radicaux fibres dans le cancer et la pathologie bilharzienne.
Exploitation des proprietes anti-radicalaires de l'hydroge ne moleculaire.
JURY: Pr. Franck BLADOU : President, Dr. Jean-claude DRAPIER : Rapporteur Dr.
Bernard GARDETTE : Rapporteur Dr. Thierry DOUKI : Examinateur Dr. Max DE
REGG1 : Directeur de these EVALUATION DES EFFETS BIOLOGIQUES DE L'HYDROGENE
GAZEUX SUR DES LIGNEES DE CELLULES CANCEREUSES (ETUDE
DE FAISABWITE) H. BENSALEM, J. SAMPOL, F. BLADOU, B. GARDETTE. COMEX, Direction Scientifique, 36 Bd des Oceans. 13275 Marseille cedex 09. INSERM U399, Laboratoire d'immunologie et genetique des maladies parasitaires, Faculte de medecine ¨
Timone ¨ 27 Bd Jean Moulin. 13385 Marseille cedex 05. Service d'Hematologie, Laboratoire de culture cellulaire, HOpital de la Conception, 147 Bd Baille. 13385 Marseille cedex 05, Service d'Urologie, Hopital SAL VATOR, 249 Bd Ste Marguerite. 13274 Marseille cedex 09.
(France) ABSTRACT
Evaluation of the effects of molecular hydrogen on cancer cells H. Bensalem, J. Sampol, F. Bladou, B. Gardette. Bunt. Medsubhyp. 2002, 12 (1) : 15-24. Hydrogen is used in experimental deep-sea diving, because of its low density which reduces breathing efforts in hyperbaric atmosphere, in addition with the absence of narcotic effects below 1 Mpa.
Morever, the harmelessness of hydrogen under physiological conditions has been clearly demonstrated. However under pathological conditions such as inflammation and cancer,
34. J. therm. Bio/. Vol. 22. No. I. pp 3141. 1997 Published by Elsevier Science Ltd Printed in Great Britain PH: S0306-4565(%)00032-0 0306-456519$71 7.00+ 0.00 SUSAN R. KAYAR,* ERICH C. PARKER and ANDREA L. HARABIN
Naval Medical Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5607, U.S.A
METABOLISM AND THERMOREGULATION IN GUINEA
PIGS IN HYPERBARIC HYDROGEN: EFFECTS OF PRESSURE
35. On the Physiology of Hydrogen Diving and Its Implication for Hydrogen Biochemical Decompression, 216 pages by Andreas Fahhnan B.Sc. Hawaii Pacific University, 1996, A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy , Department of Biology, Carleton University Ottawa, Ontario Canada, August, 2000,
36. J. therm. Biol. Vol. 22, No. I. pp. 31-41, 1997, Published by Elsevier Science Ltd SUSAN R. KAYAR,* ERICH C. PARKER and ANDREA L. HARABIN
Naval Medical Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5607, U.S.A. \
METABOLISM AND THERMOREGULATION IN GUINEA PIGS IN HYPERBARIC
HYDROGEN: EFFECTS OF PRESSURE
37. http://www.jap.org, Received 2 July 1997; accepted in final form 1 May 1998., pgs 798-806 SUSAN R. KAYAR, ERICH C. PARKER, AND EUGENIA 0. AUKHERT
Albert R. Behnke Diving Medicine Research Center, Naval Medical Research Institute, Bethesda, Maryland 20889-5607 Relationship between T-wave amplitude and oxygen pulse in guinea pigs in hyperbaric helium and hydrogen
38. PLOS ONE [1932-6203] Siulber, Stefan r:2012 vol:7 iss:7 .=:e42078 Stefan Spulberl *, Karin Edoffl , Lie Hongl , Shinkatsu Morisawa2 , Sanetaka Shirahata3 , Sandra Ceccatellil 1Department of Neuroscience, 1Carolinska Institutet, Stockholm, Sweden, 2Nihon Trim Co Ltd., Osaka, Japan, 3Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Kyushu, Japan Molecular Hydrogen Reduces LPS-Induced Neuroinflammation and Promotes Recovery from Sickness Behaviour in Mice ,6 Abstract Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERVV) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation.
Seven days after the initiation of H-ERW treatment, C57B1/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS.
The mice were killed in the acute or recovery phase, and the expression of pro- and antfinflammatory cytoldnes in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- a and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microgfial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.
39. archivesoforalbiology57 ( 2012)1615-1622 Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model Daisuke Elcuni a, Takaaki Tomofuji a,*, Yasumasa Endo a, Kenta Kasuyamaa, Koichiro Irie a, Tetsuji Azumaa, Naofumi Tamaki b, Shinsuke Mizutani a, Azusa Kojimaa, Manabu Morita a a Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-lcu, Okayama 700-8558, Japan b Department of Preventive Dentistry, The University of Tokushima Institute of Health Biosiences, Graduate School 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
40. Heart, Lung and Circulation, Volume 21, Issue 9, September 2012, Pages 556-Jianxin Shi, Feng Yao, Chenxi Zhong, Xufeng Pan, Yu Yang, Qiang Lin Department of Thoracic Surgery, ShanghaiChest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic ofChina Published by Elsevier Inc on behalf of Australian and New ZealandSociety ofCardiac andThoracicSurgeons (ANZSCTS) andthe Cardiac Society of Australia and New Zealand (CSANZ).
1443-9506/04/$36.00 http://dx.doLorg/10.1016/j.hk.2012.05.782 Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats

Claims (2)

CLAIMS:
1. According to the first aspect of the invention there is provided a novel mode of introduction of molecular hydrogen to biological systems by incorporating molecular hydrogen into a stable foam/gel allows slow and continuous release of molecular hydrogen gas both to fluids and via direct close or contact with biological structures in order to transfer molecular hydrogen to tissues, organ systems and initiate a series of biochemical events which enable molecular hydrogen to exert beneficial health management and support properties to living cells, tissues, organs and entire organisms.
The literature provided as references/citations detail the biological effects derived as a result of application of this invention to biological structures namely but not limited to:
Anti -aging namely for developing and maintaining , youthful body function and general good health or enhanced health and wellness; as well as supporting biological processes reducing the rate of aging as manifested by cellular, organ system and whole body dysfunction namely the 8 root causes of aging 1-junk inside cells, 2 junk outside cells , 3-too few cells, 4-too many cells, 5-chromasome mutations , 6-mitochondrial mutations, 7-protein crosslinks, 8 Regulatory mutations (centriole and chromatin) ; as well as degenerative metabolic pathways namely inflammation, oxidative stress, metabolic syndromes and derivative pathology and intra phagocytic metagenomic microbiota pathology all of which singly or in combination eventually result in cataract, osteoporosis, type 2 diabetes, hypertension ,inflammatory connective, tissue diseases and inflammation of the joints, subclinical inflammatory metabolic syndrome, cancer;
autoimmune diseases namely ; crohns disease, multiple sclerosis, rheumatoid arthritis;
cardiovascular diseases and neurological disorders, namely Alzheimer's, epilepsy, . stroke, motor neuron disease, parkinson's disease, dementia
2. According to the second aspect of the invention there is provided a method which deregulates and derisks commercial availability of molecular hydrogen to mass market consumers. This invention allows molecular hydrogen to be broadly commercialized for human and animal consumption in a novel manner. Molecular Hydrogen is currently considered an inert gas by food, supplement and pharmaceutical regulators.
Since antiaging applications are ultra vires of regulation as health claims as aging is not yet recognized as a disease which ought to be prevented, treated and cured this patent seeks to position molecular hydrogen into a commercial designation which will allow mass commercialization in a relatively deregulated manner. This has significant economic benefits to the inventor. Should the regulatory environment change the regulators will have to address the economic loss they will cause the holder of this patent and make mutually satisfactory reparations.

The invention will now be described by examples; however the invention is in no way limited by these examples:
A foam which has the consistency of a cream or jel composed of hydrogen gas in bubbles comprised of a number of substances which can be whipped up or sonicated into a firm and stable material. Complementary nutraceutical and cosmeceutical substances are compounded or suspended in solution or suspension into this foam/gel to enhance the functionality of the molecular hydrogen gas.
One embodiment is a cream which is primarily a sexual experience enhancer which lubricates and stimulates while transferring hydrogen to the body fluids and tissues.
This embodiment is flavored with pleasant tasting nutraceuticals such as orange oil and is also meant to be consumed by the participants both dermally and orally.
Another embodiment is a foam/gel designed to be applied to skin and transfer hydrogen to the body fluids and tissues it is placed into contact with.
Another embodiment is for oral consumption to be absorbed by the body fluids and tissues of the tongue, mouth, throat, stomach and duodenum with residual release as it passes through the entire digestive tract.
One embodiment is the use of this invention to make molecular hydrogen available in a stable foam delivery medium which does not carry with it the insurance and safety of use liabilities of free molecular hydrogen in uncompressed free gas or hyperbaric compressed gas state.
While the preferred embodiments of the invention may have been described above it will be recognized and understood that various modifications may be made therein and the appended claims are intended to cover all such modifications which may fall within the spirit and scope of the invention The embodiment of this invention is the combination of hydrogen gas with a variety of carriers ranging from foodstuffs to food supplements/nutraceuticals to cosmeceuticals to compounded chemistries which may be regulated as pharmaceuticals.
Another embodiment is the use of as small a bubble size as technically possible with each substrate carrier so as to facilitate easier assimilation of molecular hydrogen into and slower release in all locations the foam containing molecular hydrogen is introduced into or onto.
Another embodiment is bioavailability via assimilation of an injectible stable foam carrier into internal body spaces and tissues including into joints , intravenous and intramuscular is yet another aspect of this invention These embodiments allow hydrogen to be present in very small gas bubbles with and make hydrogen gas stable and available to be more readily adsorbed, absorbed or captured via cellular /nano/atomic scale chemical and physical means. These embodiments allow tissues to be in prolonged close contact with molecular hydrogen in a manner which enables molecular hydrogen to be assimilated at points of the biological systems where inflammatory and other degenerative or pro-aging, or disease related processes such as detailed in ongoing medical literature describing molecular hydrogen (e. g. the efficaciousness of hydrogen once it is incorporated into biological systems at an atomic scale) are at work.
This invention allows molecular hydrogen to be broadly commercialized for human and animal consumption in a novel manner. Molecular Hydrogen is currently considered an inert gas by food, supplement and pharmaceutical regulators.
However lactulose one current alternatives to access molecular hydrogen is regulated as a pharmaceutical or behind the counter health management product and site of bioavailability is restricted to the colon.
Molecular Hydrogen gas provided as a breathable gas or in a hyperbaric chamber faces both economic and regulatory barriers to mass public access both from the aspect that continuous bioavailability is extremely difficult and the hazard posed by handling an explosive gas restricts continuous bioavailability. Facilities and equipment to deliver molecular hydrogen safely introduce impediments to mass market bioavailability of molecular hydrogen as a health promoting substance. Incorporation of molecular hydrogen into foods and supplements and cosmeceuticals which have a lesser restricted access is an innovation and improvement in the state of the art of delivery of hydrogen as a novel API to the mass consumer market. Since molecular hydrogen is extremely insoluble in liquids the novel format of use of a stable foam is an improvement over the current state of the art. While any size of bubble that creates a stable foam is such an improvement, the finer the size of the bubble, the more surface area to contain the molecular hydrogen and the more finely divided the molecular hydrogen is and thus the more bioavailable the molecular hydrogen content becomes and the slower it will be released and made available to tissues, thus enhancing its bioavailability.
Description of the preferred embodiments unless defined otherwise , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned hereunder are incorporated herein by reference.
CA2821870A 2013-07-26 2013-07-26 Method to use a stable foam composed of bubbles of various food/supplement/cosmetic/pharmaceutical substances to increase the bio-availability of otherwise inert molecular hydrogen gas for medically useful health maintenance, health promotion, anti-aging and generalized disease process interference purposes in biological living systems in a manner which... Abandoned CA2821870A1 (en)

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CA2821870A CA2821870A1 (en) 2013-07-26 2013-07-26 Method to use a stable foam composed of bubbles of various food/supplement/cosmetic/pharmaceutical substances to increase the bio-availability of otherwise inert molecular hydrogen gas for medically useful health maintenance, health promotion, anti-aging and generalized disease process interference purposes in biological living systems in a manner which...

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111263637A (en) * 2017-10-27 2020-06-09 米托斯株式会社 Preventive and/or therapeutic agent for dementia

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111263637A (en) * 2017-10-27 2020-06-09 米托斯株式会社 Preventive and/or therapeutic agent for dementia

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