阅读说明：本技术 氮系气体缓释剂和由其构成的氮系气体缓释体以及使用该缓释体的氮系气体的缓释方法、呼吸器具、包装体和缓释装置 (Nitrogen-containing gas sustained-release agent, nitrogen-containing gas sustained-release body comprising same, and method for sustained release of nitrogen-containing gas, respirator, package, and s) 是由 石原伸辅 井伊伸夫 于 2020-04-01 设计创作，主要内容包括：本发明的课题在于提供在常温、大气中具有氮系气体缓释性、能够安全操作的缓释氮系气体的缓释剂和由其构成的氮系气体缓释体、以及使用该缓释体的氮系气体的缓释方法、呼吸器具、包装体和缓释氮系气体的装置。作为解决方法,将氮系气体的缓释剂设为含有在层间包合有亚硝酸根离子(NO-(2)～(-))和/或硝酸根离子(NO-(3)～(-))的层状双氢氧化物的物质。此外,将由上述缓释剂构成的氮系气体缓释体暴露于含有二氧化碳、水蒸气的气体,通过引发亚硝酸的缓释、亚硝酸的自分解、亚硝酸的氧化/还原、亚硝酸根离子/硝酸根离子的还原中的任一种或多种过程,来缓释氮系气体。(The present invention addresses the problem of providing a sustained-release agent for sustained-release of a nitrogen-based gas, which has a sustained-release property for a nitrogen-based gas at normal temperature and in the atmosphere and can be safely handled, a nitrogen-based gas sustained-release body composed of the sustained-release agent, and a method for sustained-release of a nitrogen-based gas, a respirator, a package, and a device for sustained-release of a nitrogen-based gas using the sustained-release body. As a solution, nitrogen is usedThe gas sustained-release agent contains nitrite ions (NO) included between layers 2 ‑ ) And/or nitrate ion (NO) 3 ‑ ) A layered double hydroxide of (a). Further, the nitrogen-based gas slow-release agent is exposed to a gas containing carbon dioxide and water vapor, and the nitrogen-based gas is slowly released by initiating one or more processes of slow release of nitrous acid, self-decomposition of nitrous acid, oxidation/reduction of nitrous acid, and reduction of nitrite ions/nitrate ions.)

1. A sustained-release agent for sustained-release of nitrogen-based gas comprises a layer including nitrite ions (NO)₂ ^-) And/or nitrate ion (NO)₃ ^-) The layered double hydroxide of (1).

2. The sustained release formulation according to claim 1, wherein the nitrogen-based gas is selected from the group consisting of nitric oxide gas (NO), nitrous acid vapor (HNO)₂) Nitrogen dioxide gas (NO)₂) Nitrous oxide gas (N)₂O) and ammonia (NH)₃) At least one gas of the group.

3. The sustained-release agent according to claim 1 or 2, wherein the layered double hydroxide is represented by the following general formula (1),

Q_xR(OH)_2(x+1){(NO₂ ^-)_d(NO₃ ^-)_gZ_j}·nH₂O···(1)

in the formula (1), Q is a metal ion having a valence of 2, R is a metal ion having a valence of 3, and Z is NO₂ ^-And NO₃ ^-Other anions, and x, d, g and j in the formula (1) are numbers satisfying 1.8. ltoreq. x.ltoreq.4.2, 0.01. ltoreq. d + g.ltoreq.2.0, and 0. ltoreq. j.ltoreq.1.0, respectively, and n is a number varying depending on the humidity of the environment.

4. The sustained-release agent according to claim 3, wherein in the general formula (1),

q is selected from Mg²⁺、Mn²⁺、Fe²⁺、Co²⁺、Ni²⁺、Cu²⁺、Zn²⁺And Ca²⁺One or more of the group consisting of,

r is selected from Al³⁺、Ga³⁺、Cr³⁺、Mn³⁺、Fe³⁺、Co³⁺And Ni³⁺One or more of the group consisting of.

5. The sustained-release agent according to claim 4, wherein in the general formula (1), Q is Mg²⁺R is Al³⁺。

6. A sustained-release agent for sustained release of a nitrogen-containing gas, which comprises the sustained-release agent according to any one of claims 1 to 5.

7. The extended release formulation of claim 6, further comprising a solid reducing agent or a solid oxidizing agent.

8. The delay volume of claim 7, wherein the delay agent is mixed with the solid reducing agent or the solid oxidizing agent.

9. The sustained release formulation according to claim 7 or 8, wherein the solid reducing agent contains at least 2-valent iron ions or 2-valent tin ions.

10. The sustained release formulation according to claim 7 or 8, wherein the solid reducing agent contains at least one selected from the group consisting of iron (II) sulfate, tin (II) chloride and zinc.

11. The sustained-release preparation according to any one of claims 8 to 10, wherein the solid reducing agent or the solid oxidizing agent is mixed in an amount of 10 mass% or more and 10000 mass% or less with respect to the layered double hydroxide.

12. A method for slowly releasing a nitrogen-based gas, which comprises using a slow releasing body for slowly releasing a nitrogen-based gas,

the sustained release body is composed of a sustained release agent for sustained release of a nitrogen-based gas, and the sustained release agent contains nitrite ions (NO) included between layers₂ ^-) And/or nitrate ion (NO)₃ ^-) The layered double hydroxide of (1).

13. The method for releasing nitrogen-containing gas according to claim 12, wherein said layered double hydroxide is a layered double hydroxide having at least nitrite ions (NO) included between layers₂ ^-) The layered double hydroxide of (a) is,

and comprising the step of contacting a gas comprising carbon dioxide and/or water vapour with the delay-releasing body.

14. The method for sustained release of a nitrogen-based gas according to claim 13, further comprising: a step of contacting the nitrous acid vapor obtained in the step of contacting the gas with a solid reducing agent or a solid oxidizing agent.

15. The method for releasing a nitrogen-containing gas according to claim 12, wherein a mixture of the sustained-release agent and the solid reducing agent or the solid oxidizing agent is used as the sustained-release body,

and comprising the step of bringing a gas having a relative humidity of 40% or more into contact with the sustained-release body.

16. The method for releasing a nitrogen-based gas according to any one of claims 12 to 15, further comprising a step of removing impurities in the gas released from the release agent by using an adsorbent.

17. The method for releasing nitrogen-based gas according to claim 16, wherein said adsorbent contains magnesium hydroxide or calcium hydroxide.

18. A medical respirator comprising the sustained-release body according to any one of claims 6 to 11.

19. A package comprising the sustained-release body according to any one of claims 6 to 11 and a packaging material for hermetically containing the sustained-release body.

20. The package of claim 19, wherein the packaging material is an atmosphere selected from the group consisting of void-free, vacuum, inert gas atmosphere, and dry atmosphere.

21. An apparatus for slowly releasing a nitrogen-based gas, comprising:

an atmosphere gas supply unit for supplying an atmosphere gas; and

a nitrogen-based gas slow-releasing part for slowly releasing the nitrogen-based gas by the atmosphere gas supplied from the atmosphere gas supplying part,

the nitrogen-based gas slow-release part is provided with a slow-release body of the nitrogen-based gas, which is composed of a slow-release agent for slowly releasing the nitrogen-based gas, and the slow-release agent contains nitrite ions (NO) included between layers₂ ^-) And/or nitrate ion (NO)₃ ^-) The layered double hydroxide of (1).

22. The device according to claim 21, further comprising an impurity removing unit that removes impurities in the nitrogen-based gas that is slowly released by the nitrogen-based gas slow-release unit.

23. The device of claim 22, said delay-release body further comprising a solid reducing agent or a solid oxidizing agent, said solid reducing agent or said solid oxidizing agent being mixed with said delay-release agent.

24. The apparatus according to claim 23, wherein the atmosphere gas supply unit supplies a gas having a relative humidity of 40% or more.

25. The device of claim 21 or 22, said delay body further comprising a solid reducing agent or a solid oxidizing agent downstream of said delay agent.

26. The apparatus according to claim 25, wherein the atmosphere gas supply unit supplies a gas containing at least water vapor or carbon dioxide.

27. The apparatus of any one of claims 21-26, wherein the nitrogen-based gas is nitric oxide.

Technical Field

The present invention relates to a nitrogen-based gas sustained-release agent comprising a layered double hydroxide, a method for sustained release of a nitrogen-based gas using the sustained-release agent, a respirator, a package, and a sustained-release device using the sustained-release agent.

Background

In this specification, nitrogen monoxide (NO) and nitrogen dioxide (NO)₂) Dinitrogen monoxide (N)₂O) and dinitrogen trioxide (N)₂O₃) Equal Nitrogen Oxides (NO)_x) Nitrogen (N)₂) And ammonia (NH)₃) Such as inorganic molecular species containing nitrogen atoms and being gaseous at normal temperature and pressure, and nitrous acid (HNO)₂) And nitric acid (HNO)₃) The vapor of the nitrogen-oxygen acid is collectively called "nitrogen-based gas".

Nitrogen Oxides (NO)_x) It is a gas component also called Nox, and is contained in combustion gas generated from automobiles and factories, and is known to be a harmful gas causing respiratory diseases such as photochemical smog, acid rain, and asthma. Nitrogen oxides come in a variety of chemical species (e.g., nitric oxide, nitrogen dioxide, nitrous oxide, etc.).

In recent years, it has been found that nitrogen oxides include gases that exhibit specific physiological actions when applied in a trace amount to living bodies. Therefore, studies on the action of such nitrogen oxides on living bodies and tissues are actively being conducted, and the application of nitrogen oxides to medical treatment is also being studied. In particular, since the existence of vasodilatation has been found, Nitric Oxide (NO) has attracted attention for its application to medical treatment, and a nitric oxide inhalation method using the same has been adopted for the treatment of severe respiratory failure (persistent pulmonary hypertension in newborn, etc.) accompanied by pulmonary hypertension (non-patent document 1).

However, nitric oxide is a gas at normal temperature and normal pressure, and is often supplied from a pressure gas cylinder when used. In such a utilization system, transport and installation are not easy due to the capacity and weight of the gas cylinder, and if the control of the flow rate and concentration of the gas is mistaken, a serious accident is caused. Therefore, the development of nitric oxide in medical treatment is limited to hospitals with complete equipment. In addition, there are generally various regulations associated with the operation of high pressure gases, which are limited in their portability and use.

In addition, nitrogen atoms form a variety of oxidation states, and thus attention must also be paid to the stability of nitrogen oxides. In particular, since nitric oxide is likely to react with oxygen in the air and change into harmful nitrogen dioxide, it is necessary to carefully adjust and monitor the concentrations of nitric oxide and nitrogen dioxide using advanced medical equipment when applied to a medical field.

Under such circumstances, as a method of supplying nitric oxide instead of the pressure cylinder, a reagent for releasing nitric oxide has been developed. Such a reagent is a substantially solid organic or inorganic compound, and its action mechanism is that it is directly applied to a living body to cause hydrolysis, oxidation/reduction, and nitric oxide is generated in vivo. Nitroglycerin, isoamyl nitrite, sodium nitrite are representative thereof.

However, in general, nitric oxide generated in vivo by the application of nitric oxide-releasing agents relaxes all blood vessels in the whole body. As a result, a decrease in blood pressure of the whole body is caused, which may be problematic. On the other hand, when air containing about 1 to 40ppm of nitric oxide is directly inhaled into the lung, nitric oxide relaxes the pulmonary blood vessels to lower the pulmonary blood pressure, and then is taken into the blood vessels by the lung and immediately binds to hemoglobin in the blood to produce methemoglobin, which is inactivated. As a result, it is possible to selectively lower only the pulmonary blood pressure and improve the oxygen uptake capacity. The nitric oxide inhalation method utilizing this effect has been applied as a selective and effective therapeutic method for severe respiratory failure (persistent pulmonary hypertension in newborn, etc.) accompanied by pulmonary hypertension.

Further, as another method of supplying nitric oxide instead of the pressure cylinder, a method utilizing a reaction between copper and dilute nitric acid, a reaction between sodium nitrite and sulfuric acid and iron (II) sulfate, or the like is also known. However, these methods have a problem in safety because a highly reactive chemical substance is used, and further have a problem in that the release of nitric oxide lacks the persistence and it is difficult to control the concentration and the release time. Therefore, the nitric oxide supply method using this method has not received much attention as a replacement for the pressure cylinder.

Further, in addition to the above-described method of generating nitric oxide, it has long been known that nitric oxide can be generated using arc discharge (non-patent document 2). However, in the method of generating nitric oxide by arc discharge, it is necessary to precisely control various conditions such as current and voltage in order to control the concentration and the discharge time, and it is also indispensable to confirm the normal operation of the apparatus and the power supply (such as a battery) and to perform regular maintenance. In addition, nitrogen dioxide and ozone (O) are simultaneously generated during arc discharge₃) And other impurities that are highly irritating to human tissues, it is necessary to use a chemical substance such as an adsorbent in combination in order to remove them.

It is considered that if a gas supply method using a solid material for slowly releasing a nitrogen-based gas is developed instead of the above-described gas supply by a pressure gas cylinder, a chemical reaction using a hazardous reagent, and arc discharge, a lightweight, compact, and simple gas slow release mechanism can be expected to be constituted, and is useful in various research fields. In particular, if a solid material that sustains nitric oxide, which is unstable and is often difficult to handle, can be obtained, it is expected that nitric oxide can be inhaled in developing countries where medical devices are not available, at home, and the like, and the solid material can be applied to various medical applications. However, there has been no report on an inorganic solid material having a property of releasing nitric oxide at a low concentration in the atmosphere at normal temperature and being safe to handle. For example, a solid material has been proposed in which nitric oxide is adsorbed to unsaturated Metal sites of a porous material (zeolite or Metal-organic framework) and nitric oxide is released by a mechanism (ligand exchange) in which water molecules in the atmosphere are substituted with nitric oxide (non-patent document 6).

Documents of the prior art

Non-patent document

Non-patent document 1: roberts et al, "inhaled nitric oxide and persistent pulmonary hypertension of the newborns", N.Eng.J.Med., 1997, Vol.336, p.605-610.

Non-patent document 2: yu et al, "generating nitric oxide by pulsed discharge in air for portable inhalation therapy (generating nitric oxide by pulsed electrical discharge in air)", sci.

Non-patent document 3: iyi et al, "the Effect of KBr on the FTIR Spectra of NO3-LDHs (layered Double hydroxides) (Effect of KBr on the FTIR Spectra of NO3-LDHs (Layered Double hydroxides)", chem.Lett.2009, Vol.38, 808-.

Non-patent document 4: iyi et al, "Factors that influence the hydration of Layered Double Hydroxides (LDHs) and the appearance of intermediate second phases (LDHs) and the appearance of the intermediate second phases," Applied Clay Science 2007, Vol.35, 218- "Applied to the present invention.

Non-patent document 5: iyi et al, "Efficient decarbonization of carbonate-type layered double hydroxides (CO32-LDH) by ammonium salts in alcoholic medium (CO 32-LDH)" Applied Clay Science 2012, Vol.65-66, 121-.

Non-patent document 6: e.d. bloch et al, "Gradual release of strongly bound nitric oxide from Fe2(NO)2 (dobdc)", Gradual release of strong bound nitric oxide from Fe2(NO)2(dobdc) ", j.am.chem.soc., 2015, vol.137, p.3466-3469.

Disclosure of Invention

Problems to be solved by the invention

Since nitrogen-based gases are often unstable and difficult to handle, if a solid material that sustains the release of nitrogen-based gases can be obtained, it is considered that nitrogen-based gases are useful in various fields of research as a method of supplying nitrogen-based gases instead of a method of utilizing a chemical reaction of a pressure gas cylinder or a hazardous reagent. In particular, if a solid material having a sustained nitric oxide release property can be obtained, it is expected that nitric oxide can be inhaled in developing countries where medical equipment is not available or at home, and the application to various medical applications is expected. However, there has been no report on an inorganic solid material having a property of releasing nitric oxide at a low concentration in the atmosphere at normal temperature and being safe to handle.

Accordingly, an object of the present invention is to provide a nitrogen-based gas sustained-release agent having a nitrogen-based gas sustained-release property at normal temperature and in the atmosphere and capable of safe handling, a nitrogen-based gas sustained-release body composed of the same, a method for sustained release of a nitrogen-based gas using the sustained-release body, a respirator, a package, and a nitrogen-based gas sustained-release device.

Means for solving the problems

As a solid material for realizing the slow release of a nitrogen-based gas, Layered Double Hydroxide (LDH) has been attracting attention. As an inorganic solid material having a hydrogen sulfide slow-releasing property at ordinary temperature and in the atmosphere and capable of safe handling, the present inventors have invented the use of an inorganic solid material having a sulfide ion (HS) included between layers^-Etc.) and applied for japanese patent (japanese patent application No. 2018-132081). The Layered Double Hydroxide (LDH) is formed by sulfide ions (HS) between layers^-Etc.) and in the airThe water and the carbon dioxide are subjected to anion exchange to slowly release the hydrogen sulfide gas. It was also shown that the sustained release concentration and time can be controlled by controlling the composition and synthesis conditions using the LDH. If Layered Double Hydroxide (LDH) can be used also for the slow release of nitrogen-based gas, it is likely that the above problem can be solved.

Further, similar to nitric oxide, if other nitrogen-based gases can be released slowly by simply and safely controlling the concentration and time using Layered Double Hydroxide (LDH), it is considered that the method of supplying nitrogen-based gases is useful in various research fields as a method of replacing the method of chemical reaction using a gas cylinder or a hazardous agent. Further, since the total amount of gas released from the Layered Double Hydroxide (LDH) does not exceed the amount of substance of the active ingredient contained in the Layered Double Hydroxide (LDH) used, the upper limit of the total amount of gas released can be specified clearly, and high safety can be ensured.

Therefore, the present inventors have also considered the following characteristics of the Layered Double Hydroxide (LDH), and paid attention to the Layered Double Hydroxide (LDH) in which anions that can be a nitrogen-based gas source are included between layers as a candidate for an inorganic solid material having a possibility of releasing a nitrogen-based gas.

Unlike many other inorganic layered compounds, LDHs are a few layered inorganic solid materials that can include anions between layers because the layers have positive charges, and also can exchange anions between layers, and thus become the host of inorganic and organic anions. Since the charge density of the layer can be changed, the characteristics such as ion exchange property and the size of crystal can be changed, and there is an advantage that the selectivity of material design is large, it is considered that the method is suitable for the purpose of including the anion species of the nitrogen-based gas source between the layers.

Further, the above-mentioned anion species serving as the nitrogen-based gas source are included in a two-dimensional space having a bottom surface interval of about 1 nm, and it is necessary to diffuse in the two-dimensional space in order for molecules and ions outside the LDH to come into contact with the anion species and interact with each other. Therefore, the anion species that becomes the nitrogen-based gas source does not immediately react with molecules and ions outside the LDH, and the reaction proceeds with diffusion as a rate-determining factor in many cases. Therefore, LDH is expected to be a material for realizing sustained release such as release of a nitrogen-based gas at a low concentration for a long time.

Further, as a property of LDH, in the case where an anion between layers is a conjugate base of a weak acid, if left in the atmosphere, it is taken in from the atmosphere to carbon dioxide (CO) between layers₂) With interlayer water (H)₂O) to carbonic acid (H)₂CO₃) The conjugate base is protonated to form a weak acid molecule, and the anion site is carbonate ion (CO)₃ ^2-) When the weak acid molecule is volatile, the substitution is released into the atmosphere (Japanese patent application No. 2018 132081), and thus the system may function by the same mechanism.

However, releasable hydrogen sulfide (H) has been reported in Japanese patent application No. 2018-132081₂S) by the corresponding stabilizing anion species (HS)^-) Additional proton (H)⁺) The stable anion species inserted between the layers is generated by removing protons from the target gas species. On the other hand, in the case of many nitrogen-based gases including nitric oxide, since there is no proton capable of being dissociated in the molecule, there is no stable anion species corresponding to the conjugate base. Therefore, there are problems as follows: it is theoretically impossible to produce a nitrogen-based gas by directly applying the method described in the specification of Japanese patent application No. 2018-132081, in which a stable anion species, which is a conjugate base of a weak acid to be produced, is introduced between LDH layers.

Therefore, first, studies have been made on LDHs containing anion species that can be a nitrogen-based gas source. As a representative anion species, there is a nitrate ion (NO)₃ ^-) Layered Double Hydroxides (LDHs) comprising the same are widely known. However, LDH containing nitrate ions is stable in the atmosphere, and release of nitrogen-based gas by reaction with atmospheric components has not been reported. The reason for this is considered to be that: the nitrate ion is a co-substitution of nitric acid (pKa ═ 1.4) as a strong acidThe conjugate base, carbonic acid produced from carbon dioxide and water in the atmosphere, is a weak acid, and therefore, in terms of equilibrium theory, protonation of nitrate ions is hardly achieved. Nitrous acid (HNO), on the other hand₂) Since the pKa of (a) is about 3.4 and the acidity is lower than that of nitric acid, it is thought whether or not nitrite is protonated by carbonic acid to generate nitrous acid, and the nitrous acid is vaporized and released as nitrous acid vapor if nitrite ion is a conjugate base.

However, since the oxidation number of nitrogen atoms in nitrous acid is +3 and that in nitric oxide is +2, even if a material generating nitrous acid vapor can be produced, generation of other nitrogen-based gases including nitric oxide does not immediately occur. However, nitrous acid is an unstable acid, and if nitrous acid is generated, it is considered that nitric oxide may be generated by an auto-oxidation-reduction reaction. Further, it is thought whether or not various nitrogen-based gases including nitric oxide can be obtained by changing the oxidation number of nitrogen atoms if an oxidizing agent or a reducing agent is allowed to act on the released nitrous acid vapor without relying on the auto-oxidation-reduction reaction.

Therefore, first, the present inventors synthesized nitrite ions (NO) between layers₂ ^-) The properties of the LDH (b) were examined, and it was confirmed that nitrous acid vapor was slowly released by contact with the atmosphere at normal temperature. In addition, it was also confirmed that the nitrous acid released slowly generates nitric oxide and nitrogen dioxide by an auto-oxidation-reduction reaction. Further, it was also confirmed that the purity of nitric oxide can be improved by removing nitrous acid vapor and nitrogen dioxide from the mixture after the reaction.

In addition, it has been confirmed that the nitrous acid vapor released slowly can be converted into various nitrogen-based gases (for example, nitrous oxide, nitrogen dioxide, ammonia, and the like) instead of only nitric oxide by reacting the nitrous acid vapor with an appropriate oxidizing agent and reducing agent. That is, the present inventors have found that a slow-release agent which slowly releases various nitrogen-based gases can be obtained by 2-stage reactions by forming a complex system by reacting an oxidizing agent or a reducing agent with a material which slowly releases nitrous acid vapor by reacting with carbon dioxide and/or water in the atmosphere, and have completed the present invention by solving the above-mentioned problems with the slow-release agent.

On the other hand, as the properties of LDHs, it has been reported that if mixed with a solid salt, an anion exchange reaction may proceed between a solid phase and a solid phase, and anions derived from the solid salt are inserted between the layers of the LDH, whereby the anions between the layers of the LDH are released to the outside of the LDH (non-patent document 3). As a specific example, if LDH having nitrate anions between layers is mixed with KBr, a solid-phase-solid-phase anion exchange reaction proceeds, Br^-Intercalated between the layers of the LDH and nitrate anions between the layers of the LDH are released into the KBr phase outside the LDH. It has been reported that this solid-phase anion exchange reaction is accelerated by the increase in relative humidity in the atmosphere of the mixed working, which can be considered as anion exchange in response to water vapor.

If the LDH including the anion species of the nitrogen-based gas source releases the anion species by the solid-phase-solid-phase anion exchange reaction as described above, and the anion species is converted into a nitrogen-based gas by contact with a reactive agent (e.g., an oxidizing agent, a reducing agent) other than the LDH, it is possible to design a mixed material that sustains the release of the nitrogen-based gas by contact with a gas containing water vapor. It is also expected that the concentration and time of sustained release can be controlled by adjusting the amount of water vapor contained in the gas to be contacted with the mixed material.

Actually, the present inventors synthesized LDH having nitrite ions and/or nitrate ions between layers, mixed it with a reducing agent containing iron (II) sulfate as a solid salt, and brought it into contact with a gas containing water vapor, and as a result, they confirmed that various nitrogen-based gases including nitrogen monoxide were produced. Iron (II) sulfate used as solid salt is a sulfate anion (SO) having high affinity for LDH₄ ^2-) And 2-valent iron ion (Fe)²⁺) And functions as a reducing agent.

The nitrogen-based gas release agent of the present invention has a property of releasing a nitrogen-based gas by reacting with carbon dioxide and water vapor also contained in the atmosphere, and therefore, for the purpose of blocking contact with the atmosphere before use, it is preferably provided as a package hermetically housed in a packaging material. Further, for the purpose of suppressing the release of the nitrogen-based gas in the packaging material, it is more preferable that no void or vacuum be formed or an inert gas atmosphere or a dry atmosphere be formed in the packaging material by reduced pressure sealing. The void-free state means a state in which the packaging material is soft and the volume inside the packaging material is reduced to half or less of the original volume by decompression sealing. On the other hand, the vacuum is a state in which the packaging material is rigid and the pressure inside the packaging material is reduced to half or less of the atmospheric pressure by reduced pressure sealing.

Based on the above, the inventors have conceived the following invention.

The sustained-release agent for sustained-release of a nitrogen-based gas of the present invention contains nitrite ions (NO) included between layers₂ ^-) And/or nitrate ion (NO)₃ ^-) Thereby solving the above problems.

The nitrogen-containing gas may be selected from the group consisting of nitric oxide gas (NO) and nitrous acid vapor (HNO)₂) Nitrogen dioxide gas (NO)₂) Nitrous oxide gas (N)₂O) and ammonia (NH)₃) At least 1 gas of the group.

The layered double hydroxide can be represented by the following general formula (1).

Q_xR(OH)_2(x+1){(NO₂ ^-)_d(NO₃ ^-)_gZ_j}·nH ₂O···(1)

In the formula (1), Q is a metal ion having a valence of 2, R is a metal ion having a valence of 3, and Z is NO₂ ^-And NO₃ ^-Other anions. Further, x, d, g and j in the formula (1) are numbers satisfying 1.8. ltoreq. x.ltoreq.4.2, 0.01. ltoreq. d + g.ltoreq.2.0, 0. ltoreq. j.ltoreq.1.0, respectively, and n is a number varying depending on the humidity of the environment.

In the general formula (1), Q may be selected from the group consisting of Mg²⁺、Mn²⁺、Fe²⁺、Co²⁺、Ni²⁺、Cu²⁺、Zn²⁺And Ca²⁺R may be one or more selected from the group consisting of Al³⁺、Ga³⁺、Cr³⁺、Mn³⁺、Fe³⁺、Co³⁺And Ni³⁺Composition ofMore than one of the group (b).

In the general formula (1), Q may be Mg²⁺R may be Al³⁺。

The sustained-release agent can constitute a sustained-release body of a nitrogen-based gas.

The sustained-release body may further contain a solid reducing agent or a solid oxidizing agent.

In the sustained-release body, the sustained-release agent is mixed with the solid reducing agent or the solid oxidizing agent.

The solid reducing agent may contain at least 2-valent iron ions or 2-valent tin ions.

The solid reducing agent may be at least one selected from the group consisting of iron (II) sulfate, tin (II) chloride, and zinc.

The solid reducing agent or the solid oxidizing agent may be mixed in an amount of 10 mass% to 10000 mass% with respect to the layered double hydroxide.

The method of the present invention for sustained release of a nitrogen-based gas uses a sustained release body for sustained release of a nitrogen-based gas, and uses a sustained release agent containing a nitrite ion (NO) included between layers as the sustained release body₂ ^-) And/or nitrate ion (NO)₃ ^-) Thereby solving the above problems.

As the layered double hydroxide, at least nitrite ion (NO) is included between layers₂ ^-) And a step of bringing a gas containing carbon dioxide and/or water vapor into contact with the sustained-release body.

May further include: and a step of bringing the nitrous acid vapor obtained in the step of bringing the gas into contact with a solid reducing agent or a solid oxidizing agent.

The sustained release agent may be a mixture of the sustained release agent and a solid reducing agent or a solid oxidizing agent, and the method may further include a step of bringing a gas containing at least water vapor into contact with the sustained release agent.

May further comprise a step of removing impurities in the gas sustained-released by the above sustained-release body using an adsorbent.

The adsorbent may contain magnesium hydroxide or calcium hydroxide.

The medical respirator of the present invention is provided with the sustained-release body, thereby solving the above problems.

The package of the present invention comprises the sustained-release preparation and a packaging material for hermetically containing the sustained-release preparation, thereby solving the above problems.

The above-mentioned packaging material may be an atmosphere selected from the group consisting of a void-free atmosphere, a vacuum atmosphere, an inert gas atmosphere, and a dry atmosphere.

The device for slowly releasing a nitrogen-based gas according to the present invention includes an atmosphere gas supply unit for supplying an atmosphere gas, and a nitrogen-based gas slow release unit for slowly releasing a nitrogen-based gas by using the atmosphere gas supplied from the atmosphere gas supply unit, wherein the nitrogen-based gas slow release unit includes a nitrogen-based gas slow release body formed of a slow release agent for slowly releasing a nitrogen-based gas, and the slow release agent contains a nitrite ion (NO) included between layers₂ ^-) And/or nitrate ion (NO)₃ ^-) Thereby solving the above problems.

The nitrogen-based gas slow-release part may further include an impurity removal part for removing impurities in the nitrogen-based gas that is slowly released from the nitrogen-based gas slow-release part.

The sustained release body may further contain a solid reducing agent or a solid oxidizing agent, and the solid reducing agent or the solid oxidizing agent may be mixed with the sustained release agent.

The atmosphere gas supply unit may supply a gas containing at least water vapor.

The sustained-release body may further include a solid reducing agent or a solid oxidizing agent downstream of the sustained-release agent.

The atmosphere gas supply unit may supply a gas containing at least water vapor or carbon dioxide.

The nitrogen-based gas may be nitric oxide.

Effects of the invention

The nitrogen series gas slow release agent of the inventionContaining nitrite ions (NO) between layers₂ ^-) And/or nitrate ion (NO)₃ ^-) Thereby slowly releasing the nitrogen-based gas. The layered double hydroxide having the specific anion included between the layers has a characteristic of releasing a plurality of nitrogen-based gases slowly at normal temperature in the atmosphere. Further, such a layered double hydroxide is not deliquescent and is excellent in safety, and therefore is easy to handle. The packaging material which is obtained by hermetically containing the nitrogen-based gas sustained release material composed of the sustained release agent in a packaging material has excellent long-term storage stability and stability. By using such a sustained-release material or a package, a medical respirator can be provided.

The method for sustained release of a nitrogen-based gas of the present invention uses the above-described sustained release agent, and when it is used, it is only necessary to contact a gas containing carbon dioxide and/or water vapor, and therefore, it is simple and convenient. In addition, since a chemical reaction using a hazardous reagent is not required, safety is excellent.

The device for slowly releasing a nitrogen-based gas of the present invention includes an atmospheric gas supply unit and a nitrogen-based gas slow release unit, wherein the nitrogen-based gas slow release unit includes a slow release body of a nitrogen-based gas composed of a slow release agent for slowly releasing a nitrogen-based gas, and the slow release agent contains nitrite ions (NO) included between layers₂ ^-) And/or nitrate ion (NO)₃ ^-) The layered double hydroxide of (1). The slow release device can replace a gas cylinder. Further, the sustained-release device of the present invention can release a nitrogen-based gas slowly without using a power source such as a battery, and therefore, can be miniaturized, carried, and stored for a long period of time.

Drawings

FIG. 1 is a schematic diagram showing the structure of a layered double hydroxide having anions included between layers.

FIG. 2 is a schematic diagram showing an example of a scheme for synthesizing an LDH containing nitrite ions from a carbonic acid type LDH by using a decarbonation method and an ion exchange method.

FIG. 3 is a schematic diagram showing a mechanism of releasing nitrogen-based gas from a nitrogen-based gas release agent using a nitrogen-based gas release agent containing LDH as a main component, which is used alone.

FIG. 4 is a schematic view showing a mechanism of releasing nitrogen-based gas from a nitrogen-based gas release agent comprising an LDH containing nitrite ions as a main component and a reducing agent directly mixed therewith.

FIG. 5 is a schematic view showing a package of the present invention.

FIG. 6 is a schematic view showing a slow release device for slowly releasing a nitrogen-based gas.

FIG. 7 is a schematic view showing the apparatus and experimental system used in example 1.

FIG. 8 is a graph showing the change in Griess reagent and the change in absorption spectrum before and after aeration in example 1.

FIG. 9 is a schematic view showing the apparatus and experimental system used in example 2.

FIG. 10 is a schematic view showing the apparatus and experimental system used in example 3.

FIG. 11 is a schematic view showing the apparatus and experimental system used in example 4.

FIG. 12 is a schematic view showing the apparatus and experimental system used in example 5.

FIG. 13 is a schematic view showing the apparatus and experimental system used in example 6.

FIG. 14 is a graph showing the temporal change in concentration of nitric oxide released in example 6.

Fig. 15 is a graph showing a Thermogravimetry (TG) · Differential Thermal (DTA) curve (fig. 15a) and an infrared absorption spectrum (fig. 15b) for the LDH containing nitrite ions before and after the exhalation contact in example 6, and powder X-ray diffraction curves (fig. 15c) for the LDH containing nitrite ions, the carbonic acid-type LDH used in example 1, and the LDH containing Cl, respectively.

FIG. 16 is a schematic view showing the apparatus and experimental system used in example 7.

FIG. 17 is a schematic view showing an apparatus and an experimental system used in example 8.

FIG. 18 is a graph showing the relationship between the number of connected glass containers and Pasteur (Pasteur) columns 1110 and the concentration of nitric oxide released in examples 7 and 8.

FIG. 19 is a schematic view showing an apparatus and an experimental system used in example 9.

Fig. 20 is a diagram showing the state of the mixture before and after the nitrogen-based gas release experiment in the plastic syringe 1920 in example 9.

FIG. 21 is a graph showing the temporal change in concentration of nitric oxide released in example 9.

FIG. 22 is a graph showing the temporal change in concentration of nitric oxide released in example 10.

Fig. 23 shows a diagram of an XRD pattern of the mixture after the release experiment in example 10.

Fig. 24 is a diagram showing a medical respirator according to example 11.

FIG. 25 is a schematic view showing the apparatus and experimental system used in example 12.

FIG. 26 is a graph showing the temporal change in concentration of nitric oxide released in example 13.

FIG. 27 is a schematic view showing the apparatus and experimental system used in example 14.

FIG. 28 is a schematic view showing the apparatus and experimental system used in example 15.

[ FIG. 29 ]]An infrared absorption spectrum (FIG. 29a) of the released nitrogen-based gas, a temporal change in the concentration of nitrous oxide in the gas (FIG. 29b), and 2237cm in the concentration of nitrous oxide in the gas and the infrared absorption spectrum in example 15 are shown, respectively^-1FIG. 29c shows the relationship between absorbance values of (A) and (B).

FIG. 30 is a schematic view showing the apparatus and experimental system used in example 16.

FIG. 31 is a graph showing the temporal change in the concentration of nitric oxide released in example 16.

FIG. 32 is a schematic view showing an apparatus and an experimental system used in example 17.

Detailed Description

Hereinafter, the nitrogen-based gas sustained-release agent according to the aspects of the present invention, the nitrogen-based gas sustained-release material composed of the same, the package using the sustained-release material, the method for sustained release of a nitrogen-based gas, the respirator, and the sustained-release device (hereinafter, each aspect may be referred to as "first aspect" or the like) will be described with reference to the drawings.

(first aspect)

The nitrogen-based gas sustained-release agent and the method for producing the same according to the first aspect of the present invention will be described.

The nitrogen-based gas release agent of the first aspect uses, as an essential component, a Layered Double Hydroxide (LDH) in which nitrite ions and/or nitrate ions are included between layers.

Fig. 1 is a schematic diagram showing the structure of a Layered Double Hydroxide (LDH) including anions between layers.

The Layered Double Hydroxide (LDH)100 is composed of layers 110 with anions 120 included between the layers. Layer 110 is a metal hydroxide layer having a positive charge. The anion 120 contains at least nitrite ion and/or nitrate ion. The anions 120 may all be nitrite ions (NO)₂ ^-) All of them may be nitrate ions (NO)₃ ^-) Both may coexist. Furthermore, the anion 120 may comprise other anions in addition to nitrite ions and/or nitrate ions. From such a viewpoint, the layered double hydroxide 100 is hereinafter referred to as "nitrite ion/nitrate ion-containing LDH".

In the present specification, a layered double hydroxide in which the anion 120 contains at least a nitrate ion is sometimes referred to as "nitrate ion-containing LDH", and a layered double hydroxide in which the anion 120 contains at least a nitrite ion is sometimes referred to as "nitrite ion-containing LDH".

As described above, unlike many other inorganic layered compounds, LDH is a small number of inorganic compounds capable of including anions 120 between layers 110 because the layers 110 have positive charges. Due to this characteristic, the LDH is considered to include nitrite ions and nitrate ions as anions 120 between the layers 110.

The nitrite ion/nitrate ion-containing LDH100 is preferably represented by the following general formula (1).

Q_xR(OH)_2(x+1){(NO₂ ^-)_d(NO₃ ^-)_gZ_j}·nH₂O···(1)

In the formula (1), Q is a metal ion having a valence of 2, R is a metal ion having a valence of 3, and Z is an anion other than nitrite ion and nitrate ion. Further, x, d, g and j in the formula (1) are numbers satisfying 1.8. ltoreq. x.ltoreq.4.2, 0.01. ltoreq. d + g.ltoreq.2.0, 0. ltoreq. j.ltoreq.1.0, respectively, and n is a number varying depending on the humidity of the environment. nH₂O is called interlayer water, and is not limited to anion species { (NO)₂ ^-)_d(NO₃ ^-)_gZ_jAnd the same is included among LDH layers. Typically, n is 0 to 4. The range of x (1.8. ltoreq. x.ltoreq.4.2) is a value which is conventional in the case of a crystalline layered double hydroxide, and the possibility that x represents a value of less than 1.8 or more than 4.2 is not denied for a layered double hydroxide obtained by a special synthesis method in the case of a large amount of impurities, an amorphous layered double hydroxide, or the like.

"Z" in the formula (1) is derived from a raw material or a solvent used for producing the nitrite ion/nitrate ion-containing LDH100 or an anion in the atmosphere at the time of production or storage of the nitrite ion/nitrate ion-containing LDH100, and OH can be exemplified^-、Cl^-、Br^-、I^-、F^-、NO₃ ^-、ClO₄ ^-、SO₄ ^2-、CO₃ ^2-Acetate anion (CH)₃COO^-) Propionate anion (CH)₃CH₂COO^-) Lactate anion (CH)₃-CH(OH)-COO^-) And isethionate anion (HOC)₂H₄SO₃ ^-) And the like.

In the nitrite ion/nitrate ion-containing LDH100 represented by the general formula (1), Q is preferably selected from the group consisting of Mg²⁺、Mn²⁺、Fe²⁺、Co²⁺、Ni²⁺、Cu²⁺、Zn²⁺And Ca²⁺One of the groupMore than one, more preferably Mg²⁺. Further, R is preferably selected from the group consisting of Al³⁺、Ga³⁺、Cr³⁺、Mn³⁺、Fe³⁺、Co³⁺And Ni³⁺More preferably Al³⁺。

Layered double hydroxides of MgAl type, which are the most common solid materials among layered double hydroxides and have Mg and Al as constituent elements, have been industrially produced (for example, synthetic hydrotalcite for harmonizing chemical industry) because they can be synthesized at low cost.

Safety is not at all problematic even when it adheres to the skin, and it is also used for gastrointestinal drugs (antacids) and the like. Further, studies from a medical point of view have been conducted as carriers of Drug Delivery Systems (DDS), and there have been practical results in medical applications. Therefore, the above-mentioned Q is Mg having MgAl type layered double hydroxide as a basic structure^{2 +}R is Al³⁺The nitrite ion/nitrate ion-containing LDH of (a) is considered to be particularly excellent in safety even when used for medical purposes.

The total amount of the nitrogen-based gas that is slowly released by the nitrogen-based gas slow-release agent is substantially proportional to the ratio of nitrite ions and/or nitrate ions in the interlayer anion sites (values of d and g in the general formula (1)) in the nitrite ion/nitrate ion-containing LDH 100. This ratio can be adjusted by changing the ratio: the ratio of the number of moles of nitrite ions and/or nitrate ions in a solution in contact with a raw material LDH used in the production of the nitrite ion/nitrate ion-containing LDH100 or an LDH (easily anion-exchangeable LDH) derived from the raw material and having an anion that is easily exchanged. When the above ratio or ratio is small, a part of the anion component contained in the raw material LDH or the easily anion-exchangeable LDH remains between the layers of the nitrite ion/nitrate ion-containing LDH 100.

By adjusting the composition of the LDH, the slow release concentration and the slow release time of the nitrogen-containing gas can be controlled. The composition of the LDH can be adjusted by changing Q, R, Z, x, d, g, j in formula (1), and furthermore, all the compositions of LDHs that can be generally thought by those skilled in the art can be applied.

The nitrogen-based gas release agent of the first aspect contains the above-mentioned nitrite ion/nitrate ion-containing LDH100 as an essential component, but may contain various additives such as a component for adjusting the release concentration and speed, a diluent, a surface coating agent, and a component for reacting with a nitrogen-based gas to generate another compound, in addition to the above-mentioned components, within a range in which the object of the present invention can be achieved. Further, the nitrogen-containing gas slow-release body according to the second aspect described below may be formed by physical processing such as packaging with a ventilation-restricted wrapping tape.

Next, a method for producing the nitrogen-based gas sustained-release agent of the first aspect described above will be described. The nitrogen-based gas sustained-release agent of the first aspect can be obtained by synthesizing LDH100 containing nitrite ions/nitrate ions by the following method.

In the synthesis of LDH containing nitrite ions/nitrate ions, 3 synthesis methods, i.e., an ion exchange method, a reconstitution method, and a coprecipitation method, are mainly applied. These syntheses are described in detail below. Needless to say, a synthesis method of LDH other than these main synthesis methods (for example, a special synthesis method in which a solution containing a predetermined anion is added to a swollen or nanoshelated LDH to cause agglomeration thereof) may also be applied. As will be described later, in the synthesis of LDHs, ripening is often performed to improve crystallinity, but "LDH-like" compounds having low crystallinity, such as those which are not sufficiently cured, are also included in LDHs containing nitrite ions/nitrate ions referred to in this specification, as long as diffraction corresponding to the basal plane spacing (layer-to-layer spacing) is detected in powder X-ray structural analysis and nitrite ions and/or nitrate ions are contained as a nitrogen-based gas source.

[ ion exchange method ]

Here, among the nitrite ion/nitrate ion-containing LDHs, a method for synthesizing the nitrite ion-containing LDH is described in detail. The method for synthesizing the nitrite ion-containing LDH using the ion exchange method includes: preparing a layered double hydroxide having a layer containing 1-valent anion other than nitrite and a solvent; preparing a solution by allowing the solvent to contain nitrite ions; contacting a layered double hydroxide having 1-valent anions other than nitrite ions included between layers with the solution; the solid material of the LDH containing nitrite ions synthesized by this contact is separated from the solution, washed and dried.

The layered double hydroxide (hereinafter, referred to as "raw material LDH") used as the starting material and having 1-valent anions other than nitrite ions included between layers is not limited as long as the anions can be desorbed by ion exchange or the like. Examples thereof include those represented by the following general formula (1)'.

Q_xR(OH)_2(x+1){(CO₃ ^2-)_0.5-a/2(X)_a}·nH₂O···(1)’

In the formula (1)', Q is a metal ion having a valence of 2, R is a metal ion having a valence of 3, and X is selected from the group consisting of chloride (Cl)^-) Bromine ion (Br)^-) Nitrate ion (NO)₃ ^-) Perchlorate ion (ClO)₄ ^-) Chlorate ion (ClO)₃ ^-) Acetate anion (CH)₃COO^-) Propionate anion (CH)₃CH₂COO^-) Lactate anion (CH)₃-CH(OH)-COO^-) And isethionate anion (HOC)₂H₄SO₃ ^-) One or more kinds of anions having high plasma exchange property. Further, x and a in the formula (1)' are numbers satisfying 1.8. ltoreq. x.ltoreq.4.2, 0. ltoreq. a.ltoreq.1, respectively, and n is a number varying depending on the humidity of the environment.

The solvent used is not limited as long as it can dissolve a substance that generates nitrite ions (nitrite ion source), can stably disperse the generated nitrite ions, and can supply nitrite ions to the interlayer of the raw material LDH. Examples thereof include ion-exchanged water, methanol, and ethanol. In order to ensure the improvement in quality and the constancy of quality of the contained nitrite ion and the produced nitrite ion-containing LDH, it is preferable that these solvents have their dissolved oxygen and carbon dioxide concentrations reduced by bubbling nitrogen gas or a rare gas before the nitrite ion is contained, or by heating or the like in the case of water. In each synthesis method described later, it is preferable to use a solvent such as ion-exchanged water used for the reaction, which is treated similarly.

The nitrite ion is contained in the solvent by adding a substance (nitrite ion source) which is dissolved in the solvent and generates nitrite ions. The above operation is preferably performed in an inert atmosphere from the viewpoint of ensuring the quality improvement and quality constancy of the nitrite ions in the solvent and the generated nitrite ion-containing LDH. As a method for performing the operation under an inert atmosphere, a glove box filled with an inert gas is used. Further, by a method using a vacuum line or schlenk tube without using a glove box or the like, it is also possible to perform an operation of containing nitrite ions in a solvent under an inert atmosphere. In the respective operations described later, the operations performed in the inert gas atmosphere can be performed in the same manner as described above, and therefore, the description of the atmosphere will be omitted hereinafter.

The source of nitrite ions to be added to the solvent is not limited as long as nitrite ions are released in the solvent, and typical examples thereof include those represented by the following general formula (2).

MH_p(NO₂)_q·mH₂O···(2)

In the formula (2), M is an alkali metal or an alkaline earth metal. However, the alkaline earth metal referred to herein also contains Mg. In the formula (2), p is 0 or 1, q is 1 or 2, and m is a number that varies depending on the method for producing the reagent and the humidity of the environment. An example of the source of nitrite ions represented by formula (2) is sodium nitrite (NaNO)₂)。

The method of contacting the raw LDH with the solution containing nitrite ions is not limited as long as both are sufficiently contacted and nitrite ions are supplied between the layers of the raw LDH. Examples are: injecting said solution into a vessel containing said starting LDH; charging the raw material LDH into a container containing the solution; the raw material LDH and the like are continuously fed into a flow path through which the solution flows. When the two are brought into contact in the vessel, it is preferable to stir the mixture in the vessel in order to promote the interlaminar supply of nitrite ions to the raw material LDH.

As the starting material LDH, a starting material having a small a value in the above general formula (1)' is used (exemplified in the range of 0. ltoreq. a.ltoreq.0.4), that is, carbonate ions (CO) in anions between layers₃ ^2-) In the case of a raw material having a large proportion (hereinafter referred to as "carbonic acid type LDH"), carbonate ions are less likely to be desorbed from the interlayer, and therefore, it is preferable to remove at least a part of the carbonate ions from the interlayer by the following treatment before contacting with the solvent.

The method for removing carbonate ions from between layers is as follows: the carbonic acid type LDH is reacted with an alcohol containing 1-valent anion (Cl) by the method described in Japanese patent No. 5867831^-、NO₃ ^-Etc.) to convert them into LDH (decarbonation) which is easily anion-exchanged with the anions taken into the interlayer. The LDH easily exchangeable for anions obtained by the treatment is brought into contact with a solution containing nitrite ions (ion exchange), thereby exchanging the LDH for other anions in a solvent. As described above, the nitrite ion-containing LDH can be synthesized by the above-described decarbonation method using a carbonate-type LDH as a starting material.

Fig. 2 is a schematic diagram showing an example of a scheme for synthesizing a nitrite ion-containing LDH from a carbonic LDH using a decarbonation method and an ion exchange method.

In the figure, (a) shows a reaction of producing an anion-exchange-susceptible LDH from a carbonic acid type LDH, and (b) shows a reaction of producing a nitrite ion-containing LDH from the anion-exchange-susceptible LDH. In the figure, an LDH (Cl type LDH) in which chloride ions are included between layers is shown as an LDH easily exchangeable for anions, but the same reaction occurs when another LDH easily exchangeable for anions is used. In the figure, (a) is also a reaction used when directly synthesizing nitrate ion-containing LDH from carbonic acid type LDH. The anion-exchange-susceptible LDH obtained by completely removing (decarbonating) carbonate ions from a carbonated LDH is represented by the following general formula (3).

Q_xR(OH)_2(x+1)X·nH₂O···(3)

In the formula (3), Q is a metal ion with a valence of 2, R is a metal ion with a valence of 3, and X is an anion with a valence of 1. In addition, x in the formula (3) is a number satisfying 1.8. ltoreq. x.ltoreq.4.2, and n is a number varying depending on the humidity of the environment.

By bringing the thus obtained LDH susceptible to anion exchange into contact with a solvent containing nitrite ions, the anions between the layers are exchanged for nitrite as shown in fig. 2 (b), and an LDH containing nitrite ions is obtained. In the case where the anion-exchange susceptible LDH is a nitrate ion-containing LDH and a part of the nitrate ions is exchanged for nitrite ions by the reaction shown in fig. 2 (b), an LDH including nitrite ions and nitrate ions between layers is obtained.

Note that nitrous acid (HNO)₂) Is also an acidic compound, so if HNO can be applied at the reaction stage shown in FIG. 2 (a)₂It is possible to ion-exchange the carbonate ions of the carbonic LDH into nitrite ions in one step, to convert into an LDH containing nitrite ions.

The above shows a method for synthesizing LDH containing nitrite ions/nitrate ions, such as nitrite ions and/or nitrate ions, by "ion exchange" for introducing the nitrite ions/nitrate ions between the layers.

[ reconstitution method ]

When a carbonic acid type LDH is used as the raw material LDH, a "restructuring method" may be employed in addition to the decarbonation method described above. This is a method in which a carbonic acid type LDH is heated at 400 to 600 ℃ to break the layered structure, decarbonated, and then contacted with a solution containing anions to be included (here, nitrite ions and/or nitrate ions) to age the solution. Since anions in the solvent are introduced into the interlayer while the layered structure is reconstituted by contact with the solution, an LDH containing nitrite ions/nitrate ions can be obtained. The term "aging" means that the reaction solution is left to stand or is kept at room temperature for a suitable period of time while being stirred. In the synthesis of LDH, the temperature and time for aging are often increased in order to improve the crystallinity of the product.

[ coprecipitation method ]

Further, as a method for synthesizing the nitrite ion/nitrate ion-containing LDH, a method may be employed in which an aqueous solution containing a plurality of metal ions forming a cation layer is mixed with an alkaline aqueous solution containing nitrite ions and/or nitrate ions, and the resulting precipitate or precipitate is aged. This is called "coprecipitation method", and is a method utilizing a phenomenon that an anion component in an alkaline aqueous solution used when constructing an LDH structure by coprecipitation and aging is included between layers, and is widely performed as a method for synthesizing LDH. In the coprecipitation method, the temperature and time for aging are often increased in order to improve the crystallinity of the product.

In any of the above-mentioned synthesis methods, it is necessary to separate the LDH containing nitrite ions/nitrate ions as a solid substance produced in the solution from the solution, and a conventional solid-liquid separation method such as filtration or centrifugal separation can be used as the separation method.

The separated solid matter is washed with a clean solvent, and the solvent is removed and dried. The clean solvent to be brought into contact with the solid substance is preferably such that the concentration of dissolved oxygen and carbon dioxide is reduced in advance by bubbling nitrogen gas or a rare gas, heating, or the like, as in the case of synthesis.

As a method for drying the washed solid matter, a conventional method such as heat drying or drying under reduced pressure can be used. From the viewpoint of suppressing deterioration of the nitrite ion/nitrate ion-containing LDH, drying under reduced pressure is preferable.

The obtained nitrite ion/nitrate ion-containing LDH may be mixed with various additives such as a component for adjusting the sustained-release concentration and rate, a diluent, a surface coating agent, a dehydrating agent, a decarbonating agent, a deoxidizer, and a component for generating other compounds by reacting with a nitrogen-based gas, if necessary.

In this way, the nitrogen-based gas release agent of the first aspect can be obtained. The sustained-release agent can be used alone to form a nitrogen-based gas sustained-release body as described later (first embodiment of the second aspect). As described later, the nitrogen-based gas slow-releasing agent obtained may be spatially separated from the reducing agent (or oxidizing agent) so as not to be in direct contact therewith, thereby forming a nitrogen-based gas slow-releasing body (second aspect of the second aspect).

Further, as described later, the nitrogen-based gas release agent obtained may be directly mixed with a reducing agent (or an oxidizing agent) to form a nitrogen-based gas release body (third aspect of the second aspect).

(second aspect)

The nitrogen-based gas sustained-release agent of the first aspect can be produced as a powder or an aggregate of granules thereof, or can be physically processed by packaging with a ventilation-restricted bag or the like, or can be combined with other components or constituent elements. Examples of such a sustained-release body include 3 types of modes, namely, a mode in which the nitrogen-based gas sustained-release agent of the first aspect is used alone as an active ingredient (first mode), a mode in which the sustained-release agent and a reducing agent spatially separated from and juxtaposed with the sustained-release agent are provided (second mode), and a mode in which the sustained-release agent and a reducing agent directly mixed therewith are provided (third mode). In the embodiment using the reducing agent, it is preferable to use the reducing agent in a solid state from the viewpoint of facilitating handling at the time of production or at the time of use. Further, an oxidizing agent may be used instead of the reducing agent, depending on the kind of the nitrogen-based gas to be slowly released.

As an example of the reducing agent, inorganic salts or inorganic compounds containing 2-valent iron ions, 2-valent tin ions, 1-valent copper ions, 2-valent cobalt ions, and the like, metals such as zinc, magnesium, and the like, organic substances such as sulfamic acid, hydroquinone, ascorbic acid, and the like, organic metals, enzymes, reduction electrodes, and the like can be given. For example, by reacting withIron (II) sulfate, tin (II) chloride, zinc or sulfamic acid of the raw agent reacts, thereby slowly releasing nitrous acid (HNO) from LDH100 containing nitrite ions/nitrate ions₂) Respectively converted into Nitric Oxide (NO) and dinitrogen monoxide (N)₂O), ammonia (NH)₃) Or nitrogen (N)₂)。

In particular, for the purpose of releasing nitric oxide as a nitrogen-based gas, a reducing agent containing at least 2-valent iron ions is preferable, and a reducing agent containing at least iron (II) sulfate is more preferable.

Illustrative examples of the oxidizing agent include hexavalent chromium and oxygen (O)₂) And the like. For example, nitrous acid (HNO) can be reacted with hexavalent chromium as an oxidizing agent₂) Conversion to nitrogen dioxide (NO)₂)。

The reducing agent (or oxidizing agent) may be supported on a solid inorganic material such as zeolite, silica gel, or activated carbon.

The amount of such a reducing agent (or oxidizing agent) is not particularly limited, and the reducing agent (or oxidizing agent) preferably satisfies 10 mass% or more and 10000 mass% or less with respect to the nitrite ion/nitrate ion-containing LDH 100. The reducing agent (or oxidizing agent) more preferably satisfies 100 mass% or more and 1700 mass% or less with respect to the nitrite ion/nitrate ion-containing LDH 100. For example, if the reducing agent (or oxidizing agent) is set to a small amount (for example, 300 mass% or less), the sustained-release concentration can be suppressed, and extension of the sustained-release time can be expected. If the mass range is within the above range, a desired sustained-release concentration and sustained-release time can be achieved.

In the nitrogen-based gas sustained-release product obtained by directly mixing the nitrogen-based gas sustained-release agent and the reducing agent (or the oxidizing agent), the nitrogen-based gas sustained-release agent and the reducing agent (or the oxidizing agent) are preferably made into a powder form. This accelerates the reaction and increases the concentration of the nitrogen-containing gas that is slowly released.

When a powdery nitrogen-based gas release agent and a reducing agent (or oxidizing agent) are used, the contact area can be controlled by appropriately selecting the particle size of these powders. If the contact area is small, the sustained-release concentration can be suppressed, and the sustained-release time can be prolonged. On the contrary, if the contact area is large, the sustained-release concentration can be increased. For example, the particle size of the nitrogen-based gas release agent may be adjusted to a range of 0.5 μm to 500 μm, and the particle size of the reducing agent (or oxidizing agent) may be adjusted to a range of 0.5 μm to 2000 μm. In the case of LDH, since the crystals are plate-like crystals that grow on a plane perpendicular to the stacking direction (vertical direction in the paper plane in fig. 1), the particle diameter of the nitrogen-based gas release agent containing the crystals as a main component is defined as the median of the equivalent circle diameter or Feret diameter on the plate-like plane in each particle (crystal). The particle size is an average value measured from an observation image by an electron microscope such as a Scanning Electron Microscope (SEM).

Further, as the LDH100 containing nitrite ions/nitrate ions as the main component of the nitrogen-based gas release agent, an LDH having reducibility (for example, an LDH containing 2-valent iron ions as Q in formula (1)) may be used. In this case, by using the nitrogen-based gas release agent alone as the nitrogen-based gas release agent (first aspect), the same nitrogen-based gas as the nitrogen-based gas release agent (third aspect) in which the nitrite ion/nitrate ion-containing LDH100 and the reducing agent (or the oxidizing agent) are directly mixed can be released.

The following will describe the 3 types of sustained-release substances in detail together with the mechanism of release and sustained-release of the nitrogen-based gas.

[ nitrogen-based gas release agent of the first embodiment: nitrogen-based gas-releasing body using separately nitrite ion/nitrate ion-containing LDH ]

Fig. 3 is a schematic diagram showing a mechanism of slow release of nitrogen-based gas from a nitrite ion-containing LDH that is one of nitrite ion/nitrate ion-containing LDHs.

Referring to fig. 3, a nitrogen-based gas sustained-release material using a nitrogen-based gas sustained-release agent containing LDH200 containing nitrite ions as a main component alone will be described as a nitrogen-based gas sustained-release material of a first embodiment. Nitrite ion-containing LDH200 is brought into contact with the atmosphere containing carbon dioxide and/or water vapor as described later to generate nitrous acid (HNO) as a weak acid₂). Nitrous acid can be vaporized as nitrous acid vapor. Nitrous acid is an unstable compound which undergoes an auto-redox reaction to form nitric oxide with the passage of timeNitrogen and nitrogen dioxide. Therefore, the nitrite ion-containing LDH200 alone can be a nitrogen-based gas releasing agent. The nitrogen-based gas at this time forms nitrous acid vapor, nitric oxide and nitrogen dioxide. Further, when the behavior of releasing the nitrogen-based gas satisfies the definition of "sustained release" described later, the nitrite ion-containing LDH alone forms a nitrogen-based gas sustained release agent.

The reason why the nitrite ion-containing LDH is used as the nitrogen-based gas releasing agent, which is a constituent of the solid material for releasing the nitrogen-based gas, is considered that the nitrite ion-containing LDH can release the nitrogen-based gas through nitrous acid generated by the following mechanism of action. This reaction is illustrated by using a chemical formula.

As described in Japanese patent application No. 2018-132081, the conjugate base of a weak acid included between the layers of an LDH is carbonic acid (H) generated by the reaction of carbon dioxide in the atmosphere with water between the layers₂CO₃) And is protonated to form weak acid molecules, which may be released into the atmosphere if the molecules are volatile. Nitrite ion (NO)₂ ^-) Is nitrous acid (HNO) as a weak acid₂) In the case where the LDH containing nitrite ions is left in the atmosphere, it is considered that, based on the equilibrium theory, nitrous acid is generated between LDH layers, which is released into the atmosphere as vapor. The chemical reaction at this time is represented by the following formula (4).

CO₂+H₂O+2NO₂ ^-→2HNO₂↑+CO₃ ^2-···(4)

This series of reactions can be considered as "solid-gas phase anion exchange reactions", and as shown in FIG. 3, it is considered that carbon dioxide in the atmosphere enters the interlayers of the LDH containing nitrite ions and reacts with interlayer water to produce protons H⁺And carbonate ions, the resulting carbonate ions being anion-exchanged with interlayer nitrite ions while H is present⁺Combines with nitrite ions to form nitrous acid, a portion of which is released to the atmosphere as vapor.

The interlayer water (H) reacted in the formula (4)₂O) water previously contained in the LDH may be used, and in addition, water vapor contained in the atmosphere may be used for supply. When water vapor contained in the atmosphere is used, the supplied gas contains carbon dioxide and water vapor according to equation (4). On the other hand, when the water reacted in the formula (4) is interlayer water, the formula (4) is performed by supplying a gas containing at least carbon dioxide, and nitrite vapor is released from the LDH containing nitrite ions.

Further, as a mechanism of releasing nitrous acid vapor which was not expected at first, the existence of the reaction pathway shown by the formula (4)' is shown by example 17 described later. In the case where the supplied gas contains a large amount of water vapor, the reaction shown by the formula (4)' proceeds with little but no effect on the equilibrium theory, resulting in the release of nitrous acid vapor and hydroxide ions (OH)^-) Residues between LDH layers. In the formula (4)', water molecules function as an acid as a proton supply source, and carbon dioxide is not required for the release of nitrous acid vapor. Therefore, in the mechanism for releasing nitrous acid vapor based on the formula (4)', by supplying a gas containing at least water vapor to the LDH containing nitrous acid, nitrous acid vapor can be released even in a trace amount. However, since the acidity (pKa 14.0) of water is lower than that of nitrous acid, the equilibrium of nitrous acid generation in the formula (4) 'is greatly biased toward the reactant side (i.e., the left side of the formula (4)'), and the amount of nitrous acid generated is not large. In addition, if the OH as a reaction product of the formula (4)' is OH^-The type LDH is contacted with a gas containing carbon dioxide, then passes through 2 molecular OH^-Reacts with 1 molecule of carbon dioxide to generate 1 molecule of carbonate ions and 1 molecule of water, and the carbonate ions are remained between LDH layers.

H₂O+2NO₂ ^-→2HNO₂↑+2OH^-···(4)’

The reactions of the above-mentioned formulae (4) and (4)' require diffusion processes such as intrusion of gas into and desorption of gas from the interlayer, and thus can be understood as sustained release of nitrous acid vapor for a long period of time.

Further, nitrous acid is decomposed into one by autoredox reaction represented by formula (5)Nitrogen Oxide (NO) and nitrogen dioxide (NO)₂) Therefore, if nitrous acid can be generated, nitrogen monoxide and nitrogen dioxide, which are other nitrogen-based gases, may be generated.

2HNO₂→NO₂+NO+H₂O···(5)

Here, the nitrogen-based gas releasing property in the present specification means a property that a nitrogen-based gas can be detected by some qualitative or quantitative method in a nitrogen-based gas release experiment described later, and the nitrogen-based gas releasing agent means a material having a nitrogen-based gas releasing property.

On the other hand, the nitrogen-based gas slow release property in the present specification means a property that a maximum nitrogen-based gas concentration of 1/100 or more is continuously detected for 30 minutes or more or a property that a certain nitrogen-based gas concentration is detected for 30 minutes or more within a range of 25% of a fluctuation range in a nitrogen-based gas release experiment described later, and the nitrogen-based gas slow release agent means a material having a nitrogen-based gas slow release property.

In the present specification, a material having a property of releasing a plurality of nitrogen-based gases simultaneously is considered to be a release agent for each nitrogen-based gas. For example, a sustained release agent that simultaneously sustains both nitric oxide and nitrogen dioxide is a nitric oxide sustained release agent, and is also a nitrogen dioxide sustained release agent.

Through the chemical reactions represented by the above-described formulae (4) and (5), a mixed gas of nitrous acid vapor, nitric oxide, and nitrogen dioxide is generated from the nitrite ion-containing LDH200 in the atmosphere. Since nitrous acid and nitrogen dioxide are acidic gases, nitrous acid vapor and nitrogen dioxide can be removed by introducing gas into a column packed with an alkaline adsorbent, and as a result, the purity of nitrogen monoxide can be improved. Further, by bringing the mixed gas into contact with air for a certain period of time or heating the mixed gas, the auto-oxidation-reduction reaction of nitrous acid represented by formula (5) and the air oxidation of nitric oxide represented by formula (6) can be advanced, and the concentration and purity of nitrogen dioxide can be improved. Nitrogen dioxide reacts with water to produce nitric acid and nitric oxide and/or nitrous acid as in the formula (7) and/or the formula (8).

2NO+O₂→2NO₂···(6)

3NO₂+H₂O→2HNO₃+NO···(7)

2NO₂+H₂O→HNO₃+HNO₂···(8)

[ nitrogen-based gas release agent of the second embodiment: nitrogen-based gas-releasing agent in which nitrogen-based gas-releasing agent and reducing agent (or oxidizing agent) are spatially separated and juxtaposed ]

Next, as a nitrogen-based gas sustained-release body of the second embodiment, a nitrogen-based gas sustained-release body in which a nitrogen-based gas sustained-release agent and a reducing agent are spatially juxtaposed will be described. As described above, the nitrite ion-containing LDH200 (see fig. 3), which is one of nitrite ion/nitrate ion-containing LDHs, generates nitrous acid vapor by causing a "solid-phase-gas phase anion exchange reaction" with carbon dioxide and/or water in the atmosphere. The nitrous acid vapor can be converted into a desired nitrogen-based gas by reduction (or oxidation) using a suitable reducing agent (or oxidizing agent). For example, by reaction with iron (II) sulfate, tin (II) chloride, hexavalent chromium, zinc, or sulfamic acid, can be converted to Nitric Oxide (NO), nitrous oxide (N), respectively₂O), nitrogen dioxide (NO)₂) Ammonia (NH)₃) Or nitrogen (N)₂). The reducing agent (or oxidizing agent) used is preferably a solid, and more preferably free from deliquescence, from the viewpoint of convenience of handling and safety.

As described above, since the nitrite ion-containing LDH has a property of releasing nitrous acid vapor by the "solid-phase/gas-phase anion exchange reaction", it is possible to release nitrogen-based gases other than nitrous acid vapor by merely converting the released nitrous acid vapor into other nitrogen-based gases using a reducing agent (or an oxidizing agent). The nitrogen-based gas release agent according to the second embodiment is based on the idea that the nitrogen-based gas release agent exemplified by the LDH containing nitrite ions as a main component is spatially separated from the reducing agent (or oxidizing agent) and does not physically contact with the reducing agent (or oxidizing agent). The nitrous acid vapor slowly released from the nitrogen-based gas slow releasing agent reaches the reducing agent (or oxidizing agent) by diffusion or a gas flow, and is reduced (or oxidized) to be converted into a nitrogen-based gas other than nitrous acid vapor, thereby playing a role of slowly releasing a desired nitrogen-based gas. That is, the nitrogen-based gas sustained-release body described herein is a composite body composed of LDH containing nitrite ions and a reducing agent (or an oxidizing agent).

In the nitrogen-based gas sustained-release material according to the second aspect, as a method of spatially separating and juxtaposing the nitrogen-based gas sustained-release agent and the reducing agent (or the oxidizing agent), any method that can be generally considered by those skilled in the art as a method capable of controlling the diffusion of nitrous acid vapor or the progress of a chemical reaction between nitrous acid vapor and the reducing agent (or the oxidizing agent) can be used, such as: a method of disposing a nitrogen-based gas slow-release agent and a reducing agent (or an oxidizing agent) on the inlet side and the outlet side of an atmospheric gas under a flowing gas flow; a method in which a permeable membrane such as a filter is disposed between a nitrogen-based gas slow-releasing agent and a reducing agent (or an oxidizing agent); and a method of covering the nitrogen-based gas sustained-release agent with a reducing agent (or an oxidizing agent).

[ nitrogen-containing gas release agent of the third embodiment: nitrogen-containing gas sustained-release body obtained by directly mixing nitrogen-containing gas sustained-release agent and reducing agent (or oxidizing agent) ]

Fig. 4 is a schematic diagram showing a mechanism of releasing nitrogen-based gas from a nitrogen-based gas release agent including a nitrite ion-containing LDH as one of nitrite ion/nitrate ion-containing LDHs as a main component and a reducing agent directly mixed therewith.

Referring to fig. 4, a nitrogen-based gas sustained-release material 300 including a nitrogen-based gas sustained-release agent containing LDH310 containing nitrite ions as a main component and a reducing agent 320 directly mixed therewith will be described as a nitrogen-based gas sustained-release material of a third embodiment. As described above, it has been reported that LDHs, when mixed with solid salts, undergo a solid-phase anion exchange reaction to insert anions derived from the solid salts between the layers of the LDHs, while anions between the layers of the LDHs are released to the outside of the layers (non-patent document 3). Although the former example in which the "solid phase-solid phase" anion exchange reaction in the nitrite ion-containing LDH310 as shown in fig. 4 is applied as a mechanism of gas release is not given, since the anion in the LDH layer is diffused during the "solid phase-solid phase" anion exchange, it is thought that the anion exchange is performed for a certain period of time, and it is useful for realizing the release of nitrogen-based gas.

Further, it has been reported that the anion exchange reaction between the solid phase and the solid phase in LDH can be accelerated by increasing the relative humidity in the atmosphere (non-patent document 3), and it is considered that the anion exchange reaction can be performed at a freely controlled starting timing and proceeding speed by using a gas containing water vapor.

A nitrogen-based gas slow-release agent containing nitrite ion-containing LDH310 as a main component is mixed with a reducing agent 320 containing a solid salt, and brought into contact with a gas containing at least water vapor, whereby nitrogen monoxide (NO) and nitrogen dioxide (NO) can be slowly released₂) Nitrous acid vapor (HNO)₂) Dinitrogen monoxide (N)₂O) of nitrogen-based gas. Iron (II) sulfate shown as the reducing agent 320 in fig. 4 is a sulfate anion (SO) having high affinity for LDH₄ ^2-) And has 2-valent iron ion (Fe) functioning as a reducing agent²⁺) The solid salt of (4). The iron (II) sulfate coexists with the LDH310 containing nitrite ions, whereby nitric oxide can be released slowly. Therefore, the nitrogen-based gas sustained-release agent obtained by mixing the nitrogen-based gas sustained-release agent mainly composed of the nitrite ion-containing LDH310 and the reducing agent 320 containing the solid salt can be a sustained-release agent of nitric oxide. In fig. 4, iron (II) sulfate is shown as the reducing agent 320, but is not limited thereto.

The aforementioned nitric oxide release (sustained release) reaction is expressed by a chemical formula, which is specifically as follows.

[2NO₂ ^-]_LDH+4Fe^(II)SO₄+2H₂O→[SO₄ ^2-]_LDH

+Fe^(III) ₂(SO₄)₃+2Fe^(II)(OH)₂+2NO····(9)

Wherein, the [ alpha ], [ beta ] -a]_LDHIndicating the presence between the LDH layers.

As another example, a mixture of a nitrogen-based gas release agent containing nitrite ion-containing LDH310 as a main component and tin (II) chloride can function as a nitrous oxide release carrier.

On the other hand, the nitrate ion of the nitrate ion-containing LDH, which is the other of the nitrite ion/nitrate ion-containing LDH, is the conjugate base of nitric acid, which is a strong acid, and thus nitric acid is not theoretically released by direct reaction with water and carbon dioxide from equilibrium. However, the coexistence of the reducing agent containing the solid salt causes the aforementioned anion exchange reaction between the solid phase and the solid phase, and when the nitrate ions contained in the nitrate ion-containing LDH are released to the outside of the LDH, they can contact and react with the reducing agent outside the LDH to be converted into the nitrogen-based gas. Since nitrate ion-containing LDH does not release nitric acid by reaction with water and carbon dioxide, a nitrogen-based gas sustained-release agent containing the nitrate ion-containing LDH as a main component and a nitrogen-based gas sustained-release body formed from the sustained-release agent can be stably stored in the atmosphere.

Thus, in the solid-gas phase anion exchange, carbonic acid (H) is produced₂CO₃)，CO₃ ^2-Since the pKa of an acid generated from an interlayer anion is an important index for controlling the sustained-release property by exchanging with an interlayer anion, the pKa is not related to the occurrence of anion exchange between a solid phase and a solid phase, and therefore, the following characteristics are obtained: there is a possibility that a reaction process which is difficult to occur in solid-gas phase anion exchange may occur.

In order to efficiently reduce nitrate ions to nitric oxide, it is preferable to use a more powerful reducing agent than in the case of nitrite ions that can be easily reduced to nitric oxide by iron ions having a valence of 2. As such a reducing agent, for example, a reducing agent obtained by mixing iron ions having a valence of 2 with zinc powder, a reducing agent obtained by mixing iron ions having a valence of 2 with iron powder, or the like can be used, but the reducing agent for reducing nitrate ions to a desired nitrogen-based gas is not limited thereto, and any reducing agent that can be generally thought of by those skilled in the art can be used.

The reducing agent obtained by mixing iron (II) sulfate and zinc can be mixed with a nitrogen-based gas sustained-release agent containing LDH containing nitrate ions as a main component to form a nitric oxide sustained-release body. Further, the released nitric oxide is oxidized by oxygen in the air, whereby the nitrogen dioxide can be released slowly.

In this way, in the nitrogen-based gas release agent 300 according to the third embodiment, nitrite ions and/or nitrate ions released slowly by the LDH310 containing nitrite ions/nitrate ions react with the reducing agent 320 outside the LDH layer by the anion exchange reaction between the solid phase and the solid phase, and are converted into another nitrogen-based gas, whereby the nitrogen-based gas can be released slowly. Depending on the type of nitrogen-based gas to be slowly released, an oxidizing agent may be used instead of the reducing agent.

The nitrogen-based gas slow-release agent and the reducing agent (or the oxidizing agent) for obtaining the nitrogen-based gas slow-release body 300 according to the third embodiment may be mixed in advance, or may be mixed immediately before being brought into contact with a gas for slow release of the nitrogen-based gas.

When the nitrogen-based gas slow-release agent and the reducing agent (or the oxidizing agent) are mixed in advance, it is preferable to store a mixture of the nitrogen-based gas slow-release agent and the reducing agent (or the oxidizing agent) in a closed container and further to set the atmosphere in the closed container to a void-free, vacuum, inert atmosphere, or dry atmosphere for the purpose of suppressing the progress of the anion exchange reaction between the solid phase and the solid phase during the storage period.

On the other hand, in the case where the nitrogen-based gas slow-release agent and the reducing agent (or the oxidizing agent) are mixed immediately before being brought into contact with the gas for slow release of the nitrogen-based gas, it is preferable that the agent that reacts with at least carbon dioxide and/or moisture in the atmosphere is contained in a closed container, and further the atmosphere in the closed container is a void-free atmosphere, a vacuum atmosphere, an inert atmosphere, or a dry atmosphere. As a specific method of mixing, all mixing methods that can be generally thought of by those skilled in the art can be selected, such as: a method of mixing a nitrogen-based gas slow-releasing agent and a reducing agent (or an oxidizing agent) by operating a movable partition wall provided between the nitrogen-based gas slow-releasing agent and the reducing agent (or the oxidizing agent); a method of mechanically pulverizing and mixing the nitrogen-containing gas slow-release agent and the reducing agent (or oxidizing agent) using a device such as a pepper mill.

In the nitrogen-based gas sustained-release product obtained by directly mixing the nitrogen-based gas sustained-release agent and the reducing agent (or the oxidizing agent), it is preferable that both components are stored in the same container with a partition wall interposed therebetween. This prevents the powdered reducing agent (or oxidizing agent) from scattering, and allows mixing by external mechanical operation, thereby providing high safety.

In addition, when the reducing agent contains 2-valent iron ions, the container for containing the nitrogen-based gas slow-release agent and the reducing agent is preferably transparent. This is because, in the reaction between the nitrite ion/nitrate ion-containing LDH and the Iron Ion (II), the Iron Ion (II) changes to the iron ion (III) to give a brown color, and therefore the degree of progress of the reaction can be confirmed qualitatively by the color of the mixture. As the transparent container, a container using glass or plastic can be exemplified.

As described above, the nitrogen-based gas sustained release formulation of the second aspect sustains release of a nitrogen-based gas selected from the group consisting of nitric oxide gas, nitrous acid vapor, nitrogen dioxide gas, nitrous oxide gas, and ammonia.

In the nitrogen-based gas release agent of any embodiment, a dehydrating agent, a decarbonating agent, a deoxidizing agent, or the like may be coexisted in order to improve the long-term storage stability.

(third aspect)

As a third aspect, a package using the nitrogen-based gas release agent of the second aspect as another aspect of the present invention will be described.

Fig. 5 is a schematic view showing a package of the third aspect.

In the package 500 of the third aspect, the nitrogen-based gas release liner 510 is hermetically contained in a packaging material 520. The nitrogen-based gas release material 510 is a nitrogen-based gas release material represented by the first to third embodiments of the second aspect, and therefore, the description thereof is omitted. The nitrogen-based gas release liner 510 of the first to third embodiments may be used as it is, or may be modularized by combining it with other members.

As described above, in any of the first to 3 rd embodiments, the nitrogen-based gas slow-releasing body 510 is exposed to the atmosphere and reacts with carbon dioxide and water to slowly release the nitrogen-based gas. Thus, by forming the package 500 in this manner, contact with carbon dioxide and water in the atmosphere can be avoided until immediately before use.

The material of the packaging material 520 is not limited as long as it does not react with the nitrogen-based gas release agent 510, has gas barrier properties that prevent permeation of carbon dioxide, water, oxygen, and the like, and is not broken by a usual storage method. The packaging material 520 may be a sealed bag obtained by welding and sealing the peripheral edge portion of an aluminum laminated film, a glass container obtained by sealing the opening, or the like. Fig. 5 shows the packaging material 520 as a sealed bag, but the shape, structure, size, and the like of the packaging material are not limited as long as a predetermined amount of the nitrogen-based gas release agent can be stored and the nitrogen-based gas release property can be maintained for a predetermined time.

The inside of the package 500 is preferably set to a void-free, vacuum or inert gas atmosphere, or a dry atmosphere containing no water, from the viewpoint of improving the storage stability of the nitrogen-based gas release material 510.

In the present specification, "vacuum" means a state of being reduced in pressure to half or less of the atmospheric pressure, "inert gas atmosphere" means an atmosphere in which the contents of oxygen and carbon dioxide gas are less than that of the atmosphere, and "dry atmosphere" means an atmosphere having a relative humidity of 50% or less. Examples of the inert gas atmosphere include a nitrogen atmosphere in which the nitrogen content is higher than that of the atmosphere, a rare gas atmosphere in which the rare gas content is higher than that of the atmosphere, and the like.

An exemplary method of manufacturing the package 500 will be described.

The package 500 may be formed by hermetically storing the nitrogen-based gas release liner 510 in the packaging material 520, and a method of placing the nitrogen-based gas release liner 510 in the packaging material 520 having an opening and sealing the opening may be employed. This operation, if it can be done quickly, can be carried out in the atmosphere. In this case, it is preferable to degas the packaging material 520 to expel the internal atmosphere and seal the opening, from the viewpoint of reducing the amount of contact between the atmosphere and the nitrogen-based gas release liner 510 and improving the storage stability of the nitrogen-based gas release liner 510. Further, this operation is performed in an inert gas atmosphere or a dry atmosphere, so that the inside of the packaging material 520 can be made into an inert gas atmosphere or a dry atmosphere, and if the inside of the packaging material 520 is depressurized before the opening is sealed, the inside of the packaging material 520 can be made into a vacuum, which is more preferable from the viewpoint of improving the storage stability and stability of the nitrogen-based gas release liner 510. The method of placing the packaging material 520 in a vacuum, an inert gas atmosphere, or a dry atmosphere is not limited to this, and any method that can be generally conceived by those skilled in the art can be used.

Alternatively, the nitrogen-based gas release liner 510 may be dried under reduced pressure before sealing. This makes it possible to remove interlayer water, crystal water, and/or adsorbed water contained in the LDH containing nitrite ions/nitrate ions and the reducing agent (or oxidizing agent) contained as necessary, and is therefore more preferable from the viewpoint of improving the storage stability and stability of the nitrogen-based gas sustained release material 510. The nitrogen-based gas release material 510 may be dried under reduced pressure by heating in a temperature range in which neither the contained LDH containing nitrite ions/nitrate ions nor the contained reducing agent (or oxidizing agent) is modified as necessary.

The package 500 thus obtained can be stored in a refrigerator or freezer.

(fourth aspect)

As a fourth aspect, a method for releasing a nitrogen-based gas using the nitrogen-based gas release agent of the second aspect as another aspect of the present invention will be described.

The nitrogen-based gas sustained-release method uses at least a nitrogen-based gas sustained-release body composed of a nitrogen-based gas sustained-release agent containing the above-mentioned nitrite ion/nitrate ion-containing LDH. As described above, as the nitrogen-based gas retarder, 3 types can be typically employed. Specifically, a sustained-release body using a nitrogen-based gas sustained-release agent alone (first mode), a sustained-release body in which a nitrogen-based gas sustained-release agent and a reducing agent (or an oxidizing agent) are spatially separated and juxtaposed (second mode), and a sustained-release body in which a nitrogen-based gas sustained-release agent and a reducing agent (or an oxidizing agent) are directly mixed (third mode). Hereinafter, the method of releasing a nitrogen-based gas using the 3 types of release agents will be described in different cases.

[ method for sustained Release of Nitrogen-based gas Using sustained Release body of Nitrogen-based gas sustained Release agent alone (first embodiment) ]

The method for releasing a nitrogen-based gas using the nitrogen-based gas release agent of the first embodiment includes a step of bringing a gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas release agent of the first embodiment. The slow release method is based on the above described "solid phase-gas phase anion exchange reaction" between atmospheric carbon dioxide and/or water and the nitrite ion containing LDH.

The nitrogen-based gas release agent of the first aspect generates nitrous acid through a "solid-phase/gas-phase anion exchange reaction" between LDH containing nitrite ions as a main component and carbon dioxide and/or water in the atmosphere, and releases nitrous acid vapor as a nitrogen-based gas through vaporization of the nitrous acid. Further, nitrous acid and nitrous acid vapor are unstable compounds and thus are decomposed into nitrogen monoxide and nitrogen dioxide by an auto-oxidation-reduction reaction. As a result, the nitrogen-based gas sustained-release agent of the first embodiment can sustain the nitrogen monoxide and the nitrogen dioxide as the nitrogen-based gas.

In the step of bringing a gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas-releasing body of the first embodiment, any method may be used as long as the nitrogen-based gas-releasing body is brought into contact with carbon dioxide and/or water. As an example of the contact method, there is a method in which the nitrogen-based gas sustained-release agent of the first embodiment is disposed in a container such as a vial or a glass cartridge, and a gas containing carbon dioxide and/or water vapor is supplied into the container by a pump or the like. The supply rate of the gas containing carbon dioxide and/or water vapor may be, for example, 10(mL/min) to 20 (L/min).

The content of carbon dioxide in the gas is not particularly limited, and is illustratively in the range of 0.03% to 5%. The content of water (water vapor) in the gas is represented by relative humidity, and may be 40% to 100%.

In the step of bringing a gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas release agent of the first embodiment, the gas can be prepared by adding water vapor and carbon dioxide to air or an inert gas such as nitrogen or a rare gas. As the method of adding water vapor, any method that can be generally thought by those skilled in the art can be selected, such as: a method of bubbling air through water; a method of ventilating a column packed with water-wetted paper or cloth; a method of utilizing water produced by a chemical reaction; a method of concentrating moisture in the air, a method of using exhaled air, and the like. Further, as the method of adding carbon dioxide, any method that can be generally thought by those skilled in the art can be selected, such as: a method using a high pressure gas cylinder; a method using carbonated water; a method using dry ice; a method of producing a solid of carbon dioxide by contacting water with bath salt or the like; a method of producing a solid of carbon dioxide by contact with oxygen; a method of producing by a combustion reaction; a method of removing carbon dioxide by heating a material to which carbon dioxide is adsorbed; a method of producing by a chemical reaction; a method of concentrating carbon dioxide in the air; methods using exhalation, and the like.

In the step of bringing a gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas sustained release material of the first embodiment, the nitrogen-based gas sustained release material may be heated. This promotes auto-oxidation-reduction reaction of nitrite vapor, diffusion of molecules and ions in the nitrite ion-containing LDH, vaporization of nitrous acid, and the like, thereby increasing the sustained release concentration of the nitrogen-based gas. The heating may be performed at a temperature ranging from 30 ℃ to 150 ℃.

In the case where the package 500 of the third aspect is formed using the nitrogen-based gas release material of the first aspect, the package 500 is opened, and carbon dioxide and/or water vapor is brought into contact with the nitrogen-based gas release material 510, whereby the nitrogen-based gas can be released.

As described above, by the step of bringing the gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas sustained release material of the first embodiment, nitrous acid vapor, nitric oxide, and nitrogen dioxide can be released slowly from the nitrogen-based gas sustained release material. A method of removing only nitric oxide therefrom will be described.

As an example of this method, a basic adsorbent is disposed downstream of the nitrogen-based gas sustained release material of the first embodiment, and the gas sustained released from the sustained release material is brought into contact with the adsorbent. In the gas component, since nitrous acid vapor and nitrogen dioxide are acidic gases and nitric oxide is a neutral gas, the nitrous acid vapor and nitrogen dioxide are adsorbed by the adsorbent by contact with the adsorbent, and only nitric oxide is slowly released. Specific examples of the method include: magnesium hydroxide filled in a glass cylinder or the like is prepared as an alkaline adsorbent, and the gas slowly released from the nitrogen-based gas slow-releasing body of the first embodiment is brought into contact with magnesium hydroxide.

As the basic adsorbent, in addition to the above-mentioned magnesium hydroxide, basic polymers such as calcium hydroxide, sodium hydroxide, hydrated lime, quicklime, soda lime, and polyvinyl pyridine, organic compounds having amino groups, silica gel modified with amino groups, and the like can be used. From the viewpoint of safety, a substance having low hygroscopicity, no deliquescence, and being soluble in water without generating a strong alkaline liquid having irritation is preferable. The alkaline adsorbent is preferably magnesium hydroxide, which is a solid base with low water solubility. In addition, the characteristics of the nitrogen-based gas to be removed from the mixed gas species and the characteristics of the nitrogen-based gas to be purified are compared, and any adsorbent that can be generally considered by those skilled in the art can be selected.

As another example of the method of releasing only nitric oxide, a method of bubbling a gas released by the nitrogen-based gas release agent of the first embodiment into water may be mentioned. Since nitric oxide is a gas insoluble in water, and nitrous acid vapor and nitrogen dioxide are highly water-soluble gases, nitrous acid vapor and nitrogen dioxide can be dissolved in water by bubbling, and only nitrous acid and nitrogen dioxide can be selectively removed. In this case, the water to be bubbled is preferably alkaline in view of removal efficiency. The method of releasing only nitric oxide from a gas containing nitrous acid vapor, nitric oxide, and nitrogen dioxide, in other words, the method of removing only nitrous acid vapor and nitrogen dioxide, is not limited to these methods, and any method that can be generally conceived by those skilled in the art may be employed.

Next, a method of extracting only nitrogen dioxide from nitrous acid vapor, nitrogen monoxide, and nitrogen dioxide slowly released from the nitrogen-based gas slow release agent of the first embodiment will be described.

As an example of this method, a gas released from the nitrogen-based gas release agent of the first embodiment may be brought into contact with the atmosphere. Nitrous acid generates nitric oxide and nitrogen dioxide by an auto-oxidation-reduction reaction represented by formula (5). Further, nitrogen monoxide reacts with oxygen in the air by the reaction represented by formula (6) to generate nitrogen dioxide. Therefore, by bringing the gas whose nitrogen-based gas slow-release agent has been released in the first aspect into contact with the atmosphere for a certain period of time, the reactions represented by the expressions (5) and (6) can be advanced, and nitrous acid vapor and nitric oxide contained in the gas can be converted into nitrogen dioxide. The nitrogen-based slow-release material and/or the nitrogen-based gas after slow release according to the first aspect may be heated when the gas after slow release is brought into contact with the atmosphere. This is preferable because the reaction of formula (5) and formula (6) is accelerated. The heating may be performed at a temperature ranging from 30 ℃ to 150 ℃.

In this way, only a desired gas can be taken out from the nitrogen-based gas sustained-release material of the first embodiment depending on the application.

[ method for releasing a nitrogen-based gas using a release body (second embodiment) in which a nitrogen-based gas release agent and a reducing agent (or oxidizing agent) are spatially separated and juxtaposed ]

The method for releasing a nitrogen-based gas using the nitrogen-based gas release agent of the second aspect includes: bringing a gas containing carbon dioxide and/or water vapor into contact with a nitrogen-based gas sustained-release agent constituting the sustained-release body; and a step of bringing the nitrous acid vapor obtained in the step into contact with a solid reducing agent (or a solid oxidizing agent) constituting the slow-release body. The slow release method is based on the above described "solid phase-gas phase anion exchange reaction" between atmospheric carbon dioxide and/or water and the nitrite ion containing LDH.

The step of bringing the gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas slow-release agent is the same as the step of bringing the gas into contact with the nitrogen-based gas slow-release agent of the first embodiment described above, and therefore, the description thereof is omitted.

The step of bringing the nitrous acid vapor into contact with the solid reducing agent (or the solid oxidizing agent) is performed, for example, by passing the nitrous acid vapor gradually released from the nitrogen-based gas slow-release agent through the solid reducing agent (or the solid oxidizing agent) constituting the nitrogen-based gas slow-release body of the second embodiment. Thereby, nitrous acid is converted into another nitrogen-based gas. Nitrous acid vapor is converted into Nitric Oxide (NO) and dinitrogen monoxide (N) by a reducing agent (or an oxidizing agent) due to its high reactivity₂O), nitrogen dioxide (NO)₂) Ammonia (NH)₃) Or nitrogen (N)₂). The solid reducing agent (or the solid oxidizing agent) may be packed in a column as long as it is spatially separated from the nitrogen-based gas sustained-release agent and is not directly mixed therewith.

The solid reducing agent or the solid oxidizing agent Is Iron (II) sulfate, tin (II) chloride, hexavalent chromium, zinc, sulfamic acid, or the like, and when nitrous acid vapor reacts with them, nitrous acid vapor can be converted into Nitric Oxide (NO), nitrous oxide (N), respectively₂O), nitrogen dioxide (NO)₂) Ammonia (NH)₃) Or nitrogen (N)₂). That is, when nitrous acid vapor is passed through a solid containing iron ions having a valence of 2, for example, a column packed with iron (II) sulfate, it is converted into nitric oxide. Furthermore, dinitrogen monoxide was produced in the column packed with tin (II) chloride, nitrogen dioxide was produced in the column packed with hexavalent chromium, ammonia was produced in the column packed with zinc powder, and nitrogen gas (N) was produced in the column packed with sulfamic acid₂). After nitrous acid vapor is converted into nitric oxide by passing through a column packed with iron (II) sulfate, a column packed with hexavalent chromium may be used to convert nitric oxide into nitrogen dioxide. In this way, by using a plurality of reducing agents or oxidizing agents in combination, cascade reaction can be caused, and only the desired nitrogen-based gas can be slowly released. In the examples described later, iron (II) sulfate heptahydrate was used as a reducing agent for causing the sustained release of nitric oxide, but the above-described reducing agent may be suitably used.

The step of bringing the gas containing carbon dioxide and/or water vapor into contact with the nitrogen-based gas slow-release agent and the step of bringing the nitrous acid vapor slowly released from the nitrogen-based gas slow-release agent into contact with the solid reducing agent (or the solid oxidizing agent) may be repeated. Thereby, the nitrogen-based gas can be accumulated to slowly release the nitrogen-based gas at a high concentration. All methods that can be generally thought by those skilled in the art, such as a method of alternately connecting a nitrogen-based gas releasing agent and a reducing agent using a tube or the like, a method of alternately packing a nitrogen-based gas releasing agent and a reducing agent in a column, and the like, can be applied.

In the method for releasing a nitrogen-based gas using the nitrogen-based gas releaser of the second aspect, an adsorbent may be disposed downstream of the releaser to adsorb a predetermined gas. The adsorption step is the same as described above, and therefore, the description thereof is omitted. This can improve the purity of the desired nitrogen-based gas.

In this manner, in the nitrogen-based gas release carrier of the second embodiment, the LDH containing nitrite ions is spatially separated from the solid reducing agent (or solid oxidizing agent), and 2 reagents are not in contact with each other. Characterized in that the nitrous acid vapor released from the nitrite ion-containing LDH reaches the reducing agent (or oxidizing agent) and is converted into a nitrogen-based gas other than nitrous acid, thereby releasing the nitrogen-based gas. Since various oxidation and reduction reactions are known for nitrous acid, it is possible to generate and release a wide variety of nitrogen-based gases by combining a nitrite ion-containing LDH with an appropriate oxidizing agent or reducing agent.

It is noted that nitrous acid or nitrous acid vapor may be oxidized/reduced by an electrochemical method or an electrochemical catalyst, in addition to a solid oxidizing agent or a solid reducing agent as a chemical substance.

[ method for releasing nitrogen-containing gas by use of a release agent comprising a nitrogen-containing gas release agent and a solid reducing agent (or a solid oxidizing agent) directly mixed therewith (third embodiment) ]

The method for slowly releasing a nitrogen-based gas using the nitrogen-based gas slow-release material according to the third aspect includes a step of bringing a gas containing at least water vapor into contact with the slow-release material. The slow release method is based on the above described "solid phase-solid phase anion exchange reaction" between atmospheric water and a solid reductant (or solid oxidant) and a nitrite/nitrate ion containing LDH. Since the anion exchange reaction between the solid phase and the solid phase is accompanied by diffusion of ions and gas molecules in the layer, the nitrogen-based gas can be sustained and released for a long time.

In the step of bringing a gas containing at least water vapor into contact with the nitrogen-based gas sustained release material of the third embodiment, any method may be used as long as the sustained release material is brought into contact with the gas containing water vapor. As an example of the contact method, a nitrogen-based gas sustained-release agent of the third method is disposed in a column such as a vial or a glass cylinder, and a gas containing water vapor is supplied into the column by a pump or the like. The supply rate of the gas containing water vapor may be, for example, 10(mL/min) to 20 (L/min). The content of water in the gas is expressed by relative humidity, and may be 40% to 100%. The gas containing water vapor (water vapor) is prepared as described above. For the purpose of adjusting the sustained release concentration, carbon dioxide may be added to the gas flow or the nitrogen-based gas sustained release body may be heated. The heating may be performed at a temperature ranging from 30 ℃ to 150 ℃.

As the nitrogen-based gas sustained release body of the third aspect, when a column is filled with a substance whose main component is LDH containing nitrite ions and a solid reducing agent Is Iron (II) sulfate, and a gas containing water vapor is introduced into the column, nitrite ions released outside the LDH layer react with iron ions having a valence of 2 as a reducing agent to be converted into nitrogen monoxide. At this time, by adding steam to the air, the anion exchange reaction between the solid phase and the solid phase can be accelerated, and nitric oxide of a higher concentration can be released slowly.

In addition, as the nitrogen-based gas sustained release body of the third embodiment, when the column is filled with a substance in which the main component of the nitrogen-based gas sustained release agent is LDH containing nitrite ions and the solid reducing agent is tin (II) chloride, and a gas containing water vapor is introduced into the column, dinitrogen monoxide is slowly released.

In addition, as the nitrogen-based gas sustained release agent of the third embodiment, when the column is filled with LDH containing nitrate ions as a main component and zinc and iron (II) sulfate as a solid reducing agent, and a gas containing water vapor is introduced into the column, nitric oxide, nitrogen dioxide, and nitrous acid are sustained released.

In the method for releasing a nitrogen-based gas using the nitrogen-based gas release agent of the third aspect, an adsorbent may be disposed downstream of the release agent, and a step of adsorbing a predetermined gas may be performed. The adsorption step is the same as described above, and therefore, the description thereof is omitted. This can improve the purity of the desired nitrogen-based gas.

In the case where the nitrogen-based gas slow-release agent of the third aspect is obtained immediately before contact with the gas containing at least water vapor, that is, in the case where the nitrogen-based gas slow-release agent and the solid reducing agent are mixed immediately before the contact, all mixing methods that can be conceived by those skilled in the art, such as a method of removing a movable partition wall provided between the nitrogen-based gas slow-release agent and the solid reducing agent (or the solid oxidizing agent), a method of mechanical stirring, and a method of pulverizing and mixing by an apparatus such as a pepper mill, can be applied.

In addition, when the package 500 of the third aspect is formed using the nitrogen-based gas sustained release material of the third aspect, the nitrogen-based gas can be released slowly by opening the package 500, taking out the nitrogen-based gas sustained release material 510, and bringing it into contact with a gas containing water vapor. Alternatively, the nitrogen-based gas slow-release agent and the solid reducing agent (or the solid oxidizing agent) may be sealed and contained in respective packages, and just before contacting with the gas containing water vapor, the respective packages may be unsealed and mixed, and then contacted with the gas containing water vapor.

In the method for releasing a nitrogen-based gas according to the fourth aspect described above, the nitrogen-based gas release agent is placed in an inert gas atmosphere or a vacuum during the release, whereby the release of the nitrogen-based gas can be temporarily stopped at an intermediate stage.

(fifth aspect)

As a fifth aspect of the present invention, an apparatus for releasing a nitrogen-based gas using the nitrogen-based gas release agent of the second aspect will be described.

Fig. 6 is a schematic view showing a slow release device that releases a nitrogen-based gas slowly.

The slow release device 600 according to the fifth aspect includes at least an atmosphere gas supply unit 610 for supplying an atmosphere gas, and a nitrogen-based gas slow release unit 620 for slowly releasing a nitrogen-based gas by the atmosphere gas supplied from the atmosphere gas supply unit 610. In fig. 6, the slow release device 600 of the present invention further includes an impurity gas removing part 630 for removing impurities from the nitrogen-based gas that is slowly released from the nitrogen-based gas slow release part 620, but it is not essential.

The atmosphere gas supply unit 610 may employ any mechanism capable of supplying a gas containing at least water vapor. Illustratively, there may be a pump, a gas cylinder, an exhalation introduction port, and the like. When a pump is used, it may be combined with a humidifier or the like. The atmosphere gas supply unit 610 may supply carbon dioxide in addition to the gas containing water vapor. The atmosphere gas supply unit 610 may include a plurality of types of gas cylinders, and the gases in the gas cylinders may be combined and supplied to the nitrogen-based gas slow release unit 620.

The nitrogen-based gas slow-releasing part 620 includes at least the nitrogen-based gas slow-releasing body of the second aspect. The nitrogen-based gas retarder is the same as described above, and therefore, the description thereof is omitted. The nitrogen-based gas release agent may be disposed by filling the nitrogen-based gas release agent in a column or the like. The nitrogen-based gas slow-release part 620 is connected by a gas supply pipe or the like so that the atmosphere gas supplied from the atmosphere gas supply part 610 contacts the nitrogen-based gas slow-release body. The package of the third aspect may be used, and the nitrogen-based gas release material of the second aspect may be disposed by opening the package immediately before the supply of the atmospheric gas is started.

In the nitrogen-based gas-releasing part 620, when the nitrogen-based gas-releasing body is the nitrogen-based gas-releasing body of the second embodiment, a plurality of nitrogen-based gas-releasing bodies each composed of a set of a nitrogen-based gas-releasing agent and a solid reducing agent (or a solid oxidizing agent) may be disposed. In this case, the solid reducing agent or the solid oxidizing agent is located downstream of the nitrogen-based gas slow-release agent. By disposing a plurality of the nitrogen-based gas release agents, a high-concentration nitrogen-based gas can be released slowly.

The nitrogen-based gas releasing part 620 may further include a heating mechanism such as a heater. This causes diffusion of molecules and ions in the nitrite ion/nitrate ion-containing LDH in the nitrogen-based gas retarder, thereby promoting the anion exchange reaction and increasing the sustained release concentration of the nitrogen-based gas.

The impurity gas removing unit 630 is a mechanism for adsorbing and removing unnecessary components (impurities) contained in the slowly released gas. For example, one of the mechanisms for adsorption and removal is an adsorbent packed in a column or the like. When the adsorbent is an alkaline adsorbent, nitrous acid vapor and nitrogen dioxide can be adsorbed and removed. Such an alkaline adsorbent is the same as described above, and therefore, the description thereof is omitted. Further, as another example of the mechanism for adsorption and removal, a bubbling device for discharging water may be mentioned. This allows nitrous acid vapor and nitrogen dioxide to be adsorbed and removed. Further, when nitrogen monoxide is oxidized to nitrogen dioxide, it can be removed by an alkaline adsorbent. This enables the purification of chemically stable nitrous oxide. It is also known that nitric oxide is coordinated to a central metal such as a ruthenium complex to form a nitrosyl complex, and therefore, nitric oxide can be adsorbed and removed by the formation of the nitrosyl complex.

The nitrogen-based gas-releasing device 600 according to the fifth aspect may further include a mechanism for supplying the atmosphere gas from the atmosphere gas supply unit 610 downstream of the impurity gas removal unit 630, or may include another atmosphere gas supply unit, as necessary. Thereby, the concentration of the nitrogen-based gas released by impurity gas removal unit 630 can be adjusted. The slow release device 600 according to the fifth aspect can be reduced in size of the bag by the above configuration, and is therefore advantageous for transportation.

Next, the operation of the slow release device 600 of the fifth aspect will be described. Here, for convenience, the nitrogen-based gas sustained-release material of the third embodiment described above having the reducing agent containing iron ions having a valence of 2 is disposed in the nitrogen-based gas sustained-release portion 620 as the nitrogen-based gas sustained-release material of the second embodiment, and the sustained-release device 600 sustains the release of nitric oxide gas.

The atmosphere gas supply unit 610 supplies a gas containing at least water vapor to the nitrogen-based gas slow release unit 620. In the nitrogen-based gas sustained-release section 620, a "solid-phase anion exchange reaction" between the supplied water and the reducing agent and the nitrite ion/nitrate ion-containing LDH occurs, and nitrite ions are released from the nitrite ion/nitrate ion-containing LDH. Then, nitrite ions react with 2-valent iron ions to be converted into nitric oxide, thereby slowly releasing nitric oxide.

In the nitrogen-based gas sustained-release apparatus shown in fig. 6, since the impurity gas removal unit 630 is further provided, the nitric oxide generated in the nitrogen-based gas sustained-release unit 620 and the nitrous acid vapor and nitrogen dioxide remaining without conversion are supplied to the impurity gas removal unit 630, and the nitrous acid vapor and nitrogen dioxide are adsorbed and removed therein, whereby the sustained-release apparatus 600 can slowly release the purified nitric oxide gas.

Thus, if the nitrogen-based gas sustained-release material according to the second aspect is used, a medical respirator can be provided as the sustained-release device 600. For example, the nitrogen-based gas slow-release device provided with the manual pump as the atmosphere gas supply unit 610 and the nitrogen-based gas slow-release member as the second aspect of the nitrogen-based gas slow-release unit 620, and provided with the humidifier and the adsorbent as necessary, can slowly release only nitric oxide. The sustained release nitric oxide is administered to the patient via a ventilator.

The nitrogen-based gas sustained-release device having such a configuration can supply nitric oxide at a concentration required to meet medical standards by only manual operation without using any power source such as a battery, and therefore, is useful for emergency treatment of a patient with respiratory distress, or for use in situations and environments where the current technology cannot cover such as at home, in a developing country, or in the event of a power failure.

Hereinafter, the following description will be specifically made based on examples. However, these examples are shown to help the easy understanding of the present invention, and do not limit the present invention in any way.

Examples

[ method for measuring Nitrogen-containing gas component ]

Before the examples, a method for measuring a component of a nitrogen-based gas to be slowly released will be described.

(1) Method for quantitative determination of nitrogen dioxide, nitric oxide and nitrous acid vapor using Griess reagent and detector tube

The gas containing nitrous acid vapor generated from the nitrogen-based gas retarder or retarder was bubbled into an aqueous solution of Griess reagent containing a developing reagent for nitrite ions, and the emission of nitrous acid vapor was confirmed by the color change from colorless to purple of the aqueous solution. The quantification of nitrous acid can be performed by measuring the visible ultraviolet absorption spectrum of an aqueous solution of Griess's reagent that develops color in response to nitrous acid.

Further, the gas generated from the nitrogen-based gas sustained-release agent or the sustained-release body was passed through a nitric oxide + nitrogen dioxide detection tube (product of Gastec, No.11L), whereby the amount of nitric oxide + nitrogen dioxide + nitrous acid was determined in a cost-effective manner. In the detector tube, a strong oxidizing agent (Cr) is provided in advance at the tip of the detector tube for the purpose of oxidizing nitric oxide to nitrogen dioxide⁶⁺+H₂SO₄) Therefore, nitrous acid in the gas to be ventilated is also oxidized and converted into nitrogen dioxide. Therefore, the total of nitrogen monoxide, nitrogen dioxide and nitrous acid is obtained as the amount of nitrogen dioxide. This reaction can also be used as a method of generating nitrogen dioxide from nitrous acid vapor using an oxidizing agent.

Further, only nitrogen dioxide was quantified by introducing a gas generated from the nitrogen-based gas retarder or the retarder into a detector tube for detecting nitrogen dioxide (manufactured by Gastec, Inc., No.10 or No. 9P). The detection tube is not provided with a strong oxidizing agent (Cr) at the front end⁶⁺+H₂SO₄) And thus are not responsive to nitric oxide and nitrous acid. Thus, only nitrogen dioxide in the gas is quantified. Since o-tolidine, which is an organic amine, is used as a color developing reagent in the nitrogen dioxide detection tube (product of Gastec corporation, No.10), nitrous acid, which is an acidic gas, is neutralized and adsorbed in the detection tube, and the color developing reagent does not develop a color.

Further, only nitric oxide was quantified by introducing a gas generated from the nitrogen-based gas retarder or retarder into a detector tube for detecting nitrogen dioxide (manufactured by Gastec, No.10) to remove nitrogen dioxide and nitrous acid, and then measuring the gas with a detector tube for detecting nitric oxide + nitrogen dioxide (manufactured by Gastec, No. 11L). This process can also be considered as a method for purifying nitric oxide using a detector tube for detecting nitrogen dioxide (manufactured by Gastec, Inc., No. 10). It can be confirmed by the aforementioned color development method using Griess reagent that: the gas passing through the nitrogen dioxide detecting tube (No. 10, manufactured by Gastec corporation) was removed not only nitrogen dioxide but also nitrous acid.

Based on the above measurement results, the concentrations of nitrogen dioxide and nitrogen monoxide were subtracted from the concentrations of nitrogen monoxide + nitrogen dioxide + nitrous acid to calculate the concentration of nitrous acid.

(2) Method for quantitative measurement of nitrous oxide by infrared spectroscopic measurement

The measurement of dinitrogen monoxide released slowly from the nitrogen-based gas release agent was performed by infrared spectrometry using a gas cell. Gas generated from the nitrogen-based gas release agent was introduced into an infrared absorption spectrum gas cell (manufactured by GL Sciences, optical path length 10cm, window frame of NaCl single crystal) at a flow rate of 100mL/min, Fourier transform infrared absorption spectrum was measured at 2-minute intervals, and gas components were analyzed. When the gas to be introduced contains not less than 50% of water vapor, the gas is introduced into a column packed with molecular sieve 3a1/16 to dehumidify and then introduced into a gas chamber in order to protect the NaCl single crystal of the window material. As the molecular sieve 3a1/16, a molecular sieve which was activated by drying in an electric oven at 200 ℃ for 1 day or more in the air and cooled from 200 ℃ to room temperature under vacuum was used. In the measurement of Fourier transform infrared absorption spectrum, NEXUS 670-FT-IR manufactured by NICOLET was used, and the measurement range was 4000-600cm^-1The number of times of integration was set to 16 times. The gas chamber was provided in a sample chamber in the spectrometer, and the sample chamber was set to a dry nitrogen atmosphere.

(3) Method for quantitative determination of ammonia using detection tube

The measurement of ammonia released slowly from the nitrogen-based gas release agent was carried out using a detector tube (Gastec 3L).

[ method of releasing Nitrogen-containing gas component ]

The experiments for releasing various nitrogen-based gases were performed substantially as follows.

First, the nitrogen-based gas release device 600 shown in fig. 6 is assembled. As the atmosphere gas supply part 610, there is provided,

as the nitrogen-based gas release part 620, a container containing LDH containing nitrite ions/nitrate ions was used using a pump, and when the impurity gas removal part 630 was provided, a column filled with magnesium hydroxide was used.

As the nitrogen-based gas release agent, LDH containing nitrite ions/nitrate ions is used, and LDH containing nitrite ions or LDH containing nitrate ions is used as the nitrogen-based gas release agent. Further, the nitrogen-based gas release agent is prepared by juxtaposing, as necessary, LDH containing nitrite ions/nitrate ions, separately from a reducing agent (iron (II) sulfate heptahydrate, zinc, etc.), or by directly mixing them. In the case where the reducing agent is juxtaposed with the nitrogen-based gas retarder, a column packed with the reducing agent is used.

The pump was connected to a container containing LDH containing nitrite/nitrate ions via a gas supply line, and air at 20 ℃ from the pump was introduced at a constant flow rate of 50mL/min or 100 mL/min. The air supplied to the container is appropriately increased or decreased in temperature, humidity, and carbon dioxide amount. The humidity and carbon dioxide concentration were adjusted by pumping out the expired air (relative humidity 100%, carbon dioxide 4.0%) stored in a humidifier or Tedlar (registered trademark) bag.

On the side of the container containing the LDH containing nitrite ions/nitrate ions opposite to the gas supply pipe, a discharge pipe is connected, and the gas discharged from the discharge pipe is introduced into the Griess reagent or the detection pipe through a filter to detect the nitrogen-based gas.

Further, the gas discharged from the discharge pipe is passed through a column packed with iron (II) sulfate and, if necessary, a column packed with magnesium hydroxide, and the nitrogen-based gas is detected by a detection tube or the concentration of nitric oxide is measured by using a nitric oxide concentration sensor (ToxiRAE Pro (detection range 0.5 to 250ppm) manufactured by RAE System). The change with time of the nitric oxide concentration every 1 minute was measured by a nitric oxide concentration sensor. The measurement interval is adjusted at intervals of 1 minute to 5 minutes according to the sustained-release time.

In the measurement of the nitrogen-based gas concentration, other concentration measuring devices such as a gas chromatograph device, an infrared spectrophotometer, and an ozone light emitting device may be used instead of the detector tube and the nitric oxide concentration sensor.

(example 1)

As the carbonic acid type LDH, a carbonate type LDH having a general formula of Mg ion as a 2-valent metal ion and Al ion as a 3-valent metal ion₃Al(OH)₈(CO₃ ^2-)_0.5·2H₂A commercially available carbonic acid type layered double hydroxide represented by O (DHT-6, manufactured by Kyowa chemical industries Co., Ltd., particle size distribution of about 0.1 to 1 μm, Mg/Al molar ratio of 2.99 (+ -0.06)). Hereinafter, this LDH will be described as CO₃ ^2-MgAl-LDH3。

First, the carbonic acid type LDH is converted to the Cl type LDH by the method described in japanese patent No. 5867831. Specifically, first, 2.0g of CO was weighed₃ ^2-MgAl-LDH3, and 300mL of ethanol was added to the flask. Then, the suspension was stirred with a magnetic stirrer under a nitrogen flow (500mL/min), and 16.1mL of a hydrochloric acid alcohol solution (3 mass%) was added dropwise thereto, followed by stirring at 35 ℃ for 2 hours to effect reaction. Then, the mixture was filtered through a membrane filter having a pore size of 0.2 μm in a nitrogen stream, and the filtrate (residue) was sufficiently washed with methanol. The residue of the filtrate was collected and recovered, immediately reduced in pressure, and dried under vacuum for 1 hour or more to obtain a white powder.

As a result of measuring the infrared absorption Spectrum of the obtained white powder using a Fourier transform infrared spectrophotometer (Perkin-Elmer Spectrum One, ATR accessory), 1360cm was not observed^-1Based on carbonate ions (CO)₃ ^2-) Thereby judging that the carbonate ion is absorbed by the chloride ionAnd (4) replacement. Hereinafter, the LDH is described as Cl^-MgAl-LDH3。

Then, from Cl^-MgAl-LDH3 makes LDHs containing nitrite ions. In a glove box under a nitrogen atmosphere, 182.7mg of NaNO was dissolved in 30mL of degassed ion-exchanged water₂(Wako pure chemical industries) to prepare NaNO₂And (3) solution. The degassed ion-exchanged water was obtained by boiling the ion-exchanged water and bubbling nitrogen gas during cooling, and the same operation was performed in other examples described later.

40mg of Cl are weighed^-MgAl-LDH3 was filled into a 30mL glass vial, and the NaNO was added to the glove box₂The solution was thoroughly shaken to disperse it. After the vial was sealed and allowed to react for 2 days, the reaction mixture was filtered through a membrane filter having a pore size of 0.2 μm in the glove box, and the filtrate (residue) was washed with degassed ion-exchanged water, and dried under vacuum for about 120 minutes together with the membrane filter to obtain a white powdery sample.

FTIR measurement was performed on a white powdery sample. As a result, 1227cm based is observed^-1Nitrite ion (NO)₂ ^-) Since the absorption of (b) shows sufficient absorption strength as compared with other infrared absorption bands derived from interlayer water, LDH skeleton, etc., it is judged that chloride ions are sufficiently substituted with nitrite ions to obtain LDH containing nitrite ions. The Mg/Al ratio was measured by SEM-EDS (JSM 6010LA, 10kV, manufactured by Japan electronics), and the Mg/Al ratio of the carbonic acid type LDH as the raw material was maintained. Further, Cl is a value of about 8 to 9% with respect to Al, and is considered to correspond to Cl^-MgAl-LDH3 shows the amount of chloride ions remaining without being substituted with nitrite ions when LDH containing nitrite ions is produced. Further, as is clear from the comparison of (i) and (iii) in fig. 15c, since the X-ray diffraction pattern reflects the characteristics of the layered double hydroxide, it is considered that the carbonic acid type LDH (Mg) as the starting material is not destroyed₃Al(OH)₈(CO₃ ^2-)_0.5·2H₂O) under the condition of layer structureThe resulting LDH containing nitrite ions satisfies the above general formula (1) by ion exchange.

Next, a package in which LDH containing nitrite ions was hermetically contained was produced. The obtained white powdery sample of LDH containing nitrite ions (100mg) was put in a 13.5mL glass container (packaging material) together with a membrane filter in the glove box described above and sealed to prepare a package.

Next, the package was opened, and nitrite vapor was released from LDH containing nitrite ions using the apparatus shown in fig. 7, and detected using Griess reagent.

Fig. 7 is a schematic diagram showing the apparatus and experimental system used in example 1.

Specifically, a powdery sample 720 of LDH containing nitrous acid in a glass container (also referred to as a glass vial) was passed through a filter 730 having a pore size of 0.45 μm by feeding the sample into the atmosphere (20 ℃, 35% relative humidity, carbon dioxide concentration: about 500ppm) at a flow rate of 100mL/min using a pump 710, and then bubbled through 3mL of an aqueous solution 740 in which a Griess reagent (1g/25mL) was dissolved for 15 minutes. The change of the Griess reagent was observed, and the absorption spectrum of the Griess reagent before and after aeration was measured by a spectrophotometer (model UV-3600, manufactured by Shimadzu). The results are shown in FIG. 8.

Fig. 8 is a graph showing changes in Griess reagent and changes in absorption spectrum before and after aeration in example 1.

As shown in FIG. 8, the aqueous solution of Griess's reagent before aeration was substantially colorless and transparent, but turned pink after aeration. Fig. 8 is represented by a gray scale, and a dark portion in the container corresponds to pink. Thus, it was confirmed that the powdery sample of LDH containing nitrous acid generates nitrous acid vapor when it is brought into contact with the atmosphere.

Further, from the absorption spectrum of fig. 8, the absorption spectrum before aeration (bubbling) had no absorption peak in the measured wavelength range, but showed a significant absorption peak near 543nm after aeration (bubbling). This peak corresponds to an absorption peak of an azo dye generated by the reaction of nitrite ions with a Griess reagent. From this, it was also confirmed that nitrous acid vapor was generated by contacting the powdery sample of LDH containing nitrous acid with the atmosphere, that is, a gas containing carbon dioxide and water vapor.

(example 2)

Next, using the apparatus shown in fig. 9, a nitrogen-based gas release experiment was performed on the LDH containing nitrite ions obtained in example 1, and the LDH was measured using a detection tube.

Fig. 9 is a schematic diagram showing the apparatus and experimental system used in example 2.

Specifically, a powdery sample 720(100mg) of LDH containing nitrous acid in a glass container was stabilized by being sent to the atmosphere (20 ℃ C., relative humidity 35%) at a flow rate of 100mL/min by a pump 710 for about 1 hour, and then the components in the gas after contact with LDH containing nitrite ions were measured by a plurality of kinds of detection tubes 910. Although the pump 710 was used to send the atmospheric air (20 ℃ C., relative humidity 35%) to the LDH containing nitrite ions at a flow rate of 100mL/min, the detection tube 910 was used to suck 50mL/min of air as needed, and the remaining 50mL/min portion was vented to the outside using a branch line.

First, a detection tube No.11L (for NO + NO) manufactured by Gastec corporation was used₂) The total amount of nitric oxide + nitrogen dioxide + nitrous acid vapor was measured. A detection tube No.11L made by Gastec corporation has a strong oxidizing agent (Cr) carried at its tip³⁺+ sulfuric acid) to convert nitric oxide to nitrogen dioxide, o-tolidine was used to quantify the total amount of nitrogen dioxide. The nitrous acid vapour is thus also converted into nitrogen dioxide, which is metered out as the total amount of nitrogen dioxide. The mixture was sucked at a flow rate of 50mL/min for 4 minutes using a quantitative pump (GSP-300 FT-2, manufactured by Gastec Co., Ltd.) exclusively for a detection tube, and as a result, the concentration of nitric oxide + nitrogen dioxide + nitrous acid vapor was 0.7 ppm.

Next, a detection tube No.9P (for NO) manufactured by Gastec corporation was used₂) Only nitrogen dioxide was measured. Unlike the aforementioned No.11L, the detection tube No.9P manufactured by Gastec corporation does not carry an oxidizing agent (Cr) at its tip³⁺+ sulfuric acid), only nitrogen dioxide is quantified with o-tolidine. Using a quantitative pump dedicated to the detection tube, the mixture was aspirated at a flow rate of 100mL/min for 30 minutes, resulting in oxidation of dioxideNitrogen was 0.2 ppm.

Next, a detection tube No.10 (for NO) manufactured by Gastec corporation₂) Detection tube No.11L manufactured by Gastec corporation for NO + NO₂) The connection was made by using a detection tube No.10 (for NO) manufactured by Gastec corporation₂) After removing nitrogen dioxide and nitrous acid vapor from the o-tolidine contained therein, a detection tube No.11L (for NO + NO) manufactured by Gastec corporation was used₂) To measure only nitric oxide. The flow rate of the sample was 50mL/min for 4 minutes by using a metering pump dedicated to the detection tube, and the nitric oxide concentration was 0.2 ppm.

The concentrations of nitric oxide and nitrogen dioxide are about the same, indicating that these 2 gases are produced by the auto-redox reaction of nitrous acid (2 HNO)₂→NO₂+NO+H₂O).

These results are summarized.

Gastec No.11L(NO+NO₂+HNO₂＝0.7ppm)

Gastec No.10+No.11L(NO＝0.2ppm)

Gastec No.9P(NO₂＝0.2ppm)

HNO₂＝0.3ppm

Based on the above results, since nitrogen monoxide + nitrogen dioxide + nitrous acid vapor was 0.7ppm, nitrogen dioxide was 0.2ppm, and nitrogen monoxide was 0.2ppm, nitrous acid vapor was calculated to be 0.3ppm by subtraction.

It should be noted that since the concentrations of nitric oxide, nitrogen dioxide, and nitrous acid vapor released reach the maximum approximately 15 to 30 minutes after the start of release and are substantially maintained at the maximum concentration even after release for further 6 hours, the nitrite ion-containing LDH exhibits sustained release of nitric oxide, nitrogen dioxide, and nitrous acid vapor.

(example 3)

Using the apparatus shown in fig. 10, a nitrogen-based gas release experiment was performed on the LDH containing nitrite ions obtained in example 1, and the composition of the released gas was measured by using the detection tube 910.

Fig. 10 is a schematic diagram showing the apparatus and experimental system used in example 3.

The procedure of example 3 was carried out in the same manner as in example 2 except that the air was replaced by sending the expired air (20 ℃, carbon dioxide concentration 4.0%, relative humidity 100%) stored in the 50L tedlar bag 1010 at a flow rate of 100mL/min by using the pump 710.

The relative humidity of the expired air is 100% out of the allowable humidity range (0-90%) of the detection tube, so that the relative humidity is adjusted to 50% by mixing with the same amount (100mL/min) of dry air. Therefore, for the release concentration, the detected value was corrected by multiplying by 2.

The corrected results are summarized.

Gastec No.11(NO+NO₂+HNO₂＝7.0ppm)

Gastec No.10+No.11(NO＝1.0ppm)

Gastec No.9P(NO₂＝1.1ppm)

HNO₂＝5.9ppm

The corrected concentrations were 1.0ppm for nitric oxide, 1.1ppm for nitrogen dioxide and 5.9ppm for nitrous acid vapor, and the emission concentrations were increased as compared with example 2. In this case, the concentrations of nitrogen monoxide and nitrogen dioxide are also substantially the same, and it is assumed that these 2 gases are produced by the auto-oxidation-reduction reaction (2 HNO) of nitrous acid₂→NO₂+NO+H₂O) is generated.

From this, it is found that the LDH containing nitrite ions releases a nitrogen-based gas at a high concentration if it is brought into contact with a gas containing a large amount of carbon dioxide and water vapor.

(example 4)

Using the apparatus shown in fig. 11, a nitrogen-based gas release experiment was performed on the nitrite ion-containing LDH obtained in example 1, and the measurement was performed using the detection tube 910.

Fig. 11 is a schematic diagram showing the apparatus and experimental system used in example 4.

The procedure of example 4 was carried out in the same manner as in example 3 except that the breath after contact with LDH (100mg) containing nitrite ions was passed through a Pasteur column 1110 packed with 750mg or 1500mg of iron (II) sulfate heptahydrate (manufactured by Fuji film and Wako pure chemical industries, Ltd.). The Pasteur column 1110 was made of 2mL of glass, and the length of the iron (II) sulfate heptahydrate packed in the Pasteur column 1110 was about 3cm (when the packing amount was 750 mg).

The results at a loading of 750mg of iron (II) sulfate heptahydrate are summarized.

Gastec No.11(NO+NO₂+HNO₂＝7.0ppm)

Gastec No.10+No.11(NO＝6.6ppm)

Gastec No.9P(NO₂＝0.55ppm)

HNO₂＝0ppm

Based on the above results, the concentration of nitrous acid vapor was almost zero since nitric oxide was 6.6ppm, nitrogen dioxide was 0.55ppm, and nitric oxide + nitrogen dioxide + nitrous acid vapor was 7.0ppm, showing that nitrous acid vapor can be converted to nitric oxide by passing through a pasteur column 1110 packed with iron (II) sulfate heptahydrate.

Note that, in the case where the amount of iron (II) sulfate heptahydrate packed in the pasteur column 1110 was doubled (length was about 6cm), the concentration of the generated nitric oxide was not changed. Thus, the upper limit of the amount of iron (II) sulfate heptahydrate relative to the nitrite ion-containing LDH is preferably 1700 mass%.

(example 5)

Using the apparatus shown in fig. 12, a nitrogen-based gas release experiment was performed on the nitrite ion-containing LDH obtained in example 1, and the composition of the released gas was measured by using the detection tube 910.

Fig. 12 is a schematic diagram showing the apparatus and experimental system used in example 5.

The procedure of example 5 was carried out in the same manner as in example 4 except that the nitrite ion-containing LDH and the contacted exhaled breath were passed through a pasteur column 1110 packed with 750mg of iron (II) sulfate heptahydrate and further passed through a pasteur column 1210 packed with 250mg of magnesium hydroxide (manufactured by kanto chemical co.). Wherein the lengths of iron (II) sulfate heptahydrate and magnesium hydroxide packed in each Pasteur column are about 3cm, respectively.

The results are summarized.

Gastec No.11(NO+NO₂+HNO₂＝4.0ppm)

Gastec No.10+No.11(NO＝4.0ppm)

Gastec No.9P(NO₂＝0.02ppm)

HNO₂＝0ppm

Based on the above results, since the concentration of nitric oxide was 4.0ppm, nitrogen dioxide was 0.02ppm, and the concentration of nitric oxide + nitrogen dioxide + nitrous acid vapor was 4.0ppm, the concentration of nitrous acid vapor was almost zero, and the concentration of nitrogen dioxide was also significantly reduced. This is considered because nitrogen monoxide is neutral and therefore does not pass through the magnesium hydroxide, whereas nitrogen dioxide and nitrous acid vapor are acidic gases and therefore removed by the neutralization reaction with magnesium hydroxide. From this, it was found that nitrogen dioxide and nitrous acid as impurities were hardly contained and high-purity nitric oxide could be produced by passing through a column packed with iron (II) sulfate heptahydrate and a column packed with magnesium hydroxide.

It is noted that the concentration of nitric oxide released reached a maximum approximately 15 to 30 minutes after the start of release, and was maintained at the maximum substantially even after release continued for 6 hours, showing that the LDH containing nitrite ions has a sustained release of nitric oxide.

(example 6)

In example 6, a nitrogen-based gas release experiment was performed on the LDH containing nitrite ions obtained in example 1 using the apparatus shown in fig. 13, and the composition of the released gas was measured using an electrochemical nitric oxide sensor.

Fig. 13 is a schematic diagram showing the apparatus and experimental system used in example 6.

The procedure of example 6 was repeated in the same manner as in example 4 except that the breath (50mL/min) after contact with the LDH containing nitrite ions (100mg) was introduced into a Pasteur column 1110 packed with 750mg of iron (II) sulfate heptahydrate, and then introduced into an electrochemical nitric oxide sensor (TOXIRAE Pro, detection range 0.5 to 250ppm))1310 instead of the detection tube 910.

Iron (II) sulfate heptahydrate packed in the pasteur column 1110 was periodically replaced with fresh and nitric oxide concentrations were measured over a 15 day period. The results are shown in FIG. 14. Further, infrared absorption spectra of LDH containing nitrite ions before and after 2 weeks of contact with breath are shown in fig. 15 b.

Fig. 14 is a graph showing the temporal change in the concentration of nitric oxide released in example 6.

In fig. 14, arrows indicate the timing of replacement of iron (II) sulfate heptahydrate. From fig. 14, it is understood that the release of nitric oxide is continued for 2 weeks or more, and the half-life of the concentration is about 6 days, and that the LDH containing nitrite ions of the present invention has excellent nitrogen-based gas release characteristics and functions as a nitrogen-based gas release agent.

This excellent sustained release property of nitric oxide is expected to be a method for supplying nitric oxide at a low concentration for a long period of time, and by combining with a device such as a quantitative pump or a nitric oxide sensor, application to home treatment of pulmonary hypertension and the like can be expected.

Fig. 15 is a graph showing a Thermogravimetry (TG) · Differential Thermal (DTA) curve (fig. 15a), an infrared absorption spectrum (fig. 15b), and a powder X-ray diffraction curve (fig. 15c) for the LDH containing nitrite ions before and after the expiratory contact in example 6, respectively.

In fig. 15, the curve of (i) is carbonic acid type LDH, (ii) is Cl type LDH, (iii) is nitrite ion-containing LDH before exhalation contact, and (iv) is nitrite ion-containing LDH after 2 weeks of exhalation contact.

In the infrared absorption spectrum of FIG. 15b, at 1227cm^-1The signal seen nearby corresponds to nitrite ions at 1360cm^-1The signal seen nearby corresponds to carbonate ions. Before contact with the breath, the signal of nitrite ion was stronger than that of carbonate ion, but after two weeks of contact with the breath, the signal of nitrite ion decreased and the signal of carbonate ion became stronger. This result supports the following mechanism described with reference to fig. 3: by solid-gas phase anion exchange reaction based on carbon dioxide in air, thereby separating from nitriteThe LDH of the seeds releases nitrous acid vapor, while carbonate ions remain within the LDH layer.

(examples 7 to 8)

In examples 7 and 8, the nitrogen-based gas release experiment was performed while changing the linkage form of the nitrite ion-containing LDH and iron (II) sulfate heptahydrate obtained in example 1, and the composition of the released gas was measured using an electrochemical nitric oxide sensor.

Fig. 16 is a schematic diagram showing the apparatus and experimental system used in example 7.

Fig. 17 is a schematic diagram showing an apparatus and an experimental system used in example 8.

As shown in fig. 16, the apparatus used in example 7 was formed as follows: in the apparatus used in example 6, 2 or 3 glass vessels containing 100mg each of the powdery samples 720 containing LDH containing nitrite ions were connected by a teflon (registered trademark) tube and a septum cap, and a same number of pasteur columns 1110 packed with 750mg each of iron (II) sulfate heptahydrate as the above glass vessels were connected downstream thereof. Fig. 16 shows a structure in which 3 powdery samples 720 of LDHs containing nitrite ions are connected to 3 pasteur columns 1110. In example 7, using this apparatus, exhaled breath was fed at a flow rate of 50mL/min, and after 15 minutes of stabilization, the concentration of nitric oxide in the released gas was measured using an electrochemical nitric oxide sensor. The results are shown in white bar graph in fig. 18.

On the other hand, as shown in fig. 17, the apparatus used in example 8 was formed as follows: in the apparatus used in example 6, a glass container containing a powdery sample 720 of 100mg of LDH containing nitrite ions and a pasteur column 1110 packed with 750mg of iron (II) sulfate heptahydrate were alternately connected to 2 or 3 groups using teflon (registered trademark) tubes. Fig. 17 shows a configuration in which a combination of a glass container containing a powdery sample 720 of LDH containing nitrite ions and a pasteur column 1110 was connected into 3 groups. In example 8, the concentration of nitric oxide in the released gas was measured using an electrochemical nitric oxide sensor under the same conditions as in example 7. The results are shown in a diagonal line-shaped graph in fig. 18.

Fig. 18 is a graph showing the relationship between the number of connected glass containers and the pasteur pillars 1110 and the concentration of nitric oxide released in examples 7 and 8.

In either of the configurations of example 7 and example 8, the concentration of nitric oxide tended to increase as the number of glass containers and the number of pasteur pillars 1110 increased. However, in the configuration of example 7, the rate of increase in the nitric oxide concentration was not directly proportional to the number of glass vessels and the number of pasteur pillars 1110, and tended to increase gradually. On the other hand, in the configuration of example 8, the ratio of increase in the nitric oxide concentration tended to increase in proportion to the number of glass vessels and the number of pasteur pillars 1110.

This is considered to be because, as in the constitution of example 8, in each of the glass vessel and the Pasteur column 1110, the nitric acid vapor was converted into nitric oxide by iron (II) sulfate heptahydrate, and the equilibrium of nitrous acid generation was not saturated. That is, it was revealed that a combination of LDH containing nitrite ions and a reducing agent, in other words, a composition of a nitrogen-based gas release agent, can release and release nitric oxide at a high concentration.

(example 9)

Using the apparatus shown in fig. 19, a nitrogen-based gas evolution experiment was performed on the mixture of LDH containing nitrite Ions and Iron (II) sulfate heptahydrate obtained in example 1, and the composition of the evolved gas was measured using an electrochemical nitric oxide sensor and a detector tube.

Fig. 19 is a schematic diagram showing an apparatus and an experimental system used in example 9.

The apparatus shown in fig. 19 was an apparatus obtained by changing the atmosphere gas supply unit 610 to a pump 710 and a 30mL plastic syringe 1910 filled with gauze wetted with water for humidification, the nitrogen-based gas slow-release unit 620 to a 3mL plastic syringe 1920 filled with a mixture of a powdery sample containing LDH containing nitrite ions obtained in example 1 sandwiched between cotton wool and iron (II) sulfate heptahydrate, and the impurity gas removal unit 630 to a 12mL plastic syringe 1210 filled with 4g of magnesium hydroxide, in the apparatus shown in fig. 6. In the apparatus of fig. 19, filters 730 are disposed in front of and behind a plastic syringe 1210, and the mixing of powder from the plastic syringe 1920 is suppressed. Further, a check valve for preventing backflow is provided downstream of the plastic syringe 1210.

As the plastic syringe 1920, 2 kinds of syringes each filled with a mixture of 100mg of LDH powder containing nitrite ions and 1.0g of iron (II) sulfate heptahydrate and a mixture of 50mg of LDH powder containing nitrite ions and 0.5g of iron (II) sulfate heptahydrate were used. Both the nitrite Ion and Iron (II) sulfate heptahydrate were made into powder using an agate mortar, and then mixed.

The operation of the apparatus proceeds in the following order. The atmosphere was supplied at a flow rate of 100mL/min by using a pump 710, and humidified by introducing it into a plastic syringe 1910. The measured relative humidity after humidification was 93%. The humidified air was introduced into a plastic syringe 1920 and a plastic syringe 1210 in this order. After passing through the syringe 1210, the gas having a flow rate of 100mL/min is mixed with 4L/min of atmospheric air, and introduced into the electrochemical nitric oxide sensor 1310 or the detection tube 1930, thereby measuring the nitric oxide concentration or the nitrogen dioxide concentration. The results are shown in fig. 20 and 21.

Fig. 20 is a diagram showing the state of the mixture before and after the nitrogen-based gas release experiment in the plastic syringe 1920 in example 9.

The area indicated by the dotted line in fig. 20 represents the mixture. The mixture before use (release experiment) had a pale blue colour but a brown colour after use (release experiment). In fig. 20, indicated by gray scale, a light color portion of the dotted line region corresponds to light blue, and a dark color portion of the dotted line region corresponds to brown. The color reaction is based on the oxidation of iron (II) sulfate heptahydrate in the mixture, and the iron ions with valence 2 before the release test become iron ions with valence 3 after the release test, suggesting that the iron ions with valence 2 function as a reducing agent. The color reaction can be used for qualitatively judging the preservation state of the nitrogen-containing gas slow-release body, particularly the nitric oxide slow-release body and the slow-release state of the nitric oxide.

Fig. 21 is a graph showing the temporal change in the concentration of nitric oxide released in example 9.

According to fig. 21, it is shown that a maximum of 16ppm nitric oxide can be sustained in 4.1L/min flow of air with 100mg of LDH containing nitrite ions, indicating that concentrations (5-20ppm) and respiration rates available for nitric oxide inhalation (about 0.5L/min for neonates, about 2.5L/min for toddlers) can be achieved. In the case of using 50mg of LDH containing nitrite ions, the sustained release concentration of nitric oxide was shown to be about half, and the carbon monoxide concentration could be increased or decreased by adjusting the amount of LDH containing nitrite ions, and the desired nitric oxide concentration could be easily obtained.

From fig. 21, it is understood that 1/100 of maximum 16ppm, i.e., 0.16ppm or more of nitric oxide was detected for 30 minutes or more. Therefore, the mixture of LDH powder containing nitrite Ions and Iron (II) sulfate heptahydrate used has a nitric oxide eluting property, and may be referred to as a nitrogen-based gas eluting body.

Furthermore, the concentration of nitrogen dioxide in combination with 16ppm of nitric oxide was measured using a detector tube (Gastec No.9P) and found a maximum of 0.075ppm, well below 0.2ppm, which is the environmental standard for 8-hour workers.

If the concentration of nitric oxide generated by 100mg of LDH containing nitrite ions and 1g of iron (II) sulfate heptahydrate is calculated, a maximum of 640ppm at a flow rate of 100mL/min is diluted to 5-16ppm by mixing it with 4L/min of air.

(example 10)

In example 10, CO in place of that of example 1₃ ^2-MgAl-LDH3, wherein the carbonate type LDH is represented by the general formula Mg, in which the metal ion having a valence of 2 is Mg ion, the metal ion having a valence of 3 is Al ion₂Al(OH)₆(CO₃ ^2-)_0.5·2H₂CO represented by O₃ ^2-MgAl-LDH2。CO₃ ^2-MgAl-LDH2 is synthesized by the method described in Japanese patent laid-open publication No. 2005-335965.

Specifically, first, MgCl was weighed₂·6H₂O(508mg)、AlCl₃·6H₂O (302mg), ion-exchanged water was added to prepare a 12.5mL solution, and to this solution, 12.5mL of an aqueous solution prepared by dissolving hexamethylenetetramine (613mg) was added and mixed. Subsequently, the resulting mixed solution was filtered with a membrane filter having a pore size of 0.2 μm, and then charged into a 50 mL-capacity pressure-resistant Teflon (registered trademark) container, and the container was sealed with a pressure-resistant stainless steel container, followed by hydrothermal treatment at 140 ℃ for 1 day. The mixture solution after the hydrothermal treatment was filtered, and the filtrate (residue) was washed with water and dried in vacuo to obtain 279mg of a white powder.

The resulting white powder had a particle size of about 0.5 to 2 μm and a Mg/Al molar ratio of 1.94 (+ -0.04). The Fourier transform Infrared absorption (FTIR) spectra are in complete agreement with the reported curves (e.g., Japanese patent application No. 2018-132081).

Then, the obtained carbonic acid type LDH (CO)₃ ^2-MgAl-LDH2) to Cl type LDH. The detailed description is as follows. Weigh 1.15g of CO₃ ^2-MgAl-LDH2 was placed in a three-necked flask, and 200mL of methanol was added to prepare a suspension. While the suspension was stirred by a magnetic stirrer under a nitrogen stream (500mL/min), 9.0mL of a hydrochloric acid alcohol solution (3 mass%) was added dropwise, and the mixture was stirred at 35 ℃ for 2 hours to react. Then, filtration, washing and drying were carried out under the same conditions as those for obtaining Cl-type LDH in example 1 to obtain 984mg of white powder.

The Fourier transform infrared absorption (FTIR) spectrum of the obtained white powder was measured, and 1360cm was not observed^-1Based on carbonate ions (CO)₃ ^2-) Thus judging that the carbonate ion is replaced with chloride ion. Hereinafter, the LDH is described as Cl^-MgAl-LDH2。

Then, from Cl^-MgAl-LDH2 makes LDHs containing nitrite ions. 400mg of Cl was added to a 3-neck flask under atmospheric pressure^-MgAl-LDH2, the flask was sufficiently purged with dry nitrogen. 150mL of degassed ion-exchanged water was added to the flask using a syringe to add Cl^-MgAl-LDH2 was thoroughly separatedAnd (6) dispersing. 1.89g of NaNO₂(Wako pure chemical industries, Ltd.) was dissolved in 30mL of degassed ion-exchanged water to prepare NaNO₂And (3) solution. Using a syringe to add NaNO₂The solution was added to the flask, stirred for 1 day, and then stirred and allowed to stand for 1 day. The filtrate (residue) was washed with degassed ion-exchanged water, and the filtrate was further washed with methanol, and the filtrate was dried under reduced pressure together with the membrane filter for about 120 minutes under vacuum to obtain a white powdery sample.

For the white powdery sample, FTIR measurement was carried out and was found to be based on 1227cm^-1Nitrite ion (NO)₂ ^-) Since the chloride ions were replaced by nitrite ions, LDH containing nitrite ions was obtained. The Mg/Al ratio was measured by SEM-EDS (JSM 6010LA, 10kV, manufactured by Japan electronics), and the Mg/Al ratio of the carbonic acid type LDH as the raw material was maintained. In addition, Cl is present to the extent of 8 to 9% relative to Al, supporting the formation of Cl groups^-The anion exchange of MgAl-LDH2 to LDH containing nitrite ions proceeded sufficiently. X-ray diffraction pattern and TG-DTA curve (Thermoplus 8120, RIGAKU) are characteristic of layered double hydroxide, and can be judged as carbonic acid type LDH (Mg)₂Al(OH)₈(CO₃ ^2-)_0.5·2H₂O) as a starting material, anion exchange was performed without destroying the layer structure. From this, it was judged that the obtained nitrite ion-containing LDH satisfied the above general formula (1).

Next, a package containing the LDH containing nitrite ions in a sealed manner was produced. The resulting white, powdery sample of LDH containing nitrite ions was put in a 13.5mL glass container (packaging material) together with a membrane filter in a glove box and sealed to prepare a package.

The LDH containing nitrite ions is taken out from the obtained package to constitute a nitrogen-based gas releasing device. The nitrogen-based gas release device used in example 10 is as follows: in the apparatus shown in FIG. 19 used in example 9, a plastic syringe 1920 was filled with Cl^-Powdery sample of LDH containing nitrite ions synthesized from MgAl-LDH2A syringe of 100mg mixed with 1.0g of powdered iron (II) sulfate heptahydrate measures the nitric oxide concentration in the released gas using an electrochemical nitric oxide sensor 1310. The results are shown in FIG. 22. Further, the state of the mixture after the release test was visually confirmed, and the X-ray diffraction (XRD) pattern thereof was measured using a powder X-ray diffraction apparatus (manufactured by RIGAKU, model RINT-2200V). The obtained XRD pattern is shown in fig. 23.

Fig. 22 is a graph showing the temporal change in the concentration of nitric oxide released in example 10.

Fig. 22 also shows the change with time in the concentration of nitric oxide released in example 9 (fig. 21). According to FIG. 22, in use, the catalyst is prepared from Cl^-In the case of LDH containing nitrite ions synthesized from MgAl-LDH2 (example 10), use was made of Cl^-Compared to the case of LDH containing nitrite ions synthesized from MgAl-LDH3 (example 9), the nitric oxide release concentration became more stable, and a prolonged sustained release time was observed. This shows that the sustained-release concentration and sustained-release time of nitric oxide can be controlled by adjusting the composition of the LDH containing nitrite ions/nitrate ions (e.g., Q, R, Z, x, d, g, j, etc. in the formula (1)).

Although not shown, the mixture before the release test had a pale blue color, but it was brown after use (release test) as in example 9. This suggests that the iron ions having a valence of 2 function as a reducing agent.

Fig. 23 is a graph showing an XRD pattern of the mixture after the release experiment in example 10.

In fig. 23, XRD patterns measured under dry nitrogen and under a nitrogen atmosphere with a relative humidity of 60%, respectively, are shown for the mixture of LDH powder containing nitrite Ions and Iron (II) sulfate heptahydrate after the release experiment. The basal spacing (spacing of the (003) -plane d) of LDH in the mixture was calculated from the results₀₀₃) Under dry nitrogen isUnder a nitrogen atmosphere with a relative humidity of 60%These values are in agreement with the bottom surface spacing and relative humidity responsiveness of LDH containing sulfate ions between layers, which have been reported in non-patent document 4 (Mg: Al ═ 2: 1), under a dry nitrogen atmosphereUnder a nitrogen atmosphere with a relative humidity of 60%The values of (a) are very close.

This result suggests that a solid-phase-solid-phase anion exchange reaction occurs between the LDH containing nitrite Ions and Iron (II) sulfate heptahydrate, and that the release of nitrite ions out of the outer layer and the introduction of sulfate ions into the LDH layers in the LDH containing nitrite ions occur, supporting a mechanism of slow release of nitrogen-based gas by the solid-phase-solid-phase anion exchange reaction.

(example 11)

In example 11, a medical respirator was produced using the mixture of LDH containing nitrite Ions and Iron (II) sulfate heptahydrate obtained in example 1.

Fig. 24 is a diagram showing a medical respirator according to example 11.

A respirator is provided with: a manual pump 2410 with a flow control cock, a humidifier 2420, a nitrogen-based gas release system 2430 of the present invention, an adsorbent 2440, and a ventilator 2450. Filters 2460 are provided before and after the adsorbent 2440 to prevent the powder from being mixed. Further, a backflow prevention check valve is preferably provided.

As the humidifier 2420, a 30mL plastic syringe filled with gauze moistened with water was used as in example 9. As the nitrogen-based sustained release agent 2430, a mixture of LDH containing nitrite ion (100mg) obtained in example 1 and iron (II) sulfate heptahydrate (1.0g) was used in the same manner as in example 9. As the adsorbent 2440, a 12mL plastic syringe filled with 4g of magnesium hydroxide was used in the same manner as in example 9. As the filter 2460, a filter having a pore size of 0.45 μm was used.

Air (0.1L/min) is supplied from the manual pump 2410 to the humidifier 2420, the humidified air is supplied to the nitrogen-based gas sustained release body 2430 to slowly release the nitrogen-based gas, and the nitric oxide having passed through the adsorbent 2440 is mixed with the air and supplied to the artificial respirator 2450. The concentration of nitric oxide supplied from the artificial respirator 2450 was measured by an electrochemical nitric oxide sensor, and found to be in the range of 5ppm to 20 ppm. Therefore, it was shown that the respirator can supply nitric oxide at a concentration required to meet the medical level only by manual operation without using any power source such as a battery.

The use of the nitrogen-containing gas sustained-release agent or sustained-release body of the present invention can provide a medical respirator that can be used as a nitric oxide supply mechanism that can be stored at room temperature and can be transported. By increasing the amount of the mixture of the powdery LDH containing nitrite Ions and Iron (II) sulfate heptahydrate or the number of syringes used for the mixture of the powdery LDH containing nitrite Ions and Iron (II) sulfate heptahydrate, it is possible to supply nitric oxide at a higher concentration, and in addition, it is possible to supply nitric oxide at a medical level (5 to 20ppm) to the artificial respirator even at a high flow rate of 4L/min or more. Longer nitric oxide delivery can also be achieved by periodic replacement of the syringe or equivalent containing a mixture of powdered LDH containing nitrite Ions and Iron (II) sulfate heptahydrate, either manually or mechanically.

(example 12)

In example 12, the carbonic acid type LDH (CO) used in example 1 was synthesized according to the method described in non-patent document 5₃ ^2-MgAl-LDH3) synthesized LDH containing nitrate ions.

Weigh 100mg of CO₃ ^2-MgAl-LDH3 was placed in a three-necked flask, and 40mL of methanol was added thereto to prepare a suspension. The suspension was stirred under a nitrogen stream (500mL/min) using a magnetic stirrer, and 10mL of methanol in which 132.5mg of ammonium nitrate was dissolved was added dropwise, followed by stirring at room temperature for 1 hour to effect reaction. Then, the same procedure as in example 1 was repeatedThe Cl type LDH was filtered, washed, and dried under the same conditions to obtain a white powdery sample.

The fourier transform infrared absorption (FTIR) spectrum and XRD pattern of the obtained white powdery sample were consistent with those reported in the related art (for example, non-patent document 5), and it was judged that the obtained white powdery sample was LDH containing nitrate ions. The nitrate ion-containing LDH is described as NO₃ ^-MgAl-LDH3。

The nitrogen-based gas release apparatus shown in fig. 25 was constructed using the LDH containing the nitrate ions thus obtained, and a nitrogen-based gas release experiment was performed.

Fig. 25 is a schematic diagram showing an apparatus and an experimental system used in example 12.

The apparatus shown in fig. 25 includes a pump 710, a humidifier 2510 as a gas washing bottle containing water, and a 2mL glass pasteur pipette 2520 filled with a nitrogen-based gas slow-release agent, and is configured to detect a nitrogen-based gas using a detection tube 2530. The pasteur pipette 2520 is filled with NO in the form of a powder with a spatula inserted with absorbent cotton₃ ^-MgAl-LDH3(38.4mg), powdered iron (II) sulfate heptahydrate (384mg), and sand-like zinc (3.84g, manufactured by Nacalai Tesque). The zinc sand was washed with 0.1mol/L diluted hydrochloric acid to remove oxides on the surface, washed with pure water and methanol, and sufficiently dried in vacuum. The zinc sand showed a silvery metallic luster after washing with hydrochloric acid.

The operation of the apparatus proceeds in the following order. The mixture was humidified by sending the mixture into the atmosphere at a flow rate of 100mL/min using a pump 710 and introducing the mixture into water in a gas washing bottle 2510 while bubbling. This humidified air is introduced into a pasteur pipette 2520 filled with a nitrogen-based gas retarder. After mixing 100mL/min of air passed through the pasteur pipette 2520 with 100mL/min of air (relative humidity 30%), adjusting the relative humidity to an appropriate range (90% RH or less) of the detection tube 2530, the concentration of the nitrogen-based gas contained in the gas was measured by the detection tube 2530. The concentration of the nitrogen-containing gas indicated by the detection tube was half of the actual concentration, and therefore, the correction was performed by a factor of 2. For stabilization of the released gas concentration, the measurement was started after feeding humidified air at 100mL/min to a pasteur pipette 2520 filled with a mixture of LDH containing nitrate ions, iron (II) sulfate heptahydrate, and zinc sand for about 1 hour.

A detection tube No.11L (for NO + NO) manufactured by Gastec corporation was used₂) The total amount of nitric oxide + nitrogen dioxide + nitrous acid vapour in the released gas is determined. The mixture was aspirated at a flow rate of 50mL/min for 4 minutes using a quantitative pump dedicated to the detection tube, and as a result, the concentration of nitric oxide + nitrogen dioxide + nitrous acid vapor was 1.4 ppm. This value is obtained by applying a 2-fold correction to the measurement value of the detection tube.

Next, a detection tube No.9P (for NO) manufactured by Gastec corporation was used₂) The concentration of only nitrogen dioxide in the released gas is determined. The nitrogen dioxide was 0.06ppm as a result of 10 minutes of suction at a flow rate of 100mL/min using a quantitative pump dedicated to the detection tube. This value is obtained by applying a 2-fold correction to the measurement value of the detection tube.

Next, a detection tube No.10 (for NO) manufactured by Gastec corporation₂) Detection tube No.11L manufactured by Gastec corporation for NO + NO₂) The coupling is performed to measure the concentration of nitric oxide in the released gas. Using a detection tube No.10 (for NO) manufactured by Gastec₂) O-tolidine contained in (1) after removing nitrogen dioxide and nitrous acid vapor, detection tube No.11L (for NO + NO) manufactured by Gastec corporation₂) The mixture was aspirated at a flow rate of 50mL/min for 4 minutes using a quantitative pump dedicated to the detection tube, and as a result, nitric oxide was 1.1 ppm. This value is obtained by applying a 2-fold correction to the measurement value of the detection tube.

Next, the ammonia concentration in the released gas was measured using a detection tube No.3L (for ammonia) manufactured by Gastec corporation. The ammonia concentration was judged to be 0.2ppm or less, since no reaction was observed at all, by using a quantitative pump dedicated to the detection tube and sucking the sample at a flow rate of 100mL/min for 2 minutes.

In addition, nitrous oxide (N) was collected from a high-pressure push tube (manufactured by GL Sciences)₂O), mixed with the atmosphere in a Tydla bag to about 10000ppm, using a detection tube No.11L manufactured by Gastec corporation (for NO + NO)₂) Or No.9P (for NO)₂) No reaction was seen at all in the results of sampling, so it can be said that these detection tubes were not reactive to nitrous oxide.

The above results are summarized.

Gastec No.11L(NO+NO₂+HNO₂＝1.4ppm)

Gastec No.10+No.11L(NO＝1.1ppm)

Gastec No.9P(NO₂＝0.06ppm)

HNO₂＝0.24ppm

In the gas generation method, nitrate ions released from LDH interlayer are reduced by 2-valent iron ions and/or metallic zinc, and converted into other nitrogen-based gas. In the case of considering the oxidation number of nitrogen atoms, the nitrate ion is +5, while nitrogen dioxide is +4, nitrous acid is +3, nitric oxide is +2, and nitrous oxide is +1, and therefore it is considered that these chemical species are mixed together depending on the degree of reduction of the nitrate ion as the starting material. By appropriately selecting the kind and combination of the reagents for reducing nitrate ions and the method of application thereof, it is expected that only a desired nitrogen-based gas can be slowly released, or the controlled release concentration and time can be controlled.

(example 13)

In example 13, with respect to the mixture of LDH containing nitrate ions, iron (II) sulfate heptahydrate, and zinc sand obtained in example 12, in the operation of example 9 using the apparatus shown in fig. 19, a nitrogen-based gas release experiment was performed without diluting the released gas with air at 4L/min, and the concentration of nitric oxide in the released gas was measured by an electrochemical nitric oxide sensor.

In the apparatus of fig. 19, the concentration of nitric oxide was measured by an electrochemical nitric oxide sensor 1310 in the same manner as in example 9, except that a mixture of 100mg of a powdery sample of LDH containing nitrate ions, 1.0mg of powdery iron (II) sulfate heptahydrate, and 10.0g of sand-like zinc was filled in a plastic syringe 1920, and the released gas was not diluted with air at 4L/min. The results are shown in FIG. 26. The sand-like zinc was pretreated in the same manner as in example 12.

Fig. 26 is a graph showing the temporal change in the concentration of nitric oxide released in example 13.

According to fig. 26, the measurement reached about 80ppm after the first 10 hours, the peak of attack, about 60ppm after 15 hours, and about 6ppm after 30 hours, indicating that the mixture of LDH containing nitrate ions, iron (II) sulfate heptahydrate, and zinc sand showed excellent nitric oxide-releasing properties.

(example 14)

In example 14, a nitrogen-based gas release experiment was performed on the mixture of LDH containing nitrite ions and sandy zinc obtained in example 1 using the apparatus shown in fig. 27, and the composition of the released gas was measured using a detection tube.

Fig. 27 is a schematic diagram showing the apparatus and experimental system using example 14.

The measurement was performed as follows. In the apparatus shown in FIG. 27, expired air (20 ℃, carbon dioxide concentration 4.0%, relative humidity 100%) stored in a 5L Tyndard bag 2710 was aerated into a 2mL glass Pasteur pipette 2720 at a flow rate of 100mL/min for 5 minutes by using a pump 710. A glass pasteur pipette 2720 was packed with a nitrogen-containing gas release agent obtained by wrapping a mixture of 100mg of a powdery sample of LDH containing nitrite ions and 6.70g of sandy zinc with absorbent cotton.

Then, the tedlar bag 2710 was removed, and the ammonia concentration in the gas on the outlet side was measured by introducing atmospheric air (relative humidity 42% to 46%) into the pasteur pipette 2720 at a flow rate of 100mL/min using a detection tube (gastec No.3l) 2730.

As a result, ammonia was not detected 1 minute and 5 minutes after the start of the atmospheric air supply to the nitrogen-based gas release agent. Then, 1ppm of ammonia was detected 10 minutes after the start of the atmospheric air supply, 0.5ppm of ammonia was detected 30 minutes later, 0.35ppm of ammonia was detected 1 hour later, and 0.1ppm of ammonia was detected 1 hour and 20 minutes later. Then, after 1 hour and 40 minutes from the start of the aeration, the ammonia concentration reached the detection limit (0.02ppm) of the detection tube 2730 or less. From the above results, it was shown that the mixture of LDH containing nitrite ions and zinc has ammonia-releasing property.

(example 15)

In example 15, a nitrogen-based gas release experiment was performed on the mixture of LDH containing nitrite ions and tin (II) chloride dihydrate obtained in example 1 using the apparatus shown in fig. 28, and the released gas was measured by infrared absorption spectroscopy.

Fig. 28 is a schematic diagram showing an apparatus and an experimental system used in example 15.

The apparatus of fig. 28 includes a pump 2810 for supplying nitrogen gas and a 30mL plastic syringe 1910 filled with gauze wetted with water for humidification as an atmosphere gas supply unit, and includes a 3mL plastic syringe 2820 as a nitrogen-based gas slow release unit. Further, a 30mL plastic syringe 2830 packed with 17.5g of molecular sieve 3a1/16 (manufactured by kanto chemical corporation) as an adsorbent for dehumidifying gas released from the slow-release part was provided downstream of the nitrogen-based gas slow-release part. The plastic syringe 2820 was filled with a nitrogen-based gas release agent obtained by sandwiching a mixture of 100mg of the powdery sample of the LDH containing nitrite ions obtained in example 1 and 1.0g of tin (II) chloride dihydrate (manufactured by Nacalai Tesque corporation) with absorbent cotton.

The operation of the apparatus is performed in the following order. Nitrogen gas was fed at a flow rate of 100mL/min by using a pump 2810, and the mixture was humidified by being introduced into a plastic syringe 1910. The relative humidity after humidification was 93%. The humidified nitrogen gas is introduced into a plastic syringe 2820 to generate a nitrogen-based gas, and the nitrogen-based gas is introduced into a plastic syringe 2830 to be dehumidified. The dehumidified gas was introduced into an infrared absorption spectrum gas chamber 2840 (manufactured by GL Sciences, having an optical path length of 10cm, and a window frame of NaCl single crystal), and the Fourier transform infrared absorption spectrum was measured. The results are shown in FIG. 29 a.

Fig. 29a shows the infrared absorption spectrum of the gas released 2 minutes after the start of the measurement. Referring to fig. 29a, it is shown that nitrous oxide, nitric oxide, nitrogen dioxide are contained in the gas released from the mixture of LDH containing nitrite ions and tin (II) chloride dihydrate.

Fig. 29b shows the temporal variation of the nitrous oxide concentration in the released gas. Furthermore, FIG. 29c shows the concentration of nitrous oxide in the released gas versus 2237cm in the infrared absorption spectrum of the gas^-1The infrared absorption intensity of (a) is a standard curve of the nitrous oxide concentration.

A standard curve for the nitrous oxide concentration was made as follows. Dinitrogen monoxide (10, 50, 100, 500, 1000ppm) was prepared at a known concentration by collecting a dinitrogen monoxide standard gas (100% concentration, manufactured by GL Sciences) with a syringe and diluting the gas with dry nitrogen in a 5L Tydlar bag. About half of the amount of the gas in the tedlar bag was introduced into the gas chamber for infrared absorption spectroscopy, and then the cock for introduction of the gas into the gas chamber was closed to measure the fourier transform infrared absorption spectroscopy. Because the concentration of nitrous oxide is 2237cm^-1The infrared absorption intensity of (A) can be seen as a good straight-line relationship (R)²0.9997) and can therefore be used as a standard curve.

Fig. 29b shows the temporal change in the nitrous oxide concentration calculated using the standard curve obtained in fig. 29c, the nitrous oxide concentration reaching 1108ppm after 2 minutes from the start of the measurement, 100ppm after 10 minutes and 28ppm after 30 minutes. Based on the results, it was shown that the mixture of LDH containing nitrite ions and tin (II) chloride dihydrate has a sustained release of nitrous oxide.

(example 16)

In example 16, a nitrogen-based gas evolution experiment was performed on the mixture of LDH containing nitrite Ions and Iron (II) sulfate heptahydrate obtained in example 1 using the apparatus shown in fig. 30, and the composition of the evolved gas was measured using an electrochemical nitric oxide sensor.

Fig. 30 is a schematic diagram showing an apparatus and an experimental system used in example 16.

The apparatus of fig. 30 includes, as an atmosphere gas supply unit, a pump 710 for supplying atmospheric gas, a pump 2810 for supplying nitrogen gas, and a 30mL plastic syringe 1910 connected to the pump 2810. The plastic syringe 1910 is filled with gauze moistened with water for humidification. In addition, the apparatus of fig. 30 includes a 3mL plastic syringe 1920 as a nitrogen-containing gas slow-release portion. The plastic syringe 1920 was filled with a nitrogen-based gas release agent obtained by sandwiching a mixture of 50mg of the powdery sample of LDH containing nitrite ions obtained in example 1 and 0.5g of iron (II) sulfate heptahydrate with absorbent cotton. An electrochemical nitric oxide sensor 1310 for detecting nitric oxide gas in the released gas is disposed downstream of the plastic syringe 1920. In fig. 30, the atmosphere from the pump 710 and the nitrogen gas from the pump 2810 can be switched.

The operation of the apparatus is performed in the following order. First, an atmosphere having a relative humidity of 38% was introduced into a plastic syringe 1920 at a flow rate of 100mL/min by using a pump 710, and diluted with 4.0L/min of atmosphere, and then the nitric oxide concentration was measured for 3 hours by using an electrochemical nitric oxide sensor 1310. Then, the pump 710 was switched to the pump 2810, nitrogen gas was fed at a flow rate of 100mL/min, and the mixture was introduced into the plastic syringe 1910 for humidification. The relative humidity after humidification was 93%. The humidified nitrogen gas was introduced into a plastic syringe 1920, and the nitric oxide concentration was measured for 3 hours using an electrochemical nitric oxide sensor 1310 in the same manner as in the case of introducing air. The results are shown in FIG. 31.

Fig. 31 is a graph showing the change with time in the nitric oxide concentration in example 16.

Even when the atmosphere was brought into contact with the nitrogen-based gas release agent, no nitric oxide was detected. However, when nitrogen saturated with water vapor is brought into contact with the nitrogen-based gas sustained release material, release of nitric oxide is observed immediately after the contact, indicating that nitric oxide can be sustained released.

The sustained release profile shown in fig. 31 closely resembles the sustained release behavior when the same amount of the mixture of LDH powder containing nitrite Ions and Iron (II) sulfate heptahydrate in fig. 21 (example 9) is brought into contact with humidified air, and shows that if a gas having a relative humidity of at least 40% or more is supplied to the mixture of LDH containing nitrite ions and the reducing agent, nitric oxide can be sustained released.

In the method, nitrogen gas or a rare gas is used as a base, and a gas containing no oxygen and/or carbon dioxide is supplied to release nitric oxide, so that oxidation of nitric oxide by oxygen can be prevented. Therefore, the released nitric oxide can be stored stably for a certain period of time in a tedlar bag or the like, and can be used even after the lapse of time from the start of release. Further, if nitrogen gas or a rare gas containing nitric oxide and water vapor is brought into contact with the molecular sieve 3A, only water molecules having a small molecular diameter can be adsorbed and removed to purify nitric oxide. On the other hand, in the conventional method of generating nitric oxide from nitrogen and oxygen in the atmosphere by arc discharge, the generated nitric oxide is not easily stored stably because nitric oxide and oxygen are mixed in principle.

(example 17)

In example 17, a nitrogen-based gas release experiment was performed by introducing dry nitrogen, nitrogen containing saturated water vapor, and dry nitrogen containing carbon dioxide into the LDH containing nitrite ions obtained in example 1 using the apparatus shown in fig. 32, and the composition of the released gas was measured using a detection tube.

Fig. 32 is a schematic diagram showing an apparatus and an experimental system used in example 17.

The apparatus shown in fig. 32 includes, as an atmosphere gas supply unit, 2 pumps 2810 for supplying dry nitrogen gas, a 30mL plastic syringe 1910 connected to 1 of the pumps 2810, a tedlar bag 3210 filled with dry nitrogen gas containing 4.0% carbon dioxide, and a pump 710 connected to the tedlar bag 3210 for supplying the gas inside to the nitrogen-based gas release unit. The plastic syringe 1910 is filled with gauze moistened with water for humidification. In the above-described atmosphere gas supply unit, a pump 2810 for supplying dry nitrogen gas, a plastic syringe 1910, and a pump 710 were connected to a 13.5mL glass vial constituting the nitrogen-based gas release unit, and 100mg of the nitrite ion-containing LDH720 obtained in example 1 was placed in the glass vial. Then, a detection tube 910 was disposed downstream of the glass vial to measure the composition of the gas released from LDH720 containing nitrite ions. In fig. 32, the gases supplied to LDH720 containing nitrite ions are 3 types of dry nitrogen, nitrogen containing saturated water vapor, and dry nitrogen containing 4.0% carbon dioxide, and they can be switched.

The operation of the apparatus is performed in the following order. First, a 13.5mL glass vial containing LDH720 containing 100mg of nitrite ions was prepared. The dried sample was placed in a desiccator, and dried for 30 minutes or more by starting a vacuum pump connected to the desiccator, thereby completely removing nitrogen-containing gas generated during storage or by contact with the atmosphere during weighing of LDH720 containing nitrite ions. After drying, the dryer was opened by nitrogen gas charging, the glass vial was connected to the apparatus shown in FIG. 32, and the pump 2810 was started to supply dry nitrogen gas at 50mL/min into the glass vial. The nitrogen-based gas contained in the dry nitrogen gas after contact with the LDH720 containing nitrite ions was measured by the nitrogen monoxide + nitrogen dioxide detection tube 910(Gastec No.11L), but no response was observed.

Next, the gas supplied to LDH720 containing nitrite ions was switched to nitrogen gas containing saturated water vapor, and as a result, release of nitrogen-based gas was observed immediately after switching, and the detection tube 910 showed 0.2 ppm. Since the 0.2ppm level was still observed in the detection tube 910 after 1 or 2 hours, it was found that the gas having a relative humidity of 40% or more was brought into contact with the LDH containing nitrite ions, whereby the nitrogen-based gas was slowly released by the gas containing no carbon dioxide. The composition of the released gas was measured in the same manner as in example 3 using another measuring tube, and as a result, the nitrogen dioxide was about 0.02ppm and the nitric oxide was 0.01ppm or less, and it was considered that the nitrogen-based gas of 0.2ppm was mainly composed of nitrous acid vapor. Further, it is predicted that the anion remaining in the LDH layer in exchange for generation of nitrous acid vapor is hydroxide ion (OH) derived from water^-)。

Next, the glass vial was temporarily taken out from the apparatus of fig. 32, and LDH720 containing nitrite ions was vacuum-dried in the above-described dryer for 40 minutes. After drying, the dryer was opened by charging nitrogen gas, and the glass vial was quickly connected to the apparatus shown in FIG. 32, and dry nitrogen gas was supplied at 50 mL/min. The nitrogen-based gas contained in the dry nitrogen gas after contact with the nitrite ion-containing LDH720 was measured by a nitrogen monoxide + nitrogen dioxide detecting tube 910(Gastec No.11L), and no response was confirmed.

Next, the gas supplied to LDH720 containing nitrite ions was switched to dry nitrogen containing 4.0% carbon dioxide, and as a result, release of nitrogen-based gas was confirmed immediately after the switching, and detection tube 910 showed 4.0 ppm. Dry nitrogen gas containing 4.0% carbon dioxide is supplied to the material filled in the tedlar bag 3210 using the pump 710. The detection tube 910 showed 4.5ppm after switching for 10 minutes, 4.5ppm after 26 minutes, 4.5ppm after 50 minutes, and 4.5ppm after 77 minutes, thus indicating that slow release of the nitrogen-based gas can be performed by bringing the gas containing at least carbon dioxide into contact with the LDH containing nitrite ions. It is considered that the proton source when generating the nitrous acid vapor is interlayer water of LDH.

Based on the above results, it was demonstrated that the nitrogen-based gas can be slowly released by bringing the LDH containing nitrite ions into contact with a gas containing water vapor and/or carbon dioxide.

Industrial applicability

According to the present invention, a solid material which sustains a nitrogen-based gas in the atmosphere at normal temperature can be obtained simply and more safely. The obtained nitrogen-based gas sustained-release agent generates a nitrogen-based gas by contacting with the atmosphere or exhaled breath, and does not require any operation using external energy such as heating or light irradiation. Further, the nitrogen-based gas concentration is substantially proportional to the ratio of nitrite ions/nitrate ions included between the layers of the LDH, and therefore, the nitrogen-based gas can be easily controlled. Therefore, it is expected to be applied to a nitric oxide gas supply source for medical use such as long-term exposure at a low concentration.

Specific examples of the method of use include treatment of pulmonary hypertension by supplying nitric oxide to inhaled breath in a concentration harmless to living bodies in the form of a disposable device such as an artificial respirator or a mask, which is free of maintenance. At present, expensive medical equipment is required for the treatment of nitric oxide inhalation, and facilities, countries, and regions where nitric oxide inhalation is possible are limited. However, according to the present invention, by exposing the nitrogen-based gas sustained-release agent or sustained-release body including LDH containing nitrite ions/nitrate ions to air, nitric oxide of a therapeutic concentration can be easily generated. Therefore, the present invention is useful from the viewpoint of contributing to the spread of the nitric oxide inhalation method, which can be performed in the circumstances and environments where the conventional technique cannot cover first aid of patients with dyspnea, home, developing countries, power outage, and the like.

In addition, nitric oxide is known to have physiological effects such as anti-oxidation, anti-inflammation, angiogenesis, and sterilization, in addition to vasodilation. According to the present invention, since nitric oxide can be easily generated at a ppm concentration by exposing a nitrogen-based gas sustained-release agent or a sustained-release body including LDH containing nitrite ions/nitrate ions to air, nitric oxide can be locally applied to external tissues such as skin. Thus, it is expected that nitric oxide can be used for beauty medical care and wound treatment.

Further, the present invention is expected to be a nitrogen-based gas source as a substitute for a heavy gas cylinder which is difficult to handle and has a risk of an accident, not only for medical use but also in industrial and research fields. In the present invention, commercially available, inexpensive LDH and nitrite/nitrate can be used as the raw materials, and a special production apparatus is not required, so that the production cost can be reduced. Further, the nitrogen-based gas release agent of the present invention retains the structure of LDH even after the release of the nitrogen-based gas is completed, and therefore, is useful as a nitrogen-based gas release agent, particularly a nitric oxide release agent, which is chemically stable, deliquescent, and highly safe.

Description of the symbols

100: layered Double Hydroxide (LDH), 110: layer, 120 anion, 200, 310, 720: LDH containing nitrite ions, 300, 510, 2430: nitrogen-based gas release, 320: reducing agent, 500: package, 520: packaging material, 600: sustained release device, 610: atmosphere gas supply unit, 620: nitrogen-based gas slow-release portion, 630: impurity gas removal units, 710, 2810: pump, 730, 2460: a filter, 740: aqueous solution obtained by dissolving Griess reagent, 910, 1930, 2530, and 2730: detection tube, 1010, 2710, 3210: tedlar bag, 1110: pasteur column packed with iron (II) sulfate heptahydrate, 1210: plastic syringe packed with magnesium hydroxide, 1310: electrochemical nitric oxide sensor, 2410: manual pump, 1910, 2420, 2510: humidifier (plastic syringe or gas washing bottle), 1920, 2820: plastic syringe filled with nitrogen-based gas sustained release body, 2520, 2720: pasteur pipette filled with nitrogen-based gas slow-release body, 2440, 2830: adsorbent or adsorbent-filled plastic syringe, 2450: artificial respirator, 2840: an air chamber.