WO2023092022A1 - Hydrogen gas production for medical use - Google Patents

Abstract

Various embodiments disclosed relate to production of hydrogen gas for medical use. The present disclosure includes systems and methods including a device for production of hydrogen gas. The device can include a reaction chamber for oxidizing a reactive metal with an acid or base, a fluid inlet, and a gas outlet. A system can include the device, a fluid reservoir for medical fluid, and an infusion line.

Description

HYDROGEN GAS PRODUCTION FOR MEDICAL USE

PRIORITY CLAIM

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63/264,186, filed November 17, 2021, the contents of which are incorporated herein by reference in their entirety.

BACKGROUND

[0002] After a period of ischemia, anoxia, or hypoxia (e.g., lack of oxygen), tissue can be subject to damage by reperfusion injury when blood supply returns. The absence of oxygen and other nutrients from the tissue during the period of ischemia can create conditions where restoration of circulation can result in inflammation and oxidative damage due, in part, to reactive oxygen species that come into existence during reperfusion. This can occur, for example, through induction of oxidative stress instead of, or in addition to, restoration to normal tissue function.

SUMMARY OF THE DISCLOSURE

[0003] In an example, a device includes a reaction chamber for containing a reactive metal and an anhydrous reactant such as an acid or base. A water inlet is fluidly connected to the reaction chamber. The water inlet is configured to receive water and direct the water to the reaction chamber to mix with the reactant and oxidize the reactive metal to produce hydrogen. A gas outlet is fluidly connected to the reaction chamber and is configured to release hydrogen gas from the reaction chamber.

[0004] In an example, a system can include a device for production of hydrogen gas, a fluid reservoir coupled to the reaction chamber, the fluid reservoir for receiving hydrogen gas from the reaction chamber; and an infusion line coupled to the fluid reservoir. The device can include a reaction chamber for containing a reactive metal and an anhydrous reactant such as an acid or base; a water inlet fluidly connected to the reaction chamber, the water inlet for receiving water and directing it to the reaction chamber; and a gas outlet fluidly connected to the reaction chamber, the gas outlet for release of hydrogen gas from the reaction chamber therethrough. [0005] In an example, a method can include inserting water into a reaction chamber loaded with an anhydrous reactant and a reactive metal; producing of a predetermined amount of hydrogen gas in the reaction chamber; and saturating a medical fluid with the produced hydrogen gas to produce hydrogen saturated medical fluid.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006] In the drawings, which are not necessarily drawn to scale, like numerals may describe similar components in different views. Like numerals having different letter suffixes may represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[0007] FIG. l is a block diagram of a hydrogen gas production device in an example.

[0008] FIG. 2 illustrates a system with a hydrogen gas production device in an example.

[0009] FIGS. 3A, 3B, and 3C illustrate a system with a hydrogen gas production device in an example.

[0010] FIG. 4 illustrates a system with a hydrogen gas production device in an example.

[0011] FIG. 5 illustrates a system with a hydrogen gas production device and a liquid trap in an example.

[0012] FIG. 6 illustrates a system with two hydrogen gas production devices in an example.

[0013] FIGS. 7A, 7B, and 7C illustrate a system with multiple hydrogen gas production devices in an example.

[0014] FIGS. 8A, 8B, 8C, and 8D illustrate a system with a column of hydrogen gas production device in an example.

[0015] FIGS. 9 A, 9B, and 9C illustrate a system with a hydrogen gas production and gas purge device or gas mixing device in an example.

[0016] FIG. 10 illustrates a system with a hydrogen gas production device in an example.

[0017] FIG. 11 illustrates a system with a hydrogen gas production device in an example. [0018] FIG. 12 illustrates a system with a hydrogen gas production device in an example.

[0019] FIG. 13 illustrates a system with a hydrogen gas production device in an example.

[0020] FIGS. 14A and 14B illustrate a system with a hydrogen gas production device in an example.

[0021] FIGS. 15A-15B illustrate a system with a hydrogen production device combined with a gas exchanger in an example.

[0022] FIGS. 16A-16B illustrate a system having a hydrogen gas production device and a reactant mixing syringe in an example.

DETAILED DESCRIPTION

[0023] The present disclosure describes, among other things, a disposable hydrogen gas production device for use in medical settings. The device can include a disposable chemical reaction chamber attached to a fluid reservoir. Production of a predetermined amount of hydrogen gas can be initiated in the reaction chamber by addition of water, causing a hydrolysis reaction. The produced hydrogen gas can be directed to the fluid reservoir, where it can be captured as an enclosed volume at the top of the fluid reservoir. The hydrogen gas can equilibrate with the fluid in the fluid reservoir, such as to saturate the fluid in the reservoir with hydrogen, without excess production of hydrogen gas, or mixing of hydrogen gas with other medical gases.

[0024] The relatively small quantity of hydrogen gas produced by the device can remain isolated in the reservoir, unmixed with outside air or other medical gases. The operator can initiate the production of hydrogen gas when desired with a small amount of water in order to prepare a medically useful hydrogen-saturated medical fluid.

[0025] When hydrogen that is produced in this manner is allowed to dissolve in tissue and blood, the hydrogen can diffuse rapidly across barriers, such as membranes, into cells. The hydrogen can then operate to scavenge and neutralize reactive oxygen species, such as those found in cellular metabolic processes and the innermost regions of cells during reperfusion. This mode of hydrogen gas therapy can allow for reduction in oxidative stress, cell apoptosis, and tissue inflammation. Hydrogen gas therapy can also help reduce tissue injury, allow for higher function, and aid in viability of both tissue and organs. [0026] Disclosed herein are system and methods for hydrogen gas production for medical uses, such as in clinical or operating room settings. Hydrogen gas can be used to help protect tissue during processes such as reperfusion or ischemia. However, hydrogen is not commonly used in medical settings such as ORs due to safety concerns with hydrogen production and storage. In particular, hydrogen is highly flammable. Discussed herein is a safer, effective, way to produce hydrogen gas for medical application with a disposable chemical reaction chamber. The chamber and method allow for production of a predetermined amount of hydrogen in a controlled setting.

[0027] However, use of hydrogen, such as for hydrogen gas therapy in tissue, has been limited in a clinical setting. Hydrogen gas is highly flammable, at a large variety of concentrations, and induces a wide range of safety concerns. For example, mixing of hydrogen gas with air or other medical gases can involve error-prone and hazardous processes. For these reasons, hydrogen gas is problematic to store and use in a medical setting.

[0028] The apparatuses and methods discussed herein allow for production of a limited, predetermined amount of hydrogen gas on demand. This specific amount of hydrogen gas can be produced in a clinical or medical setting in a targeted way to allow application to therapeutic goals, such as treatment to prevent reperfusion injury. This predetermined amount of hydrogen gas can be produced without excess. The devices discussed herein can automatically stop producing hydrogen gas when the predetermined amount has been made.

Smaller, specified amounts of hydrogen gas production can allow for gas isolation in clinical settings, significantly reduces hazards and safety concerns typically associated with the use of hydrogen gas, hydrogen gas storage, and mixing of hydrogen gas with other medical gases. [0029] FIG. 1 illustrates a hydrogen gas production device 101 in an example. The device 101 can be a portable, disposable, device 101. For example, the device 101 can be used in a clinical setting in conjunction with a fluid reservoir to produce a predetermined amount of hydrogen for a specific, one-time use, such as reperfusion injury prevention.

[0030] The device 101 can include a reaction chamber 102, an inlet 103, and an outlet 104. The reaction chamber 102 can include a reactive metal 105 and an anhydrous reactant 106, such as an anhydrous acid or inorganic base. In the device 101, water delivery device 107 can be used to insert water into the reaction chamber 102 through the inlet 103 to mix with the reactant 106 and oxidize the metal to produce hydrogen gas 108. The produced hydrogen gas 108 can be released through the outlet 104. The inlet 103 can be, for example, on a bottom surface of the reaction chamber 102, and the outlet 104 can be on a top surface of the reaction chamber 102, such as across from the inlet 103. The top and bottom correspond to the position of the device 101 during normal use to produce hydrogen for infusion into the medical fluid, such as a liquid. As discussed herein, “normal use” can include reliance on gravitational force for separation of hydrogen gas from the liquid or solid phase reactants. [0031] The reaction chamber 102 can be a gas impermeable container, such as for holding reactants and produced hydrogen gas without substantial gas leakage. The reaction chamber 102 can be a container sized and shaped to hold the reaction components of a reactive metal 105 and a reactant 106 such as an anhydrous acid or inorganic base. The reaction chamber 102 can be made of a material appropriate to allow for a hydrolysis reaction therein without breaking or leaking, to contain the generated pressure, or to expand up to about 25% or more in volume to contain the generated gas. For example, the reaction chamber 102 can be formed of a section of tubing, a metallic, plastic, or composite, material, or other shape or material that is impermeable to the reaction components and products.

[0032] The reaction chamber 102 can be pre-loaded with the reaction components, the reactive metal 105 and reactant 106. The reactive metal 105 and the reactant 106 can be in predetermined quantities depending on the desired amount of hydrogen gas. In one example, an inside liner of reaction chamber 102 may formed of a reactive metal, or the entire reaction chamber 102 may be formed with the reactive metal.

[0033] The reactive metal 105 can be, for example, magnesium, aluminum, zinc, iron, combinations thereof, or other reactive metals suitable for a hydrogen-generating reaction. The reactive metal 105 can be, for example, a solid phase, such as a bar, a powder, cubes, chips, or other shapes as appropriate. In some cases the reactive metal 105 can be in the form of powder, granules, particles, ribbons, wires, or other solid shape and form, or combinations of the same.

[0034] The reactant 106 can be, for example, a solid phase anhydrous acid or inorganic base capable of a hydrolysis reaction with the reactive metal 105 to produce hydrogen gas. The anhydrous acid reactant 106 can be, for example, citric acid, lactic acid, oxalic acid, malic acid, tartaric acid, or mixtures thereof. In some cases, the anhydrous acid 106 can be replaced with an anhydrous base, and the metallic component can be a metallic silicon instead of a reactive metal, such as a mixture of sodium hydroxide and ferrosilicon. Example anhydrous base materials can be sodium hydroxide (NaOH), potassium hydroxide (KOH), or lithium hydroxide (LiOH).

[0035] The reactive metal 105 and the reactant 106 are stable and non-reactive in a solid state. However, the reactive metal 105 and the reactant 106 will react when water is added to the reaction chamber via inlet 103 such as by a syringe having a mating coupling (e.g., threads) with inlet 103, making the reactant 106 an aqueous acid or base. In this case, the protons (H⁺) can dissociate in the aqueous solution and react with the metal 105, allowing evolution of hydrogen gas (H2). Example reactions between a reactive metal (M) and appropriate aqueous acid are shown for divalent reactive metals Mg or Zn as:

or for trivalent reactive metal Al as

6H aq + 2M(solid) 2 ³ aq + 3H2(gas)

[0036] Example reactions between reactive metal (M) and appropriate aqueous bases where M is Zinc, forming a Zincate ion are shown as

or where M is Al and forms an aluminate ion as

[0037] The reactive metal 105 and the reactant 106 can be selected in stoichiometric or near-stoichiometric quantities to produce the desired amount of hydrogen gas. The quantities of both the reactive metal 105 and the reactant 106 can be specifically limited to control the amount of hydrogen gas that will be produced. After adding water with the water delivery device 107 to start the reaction, the final reaction products are hydrogen gas 108 which flows out through the gas outlet port 104, and metal ions dissolved in the reactant, which remain in the aqueous phase in the reaction chamber 102. In some cases, leftover reactive metal may remain in the reaction chamber as solid precipitates.

[0038] In an example 0.8 mmol of hydrogen gas at standard temperature and pressure (STP) will saturate one liter of water. Thus, if a medical professional desires to saturate one liter of water with hydrogen gas for medical use, about 18 mL or less of hydrogen gas should be produced. Either the initial quantity of the reactive metal 105 or the initial quantity of the reactant 106 can be limited to control the amount of produced hydrogen gas.

[0039] In an example, the reactive metal 105 can be magnesium and the anhydrous reactant can be citric acid. If 18 mL of hydrogen gas is desired, about 0.02 grams of magnesium or about 0.17 grams of anhydrous citric acid can limit the reaction to produce no more than 18 mL of hydrogen gas. When the citric acid is saturated with water, the following reaction can occur to produce hydrogen gas:

2H aq + Mg(solid) Mg² aq + H2 (gas)

[0040] In this case, the citric acid can be dissolved, initiating the reaction. In some cases, depending on the types of anhydrous reactant and reactive metal chosen, a greater- than-stoichiometric ratio may be desired to fully immerse the reactive metal and drive the hydrolysis reaction to completion.

[0041] Example reactions using a base include:

Zn +_2NaOH-> Na2ZnC>2 + H2 (gas)

OR

Potassium hydroxide or lithium hydroxide may be used in place of sodium hydroxide.

[0042] In some cases, the reactive metal 105 and the reactant 106, can be mixed with a defoaming agent. Such a defoaming agent can help reduce foaming during the hydrolysis reaction as the hydrogen gas 108 is produced. The defoaming agent can include, for example, silicone oil, stearates, or glycols.

[0043] The hydrolysis reaction for production of hydrogen gas is an exothermic reaction. For this reason, in some cases, the reaction chamber can be further equipped with heat sink or heat transfer elements. For example, such elements can be embedded in the walls of the reaction chamber 102 to help maintain a steady temperature over the course of the reaction.

[0044] The water inlet 103 can be sized, shaped, or arranged, for insertion of a predetermined amount of water through the water delivery device 107 into the reaction chamber 102 to initiate the reaction for production of hydrogen gas. As discussed below with reference to FIGS. 2 to 10, various valves, couplings, and connections can be used to allow for easy insertion of water into the reaction chamber 102, such as by syringe. [0045] In some cases, the water and the water delivery device 107 can be prepackaged with the reaction chamber 102. For example, the water can be isolated in a predetermined amount separated from the reaction chamber 102, such as by a membrane or other barrier. The barrier can be breakable when desired to initiate a flow of water into the reaction chamber 102 to initiated hydrogen gas production.

[0046] In some cases, only the reactive metal 105 can be packaged alone in the reaction chamber 102, without the anhydrous acid or base. In this case, an aqueous acid or base can be injected into the reaction chamber instead of water at the inlet 103, such as by syringe or tube. The inlet 103 can include coupling (e.g., threads or another type of connection) to allow for fluid-tight connection to a syringe, tube, or other water source. The inlet 103 can be couplable to a water delivery device for provision of water into the system 100.

[0047] In some cases, the device 101 can incorporate various monitors and measurement devices, such as for monitoring and control of temperature, hydrogen concentration, hydrogen flow rate, and pressure.

[0048] The outlet 104 can allow for release of hydrogen gas 108 out of the reaction chamber 102, such as to a fluid reservoir or other gas pathway for medical use. In some cases, liquid absorbing elements, or hydrophilic traps, can be used along the outlet 104 to prevent liquid reactants from moving with the hydrogen gas 108 as it migrates out of the device 101. Examples of such reservoirs and gas pathways are discussed below in more detail with reference to FIGS. 2-10.

[0049] In some cases, the device 101 can be used for organ or tissue transport. In some cases, the device 101 can be connected to an ex vivo organ or tissue device, such as a perfusion device, a dialysis or chelation device, or a diagnostic device.

[0050] FIG. 2 illustrates a system 200 with a hydrogen gas production device 201 in an example. The system 200 can include the device 201, having a reaction chamber 202 with a reactive metal 205 and an anhydrous reactant 206 such as an acid or inorganic base, an inlet 203 for water delivery device 207, an outlet 204 for hydrogen gas 208. The device 201 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[0051] The system 200 can further include a fluid reservoir 209 with a medical fluid 210 and medical infusion line 211 connecting to the target tissue 212. In system 200, the reaction chamber 202 can be connected to the fluid reservoir 209 through the outlet 204. The fluid reservoir 209 can be secured to the outlet 204 through one or more connection ports. The fluid reservoir can be connected to a patient, organ, or target tissue 212 through a line, such as the medical infusion line 211. The medical infusion line 211 can include tubing, needles, catheters, or another appropriate passageway type to infuse the target tissue 212. [0052] The fluid reservoir 209 can be, for example, an IV bag, plastic bottle, rigid container, or other standard container used to move medical fluid to a patient or other target tissue 212. The fluid reservoir 209 can, in some cases, be connected to a pressurized container for receiving the hydrogen gas 208. In this case, the pressurized container can allow for diffusion of hydrogen 208 through the container walls, or through a flow-restricting element or orifice, such as to the fluid reservoir 209.

[0053] The medical fluid 210 can be a fluid used to treat or maintain a patient during surgery, to maintain tissue requiring perfusion, or some other medical fluid. The medical fluid 210 can be, for example, saline, whole blood, partial blood, cardioplegia solution or an aqueous solution with other chemical components, such as drugs or stabilizers for the designated use. In some cases, whole blood, partial blood, or mixtures of blood components with other medical fluids can be used.

[0054] The medical infusion line 211 can allow for infusion of the medical fluid 210 into the patient or other target tissue 212. The target tissue 212 can be, for example, a patient undergoing open-heart surgery, a heart or other organ, perhaps disposed in a body or in movement for transplant, or other tissue.

[0055] Similar to the device 101 discussed above, when water is injected through the water inlet 203 with a water delivery device 207, a hydrolysis reaction is initiated in the reaction chamber 202, where the reactive metal 205 and the reactant 206 react to evolve hydrogen gas 208 by oxidation of the reactive metal 205. In device 201, the water can be inserted through the water delivery device 207 (e.g., a syringe) connected to the water inlet 203, such as by threading or a syringe port. Such a syringe can be used to measure out a desired amount of water 207 depending on the desired amount of hydrogen gas 208.

[0056] Once produced, the hydrogen gas 208 can migrate through the outlet 204 and migrate through the medical fluid 210. The medical fluid 210 can be saturated with the dissolved hydrogen gas 208. In some cases, the medical fluid 210 can be partially saturated, such as up to 50%, 70%, or 90% saturated. This can depend on the initial conditions of the system, and how many saturation cycles (e.g., gas exchanges) are used. In some cases, the medical fluid 210 can be supersaturated, such as if prepared under high pressure. The hydrogen 208 saturated medical fluid 210 can be directed from the fluid reservoir 209 through the medical infusion line 211 to the patient or other target tissue 212. The top and bottom correspond to the position of the device 201 during normal use to produce hydrogen for infusion into the medical fluid, such as a liquid.

[0057] In some cases, the outlet 204, instead of being connected to a fluid reservoir 209, can be connected to an expandable container, such as a balloon, bladder, syringe, or other pressurized container. In this case, hydrogen gas can accumulate therein. The expandable container can be used to transfer of hydrogen gas to another medical apparatus that is not otherwise fluidly coupled to the outlet 204.

[0058] In some cases, a gas exchanger 290 can be connected to the system 200. For example, a gas permeable membrane, a hollow-fiber gas exchanger, or a bubble gas exchanger can be used. The gas exchanger 290 can be used, for example, with the hydrogen gas production device.

[0059] FIGS. 3A, 3B, and 3C illustrate a system 300 with a hydrogen gas production device 301 in an example. The system 300 can include the device 301, having a reaction chamber 302 with a reactive metal 305 and an anhydrous reactant 306, an inlet 303 for water delivery device 307, an outlet 304 for hydrogen gas 308. The device 301 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted. The system 300 can further include a fluid reservoir 309 with a medical fluid 310 and medical infusion line 311 connecting to the target tissue 312, in addition to an air evacuation port 320, one-way valves 321, 330, 340, syringe ports 322, 341, fluid connector 331, syringes 350, 360, gas 355. The gas 355 can include air, nitrogen, carbon dioxide, or other gases initially present in the headspace 380. In some variations, FIGS. 3A- 3C depict aqueous acid or base 370 and headspace 380.

[0060] FIG. 3A depicts a close up view of the device 301, while FIGS. 3B-3C depict a view of the larger system 300 including the device 301. FIG. 3B depicts the system 300 at rest (e.g., prior to use or out of the package), while FIG. 3C depicts the system 300 in use. In the system 300, the inlet 303 can include a closed syringe port 341 and a one-way valve 340 (e.g., a check valve) for controlled flow of water therethrough when the flow of water is induced with the syringe 360. The outlet 304 can similarly include a one-way valve 330. Additionally, the air evacuation port 320, including its own one-way valve 321 and syringe port 322, can extend from the outlet 304, reaction chamber 302 or any fluidly connected location on 301 between one-way valves 330 and 340. The syringe port 322 can be used with the air evacuation port 320. In system 300, the use of the air evacuation port 320, the one-way valves 321, 330, 340, and the syringe ports 322, 341, can allow for improved effectiveness and convenience for the device 301.

[0061] The water inlet port 303 can be fitted with the one-way valve 340 to allow water flow into the reaction chamber 302 but not in the reverse direction. The normally closed syringe port 341 can be open to fluid flow only when the syringe 360 or other coupling device are connected. Otherwise, the inlet 303 does not allow fluid flow in either direction.

[0062] The gas outlet 304 can also be fitted with a one-way valve 330 to allow fluid flow only in the upward direction, out of the device. The fluid connector 331 can be used for convenient connection to the medical fluid reservoir 309. In some cases, the fluid connector 331 can be a luer fitting, or other fluid tight connection.

[0063] The air evacuation port 320, shown in use in FIG. 3B, can be connected on the outlet 304, such as by a tee or wye connection. The air evacuation port 320 can include the one-way valve 321 and a normally closed syringe port 322. The one-way valve 321 can allow air or fluid to flow out of the system 300 without returning into the device 301. The syringe port 322 can be open to fluid flow when connected to the syringe 350. Thus, when a syringe 350 is attached through the air evacuation port 320, the system 300 can be evacuated or depressurized.

[0064] In some cases, the air evacuation port 320 can instead be connected in parallel with the water injection port 303, instead of the gas outlet 304. In some cases, the air evacuation port 320 can be connected directly to the reaction chamber 302. In some cases, both the air evacuation port 320 and the water injection port 303 can vary between different sides or surface of the reaction chamber 302. For example, the evacuation port 320 can be on a side wall of the system 300, north of the injection port 303. However, shown in system 300, the outlet 304 can generally be located at a top surface of the reaction chamber 302 to allow for release of hydrogen gas.

[0065] FIG. 3B depicts air evacuation of the device 301 while connected to the fluid reservoir 309. The flow of fluid from the reservoir 309 is prevented by the one-way valve 330. During evacuation, an empty syringe 350 can be connected to the syringe port 322. The syringe 350 can have a higher volumetric capacity compared to the internal volume of the device 301. For example, the syringe 350 can have a capacity of about 50 mL, compared to about 10 mL capacity of the device 301. When the syringe 350 plunger is withdrawn, a vacuum can be created in the device 301 reaction chamber 302. The syringe 350 can be used to draw out air (or other gases initially filling the headspace of the chamber, such as nitrogen, carbon dioxide, or other) filling the reaction chamber 302, in addition to the lines connecting the inlet 303 and the outlet 304.

[0066] The one-way valve 321 can prevent reintroduction of air back into the device. Additionally, the syringe port 341 can prevent air ingress at the water injection port 303 during vacuuming. The syringe 350 can be disconnected, and the syringe port 322 can prevent fluid flow in through the air evacuation port 320. In some cases, the one-way valves or syringe ports can be replaced by stopcocks.

[0067] When under vacuum, the air 355 can be substantially eliminated, preventing air mixing and subsequent dilution of the hydrogen gas. Additionally, the vacuum can automatically pull in the required volume of water in the next steps.

[0068] FIG. 3C depicts use of the system 300 under a vacuum. The vacuum can be an absolute vacuum or a partial vacuum, such as about one fifth or one tenth of the atmospheric pressure. The syringe 360 can be loaded with a predetermined amount of water 307. When the syringe 360 is connected to the syringe port 341, the water 307 can be pulled into the reaction chamber 302 by the vacuum environment. This can form the aqueous acid or base 370 in the reaction chamber 302, beginning evolution of hydrogen gas 308.

[0069] The volume of the water 307 can be determined by the minimum volume required to dissolve the anhydrous reactant 306, plus whatever overage to completely wet the reactive metal 305. The upper limit on the volume of water can be calculated to maintain a high (e.g., near saturation) concentration of the acid or base 370. The injected water volume 307 can also be small enough to leave headspace 380 above the reactants (the reactive metal 305 and aqueous acid or base 370) in the reaction chamber 302. The headspace 380 above the reactants can allow the hydrogen gas 308 to flow into the medical fluid 310 but can inhibit the flow of reactants (the reactive metal 305 and aqueous acid or base 370) upward and into the gas outlet 304 and medical fluid 310. In this case, the headspace 380 can occupy, for example, about half of the volume of the reaction chamber 302.

[0070] The hydrogen gas 308 can migrate through the outlet 304 to the fluid reservoir 309. The syringe port 322 and the one-way valve 321 can prevent movement of the hydrogen gas 308 out the air evacuation port 320. The one way valve 330 can provide the pathway for exit of the produced hydrogen gas 308, allowing flow of the hydrogen gas 308 into the fluid reservoir 309 to saturate the fluid 310. After the water 307 is injected with the syringe 360, the syringe 360 can then be disconnected from the syringe port 341 or left in place.

[0071] In some cases, metal hydrides can be used in the reaction chamber 302 instead of the combination of the reactive metal 305 and the anhydrous reactant 306. In this case, the use of air evacuation and water injection features discussed above with reference to FIGS. 3A-3C can be used in combination with the metal hydrides.

[0072] FIG. 4 illustrates a system 400 with a hydrogen gas production device 401 in an example. In system 400, a separate air evacuation port is not used, and air evacuation is accomplished by initial packaging conditions. The system 400 can, for example, be vacuum packed, such as by hermetically sealing a package 499 while the system 401 and surrounding space 498 is under vacuum.

[0073] The system 400 can include the device 401, having a reaction chamber 402 with a reactive metal 405 and an anhydrous reactant 406, an inlet 403 for water source 407, an outlet 404 for hydrogen gas 408. The device 401 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted. The system 400 can further include one-way valves 430, 440, and a syringe port 441.

[0074] By vacuum packaging the device 401 within a hermetically sealed packaging 499, the reaction chamber 402 can remain under vacuum 498 until the water injection syringe is connected to the normally closed syringe port 441, at which point the water 407 can be drawn out of the syringe and into the reaction chamber 402 to initiate the reaction. After hydrogen gas pressure 408 is generated within the reaction chamber 402, the one-way valve 440 can prevent reflux of the reactants down through the water injection port 403, and the hydrogen 408 can move up through the one-way valve 430 of gas exit port 404.

[0075] In some cases, the water injection port 403 and its elements 440 and 441 can be connect to the top of the reaction chamber instead of at the bottom.

[0076] FIG. 5 illustrates a system 500 with a hydrogen gas production device 501 having a reaction chamber 502 and a liquid trap 511, in an example.

[0077] The system 500 can include the device 501, having a reaction chamber 502 with a reactive metal 505 and an anhydrous reactant 506, a water inlet 503, an outlet 504 for hydrogen gas 508. In device 501, a liquid trap chamber 511 can be included to trap non- gaseous reaction byproducts 570 The device 501 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted. The system 500 can further include fluid reservoir 509 with hydrogen gas 508. [0078] The liquid trap chamber 511 can allow for trapping and separation of liquid reaction byproducts 570 that exit the reaction chamber 502 through the outlet 504. The liquid trap chamber 511 can provide an additional function such that that only the hydrogen gas 508 will exit to the fluid reservoir 509, and that the reactive metal 505 and other byproducts 570 remain in the device 501.

[0079] In some cases, a gas-permeable membrane can be used to filter out the byproducts in the device 501. In this case, a gas-permeable membrane can be used to allow the hydrogen gas 508 to flow out to the fluid reservoir 509, while filtering the other byproducts 570 and reactants out.

[0080] FIG. 6 illustrates a system 600 with two hydrogen gas production devices 602 in an example. The system 600 can include the devices 602 in parallel. Each of the devices 602 can include its own outlet 612 for evolution of hydrogen gas to a third reaction chamber 611. Each of the devices 602 can additionally include its own air evacuation line 613. The system 600 can have a single outlet 604 for connection to a fluid reservoir. The device 601 contains similar components, connected in a similar manner, to device 501 discussed above, except where otherwise noted.

[0081] In system 600, the reaction chambers 602 can be arranged in parallel fluid connections to the common liquid trap 611 and outlet 602. In some cases, additional reaction chambers 602 can be added in parallel. The use of multiple reaction chambers 602 can allow for either simultaneous multiplication (e.g., doubling) of hydrogen production, or sequentially produced discrete quantities of hydrogen gas. For example, 20mL of hydrogen gas can be produced in each reaction chamber 602, for a total of 40mL. These can be produced in sequence, or simultaneously. The produced hydrogen gas can then travel through the liquid trap 611, where any extraneous byproducts 670 can collect, and the hydrogen gas can exit through outlet 604 for medical use.

[0082] In some cases, sequential production of hydrogen gas can be used when a multi-step gas equilibrium procedure would be beneficial. In this case, the first reaction chamber 602 hydrogen gas can equilibrate with a medical fluid connected via outlet 604. The first production of hydrogen gas from the first reaction chamber 602 can displace other gases dissolved in the medical fluid. During this stage, the hydrogen concentration in the medical fluid can partially saturate the fluid, such as at about 60-90% saturation. This can depend on the quantity of any preexisting dissolved gases in the medical fluid, and on a preexisting equilibrium correlating to gas partial pressures therein. [0083] Subsequently, any hydrogen or mixed gas headspace in the fluid reservoir can be cleared, and a second amount of hydrogen gas can be produced in the second reaction chamber 602. The second production of hydrogen gas can be added to the medical fluid, to saturate the fluid above, for example about 90% saturation or greater. Thus, the multiple reaction chambers 602 can allow for a more hydrogen saturated medical fluid. In some cases, hydrogen gas can be produced to pressurize the medical fluid 609 above atmospheric pressure to achieve a supersaturated concentration of hydrogen gas in the medical fluid. [0084] FIGS. 7A-7C illustrate multiple variations of a system 700 with multiple hydrogen gas production reaction chambers 702, 714, 715, in an example. The system 700 can include inlet 703, outlet 704, and reaction chambers 702, 714, and 715. The device 701 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[0085] In system 700, the multiple reaction chambers 702, 714, and 715 can be arranged in serial connection to a single common gas exit port 704 and water injection port 703. Each reaction chamber can produce a limited amount of hydrogen gas in sequence, beginning with initiation of the reaction in the bottom chamber 702, followed by the middle chamber 714, and finally by the top chamber 715.

[0086] The timing of hydrogen production can be dictated by the pace of water injection at the inlet 703. For example, a first amount of water can be injected at inlet 703, such as by a syringe, and in the reaction chamber 702, the reaction can run to completion before a new amount of water is introduced (FIG. 7A). Introduction of another (e.g., second) injection of water can initiate the reaction within the second reaction chamber 714 (FIG. 7B). Finally, a subsequent (e.g., third) injection of water can initiate the reaction within the third reaction chamber 715 (FIG. 7C).

[0087] The hydrolysis reaction in each chamber between the aqueous acid or base and the reactive metal can run to completion before more water is injected to activate the next chamber above as depicted in sequence from FIG. 7A to FIG. 7C. In FIG. 7A, enough water is injected at the inlet 703 to complete the reaction in the lowest reaction chamber 702. In FIG. 7B, the reaction in reaction chamber 702 has completed and more water is injected to initiate reaction in the middle reaction chamber 714. In FIG. 7C, the reactions in reaction chamber 702 and reaction chamber 714 can be complete and the reaction in the final reaction chamber 715 can be initiated by the final injection of water. [0088] The arrangement in system 700 can provide for flexibility in the total amount and pace of hydrogen gas produced, depending on the chosen pace of initiation and quantity of water injected. In some cases, additional discrete reaction chambers can be connected in series. Water can be injected through the single water injection port 703 and the hydrogen gas can pass from the chamber in which it is produced, up through the dry chambers above it, without significant inhibition, to reach the gas outlet port 704.

[0089] FIGS. 8 A, 8B, 8C, and 8D illustrate a system 800 with a column hydrogen gas production device 802 in an example. The device 802 can include reactive metal 805, anhydrous reactant 806, water 807, and reaction front 818. The device 801 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[0090] FIG. 8A depicts the system 800 at rest. FIG. 8B depicts the system with a first injection of water 807. FIG. 8C depicts the system with additional water 807 pushing the reaction front 818 upstream, in linear fashion from FIG. 8A to FIG. 8C.

[0091] The length of the reaction chamber 802 can be extended to allow for continuous generation of hydrogen gas. The production rate of hydrogen gas, and the total amount of produced hydrogen gas, can depend on the flow rate of water into the reaction chamber 702 and the total volume of water injected.

[0092] As water works up the column in reaction chamber 802, the reaction front 818 moved upwards. The reaction front 818 can continue to propagate upwards concurrent with liquification of the anhydrous reactant 806 by the rising water column 807.

[0093] In FIGS. 8A to 8C, the reactive metal 805 can be homogeneously dispersed particles or pieces of the reactive metal within the anhydrous reactant 806. In FIG. 8D, the reactive metal 805 can be a rod, ribbon, wire, or continuous piece of metal that runs the length of the column, surrounded by the anhydrous reactant 806. In some cases, the reaction chamber 802 can additionally include one or more heat sink or heat transfer elements, such as to dissipate heat from the exothermic hydrolysis reaction as the reaction progresses up the column.

[0094] FIGS. 9A, 9B, and 9C illustrate a system 900 with multiple hydrogen gas production devices in an example. The system 900 can include the reaction chamber 902, water inlet 903, gas outlet 904, anhydrous reactant 906, reactive metal 905, syringe 907, hydrogen gas 908, fluid trap chamber 911, syringe 919, a purging chamber 925, pre-loaded mixture 926, and gas 927. The device 901 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[0095] In system 900, the purging chamber 925 can be added in parallel or in series to the reaction chamber 902. The purging chamber 925 can, for example, be used to gas purge the system with carbon dioxide gas. The purging chamber 925 can be used to generate an initial quantity of carbon dioxide gas to purge and displace air from downstream elements, such as to prevent mixing of hydrogen gas with downstream gases and air. Thus, the produced hydrogen gas can initially mix with carbon dioxide, which is a nonflammable mixture, and avoid mixing of hydrogen with air, which is flammable.

[0096] FIG. 9A depicts a system 900 with the purging chamber 925 connected in parallel to the reaction chamber 902. Here, both the purging chamber 925 and the reaction chamber 902 are connected to a common liquid trap 911 and gas outlet 904. The purging chamber 925 can be supplied with a pre-loaded mixture 926, including an anhydrous acid and an anhydrous bicarbonate base such as sodium bicarbonate. This pre-loaded mixture can produce carbon dioxide when exposed to the water coming in from the syringe 919. In FIG. 9A, once carbon dioxide has been produced and purged the system 900, a reaction can be initiated in the reaction chamber 902 with water through the syringe 907, to produce hydrogen gas. In parallel, the products of the reaction in the purging chamber 925 are not mixed with the products of the reaction chamber 902.

[0097] In FIG. 9B, the reaction chamber 902 and the purging chamber 925 are arranged in series. A single water inlet 903 can be used, along with a single hydrogen gas outlet 904. Here, the water can be injected at the inlet 903 with a syringe 907. The water can travel through purging chamber 925 first, initiating the acid-base reaction and producing carbon dioxide, which can move upwards through the reaction chamber 902. A second volume of water can be injected with a water delivery device, such as a syringe, at the inlet 903 to raise the water level and induce the reaction in the reaction chamber 902. In this case, the sequence of carbon dioxide (CO2) production before hydrogen gas production occurs according to the water filling order of the two chambers 925 and 902.

[0098] In FIG. 9C, the single reaction chamber 902 contains the reactive metal 905, and a dry mixture (956) of sodium bicarbonate and anhydrous acid. In this embodiment, a single injection of water at port 903 can simultaneously produce carbon dioxide gas and hydrogen gas as a mixture 908. Such mixtures may be desirable when used to prepare medical solutions that are buffered by the bicarbonate buffering system. A mixture of 95% hydrogen gas and 5% carbon dioxide gas would balance the pH of a typical bicarbonate- buffered medical solution at 7.4, for example. The molar ratio of hydrogen gas to carbon dioxide gas can be controlled by adjusting the ratio of amounts of reactive metal 905 to sodium bicarbonate in the mixture 956.

[0099] FIG. 10 illustrates a system 1000 with a hydrogen gas production device 1001 in an example. The system 1000 can include the device 1001, reaction chamber 1002, gas outlet 1004, reactive metal 1005, anhydrous reactant 1006, a container 1090 with flexible side 1091, glass vial 1092 containing water 1095, and connector 1093. The device 1001 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[00100] In system 1000, the water 1095 can be packaged in the container 1090 for easy application to the device 1001 without an additional or external water source. Here, the water 1095 can be packaged in the device 1001 but separate by a physical barrier from the reaction chamber 1002 having the anhydrous reactant 1006 and reactive metal 1005. The device 1001 can be shelf stable (e.g., non-reactive until the time of use); the reaction for production of hydrogen gas can be initiated by breaking the physical barrier to introduce the water 1095 into the reaction chamber 1002.

[00101] For example, the water 1095 can be contained within a sealed glass vial 1092 enclosed in a flexible container 1091, such as a flexible tubing. The outer flexible container

1091 can be fluidly connected to the reaction chamber 1002. When the glass vial 1092 is broken, such as by bending or crushing the glass vial 1092, the water 1095 can flow into the reaction chamber 1002 and initiate the production of hydrogen gas. The outer flexible container 1091 can be hermetically sealed so that hydrogen gas flow out of the outlet 1004, not back into the chamber 1090.

[00102] In some cases, the dry reactants 1005 and 1006 can be contained within the breakable glass vial 1092, instead of the water 1095. In some cases, the breakable glass vial

1092 (e.g, hosting either of the dry reactants 1005 and 1007, or the water 1095), can be contained within the volume of the reaction chamber 1002 instead of within a side chamber such as the flexible container 1091. In this case, a flexible or deformable portion of the reaction chamber 1002 can facilitate breakage of the glass vial 1092. In some cases, the anhydrous reactant 1006 can be replaced by storage of aqueous acid or base within the glass vial 1092 instead of neutral water 1095. [00103] FIG. 11 illustrates as system 1100 with a hydrogen gas production 1101. The system 1100 can include the device 1101, reaction chamber 1102, gas outlet 1104, reactive metal 1105, anhydrous reactant 1106, and a glass vial 1192 containing water 1195. The device 1101 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[00104] In system 1100, the reaction chamber 1102 can be made of a flexible material. The glass vial 1192 containing the water 1195 can be packaged inside the reaction chamber 1102 itself, without a side chamber. When hydrogen production is desired, the user can break the glass vial 1192 to release the water 1195 into the reaction chamber 1102 with the anhydrous reactant 1106 and the reactive metal 1105.

[00105] FIG. 12 illustrates as system 1200 with a hydrogen gas production device 1201. The system 1200 can include the device 1201, reaction chamber 1202 with vacuum 1203, gas outlet 1204, reactive metal 1205, and a glass vial 1292 containing reactant 1206. The device 1201 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[00106] In the system 1200, the reaction chamber 1202 can host the glass vial 1292. The reaction chamber 1202 can start at a vacuum 1203 (either partial or full vacuum). The reactant 1206 can reside in the glass vial 1292, and can be an aqueous acid or base instead of an anhydrous acid or base. Breaking the glass vial 1292 initiates a reaction with the metal 1205 in the reaction chamber, producing hydrogen gas.

[00107] FIG. 13 illustrates as system 1300 with a hydrogen gas production device 1301. The system 1300 can include the device 1301, reaction chamber 1302 containing a reactive metal, and with a vacuum 1303, gas outlet 1304, and glass vial 1392 containing reactant 1395. The device 1301 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted. In one example, the reaction chamber containing the reactive metal may be formed of the reactive metal or have a liner or an inner surface or lined or otherwise containing the reactive metal

[00108] The system 1300 can include a reaction chamber 1302 that starts under vacuum. The reaction chamber 1302 can also be made of a reactive metal, such as aluminum, zinc, or magnesium. In some cases the reaction chamber 1302 can be a tube. The glass vial 1392 can contain an aqueous acid or base 1395. Upon breaking the glass vial 1392, the acid or base 1395 can react with the walls of the reaction chamber 1302. In this case, the acid or base can act as a limiting reagent. [00109] FIGS. 14A and 14B illustrate as system 1400 with a hydrogen gas production device 1401. The system 1400 can include the device 1401, reaction chamber 1402 and gas outlet 1404.. The device 1401 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted.

[00110] In system 1400, the reaction chamber 1402 can be an elastic chamber, such as a balloon or other expandable medium that may expand up to 1000% or more in one example. In FIG. 4A, the reaction chamber 1402 is shown in a deflated or collapsed state, such as before production of hydrogen. In FIG. 4B, the reaction chamber 1402 is shown in an inflated or expanded state, such as during production of hydrogen within the system 1400. [00111] FIGS. 15A and 15B illustrate a system 1500 with a hydrogen production device 1501 combined with a gas exchanger 1582. In system 1500, the hydrogen production device 1501 is connected to or incorporated into a gas exchanger module 1582 to facilitate rapid dissolution of the hydrogen gas into the medical solution.

[00112] In system 1500, the hydrogen production device 1501 contains similar components, connected in a similar manner, to device 101 discussed above, except where otherwise noted. Production of hydrogen gas is initiated by injection of water into the reaction chamber 1502 via the inlet 1503, whereupon the anhydrous acid or base 1506 is wetted and reacts with the reactive metal 1505 to produce hydrogen gas. The hydrogen gas exits the reaction chamber at the outlet 1504 and is directed by channel 1581 to the inlet on the gas exchanger 1582. In the gas exchanger 1582 the gas flows through gas channels 1585 while the liquid flows through liquid channels 1586. Channels 1585 and 1586, carrying the gas and liquid phases respectively, are separated by a gas exchange membrane such as silicone or polysulfone, as in the standard hollow-fiber membrane oxygenator design.

Although not illustrated here, a heat exchanger may also be integrated into the gas exchanger (Medtronic Affinity Oxygenator, for example). In the embodiment shown, the gas and liquid phases flow past each other in antiparallel or countercurrent directions to facilitate optimal transfer of hydrogen from the gas phase to the liquid phase. The hydrogen gas flows out of the gas exchanger through port 1583. The medical liquid flows from a reservoir into the gas exchanger through inlet port 1511 and out through the outlet port 1512 to the patient or tissue to be treated or may be collected for later use.

[00113] FIG. 15B illustrates an arrangement of system 1500 in which the system 1500 comprises the hydrogen production system 1501 and the oxygen exchanger 1582. The system 1500 receives medical fluid 1510 from a reservoir 1509 (such as an IV bag) via an inlet line 1511. After flowing through the gas exchanger 1582 the medical fluid flows through the outlet line 1512 to be collected in a second reservoir 1587. The hydrogen gas flows from hydrogen production device 1501 through the gas exchanger 1582 in a direction opposite to the liquid flow, and exits the gas exchanger 1582 at gas line 1583. Gas line 1583 directs the hydrogen gas 1508 into the medical fluid reservoir 1509. (For ease of illustration the gas and liquid phases are depicted flowing through separate IV bag ports, but a single bag spike of dual lumen configuration could enable the system to simultaneously inject hydrogen gas 1508 into the reservoir while draining medical fluid 1510 from the same port). By use of this arrangement the initially hydrogen-free medical fluid can be induced to flow out of the first reservoir 1509 either by gravity or by buildup of pressure from collected hydrogen gas 1508. As it flows through the gas exchanger 1582 the medical fluid 1510 becomes hydrogen- enriched medical fluid 1588, which finally collects in reservoir 1587 for use.

[00114] Both IV bags 1587 and 1509 can be suspended at the same height, and the buildup of pressure from hydrogen gas 1508 in the first reservoir 1509 will push the medical fluid 1510 through the gas exchanger 1582 to fill up the second reservoir 1587 with hydrogen-enriched medical fluid 1588.

[00115] FIGS. 16A and 16B Illustrate a system 1600 having a hydrogen gas production device 1601 and a reactant mixing syringe 1613. The device 1601 contains similar components, connected in a similar manner, to device 101 listed above, except where otherwise noted. The device 1601 features an inlet port 1603, and outlet port 1604, and contains the reactive metal 1605 but does not contain an acid or base reactant 1606.

[00116] In system 1600, the acid or base reactant 1606 is supplied in the separate syringe 1613 to facilitate immediate mixing of the dry acid or base with water prior to initiating the metal-acid or metal -base reaction to produce hydrogen. FIG. 16B Illustrates the mixing of water with the anhydrous reactant as a first step. A syringe of water 1607 is connected to the mixing syringe 1613 using a connector 1639. Alternating depression of the syringe plungers mixes the water with the anhydrous reactant. After at least two back-and- forth passes of the water/reactant mixture between the two syringes 1613 and 1607, the reactant is ready to be injected directly into the inlet port 1603 of the hydrogen gas production device 1601. The advantage of the method depicted in FIGS. 16A-16B is enhanced control of the rate of hydrogen gas production.

Various Notes & Examples [00117] Example 1 can include a device comprising: a reaction chamber for containing a reactive metal and an anhydrous reactant; a water inlet fluidly connected to the reaction chamber, the water inlet configured to fluidly couple to a water delivery device, the water inlet for receiving water and directing it to the reaction chamber; and a gas outlet fluidly connected to the reaction chamber, the gas outlet for release of hydrogen gas from the reaction chamber therethrough.

[00118] Example 2 can include Example 1, wherein the reaction chamber comprises a gas impermeable container.

[00119] Example 3 can include any of Examples 1-2, wherein the reaction chamber comprises a volume configured to contain a predetermined amount of reaction products. [00120] Example 4 can include any of Examples 1-3, wherein the reactive metal comprises magnesium, aluminum, zinc, iron, or combinations thereof.

[00121] Example 5 can include any of Examples 1-4, wherein the reactive metal comprises powder, granules, particles, ribbons, wires, or combinations thereof.

[00122] Example 6 can include any of Examples 1-5, wherein the anhydrous reactant comprises citric acid, lactic acid, malic acid, tartaric acid, or mixtures thereof.

[00123] Example 7 can include any of Examples 1-6, wherein the reaction chamber further comprises a vacuum.

[00124] Example 8 can include any of Examples 1-7, wherein the reactive metal and the anhydrous reactant are present in stoichiometric quantities to produce a predetermined amount of hydrogen gas.

[00125] Example 9 can include any of Examples 1-8, wherein the reactive metal and the anhydrous reactant are present in non-stoichiometric quantities to produce a predetermined amount of hydrogen gas.

[00126] Example 10 can include a system comprising: a device for production of hydrogen gas, the device comprising: a first reaction chamber for containing a reactive metal and an anhydrous reactant; a water inlet fluidly connected to the first reaction chamber, the water inlet for receiving water and directing it to the first reaction chamber; a gas outlet fluidly connected to the first reaction chamber, the gas outlet for release of gas from the first reaction chamber therethrough; a fluid reservoir to couple to the first reaction chamber, the fluid reservoir for receiving hydrogen gas from the first reaction chamber; and a fluid conduit connecting the fluid reservoir to the patient, organ or tissue being treated. [00127] Example 11 can include ExamplelO, further comprising one or more air evacuation ports configured to allow evacuation of the first reaction chamber.

[00128] Example 12 can include any of Examples 10-11, further comprising one or more check valves for directing a flow of produced hydrogen gas.

[00129] Example 13 can include any of Examples 10-12, further comprising a luer fitting for connection of a syringe to the water inlet.

[00130] Example 14 can include any of Examples 10-13, further comprising a liquid trap fluidly connected between the first reaction chamber and the gas outlet.

[00131] Example 15 can include any of Examples 10-14, further comprising a second reaction chamber coupled to the first reaction chamber.

[00132] Example 16 can include any of Examples 10-15, wherein the second reaction chamber is connected in parallel with the first reaction chamber.

[00133] Example 17 can include any of Examples 10-16, wherein the second reaction chamber is connected in series with the first reaction chamber.

[00134] Example 18 can include any of Examples 10-17, wherein the second reaction chamber comprises a chamber for production of carbon dioxide.

[00135] Example 19 can include a method comprising: inserting water into a reaction chamber loaded with an anhydrous reactant and a reactive metal; producing of a predetermined amount of hydrogen gas in the reaction chamber; and combining the produced hydrogen gas with a medical fluid to produce a medical fluid containing dissolved hydrogen gas.

[00136] Example 20 can include Example 19, wherein producing the predetermined amount of hydrogen gas comprises stoichiometric proportions of water, the anhydrous reactant, or the reactive metal.

[00137] Example 21 can include a device comprising a reaction chamber for containing a reactive metal, an inlet fluidly connected to the reaction chamber, the inlet configured to receive and direct liquid to the reaction chamber and oxidize the reactive metal to produce hydrogen gas, and a gas outlet fluidly connected to the reaction chamber to release the hydrogen gas from the reaction chamber.

[00138] Example 22 can include Example 21 and further comprising a gas exchanger fluidly coupled to the gas outlet.

[00139] Example 23 can include any of Example 21-22 and further comprising a gas exchanger having a liquid inlet fluidly coupled an outlet port of a medical fluid reservoir. [00140] Example 24 can include any of Example 21-23 and further comprising a gas exchanger having a gas outlet port fluidly coupled to a port on a medical fluid reservoir. [00141] Example 25 can include any of Example 21-24 and further comprising a second medical fluid reservoir having a liquid inlet coupled to the liquid outlet from a gas exchanger.

[00142] Example 26 can include any of Example 21-25 wherein the reaction chamber comprises a gas impermeable container.

[00143] Example 27 can include any of Example 21-26 wherein the reaction chamber comprises a volume configured to contain a predetermined amount of reaction products.

[00144] Example 28 can include any of Example 21-27 wherein the reactive metal comprises magnesium, aluminum, zinc, iron, or combinations thereof.

[00145] Example 29 can include any of Example 21-28 wherein the reactive metal comprises powder, granules, particles, ribbons, wires, a lining of all or part of an internal surface of the reaction chamber, or combinations thereof and wherein the liquid comprises an acid or a base, or water to mix with an anhydrous acid or base.

[00146] Example 30 can include a system comprising a reaction chamber for containing a reactive metal, an inlet fluidly connected to the reaction chamber, the inlet configured to receive and direct liquid to the reaction chamber and oxidize the reactive metal to produce hydrogen gas, a gas outlet fluidly connected to the reaction chamber to release the hydrogen gas from the reaction chamber, a fluid reservoir coupled to the gas outlet to receive hydrogen gas from the reaction chamber and infuse fluid with hydrogen, and a fluid conduit coupled to the fluid reservoir to provide hydrogen infused fluid to a patient, organ or tissue being treated.

[00147] Example 31 can include Example 30 and further comprising one or more check valves for directing a flow of produced hydrogen gas.

[00148] Example 32 can include any of Example 30-31 and further comprising a luer fitting for connection of a syringe to the inlet and wherein the reactive metal comprises powder, granules, particles, ribbons, wires, a lining of all or part of an internal surface of the reaction chamber, or combinations thereof and wherein the liquid comprises an acid or a base, or water to mix with an anhydrous acid or base.

[00149] Example 33 can include a method comprising loading a first chamber with a liquid, inserting liquid from the first chamber into a second chamber comprising a closed volume containing a reactive metal, producing hydrogen gas in the second chamber by oxidizing the reactive metal, and combining the produced hydrogen gas with a medical fluid to produce a medical fluid containing dissolved hydrogen gas.

[00150] Example 34 can include Example 33 wherein the liquid comprises water and the second chamber contains an anhydrous acid or base that mixes with the liquid to oxidize the reactive metal.

[00151] Example 35 can include Example 34 wherein an amount of hydrogen gas produced is controlled by selecting stoichiometric proportions of water, the anhydrous acid or base, or the reactive metal.

[00152] Each of these non-limiting examples can stand on its own or can be combined in various permutations or combinations with one or more of the other examples.

[00153] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as “examples.” Such examples can include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. Moreover, the present inventors also contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[00154] In the event of inconsistent usages between this document and any documents so incorporated by reference, the usage in this document controls.

[00155] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

[00156] Method examples described herein can be machine or computer-implemented at least in part. Some examples can include a computer-readable medium or machine- readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods can include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code can include computer readable instructions for performing various methods. The code may form portions of computer program products. Further, in an example, the code can be tangibly stored on one or more volatile, non-transitory, or nonvolatile tangible computer-readable media, such as during execution or at other times. Examples of these tangible computer-readable media can include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like.

[00157] The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to comply with 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it is contemplated that such embodiments can be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

CLAIMS What is claimed is:

1. A device comprising: a reaction chamber for containing a reactive metal; an inlet fluidly connected to the reaction chamber, the inlet configured to receive and direct liquid to the reaction chamber and oxidize the reactive metal to produce hydrogen gas; and a gas outlet fluidly connected to the reaction chamber to release the hydrogen gas from the reaction chamber.

2. The device of claim 1 and further comprising a gas exchanger fluidly coupled to the gas outlet.

3. The device of claim 1 and further comprising a gas exchanger having a liquid inlet fluidly coupled an outlet port of a medical fluid reservoir.

4. The device of claim 1 and further comprising a gas exchanger having a gas outlet port fluidly coupled to a port on a medical fluid reservoir.

5. The device of claim 1 and further comprising a second medical fluid reservoir having a liquid inlet coupled to the liquid outlet from a gas exchanger.

6. The device of any one of claims 1-5, wherein the reaction chamber comprises a gas impermeable container.

7. The device of any one of claims 1-5, wherein the reaction chamber comprises a volume configured to contain a predetermined amount of reaction products.

8. The device of any one of claims 1-5, wherein the reactive metal comprises magnesium, aluminum, zinc, iron, or combinations thereof.

27

9. The device of any one of claims 1-5, wherein the reactive metal comprises powder, granules, particles, ribbons, wires, a lining of all or part of an internal surface of the reaction chamber, or combinations thereof and wherein the liquid comprises an acid or a base, or water to mix with an anhydrous acid or base.

10. A system comprising: a reaction chamber for containing a reactive metal; an inlet fluidly connected to the reaction chamber, the inlet configured to receive and direct liquid to the reaction chamber and oxidize the reactive metal to produce hydrogen gas; a gas outlet fluidly connected to the reaction chamber to release the hydrogen gas from the reaction chamber; a fluid reservoir coupled to the gas outlet to receive hydrogen gas from the reaction chamber and infuse fluid with hydrogen; and a fluid conduit coupled to the fluid reservoir to provide hydrogen infused fluid to a patient, organ or tissue being treated.

11. The system of claim 10, further comprising one or more check valves for directing a flow of produced hydrogen gas.

12. The system of any one of claims 10-11, further comprising a luer fitting for connection of a syringe to the inlet and wherein the reactive metal comprises powder, granules, particles, ribbons, wires, a lining of all or part of an internal surface of the reaction chamber, or combinations thereof and wherein the liquid comprises an acid or a base, or water to mix with an anhydrous acid or base.

13. A method compri sing : loading a first chamber with a liquid; inserting liquid from the first chamber into a second chamber comprising a closed volume containing a reactive metal; producing hydrogen gas in the second chamber by oxidizing the reactive metal; and combining the produced hydrogen gas with a medical fluid to produce a medical fluid containing dissolved hydrogen gas.

14. The method of claim 13 wherein the liquid comprises water and the second chamber contains an anhydrous acid or base that mixes with the liquid to oxidize the reactive metal.

15. The method of claim 14 wherein an amount of hydrogen gas produced is controlled by selecting stoichiometric proportions of water, the anhydrous acid or base, or the reactive metal.