Implantable device for producing hydrogen

Abstract

A device intended to be implanted in a human or animal body, in order to produce hydrogen in situ from molecules present in the body medium in which the device is implanted, this device having an anode and a cathode, which are each electrically connected to a pole of an electrical energy source, and having a semi-permeable material separating the electrodes from the body medium, in which device, when the connection to the electrical energy source is effective in situ, in the presence of body fluid, a closed electrical circuit is formed, with production of hydrogen at the cathode, the semi-permeable material having a cutoff threshold of between 50 and 500 Da.

Claims

1. A device intended to be implanted in a human or animal body, in order to produce hydrogen in situ from molecules present in a body medium in which the device is implanted, this device comprising two electrodes: an anode and a cathode, the anode is electrically connected to a pole of an electrical energy source and the cathode is electrically connected to an other pole of the electrical energy source, and comprising a semi-permeable material separating the electrodes from the body medium, and wherein, when the connection to the electrical energy source is effective in situ, in the presence of body fluid, a closed electrical circuit is formed, with production of hydrogen at the cathode, the semi-permeable material having a cutoff threshold of between 50 and 500 Da.

2. The device according to claim 1, wherein the semi-permeable material has a cutoff threshold between 50 and 500 Da, and the device is intended to induce electrolysis of water, with production of dioxygen at the anode.

3. The device according to claim 2, wherein the electrodes are individually or collectively separated from the body medium by the semi-permeable material.

4. The device according to claim 1, wherein the semi-permeable material has a cutoff threshold between 200 and 500 Da, and wherein the anode contains or carries an enzyme able to catalyse the oxidation of a carbohydrate at the anode.

5. The device according to claim 4, wherein the electrodes are individually and/or collectively separated from the body medium by the semi-permeable material and wherein the anode and cathode are separated one from the other by a semi-permeable membrane or by a proton exchange membrane.

6. The device according to claim 1, wherein the semi-permeable material that separates the electrodes from the body medium is formed by a semi-permeable membrane that surrounds the two electrodes, or by a semi-permeable membrane that surrounds each electrode.

7. The device according to claim 1, wherein the semi-permeable material that separates the electrodes from the body medium forms a portion of a container that encloses the electrodes.

8. The device according to claim 1, wherein the semi-permeable material that separates the electrodes from the body medium consists of a three-dimensional porous matrix, in at least one block, containing the two electrodes.

9. The device according to claim 5, wherein the semi-permeable material is surrounded by a biocompatible surface layer and with anti-biofouling property, also in semi-permeable material for separation with the body medium, or the semi-permeable material has an anti-biofouling property.

10. The device according to claim 1, wherein the semi-permeable material is polyvinyl alcohol (PVA).

11. The device according to claim 1, wherein the electrodes are made of or comprise: carbon; platinum; gold.

12. The device according to claim 1, wherein the anode contains or carries an enzyme able to catalyse the oxidation of the glucose at the anode, the enzyme being chosen from among glucose oxidase and glucose dehydrogenase, and a catalase able to be used as a second catalyst when the enzyme is glucose dehydrogenase.

13. The device according to claim 1, wherein the electrical energy source is one of a battery; a biobattery able to produce electricity by consuming chemical species that are naturally present in a human or animal organism; a mechanical device that recovers piezoelectric energy.

14. The device according to claim 1, wherein said device has dimensions that represent a volume less than or equal to 12 ml.

15. The device according to claim 1, wherein the electrical energy source produces a voltage of at least about 1.3 V and a power of at least about 5 microWatts.

16. The device according to claim 1, wherein the anode and cathode are separated by a distance between about 0.1 mm and about 1 cm.

17. A method for in vivo production of hydrogen and/or oxygen inside a human or animal body, comprising an implantation of at least one device according to claim 1 in the human or animal body, an operation of the device to produce hydrogen and/or oxygen inside in the human or animal body.

18. The method according to claim 17, further comprising electrically connecting the device to a remote electrical energy source.

19. The method according to claim 17, wherein the operation of the device comprises controlling closing and opening of the electrical circuit by an element for controlling the opening and the closing of the electrical circuit.

Description

BRIEF INTRODUCTION OF THE DRAWINGS

(1) The invention shall now be described in more detail using embodiments described by way of non-limiting examples and in reference to the accompanying drawing, wherein:

(2) FIG. 1 is a diagram of a first device for the hydrolysis of water.

(3) FIG. 2 is a diagram of a second device for the hydrolysis of water.

(4) FIG. 3 is a diagram of a first device using the glucose.

(5) FIG. 4 is a diagram of a rigid device.

(6) FIG. 5 is a diagram of a third device for the hydrolysis of water.

(7) FIG. 6 is a diagram of a second device using the glucose.

DETAILED DESCRIPTION

Example 1: Device for the Hydrolysis of Water

(8) The device is formed from an anode 1 and from a cathode 2, placed inside a semi-permeable membrane 3, insulated conductor wires, namely conductor 4 connecting the cathode 2 to the pole (−) of a source of energy, and conductor 5 connecting the cathode 2 to the pole (+) of the source of energy. The energy source is a Lithium battery 7 (Lithium-CFx), delivering between 3.2 V and 2.5 V, and connected to a circuit making it possible circulate between anode and cathode a current of 8 microAmperes under 1.3 V. The semi-permeable membrane has a cutoff threshold of 100 Da. The electrodes are platinum strips, they are disposed in parallel and separated by a space 6 of 3 mm.

(9) In operation, water and electrolytes present in the medium penetrate inside the space created by the semi-permeable membrane. Under the effect of the electric current delivered by the Lithium battery, the water is electrolysed, leading to the release of hydrogen at the cathode and of oxygen at the anode.

Example 2: Device for the Hydrolysis of Water

(10) This device differs from the one of example 1 by the fact that the membrane 3 is replaced with two semi-permeable membranes 8 and 9, surrounding the anode, respectively the cathode. The semi-permeable membranes have a cutoff threshold of 150 Da.

Example 3: Device for Producing Hydrogen Using Glucose

(11) The device is formed from an anode 10 and from a cathode 12, each placed inside a semi-permeable membrane 11, respectively 13, insulated conductor wires, namely conductor 14 connecting the cathode 12 to the pole (−) of a source of energy, and conductor 15 connecting the anode 10 to the pole (+) of the source of energy. The source of energy is a Lithium battery 16, delivering between 3.2 V and 2.5 V, and connected to a circuit making it possible circulate between anode and cathode a current of 1 milliAmpere under 0.3 V. The cathode is an electrode 3D made of carbon nanotubes, laccase, chitosan and genepin, the anode is an electrode 3D formed from carbon nanotubes, glucose oxidase, chitosan and genepin, according to the teaching of FR 3 019 384. The membrane 11 has a cutoff threshold of 500 and the membrane 13 has a cutoff threshold of 200.

(12) Alternatively, the membrane 11 has a cutoff threshold of 200 and the membrane 13 has a cutoff threshold of 100. In an alternative not shown, a Nafion® membrane is provided between the two electrodes.

(13) In operation,

(14) at the anode: the glucose passes through the semi-permeable membrane the glucose oxidase transforms it into gluconate+2 H.sup.++2 e.sup.−. The electrons are captured by the anode. The gluconate passes back through the membrane, as well as the protons.

(15) at the cathode: 2 electrons are combined with two protons to give H.sub.2.

(16) According to the invention, when glucose is used, it is possible to provide catalase to retransform H.sub.2O.sub.2 into H.sub.2O and ½ O.sub.2, in which case the presence of O.sub.2 at the anode would allow for a parasite reaction with the glucose leading to the formation of H.sub.2O.sub.2.

(17) Another alternative consists, with or without the presence of catalase, of applying a high voltage at the anode (>0.6V) in order to oxidise H.sub.2O.sub.2.

(18) Further alternatively, the glucose oxidase is replaced with the glucose dehydrogenase. The anode then includes this enzyme and, in addition, a cofactor.

Example 4: Hydrolysis of Water, Lithium Battery

(19) Many clinical studies demonstrate a beneficial effect of the ingestion of water saturated with H.sub.2, corresponding to a minimum intake of about 240 micromoles/24 h. The continuous production of H.sub.2 by a device implanted according to the invention makes it possible to obtain an average concentration in the extra-cellular and intra-cellular fluid greater than the average concentration obtained by oral ingestion, with significantly lower initial quantities.

(20) In this example, the production of 240 micromoles/24 h of hydrogen by the devices of the diagrams in FIGS. 1 and 2 is described.

(21) By way of example, the device is implanted in patients carrying an Alzheimer's disease and carriers of the apolipoprotein genotype E4 (APOE4) (cf. https://www.ncbi.nlm.nih.ciov/pubmed/29110615, this study showing an interest of the ingestion of 300 mL per day of hydrogen water).

(22) In this example, the source of energy is a Lithium-CFx battery of the type of those used in wireless pacemakers, that operate under a voltage comprised between 3.2 V and 2.5 V.

(23) TABLE-US-00001 NanoStim ® Medtronic Capsule dimensions Length 41.4 mm, Length 25.9 mm, diameter 6 mm, diameter 6.7 mm, volume 1-1.2 cc volume 0.8-1 cc Masse capsule 2 g 1.75 g Battery capacity 220 mAh 120 mAh Battery dimensions length 25 mm, length 11 mm, diameter 6 mm diameter 6.7 mm

(24) The power embarked in the Nanostim battery is therefore 2376 J, in a volume of 760 microL, which is about 3 J/microL. However, to produce H.sub.2 via water hydrolysis, with a yield of 70%, about 0.4 J/(micromole of H.sub.2) can be provided. Therefore, in order to produce 240 micromoles of H.sub.2 per 24 h, a battery with a volume of about 32 microL can be used. A 12.8 mL battery then makes it possible to embark the required power for 400 days, which is more than one year.

(25) The electrodes will be constituted of platinum strips 0.1 mm thick, 4 cm long, 2.5 cm wide, placed in a semi-permeable membrane.

(26) The entire device can be positioned, just like a conventional pacemaker, under the collarbone.

(27) This example describes the formation of H.sub.2. But of course, it also applies to the generation of O.sub.2, taking into account the fact that twice the amount of energy is required to produce one mole of O.sub.2 than one mole of H.sub.2.

Example 5

(28) In this example, the anode of the device of FIG. 3 includes a glucose oxidase and a mediator (ferrocene, osmium complex, methylene blue, or quinone derivative). A difference in potential of 0.3 V is then sufficient to oxidise the glucose at the anode and to reduce the proton at the cathode. The power needed is therefore divided by 1.3/0.3=4.33. The dimension of the battery is then reduced to 12.8/4.33=2.9 mL. Alternatively, by retaining a dimension of 12 mL for the battery, a service life of the device of 1,732 days is obtained, which is nearly 5 years.

(29) This device can be used in the application of the preceding example, for the production of hydrogen.

Example 6

(30) With respect to example 5, the battery that supplies the 0.3 V is a glucose biobattery, according to the teachings of patents such as FR 3 019 384 and FR 2 958 801.

Example 7: Implantation Sites of the Device

(31) According to the needs, it is possible to implant 1 or several devices according to the invention. The choice is made in particular with regards to the extent of the area to be treated, the need for hydrogen and/or oxygen of this area, the capacity of the implantation site to receive in terms of volume one or several devices, the power of each device in terms of production and the diffusion and distribution capacity of the hydrogen and/or of the oxygen in this site/this area.

(32) As implantation sites, mention can be made of under the skin, in the or in the vicinity of the brain (in particular inside the brain ventricles), in the intestine, the heart.

(33) Under the skin: subcutaneous: volume up to 20 mL intra-muscular: volume up to 125 microL in the intestine: it is possible to consider several devices threaded one after the other on a line which is itself attached in the stomach, according to the teachings of patent FR1552927, each one of a diameter of 6 mm and of a length of 5 cm, which is 1.4 mL. For example, from 10 to 20 segments can be considered in the heart: typical size of the “lead less pacemaker” stimulators=6 mm diameter×25 mm long, which is 700 microL

Example 8

(34) FIG. 4 diagrammatically shows a device in the form of a cylindrical container, of which the body 19 is made of glass covered with parylene, or could be entirely of parylene. This body has an opening at one of the tops of the cylinder, which is closed by a disc 20 made of semi-permeable composite material. The two electrodes 18 and a simplified electrical circuit 21 are shown, whereas the source of energy is not shown

Example 9: Dispositive for the Electrolysis of Water in a Porous Matrix

(35) The device is formed from an anode 101 and from a cathode 102 which are placed in a porous matrix 103. Conductor wires 104 and 105 respectively connect the cathode 102 to the pole (−) and the anode 101 to the pole (+) of the source of energy 107.

(36) The porous matrix 103 is formed from a semi-permeable material, has a cutoff threshold from 50 to 100 Da and is covered with a biocompatible surface layer 122 and has anti-biofouling properties. This surface layer 122 is also semi-permeable and has a cutoff threshold from 50 to 100 Da.

(37) The porous matrix 103 makes it possible to prevent any cell growth inside the latter and an electrical current from circulating in the living tissues surrounding the device.

(38) In the electrolysis of the water, the ions H.sup.+ are reduced at the cathode in order to produce dihydrogen and the water is oxidised at the anode with production of dioxygen.

(39) It can be noted that the case is also considered where the matrix 103 itself has anti-biofouling properties, in which case the layer 122 is not used.

Example 10: Device with Enzymatic Catalysis in a Porous Matrix

(40) The device is formed from an anode 110 and from a cathode 112 which are each placed in a semi-permeable membrane respectively 111 and 113. Conductor wires 114 and 115 respectively connect the cathode 112 to the pole (−) and the anode 110 to the pole (+) of the source of energy 116.

(41) The anode 110 and the cathode 112 each covered by a semi-permeable membrane, respectively 111 and 113 are placed in a porous matrix 123. The porous matrix is covered with a biocompatible surface layer 124 and with anti-biofouling properties.

(42) The anode 110 has an enzyme that makes it possible to conduct the oxidation of the glucose into gluconate.

(43) So that the glucose can reach the anode 110, the surface layer 124, the porous matrix 123 as well as the semi-permeable membrane 111 all have a cutoff threshold greater than 200 Da.

(44) The cutoff threshold of the semi-permeable membrane 113 which is disposed on the cathode 112 is from 50 to 100 Da.

(45) It is also possible to not cover the anode 110 and the cathode 112, in that the matrix 123 already provides the selectivity.

(46) It can be noted that the case is also considered where the matrix 123 itself has anti-biofouling properties, in which case the layer 124 is not used.