Nitric oxide sterilization device and method

Abstract

The sterilization systems and methods presented herein include a reaction vessel in which nitric oxide is generated on demand from a nitric oxide donor in solution, and the nitric oxide so generated is moved from the reaction vessel through a surge vessel into a sterilization chamber via a negative pressure gradient, where residual nitric oxide is then adsorbed or catalytically destroyed.

Description

Detailed Description of the Invention

[0001] [Cross - Reference to Related Applications]

[0001] This application claims the benefit of priority of U.S. Patent Provisional Application No. 63 / 438,445, filed on January 11, 2023, which is incorporated herein by reference.

[0002] [Field of the Invention]

[0002] The field of the present invention is devices, systems, and methods for sterilizing objects using nitric oxide as a gaseous sterilant, and in particular, the present invention relates to the on - demand generation and delivery of nitric oxide at low pressures or pressures below atmospheric pressure.

[0003] [Background of the Invention]

[0003] The background description may include information that can be useful for understanding the present invention. It is not admitted that any of the information provided in this specification is prior art, or related to the invention claimed in this specification, or that any of the publications specifically or implicitly referenced herein is prior art.

[0004]

[0004] All publications and patent applications in this specification are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. If the definition or use of a term in an incorporated reference conflicts with or contradicts the definition of that term provided in this specification, the definition of that term provided in this specification applies and the definition of that term in the reference does not apply.

[0005]

[0005] Sterilization of medical devices and equipment is of paramount importance for their safe use, and the most common sterilization methods include steam autoclaving and irradiation. However, not all medical devices, equipment, and biopharmaceuticals can withstand such harsh conditions, and other sterilization methods must also be used. To avoid these challenges, sterilization can be carried out using selected gases, and ethylene oxide is the most commonly used sterilization gas for items such as surgical kits, catheters, cardiac implants, stents, and IV sets. Unfortunately, however, ethylene oxide has several physical and health hazards that require special attention. According to the U.S. Department of Labor's Occupational Safety and Health Administration, acute exposure to ethylene oxide gas can lead to respiratory irritation and lung damage, headache, nausea, vomiting, diarrhea, shortness of breath, and cyanosis. Chronic exposure has been linked to the development of cancer, reproductive toxicity, mutagenic changes, neurotoxicity, and sensitization. In fact, the Environmental Protection Agency classifies ethylene oxide as a carcinogen.

[0006]

[0006] To avoid some of the problems associated with ethylene oxide, various alternative sterilization gases have been used. For example, formaldehyde can be produced from formalin, which has been used as a sterilization gas at relatively high concentrations (e.g., 8-16 mg / l). Although it is significantly less flammable than ethylene oxide, formaldehyde gas is produced / used at an operating temperature of approximately 70-75°C, so it cannot be used with thermally sensitive materials or equipment. Alternatively, hydrogen peroxide vapor can be used as a sterilization gas. Hydrogen peroxide vapor is typically produced by vacuum evaporation. Among other advantages, hydrogen peroxide vapor typically has a rapid cycle time (e.g., 30-45 minutes), is effective at low temperatures (e.g., 20°C), and produces environmentally safe byproducts (water, oxygen). In addition, hydrogen peroxide vapor is generally quite material-compatible and easy to operate. However, hydrogen peroxide vapor may react with certain polymers and is not approved by the U.S. Food and Drug Administration for sterilization of medical devices. On the other hand, ozone can be used as a sterilization gas, which is relatively effective even at low temperatures. Unfortunately, however, ozone is chemically very unstable and can react with biopharmaceuticals. Furthermore, producing a sufficient amount for sterilization typically requires specialized equipment.

[0007]

[0007] As recently described in International Publication No. 2022 / 164894, sterilization using nitric oxide gas as a sterilizer has also been reported. Here, nitric oxide is produced from a nitric oxide donor compound and then exposed to conditions that lead to the release of nitric oxide. In a typical example, the donor compound is immobilized on or within a carrier in close proximity to the object to be sterilized. In particular, such systems and methods avoid most of the challenges associated with sterilization with hydrogen peroxide or ethylene oxide. However, the use of a donor compound in close proximity to the object is difficult to scale up to larger operations. To increase the scale, theoretically, nitric oxide gas from a large-scale source can be used. However, since high-pressure nitric oxide readily undergoes disproportionation to N2O and NO2, it is undesirable to replace the nitric oxide donor compound with commercially available compressed nitric oxide gas.

[0008]

[0008] Therefore, various compositions and methods for sterilizing various objects using sterilization gases containing nitric oxide are known in the art, but all or almost all of them have some drawbacks. Thus, improved devices, systems, and methods for sterilizing objects using nitric oxide as a gaseous sterilizer are still needed.

[0009] [Overview of the prefecture]

[0009] The subject matter of the present invention relates to various devices, systems, and methods for sterilizing objects using nitric oxide as a sterilization gas, wherein the nitric oxide is produced from a precursor solution under controlled reaction conditions, and the nitric oxide thus produced is moved through a sterilization system, including a sterilization chamber, via a negative pressure gradient. Finally, residual nitric oxide after sterilization is destroyed or otherwise removed from the exhaust of the sterilization system using a suitable filter or reactor.

[0010]

[0010] In one aspect of the subject matter of the present invention, the inventors envision a nitric oxide generator comprising a reaction vessel configured to maintain a solution containing a nitric oxide donor, and a metering system configured to provide the solution with the nitric oxide donor or one or more reagents that generate a nitric oxide donor in the solution. The envisioned nitric oxide generator further comprises an energy source coupled to the reaction vessel and configured to provide the solution with an amount of energy sufficient to produce nitric oxide by decomposing the nitric oxide donor. A control circuit is operably coupled to the metering system and one or more sensors, and the control circuit thus controls the operation of the sensors in accordance with the concentration of the nitric oxide donor in the solution, one or more reagents, and / or the concentration or amount of nitric oxide produced.

[0011]

[0011] In some embodiments, the nitric oxide generator is configured to protect the solution containing the nitric oxide donor from ambient light, and / or the container may be configured to allow the introduction of an inert gas to replace atmospheric oxygen from the container. The solution is an aqueous solution and may or may not contain a metal ion chelating agent. Although not essential, the solution is preferably pH 4.0 or lower (e.g., pH 2-4 or 3-5). In further embodiments, the nitric oxide donor comprises a nitrosothiol group, and / or one or more reagents comprise an organic thiol compound and a nitrite, and the nitric oxide donor is produced in situ in the solution by the reaction of the organic thiol compound and the nitrite.

[0012]

[0012] If desired, the metering system may include a liquid pump or screw drive configured to dispense a nitric oxide donor or one or more reagents into a solution. In further intended embodiments, preferred energy sources include a light source, a heater, an ultrasonic emitter, and / or an impeller, and preferred sensors include a pH sensor, a UV-VIS sensor, a nitric oxide sensor, and / or a gas flow meter.

[0013]

[0013] In addition, the nitric oxide generator is intended to be fluidically coupled to an inert gas (e.g., nitrogen gas) source, and / or the generator is intended to be fluidly coupled to a surge vessel. Furthermore, the generator is intended to be fluidly coupled to a sterilization chamber, and / or to a vacuum pump.

[0014]

[0014] Accordingly, the inventors have also conceived a method for producing nitric oxide, which includes the step of reacting an organic thiol compound and a nitrite in a vessel, thereby producing a solution containing a nitric oxide donor by reacting the organic thiol compound and the nitrite; and the further step of providing energy to the solution in the reaction vessel to decompose at least a portion of the nitric oxide donor, thereby producing nitric oxide by decomposing at least a portion of the nitric oxide donor. In yet another step, the produced nitric oxide is then moved out of the reaction vessel using a negative pressure gradient, and the nitric oxide donor is replenished by supplying additional organic thiol compounds and nitrites to the solution.

[0015]

[0015] The solution is also intended to contain a metal ion chelating agent and / or have a pH of 4.0 or less (for example, pH 2-4 or 3-5). Although not essential, it is preferable that an inert gas is flowed in the upper space above the solution, typically protecting the solution from ambient light. The energy in such a method is further intended to be provided in the form of light energy, thermal energy, mechanical energy, and / or ultrasonic energy. If desired, the intended method may further include the step of measuring the nitric oxide concentration in the reaction vessel.

[0016]

[0016] Most typically, the generated nitric oxide is moved from the reaction vessel into a surge vessel and from the surge vessel into a sterilization chamber. Furthermore, it is generally preferable that the generated nitric oxide is moved through at least part of the system using a vacuum pump. As is easily understood, the method to be conceived may further include the step of measuring the concentration of nitric oxide, and the nitric oxide donor is replenished in response to the measured nitric oxide concentration in the solution. Furthermore, residual nitric oxide is intended to be adsorbed or catalyst-destroyed after use as a sterilizer.

[0017]

[0017] Accordingly, in yet another aspect of the subject matter of the present invention, the inventors have also conceived of a sterilization system for sterilizing an object using gaseous nitric oxide, the sterilization system comprising a reaction vessel fluidly coupled to a surge vessel and a sterilization chamber, so that nitric oxide produced in the reaction chamber moves from the reaction vessel through the surge vessel to the sterilization chamber. Such a system further comprises a vacuum pump fluidly coupled to the sterilization chamber, which comprises an energy source coupled to the vessel and configured to provide to a solution in the vessel a sufficient amount of energy to produce nitric oxide by decomposing a nitric oxide donor in the solution, so that the vacuum pump draws nitric oxide from the vessel, the surge vessel and the sterilization chamber to a nitric oxide adsorbent or catalyst.

[0018]

[0018] Most typically, the reaction vessel has one or more ports configured to receive a nitric oxide donor or one or more reagents that produce a nitric oxide donor, and / or a preferred energy source includes a light source, a heater, an ultrasonic emitter, or an impeller. In further embodiments, the intended sterilization system may further include a plurality of nitric oxide sensors for measuring the concentration of nitric oxide in one or more of the exhausts of the reaction vessel, the sterilization chamber, and the vacuum pump, and / or a sensor for measuring the concentration of the nitric oxide donor in the reaction vessel.

[0019]

[0019] As a result, from a different perspective, the inventors have conceived a method for sterilizing an object using nitric oxide, the method comprising the steps of generating nitric oxide from a solution containing a nitric oxide donor in a reaction vessel, the further step of moving the generated nitric oxide from the reaction vessel to a sterilization chamber using a negative pressure gradient, and the further step of maintaining a sterile nitric oxide concentration in the sterilization chamber for a time sufficient to sterilize the object.

[0020]

[0020] Typically, although not essential, the nitric oxide donor contains a nitrosothiol group and can be produced in solution from a reaction between an organic thiol compound and a nitrite. Nitric oxide is also intended to be produced from the nitric oxide donor by photodegradation of the nitric oxide donor, and the nitric oxide thus produced is intended to be moved from the reaction vessel to the sterile chamber via a surge vessel (typically having a volume larger than that of the sterile chamber).

[0021]

[0021] In a further aspect of the subject matter of the present invention, a negative pressure gradient is generated using a vacuum pump located downstream of the sterilization chamber. Furthermore, the sterile nitric oxide concentration is intended to be 1 to 50 ppb or higher, and / or the sterile nitric oxide concentration is intended to be maintained for a period of 10 to 120 minutes and / or at a temperature of 0 to 50°C or 20 to 50°C. As described above, residual nitric oxide is also intended to be adsorbed or catalyst-destroyed after use as a sterilizing agent.

[0022]

[0022] Various objects, features, aspects, and advantages of the subject matter of the present invention will become more apparent from the following detailed description of preferred embodiments in conjunction with the accompanying drawings. In the accompanying drawings, similar numbers represent similar components. [Brief explanation of the drawing]

[0023] [Figure 1] This is an illustrative schematic diagram of a nitric oxide sterilization system according to the subject of the present invention.

[0024] [Detailed Description]

[0024] The inventor has found a system, device, and method for sterilizing an object using nitric oxide as a sterilizing agent. Nitric oxide is generated on demand within a reaction vessel, and the nitric oxide thus generated is moved through a sterilization chamber using a negative pressure gradient. Subsequently, the residual nitric oxide after sterilization is adsorbed or catalytically destroyed. The systems, devices, and methods presented herein are advantageously conceptually simple, effective, and economically attractive while enabling large-scale rapid sterilization at low temperatures (e.g., 0 to 50 °C or 0 to 70 °C, optionally even higher) and short cycle times.

[0025]

[0025] In one exemplary embodiment schematically shown in FIG. 1, the sterilization system comprises a reaction vessel 250 in which nitric oxide is generated on demand. Then the nitric oxide is moved via a valve 170 to a surge vessel (or nitrogen bladder) 180, and then the nitric oxide is moved from the surge vessel 180 to a sterilization chamber 200. At this time, the residual nitric oxide leaves the sterilization chamber and is catalytically oxidized by a hopcalite filter 210. The residual odor can be removed within an activated carbon filter 230.

[0026]

[0026] In this context, it should be understood that the gas stream containing nitric oxide is not compressed, thus avoiding the significant problem associated with the disproportionation of nitric oxide (NO), 3NO → NO2 + N2O. Initial kinetic studies by others have shown that the disproportionation reaction strongly depends on the pressure of nitric oxide. For example, at 200 atm, it may take up to 10 days before the mole fractions of NO2 and N2O can rise as high as 12 - 13% (see, for example, Free Radic Res. 2003 Feb;37(2):171 - 7). Instead, nitric oxide is generally preferably moved by a negative pressure gradient generated by a vacuum (or suction) pump 220 located downstream of the sterilization chamber. For example, in some embodiments, the negative pressure gradient at least temporarily reduces the pressure within the sterilization chamber to about 10 Torr, as shown in FIG. 1, and in so doing, draws nitric oxide (typically in a carrier gas) from the reaction vessel into the sterilization chamber by a vacuum pump. When nitric oxide exits the sterilization chamber, it is drawn into a Hopcalite filter and catalytically oxidized. Subsequently, the exhaust of the vacuum pump can be passed through an activated carbon filter to remove odorous compounds.

[0027]

[0027] Without limiting the subject matter of the present invention, it is generally preferred to include a surge vessel that can act as a nitric oxide reservoir between the nitric oxide reaction vessel and the sterilization chamber. Most typically, the surge vessel has a capacity for nitric oxide that is at least equal to or significantly larger than (e.g., at least 1.5 times, or at least 2.0 times, or at least 3.0 times, or at least 5.0 times) the volume of the sterilization chamber. In some embodiments, the surge vessel can have an internal volume of at least 1 m 3 or at least 3 m 3 or at least 5 m 3 or an internal volume of 2 m 3 less than or an internal volume of 10 - 500 cm 3 or an internal volume of 100 - 5,000 cm 3 .

[0028]

[0028] Referring further to Figure 1, nitric oxide is preferably generated on demand from the precursor solution 120 in the reaction vessel, and the precursor solution is more generally preferred to contain a nitrosothiol compound. Furthermore, it is also preferable that the concentration of the nitrosothiol compound in the solution can be maintained by generating the nitrosothiol compound in situ from the reactants supplied to the solution. In some embodiments, the precursor solution can be an aqueous solution with a relatively acidic pH (e.g., pH 4.0) and may further contain a metal ion chelating agent (e.g., EDTA) to thus increase the chemical stability of the nitrosothiol compound. For this purpose, the pH can be actively controlled using a control system that can buffer the solution or supply an acid or base to the solution as needed to maintain a set point or pH range for the solution.

[0029]

[0029] Among other suitable reagents, the intended nitrosothiol compound can be produced from an organic thiol compound 100 and a nitrite 140. For example, if the nitrosothiol compound is S-nitrosoglutathione or S-nitrosocysteine, the reactants can be glutathione or cysteine ​​relative to the thiol compound and sodium nitrite relative to the nitrite. As can be easily understood, the appropriate molar ratio of the thiol and nitrite reagents can be easily determined by those skilled in the art (for example, the ratio of thiol to nitrite is 1:1.1), and suitable amounts can be added to achieve the desired final concentration. Of course, it should be understood that the addition of reagents may be continuous or discontinuous (for example, in response to the sensed amount of the nitrosothiol compound). Most typically, the nitrosothiol compound has a concentration of 0.1 M to 1.0 M in solution.

[0030]

[0030] In a more desirable embodiment, as also illustrated in Figure 1, the concentration of the formed nitrosothiol compound (RSNO) can be monitored by UV-VIS spectroscopy 125 (for example, using a point analysis method such as an optical UV-VIS spectrometer from Ocean Optics). Similarly, it should be noted that the pH of the solution can also be monitored by UV-VIS spectroscopy using a ratiometric measurement which can be enabled by a pH indicator in the solution (such as thymol blue or methyl orange). Such a ratiometric system has the advantage of not requiring calibration. As a result, it should be understood that these two feedback parameters (the amount of nitrosothiol compound and the pH of the solution) make it possible to maintain a constant level of the nitrosothiol compound (via a control system that dispenses thiol and nitrite reagents in response to the determined amount of nitrosothiol compound).

[0031]

[0031] Next, by adding energy, nitric oxide 130 can be produced from the nitrosothiol compound in the solution, and it is generally preferred that the energy source be light sources 150 and 160 (whose frequency and / or intensity can be adjusted to match different nitrosothiol compounds and / or nitric oxide production rates). As is easily understood, the amount / concentration of nitric oxide in the upper space of the reaction vessel can be monitored by an electrochemical NO sensor 110 (such as the SGX-4NO-250 Nitric Oxide Gas sensor from Sensortech) which enables real-time measurement of the nitric oxide concentration / amount when the solution is illuminated. In the most typical embodiment, an inert gas (e.g., nitrogen) is flowed and maintained throughout the nitric oxide channel to reduce, or even completely avoid, the presence of oxygen in the channel. One or more flow meters can then be used to monitor the gas flow rate into the sterile chamber. Finally, it is preferable that the solution containing the nitrosothiol compound be protected from ambient light and that the solution can be sparged or purged with an inert gas. Therefore, nitric oxide is only produced in response to light from an illumination source.

[0032]

[0032] With regard to the sterilization cycle, it is intended that the objects in the sterilization chamber may be exposed to a static atmosphere containing nitric oxide or a dynamic atmosphere containing nitric oxide. For this purpose, nitric oxide in the carrier gas may be delivered to a steady-state concentration in the sterilization chamber, and the carrier gas containing nitric oxide may be maintained in the chamber for a sufficient amount of time. Alternatively, nitric oxide in the carrier gas may be delivered in a continuous flow throughout the entire sterilization cycle, and in either case, the nitric oxide may be present at a sterile nitric oxide concentration. Naturally, it should be noted that the articles for sterilization may be placed directly into the sterilization chamber, or they may be placed / sealed in a container containing a nitric oxide permeable microbial barrier, as described in U.S. Provisional Patent Application No. 63 / 438073, filed January 10, 2023, which is incorporated herein by reference.

[0033]

[0033] Accordingly, referring further to Figure 1, the sterilization chamber is intended to include one or more sensors 190 to confirm the presence and amount of nitric oxide in the sterilization chamber, and to help the operator confirm the absence of nitric oxide before opening the sterilization chamber after the completion of the sterilization cycle. Most typically, after the completion of the sterilization cycle, the nitric oxide channel is purged with an inert gas, and all residual nitric oxide is moved from the system to an adsorbent or catalyst that decomposes nitric oxide. In addition, an activated carbon filter may be included in the channel to remove any odorous components from the gas leaving the sterilization chamber. Finally, a further nitric oxide sensor 240 may be included at the end of the channel to confirm the adsorption or catalyst decomposition of a desired degree (e.g., at least 95%) of nitric oxide in the channel.

[0034]

[0034] In further intended embodiments, it should be understood that various modifications can be made to the exemplary systems described above without departing from the concept of the invention presented herein. For example, it is generally preferred that the nitric oxide and carrier gas be moved through the system at a pressure below 1 atmosphere (for example, a vacuum pump produces a pressure reduction of about 5 to 10 Torr, or about 10 to 50 Torr, or about 50 to 100 Torr, or about 100 to 300 Torr, or about 300 to 700 Torr), but a moderate positive pressure level for moving the carrier is also considered suitable for use herein, and includes pressures of 800 to 1,500 Torr, or 1,500 to 2,500 Torr, or 2,500 to 6,000 Torr, and possibly even higher. Moderate positive pressure may be particularly suitable when the residence time of nitric oxide in the flow path between the reaction vessel and the sterilization chamber is less than 48 hours, or less than 24 hours, or less than 12 hours, or even shorter.

[0035]

[0035] Furthermore, regarding the generation of nitric oxide, it should be noted that the generation of nitric oxide from the precursor solution may be discontinuous (especially when the surge container has a relatively large volume relative to the sterilization chamber) or continuous, thereby generating a sterile nitric oxide concentration in the carrier gas. In most embodiments, the sterile nitric oxide concentration is a steady-state concentration of nitric oxide of 1 to 500 ppb, or 1 to 10 ppb, or 10 to 50 ppb, or 50 to 250 ppb, or 250 to 500 ppb, or even higher. Therefore, suitable sterile nitric oxide concentrations are 1 ppb, or at least 5 ppb, or at least 10 ppb, or at least 50 ppb, or at least 100 ppb, or at least 200 ppb, and even higher.

[0036]

[0036] Furthermore, it should be noted that the properties of thiol and nitrite reagents can vary considerably, and in practice, all reagents are intended to be suitable for use herein, as long as they enable the formation of nitric oxide donors in the solution within the reaction chamber and can produce nitric oxide by decomposing the nitric oxide donors. In addition, it should be understood that in further intended embodiments, the solution containing nitric oxide donors can be replaced with solid particles containing nitric oxide donors that release nitric oxide when exposed to energy. For example, the solid particles may include polymers surrounding the nitric oxide donors or polymers to which the nitric oxide donors are bound. Suitable particle materials are described in International Publication No. 2022 / 164894, which is incorporated herein by reference. In such embodiments, the particles can be supplied to the reaction vessel (e.g., by screw or auger drive), and the used particles can then be discarded from the reaction vessel (lump together or sequentially). Regardless of the specific properties of the nitric oxide donor, it should be understood that the nitric oxide donor is an environmentally safe and chemically stable source of nitric oxide that can be easily replenished. Furthermore, the generation of nitric oxide is conceptually simple and does not require complex equipment. Finally, it should be understood that the systems and methods presented herein can be integrated into existing gas sterilization equipment, or at least partially formed by existing gas sterilization equipment. From another perspective, existing gas sterilization systems can be modified to include a nitric oxide generator, surge vessel, and vacuum pump in add-on components, thereby adding an alternative form of gas sterilization or replacing an existing form of gas sterilization (e.g., using ethylene oxide or hydrogen peroxide).

[0037]

[0037] In some embodiments, it should be understood that numbers representing properties such as components and concentrations, and quantities such as reaction conditions used for describing embodiments and claims of the present invention are modified in some cases by the term “about”. In this specification, when referring to a specified measurable value (parameter, quantity, time length, etc.), the terms “about” and “approximately” mean to include the specified value, as well as variations from the specified value, variations from the specified value, for example, ±10% or less, or alternatively ±5% or less, or alternatively ±1% or less, or alternatively ±0.1% or less, insofar as such variations are appropriate for implementation in the disclosed embodiments. Thus, the values ​​themselves that the modifying phrases “about” or “approximately” refer to are also specifically disclosed. The description of ranges of values ​​in this specification is intended only to serve as a concise way for referring individually to each distinct value that falls within that range. Unless otherwise stated herein, each individual value is incorporated herein as if it were described individually.

[0038]

[0038] All methods described herein may be carried out in any preferred order, unless otherwise specified herein or otherwise clearly inconsistent with the context. Any examples or exemplary language (e.g., "etc.") provided herein with respect to a particular embodiment are intended solely to better illustrate the invention and do not constitute a limitation to the scope of the invention as otherwise claimed. No language herein should be construed as indicating any unclaimed element necessary for carrying out the invention.

[0039]

[0039] When used throughout this specification and the subsequent claims, the meanings of “a,” “an,” and “the” include multiple references unless otherwise explicitly indicated by the context. Also, when used in this specification, the meaning of “in” includes “in” and “on” unless otherwise explicitly indicated by the context. Also, when used in this specification, the term “coupled to” is intended to include both direct coupling (two coupled elements touching each other) and indirect coupling (at least one additional element between two elements). Thus, the terms “coupled to” and “coupled with” are used synonymously.

[0040]

[0040] It will be apparent to those skilled in the art that many further modifications are possible without departing from the concept of the invention herein, in addition to those already described. Therefore, the subject matter of the present invention should not be limited except within the scope of the appended claims. Furthermore, in interpreting both this specification and the claims, all terms should be interpreted as broadly as possible, consistent with the context. In particular, the terms “comprises” and “comprising” should be interpreted as non-exclusively referring to an element, component, or step, indicating that the referenced element, component, or step may exist, or may be utilized, or may be combined with other elements, components, or steps not explicitly referenced. Where this specification or the claims refer to at least one selected from the group consisting of A, B, C.... and N, the sentence should be interpreted as requiring only one element from that group, and not A and N or B and N, etc.

Claims

1. A reaction vessel configured to maintain a solution containing nitric oxide donor, A weighing system configured to provide the solution with the nitric oxide donor or one or more reagents that generate the nitric oxide donor in the solution, An energy source coupled to the reaction vessel and configured to provide the solution with an amount of energy sufficient to produce nitric oxide by decomposing the nitric oxide donor, A control circuit operably coupled to the metering system and one or more sensors controls the operation of the sensors according to the concentration of nitric oxide donor in the solution, the one or more reagents, and / or the concentration or amount of nitric oxide produced. A nitric oxide generator, which is fluidly coupled to a surge vessel and fluidly coupled to a vacuum pump, is provided.

2. The nitric oxide generator according to claim 1, wherein the container is configured to protect the solution containing the nitric oxide donor from ambient light.

3. The nitric oxide generator according to claim 1, wherein the container is configured to allow the introduction of an inert gas to replace the oxygen in the atmosphere inside the container.

4. The nitric oxide generator according to claim 1, wherein the solution is an aqueous solution and optionally contains a metal ion chelating agent.

5. The nitric oxide generator according to claim 4, wherein the solution has a pH of 4.0 or less.

6. The nitric oxide generator according to claim 1, wherein the nitric oxide donor contains a nitrosothiol group.

7. The nitric oxide generator according to claim 1, wherein the one or more reagents include an organic thiol compound and a nitrite, and the nitric oxide donor is generated in situ in the solution by the reaction of the organic thiol compound and the nitrite.

8. The nitric oxide generator according to claim 1, wherein the metering system comprises a liquid pump or screw drive configured to dispense the nitric oxide donor or the one or more reagents into the solution.

9. The nitric oxide generator according to claim 1, wherein the energy source is a light source, a heater, an ultrasonic emitter, or an impeller.

10. The nitric oxide generator according to claim 1, wherein the sensor is a pH sensor, a UV-VIS sensor, a nitric oxide sensor, and / or a gas flow meter.

11. The nitric oxide generator according to claim 1, wherein the generator is fluidly coupled to an inert gas source.

12. The nitric oxide generator according to claim 1, wherein the generator is fluidly coupled to a sterilization chamber.

13. A method for producing nitric oxide, The step involves reacting an organic thiol compound and a nitrite in a reaction vessel, thereby generating a solution containing a nitric oxide donor. The step of supplying energy to the solution in the reaction vessel to decompose at least a portion of the nitric oxide donor, thereby generating nitric oxide by decomposing at least a portion of the nitric oxide donor, and the step of decomposition, The steps include using a negative pressure gradient provided by a vacuum pump to move the generated nitric oxide out of the reaction vessel, The step of supplying the nitric oxide donor by supplying additional organic thiol compounds and nitrites to the solution, Includes, The method involves transferring the generated nitric oxide from the reaction vessel to a surge vessel.

14. The method according to claim 13, wherein the solution contains a metal ion chelating agent.

15. The method according to claim 13, wherein the solution has a pH of 4.0 or less.

16. The method according to claim 13, wherein an inert gas is flowed into the upper space above the solution and / or the solution is protected from ambient light.

17. The method according to claim 13, wherein the energy is provided in the form of light energy, thermal energy, mechanical energy, and / or ultrasonic energy.

18. The method according to claim 13, further comprising the step of measuring the nitric oxide concentration in the reaction vessel.

19. The method according to claim 13, wherein the generated nitric oxide is moved from the reaction vessel into a sterilization chamber.

20. The method according to claim 13, further comprising the step of measuring the concentration of nitric oxide, wherein the nitric oxide donor is supplied in response to the measured concentration of nitric oxide in the solution.

21. The method according to claim 13, wherein residual nitric oxide is adsorbed or catalyst-destroyed after use as a sterilizing agent.

22. A sterilization system for sterilizing objects using gaseous nitric oxide, A reaction vessel fluidly coupled to a surge container and a sterilization chamber, wherein nitric oxide generated in the reaction vessel moves from the reaction vessel through the surge container to the sterilization chamber. An energy source connected to the container and configured to provide a sufficient amount of energy to the solution in the container to produce nitric oxide by decomposing the nitric oxide donor in the solution, A vacuum pump is fluidly coupled to the sterilization chamber and draws nitric oxide from the container, the surge container, and the sterilization chamber to the nitric oxide adsorbent or catalyst. A sterilization system equipped with the following features.

23. The sterilization system according to claim 22, wherein the reaction vessel comprises one or more ports configured to receive a nitric oxide donor or one or more reagents for generating the nitric oxide donor.

24. The sterilization system according to claim 22, wherein the energy source is a light source, a heater, an ultrasonic emitter, or an impeller.

25. The sterilization system according to claim 22, further comprising a plurality of nitric oxide sensors for measuring the nitric oxide concentration in one or more of the exhaust gases of the reaction vessel, the sterilization chamber, and the vacuum pump.

26. The sterilization system according to claim 22, further comprising a sensor for measuring the concentration of the nitric oxide donor in the reaction vessel.

27. A method of sterilizing an object using nitric oxide, The steps include generating nitric oxide from a solution containing a nitric oxide donor in a reaction vessel, The steps include moving the generated nitric oxide from the reaction vessel to the sterilization chamber using a negative pressure gradient via a surge container, The steps include maintaining a sterile nitric oxide concentration in the sterilization chamber for a sufficient amount of time to sterilize the object, and A method that includes this.

28. The method according to claim 27, wherein the nitric oxide donor comprises a nitrosothiol group.

29. The method according to claim 27, wherein the nitric oxide donor is produced in the solution from a reaction between an organic thiol compound and a nitrite.

30. The method according to claim 27, wherein the nitric oxide is produced from the nitric oxide donor by photodegradation of the nitric oxide donor.

31. The surge container has a volume greater than the volume of the sterilization chamber, and / or 10 cm³. ３ ~1,000 cm ３ The method according to claim 27, having an internal volume.

32. The method according to claim 27, wherein the negative pressure gradient is generated using a vacuum pump located downstream of the sterilization chamber.

33. The method according to claim 27, wherein the sterile nitric oxide concentration is 1 to 50 ppb.

34. The method according to claim 27, wherein the sterile nitric oxide concentration is maintained for a period of time of 10 to 120 minutes and / or at a temperature of 0 to 50°C.

35. The method according to claim 27, wherein residual nitric oxide is adsorbed or catalyst-destroyed after use as a sterilizing agent.

Images