Apparatus, system, and method for administering hydrogen gas

Abstract

The present invention provides devices, systems, and methods for providing a hydrogen gas mixture to a subject at a flow rate that does not interfere with normal or even heavy breathing.

Description

[Background technology]

[0001] Molecular hydrogen has been found to have potential therapeutic utility for a variety of diseases and injuries (see, e.g., Yoritaka A et al., Neurol Sci. 2021;42(11):4767-4770; Liu, Boyan et al., Mol Med Rep, vol. 22,4 (2020): 2860-2868; Ostojic SM, Ther Adv Respir Dis. 2020;14:1753466620951051). Devices for administering hydrogen gas to subjects either deliver insufficient hydrogen flow rates or concentrations or pose an unacceptable risk of generating explosive hydrogen-air mixtures.

[0002] Therefore, there is a need for new devices, systems, and methods for administering hydrogen to a subject. Summary of the Invention

[0003] The present invention provides devices, systems, and methods for providing a hydrogen gas mixture to a subject.

[0004] One aspect of the present invention provides a device for administering hydrogen to a subject. The device includes a hydrogen source, an oxygen source, a mixing chamber in fluid communication with the hydrogen and oxygen sources, and a conduit in fluid communication with the mixing chamber. The device mixes hydrogen and oxygen to provide a mixed gas at a flow rate that does not interfere with normal breathing, for example, up to 60 liters per minute (LPM), e.g., 4-12 liters per minute (LPM).

[0005] In some embodiments, the device delivers the mixed gas to the subject at a flow rate of 4-8 LPM. In some embodiments, the device delivers the mixed gas at a flow rate that matches the subject's minute ventilation. In some embodiments, the device further comprises a reservoir for the mixed gas. In some embodiments, the device further comprises a source of a third gas (e.g., a therapeutic gas, e.g., nitrous oxide, a gas transmitter (e.g., carbon monoxide, hydrogen sulfide, and / or nitric oxide, etc., each less than 25 ppm, e.g., 1-25 ppm, e.g., 1-10 ppm, e.g., 5-10 ppm, e.g., about 8 ppm), xenon, argon, halothane, isoflurane, desflurane, sevoflurane, etc.) in fluid communication with the mixing chamber. In some embodiments, the hydrogen concentration of the mixed gas is 0.1% to 90% (e.g., 0.1% to 10%, e.g., 4% to 10%, e.g., up to 80% with the remaining 20% ​​being oxygen).

[0006] In some embodiments, the device further comprises an interface with the subject. In some embodiments, the interface is an oral / nasal mask, a nasal cannula, goggles, earpieces, a full face mask, a helmet, a full body suit, a chamber, an animal cage, or a sealable tube. In some embodiments, the interface comprises a light source for red light therapy.

[0007] In some embodiments, the device further includes one or more flow regulators between the mixing chamber and the subject, the hydrogen source, the oxygen source, or a combination thereof. In some embodiments, the device further includes one or more one-way valves, for example, between the mixing chamber and the subject, the hydrogen source, the oxygen source, or a combination thereof. In some embodiments, the one or more one-way valves allow gas flow to the subject or allow gas flow from the subject (e.g., exhalation to atmosphere). In some embodiments, the one or more one-way valves prevent gas flow to the subject unless opened by negative pressure created by respiratory inhalation.

[0008] In some embodiments, the device further comprises a light source for red light therapy.

[0009] In some embodiments, the oxygen source is an air pump and the third gas source is a pure or concentrated oxygen source. In some embodiments, the hydrogen source is an electrolytic hydrogen generator, a compressed gas cylinder, or a sealable canister configured for use with the hydrogen generating composition. In some embodiments, the device further includes a computer configured to control the flow of hydrogen and oxygen to the mixing chamber. In some embodiments, the device includes a humidifier in fluid communication with the mixing chamber.

[0010] In another aspect, the present invention provides a system for administering hydrogen to a subject. The system includes an apparatus having a mixing chamber with first and second inlets and outlets, and a conduit in fluid communication with the mixing chamber. The system further includes a hydrogen source in fluid communication with the first inlet and an oxygen source in fluid communication with the second inlet. The system allows the hydrogen and oxygen to mix to provide a mixed gas at a flow rate that does not interfere with normal breathing.

[0011] In some embodiments, the system further comprises a reservoir for the mixed gas.

[0012] In some embodiments, the system further comprises an interface with the subject. In some embodiments, the interface is an oral / nasal mask, a nasal cannula, a full face mask, goggles, earpieces, a helmet, a full body suit, a chamber, an animal cage, or a sealable tube. In some embodiments, the interface comprises a light source for red light therapy.

[0013] In some embodiments, the mixing chamber includes a third inlet and further includes a source of a third gas (e.g., a therapeutic gas, such as nitrous oxide, a gas transmitter (e.g., nitric oxide, carbon monoxide, and / or hydrogen sulfide), xenon, argon, halothane, isoflurane, desflurane, or sevoflurane, etc.) in fluid communication with the mixing chamber.

[0014] In some embodiments, the system further includes one or more flow regulators, for example, between the mixing chamber and the subject, the hydrogen source, the oxygen source, or a combination thereof. In some embodiments, the system further includes one or more one-way valves between the mixing chamber and the subject, the hydrogen source, the oxygen source, or a combination thereof. In some embodiments, the one or more one-way valves allow gas flow to the subject or allow gas flow from the subject (e.g., exhalation to atmosphere). In some embodiments, the one or more one-way valves prevent gas flow to the subject unless opened by negative pressure created by respiratory inhalation.

[0015] In some embodiments, the system further comprises a light source for red light therapy.

[0016] In some embodiments, the oxygen source is an air pump and the third gas source is a pure or concentrated oxygen source (e.g., a compressed gas cylinder or an oxygen concentrator). In some embodiments, the hydrogen source is an electrolytic hydrogen generator, a compressed gas cylinder, or a sealable canister configured for use with the hydrogen generating composition.

[0017] In some embodiments, the system delivers the mixed gas to the subject at a flow rate of up to 60 LPM, e.g., 4-8 LPM, 4-12 LPM, etc. In some embodiments, the system delivers the mixed gas at a flow rate that matches the subject's minute ventilation. In some embodiments, the hydrogen concentration is between 0.1% and 90% (e.g., between 0.1% and 10%, e.g., between 4% and 10%, e.g., between 4% and 90%).

[0018] In some embodiments, the system further includes a computer configured to control the flow of hydrogen and / or oxygen to the mixing chamber. In some embodiments, the system includes a humidifier in fluid communication with the mixing chamber.

[0019] In another aspect, a device provides a method for administering hydrogen to a subject. The method includes providing a device having a hydrogen source, an oxygen source, and a mixing chamber and a conduit in fluid communication with the mixing chamber. The method further includes supplying hydrogen from the hydrogen source and oxygen from the oxygen source to the mixing chamber to generate a mixed gas, and flowing the mixed gas through the conduit to the subject, allowing the mixed gas to provide a hydrogen concentration at a flow rate that does not interfere with normal breathing.

[0020] In some embodiments, the method further includes supplying a third gas (e.g., a therapeutic gas, such as nitrous oxide, a gas transmitter (e.g., nitric oxide, carbon monoxide, and / or hydrogen sulfide), xenon, argon, halothane, isoflurane, desflurane, or sevoflurane, etc.) from a third gas source to the mixing chamber. In some embodiments, the hydrogen source and the oxygen source are integrated into the device. In some embodiments, the third gas source is integrated into the device.

[0021] In some embodiments, the mixed gas is flowed to the subject at a flow rate of up to 60 LPM, e.g., 4-8 LPM, 4-12 LPM, etc. In some embodiments, the mixed gas is flowed to the subject at a flow rate that matches the subject's minute ventilation. In some embodiments, the mixed gas is flowed to the subject at a volumetric hydrogen concentration of 0.1% to 90% (e.g., 4% to 90%).

[0022] In some embodiments, the method further includes adjusting the flow of hydrogen from the hydrogen source and / or the flow of oxygen from the oxygen source to increase or decrease the hydrogen concentration in the gas mixture. In some embodiments, the adjustment is performed via a computer that automatically adjusts the flow of hydrogen and / or oxygen to maintain a constant total flow rate.

[0023] In some embodiments, the subject is engaged in physical activity and / or respiratory exercises. In some embodiments, the method includes adding humidity to the gas mixture. In some embodiments, the method includes illuminating the subject with red light.

[0024] definition

[0025] The concentrations provided herein are % vol., i.e., volume concentrations.

[0026] As used herein, the term "about" refers to ±10% of the stated value.

[0027] As used herein, the term "cosmetic" refers to the administration of hydrogen gas mixtures to parts or all of the human body (e.g., hands, face, arms, or legs) for the purposes of beautifying, promoting attractiveness, or altering appearance.

[0028] As used herein, the term "fluidically connected" refers to a direct connection between at least two device elements (e.g., mixing chamber, reservoir, gas source, interface, etc.) that allows fluid (e.g., gas) to travel between those device elements without passing through an intervening element.

[0029] As used herein, the term "in fluid communication with" refers to a connection between at least two device elements (e.g., mixing chambers, reservoirs, gas sources, interfaces, etc.) that allows fluid (e.g., gas) to travel between those device elements, whether through one or more intervening device elements.

[0030] As used herein, the term "subject" refers to any mammal to which the hydrogen gas mixture produced by the device or system of the present invention can be administered (e.g., topically, ophthalmically, by inhalation, etc.). Mammals treatable with the devices, systems, and methods of the present invention include primates (e.g., humans, apes), livestock (e.g., cows, pigs, sheep), draft animals (e.g., oxen, horses, llamas), and companion animals (e.g., dogs, cats). A preferred subject is a human.

[0031] As used herein, the term "photobiomodulation therapy" refers to the use of light to treat a disease or condition (e.g., topical light exposure) or to produce a cosmetic effect. [Brief explanation of the drawings]

[0032] [Figure 1] FIG. 1 is a schematic diagram of the device described herein. DETAILED DESCRIPTION OF THE INVENTION

[0033] The present invention provides devices and systems for administering hydrogen gas mixtures to a subject, as well as methods for using the same. The devices and systems can provide hydrogen gas mixtures to a subject at therapeutically relevant concentrations (e.g., greater than 0.1%, greater than 0.5%, greater than 1%, or greater than 4% hydrogen by volume, such as about 1.3%, about 2.3%, or up to 80%, e.g., 2-3%, 3-5%, 4-6%, 4-8%, 5-10%, 10-50%, 20-40%, or 60-80% hydrogen) at flow rates that do not interfere with normal or more vigorous breathing (e.g., during physical activity, meditation, breathwork, etc.). Advantageously, the present invention can reduce the potential for explosive hydrogen-air mixtures by premixing the gases to safe levels before they exit the device or system.

[0034] Devices and Systems

[0035] The device of the present invention includes a mixing chamber, i.e., a volume in which hydrogen and another gas, including oxygen (e.g., air from the atmosphere (e.g., via an air pump), oxygen cylinder, oxygen-enriched air from an oxygen concentrator, or pure oxygen, etc.), are mixed. When a source of hydrogen and oxygen (e.g., an air pump) is included in the device, the mixing chamber is advantageously located near the gas source. The mixing chamber is in fluid communication (e.g., fluidly connected) with a conduit (e.g., a tube, such as rubber (e.g., natural rubber, latex rubber, silicone rubber, cross-linked polyalkylene rubber, etc.) or plastic (e.g., polyethylene, polypropylene, PTFE, etc.)). The mixing chamber may be flexible or collapsible (e.g., a bag, accordion structure, or bladder), or may be a rigid container (e.g., a cylinder, bottle, canister, etc.). The mixing chamber may be made of any material capable of containing a gas, e.g., glass, rubber, plastic, metal, or a combination thereof. The mixing chamber may have a volume larger than the volume of the subject's lungs, e.g., a volume greater than 6 L, e.g., about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 L, e.g., about 6-20 L, e.g., about 6-10 L, 8-12 L, 10-14 L, 14-18 L, 16-20 L, 20-30 L, 20-40 L, 30-40 L, 30-60 L, 40-50 L, 40-80 L, 50-60 L, 60-70 L, 60-80 L, 70-80 L, 80-100 L, or 90-100 L. The mixing chamber may include an inlet (for connection to a gas source) and an outlet (for connection to a conduit). The device may also include a separate reservoir, e.g., an inflatable bag, for holding the mixed gas generated in the mixing chamber, for example, between the mixing chamber and the conduit or between the conduit and the subject. The reservoir may be the same material as the mixing chamber or a different material (e.g., a rigid reservoir and a flexible mixing chamber, or vice versa). The mixing chamber may be a reservoir.The reservoir may have a volume of, for example, about 6 to 100 L, e.g., about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 L, e.g., about 6 to 10 L, 8 to 12 L, 10 to 14 L, 14 to 18 L, 16 to 20 L, 20 to 30 L, 20 to 40 L, 30 to 40 L, 30 to 60 L, 40 to 50 L, 40 to 80 L, 50 to 60 L, 60 to 70 L, 60 to 80 L, 70 to 80 L, 80 to 100 L, or 90 to 100 L.

[0036] The device and system may include an interface for delivering the mixed gas to a subject. The interface may be any component that can be connected to the end of a conduit (i.e., the end of the conduit opposite the mixing chamber) and deliver the gas flow from the mixing chamber to the subject. The type of interface may depend on the type of treatment the subject is receiving, e.g., topical, pulmonary, or a combination thereof. The interface may deliver the mixed gas to the subject so that it is inhaled in addition to or instead of ambient air. The interface may be a mask (e.g., an oral-nasal mask, a full-face mask, an eye mask, a non-rebreathing mask, etc.). The interface may be a helmet (e.g., a pressurizable ventilated helmet). The interface may be designed to administer hydrogen locally, e.g., to a limb or other enclosable part of the body (e.g., the torso), e.g., via a tube or sleeve with a sealable open end (e.g., that seals around the limb or torso). The interface may be a nasal cannula, goggles, or earpiece. The interface may be a full-body suit or a walk-in / sit-in chamber (e.g., a chamber such as a hyperbaric chamber, or an animal cage). The interface that contacts the subject may be any suitable material, for example, a medical grade polymer (eg, silicone).

[0037] The devices and systems may include one or more valves (e.g., one-way / check valves, pressure relief valves, etc.), flow meters, flow controllers, flow restrictors, etc. One-way valves can be used to prevent the hydrogen gas mixture in the mixing chamber or reservoir from being diluted with exhaled air. For example, a combination of two one-way valves can allow exhaled air to the environment while not allowing exhaled air to flow into the mixing chamber. For example, a one-way valve fluidly disposed between the conduit and the interface can prevent reverse airflow along the conduit. Alternatively, a one-way / check valve can be located between the conduit and the mixing chamber. The interface, e.g., a helmet or mask, may include a one-way valve that allows airflow (e.g., exhaled air) to exit but not enter. Such a design reduces or prevents dilution of the mixed gas with carbon dioxide in the exhaled air. A one-way / check valve between the gas sources can prevent hydrogen or oxygen from the mixing chamber from entering the hydrogen or oxygen source. A pressure relief valve may be included in fluid communication with the mixing chamber. There may also be a relief valve to allow air intake from the surroundings if the flow rate of the mixed gas falls below a threshold. A pressure relief valve may be in fluid communication with any gas source to prevent dangerous over-pressurization.

[0038] The devices and systems may include a computer programmed to adjust the flow from the hydrogen and / or oxygen sources in response to, for example, changes in the subject's respiratory rate or the desired hydrogen and / or oxygen concentration to be delivered. The computer may also adjust the flow of a third gas, for example, to add a therapeutic gas or increase the flow of pure or concentrated oxygen to offset a decrease in oxygen concentration in the gas mixture due to the addition of hydrogen. The computer may adjust the flow by interfacing with valves, hydrogen and / or oxygen sources (e.g., by controlling the gas production rate), or flow controllers. The computer may also be programmed to run the device or system for a set time or desired cycle, or to activate an alarm in the event of overpressurization or a change in the gas mixture composition. The computer may also stop gas production in the event of overpressurization or a change in the gas mixture composition. The computer may be physically attached to the device or may interact with the device via a wired or wireless connection as known in the art. The device or system may be controlled via an app on a mobile computer, such as a phone or tablet. The device or system may also, or alternatively, be controlled by a computer interface associated with the device or system.

[0039] The devices and systems of the present invention can deliver a mixed gas to a subject at a flow rate of at least 4 LPM, e.g., 4-8 LPM, e.g., 5-8 LPM, e.g., 5, 6, 7, or 8 LPM, or up to 60 LPM, e.g., 8-20 LPM, 15-25 LPM, 20-30 LPM, 20-40 LPM, 30-40 LPM, 30-60 LPM, 40-50 LPM, 40-80 LPM, or 50-60 LPM. The devices and systems can be configured (e.g., by manual adjustment of the flow rate, a series of valves, or a computer according to a pre-programmed set of conditions) to deliver the mixed gas at a flow rate that matches the subject's minute ventilation (e.g., 12-25 breaths per minute). The devices and systems can deliver hydrogen to a subject at a concentration of 0.1-90%, e.g., at least 0.1%, at least 0.5%, at least 1%, at least 2%, or at least 4%, e.g., 0.1-1%, 0.1-2%, 1-2.5%, 2-3%, 3-5%, 4-6%, 4-8%, 5-10%, 10-50%, 20-40%, or 60-80%. The devices of the present invention may include a hydrogen source containing sufficient hydrogen to provide a gas mixture to a subject for 5 minutes to 24 hours, e.g., 5-10 minutes, 10-20 minutes, 5-30 minutes, 15-60 minutes, 20-60 minutes, 30-45 minutes, 30-60 minutes, 45-60 minutes, 45-90 minutes, 60-90 minutes, 45-75 minutes, 90-120 minutes, 100-120 minutes, 1-2 hours, 1-4 hours, 2-5 hours, 3-6 hours, 6-12 hours, 5-10 hours, 10-15 hours, 12-18 hours, 15-20 hours, or 18-24 hours. The device may include a hydrogen source with a volume sufficient for multiple treatments. In some embodiments, the devices and systems provide oxygen as 10-25% of the gas mixture, e.g., 18-22%.

[0040] The devices and systems of the present invention may include a device capable of providing red light or photobiomodulation therapy. For example, the device may include one or more red lights, e.g., LEDs, as part of a mask, pad, chamber, wall, helmet, wrap, blanket, or nasal cannula to illuminate a subject, or a portion of a subject, with red light. The red light may be in an interface for delivering the gas mixture or may be another component of the device or system. The red light LED may include wavelengths between 600 and 1100 nm, e.g., 600-650 nm, 650-700 nm, 700-750 nm, 750-800 nm, 800-850 nm, 850-900 nm, 900-950 nm, 950-1000 nm, 1000-1050 nm, and / or 1050-1100 nm, e.g., about 570, 590, 620, 633, 680, 760, 820, and / or 830 nm. The power may be between 1 and 1000 mW.

[0041] hydrogen source

[0042] The hydrogen source can include an electrolytic hydrogen generator (e.g., a hydrolysis generator), a compressed gas cylinder, a storage tank (e.g., a hydride storage tank), or a hydrogen-producing composition (e.g., a composition that reacts to form hydrogen, such as a metal hydride (e.g., lithium hydride, sodium borohydride, lithium aluminum hydride, sodium alanate, and ammonia borane), a Mg-containing composition, an Al-containing composition, nanosized silicon (e.g., Folarin Erogbogbo, et al., Nano letters 13.2 (2013): The hydrogen source may include a sealable, pressurizable container (e.g., glass, metal, or plastic bottle, canister, etc.), including those described in U.S. Pat. No. 4,559,451-456. Exemplary compositions are those described in U.S. Pat. No. 11,266,169. The composition for producing hydrogen may be, for example, a tablet or powder containing a metal, e.g., magnesium or aluminum, that reacts with water and / or acid to form hydrogen. The hydrogen source may also include a high surface area support, e.g., zeolite, silica microspheres, etc., onto / into which compressed hydrogen is adsorbed and / or absorbed. The hydrogen source may be a carrier having a surface area of ​​up to 800 nm. The hydrogen generating composition may comprise sufficient hydrogen (e.g., in a compressed gas cylinder or from an electrolytic hydrogen generator) or hydrogen generating composition (e.g., sufficient magnesium) to generate 4-10% hydrogen gas at a flow rate of 1 LPM for 5 minutes to 12 hours, e.g., 5-10 minutes, 10-20 minutes, 5-30 minutes, 15-60 minutes, 20-60 minutes, 30-45 minutes, 30-60 minutes, 45-60 minutes, 45-90 minutes, 60-90 minutes, 45-75 minutes, 90-120 minutes, or 100-120 minutes, e.g., at least 1 hour, e.g., 1-2 hours, 1-4 hours, 1-12 hours, etc., or for example, at least 2 hours, e.g., 2-5 hours, 3-6 hours, 4-7 hours, 5-10 hours, 6-9 hours, 6-12 hours, 8-10 hours, 9-12 hours, or 10-12 hours.

[0043] oxygen source

[0044] The oxygen source may include an air pump or a fan. Alternatively, or in addition, the oxygen source may include a gas source (e.g., a cylinder, a storage tank, an electrolytic oxygen generator, an oxygen concentrator, a chemical reaction, etc.) of pure oxygen or a concentrated (e.g., superatmospheric) oxygen concentration. The pump may be a positive displacement compressor (e.g., a rotary screw, rotary vane, or reciprocating air compressor). The pump may be a diaphragm pump. The air pump may include a bellows or a piston. Oxygen may be produced by a chemical reaction, e.g., hydrogen peroxide and catalase. Oxygen supplied from ambient air may be filtered, e.g., by a HEPA filter.

[0045] Both hydrogen and oxygen may be produced by the same hydrolysis device, e.g., the two gases are stored separately before mixing. Because hydrogen is produced twice as much as oxygen, the device and system may include an additional gas source, e.g., more oxygen or an inert gas, to maintain adequate hydrogen and / or oxygen levels in a non-explosive ratio.

[0046] Other gases

[0047] A third gas may be added to the hydrogen gas mixture by connecting a third gas source to the mixing chamber. The third gas may be a therapeutic gas (e.g., desflurane, isoflurane, halothane, nitrous oxide, sevoflurane, argon, xenon, etc.). Inert gases such as nitrogen and helium are also contemplated. Therapeutic gases may also include gases such as hydrogen sulfide, carbon monoxide, ozone, and nitric oxide at appropriately low concentrations. The third gas may be oxygen or may contain oxygen, for example, a pure or concentrated oxygen source, thereby maintaining the oxygen concentration received by the subject at or above that of atmospheric oxygen (e.g., to counteract the dilution effect of added hydrogen when an air pump is used as the oxygen source).

[0048] Systems, Kits, and Additional Components

[0049] The systems of the present invention may include a separate gas source, for example, if the device does not include an integrated gas source. The gas source may be any of those described herein (e.g., a hydrogen generator, an oxygen generator or concentrator, a compressed gas cylinder, a storage tank, etc.). The systems and kits may include additional conduits (e.g., tubing and tubing connectors), for example, for attaching the device of the present invention to an external gas source. The systems may include an interface (e.g., provided with the device in a kit). The interface included in the systems of the present invention may be any of those described herein (e.g., an oral / nasal mask, nasal cannula, full-face mask, goggles, earpieces, helmet, full-body suit, hyperbaric chamber, or sealable tube or sleeve). A fixed structure (e.g., a chamber) may be part of the systems of the present invention. The systems may also include a light source for red light therapy or photobiomodulation therapy as a separate component.

[0050] The systems of the present invention may include devices in which one or more of a hydrogen source, an oxygen source, or a third gas source are integrated into the device. For example, the system may include a device with a built-in hydrogen or anesthetic gas source, while oxygen is provided by an external oxygen concentrator or cylinder. Alternatively, the system may include a device with a built-in oxygen source, such as a compressor or oxygen concentrator or cylinder, and an external hydrogen source (e.g., a compressed gas cylinder) or third gas source (e.g., a nebulizer or vaporizer).

[0051] The systems of the present invention may include components for pressurizing the gas source, such as a pump, piston, actuator (e.g., a mechanical, hydraulic, or pneumatic actuator), press (e.g., a mechanical, hydraulic, or pneumatic press), piezoelectric actuator, lever, etc. The systems of the present invention may also include a power source, such as one for powering the pump, control valve, computer, etc. The systems of the present invention may include additional pumps, reservoirs (e.g., tanks, cylinders, etc.), pressure sensors, actuators, valves, etc. The systems of the present invention may include a computer (e.g., a microcontroller) for monitoring or controlling the device, e.g., to send signals to control valves to regulate flow from the hydrogen source, oxygen source, or third gas source, and / or to open a pressure relief valve to depressurize the device. In some embodiments, the system further includes an additional reservoir for mixing gases. The systems of the present invention may include a nebulizer or vaporizer (e.g., an anesthetic vaporizer). The systems of the present invention may also include a humidifier (e.g., an ultrasonic humidifier, an impeller humidifier, an evaporator, or a steam vaporizer) in fluid communication with the device or system. The humidifier may be fluidly connected to the hydrogen source and / or the mixing chamber. Humidifying the hydrogen gas mixture can reduce the explosion risk of highly concentrated (e.g., >4%) hydrogen gas mixtures, for example, by reducing the risk of electrostatic discharge.

[0052] method

[0053] The methods of the present invention allow for the provision of a mixture of hydrogen gas to a subject. Advantageously, the methods of the present invention can provide a therapeutic concentration of hydrogen, e.g., >0.1% (e.g., higher concentrations, e.g., >4%), to a subject without interfering with normal breathing or even vigorous breathing (e.g., during exercise, certain breathing techniques, etc.). The methods of the present invention can also reduce the risk of explosion when administering hydrogen to a subject by controlling the amount of hydrogen and / or the ratio of hydrogen to oxygen.

[0054] The method includes generating a mixed gas by mixing hydrogen and oxygen in a device including a mixing chamber. A conduit in fluid communication with the mixing chamber allows the mixed gas to be delivered to a subject, for example, topically and / or pulmonary. In some embodiments, a third gas (e.g., any gas described herein) is supplied to the mixing chamber from a third gas source in fluid communication with the mixing chamber.

[0055] The mixed gas can be flowed to the subject at a flow rate of at least 4 LPM, e.g., about 4-8 LPM, e.g., about 5, 6, 7, or 8 LPM. The flow of the mixed gas can match the subject's minute ventilation. The method of the present invention can deliver hydrogen to the subject at a concentration of 0.1-90%, e.g., 1-10%, e.g., 0.5-4%, or at least 4%, e.g., 4-6%, 4-8%, or 5-10%. The hydrogen concentration can be less than 10%. The method may deliver at least 300 mL (e.g., about 300-750 mL) of hydrogen per minute, e.g., about 7.2 LPM of other gases. The mixed gas may also deliver oxygen at or near the normal breathing range, e.g., about 10-25%, e.g., about 18-22%. The system may also provide intermittent hypoxic concentrations (e.g., 10-20%), e.g., for hypoxic conditioning applications.

[0056] The method may include providing humidity with the gas mixture, e.g., from a humidifier in fluid communication with the system (e.g., in fluid communication with the device, e.g., fluidly connected to a hydrogen source or chamber, or e.g., fluidly connected to a conduit). Humidity may be provided at a level that provides comfort to the subject, e.g., >10 mg / L, e.g., about 17-42 mg / L, e.g., about 17 mg / L, about 23 mg / L, about 32 mg / L, about 42 mg / L, or e.g., >32 mg / L, at about 30-100%, e.g., 30-50%, relative humidity relative to the temperature and pressure of the gas mixture. The method may also include adjusting the relative humidity of the gas mixture (e.g., manually or via computer). The humidity level may be selected to prevent electrostatic discharge within the system.

[0057] The method may also include adjusting (e.g., manually or via a computer) the flow of hydrogen from the hydrogen source and / or the flow of oxygen from the oxygen source and / or the third gas to increase or decrease the concentration of hydrogen, oxygen, and / or the third gas provided to the subject.

[0058] The methods of the present invention may include providing a hydrogen gas mixture while a subject is engaged in physical activity (e.g., running, rowing, cycling, etc., e.g., on stationary gym equipment). Alternatively, or in addition, the subject may engage in breathing exercises (e.g., relaxation breathing, pulmonary rehabilitation, meditative breathing, etc.). Examples of breathing exercises that may be performed in combination with or as part of the methods of the present invention include, for example, pursed lip breathing, abdominal breathing (also known as diaphragmatic breathing), "4-8-8" breathing, Wim Hof ​​breathing, 60-second inhales and 60-second exhales, etc. The methods may also include establishing a pre-programmed set of conditions for the flow of the gas mixture (e.g., flow rate, pressure, oxygen concentration, hydrogen concentration, type and concentration of additional gas, etc.) appropriate for the type of exercise or breathing exercise being performed. [Example]

[0059] An exemplary device is shown in Figure 1. A water reservoir supplies water to an electrolytic cell containing a proton exchange membrane. The electrolytic cell separates the water into hydrogen and oxygen gases, which are collected separately and sent to an air blower and mixer. The air blower and mixer mix the oxygen and hydrogen gases produced by the electrolytic cell with filtered air from a room outside the machine. The mixed gases are sent to an inflatable bag, which delivers the gas to the mask and patient through a one-way valve. This valve prevents exhaled air from the patient from mixing with the mixed gases in the balloon. The machine is controlled via a touchscreen display, which is also connected to a speaker that can provide audible feedback. The touchscreen is also connected to sensors that measure and display the effluent gas percentage, airflow rate, HEPA interlock check, reservoir water level, machine tilt, electrolytic cell temperature, and total dissolved solids. These sensors, screen, speaker, and electrolytic cell are powered by the mains supply.

[0060] Table 1 shows the machine settings selected for generating the mixed gas mixture with the mask: flow rate settings, electrolysis current, and touchscreen settings. The measured amounts of H2 and O2 gas in the effluent are shown in the table.

[0061] Other embodiments are within the claims.

[0062] [Table 1]

Claims

1. 1. An apparatus for administering hydrogen to a subject, comprising: a) a hydrogen source; b) an oxygen source; and c) a mixing chamber in fluid communication with the hydrogen source and the oxygen source; d) a conduit in fluid communication with the mixing chamber; A device that allows the device to mix hydrogen and oxygen to provide a mixed gas at a flow rate that does not interfere with normal breathing.

2. 10. The apparatus of claim 1, wherein the apparatus delivers the mixed gas to the subject at a flow rate of 4 to 60 LPM.

3. 10. The device of claim 1, wherein the device delivers the mixed gas at a flow rate that matches the minute ventilation of the subject.

4. 10. The apparatus of claim 1, further comprising a reservoir for the mixed gas.

5. 10. The apparatus of claim 1, further comprising a source of a third gas in fluid communication with the mixing chamber.

6. The apparatus of claim 1 further comprising an interface with the object.

7. 7. The device of claim 6, wherein the interface is an oral-nasal mask, a nasal cannula, a full face mask, goggles, earpieces, a helmet, a full body suit, a chamber, an animal cage, or a sealable tube.

8. 10. The apparatus of claim 1, further comprising one or more flow regulators between the mixing chamber and the target, hydrogen source, oxygen source, or combinations thereof.

9. 10. The apparatus of claim 1, further comprising one or more one-way valves between the mixing chamber and the target, the hydrogen source, the oxygen source, or a combination thereof.

10. 10. The apparatus of claim 9, wherein the one or more one-way valves allow gas flow to the subject.

11. 10. The device of claim 9, wherein the one or more one-way valves prevent gas flow to the subject unless opened by negative pressure caused by respiratory inhalation.

12. 6. The apparatus of claim 5, wherein the third gas is a therapeutic gas.

13. 13. The device of claim 12, wherein the third gas is nitrous oxide, nitric oxide, xenon, argon, halothane, isoflurane, desflurane, carbon monoxide, hydrogen sulfide, or sevoflurane.

14. 6. The apparatus of claim 5, wherein the oxygen source is an air pump and the source of the third gas is a pure or concentrated oxygen source.

15. 10. The apparatus of claim 1, wherein the hydrogen source is an electrolytic hydrogen generator, a compressed gas cylinder, or a sealable canister configured for use with a hydrogen generating composition.

16. 10. The apparatus of claim 1, further comprising a computer configured to control the flow of hydrogen and / or oxygen to the mixing chamber.

17. 10. The apparatus of claim 1, further comprising a humidifier in fluid communication with the mixing chamber.

18. 10. The device of claim 1, further comprising a light source for red light therapy.

19. 7. The device of claim 6, wherein the interface comprises a light source for red light therapy.

20. 1. A system for administering hydrogen to a subject, comprising: a) i) a mixing chamber having first and second inlets and an outlet; ii) a conduit in fluid communication with the mixing chamber; an apparatus comprising: b) a hydrogen source in fluid communication with the first inlet; c) an oxygen source in fluid communication with the second inlet; A system that allows the system to mix hydrogen and oxygen to provide a mixed gas at a flow rate that does not interfere with normal breathing.

21. 21. The system of claim 20, further comprising a reservoir for the mixed gas.

22. 21. The system of claim 20, further comprising an interface with the object.

23. 23. The system of claim 22, wherein the interface is an oral-nasal mask, nasal cannula, full face mask, goggles, earpieces, a helmet, a full body suit, a chamber, an animal cage, or a sealable tube.

24. 21. The system of claim 20, further comprising a third inlet to the mixing chamber and a source of a third gas in fluid communication with the mixing chamber.

25. 25. The system of claim 24, wherein the third gas is nitrous oxide, nitric oxide, xenon, argon, halothane, isoflurane, desflurane, carbon monoxide, hydrogen sulfide, or sevoflurane.

26. 25. The system of claim 24, wherein the third gas is a therapeutic gas.

27. 21. The system of claim 20, further comprising one or more flow regulators between the mixing chamber and the target, the hydrogen source, the oxygen source, or a combination thereof.

28. 21. The system of claim 20, further comprising one or more one-way valves between the mixing chamber and the target, the hydrogen source, the oxygen source, or a combination thereof.

29. 30. The system of claim 28, wherein the one or more one-way valves permit the flow of gas to the subject.

30. 30. The system of claim 28, wherein the one or more one-way valves prevent gas flow to the subject unless opened by negative pressure caused by respiratory inhalation.

31. 25. The system of claim 24, wherein the oxygen source is an air pump and the source of the third gas is a pure or concentrated oxygen source.

32. 21. The system of claim 20, wherein the hydrogen source is an electrolytic hydrogen generator, a compressed gas cylinder, or a sealable canister configured for use with a hydrogen generating composition.

33. 21. The system of claim 20, wherein the system delivers the mixed gas to the target at a flow rate of 4 to 60 LPM.

34. 21. The system of claim 20, wherein the system delivers the mixed gas at a flow rate that matches the minute ventilation of the subject.

35. 21. The system of claim 20, further comprising a computer configured to control the flow of hydrogen and / or oxygen to the mixing chamber.

36. 21. The system of claim 20, further comprising a humidifier in fluid communication with the mixing chamber.

37. 21. The system of claim 20, further comprising a light source for red light therapy.

38. 23. The system of claim 22, wherein the interface comprises a light source for red light therapy.

39. 1. A method of administering hydrogen to a subject, comprising: a) i) a mixing chamber; ii) a conduit in fluid communication with the mixing chamber; providing an apparatus comprising: b) supplying hydrogen from a hydrogen source and oxygen from an oxygen source to the mixing chamber to produce a mixed gas; and c) allowing the mixed gas to flow through the conduit to the subject, providing the mixed gas at a flow rate that does not interfere with normal breathing.

40. 40. The method of claim 39, further comprising supplying a third gas to the mixing chamber from a third gas source.

41. 41. The method of claim 40, wherein the third gas is nitrous oxide, nitric oxide, xenon, argon, halothane, isoflurane, desflurane, carbon monoxide, hydrogen sulfide, or sevoflurane.

42. 40. The method of claim 39, wherein the mixed gas is flowed to the target at a flow rate of 1 to 60 LPM.

43. 40. The method of claim 39, wherein the mixed gas is flowed to the subject at a flow rate that matches the minute ventilation of the subject.

44. 40. The method of claim 39, further comprising adjusting the flow of hydrogen from the hydrogen source and / or the flow of oxygen from the oxygen source to increase or decrease the hydrogen concentration in the mixed gas provided to the subject.

45. 45. The method of claim 44, wherein the adjusting step is performed via a computer that automatically adjusts the hydrogen and / or oxygen flow to maintain a constant total flow rate.

46. 40. The method of claim 39, wherein the subject is engaged in physical activity and / or breathing exercises.

47. 40. The method of claim 39, further comprising adding humidity to the gas mixture.

48. The method of claim 1 , further comprising illuminating the object with red light.

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