Transdermal hydrogen delivery device

Abstract

Transdermal delivery device for dihydrogen The invention relates to a device (1) for transdermal delivery of dihydrogen comprising a body (10) comprising an anode (11) and a cathode (12), and an electrical energy source (13), characterized in that the body (10) is based on a flexible material, capable of conforming to the skin of a human or animal body (3), and the body (10) comprises a water reservoir (14), the relative arrangement of the reservoir (14), the anode (11) and the cathode (12) being configured so that the water contained in the reservoir is in contact with the anode (11) and the cathode (12) to form a closed electrical circuit, so as to produce dihydrogen at the cathode (12) from the water from the reservoir (14), to transdermally release the produced dihydrogen. The proposed delivery device is minimally invasive, while still allowing the delivery of hydrogen. Figure for abstract: Fig.1

Description

Title of the invention: Transdermal dihydrogen delivery device Technical field

[0001] The invention relates to the field of hydrogen therapy. It finds particularly advantageous application in the field of numerous pathologies, and in particular inflammatory pathologies and / or pathologies linked to oxidative stress. STATE OF THE ART

[0002] Hydrogen therapy is showing growing interest in treating a large number of pathologies, particularly inflammatory pathologies and / or those linked to oxidative stress. A review of more than 300 articles lists no fewer than 166 pathologies where the delivery of dihydrogen has been tested for its antioxidant properties (Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015), “Beneficial biological effects and the underlying mechanisms ofmolecular hydrogen-comprehensive review of321 original articles”, Medical gas research, 5(1), 12).

[0003] Various techniques are known for administering dihydrogen to the human or animal body. Dihydrogen can be administered in the form of inhaled gas, formed by electrolysis. This technique is, however, expensive and inconvenient, as it requires complex equipment such as a respirator. Dihydrogen can be administered in the form of hydrogenated water, drunk by the patient.

[0004] These techniques show major limitations: • a small quantity of dihydrogen delivered, • strong variations in the concentration of dihydrogen, and • a major constraint in terms of therapeutic compliance.

[0005] To overcome these drawbacks, dihydrogen can be produced by electrolysis of water, carried out by a device implanted in the human or animal body. In particular, document WO 2019 / 122441 A1 discloses a device implantable in the human or animal body comprising an anode and a cathode electrically connected to an energy source. The device allows a bodily fluid forming the electrolyte to pass through, making it possible to close the electrical circuit. Dihydrogen is thus produced by electrolysis of the water in a bodily fluid, inside the human body. However, the implantation of such a device remains very invasive for the patient.

[0006] An object of the present invention is therefore to provide a device for delivering dihydrogen which is minimally invasive, and preferably non-invasive, for the human and animal body, while allowing sufficient, preferably improved, delivery of dihydrogen.

[0007] Other objects, features and advantages of the present invention will become apparent from the following description and accompanying drawings. It is understood that other advantages may be incorporated. SUMMARY

[0008] To achieve this objective, according to one embodiment, a dihydrogen delivery device is provided comprising: • a body comprising at least one anode and at least one cathode, and • a source of electrical energy, the anode and the cathode being electrically connected to the electrical energy source, characterized in that, the device being configured to deliver dihydrogen through the skin of a human or animal body: • the body is made from a flexible material, capable of conforming to the skin of a human or animal body, the body having an outer surface comprising: • a lower face intended to be applied to the skin and allowing the passage of dihydrogen, • at least one side intended not to be in contact with the skin, • the body comprises a water reservoir, the relative arrangement of the reservoir, the anode and the cathode being configured so that the water contained in the reservoir is in contact with the anode and the cathode to form a closed electrical circuit, so as to produce dihydrogen at the cathode from the water from the reservoir, to transdermally release the produced dihydrogen.

[0009] Thus, the device is suitable for application to the skin of a human or animal body, the transdermal delivery makes it possible to minimize the impact on the body compared to implantable devices of existing solutions.

[0010] Furthermore, the water reservoir included in the body and therefore able to be considered as embedded, allows a delivery of dihydrogen independent of a bodily fluid, for example sweat, to allow a delivery of a sufficient quantity of dihydrogen through the patient's skin. This problem does not arise in fact for implantable devices of existing solutions, bathed in a bodily fluid capable of being used to produce dihydrogen.

[0011] The delivery device is therefore minimally, and preferably not invasive to the human or animal body, while still allowing a sufficient quantity of dihydrogen to be delivered to obtain a beneficial effect on the body. Depending on the context of use, this quantity may for example vary from 1 pmol / hour to 40 pmol / hour. Dihydrogen being a rapidly diffusing molecule, implying low persistence at the location of its release, the device is thus particularly suitable for the prevention and / or treatment of inflammatory and / or oxidative stress-related pathologies near the skin of the human or animal body, such as diabetes, obesity, inflammation of the skin or surrounding tissues, or psoriasis, skin cancer, vitiligo and any pathology involving oxidative stress. The device can also be used for muscle recovery, for example against muscle aches.

[0012] A second aspect of the invention relates to an article of clothing comprising at least one dihydrogen delivery device according to the first aspect.

[0013] A third aspect of the invention relates to a method for delivering dihydrogen comprising applying to the skin of a human or animal body the dihydrogen delivery device according to the first aspect of the invention, and activating the delivery device so as to transdermally deliver the dihydrogen.

[0014] As discussed below, in one example, transdermal delivery of hydrogen can be used for muscle recovery, for example against muscle soreness. In another example, transdermal delivery of hydrogen is used for the prevention and / or treatment of pathologies selected from diabetes, obesity, inflammation, psoriasis, skin cancer, vitiligo and any pathology involving oxidative stress. BRIEF DESCRIPTION OF THE FIGURES

[0015] The aims, objects, as well as the characteristics and advantages of the invention will emerge more clearly from the detailed description of an embodiment thereof which is illustrated by the following accompanying drawings in which:

[0016] [Fig.l] [Fig.l] represents a cross-sectional view of the delivery device according to an exemplary embodiment.

[0017] [Fig.2] [Fig.2] shows a cross-sectional view of the delivery device according to another exemplary embodiment in which the device comprises a material not permeable to dihydrogen.

[0018] [Fig.3A] Figures 3A to 3C each represent a cross-sectional view of the delivery device according to several exemplary embodiments, in which the lower face is covered by a semi-permeable material.

[0019] [Fig.3B]

[0020] [Fig.3C]

[0021] [Fig.4A] Figures 4A to 4C each represent a cross-sectional view of the delivery device according to several exemplary embodiments, in which the device has one or more localized openings.

[0022] [Fig.4B]

[0023] [Fig.4C]

[0024] [Fig.5] Figures 5, 6A and 6B each represent a cross-sectional view of the delivery device according to several exemplary embodiments, in which the electrodes form a stack.

[0025] [Fig.6A]

[0026] [Fig.6B]

[0027] [Fig.7] [Fig.7] represents a cross-sectional view of the delivery device according to another exemplary embodiment.

[0028] [Fig.8A] Figures 8A and 8B each represent a cross-sectional view of the delivery device according to several exemplary embodiments, in which the electrodes are formed from microneedles intended to penetrate the skin.

[0029] [Fig.8B]

[0030] [Fig.9] [Fig.9] shows an overview of an armband comprising several hydrogen delivery devices.

[0031] The drawings are given as examples and are not limiting of the invention. They constitute schematic representations of principle intended to facilitate the understanding of the invention and are not necessarily on the scale of practical applications. In particular, the relative dimensions of the different elements making up the delivery device are not necessarily representative of reality. DETAILED DESCRIPTION

[0032] Before beginning a detailed review of embodiments of the invention, optional features which may possibly be used in combination or alternatively are set out below: • the at least one cathode and the at least one anode are at least partly, and preferably totally, arranged in the water tank, • at least one cathode and at least one anode are in contact with a wall of the tank, • the body is partly covered by a material not permeable to dihydrogen forming at least one portion, for example a first portion, and preferably the whole, of the at least one face intended not to be in contact with the skin, • the body is at least partly covered by a material having a cut-off threshold of less than 1 pm, forming at least one portion, for example a second portion distinct from the first portion, of the at least one face intended not to be in contact with the skin, • the lower face is at least partly, and preferably completely, covered by a semi-permeable material having a cut-off threshold less than 1 pm, • the lower face is at least partly, and preferably completely, covered by a semi-permeable material having a higher permeability to dihydrogen than its permeability to dioxygen, preferably the semi-permeable material is permeable to dihydrogen and not permeable to dioxygen, • the lower face is only partly covered by a material not permeable to dihydrogen so as to form at least one opening not covered by the material not permeable to dihydrogen, • the at least one opening is covered by a material having a higher permeability to dihydrogen than its permeability to dioxygen, preferably the semi-permeable material is permeable to dihydrogen and not permeable to dioxygen, • the lower face is provided with at least one, and preferably a plurality of, microneedles intended to penetrate the skin, • the lower face being partly covered by a material not permeable to dihydrogen so as to form at least one opening not covered by the material not permeable to dihydrogen, the at least one microneedle is hollow and is arranged opposite the opening, • the water reservoir comprises, preferably is in the form of, a hydrogel. According to one example, the hydrogel is composed of at least 95% by mass, and preferably at least 99% by mass of water, • the cathode and the anode are arranged opposite the lower face intended to be in contact with the skin, • the cathode and the anode form a stack, the cathode being opposite the lower face intended to be in contact with the skin, and the anode being opposite a face intended not to be in contact with the skin, • at least one of the cathode and the anode extends transversely in the tank so as to divide the tank into two separate parts, without water circulating between the two parts. According to one example, a first part communicates with the lower face, and a second part communicates with a face intended not to be in contact with the skin, • the lower face being provided with at least one, and preferably a plurality of, microneedles intended to penetrate the skin, the cathode is formed by said microneedle. According to one example, the cathode and the anode are each formed by a microneedle.

[0033] In the remainder of the description, the term “on” does not necessarily mean "directly on". Thus, when we indicate that a part or organ A is in support "on" a part or organ B, this does not mean that the parts or organs A and B are necessarily in direct contact with each other. These parts or organs A and B can either be in direct contact or be supported on each other by means of one or more other parts.

[0034] In the detailed description which follows, use may be made of terms such as "transverse", "upper", "lower", "inner", "outer". These terms must be interpreted relatively in relation to the normal position of use of the delivery device, once applied to the skin. For example, the concept of "lower" corresponds to the faces or elements facing and / or in contact with the skin of the human or animal body on which the device is intended to be applied. The concept of "upper" corresponds to the faces or elements facing away from the skin of the human or animal body on which the device is intended to be applied.

[0035] A parameter “substantially equal / greater / less than” a given value means that this parameter is equal / greater / less than the given value, to within plus or minus 10%, or even plus or minus 5%, of this value.

[0036] An element “based” on a material A is understood to mean an element comprising this material A and possibly other materials, for example additives.

[0037] The delivery device 1 is now described according to several exemplary embodiments illustrated by FIGS. 1 to 9.

[0038] As illustrated by [Fig.l], the device 1 comprises a body 10. The body 10 comprises electrodes: at least one anode 11 and at least one cathode 12, for the production of dihydrogen by electrolysis of water. For this, the electrodes 11, 12 are connected to an electrical energy source 13. The electrical energy source 13 is only shown in [Fig.l] so as not to clutter the other figures.

[0039] The body 10 further comprises a water reservoir 14, so as to provide the water necessary for closing the electrical circuit with the electrodes 11, 12 and for producing dihydrogen by electrolysis. In a manner known to those skilled in the art, the electrodes 11, 12, the electrical energy source 13 and the water in the reservoir 14 form a closed electrical circuit, the electrical energy source 13 supplies the circuit and imposes a sufficient voltage to induce the electrolysis of the water, with the reduction of the water at the cathode to form dihydrogen, and the oxidation of the water at the anode to form dioxygen, during operation of the device.

[0040] The relative arrangement of the reservoir 14, the anode 11 and the cathode 12 is configured so that the water contained in the reservoir 14 is in contact with the anode 11 and the cathode 12 to form a closed electrical circuit. According to an example illustrated in [Fig.l], the anode and the cathode may partially penetrate, or even be completely included in, the reservoir 14. According to another example illustrated in [Fig.8A] and 8B, the anode and / or the cathode may be directly in contact with a wall of the reservoir 14. The reservoir 14 may be delimited or formed of a material allowing water to pass through, so that the electrodes 11, 12 in contact with the water reservoir are in contact with the water.

[0041] The body 10 is capable of conforming to the skin of a human or animal body 3. The body 10 is configured to have sufficient flexibility to follow the contours of the human or animal body to which it is applied. The body is based on one or more flexible materials. Preferably, the body 10 comprises at least one flexible material, such as polyethylene terephthalate, or an elastomer and more particularly a fluoroelastomer or a perfluoroelastomer (for example Viton™ marketed by the company Chemours, or Tecnoflon® marketed by the company Solvay). The external surface 100 of the body 10 thus has a lower face 101 intended to be applied to the skin, through which the delivery of dihydrogen takes place. The device 1 thus allows transdermal delivery of dihydrogen, without requiring an invasive operation such as the implantation of an electrolysis device in the body.Preferably, the lower face 101 is intended to be in total contact with the skin. The external surface 100 of the body 10 further has at least one face 102 not intended to be applied to the skin, for example an upper face and side faces.

[0042] During the development of the invention, it was in fact demonstrated that for certain pathologies or traumas, and in particular those affecting the skin or surrounding tissues such as fatty tissues or muscles, delivery of dihydrogen via the skin is sufficient to relieve and / or treat the pathology or trauma. In order to guarantee the delivery of a sufficient quantity of dihydrogen, the water reservoir 14 makes it possible to dispense with the electrolysis of a bodily fluid, and more particularly sweat.

[0043] Thus the device may be in the form of a patch to be applied to the skin, extending mainly in a plane as illustrated by Figures 1 to 8B. According to an alternative or complementary example, one or more delivery devices 1 may be included in a clothing item 2 intended to be worn by a user. The clothing item may be in the form of an armband or a ribbon to surround for example the wrist, the arm, the leg, the foot, or the forehead of the user. According to the example illustrated in [Fig.9], the item 2 may be an armband comprising a plurality of devices 1, intended to be worn on the body 3 and more particularly around the arm of a user. The clothing item may be in the form of a garment, such as a t-shirt or a top, or an undergarment, preferably configured to mold the part of the body 3 to be treated, or else.

[0044] The device 1 extends mainly in one plane in order to limit hindering the movements of the user. Preferably, the device has dimensions in this plane between one centimeter (cm) and several tens of centimeters. In a direction perpendicular to this plane, the device preferably has a dimension less than 5 cm, preferably less than 2 cm, and even more preferably less than 1 cm. These dimensions are understood to be with the energy source 13 when it is integrated into the body 10, or without the energy source 13 when the latter is remote.

[0045] The device 1 can be used in a method for delivering dihydrogen. The delivery method comprises applying the device 1 to the skin of a human or animal body and activating it so as to deliver the dihydrogen transdermally. The method can further comprise electrically connecting the device to the electrical energy source 13, in particular when it is remote from the body 10. The method can also comprise controlling the closing and opening of the electrical circuit formed by means provided for this purpose.

[0046] For the purposes of the invention, the term “animal” may in particular be understood to mean large animals such as cattle, sport animals such as horses, pets such as dogs and cats, and laboratory animals such as rats, mice and monkeys.

[0047] The device 1 is now described in detail relative to the different elements which compose it.

[0048] The reservoir 14 is configured, with the electrodes 11, 12, so that the electrodes are in contact with the water in the reservoir to form the closed electrical circuit. The reservoir may be in the form of a hollow reservoir delimited by a material and containing water. The material delimiting this material may be permeable to water, in particular when the electrodes 11, 12 are arranged in contact with the reservoir, so that the electrodes 11, 12 are in contact with water from the reservoir 14 to produce the dihydrogen.

[0049] According to an alternative or complementary example, the reservoir may comprise, preferably be formed from, a porous material in which water is contained. For example, the porous material may be a sponge or a fabric. The porous material is preferably based on one or more polymers, such as polyacrylamide (PAAm), poly(p-phenyl-p-phthalamide), aramid nanofibers, chitosan, or polyvinyl alcohol (PVA). According to a preferred example, the reservoir 14 comprises a hydrogel. According to one possibility, the reservoir 14 is formed by the hydrogel, the reservoir is made of the hydrogel. By hydrogel, we mean a gel in which the swelling agent is water. The matrix of a hydrogel is generally a network of one or more polymers. A hydrogel has the advantage of being flexible and having a high capacity to contain water.The hydrogel may be composed of at least 95%, and preferably at least 99% water, so as to maximize the amount of water contained in the reservoir 14.

[0050] Preferably, the reservoir 14 has a height substantially between 0.5 cm and 5 cm. The height is taken in a direction perpendicular to the face of the body 10 intended to be applied to the skin. The height of the reservoir contributes to defining the volume of water available for electrolysis and therefore the duration of use of the device. The height is also an important parameter for the practicality of use and the aesthetic appearance when wearing the device. The choice of the height of the reservoir can therefore be made according to the intended application and the location of the body on which the device is intended to be applied.

[0051] The water in the reservoir 14 forms an electrolyte that is sufficiently conductive to allow the electrolysis of the water at the electrodes 11, 12. In a manner known to those skilled in the art, this electrolyte contains salts comprising cations and anions such as Na+, K+, Ca2+, Cl and HCO3.

[0052] The water reservoir 14 may be rechargeable, for example by means of an injection of water by a syringe into the reservoir 14. For this, the device 14 may comprise a sealed opening, not shown in the figures, allowing communication between the reservoir 14 and the external surface 100 of the body 10. The sealed opening comprises for example a seal through which a syringe can inject water to recharge the reservoir 14. According to an alternative or complementary example, the water reservoir 14 may be removably mounted in the device 1 to be replaceable. According to another example, the body 10 of the device 1 may be a consumable intended to be changed, in particular once the water in the reservoir 14 is used.

[0053] The body 10 of the device 1 may comprise an internal structural element 106 giving structure to the body 10 and giving it flexibility. Preferably, the body 10 of the device is deformable under the pressure of a user's finger.

[0054] As illustrated in Figures 1 to 7, the body 10 is configured to receive the reservoir 14 in a hollow shape. This shape may for example be formed by the internal structural element 106, possibly in association with other elements of the body 10. The hollow shape is preferably opposite, that is to say turned towards, the lower face 101, in which the reservoir 14 is placed. As illustrated in [Fig.l], the internal structural element 106 does not necessarily act as a barrier to the gases produced by electrolysis.

[0055] The internal structural element 106, and the possible materials forming the external surface 100 of the body, described later, are preferably electrically insulating. According to one example, the internal structural element 106 is based on or made of polymer such as polyethylene terephthalate (PET), poly(methylmethacrylate) (PMMA), polyamide, graphene, a photosensitive resin of the SU-8 resin type, polyester, cellulose (for example a tattoo transfer paper).

[0056] The electrical energy source 13 can be integrated into the body 10 or be remote, i.e. arranged at a distance from the body 10 of the device 1 and connected to the body 10 by electrical connections. The energy source can be: • a battery, preferably a high energy density battery, for example a lithium battery, • a mechanical energy recovery device, for example using the piezoelectric effect, • a biofuel cell capable of producing electricity by consuming chemical species, typically naturally present in the human or animal body, such as: glucose, carbohydrates, lipids, proteins, • a solar energy recovery device, for example a photovoltaic module or a Gratzel cell, • a thermal energy recovery device, for example a thermoelectric module exploiting the Seebeck effect.

[0057] The energy source is preferably capable of producing a voltage substantially less than or equal to 1.4 V, in order to avoid the formation of Cl2 from the Cl ions. A voltage reducer may be added to the energy source 14. Unless otherwise stated below, when referring to what the energy source provides, this is what it provides alone or in association with the voltage booster. The power to produce one micromole of H2 / hour is substantially equal to 60 pW.

[0058] The device may further comprise a voltage reducer which makes it possible to obtain a supply voltage for the electrolyser substantially less than or equal to 1.4 V. This is particularly useful when the power source 14 produces a voltage greater than 1.4 V. When there are several devices 1 or several pairs of cathodes 12 and anodes 11, the energy source 14 may be specific to each or shared.

[0059] According to one example, the external surface 100 is partly covered by, or equivalently formed by, a material 103 that is not permeable to dihydrogen 103 forming at least a portion 1020, and preferably all of, the faces 102 of the body 10 intended not to be in contact with the skin. Thus, the diffusion of dihydrogen, or even further that of dioxygen, can be constrained in a plane or in a preferred direction, and in particular towards the skin, as illustrated by [Fig.2]. Gaseous molecules diffuse particularly quickly and in three dimensions compared to other active ingredients. Constraining their diffusion makes it possible to limit the loss of active ingredient during delivery, and therefore to improve the delivery of dihydrogen. This problem does not arise in existing solutions for implanted devices, the dihydrogen then being delivered to the body regardless of its delivery direction.Note that if the material 103 is not permeable to dihydrogen, the material will also not be permeable to dioxygen.

[0060] The material non-permeable to dihydrogen 103 is preferably based on or made of one or more polymers chosen from: • semi-crystalline thermoplastics, such as polyethylene, polyamide, polychlorotrifluoroethylene, polyetheretherketone (PEEK), polypropylene, chlorinated polyvinyl chloride (CPVC), polyvinyl chloride (PVC), and their derivatives, • elastomers, such as polybutadiene, polychloroprene (for example Neoprene marketed by the company Nemours), terpolymers of ethylene and propylene, copolymers of ethylene and propylene, hydrogenated poly(butadiene-coacrylonitrile), poly(isobutylene-co-isoprene), silicone rubbers with different substituents on the polymer chain (for example phenyl, vinyl, and / or methyl), nitrile rubber, fluoroelastomers, or perfluoroelastomers for example: • vinylidene fluoride and at least one of hexafluoropropylene, tetrafluoroethylene, a fluorinated vinyl ether, propylene, ethylene, • Viton™ type fluoroelastomers (polymer marketed by Chemours), Tecnoflon® type perfluoroelastomers (polymer marketed by Solvay), • silicone rubbers having fluorinated substituent groups on the polymer chain (fluorosilicone rubber),

[0061] Preferably, substantially at least 50%, preferably at least 70%, more preferably at least 90% and even more preferably all of the faces 102 not intended to be applied to the skin are formed by the material 103 which is not permeable to dihydrogen. The larger the portion of the faces 102 formed by the material 103 which is not permeable to dihydrogen, the better the targeting of the dihydrogen produced, and therefore the greater the quantity of dihydrogen delivered to the skin.

[0062] According to one example, the lower face 101 of the body may be covered or equivalently formed by a material whose cut-off threshold makes it possible to modulate the species likely to pass through this face 101 of the device 1 to the skin and vice versa. According to an example illustrated in [Fig.3A], the lower face 101 may be at least partly formed by a semi-permeable material 104 having a cut-off threshold of less than 1 μm. Thus, this material 104 forms an antimicrobial barrier preventing possible bacteria and / or microorganisms from the skin from entering the device 1, and more particularly into the reservoir 14, while allowing the passage of dihydrogen and dioxygen. Indeed, since the electrolysis of water induces the production of dioxygen, the reservoir 14 is an environment conducive to microbial growth.

[0063] As illustrated for example in [Fig.3B], the lower face 101 may be at least in part formed by a semi-permeable material 105 configured to promote the passage of dihydrogen relative to dioxygen. According to one example, the semi-permeable material 105 has a permeability to dihydrogen greater than its permeability to dioxygen. According to a more particular example, the semi-permeable material 105 is non-permeable to oxygen and is permeable to hydrogen. Those skilled in the art will be able to choose the material suitable for this purpose from among the materials existing in the field, and for example polydimethylsiloxane (PDMS), rubber, a photosensitive resin of the SU-8 resin type, polyisobutylene such as Vistanex™ (manufactured by ExxonMobil Chemical). Thus, in addition to forming an antimicrobial barrier, the semi-permeable material prevents the passage of dioxygen produced at the anode through the lower face 101 of the body 10.Only dihydrogen is delivered to the skin, which makes it possible to limit a reaction between dihydrogen and dioxygen in the patient's body and thus to increase the quantity of dihydrogen delivered. Furthermore, synergistically with the covering of the faces 102 with a material non-permeable to dihydrogen 103, the dioxygen can become trapped in the reservoir 14, which induces an increase in the pressure in the reservoir 14 and promotes the passage of dihydrogen through the lower face 101. According to one example, the material 105 has a cut-off threshold of less than 32 Da.

[0064] The semi-permeable material 105 may be a semi-permeable membrane, for example based on or made of at least one polymer chosen from poly(ethylene terephthalate) and polycarbonate, according to the example illustrated in [Fig. 3B]. The semi-permeable material 105 may be a layer formed by a porous material, for example based on or made of at least one polymer chosen from poly(ethylene terephthalate) and polycarbonate, according to the example illustrated in [Fig. 3C].

[0065] According to one example, the lower face 101 may be partly covered by the material 103 that is not permeable to dihydrogen so as to form at least one localized opening 1010 for the passage of dihydrogen. Thus, the dihydrogen is delivered to the skin only at this or these opening(s) 1010, thereby improving the targeting of the dihydrogen to the skin. Preferably, each opening has a surface area substantially less than 1 / 5th, preferably 1 / 10th of the total surface area of ​​the lower face 101.

[0066] As illustrated for example by Figures 4A to 4C, each of these openings 1010 can be covered by one of the materials 104, 105 described previously, the cut-off threshold of which will then make it possible to modulate the species likely to pass through this opening 1010 of the device 1 to the skin and vice versa. According to the examples illustrated, the opening 1010 is covered by a semi-permeable material 105 having a permeability greater to dihydrogen than its permeability to dioxygen, preferably permeable to dihydrogen and not permeable to dioxygen, such as previously described, to promote the delivery of dihydrogen.

[0067] In addition to this opening, a hollow microneedle 1011 may be arranged at the opening 1010. The microneedle 1011 may comprise a micro-channel or hollow core opening out on either side of the microneedle, according to its main direction of extension. This microneedle 1011 is intended to penetrate the skin, as illustrated for example by [Fig.4B]. The microneedle may comprise an outer wall 1011b and a hollow central core 1011a, the outer wall 1011b being arranged on either side of the localized opening, and the hollow central core 1011a communicating with the opening 1010. Thus the microneedle 1011 makes it easier to bring the lower face 101 of the body 10 into contact with the skin, and limits the risk of the device 1 becoming detached. Furthermore, since the microneedle 1011 is hollow, it makes it easier for the dihydrogen to pass through the surface of the skin.The microneedle comprises an opening micro-channel ensuring the passage of dihydrogen from the body 10 to the skin and preferably at least through the upper layers of the epidermis. The lower face 101 may have a plurality of openings 1010, for example forming a network of openings, each of which may be provided with a microneedle 1011.

[0068] It may be provided as an alternative or in addition, that the lower face 101 has at least one, and preferably a plurality of solid or hollow microneedles intended to penetrate the skin, not arranged at the level of an opening 1010, for example the lower face 101 not having an opening. Thus the microneedles facilitate the contact of the lower face 101 of the body 10 with the skin, and limit the risk of the device 1 becoming detached.

[0069] The microneedles described above may be based on or made of a rigid and biocompatible material. The rigid and biocompatible material may be a metal (for example titanium, nickel, a nickel iron alloy, gold, platinum or stainless steel) or a rigid polymer, such as polylactic acid, carboxymethylcellulose, polyglycolic acid, polyvinylpyrrolidone, polylactic glycolic acid. The microneedles are preferably of micrometric size, preferably of length less than 1,000 qm, and preferably of width or diameter less than 500 pm.

[0070] Alternatively or additionally, to promote the maintenance of the body 10 of the device 1 in contact with the skin, it may be provided that at least a portion of the lower face 101 comprises an adhesive layer, for example a glue. Alternatively or additionally, to promote the maintenance of the body 10 of the device 1 in contact with the skin, it may be provided that the article of clothing 2 or the device 1 comprises a holding support configured to maintain the body 10 in contact with the skin.

[0071] According to a first example illustrated by figures 1 to 4C, the electrodes 11, 12 can be arranged on the same face of the internal structural element 106, preferably facing the lower face 101 and therefore facing the skin. The electrodes 11, 12 are then arranged facing the lower face 101. Thus, the diffusion of the gases produced towards the lower face 101, and therefore towards the skin, is favored.

[0072] According to a second example, illustrated by Figures 5 to 7, the cathode 12 and the anode 11 form a stack. By stack, it is meant that the electrodes are at least partly juxtaposed in a direction perpendicular to the face 101 intended to be in contact with the skin, without necessarily being directly in contact with each other. The cathode 12 is preferably opposite the lower face 101, and the anode 11 is opposite a face 102 intended not to be in contact with the skin, for example the upper face 102. The cathode 12 is thus turned towards the lower face 101, and the anode 11 is turned towards a face 102 intended not to be in contact with the skin, for example the upper face 102. Thus, the oxygen is produced at the anode opposite a face 102 intended not to be in contact with the skin, and the hydrogen is produced near the lower face.The delivery of dihydrogen to the skin is favored, compared to that of dioxygen, to limit a possible reaction between these two gases and thus increase the quantity of dihydrogen delivered.

[0073] According to an example, illustrated in figures 5, 6A and 7, the anode 11 can be arranged on one face of the internal structural element 106 and the cathode on an opposite face of this element 106. The internal structural element 106 can then extend transversely inside the tank 14, so as not to completely divide it into two separate parts, and allow circulation of water in the tank 14. Alternatively or additionally, the internal structural element can for this purpose have pores allowing this circulation.

[0074] According to an example illustrated by [Fig.6B], at least one electrode 11, 12 can extend transversely inside the reservoir 14, so as to divide it into two distinct parts, without circulation of water between the two parts. Preferably, a first part 14a is then turned towards, preferably in contact with, the lower face 101, while the second part 14b is turned towards, preferably in contact with a face 102 intended not to be in contact with the skin. The cathode 12 is preferably the electrode making this separation. Thus, the hydrogen produced in the first part 14a is necessarily conveyed by the lower face to the skin, and does not escape through a face 102. The gases produced in the second part 14b, and therefore a part of the dihydrogen and the dioxygen, escape through the face 102. The face 102 can be covered by a material forming an antimicrobial barrier, as described previously.

[0075] The upper face 102 of the device may not be covered by a material limiting the diffusion of oxygen, so as to facilitate the evacuation of oxygen out of the device. of the body 10, by a face 102 not in contact with the skin, as illustrated for example by [Fig.5]. A face 102 not in contact with the skin, and preferably the upper face 102, may be formed by a material having a cutoff threshold of less than 1 μm, as described previously, to form an antimicrobial barrier.

[0076] For the two examples described above, the electrodes 11, 12 are preferably arranged in the reservoir 14. According to one example, the electrodes 11, 12 may be in the form of pads, bars or sheets.

[0077] According to a third example, illustrated by Figures 8A and 8B, only the cathode 12 or the cathode 12 and the anode 11 can each be formed by a microneedle, preferably hollow, intended to penetrate the skin. The water from the reservoir 14 can for example be conveyed by capillarity into the hollow core 11a, 12a of the electrodes 11, 12 and the electrolysis can be carried out at their external wall 11b, 12b. The electrolysis is thus carried out at the skin, improving the delivery of gases, and in particular dihydrogen, to the skin, while promoting the maintenance of the body 10 of the device 1 in contact with the skin.

[0078] According to one or other of the three examples above, the body 10 may preferably comprise several pairs of a cathode 12 and an anode 11, to form an electrode network. Thus, the surface area for producing gases by electrolysis is increased, to maximize the quantity of gas produced.

[0079] The electrodes may furthermore each be encapsulated by a semi-permeable membrane surrounding each electrode, for example of the polyether sulfone, polyamide, polymethylmethacrylate (PMMA), chitosan, polyvinyl alcohol type.

[0080] When at least one electrode 11, 12 is contained in the reservoir 14, the cathode(s) 12 may be separated from the anode(s) 11 by a proton exchange membrane or polymer electrolyte membrane (PEM), which is a semi-permeable membrane made from ionomers allowing proton conduction while being impermeable to gases such as oxygen or hydrogen. Protons pass through while gases are stopped. This feature is exploited in the MEAs (Membrane-Electrode Assembly) of PEM fuel cells and PEM electrolyzers. PEMs are made from pure polymer membranes or composite membranes where the materials form a polymer matrix. One of the most commonly used materials is Nafion, a fluorinated polymer produced by the DuPont company. The proton exchange membrane may divide the reservoir 14 into two parts.Thus, the production of dihydrogen can be isolated from the production of dioxygen in the body 10 of the device 1.

[0081] The composition of the electrodes is adapted to the function of each of them. They can be of the same material or of two different materials. They can be base or made of carbon. Preferably, the type of carbon material is chosen from graphite, carbon nanotubes, graphene, activated carbon or diamond. The material of the electrodes may be doped, in particular with platinum, iron or gold. The electrodes may be based on or made of platinum, gold, indium tin oxide (commonly abbreviated ITO for "indium tin oxide"), iridium or doped diamond, in particular at least the anode may be made of gold, or doped with gold. The electrodes may have a thickness substantially between 100 μm and 2 mm, in a direction perpendicular to the face 101 intended to be in contact with the skin, in particular when the electrodes are in the form of pads, bars or sheets.

[0082] The previously described characteristics can be combined with each other to form new embodiments, as illustrated for example in [Fig.7].

[0083] We describe in the following some particular cases. In view of the characteristics previously described, it appears for example that the device illustrated by [Fig. 2] allows delivery of both dihydrogen and dioxygen to the skin via the lower face 101. The device illustrated by figures 3B or 3C allows delivery of only the dihydrogen produced, the dioxygen being trapped in the reservoir 14. The devices illustrated by figures 4A to 4C allow targeted delivery of dihydrogen via the opening(s) 1010, while the dioxygen remains trapped in the reservoir 14. The device illustrated by [Fig. 6A] allows favored delivery of dihydrogen to the skin, a major part of the dioxygen being evacuated via the upper face 102 of the body 10.

[0084] In view of the foregoing description, it is clear that the invention provides a device for delivering hydrogen that is minimally invasive, and preferably non-invasive, to the human and animal body, while improving the delivery of hydrogen.

[0085] The invention is not limited to the embodiments previously described and extends to all embodiments covered by the invention. The present invention is not limited to the examples previously described. Many other variant embodiments are possible, for example by combining features previously described, without departing from the scope of the invention. In addition, the features described in relation to one aspect of the invention may be combined with another aspect of the invention.

[0086] LIST OF DIGITAL REFERENCES 1 Device 10 Bodies 100 External surface 101 Lower face intended to be in contact with the skin 1010 Opening 1011 Microneedle 1011a Central soul 1011b Wall 102 Side intended not to be in contact with the skin 103 Material not permeable to dihydrogen 104 Material with a cut-off threshold of less than 1 pm 105 Semi-permeable material to dihydrogen 106 Internal structural element 11 Anode lia Central soul 11b Wall 12 Cathode 12a Central soul 12b Wall 13 Source of electrical energy 14 Water tank 2 Clothing item 3 Human or animal body

Claims

Claims

1. Device (1) for delivering dihydrogen comprising: • a body (10) comprising at least one anode (11) and at least one cathode (12), and • an electrical energy source (13), the anode (11) and the cathode (12) being electrically connected to the electrical energy source (13), the device (1) being configured to deliver the dihydrogen through the skin of a human or animal body (3): • the body (10) is based on a flexible material, capable of conforming to the skin of a human or animal body (3), the body (10) having an outer surface (100) comprising: • a lower face (101) intended to be applied to the skin, • at least one face (102) intended not to be in contact with the skin, • the body (10) comprises a water reservoir (14), the relative arrangement of the reservoir (14),of the anode (11) and the cathode (12) being configured so that the water contained in the reservoir is in contact with the anode (11) and the cathode (12) to form a closed electrical circuit, so as to produce dihydrogen at the cathode (12) from the water coming from the reservoir (14), to transdermally release the dihydrogen produced, characterized in that the body (10) is partly covered by a material not permeable to dihydrogen (103) forming at least a portion (1020) of the at least one face (102) intended not to be in contact with the skin.,

2. Device (1) according to the preceding claim, in which the body (10) is at least partly covered by a material (104) having a cut-off threshold of less than 1 pm, forming at least a portion of the at least one face (102) intended not to be in contact with the skin.

3. Device (1) according to any one of the preceding claims, wherein the lower face (101) is at least partly covered by a semi-permeable material (104) having a cut-off threshold of less than 1 pm.

4. Device (1) according to any one of the preceding claims, in which the lower face (101) is at least partly covered by a semi-permeable material (105) having a higher permeability to dihydrogen than its permeability to dioxygen, preferably the semi-permeable material (105) is permeable to dihydrogen and not permeable to dioxygen.

5. Device (1) according to any one of the preceding claims, in which the lower face (101) is only partly covered by a material not permeable to dihydrogen (103) so as to form at least one opening (1010) not covered by the material not permeable to dihydrogen (103).

6. Device (1) according to the preceding claim, wherein the at least one opening (1010) is covered by a semi-permeable material (105) having a higher permeability to dihydrogen than its permeability to dioxygen, preferably the semi-permeable material (105) is permeable to dihydrogen and not permeable to dioxygen.

7. Device (1) according to any one of the preceding claims, wherein the lower face (101) is provided with at least one microneedle (1011) intended to penetrate the skin.

8. Device (1) according to the preceding claim, in which, the lower face (101) being partly covered by a material non-permeable to dihydrogen (103) so as to form at least one opening (1010) not covered by the material non-permeable to dihydrogen (103), the at least one microneedle (1011) is hollow and is arranged opposite the opening (1010).

9. Device (1) according to any one of the preceding claims, wherein the water reservoir (14) comprises a hydrogel.

10. Device (1) according to any one of the preceding claims, in which the cathode (12) and the anode (11) are arranged opposite the lower face (101) intended to be in contact with the skin.

11. Device (1) according to any one of claims 1 to 9, in which the cathode (12) and the anode (11) form a stack, the cathode (12) being opposite the lower face (101) intended to be in contact with the skin, and the anode (11) being opposite a face (102) intended to do not come into contact with skin.

12. Device according to the preceding claim, in which one of the cathode (12) and the anode (11) extends transversely in the reservoir (14) so ​​as to divide the reservoir into two separate parts, without circulation of water between the two parts, a first part (14a) communicating with the lower face (101), a second part (14b) communicating with a face (102) intended not to be in contact with the skin.

13. Device (1) according to any one of claims 1 to 9, wherein, the lower face (101) being provided with at least one microneedle (1011) intended to penetrate the skin, the cathode (12) is formed by said microneedle (1011).

14. An article of clothing (2) comprising the hydrogen delivery device (1) according to any one of the preceding claims.

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