Sterilization method and sterilization device

Abstract

A sterilization device (1) comprises a pernitric acid gas generation unit (10) and a sterilization treatment unit (20). The pernitric acid gas generation unit (10) generates pernitric acid gas by gasifying a liquid containing pernitric acid. When doing so, for example, the pernitric acid gas generation unit (10) generates a pernitric acid mist by atomizing, with the use of ultrasonic waves, the liquid containing pernitric acid, and causes the pernitric acid gas to be generated from the pernitric acid mist. The sterilization treatment unit (20) applies the pernitric acid gas to a sterilization target (22) to sterilize the sterilization target (22).

Description

[Technical Field]

[0001] The present invention relates to a sterilization method and a sterilization device. [Background technology]

[0002] Sterilization technology, such as the sterilization, disinfection, or sterilization of medical instruments, living organisms, food containers, and food, is one of the fundamental technologies that supports modern life. Conventionally, methods for disinfecting, disinfecting, or sterilizing bacteria, viruses, and the like can be broadly divided into two types: physical methods that use heat or pressure, and chemical methods that use chemicals. In this specification, "sterilization" refers to reducing the number of viable bacteria (viable bacteria concentration).

[0003] An example of a physical method is sterilization using an autoclave with pressurized steam. In physical methods, the objects to be sterilized are exposed to extreme physical conditions, so the objects to be sterilized are limited.

[0004] Chemical methods are used, for example, for precision machinery such as endoscopes and heat-sensitive plastic products. One example of a chemical method is low-temperature sterilization using gases such as ethylene oxide gas (EOG) or solutions such as hydrogen peroxide, peracetic acid, or hypochlorous acid. Because the chemical species used in chemical methods are highly toxic, they must be neutralized after sterilization (e.g., aeration), which results in increased costs and time.

[0005] As described above, both the physical and chemical methods have their advantages and disadvantages.

[0006] On the other hand, the inventors have developed a sterilization method in which a solution containing pernitric acid is applied to the object to be sterilized (see, for example, Patent Document 1 and Non-Patent Documents 1 to 3). The sterilization activity of the liquid containing pernitric acid disappears in a short time at room temperature, so no detoxification treatment is required after sterilization. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent No. 6087029 [Non-patent literature]

[0008] [Non-Patent Document 1] Tatsuya Iwaki, Tomoko Ohshima, Tatsuya Tasaki, Yasuko Momoi, Satoshi Ikawa, Katsuhisa Kitano, Takatsugu Yamamoto, Journal of Oral Biosciences “High Microbicidal Effect of Peroxynitric Acid on Biofilm-Infected Dentin in a Root Carious Tooth Model and Verification of Tissue Safety” 2020, Vol. 62, p.189-194 [Non-patent document 2] Takashi Yokoyama, Shinya Miyazaki, Satoshi Ikawa, Yoichi Nakashima, Katsuhisa Kitano, Chemical Research in Toxicology “Kinetics Analysis of the Reactions between Peroxynitric Acid and Amino Acids” (US), 2020, Vol. 33, p.1633-1643 [Non-patent document 3] Takashi Yokoyama, Shinya Miyazaki, Hiroko Akagi, Satoshi Ikawa, Katsuhisa Kitano, Applied and Environmental Microbiology “Kinetics of Bacterial Inactivation by Peroxynitric Acid in the Presence of Organic Contaminants” (US), 2021, Vol. 87, e01860-20 Summary of the Invention [Problem to be solved by the invention]

[0009] Conventionally, medical instruments and the like are sterilized in a sterilization bag, which is then placed in a container. Furthermore, the sterilized items are stored in the sterilization bag until immediately before use, thereby maintaining their sterilized state. Sterilization bags are made of nonwoven fabric or glassine paper, which not only do not allow bacteria to pass through, but also do not allow droplets of matter to pass through. Therefore, it has been difficult to sterilize items placed in a sterilization bag using liquid sterilants, such as solutions containing pernitrate.

[0010] An object of the present invention is to provide a sterilization method and apparatus using pernitric acid that can sterilize even objects placed in a sterilization bag. [Means for solving the problem]

[0011] The sterilization method according to the present invention is a method for sterilizing an object to be sterilized by applying pernitrate gas to the object to be sterilized.

[0012] The sterilization device according to the present invention comprises a pernitrate gas generator and a sterilization processor. The pernitrate gas generator generates pernitrate gas by gasifying a liquid containing pernitrate. The sterilization processor applies the pernitrate gas to an object to be sterilized to sterilize the object. [Effects of the Invention]

[0013] According to the present invention, a sterilization method and a sterilization device using pernitric acid can be provided, which can sterilize even objects placed in a sterilization bag. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 is a diagram showing a sterilization device that generates peroxynitrate gas using a nebulizer method, as an example of a sterilization device according to an embodiment. [Figure 2]1 is a graph showing the results of a first sterilization test using a large container. [Figure 3] 10 is a graph showing the results of a second sterilization test using a large container. [Figure 4] 10 is a table showing the results of a third sterilization test using a large container. [Figure 5] 10 is a table showing the results of the fourth sterilization test using a large container. [Figure 6] 10 is a graph showing the results of a fifth sterilization test using a small container. [Figure 7] 7 is a table showing the bactericidal activity determined from the survival curve shown in FIG. 6. [Figure 8] 10 is a graph showing the results of the sixth sterilization test using a pigskin contamination model. [Figure 9] FIG. 2 is a diagram showing a peroxynitrate gas generating unit that generates peroxynitrate gas by gas mixing spraying. [Figure 10] 1 is a graph showing the half-life of a pernitric acid solution. DETAILED DESCRIPTION OF THE INVENTION

[0015] <Outline of the embodiment> The present invention can take the following various forms.

[0016] That is, a sterilization method according to one embodiment is a method of sterilizing an object by applying pernitrate gas to the object. As described above, in this specification, "sterilization" refers to reducing the number of viable bacteria (viable bacteria concentration).

[0017] Peroxynitric acid gas is a vaporized gas generated from peroxynitric acid mist, which is produced by misting a liquid containing peroxynitric acid (Peroxynitric acid (PNA), HOONO2). The liquid containing peroxynitric acid may be produced by the method disclosed in the above-mentioned Patent Document 1. For example, a liquid containing peroxynitric acid is produced by mixing a peroxide (hydrogen peroxide, etc.) and a nitrite under strongly acidic conditions of pH 2 or less.

[0018] As a method for generating pernitrate mist, for example, there is a method of turning a liquid containing pernitrate into mist by ultrasonic atomization. Alternatively, for example, a liquid containing pernitrate may be turned into mist by spraying, thereby generating pernitrate mist. Alternatively, for example, a gas containing pernitrate gas may be generated by bubbling a gas (air) into a liquid containing pernitrate. Alternatively, for example, a liquid containing pernitrate may be gasified by evaporating it, thereby generating a gas containing pernitrate gas.

[0019] In this specification, mist refers to fine droplets that cannot pass through gas-permeable materials such as glassine paper used in sterilization bags. While mist cannot pass through gas-permeable materials, by converting it into a minute mist with a relatively large surface area compared to its volume, it becomes possible to efficiently generate peroxynitride gas in the mist-containing gas, which can then pass through the gas-permeable material. In other words, peroxynitride gas passes from the mist-containing gas surrounding the sterilization bag into the interior of the sterilization bag. Thus, gasification refers to converting peroxynitride molecules contained in a liquid, such as by mist, into a state that allows them to pass through the aforementioned gas-permeable material.

[0020] An example of a method for producing pernitric acid gas will be described in detail below.

[0021] <Ultrasonic atomization> Specific ultrasonic atomization techniques include a nebulizer technique, an atomizer technique, and a mesh technique. In the nebulizer technique, a second container containing a liquid containing pernitric acid (hereinafter referred to as pernitric acid liquid) is placed in a first container containing a liquid such as water. An ultrasonic vibrator provided in the first container vibrates the liquid such as water in the first container, thereby atomizing the pernitric acid liquid in the second container. In the atomizer technique, the pernitric acid liquid is atomized by directly vibrating it with an ultrasonic vibrator. In the mesh technique, the pernitric acid liquid is atomized by supplying it to a metal mesh while the metal mesh is vibrating.

[0022] 1 is a diagram showing a sterilization device 1 that generates pernitric acid gas by a nebulizer method, as an example of a sterilization device according to an embodiment. The sterilization device 1 includes a pernitric acid gas generation unit 10 and a sterilization treatment unit 20.

[0023] Pernitric acid gas generation unit 10 includes a first container 11, a second container 12, an ultrasonic vibrator 13, and a control device 14. Ultrasonic vibrator 13 is provided at the bottom of first container 11. A liquid such as water is placed inside first container 11. A second container 12 is also placed inside first container 11. A pernitric acid liquid is placed inside second container 12. A first pipe 15 and a second pipe 16 are connected to second container 12, which is in a sealed state.

[0024] The control device 14 controls the operation of the ultrasonic transducer 13. The control device 14 includes a processor such as a CPU (Central Processing Unit) or an MPU (Micro Processing Unit), and a memory such as a ROM (Read Only Memory) and a RAM (Random Access Memory). The processor controls the operation of the ultrasonic transducer 13 by executing a computer program stored in the memory.

[0025] The sterilization treatment unit 20 includes a sterilization container 21. In the illustrated example, the sterilization container 21 is a box-shaped container, but the shape, capacity, etc. may be arbitrary. Furthermore, a pipe such as the second pipe 16 may be used as the sterilization container 21. The sterilization object 22 is contained inside the sterilization container 21. The sterilization object 22 is a medical instrument, a food container, etc. The sterilization object 22 may be contained in the sterilization container 21 while being placed in a sterilization bag 23. In the illustrated example, the sterilization object 22 is placed in the sterilization bag 23. The sterilization bag 23 is made of a gas-permeable material such as nonwoven fabric or glassine paper that does not allow bacteria and liquids to pass through but allows gas to pass through. The sterilization container 21 communicates with the second container 12 via the second pipe 16. Furthermore, an exhaust port 24 is opened in the sterilization container 21.

[0026] The compressor 30 sends air into the second container 12 via the first pipe 15. The means for sending air into the second container 12 is not limited to the compressor 30, and may be a pump, a fan, or the like.

[0027] Next, the operation of the sterilization device 1 will be described. Vibration of the ultrasonic vibrator 13 in accordance with a control command from the control device 14 causes the liquid, such as water, in the first container 11 to vibrate. This causes the pernitrate liquid in the second container 12 to atomize, generating pernitrate mist. The pernitrate mist is made up of fine droplets of pernitrate liquid, which evaporate or degas to produce a vaporized gas (i.e., pernitrate gas). In other words, the gas containing the pernitrate mist also contains pernitrate gas. The gas containing the pernitrate mist and pernitrate gas flows through the second piping 16 together with gas (e.g., air) sent from the compressor 30 and is introduced into the sterilization container 21. The pernitrate gas introduced into the sterilization container 21 can pass through the sterilization bag 23 and sterilize the sterilization target 22 in the sterilization bag 23. The gas containing the pernitrate mist and pernitrate gas introduced into the sterilization container 21 is finally discharged to the outside through the exhaust port 24.

[0028] Although the sterilization apparatus 1 in the illustrated example is configured to send air into the second container 12 by the compressor 30, it may be configured not to send air, i.e., it may be configured without the compressor 30 and the first piping 15. Furthermore, although the sterilization apparatus 1 in the illustrated example is configured to discharge the pernitrate gas in the sterilization container 21 to the outside from the exhaust port 24, it may be configured to recirculate it into the second container 12.

[0029] Here, with reference to Figures 2 to 5, the results of a sterilization test using a sterilization device 1 that generates pernitrate gas by a nebulizer method will be described. Here, a sterilization test was conducted using a sterilization device 1 including a pernitrate gas generation unit 10 using a nebulizer method as shown in Figure 1 and a sterilization treatment unit 20 using a sterilization container 21 with a volume of 90 L. The amount of pernitrate liquid used in the pernitrate gas generation unit 10 was about 15 mL per minute. The pernitrate mist and pernitrate gas in the sterilization container 21 were not discharged to the outside from the exhaust port 24, but were recirculated into the second container 12.

[0030] FIG. 2 is a graph showing the results of the first sterilization test using a large container. FIG. 3 is a graph showing the results of the second sterilization test using a large container. A biological indicator (BI) for determining the sterilization effect was placed in a sterilization container 21 with a volume of 90 L as the sterilization target 22. The BI was measured at 10 5 CFU bacterial spores (Geobacillus stearothermophilus) were supported on a stainless steel disk and placed in a glassine paper sterilization bag 23. The molar concentrations of the pernitrate solution placed in the second container 12 were 10 mM (FIG. 2) and 600 mM (FIG. 3). After the sterilization test, the BI was removed from the sterilization container 21 and cultured, and the viable cell count was examined after the culture (CFU assay). Sterilization was considered successful when the viable cell count was below the detection limit. As shown in FIG. 2, when the molar concentration of the pernitrate solution was 10 mM, the BI was sterilized in 3 minutes. As shown in FIG. 3, when the molar concentration of the pernitrate solution was 600 mM, the BI was sterilized in 1 minute.

[0031] Figure 4 is a table showing the results of the third sterilization test using a large container. Figure 5 is a table showing the results of the fourth sterilization test using a large container. BI is 10 6 CFU bacterial spores (Geobacillus stearothermophilus) were supported on stainless steel disks and placed in a glassine paper sterilization bag 23. The molar concentrations of the pernitrate solution placed in the second container 12 were 10 mM (Figure 4) and 600 mM (Figure 5). After sterilization, the BIs were removed from the sterilization container 21, cultured, and examined to see if the culture solution became cloudy (referred to here as an on-off test). Because the culture solution becomes cloudy even if even a single bacterium remains, the on-off test has a lower detection limit than the CFU assay, making sterilization more difficult. Nevertheless, as shown in Figure 4, when the molar concentration of the pernitrate solution was 10 mM, the BIs were sterilized in 10 minutes. As shown in Figure 5, when the molar concentration of the pernitrate solution was 600 mM, the BIs were sterilized in 1 minute.

[0032] Next, with reference to Figures 6 and 7, the results of a sterilization test using a sterilization device 1 that generates peroxynitride gas by a nebulizer method will be described. In the sterilization tests of Figures 2 to 5, the volume of the sterilization container 21 was large at 90 L, but in the sterilization tests of Figures 6 and 7, the volume of the sterilization container 21 was small at approximately 0.3 L. The amount of peroxide solution used in the peroxynitride gas generator 10 was approximately 3 mL per minute. In addition, the peroxynitride gas in the sterilization container 21 was discharged to the outside from the exhaust port 24 and was not recirculated into the second container 12.

[0033] FIG. 6 is a graph showing the results of the fifth sterilization test using a small container. 5 CFU bacterial spores (Geobacillus stearothermophilus) were supported on a stainless steel disk and placed in a glassine paper sterilization bag 23. The molar concentrations of the pernitrate solution placed in the second container 12 were 10, 100, 200, and 600 mM. The sterilization test at 600 mM was performed twice. The CFU assay results showed a survival curve S10 when the pernitrate solution had a molar concentration of 10 mM, a survival curve S100 when the pernitrate solution had a molar concentration of 100 mM, a survival curve S200 when the pernitrate solution had a molar concentration of 200 mM, and survival curves S600a and S600b when the pernitrate solution had a molar concentration of 600 mM. These survival curves indicated that a higher molar concentration of the pernitrate solution resulted in higher sterilization power.

[0034] FIG. 7 is a table showing the bactericidal activity calculated from each of the survival curves S10, S100, S200, S600a, and S600b shown in FIG. 6. The pernitrate solution concentration [mM] shown in the table is the molar concentration of the pernitrate solution placed in the second container 12. Note that the molar concentration was lowered by diluting the original pernitrate solution, so the pH increases as the molar concentration decreases. The D value [s] is the time calculated from the survival curve for the number of viable bacteria to decrease to 1 / 10. 1 / D [1 / s] is the reciprocal of the D value and indicates the bactericidal activity. The table shows that the bactericidal activity is proportional to the molar concentration of the pernitrate solution, and that the higher the molar concentration of the pernitrate solution, the higher the bactericidal activity.

[0035] The sterilization test results shown in Figures 2 to 7 indicate that the BI placed in the sterilization bag 23 was sterilized within a few seconds to a few minutes. Because the sterilization bag 23 does not allow pernitrate mist to pass through but allows pernitrate gas to pass through, it can be concluded that the sterilization of the BI is due to the pernitrate gas. In other words, the pernitrate gas is a sterilizing agent.

[0036] As will be described later, gaseous pernitrate has a shorter half-life than liquid pernitrate. Therefore, compared to liquid pernitrate, gaseous pernitrate does not maintain its sterilization effect as easily. However, when air and pernitrate mist are mixed, the pernitrate mist evaporates or volatilizes, causing pernitrate gas to be continuously supplied to the air. This allows the sterilization effect of the pernitrate gas to be maintained. In other words, compared to a system that supplies only pernitrate gas, a system that supplies pernitrate gas together with the pernitrate mist maintains the high sterilization effect of the pernitrate gas for a longer period of time, enabling sterilization in a larger space. In fact, the sterilization test results shown in Figures 2 to 5 demonstrate that BIs can be sterilized within a few minutes, even when a large container is used as the sterilization container 21, demonstrating sufficient sterilization power.

[0037] Here, the characteristics of peroxynitrate gas and peroxynitrate mist will be described in detail. When pernitrate gas is supplied to the object to be sterilized, its concentration continues to decrease from the time of gasification, so if the time until it is applied to the object to be sterilized is long, the concentration of pernitrate gas may decrease to a concentration below the effective concentration for sterilization.On the other hand, when a gas containing pernitrate mist is supplied to the object to be sterilized, even if the pernitrate gas with a short half-life is inactivated, pernitrate gas continues to be supplied from the pernitrate mist with a relatively long half-life due to gas-liquid equilibrium.Therefore, pernitrate gas is constantly maintained at a concentration close to saturation near the pernitrate mist.This suppresses the decrease in the concentration of pernitrate gas, making it possible to maintain the sterilizing effect of high-concentration pernitrate gas for a long period of time, and making it possible to sterilize large-volume spaces such as cell culture isolators.

[0038] When comparing the application of a gas containing pernitrate mist to the object to be sterilized with the application of pernitrate liquid directly to the object to be sterilized, the application of a gas containing pernitrate mist to the object to be sterilized has the advantage that sterilization is possible by the pernitrate gas generated around the object even if the pernitrate mist does not come into contact with the object to be sterilized. In other words, since it is not necessary to completely cover the entire surface to be sterilized with pernitrate liquid, sterilization is possible with a relatively small amount of pernitrate liquid, and the amount of chemical solution used can be significantly reduced.

[0039] When the target to be sterilized has a fine structure, it is difficult to apply droplets of pernitric acid solution. On the other hand, pernitric acid gas can diffuse in the gas phase, allowing the molecules of pernitric acid to reach the fine structure, so a reliable sterilization effect can be expected.

[0040] Next, the results of a sterilization test using the sterilization device 1 that generates peroxynitrate gas by a nebulizer method will be described with reference to Figure 8. In the sterilization test of Figure 8, sterilization of a pigskin contamination model was performed by the nebulizer method, with the aim of application to biological disinfection.

[0041] FIG. 8 is a graph showing the results of the sixth sterilization test using a pig skin contamination model. 6 A CFU spore solution (Bacillus subtilis) was applied and dried to create a contamination model. This pigskin contamination model was placed in a sterilization container 21 with a volume of approximately 0.3 L as the sterilization target 22. The surface of the pigskin contamination model was positioned perpendicular to the flow direction of the gas containing pernitrate gas and pernitrate mist. The molar concentration of the pernitrate solution placed in the second container 12 was 100 mM. After the sterilization test, bacteria were collected from both the front and back surfaces of the pigskin contamination model using a stomacher, and a CFU assay was performed. As shown in Figure 8, the number of viable bacteria decreased with increasing exposure time, and the model was sterilized within 3 minutes.

[0042] The sterilization test results shown in Figure 8 demonstrate that pernitrate gas is effective for disinfecting living organisms. It has a variety of applications, including disinfecting hands (e.g., in hand-washing devices), disinfecting wounds (e.g., trauma, bedsores, burns, and ulcers), and disinfecting incisions before surgical procedures. Incidentally, 100 mM pernitrate solution is a concentration whose safety has been verified in animal experiments. Methods using pernitrate gas, such as those used in this sterilization test, are considered safer than methods in which pernitrate solution is directly applied to the target to be sterilized. Thus, pernitrate gas is expected to have a sterilizing effect for the prevention and treatment of infectious diseases.

[0043] In the above 1st to 6th sterilization tests, diluted pernitrate solution was used. For example, pernitrate was chemically synthesized at about pH 0 to produce a 1M stock solution, which was then diluted 10 times to produce a 100mM pernitrate solution with a pH of 1. Alternatively, it was diluted 100 times to produce a 10mM pernitrate solution with a pH of 2.

[0044] The closer the molar concentration of the pernitrate solution is to the 1M molar concentration of the original solution, the lower the pH, making it more difficult to atomize. Furthermore, in high-concentration pernitrate solutions, oxygen gas generated by the decomposition of pernitrate generates bubbles on the container surface, hindering ultrasonic atomization. Therefore, as a pre-sterilization process, the control device 14 controls the operation of the ultrasonic vibrator 13 to generate ultrasonic waves with a kilohertz frequency (e.g., 50 kHz). This removes bubbles contained in the pernitrate solution (i.e., degassing). During sterilization, the control device 14 controls the operation of the ultrasonic vibrator 13 to generate ultrasonic waves with a megahertz frequency suitable for atomization. Degassing before sterilization makes the pernitrate solution more easily atomized. To remove bubbles that occur during atomization, atomization and bubble removal may be alternated. Note that if the pernitrate solution has a low molar concentration and is easy to atomize, sterilization may be performed by generating megahertz-frequency ultrasonic waves without degassing.

[0045] If the pernitrate solution is difficult to atomize, the pernitrate solution may be vacuum deaerated as a pretreatment before sterilization. Vacuum deaerating the pernitrate solution before sterilization makes it easier to atomize the pernitrate solution.

[0046] <Spray> Specific methods of spraying include a one-liquid type and a gas mixing type. In the one-liquid type, pernitrate mist is generated by spraying pernitrate liquid, and pernitrate gas is generated from the pernitrate mist. In the gas mixing type, pernitrate mist is generated by mixing pernitrate liquid with air, and pernitrate gas is generated from the pernitrate mist.

[0047] 9 is a diagram showing a peroxynitrate gas generator 50 that generates peroxynitrate gas by gas mixing spraying. The peroxynitrate gas generator 50 includes a first nozzle 51, a second nozzle 52, a pump 53, a container 54, a compressor 55, and a control device 56.

[0048] A pernitrate solution is placed inside container 54. Pump 53 sends the pernitrate solution inside container 54 to first nozzle 51. Pump 53 may pressurize the pernitrate solution when sending it to first nozzle 51. First nozzle 51 sprays the pernitrate solution from the tip.

[0049] Compressor 55 sends air to second nozzle 52. Note that the means for sending air to second nozzle 52 is not limited to compressor 55 and may be a pump or the like. Second nozzle 52 blows air from its tip. Because the tip of first nozzle 51 and the tip of second nozzle 52 are positioned very close to each other, the pernitrate liquid coming out of first nozzle 51 and the air coming out of second nozzle 52 collide, generating pernitrate mist. As the pernitrate mist evaporates, a vaporized gas (i.e., pernitrate gas) is generated. In other words, the gas containing pernitrate mist contains pernitrate gas. The gas containing pernitrate mist and pernitrate gas is introduced into sterilization processing unit 20 (see FIG. 1). Sterilization target 22 contained in sterilization container 21 may be placed in sterilization bag 23.

[0050] The gas blown out from the second nozzle 52 may be heated by a heater or the like. When the hot air blown out from the second nozzle 52 mixes with the pernitrate mist sprayed from the first nozzle 51, the temperature of the gas containing the pernitrate mist rises. When the temperature of the gas rises, the saturated vapor pressure increases, and the concentration of the pernitrate gas increases. In addition, the increase in temperature has the effect of accelerating the sterilization rate (i.e., the chemical reaction rate). Therefore, it is possible to efficiently sterilize the sterilization target 22. The method of spraying pernitrate liquid is particularly suitable for sterilizing food containers such as PET bottles. Efficient sterilization by heating is expected to achieve sterilization in a short period of time and also leads to a reduction in the cost required for sterilization.

[0051] Control device 56 may control the operation of pump 53 and compressor 55 so that spraying of pernitrate solution from first nozzle 51 and blowing of heated air from second nozzle 52 alternate. Control device 56 first blows hot air to raise the atmospheric temperature inside sterilization container 21, and then sprays pernitrate solution to sterilize sterilization target 22 with pernitrate gas. Thereafter, control device 56 blows hot air to create a high-temperature environment, thereby drying sterilization target 22 and detoxifying the pernitrate.

[0052] The control device 56 may constantly blow out hot air and spray the pernitric acid solution for a short time in between.

[0053] As will be described in detail in Figure 10, the lifespan of synthesized pernitric acid is temperature-dependent, and as the temperature increases, the decomposition rate of pernitric acid increases and it changes to nitric acid in a short time (i.e., it is deactivated). Therefore, when hot air is passed through second nozzle 52, it is preferable to provide thermal insulation by maintaining a sufficient distance between second nozzle 52 and first nozzle 51 as shown in Figure 9, to prevent a rise in the temperature of the pernitric acid solution passing through first nozzle 51. Note that when room temperature or low temperature air is passed through second nozzle 52, first nozzle 51 and second nozzle 52 may be held integrally.

[0054] <Removal of pernitrate mist, etc.> The gas generated by the pernitrate gas generators 10, 50 includes not only pernitrate gas but also pernitrate mist, etc. Furthermore, when pernitrate liquid is generated by mixing nitrous acid and peroxide (e.g., hydrogen peroxide), the gas generated by the pernitrate gas generators 10, 50 may contain unnecessary chemical substances such as hydrogen peroxide, nitrite, and nitrate. Even if the gas generated by the pernitrate gas generators 10, 50 contains these unnecessary chemical substances, the sterilization effect of the pernitrate gas remains unchanged, but there is a problem in that white salts are precipitated on the surface of the sterilization target 22, etc. after sterilization. In this case, cleaning treatment, etc. after sterilization is required.

[0055] Therefore, in order to remove the peroxynitrate mist and unnecessary chemical substances from the gas generated in the peroxynitrate gas generation unit 10, 50 and apply only the peroxynitrate gas to the sterilization target 22, a separation device may be provided between the peroxynitrate gas generation unit 10, 50 and the sterilization treatment unit 20 (for example, on the second piping 16).

[0056] The separator preferably removes components other than the peroxynitrate gas from the gas generated in the peroxynitrate gas generator 10, 50. For example, the separator may be a nonwoven fabric filter that adsorbs mist. Alternatively, the separator may be a cyclone that separates the mist and gas by centrifugal separation.

[0057] To sterilize the inside of the sterilization bag 23 while preventing salt from adhering to the surface of the sterilization bag 23, the sterilization bag 23 may be double-layered. The nonwoven fabric, glassine paper, or the like that makes up the sterilization bag 23 allows only gas to pass through and not liquid. Therefore, by double-layering the sterilization bag 23, even if salt precipitates in the outer sterilization bag 23, only peroxynitride gas will penetrate into the interior, so the interior will not be contaminated with salt. Furthermore, because the mist and gas can be separated very close to the object to be sterilized 22, a high concentration of peroxynitride gas can be maintained.

[0058] If a single-layer sterilization bag 23 is used, it is sufficient to wash it with water after sterilization to remove salts deposited on the surface of the sterilization bag 23. If a double-layer sterilization bag 23 is used, it is sufficient to remove the outer sterilization bag 23 after sterilization, and washing with water is not necessary. Even if the outer sterilization bag 23 is removed, the sterilization of the sterilization target 22 is maintained by the inner sterilization bag 23.

[0059] In order to prevent salt precipitation, the pernitrate solution may be desalted using an ion exchange resin, etc. By using the desalted pernitrate solution, it is possible to generate a pernitrate mist that does not contain salt components.

[0060] Because it is desirable to apply the pernitric acid solution to the object to be sterilized under acidic conditions, an acid (e.g., nitric acid) may be added during the synthesis of the pernitric acid solution to adjust the pH. In this case, the resulting pernitric acid mist may also contain acid, which may adhere to the surface of the object to be sterilized 22. To avoid the need to wash away the acid adhering to the surface of the object to be sterilized 22, the pernitric acid solution may be synthesized using, for example, a less volatile acid. A less volatile acid is an acid with a low vapor pressure, such as sulfuric acid. The vapor pressure of sulfuric acid (0.0067 Pa at 25°C) is lower than that of nitric acid (6.4 kPa at 20°C). Adding sulfuric acid during the synthesis of the pernitric acid solution to adjust the pH may reduce the risk of acid scattering as an impurity during gasification. In addition to sulfuric acid, other less volatile acids include phosphoric acid (4 Pa at 20°C) and periodic acid (a solid that does not volatilize).

[0061] Furthermore, when synthesizing a pernitrate solution by chemically reacting nitrous acid with hydrogen peroxide, a solution containing dissolved powdered sodium nitrite may be used instead of nitrous acid. This is because nitrous acid alone is unstable. However, sodium nitrite contains Na, which leads to salt precipitation. Therefore, to prevent salt precipitation, nitrous acid gas generated from an acidified sodium nitrite solution or nitrous acid gas stored in a cylinder may be used. Furthermore, pernitrate gas may be generated by mixing nitrous acid gas with hydrogen peroxide gas.

[0062] <Half-life time of peroxynitrate gas> 10 is a graph showing the half-life of pernitrate solution. As shown in the graph, the lower the temperature of the pernitrate solution (or the ambient temperature), the longer the half-life of the pernitrate solution. For example, when the pH of the pernitrate solution is 2.9, the half-life at a temperature of 2°C is 132 minutes, the half-life at 10°C is 26 minutes, the half-life at 20°C is 7.8 minutes, the half-life at 30°C is 2 minutes, and the half-life at 40°C is 0.6 minutes. Thus, the half-life of the pernitrate solution depends on the temperature.

[0063] The following document discloses a formula for calculating the half-life of peroxynitrate gas. For example, the half-life of peroxynitrate gas under conditions of 1 atmosphere and 4.55 degrees (277.7K) is 97 seconds. Also, under conditions of 1 atmosphere and 24.85 degrees (298K), the half-life is 12 seconds. Richard A. Graham, Arthur M. Winer, and James N. Pitts Jr., The Journal of Chemical Physics “Pressure and temperature dependence of the unimolecular decomposition of HO2NO2” (US), 1978, Vol. 68, p. 4505

[0064] As described above, the decomposition rate of pernitrate mist and pernitrate gas increases at high temperatures, and they change into nitric acid in a short time (i.e., they are deactivated). Therefore, even if detoxification treatment is not performed after sterilization, the pernitrate adhering to the surface of the sterilization target 22 is deactivated simply by storing the sterilization target 22 at room temperature. In particular, since the half-life time of pernitrate gas is shorter than that of pernitrate mist, there is little need to perform detoxification treatment after sterilization using only pernitrate gas.

[0065] To prevent thermal inactivation of the pernitrate solution contained in the second container 12, the sterilizer 1 may have a structure that keeps the temperature of the pernitrate solution low. For example, a heat exchanger may be added to the second container 12, and the pernitrate solution in the second container 12 may be cooled by circulating an external coolant through the heat exchanger. Alternatively, for example, an external tank with a heat exchanger may be connected to the second container 12, and the pernitrate solution may be cooled by circulating it between the second container 12 and the external tank. The structure that keeps the temperature of the pernitrate solution low may be a structure other than the above examples.

[0066] Furthermore, under the same temperature conditions, liquid pernitrate has a longer half-life than gaseous pernitrate. Therefore, by transporting and supplying a gas containing pernitrate mist to the sterilization target 22, the decrease in the concentration of pernitrate gas is suppressed, and a wider sterilization effect can be expected from the high concentration of pernitrate gas than by supplying pernitrate gas alone. Therefore, it can be applied to sterilization of large spaces such as operating rooms, food manufacturing factories, and plant factories. Furthermore, while fumigants are sometimes used to sterilize seeds and agricultural products, it is possible to use pernitrate gas or pernitrate mist instead of fumigants.

[0067] <Detoxification processing> As mentioned above, since the half-life of pernitrate gas and pernitrate mist at room temperature is short, there is little need to perform detoxification treatment after sterilization. If detoxification treatment is performed after sterilization, aeration or ultraviolet irradiation, etc., is performed. The fact that pernitrate is decomposed by ultraviolet irradiation is described in, for example, the following document. Helene MacLeod, Gregory P. Smith, David M. Golden, Journal of Geophysical Research Atmospheres “Photodissociation of pernitric acid (HO2NO2) at 248 nm” (US), 1988, Vol. 93, p. 3813-3823

[0068] <pH of pernitrate solution> As disclosed in the above-mentioned Patent Document 1, when generating pernitric acid by reacting a peroxide (hydrogen peroxide, etc.) with a nitrite, a strong acid with a pH of 2 or less is an essential condition, and the lower the pH, the more efficient the synthesis of pernitric acid. Also, pernitric acid is more stable at lower pH, and decomposes more quickly at higher pH, shortening the half-life.

[0069] The pKa of nitric acid is about -1.4, and the pKa of pernitric acid is about 5.85. At a pH higher than pKa, the proportion of ions present is high, so it is generally difficult to evaporate. In other words, by making the pH of pernitric acid solution 5.85 or less, pernitric acid can be preferentially evaporated to obtain high bactericidal power, while making it difficult for nitric acid to evaporate. Therefore, it is preferable that the pH of the pernitric acid solution used to generate pernitric acid gas is -1.4 or more and 5.85 or less.

[0070] As disclosed in the above Patent Document 1, peroxynitric acid (HOONO2) synthesized by chemical reaction contains protons (H + ), superoxide anion radical (O2 - It is thought that the superoxide anion radical reacts with protons in the solution to generate hydroperoxy radicals (HOO·), as shown in equation (1).

[0071] O2 - + H + ←→ HOO· (1)

[0072] The hydroperoxy radical shown in the above formula (1) has an extremely short lifespan, but has a stronger bactericidal effect than the superoxide anion radical. Formula (1) is an equilibrium reaction, and since it is in an equilibrium relationship dependent on the pH of the solution, the concentration of hydroperoxy radicals increases when the proton concentration is high. In other words, the dissociation constant (acid dissociation constant) pKa, which represents the equilibrium constant of this equilibrium reaction formula, is 4.8.

[0073] When the pH is higher than 4.8, the concentration of superoxide anion radicals is high and the concentration of hydroperoxy radicals is low. When the pH is 4.8 or lower, the concentration of hydroperoxy radicals is high, resulting in extremely strong bactericidal power. By increasing the bactericidal power of pernitrate solution by keeping the pH at 4.8 or lower, high bactericidal power can also be achieved against pernitrate gas.

[0074] Although the lower the pH of the pernitrate solution, the stronger the sterilizing power, lowering the pH to about 3 or less does not significantly affect the sterilizing effect. Furthermore, if the pH is below 0.5, metal corrosion can become a problem. Therefore, it is practical to keep the pH of the pernitrate solution used to generate pernitrate gas between about 2 and 5.85.

[0075] As described above, the sterilization effect of pernitric acid increases sharply under acidic conditions (pH 4.8 or less). Therefore, it is expected that the sterilization effect will be enhanced by actively supplying an acidic gas to the sterilization target 22. Specifically, a volatile acidic substance is gasified to generate an acidic gas, and the gas containing pernitric acid mist and pernitric acid gas and the acidic gas are supplied into the sterilization container 21 and applied to the sterilization target 22. The acidic gas may also be supplied into the second container 12 or the second piping 16 upstream of the sterilization container 21. Examples of volatile acidic substances include nitric acid, hydrochloric acid, carbon dioxide, hydrofluoric acid, and chloric acid.

[0076] <Variation 1> In the sterilization processing unit 20 shown in FIG. 1, the sterilization container 21 may be a container without an exhaust port 24. For example, before sterilization, the air inside the sterilization container 21 is removed (evacuated) using a vacuum pump to reduce the internal pressure and create a negative pressure inside the sterilization container 21 that is lower than the external pressure (atmospheric pressure). Furthermore, the sterilization container 21 may be evacuated using a vacuum pump not only before sterilization but also while the pernitrate gas is being applied to the sterilization target 22 (i.e., during sterilization). This makes it easier for the pernitrate gas generated by the pernitrate gas generators 10 and 50 to fill the sterilization container 21 and thoroughly sterilize the sterilization target 22. Furthermore, if the sterilization target 22 is placed in a sterilization bag 23, the pernitrate gas is more easily filled into the sterilization bag 23 and thoroughly sterilizes the sterilization target 22. Furthermore, evacuating the sterilization container 21 allows for a larger capacity and the sterilization target 22 to be larger. Furthermore, repeated vacuuming during sterilization allows for more thorough sterilization. In addition, by exposing the pernitrate solution to a vacuum, it is expected that impurities including salts will not be generated, and only pernitrate gas will be generated efficiently. According to the above-mentioned Graham et al. document, the half-life time of pernitrate gas itself is extended when the pressure is low, so by repeatedly drawing a vacuum, the decrease in the concentration of pernitrate gas can be suppressed, and the sterilization effect can be maintained for a long time.

[0077] <Variation 2> In Figures 1 and 9, the pernitrate gas generators 10, 50 and the sterilization treatment unit 20 are configured as separate units, but they may also be configured as an integrated unit. For example, the pernitrate gas generator 10 is placed at the bottom of the sterilization container 21, and the sterilization target 22 is placed at the top. Alternatively, the sterilization target 22 and pernitrate solution may be placed in the sterilization container 21, and the sterilization container 21 may be placed in a negative pressure state to facilitate vaporization of the pernitrate solution, thereby generating pernitrate gas. As in Variation 1, the sterilization container 21 may be repeatedly evacuated during sterilization, in which case it is expected that only pernitrate gas will be generated efficiently without generating impurities containing salt. Alternatively, pernitrate gas may be generated by bubbling the pernitrate solution placed in the sterilization container 21.

[0078] <Variation 3> 1 and 9, the pernitrate gas generators 10, 50 and the sterilization treatment unit 20 are connected by the second pipe 16 or the like, but they do not have to be connected. For example, the pernitrate gas generated in the pernitrate gas generators 10, 50 is adsorbed onto a porous material such as silica gel or activated carbon. The porous material is then placed in the sterilization container 21 of the sterilization treatment unit 20, and the pernitrate gas is released from the porous material. For example, efficient sterilization can be achieved by adsorbing the pernitrate gas onto the porous material at a low temperature, at which the half-life is extended, and then releasing the pernitrate gas in a short time at a high temperature. <Variation 4> Sterilization treatment unit 20 may be equipped with a moving means for moving sterilization target 22, such as a belt conveyor. Efficient sterilization can be achieved by moving sterilization target 22 through a space in which pernitrate gas is floating while the temperature of sterilization target 22 is elevated. For example, a heating zone and a sterilization zone are arranged consecutively on the path of movement of the moving means, the temperature of sterilization target 22 is elevated in the heating zone, and then pernitrate gas is applied to sterilization target 22 in the sterilization zone.

[0079] <Variation 5> The surface temperature of the sterilization target 22 may be increased. For example, the surface temperature of the sterilization target 22 is increased by continuously irradiating the sterilization target 22 with infrared light from an infrared lamp. The increase in surface temperature has the effect of accelerating the sterilization rate (i.e., the chemical reaction rate). Therefore, the sterilization target 22 can be sterilized efficiently.

[0080] <Variation 6> To improve sterilization power, the surface of the sterilization target 22 may be acidified. For example, carbon dioxide may be filled into the sterilization container 21 as a pretreatment to acidify the surface of the sterilization target 22. Also, the carbon dioxide concentration of the air sent to the second container 12 in the peroxynitrate gas generator 10 may be increased. Also, the carbon dioxide concentration of the air sent to the second nozzle 52 in the peroxynitrate gas generator 50 may be increased.

[0081] As explained above with reference to Figures 1 to 10, gasifying pernitrate liquid significantly expands the scope of sterilization applications compared to using pernitrate liquid alone. For example, it is possible to sterilize sterilization targets 22 placed in liquid-impermeable sterilization bags 23. It is also possible to sterilize precision machinery such as endoscopes that cannot be sterilized in an autoclave, heat-sensitive plastic products, and even living organisms. Furthermore, since the sterilization target 22 does not get wet and there is little residue, it is easy to sterilize food containers and the like. Furthermore, since spatially uniform sterilization is possible throughout the entire area, it is easy to sterilize cell culture isolators, operating rooms, food manufacturing factories, plant factories, and the like. In addition, since pernitrate gas has a short half-life, there is no need for detoxification treatment after sterilization, which reduces costs and time.

[0082] The use of pernitrate mist, which generates pernitrate gas, can reduce the cost of the chemical used compared to the use of pernitrate liquid. For example, sterilizing a 100-liter container using only pernitrate liquid requires 100 liters of chemical. Furthermore, when spraying pernitrate liquid directly onto a 100-liter container containing a sterilization target, it is expected that almost no pernitrate gas will be generated, and therefore a considerable amount of chemical (e.g., several liters) is required to completely wet the target. In contrast, the use of pernitrate mist, which generates pernitrate gas, can significantly reduce the amount of chemical used, thereby reducing chemical costs. As a specific example, for the large 90-liter sterilization container 21 shown in Figures 2 to 5, the amount of chemical used per minute in the pernitrate gas generator 10 is approximately 15 mL, which is a significantly smaller amount of chemical relative to the container's volume. As mentioned above, pernitrate liquid is difficult to atomize at high molar concentrations, so depending on the molar concentration, even less chemical may actually be used for sterilization. Furthermore, since the pernitrate mist adheres to the inner surfaces of the second container 12, the second pipe 16, etc., the amount of chemical liquid that actually acts to sterilize may be even smaller.

[0083] The present invention is not limited to the above-described embodiment, and can be implemented in various forms without departing from the spirit of the present invention. [Industrial Applicability]

[0084] The present invention is applicable to the sterilization of medical instruments, cell culture isolators, living organisms, food containers, etc., and has industrial applicability. [Explanation of symbols]

[0085] 1 Sterilizer 10, 50 Nitric acid gas generator 11 1st container 12 Second container 13 Ultrasonic transducer 14, 56 Control device 15 First Pipe 16 Second piping 20 Sterilization processing section 21 Sterilization container 22 Sterilization target 23 Sterilization Bags 24 exhaust port 30, 55 compressor 51 No. 1 nozzle 52 Second nozzle 53 Pump 54 Container

Claims

1. A sterilization method comprising applying pernitrate gas to an object to be sterilized to sterilize the object.

2. The sterilization method according to claim 1, wherein the pernitrate gas is a vaporized gas produced from a pernitrate mist obtained by misting a liquid containing pernitrate.

3. The sterilization method according to claim 2, wherein the liquid containing pernitric acid is atomized by ultrasonic atomization to generate the pernitric acid mist.

4. 4. The sterilization method according to claim 3, wherein the liquid containing pernitric acid is degassed by ultrasonic waves having a frequency of kilohertz, and the degassed liquid is turned into mist by ultrasonic waves having a frequency of megahertz.

5. The sterilization method according to claim 3, wherein the liquid containing pernitric acid is vacuum degassed, and the vacuum degassed liquid is turned into mist by the ultrasonic atomization.

6. The sterilization method according to claim 2, wherein the liquid containing pernitric acid is atomized to generate the pernitric acid mist.

7. 7. The sterilization method according to claim 6, wherein heated air is collided with the liquid containing pernitric acid to generate the pernitric acid mist and the pernitric acid gas.

8. The sterilization method according to claim 6, wherein the liquid containing pernitric acid is sprayed into a space to which heated air is supplied.

9. The sterilization method according to claim 2, wherein the pernitrate mist is removed from a gas containing the pernitrate mist and the pernitrate gas, and the gas after removal is applied to the object to be sterilized.

10. 2. The sterilization method according to claim 1, wherein the pernitric acid gas is generated by bubbling a liquid containing pernitric acid.

11. The sterilization method according to any one of claims 1 to 10, wherein the pernitrate gas is applied to the object to be sterilized housed in a container under negative pressure.

12. The sterilization method according to any one of claims 1 to 10, wherein the container is evacuated to a vacuum during the period in which the pernitrate gas is applied to the object to be sterilized contained in the container.

13. The sterilization method according to any one of claims 2 to 10, wherein the liquid containing pernitric acid has a pH of 5.85 or less.

14. The sterilization method according to any one of claims 1 to 10, wherein carbon dioxide is applied to the object to be sterilized.

15. The sterilization method according to any one of claims 1 to 10, wherein an acidic gas is applied to the object to be sterilized.

16. a pernitric acid gas generating unit that generates pernitric acid gas by gasifying a liquid containing pernitric acid; a sterilization processing unit that applies the peroxynitrate gas to an object to be sterilized to sterilize the object; A sterilization device comprising:

17. The pernitrate gas is a vaporized gas generated from a pernitrate mist obtained by misting a liquid containing pernitrate, The peroxynitrate gas generating unit is The liquid containing pernitric acid is atomized by ultrasonic atomization to generate the pernitric acid mist; 17. The sterilization apparatus according to claim 16, wherein the liquid containing pernitric acid is degassed by ultrasonic waves having a frequency of kilohertz, and the degassed liquid is turned into mist by ultrasonic waves having a frequency of megahertz.

18. The peroxynitrate gas is a vaporized gas generated from a peroxynitrate mist obtained by misting a liquid containing peroxynitrate, The peroxynitrate gas generating unit is The liquid containing pernitric acid is atomized by ultrasonic atomization to generate the pernitric acid mist; The sterilization apparatus according to claim 16, wherein the liquid containing pernitric acid is vacuum-degassed, and the vacuum-degassed liquid is turned into mist by the ultrasonic atomization.

19. The pernitrate gas is a vaporized gas generated from a pernitrate mist obtained by misting a liquid containing pernitrate, The peroxynitrate gas generating unit is The liquid containing pernitric acid is atomized to generate the pernitric acid mist, 17. The sterilizer according to claim 16, wherein heated air is collided with the liquid containing pernitric acid to generate the pernitric acid mist and the pernitric acid gas.

20. The peroxynitrate gas is a vaporized gas generated from a peroxynitrate mist obtained by misting a liquid containing peroxynitrate, The peroxynitrate gas generating unit is The liquid containing pernitric acid is atomized to generate the pernitric acid mist, The sterilizer according to claim 16, wherein the liquid containing pernitric acid is sprayed into a space to which heated air is supplied.

21. The pernitrate gas is a vaporized gas generated from a pernitrate mist obtained by misting a liquid containing pernitrate, The sterilization device according to claim 16, wherein the sterilization processing unit removes the pernitrate mist from a gas containing the pernitrate mist and the pernitrate gas, and applies the gas after removal to the object to be sterilized.

22. A sterilization device as described in claim 16, which applies carbon dioxide to the object to be sterilized.

23. A sterilization device as described in claim 16, which applies an acidic gas to the object to be sterilized.

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