Portable nitric oxide generator and methods of use thereof and applications thereof in inhaled nitric oxide therapy

Abstract

The application provides a portable nitric oxide generator, a method for using the same and application of the same in inhaled nitric oxide treatment. The generator comprises a shell, a partition plate is arranged in the shell to divide the shell into an upper shell and a lower shell, and a ring-shaped hole is arranged on the partition plate in a circumferential direction; an inner side wall of the upper shell is provided with a support frame for placing a medicine bottle, and the medicine bottle is used for containing a solid-phase reaction reagent capable of reacting with water to form nitric oxide; the inner side wall of the upper shell is also provided with a nitric oxide outlet connected with a breathing mask; the lower shell is provided with a baffle to divide the lower shell into a water storage area and a gas flow area, the upper part of the baffle is in a conical structure and extends into the upper shell through the ring-shaped hole; a plurality of siphon tubes are arranged along the outer wall of the baffle, one end of each siphon tube extends into water stored in the water storage area, and the other end of each siphon tube extends into the upper shell; the bottom end of the lower shell is provided with an air inlet in the gas flow area, and the gas flow area is provided with a compression pump.

Description

TECHNICAL FIELD

[0001] The present application relates to a portable nitric oxide generator, a method for using the same and an application of the same in the treatment of inhaled nitric oxide, and belongs to the technical field of gas generating devices. BACKGROUND

[0002] Nitric oxide (NO) is a highly reactive free radical and an indispensable chemical substance for human body. It is also an important signal gas molecule involved in various physiological processes of human body (such as vasodilation, anti-inflammation, and anti-virus). In vivo, it mainly realizes its biological function by increasing cyclic guanosine monophosphate levels. The inhalation of nitric oxide (iNO) is an established medical treatment for neonatal persistent pulmonary hypertension (PPHM), acute respiratory distress syndrome or pulmonary disease in premature infants. When the concentration of inhaled NO (iNO) is about 5-40 ppm, it can be used as a selective vasodilator for pulmonary vessels. In 1999, the U.S. Food and Drug Administration first approved iNO for the treatment of pulmonary arterial hypertension (PPHN) in full-term and late preterm infants or hypoxic respiratory failure related to echocardiography. Since then, iNO therapy has been clinically applied to the treatment of PPHN in full-term and late preterm infants. However, due to the lack of stable and convenient nitric oxide transportation technology, the wide application of iNO is still limited.

[0003] When iNO is used to treat neonatal pulmonary arterial hypertension abroad, it is almost achieved by a steel cylinder device containing NO gas matched with a delivery flow control instrument. This device is similar to a high-end medical instrument such as a respirator, and there has been almost no alternative solution in the past 20 years. The inconvenience and high transportation cost of the steel cylinder containing NO gas have been a thorn in the side of clinical treatment. In addition, due to the high concentration of NO gas in the steel cylinder, if it is inhaled by mistake due to improper dilution, it is easy to cause side reactions and has large toxic side effects, which has high safety hazards. This further limits the wide application of iNO in developing countries and non-hospital locations. In recent years, in order to further enable patients to use NO more conveniently, scientists have developed a portable NO generator based on the principle of electrocatalysis. Compared with the current NO inhalation device, the portable NO generator does not require a NO storage device and has the advantage of being prepared at any time when needed. However, the NO generation method in the portable NO generator is a liquid phase reaction, which has low safety. In addition, the portable NO generator needs to be connected to an external power source, which is still a big challenge for outdoor use.

[0004] Therefore, it has become a technical problem urgently to be solved in the field to provide a new type of portable nitric oxide generator, a method for using the same and an application of the same in the treatment of inhaled nitric oxide. SUMMARY

[0005] In order to solve the above-mentioned shortcomings and deficiencies, one object of the present application is to provide a portable nitric oxide generator.

[0006] Another object of the present application is to provide the use of the above-mentioned portable nitric oxide generator in the inhalation nitric oxide therapy.

[0007] Still another object of the present application is to provide the use of the above-mentioned portable nitric oxide generator. The portable nitric oxide generator provided by the present application can be used to provide medical nitric oxide instantly, and the highest concentration of the provided medical nitric oxide can reach 40 ppm, and low-concentration (less than 40 ppm) nitric oxide can be continuously released for dozens of hours.

[0008] In order to achieve the above-mentioned objects, in one aspect, the present application provides a portable nitric oxide generator, wherein the portable nitric oxide generator comprises a shell, an external part of the shell is provided with a power switch, an internal part of the shell is provided with a partition plate to divide the shell into an upper shell part and a lower shell part, and a ring-shaped hole is formed in the partition plate in a circumferential direction.

[0009] An openable and closable upper cover is arranged on the upper shell part, an inner side wall of the upper shell part is provided with a support frame for placing a medicine bottle, and the medicine bottle is used to contain a solid-phase reaction reagent which can react with water to form nitric oxide.

[0010] An inner side wall of the upper shell part is further provided with a nitric oxide outlet, and a breathing mask is connected to the nitric oxide outlet.

[0011] The lower shell part is provided with a baffle plate to divide the lower shell part into a water storage area and a gas flow area, an upper part of the baffle plate is in a conical structure and extends into the upper shell part through the ring-shaped hole, and a gas outlet is formed in a top part of the conical structure.

[0012] An inner side wall of the shell is provided with a water adding pipe which extends into the water storage area through the partition plate to add water into the water storage area, and a plurality of siphon pipes are arranged along an outer wall of the baffle plate, one end of each of the siphon pipes extends into water stored in the water storage area, and the other end of each of the siphon pipes extends into the upper shell part through the partition plate.

[0013] A bottom end of the lower shell part is provided with an air inlet in the gas flow area, and a compression pump is further arranged in the gas flow area.

[0014] As a specific embodiment of the above-mentioned portable nitric oxide generator of the present application, the solid-phase reaction reagent comprises a mixture of a layered double hydroxide and a soluble ferrous salt, the interlayer anion of the layered double hydroxide is nitrite ion, and the double metal is a combination of a divalent metal and a trivalent metal.

[0015] As a specific embodiment of the portable nitric oxide generator described above, the mass ratio of the layered double hydroxide and the soluble ferrous salt is 0.1-10:1.

[0016] As a specific embodiment of the portable nitric oxide generator described above, the mass ratio of the layered double hydroxide and the soluble ferrous salt is 1:1.

[0017] As a specific embodiment of the portable nitric oxide generator described above, the soluble ferrous salt comprises one or a combination of ferrous sulfate, ferrous nitrate and ferrous chloride.

[0018] As a specific embodiment of the portable nitric oxide generator described above, the molar ratio of the divalent metal and the trivalent metal is 0.1-10:1.

[0019] As a specific embodiment of the portable nitric oxide generator described above, the molar ratio of the divalent metal and the trivalent metal is 1:1.

[0020] As a specific embodiment of the portable nitric oxide generator described above, the divalent metal comprises any one of Ca, Mg, Mn, Fe, Co, Ni, Cu, Ba, Sr or Zn.

[0021] The trivalent metal comprises any one of Al, Cr, Mn, Co, Ga, Mo, In, V or Fe.

[0022] In some embodiments of the present application, the layered double hydroxide with nitrite ions as interlayer anions can be, for example, MgAl-nitrite layered double hydroxide, CaAl-nitrite layered double hydroxide, MgFe-nitrite layered double hydroxide, Fe(2+)Fe(3+)-nitrite layered double hydroxide, CoFe-nitrite layered double hydroxide, NiAl-nitrite layered double hydroxide, CuAl-nitrite layered double hydroxide, and the like.

[0023] As a specific embodiment of the portable nitric oxide generator described above, the preparation method of the layered double hydroxide comprises:

[0024] (1) uniformly dissolving a soluble divalent metal nitrate and a soluble trivalent metal nitrate in deionized water to obtain solution A;

[0025] (2) uniformly dissolving sodium hydroxide and sodium carbonate in deionized water to obtain solution B;

[0026] (3) quickly pour solution A into solution B and continuously stir, and maintain the pH value at 10 ± 0.1 by adding sodium hydroxide solution dropwise during the stirring, and carry out the reaction under this condition, and obtain the layered double hydroxide with nitrate ions as interlayer anions after the reaction is completed;

[0027] (4) calcine the layered double hydroxide with nitrate ions as interlayer anions in an inert atmosphere to obtain a mixed metal oxide;

[0028] (5) add the mixed metal oxide into a nitrous acid solution and carry out ion exchange under an inert atmosphere to obtain the layered double hydroxide.

[0029] As a specific embodiment of the portable nitric oxide generator described above in the present application, in step (4), the temperature of the calcination is 350-1200℃, and the time is 0.1-10h.

[0030] In some embodiments, in step (4), the temperature of the calcination is 550℃, and the time is 1h.

[0031] As a specific embodiment of the portable nitric oxide generator described above in the present application, in step (5), the mixed metal oxide is added into a nitrous acid solution, stirred in an inert atmosphere for 0.5-48h, and then left to stand for 1-48h to complete the ion exchange.

[0032] In some embodiments, in step (5), the mixed metal oxide is added into a nitrous acid solution, stirred in an inert atmosphere for 24h, and then left to stand for 24h to complete the ion exchange.

[0033] The preparation method of the layered double hydroxide provided in the present application further comprises "reconstruction" of the layered double hydroxide with nitrate ions as interlayer anions prepared by the coprecipitation method, i.e. calcining the layered double hydroxide with nitrate ions as interlayer anions to form a layered mixed metal oxide, and then performing ion exchange of nitrite ions by using the "memory effect" and "ion exchange effect", so as to obtain the layered double hydroxide with nitrite ions as interlayer anions.

[0034] In the preparation method of the layered double hydroxide provided in the present application, sodium hydroxide and sodium carbonate are used in a conventional amount, and the addition amount of sodium hydroxide and sodium carbonate can be reasonably determined according to the pH value of the system obtained in step (3) being 10 ± 0.1. In addition, in step (5), it is necessary to ensure that the nitrite ions used are in excess, i.e. the molar amount of the nitrite ions is higher than the molar amount of the nitrate contained in the layered double hydroxide with nitrate ions as interlayer anions.

[0035] As a specific embodiment of the portable nitric oxide generator described above, the shell is further provided with a gear adjustment button, which controls the air flow rate from the air inlet into the gas flow area by controlling the power of the compression pump.

[0036] As a specific embodiment of the portable nitric oxide generator described above, the upper part of the air outlet is provided with a baffle. The baffle is more conducive to water atomization.

[0037] In the present application, the gears of the gear adjustment button can be reasonably set according to the actual needs of the site operation, which can include only two different gears, or can include multiple different gears. For example, in some embodiments of the present application, the gear adjustment button only includes two different gears, high gear and low gear, and the corresponding air flow rates are 500 mL / min and 300 mL / min, respectively.

[0038] The present application does not make specific requirements for the specific number of siphons, and the number of siphons can be reasonably set according to the actual needs of the site.

[0039] In addition, the present application does not make specific requirements for the materials of the shell, the partition plate, the upper cover, the support frame, the medicine bottle, the breathing mask, the baffle, the water filling pipe, the baffle and the siphon in the portable nitric oxide generator, and the materials thereof can be reasonably selected according to the actual needs. For example, in some embodiments of the present application, the materials of the above-mentioned components can be plastic.

[0040] On the other hand, the present application also provides the use of the portable nitric oxide generator described above in the inhalation of nitric oxide treatment.

[0041] In another aspect, the present application also provides a use method of the portable nitric oxide generator described above, wherein the use method comprises:

[0042] 1) The solid-phase reaction reagent is fully ground and mixed for standby;

[0043] 2) Open the upper cover, place the ground and mixed solid-phase reaction reagent in the medicine bottle, and add water to the water storage area through the water filling pipe;

[0044] 3) Attach the breathing mask to the user's face and cover the mouth and nose, turn on the power switch, inject air into the upper part of the shell along the gas flow area through the compression pump and form a vacuum area near the air outlet, so that the water entering the upper part of the shell through the siphon is atomized, the atomized water vapor reacts with the solid-phase reaction reagent to generate nitric oxide, and the nitric oxide enters the user's mouth and nose through the breathing mask.

[0045] As a specific embodiment of the above-mentioned use method of the present application, the use method further comprises: adjusting the power of the compression pump through the gear adjustment button to control the flow rate of the air entering the upper part of the shell along the gas flow passage to the gas flow passage area, thereby controlling the flow rate of the atomized water vapor and finally controlling the generation rate and concentration of the nitric oxide to meet the user's demand for different nitric oxide doses.

[0046] The present application atomizes liquid water by using the Venturi principle, and transmits the atomized water vapor into the upper part of the shell, where the water vapor reacts with the solid-phase reaction reagent to produce nitric oxide.

[0047] The portable nitric oxide generator provided by the present application uses a mixture of layered double hydroxide with interlayer anions of nitrite ions and soluble ferrous salt as the solid-phase reaction reagent. Under the condition of water vapor, the solid-phase reaction reagent can react with water vapor to produce nitric oxide, so that the portable nitric oxide generator can slowly, accurately and long-term release NO. The detailed reaction mechanism is as follows: after the mixture of layered double hydroxide with interlayer anions of nitrite ions (LHD-NO2) powder and soluble ferrous salt powder, in a humid environment, the nitrite ions NO2 - in the interlayer of LHD-NO2 will be released by "ion exchange"; at the same time, the sulfate ions SO4 2- released by the hydrolysis of soluble ferrous salt will also enter the interlayer of LHD-NO2 by "ion exchange", so that SO4 2- , NO2 - , Fe 2+ continuously contact and produce NO through the chemical reaction shown below;

[0048] NO2 - + Fe 2+ + 2H + → NO + Fe 3+ + H2O.

[0049] Unlike the NO generators on the market based on the principle of electrocatalysis, the portable nitric oxide generator provided by the present application uses a solid-phase reaction reagent, and the concentration of nitric oxide released by the solid-phase reaction reagent is suitable for the actual medical needs. The solid-phase reaction reagent has higher safety and convenience than the liquid-phase electrocatalysis technology, so that the portable nitric oxide generator has the characteristics of safety, low cost, lightness, compact design, easy operation and portability, and it has unprecedented potential and value in the medical field. BRIEF DESCRIPTION OF DRAWINGS

[0050] In order to make the technical solutions in the embodiments of the present application or the prior art clearer, the accompanying drawings needed in the embodiment description will be briefly introduced. Obviously, the accompanying drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without any creative effort based on these drawings.

[0051] Figure 1 The XRD pattern of the magnesium-aluminum-nitrite layered double hydroxide prepared for the embodiment 1 of the present application.

[0052] Figure 2 The structural schematic diagram of the portable nitric oxide generator provided for the embodiment 2 of the present application.

[0053] Figure 3 The effect schematic diagram of the portable nitric oxide generator in the application example 1 of the present application for generating nitric oxide.

[0054] Figure 4 The effect schematic diagram of the portable nitric oxide generator in the application example 2 of the present application for generating nitric oxide under different air inlet speeds.

[0055] Main figure number explanation:

[0056] 1, upper cover;

[0057] 2, breathing mask;

[0058] 3, water adding pipe;

[0059] 4, medicament bottle;

[0060] 5, power switch;

[0061] 6, gear adjustment key;

[0062] 7, water storage area;

[0063] 8, compression pump;

[0064] 9, air inlet;

[0065] 10, partition plate;

[0066] 11, baffle;

[0067] 12, support frame;

[0068] 13, gas flow area;

[0069] 14, conical structure;

[0070] 15, siphon pipe;

[0071] 16, upper part of shell;

[0072] 17. lower housing part;

[0073] 18. baffle. DETAILED DESCRIPTION

[0074] In order to have a clearer understanding of the technical features, objectives and beneficial effects of the present application, the technical solutions of the present application will be described in detail below in conjunction with the following specific embodiments, but it should not be understood as limiting the scope of the present application.

[0075] It should be noted that the terms "comprising" and any variations thereof in the specification and claims of the present application and the above-described drawings are intended to cover not only the inclusive but also the exclusive inclusion of the steps or units of the process, method, system, product or apparatus, for example, the process, method, system, product or apparatus comprising a series of steps or units does not have to be limited to only those steps or units clearly listed, but can include other steps or units that are not clearly listed or inherent to these processes, methods, products or apparatus.

[0076] In the present application, the terms "upper", "lower", "inner", "outer", "middle" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings. These terms are mainly used to better describe the present application and its embodiments, and are not intended to limit the indicated devices, elements or components to have a specific orientation, or to be constructed and operated in a specific orientation.

[0077] In addition, in addition to being used to indicate the orientation or positional relationship, the above-mentioned part of the terms can also be used to indicate other meanings, for example, the term "upper" can also be used to indicate a certain dependent relationship or connection relationship in some cases. For those skilled in the art, the specific meaning of these terms in the present application can be understood according to the specific circumstances.

[0078] In addition, the terms "provided", "connected" should be broadly understood. For example, "connected" can be fixedly connected, detachably connected, or integrally constructed; can be mechanically connected, or electrically connected; can be directly connected, or indirectly connected through an intermediate medium, or internal communication between two devices, elements or components. For those skilled in the art, the specific meaning of the above-mentioned terms in the present application can be understood according to the specific circumstances.

[0079] The ranges disclosed herein are presented in terms of "about" a range along with the upper and lower limits thereof. The ranges can each be independently a sub-range of any of the ranges disclosed herein. For example, a range of 60-120 and 80-110 is understood to include the ranges of 60-110 and 80-120. In addition, if a minimum range value of 1 and 2 is listed, and a maximum range value of 3, 4 and 5 is listed, then the following ranges are all contemplated: 1-3, 1-4, 1-5, 2-3, 2-4 and 2-5.

[0080] In the present application, unless otherwise stated, the numerical range "a-b" indicates a shorthand for the inclusion of any and all combinations of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in the present application, and "0-5" is merely a shorthand for these numerical combinations.

[0081] In the present application, unless otherwise stated, all embodiments and preferred embodiments mentioned in the present application can be combined with each other to form new technical solutions.

[0082] In the present application, unless otherwise stated, all technical features and preferred features mentioned in the present application can be combined with each other to form new technical solutions.

[0083] In order to make the purpose, technical solutions and advantages of the present application more clear, the present application is further described in detail below in combination with the drawings and examples. The following described examples are part of the examples of the present application, but not all the examples, and are only used to illustrate the present application, and should not be regarded as limiting the scope of the present application. Based on the examples in the present application, all other examples obtained by those skilled in the art without making creative efforts are within the scope of protection of the present application. The specific conditions not mentioned in the examples are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments not mentioned by the manufacturer are all conventional products that can be purchased in the market.

[0084] Example 1

[0085] The present example provides a magnesium-aluminum-nitrite layered double hydroxide, which is prepared by a preparation method comprising the following specific steps:

[0086] 1) Preparation of solution A:

[0087] A solution A was prepared by dissolving 12.87 g of magnesium nitrate hexahydrate and 6.26 g of aluminum nitrate nonahydrate in 130 mL of deionized water, and stirring the resulting mixture at room temperature in a 250 mL closed glass bottle.

[0088] 2) Preparation of solution B:

[0089] A solution B was prepared by dissolving 2.80 g of sodium hydroxide and 1.76 g of sodium carbonate in 65 mL of deionized water, and stirring until clear.

[0090] 3) Mixing reaction:

[0091] Solution A was quickly poured into solution B (within 10 s), and stirring was continued at room temperature for 45 min; during the stirring, the pH of the resulting solution was maintained at 10 ± 0.1 by adding sodium hydroxide solution dropwise; and the co-precipitation reaction was carried out under this condition, after which the resulting product was centrifuged, washed with deionized water, dried, ground, to obtain a layered double hydroxide with nitrate ions as interlayer anions.

[0092] 4) Calcination:

[0093] The layered double hydroxide with nitrate ions as interlayer anions was calcined at 550°C for 1 h under a nitrogen atmosphere to obtain a layered mixed metal oxide.

[0094] 5) Ion exchange:

[0095] The layered mixed metal oxide was added to a nitrous acid solution, and after stirring for 24 h under a nitrogen atmosphere, the mixture was allowed to stand for 24 h to complete the ion exchange; finally, the ion-exchanged sample was washed with deionized water, and after drying and grinding, the magnesium-aluminum-nitrite layered double hydroxide was obtained, and was stored in a glove box (inert gas atmosphere) for use.

[0096] The magnesium-aluminum-nitrite layered double hydroxide prepared in step 5) of this example 1 was subjected to XRD analysis, and the resulting XRD pattern is shown in Figure 1 From Figure 1 it can be seen that the Rietveld structure refinement shows that the XRD spectrum of the magnesium-aluminum-nitrite layered double hydroxide prepared in step 5) matches the standard spectrum of magnesium-aluminum-nitrite layered double hydroxide (MgAl-NO2-LDH), indicating that a high-purity magnesium-aluminum-nitrite layered double hydroxide was prepared in this example 1.

[0097] Example 2

[0098] The portable nitric oxide generator provided in this example has a structure as shown in the structural schematic diagram of the portable nitric oxide generatorFigure 2 As shown in the drawings, Figure 2 As can be seen from the drawings, the portable nitric oxide generator comprises a shell, the outer part of which is provided with a power switch 5, and the inner part of which is provided with a partition plate 10 to divide the shell into a shell upper part 16 and a shell lower part 17, and the partition plate 10 is provided with an annular hole in the circumferential direction;

[0099] The shell upper part 16 is provided with an openable and closable upper cover 1, and the inner side wall of the shell upper part 16 is provided with a support frame 12 for placing a medicine bottle 4, which is used to contain a solid-phase reaction reagent, which is a mixture of magnesium-aluminum-nitrite layered double hydroxide and ferrous sulfate prepared in Embodiment 1, and the mass ratio of the two is 1:1;

[0100] The inner side wall of the shell upper part 16 is also provided with a nitric oxide outlet, which is connected with a breathing mask 2;

[0101] The shell lower part 17 is provided with a baffle plate 11 to divide the shell lower part 17 into a water storage area 7 and a gas flow area 13, the upper part of the baffle plate 11 is a tapered structure 14 and extends into the shell upper part 16 through the annular hole, the top of the tapered structure 14 is provided with a gas outlet, and the upper part of the gas outlet is provided with a baffle 18;

[0102] The inner side wall of the shell is provided with a water adding pipe 3 extending through the partition plate 10 and into the water storage area 7, which is used to add water to the water storage area 7, and two siphon pipes 15 are arranged along the outer wall of the baffle plate 11, one end of the siphon pipes 15 extends into the water stored in the water storage area 7, and the other end extends into the shell upper part 16 through the partition plate 10;

[0103] The bottom end of the shell lower part 17 is provided with an air inlet in the gas flow area 13, and the gas flow area 13 is also provided with a compression pump 8;

[0104] The shell is also provided with a gear adjustment button 6 to control the air flow rate entering the gas flow area 13 from the air inlet 9 by controlling the power of the compression pump 8.

[0105] The materials of the shell, the partition plate, the upper cover, the support frame, the medicine bottle, the breathing mask, the baffle plate, the water adding pipe, the baffle and the siphon pipe in the portable nitric oxide generator provided by the embodiment are all plastic.

[0106] Embodiment 3

[0107] The embodiment provides a use method of the portable nitric oxide generator in Embodiment 2, and the use method comprises the following specific steps:

[0108] 1) The magnesium-aluminum-nitrite layered double hydroxide prepared in Example 1 and ferrous sulfate are mixed in a mass ratio of 1:1 and ground to obtain solid-phase reaction reagents, which are ready for use;

[0109] 2) The upper cover is opened, the ground solid-phase reaction reagents are placed in the medicine bottle, and an appropriate amount of clean water is added to the water storage area through the water adding pipe;

[0110] 3) The breathing mask is attached to the user's face and covers the mouth and nose, the power switch is turned on, and air is injected into the upper part of the shell along the gas flow area through the compression pump to form a vacuum area near the air outlet, so that the water entering the upper part of the shell through the siphon is atomized, the atomized water vapor reacts with the solid-phase reaction reagents to generate nitric oxide, and the nitric oxide enters the user's mouth and nose through the breathing mask;

[0111] The use process also includes adjusting the power of the compression pump through the gear adjustment button to control the flow rate of air entering the upper part of the shell along the gas flow area through the air inlet, thereby controlling the flow rate of the atomized water vapor and ultimately controlling the generation rate and concentration of nitric oxide.

[0112] Application Example 1

[0113] In order to further verify the use effect of the portable nitric oxide generator provided by Example 2 of the present application, the application example applies the portable nitric oxide generator according to the use method provided by Example 3 and tests the release of nitric oxide. In the application process, the solid-phase reaction reagents are a mixture of 0.2 g of the magnesium-aluminum-nitrite layered double hydroxide prepared in Example 1 and 0.2 g of ferrous sulfate; the gear adjustment button is in the high-speed gear, the air flow rate is controlled at 500 mL / min, and the atomized water vapor is reacted with the solid-phase reaction reagents to generate nitric oxide under this condition.

[0114] In the application example, the effect diagram of the portable nitric oxide generator generating nitric oxide at room temperature of 23±1℃ is as shown in Figure 3 From Figure 3 it can be seen that the concentration of nitric oxide can reach 40 ppm, and low-concentration (about 5 ppm) nitric oxide can be continuously released for tens of hours without replacing the medicine. Therefore, it is shown that the concentration of nitric oxide released by the solid-phase reaction reagents in the portable nitric oxide generator is suitable for the required concentration in actual medical treatment, and the cost is low, which has great application prospect.

[0115] Application Example 2

[0116] In order to further verify the effect of the portable nitric oxide generator provided in Embodiment 2 of the present application on the generation of nitric oxide under different air inlet (air) speeds, the application example applies the portable nitric oxide generator according to the use method provided in Embodiment 3 and tests the release of nitric oxide under different air inlet speeds. In the application process, the solid-phase reaction reagent is a mixture of 0.1 g of the magnesium-aluminum-nitrite layered double hydroxide prepared in Embodiment 1 and 0.1 g of ferrous sulfate; the gear adjustment button is in the high-speed gear and the low-speed gear, respectively, the control air flow rate is 500 mL / min and 300 mL / min, respectively, and the atomized water vapor is contacted with the solid-phase reaction reagent under the above conditions to generate nitric oxide.

[0117] In the application example, the schematic diagram of the effect of the portable nitric oxide generator on the generation of nitric oxide under different air inlet speeds at room temperature of 23±1℃ is shown in FIG. 2. Figure 4 As can be seen from FIG. 2, Figure 4 it can be seen that the peak concentration of the nitric oxide released by the portable nitric oxide generator is different under different air inlet (air) speeds when the gear adjustment button is in the high-speed gear and the low-speed gear. This indicates that the concentration of the nitric oxide released by the solid-phase reaction reagent in the portable nitric oxide generator can meet the needs of different users, and has a low cost and a great application prospect.

[0118] In the application example 1 and the application example 2 of the present application, the concentration of nitric oxide is measured by using the existing conventional equipment in the field and under conventional test conditions.

[0119] In summary, unlike the NO generator based on the principle of electrocatalysis on the market at present, the portable nitric oxide generator provided in the embodiments of the present application uses a solid-phase reaction reagent, and the concentration of the nitric oxide released by the solid-phase reaction reagent is suitable for the actual medical concentration required. The solid-phase reaction reagent has higher safety and convenience than the liquid-phase electrocatalysis technology, so that the portable nitric oxide generator has the characteristics of safety and low cost, as well as a light and compact design, is easy to operate and carry, has an unprecedented potential and value in the medical field.

[0120] The above description is only a specific embodiment of the present application, which cannot limit the scope of the application. Therefore, the replacement of equivalent components or equivalent changes and modifications made within the scope of the patent protection of the present application should still belong to the scope covered by the present patent. In addition, the technical features in the present application can be freely combined with each other, and the technical features can be freely combined with each other.

Claims

1. A portable nitric oxide generator, characterized by comprising: The portable nitric oxide generator comprises a shell, an external power switch of the shell, and a partition plate arranged in the shell to divide the shell into an upper shell and a lower shell, and a ring-shaped hole is arranged on the partition plate in the circumferential direction. The upper shell is provided with an openable and closable upper cover, and an inner side wall of the upper shell is provided with a support frame for placing a medicine bottle, which is used to contain a solid-phase reaction reagent capable of reacting with water to form nitric oxide. The inner side wall of the upper shell is also provided with a nitric oxide outlet connected with a breathing mask. The lower shell is provided with a baffle to divide the lower shell into a water storage area and a gas flow area, the upper part of the baffle is a tapered structure and extends into the upper shell through the ring-shaped hole, and the top of the tapered structure is provided with a gas outlet. An inner side wall of the shell is provided with a water adding pipe extending through the partition plate and into the water storage area for adding water to the water storage area, and a plurality of siphon tubes are arranged along the outer wall of the baffle, one end of each siphon tube extends into the water stored in the water storage area, and the other end extends into the upper shell through the partition plate. The bottom end of the lower shell is provided with an air inlet in the gas flow area, and the gas flow area is also provided with a compression pump, wherein the compression pump is used to inject air into the upper shell along the gas flow area and form a vacuum area near the gas outlet, so that the water entering the upper shell through the siphon tube is atomized, and the atomized water vapor reacts with the solid-phase reaction reagent to generate nitric oxide.

2. The portable nitric oxide generator of claim 1, wherein, The solid-phase reaction reagent comprises a mixture of layered double hydroxide and soluble ferrous salt, and the interlayer anion of the layered double hydroxide is nitrite ion, and the bimetallic metal is a combination of divalent metal and trivalent metal.

3. The portable nitric oxide generator of claim 2, wherein, The mass ratio of the layered double hydroxide and the soluble ferrous salt is 0.1-10:

1.

4. The portable nitric oxide generator of claim 3, wherein, The mass ratio of the layered double hydroxide and the soluble ferrous salt is 1:

1.

5. The portable nitric oxide generator of claim 2, wherein, The soluble ferrous salt includes one or a combination of several of ferrous sulfate, ferrous nitrate and ferrous chloride.

6. The portable nitric oxide generator of claim 2, wherein, The molar ratio of the divalent metal and the trivalent metal is 0.1-10:

1.

7. The portable nitric oxide generator of claim 6, wherein, The molar ratio of the divalent metal and the trivalent metal is 1:

1.

8. The portable nitric oxide generator of any one of claims 2-7, wherein, The divalent metal includes any one of Ca, Mg, Mn, Fe, Co, Ni, Cu, Ba, Sr or Zn. The trivalent metal includes any one of Al, Cr, Mn, Co, Ga, Mo, In, V or Fe.

9. The portable nitric oxide generator of any one of claims 2-7, wherein, The preparation method of the layered double hydroxide comprises: (1) uniformly dissolving soluble divalent metal nitrate and soluble trivalent metal nitrate in deionized water to obtain solution A; (2) uniformly dissolving sodium hydroxide and sodium carbonate in deionized water to obtain solution B; (3) quickly pouring solution A into solution B and continuously stirring, and adding sodium hydroxide solution dropwise to maintain the pH value at 10±0.1 during the stirring process, and reacting under this condition, and obtaining layered double hydroxide with carbonate ions as interlayer anions after the reaction is completed. (4) calcining the layered double hydroxide with interlayer anions of carbonate ions in an inert atmosphere to obtain a mixed metal oxide; (5) adding the mixed metal oxide into a nitrous acid solution and performing ion exchange under an inert atmosphere to obtain the layered double hydroxide.

10. The portable nitric oxide generator of claim 9, wherein, In step (4), the temperature of the calcination is 350-1200°C, and the time is 0.1-10 h.

11. The portable nitric oxide generator of claim 9, wherein, In step (5), the mixed metal oxide is added into a nitrous acid solution, stirred in an inert atmosphere for 0.5-48 h, and then left to stand for 1-48 h to complete the ion exchange.

12. The portable nitric oxide generator of any of claims 1-7, 10-11, wherein, The shell is further provided with a gear adjustment button for controlling the air flow rate from the air inlet into the gas flow area by controlling the power of the compression pump.

13. The portable nitric oxide generator of any of claims 1-7, 10-11, wherein, The upper part of the air outlet is provided with a baffle.

14. Use of the portable nitric oxide generator of any one of claims 1-13 in the preparation of an inhaled nitric oxide treatment device.

15. Use according to claim 14, characterized in that, The use method of the portable nitric oxide generator comprises: 1) grinding and mixing the solid-phase reaction reagent thoroughly for standby; 2) opening the upper cover, placing the ground and mixed solid-phase reaction reagent in the medicine bottle, and adding water to the water storage area through the water adding pipe; 3) attaching the breathing mask to the user's face and covering the mouth and nose, turning on the power switch, and injecting air into the upper part of the shell along the gas flow area through the compression pump and forming a vacuum area near the air outlet, so that the water entering the upper part of the shell through the siphon pipe is atomized, the atomized water vapor reacts with the solid-phase reaction reagent to generate nitric oxide, and the nitric oxide enters the user's mouth and nose through the breathing mask.

16. The use according to claim 15, characterized in that, The use method further comprises adjusting the power of the compression pump through the gear adjustment button to control the flow rate of the air entering the upper part of the shell along the gas flow area through the air inlet, thereby controlling the flow rate of the atomized water vapor and finally controlling the generation rate and concentration of nitric oxide.

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