Method for generating nitric oxide gas and apparatus therefor

Abstract

The application discloses a method for generating nitric oxide gas, and belongs to the field of gas preparation and medical treatment, and is characterized in that the method for generating nitric oxide gas is to mix liquid medicament with solid medicament, to make the liquid medicament and the solid medicament react chemically, so as to generate nitric oxide gas with a certain concentration, the effective component of the solid medicament is nitrosyl iron sulfate, and the liquid medicament is one or a mixture of several kinds of alkali solution or slurry and salt solution or slurry. The application further discloses a corresponding device for generating nitric oxide gas.

Description

Technical Field

[0001] This invention relates to a method and apparatus for generating nitric oxide gas, used to produce nitric oxide gas of a certain concentration, and particularly to the application of nitric oxide gas generation in medical and other related fields. Background Technology

[0002] Nitric oxide (NO) is a colorless gas, slightly soluble in water. Studies have found that nitric oxide acts as a messenger molecule in the human body. Nitric oxide molecules can easily cross cell membranes, causing smooth muscle cells around blood vessels to relax upon receiving the signal, thus dilating blood vessels. Therefore, inhaling a certain concentration of nitric oxide gas can help in the treatment of diseases such as those of the heart and lungs, and also has certain health benefits. However, when the amount inhaled exceeds a certain concentration and quantity, it is harmful to the body.

[0003] Currently, industrial methods for preparing nitric oxide gas, depending on the intended use, mainly include direct synthesis, ammonia catalytic oxidation, and the reaction of sodium nitrite with dilute sulfuric acid. The resulting nitric oxide gas is typically stored in pressurized steel cylinders. When used in medical procedures, the nitric oxide in the cylinders needs to be pre-diluted to a certain concentration, making it generally suitable only for centralized use in medical institutions and inconvenient for personal transport or home use. Furthermore, due to its reactive chemical properties, nitric oxide gas readily converts into nitrogen dioxide and nitrous oxide, thus it is not suitable for long-term storage.

[0004] To reduce operating costs and facilitate individual and household use, many manufacturers both domestically and internationally have developed portable nitric oxide gas generators. Based on their generation principles, these portable nitric oxide gas generators mainly fall into two categories: one utilizes gas discharge technology, as shown in Chinese Patent Publication (CN113456966A), and the other generates nitric oxide through the electrolysis of solutions such as nitrite, as shown in Chinese Patent Publication (CN111636071A). However, these nitric oxide gas generators are all active products, requiring advanced usage and maintenance techniques, and therefore have not yet achieved widespread use.

[0005] This invention utilizes the reaction of ferrous sulfate solution with nitric oxide to generate nitric oxide nitrosyl ferric sulfate (molecular formula, Fe(NO)SO4, also known as nitrosyl ferrous sulfate), and develops a method and corresponding generating apparatus for generating nitric oxide gas to meet relevant requirements. Summary of the Invention

[0006] In view of the problems existing in the prior art, the purpose of this invention is to design and provide a technical solution for a method and apparatus for generating nitric oxide gas.

[0007] The present invention specifically adopts the following technical solution: A method for generating nitric oxide gas, wherein a liquid reagent is brought into contact with and mixed with another solid reagent to cause a chemical reaction, thereby generating nitric oxide gas of a certain concentration.

[0008] The effective component of the solid pharmaceutical agent of the present invention is ferrous nitrosyl sulfate, which is prepared by reacting ferrous sulfate solution with nitric oxide gas in the gas stream to obtain ferrous nitrosyl sulfate as a product, as shown in formula (1).

[0009] FeSO4+ NO → Fe(NO)SO4 (1) The reaction temperature is generally below 65°C, preferably 20–45°C. The reaction is generally carried out in an inert gas atmosphere such as nitrogen, or after evacuation treatment to avoid the presence of oxidizing gases and substances such as oxygen, thus preventing the oxidation of ferrous ions and nitric oxide. The pH of the solution is generally below 6, preferably 0.5–3, to prevent the hydrolysis of ferrous ions to form ferrous hydroxide. Ferrous sulfate in the solution can generally be in appropriate excess. The ferrous sulfate nitrosyl sulfate described in this invention can also be prepared by reacting ferrous sulfate solution with nitric acid, with other conditions basically the same as above.

[0010] Then, a coagulant and a stabilizer are added to the solution containing ferrous nitrosyl sulfate obtained from the above reaction. The resulting solidified product is the solid reagent. The coagulant causes the solution to solidify, yielding the corresponding colloidal solid. Commonly used coagulants include pectin, xanthan gum, gelatin, calcium chloride, magnesium chloride, calcium sulfate, and calcium citrate, or a combination thereof. Substances of the same type generally have similar effects, and the amount used is sufficient to achieve solidification. The stabilizer prevents the oxidation of ferrous nitrosyl sulfate and is mainly a reducing agent, including one or more combinations of ferrous salts, sulfites, and primary iron powder, added in appropriate amounts. A certain amount of auxiliary components can also be added to the solid reagent. One function is to dilute the content of the active ingredient, and the other is to react with the liquid reagent to generate gas, thus diluting the generated nitric oxide gas. Auxiliary components are generally acidic salts, sulfates and hydrochlorides containing transition metals, including any one or a mixture of ferric chloride (or ferrous chloride), aluminum chloride, ferric sulfate (or ferrous sulfate), and aluminum sulfate, etc., with comparable effects; the amount added depends on the needs.

[0011] The liquid agent includes one or more of the following: an alkaline solution or slurry, a salt solution or slurry. The salt includes carbonates of alkali metals, alkaline earth metals and transition metals, which have comparable effects. It can also be the corresponding acid salt, basic salt or complex salt, etc. Alkali metal carbonates are preferred, including sodium carbonate and potassium carbonate.

[0012] When using alkaline solutions or slurries as liquid reagents, the pH value is generally above 8; a higher pH value results in a faster reaction. The preferred pH value for alkaline solutions is 10-12. When using carbonate solutions as liquid reagents, the carbonate solution reacts chemically with the active and auxiliary components of the solid reagent. The resulting carbon dioxide gas also dilutes the nitric oxide gas, preventing it from being oxidized by air when the nitric oxide concentration is too high, thus preventing the production of toxic nitrogen dioxide gas. The reaction is as follows when the solid reagent uses ferrous sulfate as an auxiliary component and the liquid reagent uses sodium carbonate solution: Na2CO3+ Fe(NO)SO4+ H2O → Fe(OH)2+ NO + CO2+ Na2SO4 (2) Na2CO3+ FeSO4+ H2O → Fe(OH)2+CO2+ Na2SO4 (3) According to reaction formula (2), 1 mole of NO is generated simultaneously with 1 mole of CO2. To control the release and concentration of NO, the effective and auxiliary components in the solid drug can be proportioned as needed. The content of the effective component in medical use is generally below 10%. The container space can be protected by inert gases such as nitrogen. The liquid drug can also be prepared by mixing the solution with materials such as glycerin that do not chemically react with the solid drug, which can also slow down or control the solid-liquid reaction rate. The specific proportion can be set according to actual needs. After the generated gas is diluted with air, the NO concentration is generally ≤100ppm and the CO2 concentration is generally ≤2%, preferably in the range of 0.1-1%, which can be achieved by setting the carbonate content and liquid flow rate in the solution.

[0013] The active ingredient of the solid pharmaceutical agent described in this invention, ferrous nitrosyl sulfate, can also be ferrous nitrosyl chloride (Fe(NO)Cl2). The ferrous sulfate is replaced by ferrous chloride, which undergoes a complexation reaction with nitric oxide gas. Everything else remains the same, and the effect is equivalent.

[0014] A nitric oxide generator is characterized in that the generator comprises a solid reagent container, a liquid reagent container, and pipeline valves, etc., wherein the solid reagent container is located at the lower part of the generator and is divided into an inner solid reagent container and an outer solid reagent container, the liquid reagent container is located at the upper part of the generator, the liquid reagent container has a vent valve at the top and a liquid reagent outlet at the bottom, and is connected to the solid reagent container through a connecting pipe, the connecting pipe being equipped with a liquid reagent flow regulator, the upper side of the outer solid reagent container has a gas outlet connected to a gas conduit via a gas release valve, and a gas filter layer is also provided in the upper part of the inner part of the outer solid reagent container.

[0015] The solid reagent inner container is U-shaped, with its lower end fixed to the bottom of the outer container and its upper end open. The solid reagent is loaded inside the inner container, with its top directly facing the opening of the connecting tube. A space is left above the solid reagent in the inner container to receive liquid reagent; this space is generally 1 / 3 to 1 / 5 of the solid reagent volume and can be set as needed to control the solid-liquid reaction rate. Excess liquid reagent overflows from the U-shaped port. The annular space between the inner container and the outer container is used to receive liquid reagent overflowing from the top of the inner container, and its volume can accommodate all the liquid reagent. The outer container for the solid reagent can be appropriately large to facilitate gas dilution.

[0016] In use, first open the gas outlet valve of the solid medicine container, then sequentially open the vent valve of the liquid medicine container, the liquid outlet valve of the liquid medicine container, and the liquid inlet valve of the solid medicine container. This allows the liquid and solid medicines to react and produce a certain concentration of nitric oxide gas. After passing through a filter layer for demisting, the gas is discharged through a gas conduit after the solid medicine container's gas outlet valve for the user. The amount of nitric oxide gas produced can be adjusted by regulating the liquid medicine flow meter. When used as an emergency medical device, this generator is inhaled naturally along with the surrounding air, based on a normal human ventilation rate of 5–10 L / min. The dilution factor after inhalation can typically be set between 50 and 200, depending on the specific needs.

[0017] The amount of NO generated can be controlled by adjusting the flow rate of the liquid reagent, which can generally be set to high, medium, and low. After the generated gas is diluted with air, the NO concentration is generally ≤100ppm, and the CO2 concentration is generally ≤2%, with the preferred CO2 concentration range being 0.1% to 1%. This can be achieved by setting the carbonate content in the solution and the liquid flow rate, which can be set according to medical requirements.

[0018] The release rate of nitric oxide can also be controlled by altering the contact area between the solid and liquid reagents. This can be achieved by changing the cross-sectional area of ​​the solid reagent's internal container or by adding a certain amount of neutral aggregates such as quartz sand or silicate cement to the solid reagent to form a hollow framework structure. Reducing the solid-liquid contact area by half will correspondingly reduce the solid-liquid reaction rate by approximately half.

[0019] The advantages of this invention are as follows: It uses ferrous nitrosyl sulfate as the active ingredient, and encapsulates the solid and liquid reagents in different containers. The solid and liquid reagents are mixed and react to produce a certain concentration of nitric oxide gas. The carbon dioxide gas produced in the reaction can both dilute the nitric oxide gas concentration to avoid the formation of toxic nitrogen dioxide gas and enhance respiration. The generating device is simple to operate, portable, safe, and reliable. Attached Figure Description

[0020] Figure 1This is a schematic diagram of the apparatus for generating nitric oxide gas.

[0021] Drawing number explanation: 1 Solid reagent; 2 Inner container of solid reagent; 3 Outer container of solid reagent; 4 Connecting pipe; 5 Filter layer; 6 Liquid inlet valve; 7 Liquid reagent flow regulator; 8 Liquid outlet valve; 9 Liquid reagent; 10 Liquid reagent container; 11 Vent valve; 12 Gas release valve; 13 Gas conduit. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0023] A nitric oxide gas generator such as Figure 1 As shown. The generating device includes a solid reagent 1, a solid reagent inner container 2, a solid reagent outer container 3, a connecting pipe 4, a filter layer 5, a liquid inlet valve 6, a liquid reagent flow regulator 7, a liquid outlet valve 8, a liquid reagent 9, a liquid reagent container 10, a vent valve 11, a gas release valve 12, and a gas conduit 13.

[0024] The procedure is as follows: First, open the gas release valve 12 at the gas outlet of the solid reagent outer container 3. Then, sequentially open the vent valve 11 of the liquid reagent container 10, the liquid outlet valve 8 of the liquid reagent container, and the liquid inlet valve 6 of the solid reagent outer container. This allows the liquid reagent 9 to enter the solid reagent inner container 2 through the connecting pipe 4. After contacting the solid reagent 1, the liquid reagent reacts to produce a certain concentration of nitric oxide gas. This gas is then filtered through the filter layer 5 to remove mist before being discharged through the gas release valve 12 at the gas outlet of the solid reagent outer container and the gas conduit 13 for use by the user. The concentration and flow rate of the nitric oxide gas can be adjusted by regulating the liquid solvent flow regulator 7.

[0025] Example 1: A nitric oxide gas generator, such as Figure 1As shown. The container is cylindrical, made of high-density polyethylene (HDPE) plastic. The connecting pipes and gas conduits are made of silicone tubing. The upper liquid reagent container has a diameter of approximately 80 mm and a height of approximately 100 mm. The lower solid reagent outer container has a diameter of approximately 100 mm and a height of approximately 150 mm. The filter layer is made of degreased cotton with a thickness of approximately 20 mm. The inner container has a diameter of approximately 30 mm and a height of approximately 90 mm. The gas conduit has a diameter of 8 mm. The inner container of the solid reagent is filled to a height of approximately 60 mm. The solid reagent contains approximately 0.5% ferrous nitrosyl sulfate, approximately 35% ferrous sulfate, approximately 5% xanthan gum, approximately 20% calcium chloride, and the remainder is water. The liquid reagent is approximately 400 ml of a 15% sodium carbonate solution prepared with deoxygenated water. The system space is protected by nitrogen gas at atmospheric pressure. Adjust the liquid flow rate to approximately 8 mL / min, the average concentration at the outlet of the nitric oxide generator at the gas conduit port to be in the range of 2500±500 ppm, the gas flow rate to approximately 100 mL / min, the concentration after 100-fold dilution of air to 25±5 ppm, the CO2 concentration to ≤1%, and the total release time to approximately 50 min. The room temperature is approximately 25℃.

[0026] Example 2: The solid reagent contains approximately 0.2% ferrous sulfate, 5% ferrous sulfate, 35% ferric sulfate, 5% pectin, and 20% calcium sulfate, with the remainder being water. The liquid reagent is approximately 400 ml of a 15% sodium carbonate solution prepared with deoxygenated water. The liquid flow rate is approximately 4 mL / min. Other conditions are the same as in Example 1: the average concentration of nitric oxide at the outlet of the gas conduit and the nitric oxide generator is in the range of 1600 ± 300 ppm; the gas flow rate is approximately 50 mL / min; the concentration after 200-fold dilution with air is 8 ± 3 ppm; the CO2 concentration is ≤ 0.5%; and the total release time is approximately 100 min.

[0027] Example 3: A method for preparing the solid pharmaceutical preparation described above: (1) Prepare a ferrous sulfate solution with a mass content of 20%, add an appropriate amount of dilute sulfuric acid to adjust the pH of the solution to about 2, and then pass nitrogen gas containing about 1000 ppm nitric oxide into the absorption tube containing the ferrous sulfate solution. The reaction time is about 1 hour and the reaction temperature is about 30-35℃. A solution with an effective component of ferrous nitrosyl sulfate with a content of about 3-5% is obtained (the content is determined by analyzing the amount of NO gas released after adding alkali to the absorption liquid after the reaction).

[0028] (2) Add 30% ferric sulfate and 10% calcium sulfate to the solution containing ferrous sulfate obtained from the above reaction according to the predetermined ratio. After stirring evenly, add about 5-10% pectin powder and 1% virgin iron powder. Stir evenly quickly and let stand to obtain a solid product, which is the solid agent mentioned above.

[0029] Example 4: Ferrous chloride was used instead of ferrous sulfate, and other conditions were the same as in Example 1, with roughly the same results.

[0030] The above embodiments are only used to illustrate the technical solutions of the present invention. Any modifications to the technical solutions described in the embodiments, or any equivalent substitutions, modifications, changes, and improvements to some of the technical features within the spirit and principles of the present invention, should be included within the protection scope of the present invention.

Claims

1. A method for generating nitric oxide gas, characterized in that... The method involves contacting and mixing a liquid agent with a solid agent to induce a chemical reaction, thereby generating a certain concentration of nitric oxide gas. The effective component of the solid agent is ferric sulfate nitrosyl (Fe(NO)SO4), and the liquid agent is one or a mixture of alkaline solution, slurry, salt solution, or slurry.

2. The method for generating nitric oxide gas according to claim 1, characterized in that... The preparation method of the solid agent is as follows: First, prepare a ferrous sulfate solution, add an appropriate amount of dilute acid to adjust the pH of the solution to below 6, and then pass nitrogen gas containing nitric oxide into the ferrous sulfate solution to react with the nitric oxide gas to obtain a solution containing the active ingredient nitrosyl ferric sulfate; Second, a certain amount of auxiliary components may also be added to the solution and stirred evenly; Third, a coagulant and stabilizer are added to the solution, and after rapid stirring, it is allowed to stand and solidify. The final solid material obtained is the solid agent.

3. The method for generating nitric oxide gas according to claim 2, characterized in that... The coagulant includes one or more combinations of pectin, xanthan gum, gelatin, calcium chloride, magnesium chloride, calcium sulfate, and calcium citrate, and the stabilizer includes one or more combinations of ferrous salts, sulfites, and primary iron powder.

4. The method for generating nitric oxide gas according to claim 1 or 2, characterized in that... The solid pharmaceutical preparation contains a certain amount of auxiliary acidic salts, including any one or a mixture of several of ferric chloride, ferrous chloride, aluminum chloride, ferric sulfate, ferrous sulfate, and aluminum sulfate.

5. The method for generating nitric oxide gas according to claim 1, characterized in that... The liquid agent is one or a mixture of alkaline solutions or slurries, salt solutions or slurries, and the salt includes carbonates of alkali metals, alkaline earth metals and transition metals, as well as corresponding acid salts, basic salts or complex salts.

6. The method for generating nitric oxide gas according to claim 5, characterized in that... The alkali metal carbonates mentioned include sodium carbonate and potassium carbonate.

7. The method for generating nitric oxide gas according to claim 1, characterized in that... The active ingredient in the solid pharmaceutical preparation is ferrous nitrosyl chloride.

8. A generating apparatus for a method of generating nitric oxide gas according to claim 1, characterized in that... The generating device includes a solid reagent container, a liquid reagent container, and pipeline valves. The solid reagent container is located at the bottom of the generator and consists of an inner solid reagent container and an outer solid reagent container. The liquid reagent container is located at the top of the generator. The top of the liquid reagent container has a vent valve, and the bottom has a liquid reagent outlet connected to the solid reagent container via a connecting pipe. A liquid reagent flow regulator is installed on the connecting pipe. The upper side of the outer solid reagent container has a gas outlet connected to a gas conduit via a gas release valve. A gas filter layer is also installed in the upper part of the inner side of the outer solid reagent container.

9. The apparatus for generating nitric oxide gas according to claim 7, characterized in that... The method of use is to first open the gas outlet gas release valve of the solid medicine container, and then open the vent valve of the liquid medicine container, the liquid outlet valve of the liquid medicine container, and the liquid inlet valve of the solid medicine container in sequence. After the liquid medicine comes into contact with the solid medicine, it reacts to produce a certain concentration of nitric oxide gas. After being filtered and demisted, the gas is discharged from the gas outlet gas release valve of the solid medicine container through the gas conduit for the user.

10. An apparatus for generating nitric oxide gas according to claim 1, characterized in that... The generator includes a solid agent (1), a solid agent inner container (2), a solid agent outer container (3), a connecting pipe (4), a filter layer (5), a liquid inlet valve (6), a liquid agent flow regulator (7), a liquid outlet valve (8), a liquid agent (9), a liquid agent container (10), a vent valve (11), a gas release valve (12), and a gas conduit (13). The steps of its use are as follows: first, open the gas release valve (12) of the gas outlet of the solid drug outer container (3), and then open the vent valve (11) of the liquid drug container (10), the liquid outlet valve (8) of the liquid drug container, and the liquid inlet valve (6) of the solid drug outer container (3) in sequence. This allows the liquid drug (9) to enter the solid drug inner container (2) through the connecting pipe (4) and react with the solid drug (1) to produce a mixture of nitric oxide and carbon dioxide of a certain concentration. After being filtered through the filter layer (5) to remove mist, the mixture is discharged from the gas release valve (12) of the gas outlet of the solid drug outer container (3) and the gas conduit (13). The concentration and flow rate of nitric oxide and carbon dioxide gas can be adjusted by adjusting the liquid solvent flow regulator (7).

Images