WO2021260319A1 - Passive device for generating oxygen - Google Patents

Abstract

Passive device for generating O2, comprising a chamber (1) provided with walls that are resistant to water and oxygen, and a discharge element (3) for discharging oxygen and preventing water from penetrating into the chamber, the chamber (1) further comprising sodium percarbonate (SPC) (2) of formula Na2CO3.1,5H2O2 and water with a molar ratio n(H2O)/n(SPC) greater than or equal to 0 and lower than or equal to 1.

Description

PASSIVE DIOXYGEN GENERATION DEVICE

DESCRIPTION

TECHNICAL AREA

The present invention relates to the general field of oxygen generation systems.

The invention relates to a passive device for generating oxygen.

The invention also relates to a method for generating dioxygen using such a device.

The invention finds applications in many industrial fields, and in particular for the manufacture of submerged sensors operating using a fuel cell or even in the medical field.

The invention is particularly advantageous since it makes it possible to generate oxygen passively over long periods (typically several months).

STATE OF THE PRIOR ART

Currently, to avoid immunological rejection of transplanted cells, to supply cells with O2 during transplantation or even during the transport of organs with a view to transplantation, miniaturized devices generating dioxygen are used.

For example, in document WO 2013/023013 A1, microcapsules formed from a semi-permeable membrane containing living cells, oxygen-generating particles, as well as an aqueous medium or a hydrogel, are used to avoid releases. immunology of transplanted cells. The semi-permeable membrane allows, for example, the passage of nutrients or biologically active molecules from the exterior to the interior of the microcapsule and the passage of active agents secreted by living cells from the interior to the exterior. of the microcapsule. The membrane is, for example, polyamine. Generating particles oxygen contain a biodegradable polymer as well as a hydrogen peroxide, an inorganic peroxide or a compound comprising hydrogen peroxide. For example, it can be calcium peroxide, magnesium peroxide, sodium peroxide, sodium percarbonate, benzyl peroxide or combinations thereof. It is possible to generate a flow of oxygen over 6 days, using 1500 capsules based on CaÜ ₂ or Mg0 ₂ . However, the flow obtained is discontinuous.

In WO 2017/024076 A1, alginate microcapsules 250 to 600 µm in diameter, containing a perfluorocarbon (PFC) as well as an oxygen-generating substance on contact with water can be used to feed cells. in O ₂ during transplantation. The oxygen-generating substance is, for example, selected from an inorganic peroxide, such as calcium peroxide, and an inorganic percarbonate, such as sodium percarbonate. Microcapsules are made from an aqueous solution of alginate. The generation of oxygen is studied over periods of up to 2 hours.

In WO 2018/187831 A1 a substrate for cells, tissues and / or organs is described. The substrate comprises a material which generates oxygen on contact with water and a membrane permeable to water and oxygen. The water diffuses through the membrane to the material which generates oxygen, which in turn diffuses through the membrane to the exterior of the device. This material can be a metal peroxide, such as sodium peroxide Na _2O2 , calcium peroxide or urea peroxide. The generation of oxygen is studied over periods of up to 400 min.

Finally, in document WO 2007/134304 A1, a composition capable of generating oxygen is described. This composition comprises a hydrophobic fluid as well as peroxide nanoparticles capable of generating, on contact with water, oxygen or a hydrogen peroxide. The water diffuses through the hydrophobic fluid to the nanoparticles. The peroxide nanoparticles can be an inorganic peroxide (for example a sodium peroxide), a hydrogen peroxide-urea (UHP) or a sodium percarbonate Na ₂ C0 ₃ .1,5H ₂ 0 ₂ . The composition can be encapsulated in a membrane allowing, on the one hand, the passage of water from the outside to the nanoparticles and, on the other hand, the passage of oxygen or hydrogen peroxide formed within the membrane to the outside. The generation of oxygen is also carried out over short periods (of the order of 200 minutes). These different devices generate oxygen by hydrolysis from water coming from the external environment and diffusing through a membrane or through a hydrophobic fluid to particular nanoparticles / microcapsules. This operation allows the flow control of 0 ₂ .

Nevertheless, the oxygen flows are linked to surface exchange kinetics to allow, first, the diffusion of water molecules then the diffusion of oxygen. The kinetics therefore depend, on the one hand, on the size of these nanoparticles / microcapsules and, on the other hand, on the progress of the reactions. This results in non-constant flow rates and relatively short reaction times (typically less than a week or even less than a day). The correlation between the oxygen flow rate and the shape of the oxygen-generating materials prevents the use of these devices for long-term applications (greater than a month, or even greater than a year) and / or requiring constant O flow rates. ₂ .

DISCLOSURE OF THE INVENTION

An aim of the present invention is to provide a passive device allowing the generation of a continuous flow (with a nominal value of ± 10%) of oxygen, preferably over periods of several months or even several years.

For this, the present invention provides a passive device for generating O ₂ comprising an enclosure provided with walls, impermeable to water and oxygen, and an evacuation element, allowing the evacuation of dioxygen, and preventing the penetration of water into the enclosure, the enclosure further comprising sodium percarbonate (SPC) of formula Na ₂ C0 ₃ .1,5H ₂ 0 ₂ and water with a molar ratio n ( H ₂ 0) / n (SPC) greater than or equal to 0 and less than or equal to 1.

The term “sealed wall” is understood to mean that water and gases cannot pass through the walls of the enclosure. The invention differs fundamentally from the prior art by the integration of sodium percarbonate (SPC). SPC can be prehydrated so as to initially contain the amount of water necessary for the generation and regulation of oxygen flow. The device operates passively.

The device is based on:

- thermolysis reactions (n (H ₂ 0) / n (SPC) molar ratio equal to 0),

WHERE

- reactions of thermolysis and hydrolysis (molar ratio n (H ₂ 0) / n (SPC) strictly greater than 0).

In addition, with such a quantity of water initially present in the enclosure (n (H ₂ 0) / n (SPC) molar ratio greater than or equal to 0 and less than or equal to 1), it is possible:

- generate a constant oxygen flow (with a nominal value of ±

10%),

- determine the value of this flux as a function of the molar ratio,

- fix the duration of this flow according to the initial quantities used.

On the contrary, in the prior art, the supply of water to the oxygen generation system comes from an external source by diffusion through a semi-permeable membrane. This does not make it possible to precisely control the water supply and therefore to generate a constant flow and / or over long periods.

Advantageously, the evacuation element is a capillary, which prevents the diffusion of water out of the enclosure.

According to an advantageous variant embodiment, the evacuation element contains a hydrophobic material, which prevents the diffusion of water from outside into the reservoir (diffusion against the flow of oxygen). This also prevents water from being drained out of the enclosure.

According to another advantageous variant embodiment, the evacuation element comprises a semi-permeable membrane. By semi-permeable is meant that liquids (in particular water) cannot diffuse through the membrane and that gases (in particular dioxygen) can diffuse through the membrane. Advantageously, the semi-permeable membrane is made of polyvinylidene fluoride (or PVDF for “PolyVinyliDene Fluoride”) or of polyetherimide (PEI).

Advantageously, the enclosure comprises a hydrophilic material. Advantageously, the hydrophilic material is a zeolite or a polymer.

Advantageously, the largest dimension of the enclosure is less than 5cm.

According to an advantageous variant embodiment, the molar ratio n (H ₂ 0) / n (SPC) is strictly greater than 0.

According to another advantageous variant embodiment, the molar ratio n (H ₂ 0) / n (SPC) is equal to 0.

The device according to the invention has many advantages:

- a continuous and constant flow of oxygen is ensured,

- the system overcomes the problems of kinetics of surface exchanges, which releases the constraint on the size of the elements (particles / capsules) releasing GO ₂ , and therefore allows the use of larger quantities of material, and therefore address applications requiring oxygen flow rates over long periods (typically greater than a month).

The invention also relates to a method for generating O ₂ comprising the following successive steps:

- provide a passive O ₂ generation device as defined above,

- heating or cooling the device to a temperature greater than or equal to 0 ° C and less than 107 ° C, whereby dioxygen is formed.

According to a first variant embodiment, the temperature is greater than or equal to 32 ° C and less than 107 ° C, for example from 32 ° C to 45 ° C, or from 34 ° C to 53 ° C or from 36 ° C to 40 ° C, whereby dioxygen and Na ₂ C0 ₃ .1H ₂ 0 and / or Na C0 ₃ .7H 0 are formed.

According to another variant embodiment, the temperature is ambient temperature (20-25 ° C). Preferably, the device is heated to a temperature ranging from 36 ° C to 40 ° C.

The invention also relates to a method for oxygenating a tissue, an organ and / or cells which have been extracted from a human body or from an animal body, comprising the following successive steps:

- positioning in the same container a tissue, an organ and / or cells that have been extracted from a human body or an animal body and a device as defined above,

- heating or cooling the container to a temperature greater than or equal to 0 ° C and less than 107 ° C, whereby dioxygen is formed.

Preferably, the temperature is greater than or equal to 32 ° C and less than 107 ° C, for example from 32 ° C to 45 ° C, or from 34 ° C to 53 ° C, whereby dioxygen and Na2CO3.1H20 are formed. and / or Na2CO3.7H20.

Even more preferably, the temperature ranges from 36 ° C to 40 ° C.

Other characteristics and advantages of the invention will emerge from the additional description which follows.

It goes without saying that this additional description is given only by way of illustration of the subject of the invention and should in no case be interpreted as a limitation of this subject.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be better understood on reading the description of exemplary embodiments given purely as an indication and in no way limiting, with reference to the appended drawings in which:

FIG. 1 schematically represents a device for generating oxygen according to a particular embodiment of the invention.

Fig. 2 is a graph showing the flux of 2 for 25 days at 40 ° C of an SPC / H2O mixture containing different amounts of water, according to different embodiments of the invention. FIG. 3 is a graph representing the volume of O ₂ over 80 days for an H2O / SPC mixture, the molar ratio of which is 0.3 according to a particular embodiment of the invention.

Figure 4 is a graph showing the volume of O2 for 52 days at 38 ° C for an anhydrous SPC compound, according to a particular embodiment of the invention.

Fig. 5 is a graph showing the volume of 2 per gram of SPC for 25 days for one anhydrous SPC compound, and for two SPC / H2O mixtures containing different amounts of water, according to different embodiments of the invention.

The different parts shown in the figures are not necessarily on a uniform scale, to make the figures more readable.

DETAILED PRESENTATION OF PARTICULAR EMBODIMENTS

Although this is in no way limiting, the invention is particularly advantageous for applications requiring a miniaturized device capable of generating low constant 2 flow rates over long periods in a passive manner.

The invention finds applications in the medical field or also in the field of submerged sensors operating using a fuel cell.

Reference is made first of all to FIG. 1 showing a device for generating O2.

The device for passively generating dioxygen comprises an enclosure 1 in which is placed the material 2 generating the dioxygen and water.

The material 2 generating the dioxygen is sodium percarbonate

(SPC) of formula

Na2CO3, 1.5H2O2. The H2O / SPC molar ratio ranges from 0 to 1. Preferably, it is strictly greater than 0. Sodium percarbonate decomposes by thermolysis and / or by hydrolysis.

The decomposition by thermolysis is thermally activated. It is carried out according to equation (1):

The hydrogen peroxide H2O2 formed during thermolysis then decomposes instantly according to reaction (2):

The thermolysis reaction (1) is the kinetically limiting step.

Depending on the working temperature, the water produced by the decomposition of hydrogen peroxide (reaction (2)) then hydrates the by-product Na2CÜ3 resulting from thermolysis, to form compounds of formula Na2C03.xH20 and / or hydrolyze the SPC compound. The overall reaction (3) combining thermolysis and rehydration of the by-products of thermolysis is:

With x ranging from 0 to 1.5 since the quantity of water generated by reaction (2) implies a maximum value of x = 1.5.

The thermodynamic equilibria of the compound Na2CO3xH20 have been described by Gronvold et al. (“Thermodynamic properties and phase transitions of known hydrates between 270 and 400 K II. Na2CÛ3 · H2O and Na2CÛ3 · IOH2O”, J. Chem. Thermodynamics 1983, 15, 881-889):

- for a temperature T <32 ° C, x = 10

- for a temperature 32 ° C <T <38 ° C, x = 7

- for a temperature T> 38 ° C, x = l.

At a temperature below 32 ° C, the compound is Na ₂ CO ₃ .10H ₂ O. We are in the presence of pure thermolysis because the water is completely consumed. At a temperature oscillating around 38 ° C, one can find a mixture of compounds Na ₂ C0 ₃ .1H ₂ 0 and Na ₂ C0 ₃ .7H ₂ 0. It is possible to have hydrolysis and thermolysis.

For temperatures above 38 ° C, x = 1, therefore the free water generated by reaction (3), ie 0.5 H ₂ O, will hydrolyze the SPC compound. At these temperatures, there is therefore a decomposition of the SPC via hydrolysis and thermolysis.

At a temperature of 107 ° C, x = 0 and anhydrous _{Na 2} CÜ _{3 is obtained.}

The decomposition of SPC by hydrolysis is carried out according to equation (4):

Na ₂ C0 ₃ .l, 5H ₂ 0 ₂ + yH ₂ 0 => Na ₂ C0 ₃ .xH ₂ 0 + (l, 5 + yx) H ₂ 0 + 0.75O ₂ ¾4)

Here we find the same thermodynamic equilibria as those described previously for thermolysis.

In the case of integration into an element whose temperature oscillates around 38 ° C, the by-product Na ₂ C0 ₃ .xH ₂ 0 is a combination of Na ₂ C0 ₃ .1H ₂ 0 and Na ₂ C0 ₃ . 7H ₂ 0. Consequently, by not adding water (y = 0) or by adding little additional water (typically y <l, there is no aqueous phase), it is possible to maintain a continuous flow of 0 _2. The water generated or integrated in the initial state hydrates the Na ₂ C0 ₃ and is not found in the state of free water. A hydrolysis reaction around 38 ° C can also take place.

The dioxygen-generating material 2 is integrated in an enclosure 1. The enclosure 1 is an enclosure whose only opening is an evacuation element 3 (also called gas outlet) to ensure the diffusion of oxygen from the inside. from the enclosure to the outside of the enclosure. The evacuation element 3 prevents the escape of water in liquid form.

The evacuation element 3 is preferably a capillary. The capillary has an outer diameter and an inner diameter. The internal diameter is preferably less than 100 µm. It goes, for example, from 10 to 50pm.

The enclosure 1 comprises several walls that are impermeable to liquids (in particular to water) and, preferably, to gases.

According to a first advantageous variant embodiment, a hydrophobic material is positioned at the level of the evacuation element 3 to avoid the introduction of water from the outside of the enclosure 1 to the inside of the enclosure 1. It is possible, for example, to choose as the hydrophobic material polypropylene (PP), polyethylene (PE) or polytetrafluoroethylene ( PTFE).

According to another advantageous variant embodiment, a membrane 4 is positioned at the level of the evacuation element 3 to prevent the diffusion of water from the outside of the enclosure 1 towards the inside of the enclosure 1. The membrane 4 is semi-permeable. Preferably, the semi-permeable membrane 4 is placed inside the capillary. The membrane 4 is preferably made of polyetherimide (PEI) or of polyvinylidene fluoride (PVDF).

The enclosure 1 can, in addition, comprise a material absorbing water or a desiccant to capture the residual water and limit / prevent the reaction by hydrolysis (in particular for temperatures above 40 ° C for which x is equal to 0 where x is close to zero (typically less than 1) or to decrease oxygen fluxes (for temperatures below 40 ° C). The water-absorbent material is, for example, a zeolite, a silica gel, a clay, a molecular sieve, calcium chloride, calcium sulfate or a so-called absorbent polymer, for example sodium polyacrylate.

By water-absorbent material is meant a material which can absorb from 1 to 1000 times their mass of water, for example 1g of material can absorb at least 10g of water.

When the device comprises a material absorbing water or a desiccant and / or for operating ranges for which x is equal to 0 or close to 0, the operation may be based solely on thermolysis.

According to a particular embodiment, the hydrophilic material can encapsulate the SPC and / or the water.

According to another particular embodiment, the hydrophilic material can be mixed with the SPC and / or with the water.

According to another embodiment, the hydrophilic material is positioned in the evacuation element 3. The enclosure 1 can also be provided with a water reservoir to promote the hydrolysis reaction and thus to increase the flow of O ₂ . To ensure a constant Ü2 flow, the water release flow must also be constant. This water reservoir can be a silica gel saturated with water.

The method for generating O2 using a device as described above comprises at least one step during which the device is brought (by heating or cooling it) to the desired temperature. The desired temperature may, for example, be between 0 ° C and 107 ° C, whereby dioxygen is formed. Preferably, the temperature is above 25 ° C.

The device is advantageously heated to a temperature above 32 ° C, for example from 37 ° C to 38 ° C.

Preferably, the device is heated to a temperature of 38 ° C ± 2 ° C.

The device can be incorporated into a sensor. It may be, for example, an immersed sensor operating with a fuel cell.

The device can be in contact with an element or positioned in an element whose temperature oscillates around 38 ° C.

The invention also relates to a method of oxygenating a body tissue, an organ and / or cells taken, comprising a step during which the body tissue, the organ and / or the cells taken are positioned in contact with the device as defined above whereby the body tissue, the organ and / or the cells removed are oxygenated by the oxygen generated by the device.

This oxygenation process is, for example, carried out at a temperature ranging from 20 ° C to 41 ° C, for example from 35 ° C to 41 ° C or from 20 ° C to 40 ° C, even more preferably from 36 ° C to 40 ° C and even more preferably from 37 ° C to 39 ° C.

Illustrative and nonlimiting examples of one embodiment:

In this first example, water / SPC compounds containing different amounts of water (water / SPC molar ratio of 7, 3.5 and 0.3) are placed in a sealed enclosure 1. The flow of O 2 was measured for 25 days for these different water / SPC compounds (FIG. 2). When the water content is low (molar ratio of 0.3), a flow rate of 0.5 pL / min / g SPC ± 10% was maintained for 25 days. In a second example, enclosure 1 contains an H2O / SPC mixture, the molar ratio of which is 0.3. The tank has the following dimensions: 0.5 * 2 * 2 cm (SPC density = 2.1; necessary interior volume = 1.53 cm ³ ). A capillary 3 with an internal diameter of 100 microns allows the release of GO2 to the outside. A semi-permeable membrane 4 of porous polymer of the polyvinylidene fluoride (PVDF) type is introduced into the capillary 3 to ensure the diffusion of IΌ2 without the diffusion of water into the chamber 1. With 3 g of SPC and 0.1 g of water, a flow rate of 0.5 pL / min / g SPC ± 10% is generated for 80 days (Figure 3).

In another example, the change in the Ü2 pressure of an enclosure 1 containing an anhydrous SPC compound 2 was observed for 52 days at 38 ° C (Figure 4). The continuous pressure increase in the reservoir corresponds to a flow rate of 30 nL / min / g SPC ± 10%. This flow rate is 30 times lower than in the case of pre-hydrated materials.

From these various examples, it was therefore observed that (FIG. 5): - in the case of an anhydrous SPC compound, a constant flow of Ü2 is generated at 38 ° C,

- in the case of compounds containing H2O and SPC with nH ₂ 0 / nSPC <l, a constant and higher flow of Ü2 is generated at 40 ° C,

- in the case of compounds containing H2O and SPC with nH ₂ 0 / nSPC> 1, a non-constant flow of Ü2 is generated at 40 ° C.

Claims

1. Passive device for generating O2 comprising an enclosure (1) provided with walls, impermeable to water and oxygen, and an evacuation element (3), allowing the evacuation of dioxygen, and preventing the penetration. of water within the enclosure, the enclosure (1) further comprising sodium percarbonate (SPC) (2) of formula Na2C03.1,5H202 and water with a molar ratio n (H ₂ 0) / n (SPC) strictly greater than 0 and less than or equal to 1. 2. Device according to claim 1, characterized in that the evacuation element (3) contains a hydrophobic material. 3. Device according to claim 1, characterized in that the evacuation element (3) comprises a semi-permeable membrane (4), preferably of PVDF or PEI. 4. Device according to any one of claims 1 to 3, characterized in that the evacuation element (3) is a capillary. 5. Device according to any one of claims 1 to 4, characterized in that the enclosure (1) comprises a hydrophilic material. 6. Device according to claim 5, characterized in that the hydrophilic material is a zeolite or a polymer. 7. Device according to any one of the preceding claims, characterized in that the largest dimension of the enclosure (1) is less than 5 cm. 8. A method of generating O2 comprising the following successive steps: - providing a passive device for generating O2 as defined in any one of claims 1 to 7, - heating or cooling the device to a temperature greater than or equal to 0 ° C and less than 107 ° C, whereby oxygen is formed. 9. A process for generating O2 according to claim 8, characterized in that the device is heated to a temperature ranging from 36 ° C to 40 ° C. 10. A method of oxygenating a tissue, an organ and / or cells which have been extracted from a human body or from an animal body, comprising the following successive steps: - positioning in the same container a tissue, an organ and / or cells that have been extracted from a human body or an animal body and a device as defined in one of claims 1 to 7, - heating or cooling the container to a temperature ranging from 36 ° C to 40 ° C, whereby dioxygen is formed.