Nitrogen oxide removal system

Abstract

For example, the present invention provides a nitrogen oxide removal system that prevents deterioration of target objects such as pharmaceuticals, cosmetics, food, and living organisms, and enables suitable handling of these objects. [Solution] A nitrogen oxide removal system for removing nitrogen oxides from outside air supplied to a workspace where an object is handled, comprising: a first nitrogen oxide concentration measuring means for measuring the concentration of nitrogen oxides contained in the outside air; and a nitrogen oxide removal means for removing nitrogen oxides, wherein the system is configured to measure the concentration of nitrogen oxides contained in the outside air with the first nitrogen oxide concentration measuring means, and if the concentration is below a specified value, the outside air is supplied to the workspace without being treated by the nitrogen oxide removal means, and if the concentration exceeds a specified value, clean air treated by the nitrogen oxide removal means is supplied to the workspace.

Description

[Technical Field]

[0001] The present invention relates to a nitrogen oxide removal system for preventing deterioration of objects such as pharmaceuticals, cosmetics, food, and living organisms, and enabling suitable handling of these objects. [Background technology]

[0002] Traditionally, various components contained in pharmaceuticals, cosmetics, foods, organisms used in cultivation and research, etc. (in solid, powder, semi-solid, or liquid forms) can be altered by oxidation or acid-base reactions (neutralization reactions) with acidic gases (nitrogen oxides, sulfur oxides, acetic acid, formic acid, etc.) or basic gases (ammonia, amines, etc.) in the air. In particular, the reaction of nitrogen oxides with ammonium salts or amines to produce nitrosamine compounds, which can become contaminated in pharmaceuticals and other medical products, poses a significant problem.

[0003] For this reason, when handling substances that react with nitrogen oxides, the handling space (in a room, or in a sealed or semi-sealed device installed in a room, such as a glove box or isolator) is generally replaced (or filled) with an inert gas such as nitrogen gas (see, for example, Patent Document 1). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2015-58938 [Overview of the project] [Problems that the invention aims to solve]

[0005] However, when the handling space is replaced with an inert gas as in the conventional method described above, it is necessary to constantly supply the inert gas and maintain positive pressure to prevent contamination with ambient air, which increases running costs. Furthermore, in the event of a large leak of inert gas, it is necessary to take measures to prevent oxygen deficiency (control of the supply gas amount, precise differential pressure management of the process space, gas concentration sensors, alarm systems, air cylinders, etc.), which also increases costs.

[0006] Furthermore, while the reaction between nitrogen oxides and ammonium salts or amines can be prevented to some extent by lowering the temperature, the cost of cooling becomes a problem.

[0007] In view of the above circumstances, the present invention aims to provide a nitrogen oxide removal system that prevents deterioration of target objects such as pharmaceuticals, cosmetics, food, and living organisms, and enables suitable handling of the target objects. [Means for solving the problem]

[0008] To achieve the above objectives, this invention provides the following means. [1] A nitrogen oxide removal system for removing nitrogen oxides from outside air supplied to a workspace where objects are handled, A first nitrogen oxide concentration measuring means for measuring the concentration of nitrogen oxides contained in the outside air, A means for removing nitrogen oxides, Equipped with, A nitrogen oxide removal system characterized in that the system measures the concentration of nitrogen oxides contained in the outside air using the first nitrogen oxide concentration measuring means, and if the concentration is below a specified value, the outside air is supplied to the workspace without being treated by the nitrogen oxide removal means, and if the concentration exceeds a specified value, clean air treated by the nitrogen oxide removal means is supplied to the workspace. [2] In the nitrogen oxide removal system described in [1], A nitrogen oxide removal system characterized by being configured to supply and circulate exhaust gas discharged from the aforementioned workspace back into the aforementioned workspace. [3] In the nitrogen oxide removal system described in [1] or [2], A second nitrogen oxide concentration measuring means for measuring the concentration of nitrogen oxides contained in the gas within the workspace or the concentration of nitrogen oxides contained in the exhaust gas discharged from the workspace, Furthermore, A nitrogen oxide removal system characterized in that, when the nitrogen oxide concentration measured by the second nitrogen oxide concentration measuring means is below a specified value, the gas or exhaust is supplied to the work space, and when it exceeds the specified value, the gas or exhaust is discharged outside the work space. [4] In a nitrogen oxide removal system described in any one of items [1] to [3], The object further comprises a means for measuring the content of nitrosamine compounds contained in the object, A nitrogen oxide removal system characterized in that it is configured to stop the handling of the object if the content of the nitrosamine compound measured by the nitrosamine compound content measuring means exceeds a specified value. [5] In a nitrogen oxide removal system described in any one of items [1] to [4], A nitrogen oxide removal system characterized in that the nitrogen oxide removal means is an anionic filter. [6] In a nitrogen oxide removal system described in any one of items [1] to [5], A nitrogen oxide removal system characterized in that the target substance is a drug used in the manufacture of pharmaceuticals. [7] A method for producing pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical preparations using a nitrogen oxide removal system described in any one of items [1] to [6]. [Effects of the Invention]

[0009] In the nitrogen oxide removal system of the present invention, by using the nitrogen oxide removal means, it is possible to prevent the cost from increasing.

[0010] In the nitrogen oxide removal system of the present invention, by using the nitrogen oxide concentration measurement means for measuring the concentration of nitrogen oxides, the concentration of nitrogen oxides in the supplied gas can be maintained below a specified value, so that the generation of harmful substances such as nitrosoamine compounds can be suppressed.

[0011] In the nitrogen oxide removal system of the present invention, the concentration of nitrogen oxides is measured by the first nitrogen oxide concentration measurement means. When the concentration is below the specified value, outside air is supplied to the working space without being treated by the nitrogen oxide removal means. When the concentration exceeds the specified value, clean air after being treated by the nitrogen oxide removal means is supplied to the working space, thereby suppressing the generation of harmful substances such as nitrosoamine compounds while suppressing the deterioration of the nitrogen oxide removal means such as a filter.

[0012] And since there is no need to use an inert gas, by filling the working space with a gas in which the concentration of nitrogen oxides is below the specified value, it becomes possible to handle an object in a working space where people can enter. As a result, expensive equipment for providing a sealed or semi-sealed working space becomes unnecessary, and it becomes possible to further improve the working efficiency.

Brief Description of the Drawings

[0013] [Figure 1] It is a diagram showing a nitrogen oxide removal system (outdoor air treatment · one-pass type) according to an embodiment of the present invention. [Figure 2] It is a diagram showing a nitrogen oxide removal system (outdoor air treatment · exhaust gas treatment · circulation type) according to an embodiment of the present invention. [Figure 3] It is a diagram showing a nitrogen oxide removal system (outdoor air treatment · untreated exhaust gas · circulation type) according to an embodiment of the present invention. [Figure 4]This figure shows a nitrogen oxide removal system (outside air treatment, exhaust treatment, untreated exhaust, and recirculating type) according to one embodiment of the present invention. [Figure 5] This figure shows a nitrogen oxide removal system (outside air treatment, nitrosamine compound content measurement, one-pass type) according to one embodiment of the present invention. [Figure 6] This figure shows a nitrogen oxide removal system (outside air treatment, nitrosamine compound content measurement, and circulation type) according to one embodiment of the present invention. [Figure 7] This is a flowchart illustrating a method for removing nitrogen oxides using nitrogen oxide removal system A1 according to one embodiment of the present invention. [Figure 8] This is a flowchart illustrating a method for removing nitrogen oxides using nitrogen oxide removal system A3 according to one embodiment of the present invention. [Figure 9] This is a flowchart showing a method for removing nitrogen oxides using nitrogen oxide removal system A4 according to one embodiment of the present invention. [Figure 10] This is a flowchart showing a method for removing nitrogen oxides using nitrogen oxide removal system A5 according to one embodiment of the present invention. [Figure 11] This graph shows the results of nitrogen oxide removal using a publicly known nitrogen oxide removal system. [Figure 12] This graph shows the effect of nitrogen oxide concentration on the formation of nitrosamine compounds. [Figure 13] This graph shows the effect of processing time on the formation of nitrosamine compounds. [Figure 14] This graph shows the effect of processing temperature on the formation of nitrosamine compounds. [Modes for carrying out the invention]

[0014] A nitrogen oxide removal system according to one embodiment of the present invention will be described below with reference to Figures 1 to 14.

[0015] ≪Nitrogen Oxide Removal System≫ The nitrogen oxide removal system of the present invention is a nitrogen oxide removal system for removing nitrogen oxides from outside air, indoor air, etc., supplied to a workspace where an object is handled, and comprises a first nitrogen oxide concentration measuring means for measuring the concentration of nitrogen oxides contained in the outside air, etc., and a nitrogen oxide removal means for removing nitrogen oxides, and is configured such that the concentration of nitrogen oxides contained in the outside air, etc. is measured by the first nitrogen oxide concentration measuring means, and if it is below a specified value, the outside air, etc. is supplied to the workspace without being treated by the nitrogen oxide removal means, and if it exceeds a specified value, clean air treated by the nitrogen oxide removal means is supplied to the workspace.

[0016] In this specification, "nitrogen oxides" refers to a general term for oxides of nitrogen, such as NO, NO2, N2O, and N2O3.

[0017] In this specification, "nitrosamine compounds" refers to the general term for compounds represented by the following chemical formula (1).

[0018] [ka]

[0019] In formula (1), R 1 and R 2 Each of these independently represents a hydrogen atom or a hydrocarbon group. Examples of hydrocarbon groups include substituted or unsubstituted linear or branched hydrocarbon groups having 1 to 20 carbon atoms, substituted or unsubstituted alicyclic groups having 3 to 20 carbon atoms, and substituted or unsubstituted aromatic hydrocarbon groups having 6 to 20 carbon atoms. 1 and R 2These groups may bond to each other to form a ring. The hydrogen atoms of these groups may be substituted with substituents, and the carbon atoms may be substituted with oxygen atoms, sulfur atoms, or nitrogen atoms, etc. Examples of substituents include C1-C5 alkyl groups, C1-C5 alkoxy groups, and halogen atoms. Among these, nitrosamine compounds contained in pharmaceuticals and other drugs include substituted or unsubstituted C1-C20 linear or branched hydrocarbon groups, substituted or unsubstituted C3-C20 alicyclic groups, and substituted or unsubstituted C6-C20 aromatic hydrocarbon groups, such as methyl groups, ethyl groups, isopropyl groups, n-butyl groups, piperidino groups, and morpholino groups.

[0020] For example, nitrosamine compounds are produced by the following mechanism.

[0021] [ka]

[0022] In the above reaction equation, R 1 and R 2 The same applies as above. In the above reaction equation, (R 1 )(R 2 )NH represents a primary amine compound or a secondary amine compound, but the raw materials for nitrosamine compounds may also be primary amine compounds, secondary amine compounds, tertiary amine compounds, nitrogen atom-containing aromatic heterocyclic compounds, or quaternary ammonium salts.

[0023] The ammonium salts or amines may be, for example, components contained in pharmaceuticals, cosmetics, foods, organisms used in cultivation and research, biological tissues, etc. (in solid, powder, semi-solid, or liquid form), or impurities contained therein. Examples of pharmaceutical drugs (active ingredients, raw materials) include metformin hydrochloride, pioglitazone hydrochloride, losartan potassium, losartan potassium hydrochlorothiazide, valsartan amlodipine besylate combination, valsartan, alogliptin benzoate / metformin hydrochloride combination, vildagliptin / metformin hydrochloride combination, pioglitazone hydrochloride / metformin hydrochloride combination, rifampicin, and irbesartan.

[0024] Examples of known nitrosamine compounds include N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitroso-N-methyl-4-aminobutyric acid (NMBA), N-nitrosomethylphenylamine (NMPA), N-nitrosoisopropylethylamine (NIPEA), N-nitrosodiisopropylamine (NDIPA), methylnitrosopiperazine (MeNP), N-nitrosodibutylamine (NDBA), N-nitrosomorpholine (NMOR), N-nitrosodipropylamine (NDPA), and N-nitrosoduloxetine (NDXT).

[0025] The acceptable daily intake (ng / day) of nitrosamine compounds that may be included in pharmaceuticals is as shown in Table 1 below, for example.

[0026] [Table 1]

[0027] Specifically, for example, in the nitrogen oxide removal system A1 of this embodiment, as shown in Figure 1, a sealed or semi-sealed reaction vessel H (Figure 1) is connected to an external air handling unit (not shown) including a blower and the like, and a nitrogen oxide removal means 2 including at least one filter and the like, which processes outdoor air (outside the work space G1) to generate clean air, and this clean air is supplied.

[0028] In the nitrogen oxide removal system A1 shown in Figure 1, a first nitrogen oxide concentration measuring means 1 and a nitrogen oxide removal means 2 are connected in that order outside the working space R, and the nitrogen oxide removal means 2 is connected to a reaction vessel H installed inside the working space R. A target substance C that should not react with nitrogen oxides is placed inside the reaction vessel H. A valve 3 is provided between the first nitrogen oxide concentration measuring means 1 and the nitrogen oxide removal means 2, and the first nitrogen oxide concentration measuring means 1 and the valve 3 are connected by line L1, and the valve 3 and the nitrogen oxide removal means 2 are connected by line L2. A line L4 connecting the nitrogen oxide removal means 2 and the reaction vessel H and a bypass line L3 connecting the valve 3 are provided. Exhaust gas G2 from the reaction vessel H is configured to be discharged outside the working space R through line L5.

[0029] Thus, the nitrogen oxide removal system A1 is configured to measure the concentration of nitrogen oxides contained in the outside air G1, and if it is below a specified value, the outside air G1 is supplied to the workspace R without being treated by the nitrogen oxide removal means 2. If it exceeds a specified value, the clean air treated by the nitrogen oxide removal means 2 is supplied to the workspace R.

[0030] In the nitrogen oxide removal system A1 shown in Figure 1, it is only necessary to control the amount of outside air supplied to the reaction vessel H so that the nitrogen oxide concentration is below a specified value. Therefore, the amount of outside air supplied can be reduced, which helps to prevent deterioration of nitrogen oxide removal means such as filters. The nitrogen oxide removal system A1 shown in Figure 1 has a nitrogen oxide concentration measuring means, which allows it to determine whether the nitrogen oxide concentration in the supplied outside air exceeds or falls below a specified value. Therefore, only the outside air whose nitrogen oxide concentration exceeds a specified value needs to be treated by the nitrogen oxide removal means, which reduces the amount of outside air controlled by the nitrogen oxide removal means. This suppresses the deterioration of the nitrogen oxide removal means compared to when all of the supplied outside air is controlled by the nitrogen oxide removal means. Furthermore, the nitrogen oxide removal system A1 has a bypass line connecting the reactor and the valve, allowing outside air with a nitrogen oxide concentration below a specified value to be supplied to the reactor without going through the nitrogen oxide removal means. Based on the above, the nitrogen oxide removal system A1 can reduce the number of replacements required due to deterioration of the nitrogen oxide removal means, thereby lowering the cost of removing nitrogen oxides.

[0031] Valve 3 may be, for example, a three-way cock, and may be capable of adjusting the destination and amount of gas supplied.

[0032] The aforementioned specified value is not particularly limited, and may be any concentration such that the content of nitrosamine compounds is below the upper limit value described later. Specifically, the specified value for the nitrogen oxide concentration in the nitrogen oxide concentration measuring means 1 is preferably 8.7 ppb, more preferably 8.5 ppb, and even more preferably 8.0 ppb. When the specified value for nitrogen oxides is the above value, even when the object is heat-treated, the formation of nitrosamine compounds can be suppressed, and the content of nitrosamine compounds can be kept below the specified value.

[0033] As a nitrogen oxide removal method 2, a chemical filter for removing chemical substances is an example, and an anionic filter for removing oxidizing substances is preferred. Among these, an anionic filter in which an inorganic base is supported on a substrate is preferred. Examples of inorganic bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, potassium bicarbonate, calcium hydroxide, and calcium carbonate. Examples of base materials include activated carbon, zeolite, and alumina. Examples of filter shapes include membrane filters and pleated filters. Examples of chemical filters include the anionic filter (model number: SCSA0610) and mixed (anionic + TVOC) filter (model number: SCGSA0610) from Oshidari Laboratory Co., Ltd., and GigaCall MC, GigaCall HC, Purafil, CP Blend Select, GigaWave HS, and GigaWave HC from Nitta Corporation.

[0034] It is preferable to use the nitrogen oxide removal means 2 to reduce the concentration of nitrogen oxides in the supplied gas to less than 8.7 ppb, more preferably to 8.5 ppb or less, and even more preferably to 8.0 ppb or less. When the concentration of nitrogen oxides is below the above upper limit, even when the target object is heat-treated, the formation of nitrosamine compounds can be suppressed, and the content of nitrosamine compounds can be kept below a specified value.

[0035] As the first nitrogen oxide concentration measurement means 1, for example, a "chemiluminescence measuring instrument" as specified in the Japanese Industrial Standard JIS B 7953:2004 "Automatic measuring instruments for nitrogen oxides in the atmosphere" can be used. Specifically, examples include the APNA-370 nitrogen oxide (NOx) concentration measuring instrument from Horiba, Ltd. Other examples include multi-reaction real-time mass spectrometers (SIFT-MS). Specifically, examples include the multi-reaction real-time mass spectrometer (product name: Syft Tracer (i3 / i8) type SIFT-MS) from Kinryo Electric Co., Ltd.

[0036] In the nitrogen oxide removal system A1 shown in Figure 1, a sealed or semi-sealed reaction vessel H is connected, but the nitrogen oxide removal means 2 and the working space R may also be connected. The same applies to Figures 2-6, which will be discussed later.

[0037] In this case, the outside air supplied to the entire workspace R is controlled so that the nitrogen oxide concentration remains below a specified value. Therefore, the nitrogen oxide concentration can be reduced not only in the sealed or semi-sealed reaction vessel H, but also in the entire workspace R that includes the reaction vessel H. This makes it possible to work in an open system within the workspace R, thus improving work efficiency.

[0038] In the nitrogen oxide removal system A1 shown in Figure 1, the first nitrogen oxide concentration measuring means 1, valve 3, and nitrogen oxide removal means 2 are connected in this order outside the working space R. Alternatively, the system may be configured to connect the first nitrogen oxide concentration measuring means 1, valve 3, and nitrogen oxide removal means 2 in this order inside the working space R, measure the concentration of nitrogen oxides contained in the air within the working space R, and if the concentration is below a specified value, supply the air to the reaction vessel H without treatment by the nitrogen oxide removal means 2. If the concentration exceeds a specified value, supply the clean air treated by the nitrogen oxide removal means 2 to the reaction vessel H. The same applies to Figures 2-6, which will be discussed later.

[0039] In this case, the concentration of nitrogen oxides in the air within the workspace R is controlled to be below a specified value. This allows for a more compact size for the nitrogen oxide removal system A3, making it easier to maintain and reducing costs. Furthermore, if the concentration of nitrogen oxides in the outside air outside the workspace R is higher than the concentration in the air inside the workspace R, a cleaner gas can be supplied to the reaction vessel H, which helps to further suppress the formation of nitrosamine compounds and prevents deterioration of nitrogen oxide removal means such as filters.

[0040] Furthermore, in the nitrogen oxide removal system A2 of this embodiment, as shown in Figure 2, exhaust gas G2 discharged from the sealed / semi-sealed reaction vessel H and the entire working space R in the room may be returned to the system for treatment and circulation.

[0041] In Figure 2, exhaust gas G2 is returned to the first nitrogen oxide concentration measuring means 1, and the concentration of nitrogen oxides contained in the exhaust gas is measured by the first nitrogen oxide concentration measuring means 1. If the concentration is below a specified value, the exhaust gas G2 is supplied to the workspace R without being treated by the nitrogen oxide removal means 2. If the concentration exceeds a specified value, the clean air treated by the nitrogen oxide removal means 2 is supplied to the workspace R. Unlike the nitrogen oxide removal system A1 shown in Figure 1, in the nitrogen oxide removal system A2 shown in Figure 2, the reaction vessel H and the first nitrogen oxide concentration measuring means 1 are connected by lines L5 and L6. The exhaust gas G2 from the reaction vessel H is discharged from line L5 to the outside of the working space R, and is further supplied to the first nitrogen oxide concentration measuring means 1 via line L6. In the nitrogen oxide removal system A2 shown in Figure 2, in addition to the effects obtained by the nitrogen oxide removal system A1 shown in Figure 1, if the concentration of nitrogen oxides in the exhaust is below a specified value, the exhaust is supplied to the workspace R without being treated by the nitrogen oxide removal means 2, thereby suppressing the deterioration of the nitrogen oxide removal means 2, such as filters. In particular, if no nitrogen oxides are generated from the target object C, the nitrogen oxides in the exhaust should also be below the specified value, just like the supplied gas. By reusing exhaust with nitrogen oxides below the specified value, there is no need to treat the outside air with the nitrogen oxide removal means 2 before supplying it, thus suppressing the deterioration of the nitrogen oxide removal means 2, such as filters.

[0042] In Figure 3, exhaust gas G2 is returned to the second nitrogen oxide concentration measuring means 4, and the concentration of nitrogen oxides contained in the exhaust gas is measured by the second nitrogen oxide concentration measuring means 4. If the concentration is below a specified value, the outside air is supplied to the workspace R without being treated by the nitrogen oxide removal means 2, and if the concentration exceeds a specified value, it is discharged outside the workspace R. Unlike the nitrogen oxide removal system A2 shown in Figure 2, the reaction vessel H and the second nitrogen oxide concentration measuring means 4 are connected by lines L5 and L6. The second nitrogen oxide concentration measuring means 4 and valve 31 are connected by line L8. The valve and line L4 are connected by bypass line L9. The system is configured such that the concentration of nitrogen oxides contained in the exhaust gas G2 is measured by the second nitrogen oxide concentration measuring means 4, and if it is below a specified value, the outside air G2 is supplied to the workspace R via line L9 without being treated by the nitrogen oxide removal means 2, and if it exceeds a specified value, it is discharged outside the workspace R as exhaust gas G3 via line L10. In the nitrogen oxide removal system A3 shown in Figure 3, in addition to the effects obtained by the nitrogen oxide removal system A1 shown in Figure 1, the following further effects can be obtained. When the concentration of nitrogen oxides in the exhaust is below a specified value, the exhaust is supplied to the workspace R without being treated by the nitrogen oxide removal means 2, thereby suppressing the deterioration of the nitrogen oxide removal means 2, such as a filter. If the concentration of nitrogen oxides in the exhaust exceeds a specified value, it means that nitrogen oxides have been generated from the object C. In this case, by not reusing the exhaust and discharging it outside the work space R, the deterioration of nitrogen oxide removal means 2, such as filters, can be suppressed.

[0043] As the second nitrogen oxide concentration measuring means 4, the same type as that mentioned in the first nitrogen oxide concentration measuring means 1 can be used. The specified value for the nitrogen oxide concentration in the second nitrogen oxide concentration measuring means 4 is preferably 8.7 ppb, more preferably 8.5 ppb, and even more preferably 8.0 ppb. When the specified value for nitrogen oxides is the above value, even when the object is heat-treated, the formation of nitrosamine compounds can be suppressed, and the content of nitrosamine compounds can be kept below the specified value.

[0044] In Figure 4, exhaust gas G2 is returned to the second nitrogen oxide concentration measuring means 4, and the concentration of nitrogen oxides contained in the exhaust gas is measured by the second nitrogen oxide concentration measuring means 4. If the concentration is below a specified value, the outside air is supplied to the workspace R without being treated by the nitrogen oxide removal means 2. If the concentration exceeds a specified value, the clean air treated by the nitrogen oxide removal means 2 is supplied to the workspace R.

[0045] Unlike the nitrogen oxide removal system A3 shown in Figure 3, in the nitrogen oxide removal system A4 shown in Figure 4, the valve 31 and the nitrogen oxide removal means 2 are connected by line L11. Unlike the nitrogen oxide removal system A3 shown in Figure 3, the nitrogen oxide removal system A4 shown in Figure 4 is configured such that if the concentration of nitrogen oxides in the exhaust gas G2 exceeds a specified value, the exhaust gas G2 is supplied to the nitrogen oxide removal means 2 via line L11, and the clean air treated by this means is supplied to the workspace R. In the nitrogen oxide removal system A4 shown in Figure 4, in addition to the effects obtained by the nitrogen oxide removal system A3 shown in Figure 3, the following further effects can be obtained. When the concentration of nitrogen oxides in the exhaust is below a specified value, the exhaust is supplied to the workspace R without being treated by the nitrogen oxide removal means 2, thereby suppressing the deterioration of the nitrogen oxide removal means 2, such as a filter. If the concentration of nitrogen oxides in the exhaust exceeds a specified value, it means that nitrogen oxides have been generated from object C. In this case, discharging the exhaust directly outside the work space R would lead to the release of nitrogen oxides into the atmosphere. By supplying the clean air treated by the nitrogen oxide removal means 2 to the work space R and reusing it, the environmental burden can be reduced.

[0046] The nitrogen oxide removal system of the present invention may further include a means for measuring the content of nitrosamine compounds contained in the target substance.

[0047] In Figure 5, a sealed or semi-sealed reaction vessel H is equipped with a nitrosamine compound content measuring means 5 for measuring the amount of nitrosamine compounds contained in the target substance. The system is configured to stop handling the target substance if the amount of nitrosamine compounds measured by the nitrosamine compound content measuring means 5 exceeds a specified value. Here, exhaust gas G2 containing nitrosamine compounds exceeding the specified value is not supplied to the sealed or semi-sealed reaction vessel H but is discharged outside the working space R via line L5.

[0048] Examples of the nitrosamine compound content measurement method 5 include a multi-reaction real-time mass spectrometer (SIFT-MS).

[0049] The specified content of nitrosamine compounds varies depending on the type of nitrosamine compound, but it is preferably below the acceptable daily intake (ADL). For example, 40 ppb is preferred, 10 ppb is more preferred, 5 ppb is even more preferred, and 1 ppb is particularly preferred. If the specified content of nitrosamine compounds is below the above values, it is possible to manufacture final products such as pharmaceuticals that do not pose a risk of carcinogenicity. Specifically, the control indicators for NDMA and NDEA in each active pharmaceutical ingredient are as shown in the table below.

[0050] [Table 2]

[0051] In the nitrogen oxide removal system A5 shown in Figure 5, in addition to the effects obtained by the nitrogen oxide removal system A1 shown in Figure 1, a nitrosamine compound content measuring means 5 is provided for measuring the amount of nitrosamine compounds contained in the target material. If the amount of nitrosamine compounds exceeds a specified value, the work of handling the target material is stopped, thus avoiding the provision of products with a high amount of nitrosamine compounds. This reduces waste of raw materials and the cost of disposing of products.

[0052] In Figure 6, a sealed or semi-sealed reaction vessel H is equipped with a nitrosamine compound content measuring means 5 for measuring the amount of nitrosamine compounds contained in the target substance. The system is configured to stop the manufacturing apparatus if the amount of nitrosamine compounds measured by the nitrosamine compound content measuring means 5 exceeds a specified value. Here, if the amount of nitrosamine compounds in the exhaust gas G2 exceeds a specified value, it is configured to be discharged outside the working space R as exhaust gas G4. If the amount of nitrosamine compounds in the exhaust gas G2 is below a specified value, the concentration of nitrogen oxides contained in the exhaust gas G2 is measured by the second nitrogen oxide concentration measuring means 4. If it is below a specified value, the outside air is supplied to the working space R without being treated by the nitrogen oxide removal means 2. If it exceeds a specified value, it is discharged outside the working space R as exhaust gas G3.

[0053] Unlike the nitrogen oxide removal system A5 shown in Figure 5, in the nitrogen oxide removal system A6 shown in Figure 6, the reaction vessel H and valve 32 are connected by lines L5 and L12, the valve 32 and the second nitrogen oxide concentration measuring means 4 are connected by line L13, the second nitrogen oxide concentration measuring means 4 and valve 31 are connected by line L8, and the valve 31 and line L4 are connected by bypass line L9.

[0054] Unlike the nitrogen oxide removal system A5 shown in Figure 5, the nitrogen oxide removal system A6 shown in Figure 6 is configured such that if the content of nitrosamine compounds in exhaust gas G2 exceeds a specified value, it is discharged outside the workspace R as exhaust gas G4 via line L14, and if the content of nitrosamine compounds in exhaust gas G2 is below a specified value, it is supplied to the second nitrogen oxide concentration measuring means 4 via line L13, and the concentration of nitrogen oxides contained in the exhaust gas G2 is measured by the second nitrogen oxide concentration measuring means 4. If the nitrogen oxide concentration in exhaust gas G2 is below a specified value, the outside air G2 is supplied to the workspace R without being treated by the nitrogen oxide removal means 2, similar to the nitrogen oxide removal system A3 shown in Figure 3, and if it exceeds a specified value, it is discharged outside the workspace R as exhaust gas G3.

[0055] Here, it is preferable that the nitrogen oxide removal means 2 is capable of removing both nitrogen oxides and nitrosamine compounds. As such nitrogen oxide removal means, for example, an anionic filter for removing oxidizing substances and an activated carbon filter for removing organic compounds such as nitrosamines are preferred, and among these, a filter on which an inorganic base or an organic base is supported on activated carbon is more preferred, because it avoids the organic base becoming a source of nitrogen oxides and also makes it easier to remove total volatile organic compounds (TVOCs).

[0056] In the nitrogen oxide removal system A6 shown in FIG. 6, in addition to the effects obtained by the nitrogen oxide removal system A5 shown in FIG. 5, the second nitrogen oxide concentration measuring means 4 for measuring the concentration of nitrogen oxides contained in the exhaust gas G2 is provided. Thus, when the concentration of nitrogen oxides is below the specified value, the outside air can be supplied to the work space R without being treated by the nitrogen oxide removing means 2. As a result, since the nitrogen oxide removing means 2 is not deteriorated, the cost of removing nitrogen oxides can be suppressed, and the manufacturing cost of the product can also be suppressed. When the concentration of nitrogen oxides exceeds the specified value, by discharging it outside the work space R, deterioration of the nitrogen oxide removing means 2 can be suppressed, the cost of removing nitrogen oxides can be suppressed, and the manufacturing cost of the product can also be suppressed.

[0057] In the nitrogen oxide removal system of the present invention, the filter as the nitrogen oxide removing means 2 of the present embodiment may further include, for example, a medium capable of removing gaseous substances (harmful substances) such as ion exchange resins, ion exchange fibers, activated carbon, activated carbon fibers, chemical adsorbents, etc., which have an adverse effect on the object handled in the work space R, such as quality deterioration by oxidation, from the outside air G1.

[0058] More specifically, the nitrogen oxide removing means 2 of the present embodiment may be configured to include a plurality of types of chemical filters for capturing and removing harmful substances contained in the outside air G1. For example, an adsorbent for removing oxidizing gases such as oxidant components and hydrogen peroxide; an adsorbent for removing acidic gases (anionic gases) excluding nitrogen oxides such as hydrofluoric acid, hydrogen chloride, and sulfuric acid (SO x ) etc.; an adsorbent for removing basic gas components such as ammonium salts and amines; and an adsorbent for removing total volatile organic compounds (TVOC) such as organic solvents may be combined. A filter further provided with these adsorbents may be used as the nitrogen oxide removing means 2, or may be used as a harmful substance removing means different from the nitrogen oxide removing means 2.

[0059] Also, a wet curtain type humidifier or an air washer is also effective for hydrophilic harmful substances.

[0060] For removing highly oxidizing harmful substances such as ozone, adsorbents based on activated carbon or activated carbon fibers with reducing properties, or decomposition catalysts (such as manganese dioxide catalysts) are effective. To prevent the oxidation of nitrogen atom-containing compounds in the workspace R and the provision of nitrogen oxide sources, it is preferable not to use oxidizing agents such as manganese dioxide as nitrogen oxide removal means 2 or other filters.

[0061] In the nitrogen oxide removal systems A1 to A6 of this embodiment, which have the above configuration, as the blower operates, the outside air G1 passes through the nitrogen oxide removal means 2, thereby removing nitrogen oxides contained in the outside air G1 that cause an increase in the content of nitrosamine compounds in the target object.

[0062] As a result, clean air from which nitrogen oxides have been removed is supplied and filled into the workspace R, and the air environment within the workspace R becomes free of gaseous harmful substances. In addition, in this embodiment, sterile, dust-free clean air may be supplied to the workspace R by passing it through an air conditioning unit (not shown) and a dust removal / sterilization filter such as a HEPA filter (not shown).

[0063] In the nitrogen oxide removal systems A1 to A6 of this embodiment, oxidation and deterioration of the target object can be prevented without replacing the air in the work space R with an inert gas such as nitrogen, as in conventional systems. Furthermore, by supplying clean air from which harmful substances have been removed by a harmful substance removal means 5 such as an adsorbent to the work space G, without using an inert gas such as nitrogen, running costs can be significantly reduced (for example, to less than 1 / 5). In addition, the total cost, including initial costs, can also be significantly reduced compared to conventional systems that use inert gases.

[0064] Furthermore, the nitrogen oxide removal systems A1 to A6 of this embodiment remove oxidation-promoting components using adsorbents, etc., and can be applied to supply purified air to open workspaces R such as equipment with openings that are difficult to deal with by inert gas displacement (such as clean benches), open-type push-pull equipment, and large workspaces R such as rooms where people enter and work. In other words, the nitrogen oxide removal systems A1 to A6 of this embodiment are applicable to all manufacturing processes, processing processes, etc.

[0065] For example, when handling pharmaceuticals, many of the active ingredients are easily oxidized, and ammonium salts and amine compounds in particular may oxidize to form nitrosamine compounds. In such cases, antioxidants and stabilizers are added during formulation, and if necessary, the product is sealed with inert gas or oxygen scavengers. Generally, chemically synthesized active ingredients are produced in small quantities, making it easier to control the handling environment. On the other hand, for active ingredients derived from plants and animals (such as herbal medicines and hormone preparations), the amount of raw materials is considerably larger than the amount of active ingredient extracted. Furthermore, various processes (weighing, grinding, mixing, dissolving, separating, extracting, concentrating, drying, molding, etc.) are required before the product is manufactured. It is difficult to carry out all of these pharmaceutical handling processes in a sealed space or a nitrogen-purged space that prevents exposure to air. In contrast, the nitrogen oxide removal systems A1 to A6 of this embodiment are systems that fill the workspace R with a gas that has a low nitrogen oxide content, and can be applied to open-system equipment and large spaces. Therefore, by applying them to processes and operations that handle pharmaceuticals as described above, it becomes possible to easily take measures to prevent oxidation.

[0066] Furthermore, when dealing with cosmetics, which often contain large amounts of oils and surfactants, oxidation can cause changes in their properties (discoloration, viscosity changes, separation into oil / water layers, etc.), the generation of unpleasant odors, and the formation of allergens. While fragrances and vitamins are generally present in small amounts, oxidation can also cause discoloration, changes in scent or odor, and a decrease in active ingredients. Cosmetics of this type often contain many different raw materials per product, making it difficult to prevent exposure to air during all stages of the manufacturing process, from storage to weighing, dissolution, and mixing, as well as during waiting times between manufacturing processes. In contrast, the nitrogen oxide removal systems A1 to A6 of this embodiment are systems that fill the workspace R with a gas that has a low nitrogen oxide content, and can be applied to open-system equipment and large spaces. Therefore, by applying them to the above-mentioned cosmetic handling work, it becomes possible to easily take measures to prevent oxidation.

[0067] Furthermore, when handling food products, inert gas replacement is performed during packaging to prevent oxidation (of oils, fats, proteins, vitamins, etc.), prevent discoloration, control microorganisms and pests, and improve shelf life and extend the shelf life of the food. However, oxidation occurs and progresses even during the storage and processing stages of ingredients and raw materials before packaging. Oxidant components in the atmosphere have a strong oxidizing effect, damaging (oxidizing) the surface cells of fresh food and also promoting oxidation. Seafood, in particular, contains many unsaturated fatty acids, and oxidation causes a fishy odor, leading to a decrease in its market value. Furthermore, while reducing oxidant concentrations in food handling environments is effective in maintaining food freshness (quality), nitrogen gas purging and similar methods are generally not employed when handling food products, which have lower added value compared to pharmaceuticals and cosmetics, due to both cost and oxidation prevention considerations. In contrast, the nitrogen oxide removal systems A1 to A6 of this embodiment are systems that fill the workspace R with a gas that has a low nitrogen oxide content, and are low-cost and do not require complex control, making it possible to easily take measures such as oxidation prevention in various parts of the food industry as described above.

[0068] Applications of nitrogen oxide removal systems The nitrogen oxide removal system of the present invention can be used to remove nitrogen oxides in the manufacture of pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations. The nitrogen oxide removal system of the present invention can be used in the manufacture of pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations to suppress the formation of nitrosamine compounds by removing nitrogen oxides.

[0069] The nitrogen oxide removal system of the present invention can be used to reduce the concentration of nitrogen oxides contained in the workspace to below a specified value during the manufacture of pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations.

[0070] The nitrogen oxide removal system of the present invention can be used to reduce the content of nitrosamine compounds in pharmaceuticals to below a specified value.

[0071] ≪How to use the nitrogen oxide removal system≫ Figure 7 is a flowchart illustrating the method of using the nitrogen oxide removal system A1 of the present invention. The concentration of nitrogen oxides contained in the outside air is measured using the first nitrogen oxide concentration measuring means (S1). Based on the measurement results, it is determined whether or not the nitrogen oxide concentration is below a specified value (Q1). If the nitrogen oxide concentration exceeds a specified value, the nitrogen oxide removal means is used to remove the nitrogen oxides (S2). The treated clean air is then supplied to the workspace (S3). If the nitrogen oxide concentration is below a specified value, the outside air is supplied to the workspace without being treated by the nitrogen oxide removal means (S3). After processing the object within the workspace, exhaust gas is discharged outside the workspace (S4).

[0072] Figure 8 is a flowchart illustrating the method of using the nitrogen oxide removal system A3 of the present invention. In addition to the configuration shown in Figure 7, the nitrogen oxide concentration in the exhaust gas is measured after processing the object in the workspace (S5). Based on the measurement results, it is determined whether the nitrogen oxide concentration is below the specified value (Q2). If the nitrogen oxide concentration exceeds the specified value, exhaust gases shall be discharged outside the work area (S4). If the nitrogen oxide concentration is below a specified value, the exhaust gas is supplied to the workspace without being treated by the nitrogen oxide removal means (S3).

[0073] By discharging exhaust gas outside the work area when the nitrogen oxide concentration exceeds a specified value (S4), the deterioration of nitrogen oxide removal means such as filters can be suppressed, reducing the burden of filter replacement and lowering manufacturing costs. When the nitrogen oxide concentration is below a specified value, the exhaust gas is supplied to the workspace without being treated by the nitrogen oxide removal means (S3). This makes it possible to supply gas with a lower nitrogen oxide concentration than the outside air into the workspace when no nitrogen oxides are generated from the object, thereby making it easier to suppress the formation of nitrosamine compounds.

[0074] Figure 9 is a flowchart illustrating the method of using the nitrogen oxide removal system A4 of the present invention. In the configuration shown in Figure 8, instead of discharging exhaust gas outside the work area when the nitrogen oxide concentration exceeds a specified value (S4), the exhaust gas is supplied to the nitrogen oxide removal means when the nitrogen oxide concentration exceeds a specified value (S2). If the nitrogen oxide concentration exceeds the specified value, it means that nitrogen oxides are being generated from the object in question. Therefore, if the exhaust is discharged outside the work area, the nitrogen oxide concentration in the outside air will increase. By removing nitrogen oxides from the exhaust and reusing it, it becomes easier to reduce the environmental impact.

[0075] Figure 10 is a flowchart illustrating the method of using the nitrogen oxide removal system A5 of the present invention. The concentration of nitrogen oxides contained in the outside air is measured using the first nitrogen oxide concentration measuring means (S1). Based on the measurement results, it is determined whether or not the nitrogen oxide concentration is below a specified value (Q1). If the nitrogen oxide concentration exceeds a specified value, the nitrogen oxide removal means is used to remove the nitrogen oxides (S2). The treated clean air is then supplied to the workspace (S3). If the nitrogen oxide concentration is below a specified value, the outside air is supplied to the workspace without being treated by the nitrogen oxide removal means (S3). The content of nitrosamine compounds in the treatment space is measured using a nitrosamine compound content measuring device (S6). Based on the measurement results, it is determined whether or not the content of nitrosamine compounds is below the specified value (Q3). If the nitrosamine compound content is below the specified value, exhaust gas is discharged outside the work area, as in Figure 7 (S4). If the content of nitrosamine compounds exceeds the specified value, the work involving handling the substance shall be stopped (S7).

[0076] If the nitrosamine compound content is below the specified value, the exhaust gas is discharged outside the work area (S4), as in Figure 7. This allows for the discharge of even small amounts of nitrosamine compounds, thus preventing them from adhering to the target object.

[0077] If the content of nitrosamine compounds exceeds a specified value, the handling of the object is stopped (S7), thereby stopping the reaction that produces nitrosamine compounds and allowing work to proceed to identify the cause. If the concentration of nitrogen oxides in the outside air is measured (S1), and nitrosamine compounds are produced despite the supply of outside air or clean air below a specified value, the cause may be a decrease in the performance of the nitrogen oxide removal means or the production of nitrosamine compounds from the object. If the performance of the nitrogen oxide removal means has decreased, the nitrogen oxide removal means, such as a filter, should be replaced with a new one. If nitrosamines are produced from the object, it means that the object contains ammonium salts or amine compounds and nitrogen oxides, so measures should be taken to prevent these from being included in the object (for example, using a nitrogen oxide removal system in the manufacturing process of the object or its raw materials), or measures should be taken to prevent them from reacting even if they are included in the object (for example, lowering the processing temperature of the object and shortening the processing time).

[0078] ≪Methods for producing raw materials for pharmaceuticals, active pharmaceutical ingredients for pharmaceuticals, or pharmaceutical preparations≫ The present invention relates to a method for producing pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations, characterized by using the nitrogen oxide removal system of the present invention to produce pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations.

[0079] The raw materials for pharmaceuticals are not particularly limited and include, for example, organic and inorganic compounds used to manufacture the aforementioned pharmaceuticals. When a nitrogen atom-containing organic compound is used as the active pharmaceutical ingredient (API), an organic or inorganic compound containing nitrogen atoms is used as the raw material for the pharmaceutical. However, using these may result in the formation of low-molecular-weight nitrogen atom-containing organic compounds as impurities. In the manufacture of the API for pharmaceuticals, these impurities can react with nitrogen oxides in the gas to produce nitrosamine compounds. In this invention, whether the raw material for the pharmaceutical contains nitrogen atoms or is contaminated with an organic compound containing nitrogen atoms as an impurity, the formation of nitrosamine compounds as a by-product in the manufacture of the raw material for pharmaceuticals can be suppressed by using a gas with a nitrogen oxide concentration below a specified value, and furthermore, the formation of nitrosamine compounds as a by-product in the manufacture of the API using this gas can be suppressed.

[0080] The active pharmaceutical ingredient (API) is not particularly limited, and examples include organic compounds contained in the aforementioned pharmaceuticals. For example, nitrogen atom-containing organic compounds are used. When a nitrogen atom-containing organic compound is used as the API, an organic or inorganic compound containing nitrogen atoms is used as a raw material for the pharmaceutical, but the use of these may result in the formation of low-molecular-weight nitrogen atom-containing organic compounds as impurities. These impurities can react with nitrogen oxides in the gas to produce nitrosamine compounds. In this invention, whether the API for the pharmaceutical contains nitrogen atoms or is contaminated with an organic compound containing nitrogen atoms as an impurity, the formation of nitrosamine compounds as a by-product in the manufacture of the API can be suppressed by using a gas with a nitrogen oxide concentration below a specified value.

[0081] The pharmaceutical formulation is not particularly limited and may be solid or liquid, but examples include tablets and granules. For example, granules can be produced by drying, sizing, classifying, etc., of granules obtained by known granulation methods (e.g., extrusion granulation, mixing and stirring granulation, high-speed mixing and stirring granulation, fluidized bed granulation, rolling and stirring fluidized bed granulation, rolling granulation, dry (compression) granulation, crushing granulation, spray drying granulation, etc.) as needed. Furthermore, capsules and tablets can be produced by adding other additives as needed to the granules obtained in this way and filling them into capsules or by compressing them using a known tablet press (e.g., rotary tablet press or single-stroke tablet press, etc.). In addition, tablets may be coated with a pharmaceutically acceptable film coating base as needed. Since heating may be performed during these processes, if nitrogen oxides are present in the gas, they may react with ammonium salts or amine compounds contained in the active pharmaceutical ingredient or additives to form nitrosamine compounds. According to the present invention, by using a gas with a nitrogen oxide concentration below a specified value, the by-product formation of nitrosamine compounds during formulation can be suppressed.

[0082] When using the nitrogen oxide removal system of the present invention to manufacture pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations, the processing temperature is preferably -80 to 300°C, more preferably -40 to 200°C, and even more preferably 0 to 100°C. When the processing temperature is within the above range, the heating temperature can be lowered, which makes it easier to suppress the formation of nitrosamine compounds by suppressing the reaction between ammonium salts or amine compounds and nitrogen oxides, and also makes it easier to suppress the generation of nitrogen oxides from the target material. When using the nitrogen oxide removal system of the present invention to manufacture pharmaceutical raw materials, pharmaceutical active pharmaceutical ingredients, or pharmaceutical formulations, the processing time is preferably 10 minutes to 3 days, more preferably 30 minutes to 1 day, and even more preferably 1 hour to 3 hours. When the processing time is within the above range, the time exposed to heated gas can be shortened, which makes it easier to suppress the formation of nitrosamine compounds by suppressing the reaction between ammonium salts or amine compounds and nitrogen oxides, and also makes it easier to suppress the generation of nitrogen oxides from the target material.

[0083] Here, we will explain why it can be expected that the nitrogen oxide removal systems A1 to A6 of this embodiment will suppress the formation of nitrosamine compounds. Figures 11 to 14 are quoted from Org. Process Res. Dev. 2023, 27 (11), 2123-2133.

[0084] Figure 11 is a graph showing the effect of atmospheric NO2 concentration on NDMA production at two factories. The NDMA content (ppb) in pharmaceuticals manufactured at the Osaka factory using the active pharmaceutical ingredient (API) of supplier A, the Yamagata factory using the API of supplier B, and the Yamagata factory using the API of supplier A and the Yamagata factory using the API of supplier B were plotted against the monthly average atmospheric NO2 concentration (ppb) measured near each factory. In all cases, metformin API was used. The average monthly atmospheric NO2 concentration was higher at the Osaka plant (7.8 ppb or higher) than at the Yamagata plant (less than 7.8 ppb), and the NDMA content in the formulations tended to increase with rising atmospheric NO2 concentrations. In other words, formulations manufactured at the Osaka plant tended to contain more NDMA than those manufactured at the Yamagata plant, correlated with higher atmospheric NO2 concentrations. None of the formulations manufactured in months with an average atmospheric NO2 concentration of less than 8.7 ppb exceeded the provisional standard value. The tendency for higher NDMA content in formulations to correspond to higher DMA content in active pharmaceutical ingredients was confirmed in all batches in which NDMA was measured. This trend was the same at both the Osaka and Yamagata plants. This graph shows a positive correlation between atmospheric NO2 concentration and NDMA content in the formulation.

[0085] Figure 12 is a graph showing the effect of nitrogen oxide concentration on the formation of nitrosamine compounds. Metformin active pharmaceutical ingredient from supplier A was reacted with various concentrations of NO2 (0, 25, 50, 100 ppb) under the same conditions as fluid bed granulation (65°C, 150 min). As the NO2 concentration increased up to 100 ppb, the amount of NDMA produced increased. These results indicate that nitrosation of DMA in the metformin active pharmaceutical ingredient occurs even at low concentrations of NO2, and it is clear that NDMA is generated at NO2 concentrations (5-60 ppb) flowing into the fluid bed granulator at the Osaka plant. Therefore, reducing the concentration of NO2 in the air flowing into the fluid bed granulator may reduce the amount of NDMA generated in the metformin preparation. Furthermore, even in the absence of NO2, a very small amount of NDMA was detected (5.9 ppb). Since the NDMA content in the active pharmaceutical ingredient was below the detection limit, it is thought that the DMA in the active pharmaceutical ingredient was nitrosated by the very small amount of NO2 in the air gas used in the experiment.

[0086] Figure 13 is a graph showing the effect of reaction time on the formation of nitrosamine compounds. Metformin active pharmaceutical ingredient was reacted at 65°C for 0, 30, 90, and 150 minutes in the presence of NO2 gas (50 ppb). As shown in Figure 13, the amount of nitrosamine compounds produced increased in a time-dependent manner up to 150 minutes.

[0087] Figure 14 is a graph showing the effect of reaction temperature on the formation of nitrosamine compounds. Metformin active pharmaceutical ingredient was reacted in the presence of NO2 gas (50 ppb) at 22°C or 65°C for 150 minutes. As shown in Figure 14, the amount of nitrosamine compounds produced at 22°C was low, indicating that the conversion from DMA to NDMA is accelerated by heating.

[0088] Although one embodiment of the nitrogen oxide removal system according to the present invention has been described above, the present invention is not limited to the above-described embodiment and can be modified as appropriate without departing from the spirit of the invention. [Explanation of Symbols]

[0089] A1-A6 Nitrogen Oxide Removal System 1. First nitrogen oxide concentration measuring means 2. Means for removing nitrogen oxides 3, 31, 32 valves 4. Second nitrogen oxide concentration measuring means 5 Means for measuring nitrosamine compound content C Object H reaction vessel R workspace G1 Outdoor air G2, G3 exhaust L1, L2, L4~L8, L10~L14 lines L3, L9 Bypass Line

Claims

1. A nitrogen oxide removal system for removing nitrogen oxides from outside air supplied to a workspace where objects are handled, A first nitrogen oxide concentration measuring means for measuring the concentration of nitrogen oxides contained in the outside air, A means for removing nitrogen oxides, Equipped with, A nitrogen oxide removal system characterized in that the concentration of nitrogen oxides contained in the outside air is measured by the first nitrogen oxide concentration measuring means, and if the concentration is below a specified value, the outside air is supplied to the workspace without being treated by the nitrogen oxide removal means, and if the concentration exceeds a specified value, clean air treated by the nitrogen oxide removal means is supplied to the workspace.

2. In the nitrogen oxide removal system according to claim 1, A nitrogen oxide removal system characterized by being configured to supply and circulate exhaust gas discharged from the aforementioned workspace back into the aforementioned workspace.

3. In the nitrogen oxide removal system according to claim 1, A second nitrogen oxide concentration measuring means for measuring the concentration of nitrogen oxides contained in the gas within the workspace or the concentration of nitrogen oxides contained in the exhaust gas discharged from the workspace, Furthermore, A nitrogen oxide removal system characterized in that, when the nitrogen oxide concentration measured by the second nitrogen oxide concentration measuring means is below a specified value, the gas or exhaust is supplied to the work space, and when it exceeds the specified value, the gas or exhaust is discharged outside the work space.

4. In the nitrogen oxide removal system according to claim 1, The object further comprises a means for measuring the content of nitrosamine compounds contained in the object, A nitrogen oxide removal system characterized in that it is configured to stop the handling of the object if the content of the nitrosamine compound measured by the nitrosamine compound content measuring means exceeds a specified value.

5. In the nitrogen oxide removal system according to claim 1, A nitrogen oxide removal system characterized in that the nitrogen oxide removal means is an anionic filter.

6. In the nitrogen oxide removal system according to claim 1, A nitrogen oxide removal system characterized in that the target substance is a drug used in the manufacture of pharmaceuticals.

7. A method for producing a pharmaceutical raw material, a pharmaceutical active pharmaceutical ingredient, or a pharmaceutical formulation using the nitrogen oxide removal system described in claim 1.

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