Flow continuous production method and apparatus

Abstract

To provide a flow continuous production method and apparatus that enables mass production. [Solution] By using a stirring and mixing unit, which includes a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, in each of the synthesis (PR1), extraction (PR2), concentration (PR3), and crystallization (PR4) processes, continuous flow production of compounds is made possible.

Description

Technical Field

[0001] The present invention relates to a flow continuous production method and apparatus, and more particularly to a flow continuous production method and apparatus for a compound using a plurality of stirring and mixing units each including a stirring plate attached to a shaft portion that reciprocates, a casing that houses the shaft portion and the stirring plate, an inlet for introducing a material into the casing, and an outlet for discharging the material from the casing.

Background Art

[0002] When producing various compounds such as pharmaceuticals, conventionally, for example, raw materials are charged into a tank, synthesized while being stirred, and then transferred to another tank for post-treatment of the compound, etc., and a series of operations have been performed by batch processing. Such batch processing is likely to cause non-uniform reactions, the quality is unstable, and a large amount of waste derived from unreacted substances and the like is generated.

[0003] On the other hand, as shown in Patent Document 1 or 2, a continuous production method for a compound using a fine flow path has been proposed. For example, a method has been proposed in which a plurality of flow paths are sequentially joined using a T-shaped joint pipe or the like, materials are continuously supplied into each flow path, and reactions such as sequential synthesis are performed. Also, a continuous extraction and separation system has been proposed in which a reaction solution is sent through a pipe and an extraction solution is intermittently inserted between the reaction solutions at a T-shaped joint and separated by a separator. These production methods have attracted attention as one of the continuous production methods because materials can be continuously supplied, but since the flow path itself is narrow, there is a limit to the amount (flow rate) of materials that can be supplied, and it is not suitable for mass production.

[0004] On the other hand, the present inventor has proposed various stirring and mixing devices schematically shown in FIGS. 1 to 5. The basic configuration of these stirring and mixing devices includes a stirring plate (S, S1 to 3) attached to a shaft portion (SH) that reciprocates, a casing (CA, CA1 to 2) that houses the shaft portion and the stirring plate, an inlet (IL) for introducing a material (α, α1 to 2) into the casing, and an outlet (OL) for discharging the material (β) from the casing.

[0005] These stirring and mixing devices allow for high-speed and uniform stirring and mixing of different materials introduced into the casing by reciprocating a stirring plate within the casing. Furthermore, the inventors have shown that by adjusting the size of the stirring plate, the inner diameter of the casing, changing the reciprocating frequency (strokes / second), and even adjusting the shape of the stirring plate, it is possible to achieve stirring and mixing necessary not only between liquids but also in heterogeneous solid-liquid-gas reactions. These stirring and mixing devices have been used primarily as a means of high-speed and uniform stirring and mixing of different materials, and have been responsible for the stirring and mixing process that is part of the manufacturing process of chemicals and various products. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Patent No. 5156466 [Patent Document 2] Patent No. 7121368 [Patent Document 3] Patent No. 5773683 [Patent Document 4] Japanese Patent Application No. 2024-217626 (Filing date: December 12, 2024) [Patent Document 5] Patent No. 7624755 [Patent Document 6] Patent No. 4646777 [Non-patent literature]

[0007] [Non-Patent Document 1] Daisuke Kubo et al., "Development of a Flow Continuous Production System for Peptide Pharmaceutical Raw Materials," Yokogawa Research Institute, Vol. 66, No. 1, 2023. [Non-Patent Document 2] AIST Magazine, "Development of a Flow Process Enabling Continuous Synthesis, Extraction, and Separation of Functional Chemicals," Published October 30, 2023, (URL) https: / / www.aist.go.jp / aist_j / press_release / pr2023 / pr20231030 / pr20231030.html [Overview of the project] [Problems that the invention aims to solve]

[0008] The problem that this invention aims to solve is to provide a flow continuous production method and apparatus that can solve the above-mentioned problems and enable mass production. [Means for solving the problem]

[0009] To achieve the above objectives, the flow continuous production method and apparatus according to the present invention have the following technical features. (1) A continuous flow production method for compounds using multiple stirring and mixing units, each comprising a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, wherein a synthesis step is performed in which two or more different materials containing at least one solution are continuously introduced into at least one stirring and mixing unit (A), and the mixed liquid containing the materials is stirred and mixed with the stirring plate to react the materials and produce a compound, and the solution (a) containing the compound is continuously discharged from the stirring and mixing unit (A), and at least one stirring and mixing unit (B) is used to selectively extract the solution (a) containing the compound discharged in the synthesis step and the compound. This is a continuous flow production method comprising: an extraction step in which a solvent is continuously introduced, and the solution (a) and the solvent are stirred and mixed with a stirring plate to continuously discharge a solution (b) in which the compound is dissolved in the solvent from the stirring and mixing unit (B), thereby separating the solvent (b') containing the compound from other materials from the solution (b); and a crystallization step in which either the solution (a) discharged from the synthesis step or the solvent (b') containing the compound discharged from the extraction step is continuously introduced into at least one stirring and mixing unit (C), and the solution (a) or the solvent (b') is cooled while being stirred and mixed with a stirring plate to crystallize the compound, and the solution (c) containing the crystallized compound is continuously discharged from the stirring and mixing unit (C).

[0010] (2) In the flow continuous production method described in (1) above, the material not used in the synthesis reaction is separated from the solution (a) containing the compound discharged in the synthesis step and introduced back into the stirring and mixing unit (A).

[0011] (3) In the flow continuous production method described in (1) above, the solution (a) or solvent (b') containing the compound to be introduced into the crystallization step is characterized by being concentrated before introduction.

[0012] (4) In the flow continuous production method described in (3) above, the crystallization step is characterized in that the solvent (b') containing the compound obtained in the extraction step is introduced into the crystallization step, and the solvent separated from the solvent (b') in the concentration step is introduced again into the stirring and mixing unit (B).

[0013] (5) In the flow continuous production method described in any of (1) to (4) above, the stirring and mixing unit (A) to (C) is characterized in that it heats or cools the material in the casing to control the material to a predetermined temperature.

[0014] (6) In the flow continuous production method described in any of (1) to (4) above, the stirring and mixing units (A) to (C) are characterized in that the vibration frequency of the stirring plate that performs the reciprocating motion is adjusted individually.

[0015] (7) In the flow continuous production method described in any of (1) to (4) above, the stirring and mixing units (A) to (C) are characterized in that the amount processed by each stirring and mixing unit is controlled by the amount of material supplied to each stirring and mixing unit.

[0016] (8) In a continuous flow production apparatus for compounds that utilizes multiple stirring and mixing units, each comprising a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, two or more different materials containing at least one solution are continuously introduced into at least one stirring and mixing unit (A), and the mixed liquid containing the materials is stirred and mixed with the stirring plate to react the materials and produce a compound, and the solution (a) containing the compound is discharged from the stirring and mixing unit (A). ofSynthesis means for continuous discharge, and at least one of the stirring and mixing units (B) is continuously introduced with a solution (a) containing the compound discharged by the synthesis means and a solvent for selectively extracting the compound, and the solution (a) and the solvent are stirred and mixed by the stirring plate, whereby a solution (b) in which the compound is dissolved in the solvent is continuously discharged from the stirring and mixing unit (B), and extraction means for separating a solvent (b') containing the compound and other materials from the solution (b); and at least one of the stirring and mixing units (C) is continuously introduced with either the solution (a) discharged from the synthesis means or the solvent (b') containing the compound discharged from the extraction means, and while stirring and mixing with the stirring plate, the solution (a) or the solvent (b') is cooled to crystallize the compound, and a solution (c) containing the crystallized compound is continuously discharged from the stirring and mixing unit (C). It is a flow continuous production apparatus configured by combining these components.

[0017] (9) The flow continuous production apparatus according to (8) above, characterized in that it has a circulation line (La) for separating materials not used in the synthesis reaction from the solution (a) containing the compound discharged by the synthesis means and introducing them again into the stirring and mixing unit (A).

[0018] (10) The flow continuous production apparatus according to (8) above, characterized in that it has concentration means for concentrating the solution (a) containing the compound or the solvent (b') containing the compound before introducing them into the crystallization means.

[0019] (11) The flow continuous production Device According to (10) above, the crystallization means has a circulation line (Lb) for introducing the solvent (b') containing the compound obtained by the extraction means and introducing the solvent separated from the solvent (b') by the concentration means again into the stirring and mixing unit (B).

[0020] (12) In the flow continuous production apparatus described in (8) above, when introducing material into the synthesis means, the extraction means, or the crystallization means, two or more linear pumps are connected in parallel via piping and the linear pumps are selectively driven to continuously supply the material. [Effects of the Invention]

[0021] According to the present invention, (1) a continuous flow production method for compounds using a plurality of stirring and mixing units, each comprising a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, wherein a synthesis step is performed in which two or more different materials containing at least one solution are continuously introduced into at least one stirring and mixing unit (A), and the mixed liquid containing the materials is stirred and mixed with the stirring plate to react the materials and produce a compound, and the solution (a) containing the compound is continuously discharged from the stirring and mixing unit (A), and at least one stirring and mixing unit (B) is continuously supplied with the solution (a) containing the compound discharged in the synthesis step and a solvent for selectively extracting the compound. This continuous flow production method combines an extraction step, in which the solution (a) and the solvent are introduced into a stirring plate and stirred and mixed, thereby discharging a solution (b) in which the compound is dissolved in the solvent from the stirring and mixing unit (B), and separating the solvent (b') containing the compound from other materials from the solution (b); and a crystallization step, in which either the solution (a) discharged from the synthesis step or the solvent (b') containing the compound discharged from the extraction step is continuously introduced into at least one stirring and mixing unit (C), the solution (a) or the solvent (b') is cooled while being stirred and mixed with the stirring plate, the compound is crystallized, and the solution (c) containing the crystallized compound is continuously discharged from the stirring and mixing unit (C). Therefore, a continuous flow production method capable of mass production can be provided.

[0022] Furthermore, in a continuous flow production apparatus for compounds that utilizes multiple stirring and mixing units, each comprising a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, the apparatus includes a synthesis means in which two or more different materials containing at least one solution are continuously introduced into at least one stirring and mixing unit (A), and the mixed liquid containing the materials is stirred and mixed with the stirring plate to react the materials and produce a compound, and the solution (a) containing the compound is continuously discharged from the stirring and mixing unit (A), and the solution (a) containing the compound discharged by the synthesis means and a solvent for selectively extracting the compound are continuously introduced into at least one stirring and mixing unit (B). The flow continuous production apparatus is configured by combining an extraction means that stirs and mixes the solution (a) and the solvent with the stirring plate to continuously discharge a solution (b) in which the compound has been dissolved in the solvent from the stirring and mixing unit (B), thereby separating the solvent (b') containing the compound from other materials from the solution (b); and a crystallization means that continuously introduces either the solution (a) discharged from the synthesis means or the solvent (b') containing the compound discharged from the extraction means into at least one stirring and mixing unit (C), cools the solution (a) or the solvent (b') while stirring and mixing with the stirring plate to crystallize the compound, and continuously discharges the crystallized solution (c) containing the compound from the stirring and mixing unit (C). As such, a flow continuous production apparatus capable of mass production can be provided. [Brief explanation of the drawing]

[0023] [Figure 1] This figure illustrates an example of a stirring and mixing unit applicable to the flow continuous production method and apparatus of the present invention. [Figure 2] This figure illustrates an example of a stirring and mixing unit applicable to the flow continuous production method and apparatus of the present invention. [Figure 3] This figure illustrates an example of a stirring and mixing unit applicable to the flow continuous production method and apparatus of the present invention. [Figure 4]This figure illustrates an example of a stirring and mixing unit applicable to the flow continuous production method and apparatus of the present invention. [Figure 5] This figure illustrates an example of a stirring and mixing unit applicable to the flow continuous production method and apparatus of the present invention. [Figure 6] This figure illustrates an example of a material supply unit applicable to the flow continuous production method and apparatus of the present invention. [Figure 7] This diagram illustrates an example of a synthesis process using a stirring and mixing unit. [Figure 8] This diagram illustrates an example of a synthesis or extraction process using a stirring and mixing unit. [Figure 9] This diagram illustrates the adjustment of various parameters in a processing step using a stirring and mixing unit. [Figure 10] This diagram illustrates the process of separating a solution that has been treated using a stirring and mixing unit. [Figure 11] This diagram illustrates a process for separating gas and solution from a gas-containing solution processed using a stirring and mixing unit, which can be used in concentration processes and the like. [Figure 12] This diagram illustrates the crystallization process using a stirring and mixing unit. [Figure 13] This diagram illustrates an example of using a stirring and mixing unit in the process of liquefying a gas. [Figure 14] This diagram illustrates an example in which a stirring and mixing unit separates the gas from a solution (containing gas) processed by the stirring and mixing unit, and then operates the stirring and mixing unit, which processes both the separated gas and the solution, using a single drive shaft. [Figure 15] This figure illustrates an example of the flow continuous production method (apparatus) of the present invention. [Figure 16] This is a flow diagram detailing the flow continuous production method (equipment) shown in Figure 16. [Figure 17] This diagram illustrates an example of a synthesis process consisting of multiple steps. [Figure 18] This diagram illustrates an example of using a single stirring and mixing unit in multiple processes. [Figure 19]This diagram illustrates an example of an extraction process consisting of multiple steps. [Figure 20] This diagram illustrates an example of a concentration process consisting of multiple steps. [Modes for carrying out the invention]

[0024] The flow continuous production method and apparatus according to the present invention will be described below with reference to Figures 1 to 18. In inventing the flow continuous production method and apparatus of the present invention, the inventors particularly focused on the stirring and mixing unit shown in Figures 1 to 5, and in Patent Documents 1 to 2, etc.

[0025] These stirring and mixing units (A1 to A5) have a basic configuration that includes stirring plates (S, S1 to S3) attached to a shaft (SH) that performs reciprocating motion, a casing (CA) that houses the shaft and the stirring plates, an inlet (IL) for introducing material into the casing (α), and an outlet (OL) for discharging material from the casing (β).

[0026] Specifically, in Figure 1, multiple stirring plates S are attached to the shaft SH inside the casing CA. Partition plates PA, fixed to the casing, are provided between the stirring plates S. Partition plates PA are not strictly necessary, but they play an important role in efficient stirring and mixing. The shaft SH is configured to reciprocate in the direction of arrow X by the drive unit DU. The drive unit DU is configured to convert the rotational motion of the drive motor into unidirectional reciprocating motion using a cam mechanism or the like. The vibration frequency of the shaft can be set in various ways, but as an example, it can be set from 1 (strokes / second, s / s) to 30 (s / s) or more.

[0027] Material is supplied into the casing CA from an inlet (not shown in Figure 1) as indicated by arrow α. Material α is stirred and mixed by the reciprocating motion of the stirring plate S, passing through the gaps between the stirring plate S and the casing, and between the partition plate PA and the shaft SH, as it moves to the top of the casing CA, and finally discharged outside the casing from an outlet (not shown) as indicated by arrow β. The inlet is often provided near one end of the casing, and the outlet is often formed near the other end of the casing. This ensures that the stirring and mixing process takes place while the material is passing through the casing.

[0028] An important feature of the stirring and mixing unit used in this invention is that the stirring and mixing process is performed within the casing, while the material is continuously supplied from the inlet and the stirred and mixed material is continuously discharged from the outlet. In other words, the stirring and mixing process is performed while the material moves continuously from the inlet to the outlet of the casing. Therefore, it is not a discontinuous (intermittent) process like conventional batch processing, where the material is placed in a tank, then stirred and mixed in the tank, and then the processed material is discharged from the tank.

[0029] As shown in Patent Documents 1 and 2, the stirring plate S can be a flat plate, a flat plate arranged at an angle, or even a spiral plate. Furthermore, by forming multiple openings in the stirring plate S or the partition plate PA, it is possible to perform stirring and mixing more powerfully and finely.

[0030] The advantages of the stirring and mixing unit shown in Figures 1 to 5 are not only that stirring and mixing are performed at high speed and uniformly, but also that when the material is continuously supplied at a constant pressure (α), the casing has gaps that allow the material to move continuously, so although there is some loss of internal pressure, the material (solution) that has been continuously processed at a constant pressure is discharged (β). Moreover, by adjusting the material supply pressure and the material supply flow rate, it is possible to adjust the time that the material remains in the stirring and mixing unit, thereby enabling optimal chemical reactions and processes such as synthesis and extraction.

[0031] By utilizing a configuration like this stirring and mixing unit (A1-A5), the supplied material moves through the casing CA while being continuously stirred and mixed, and the processed material can be continuously discharged. While this stirring and mixing is taking place, chemical reactions proceed between the mixed materials, resulting in the synthesis of compounds or the elution of compounds into the solvent. In other words, it becomes possible to carry out synthesis and extraction processes while continuously flowing materials, which is essential in flow continuous production methods and equipment.

[0032] Furthermore, in the stirring and mixing unit shown in Figure 1, a jacket JA is provided to cover the casing CA so that the material inside the casing can be heated or cooled, as disclosed in Patent Documents 3 and 4, etc., and a heat transfer medium HM such as a heating medium or coolant is supplied into the jacket. Not only is the temperature inside the casing set to a temperature suitable for the chemical reactions in the synthesis process, but it is also possible to set a temperature suitable for the extraction process, and furthermore, by raising the temperature of the material and vaporizing a portion of the mixed material, it is possible to concentrate the solution containing the compound. Moreover, by cooling the jacket, it is also possible to crystallize the compound in the solution. Moreover, all of these reaction processes can be carried out while stirring and mixing the material, uniformly controlling the temperature of the entire material, and continuously moving it inside the casing.

[0033] The stirring and mixing unit A2 in Figure 2 consists of a first mixing section MA1 for preliminary mixing and a second mixing section MA2 for more uniform stirring and mixing of the entire material, as disclosed in Patent Document 2. The first mixing section MA1 and the second mixing section MA2 are connected in a continuous manner, and the spiral stirring plates (S1, S2) of the first mixing section and the flat plate (S3) of the second mixing section are connected to the same shaft section SH.

[0034] The material is introduced into the casing CA1 from the inlet IL (α) and first stirred and mixed in the first mixing section MA1. Next, the material pre-mixed in the first mixing section is introduced into the casing CA2 which constitutes the second mixing section MA2, and finally discharged from the outlet OL (β). In the case of the stirring and mixing unit A2, the material is continuously supplied (α) and the processed material is continuously discharged (β). Furthermore, if necessary, a jacket can be provided on the casing constituting the first mixing section MA1 or the second mixing section MA2, allowing the materials in each mixing section to be set to a predetermined temperature.

[0035] Figures 3 and 4 both show examples of stirring and mixing units using a flat stirring plate S, but their main feature lies in the way different materials (α1-2 and α) are supplied. In stirring and mixing unit A3 in Figure 3, different materials (α1 and α2) are combined beforehand and supplied into the casing CA from the same single channel (α). On the other hand, in stirring and mixing unit A4 in Figure 4, materials (α1 and α2) are supplied separately at different positions in the casing CA, and as the supplied materials move within the casing (upward in Figure 4), they are stirred and mixed together, and finally the processed material is discharged from the casing (β).

[0036] The stage at which different materials are mixed depends on the materials used and the compounds being synthesized. Furthermore, as shown in Patent Document 5, it is also possible to configure the piping supplying materials into the casing CA as a double-walled pipe, supplying different materials to the inner and outer walls of the double-walled pipe.

[0037] Figure 5 shows an example of a stirring and mixing unit A5 specialized for cooling, as shown in Patent Document 4. By stirring and mixing the material supplied into the casing with, for example, a single stirring plate S, and simultaneously cooling the entire casing CA with a jacket, it is possible to rapidly cool the material in contact with the inner wall of the casing. Such a stirring and mixing unit can be used for processes such as efficiently cooling and crystallizing compounds. Even in this case, it is possible to continuously supply material to the stirring and mixing unit A5 (α) and continuously discharge the processed material (β). Naturally, the heat transfer medium HM flowing through jacket JA is not limited to a coolant; it can also be a heating medium for heating.

[0038] In order to continuously supply material at a predetermined flow rate (pressure) to the stirring and mixing units (A1-A5) shown in Figures 1 to 5, it is essential to employ a pump capable of stable supply. The linear pump shown in Figure 6 is suitable for stably supplying material at a constant flow rate, as described in Patent Document 6. The linear pump (PO1, PO2) consists of cylinders (CY1-2) and pistons (PS1-2). The linear pump is capable of drawing a predetermined amount of material into the cylinder and discharging the material from the cylinder at a predetermined flow rate as the piston moves inside the cylinder. Material supply (α OUT To stabilize the flow rate at a predetermined level, it is essential to use multiple linear pumps. IN ) and discharge (α OUT The task is shared among multiple linear pumps. For example, while one pump PO1 is drawing in material, the other pump PO2 is discharging it. Conversely, while one pump PO1 is discharging it, the other pump PO2 is drawing in material. By linking two or more linear pumps in this way, a continuous supply of material is made possible.

[0039] Continuous suction of such materials (α IN ) and discharge (α OUTTo enable this, precise control of the piston's movement within the cylinder is necessary. For this reason, the ball screws (BS1-2) connected to the pistons (PS1-2) are driven and controlled by the rotation of the gearbox (GB1-2). Furthermore, the ON / OFF control of the valves (V1-V4) is also performed in accordance with the piston's movement.

[0040] Next, various processing steps using the stirring and mixing unit (VM) will be explained with reference to Figures 7 to 14. For example, one of the stirring and mixing units (A1 to A3) shown in Figures 1 to 5 is used as the stirring and mixing unit (VM).

[0041] Figure 7 shows an example of the synthesis process. Materials are supplied at a constant flow rate (α1, α2) from tanks (TA, TB) containing different materials to a stirring and mixing unit VM using pump P. Here, pump P is, as an example, a combination of linear pumps as described in Figure 6.

[0042] Materials uniformly mixed in the stirring and mixing unit VM undergo a chemical reaction to produce a compound. For smooth mixing, it is preferable that at least one of the materials being mixed is a solution. Various solutions (aqueous, oily, etc.) containing the raw materials for the compound can be used in the synthesis process. The solution containing the compound is discharged (β) from the stirring and mixing unit VM and stored in tank TC before proceeding to the next processing step.

[0043] The solution containing the compound accumulated in tank TC can proceed to the compound extraction step described later, or it can proceed to the concentration step or the compound crystallization step. Furthermore, the material accumulated in tank TC can be used as raw material for the next synthesis step and introduced into another stirring and mixing unit. Furthermore, in the synthesis process shown in Figure 7, different materials are introduced separately into the stirring and mixing unit VM (α1, α2). Alternatively, the two materials may be pre-mixed in a separate tank before being introduced into the stirring and mixing unit VM, or, as shown in Figure 3 (or Figure 8 described later), the supply channels (α1 and α2) may be merged and then supplied to the stirring and mixing unit as a single channel (α).

[0044] In the synthesis process shown in Figure 7, the solution containing the compound is temporarily stored in tank TC. However, the process is not limited to this; the material discharged from the stirring and mixing unit may be directly introduced into the stirring and mixing unit for the next step without passing through tank TC.

[0045] Figure 8 shows another example of using the stirring and mixing unit VM in the synthesis process. A key feature of Figure 8 is that the material discharged from the stirring and mixing unit VM is separated into two layers, upper and lower, in a separator tank SP1. The reusable material is then returned to the material tank TB using the circulation line La. This returned material is then reused by the stirring and mixing unit VM. A pump can be used to transport the material using the circulation line La, if necessary.

[0046] To discharge a specific solution from the separator tank SP1 via the circulation line La, it is necessary to always position the interface formed by the different solutions separated in the tank (e.g., water and oil) below the outlet of the circulation line La located in tank SP1. Therefore, it is preferable to control the position of the interface by controlling the pump that discharges the lower layer of solution in tank SP1. For this reason, the tank requires means (sensors) to observe the interface and means to accurately control the amount of solution discharged. It is also possible to use a combination of linear pumps as shown in Figure 6 for such a pump.

[0047] The separator tank SP1 is suitable for cases where materials are separated quickly simply by letting them sit still. However, as described later, there is also a method of actively heating the materials to vaporize part of them for separation. The heating treatment can be performed in the stirring and mixing unit VM or in the separator tank SP1. However, in order to be suitable for flow continuous production methods and equipment, care must be taken to ensure that the processing in the separator tank is not done in a batch manner.

[0048] In synthesis processes, temperature control and pH control of materials are primarily necessary. Furthermore, these temperature and pH control parameters may also be required in other processes, such as extraction. Therefore, as shown in Figure 9, a temperature sensor Ste is installed in the stirring and mixing unit VM to measure the temperature. The temperature sensor's readings are then input to the control unit CU, which controls the heating and cooling system (H / C) of the heat transfer medium.

[0049] Furthermore, as shown in Figure 9, the pH concentration of the material discharged (β) from the stirring and mixing unit VM can be measured with a concentration sensor Sph, and the result can be fed into the control unit CU. The amount of material (e.g., α2) that affects the pH concentration can then be adjusted by controlling the valve VA. Furthermore, the mixing state of the materials significantly influences the synthesis process of the stirring and mixing unit VM. Therefore, it is important to consider the materials being mixed when determining the shape and size of the stirring plate used. However, in the stirring and mixing unit VM used in this invention, the mixing state can be easily changed by adjusting the vibration frequency of the stirring plate. For this reason, the control unit CU can be equipped with a function to control the drive unit DU that drives the shaft and adjust the vibration frequency.

[0050] Figure 10 illustrates an example of using a stirring and mixing unit VM in the extraction process. Note that Figure 10 can also be used in a process to separate excess material from the processed product in the synthesis process. In Figure 10, a solution containing the compound (for example, a material containing the compound produced in the synthesis process) is placed in tank TC, and a solvent for selectively extracting the compound is placed in another tank TD. Both are supplied to a stirring and mixing unit VM, and the compound is dissolved in the solvent by stirring and mixing. The processed material discharged from the stirring and mixing unit is placed in a separator tank SP2, where the solvent containing the compound (β') and the other materials are separated from the solution of the processed material. Figure 10 illustrates an example where the solvent containing the compound is in the upper layer, but it may also be in the lower layer. Furthermore, in the separator tank SP2, as with the separator tank SP1 in Figure 8, it is necessary to control the position of the interface between the solvent and the other solution. To achieve this, it is possible to configure the system to adjust the position of the interface by controlling the amount of solution discharged from the bottom of tank SP2.

[0051] In the extraction process, it is crucial to control the state in which the compound solution and the solvent (extraction solvent such as oil) mix. For this purpose, controlling the vibration frequency of the stirring plate is particularly important, as explained in Figure 9. For example, if the materials to be mixed are materials with low affinity, such as an oily and a watery mixture, they can be easily separated after stirring and mixing. However, if the vibration frequency of the stirring plate is high, the processed material will become an emulsion, making separation difficult.

[0052] Figure 11 shows an example of using a stirring and mixing unit VM in the concentration process. The concentration process also involves separating unwanted materials from a compound-containing solution by heating the materials. Since materials generally vaporize when heated, the difference in boiling points between the materials is utilized. For this reason, a heat transfer medium heated by heater H is supplied to the stirring and mixing unit to control the temperature of the mixed material.

[0053] For example, heated air or heated material is placed in a separator tank SP3 and separated into vaporized material and liquid material. Figure 11 shows an example where the compound is contained in the liquid and the concentrated material is discharged (β'), but this is not the only example. In some cases, the target compound may be mainly contained in the vaporized material (gas), in which case it is possible to cool the gas G afterward to obtain the concentrated material. Furthermore, even without using a separate separator tank SP3, the gas may separate from the liquid during the transport of the heated material. In this case, it is sufficient to simply provide a gas separation channel or mechanism. Another method for raising the temperature of the materials in the stirring and mixing unit is to use a high-temperature gas, such as heated hydrogen gas or an inert gas, with one of the materials to be mixed during stirring and mixing. Furthermore, as one method of heating materials in the synthesis process, it is also possible to supply a heated gas (material) responsible for the chemical reaction to the stirring and mixing unit as one of the raw materials to be mixed.

[0054] Figure 12 illustrates an example in which a stirring and mixing unit VM is used in the crystallization process. Generally, when crystallizing a compound from a solution containing the compound, a cooling operation of the material is performed. In Figure 12, to cool the material inside the stirring and mixing unit VM, a heat transfer medium is cooled by a cooler C and supplied to the jacket of the stirring and mixing unit VM. If the material needs to be heated during the crystallization process, a heater can be used instead of cooler C.

[0055] The method of cooling materials with the stirring and mixing unit VM is not limited to the method shown in Figure 12. It is also possible to use a mechanism that supplies different materials together, as shown in Figures 7 and 8, by introducing liquid nitrogen or a cooled gas into one of the materials and stirring and mixing it with a solution containing the compound to lower the temperature of the compound and induce crystallization.

[0056] Figure 13 illustrates an example of using a stirring and mixing unit VM in a process that cools and liquefies vaporized gas, such as in a concentration process. To efficiently cool the gas, it is necessary to bring the gas into contact with a cooled surface (the inner surface of the stirring and mixing unit's casing or the surface of the partition plate). Therefore, the gas is introduced into the stirring and mixing unit VM, and the gas is cooled by bringing it into contact with the inner surface of the casing, etc., while being stirred by the stirring plate. It is also possible to introduce other liquefied gases into the casing at the same time to promote the cooling of the gas.

[0057] A vacuum pump is typically used to supply gas (α(G)) to the stirring and mixing unit VM. In Figure 13, gas is supplied from the lower inlet of the stirring and mixing unit VM, but it is also possible to configure the unit to have an inlet on the upper side and discharge the cooled liquid from the bottom. Furthermore, the orientation of the stirring and mixing unit can be set to the horizontal direction of the reciprocating motion of the shaft, as needed, not only in the concentration process but also in other processing processes.

[0058] Figure 14 shows an example of a concentration process composed of multiple stirring and mixing units (VM1-3). Material α1 is introduced into stirring and mixing unit VM1 and stirred and mixed while being heated, separating the processed material (β1) into gas G and liquid (β1'). Furthermore, gas G is introduced into another stirring and mixing unit VM2 and stirred while being cooled, efficiently liquefying it and discharging the liquid (β4). The liquid (β4) can be used as part of the raw materials for synthesis or extraction processes as needed. For example, the concentration process in Figure 14 can be used as a means of recovering the solvent in the extraction process, and a circulation line Lb can be provided to return the recovered liquid (β4) to the solvent tank.

[0059] On the other hand, the solution separated in the separator tank SP3 is supplied to another stirring and mixing unit VM3 (α2), where the liquid temperature can be cooled, or the liquid can be further actively cooled to crystallize the compound. Furthermore, when using multiple stirring and mixing units, if they can be driven at the same frequency as shown in Figure 14, it is possible to connect them with the same shaft SH and operate multiple stirring and mixing units simultaneously.

[0060] Next, we will describe an example of how to combine various processes using the stirring and mixing unit VM shown in Figures 7 to 14 to configure a flow continuous production system. Figure 15 shows a process in which the first step PR(1) incorporates a compound synthesis step, the second step PR(2) incorporates an extraction step to extract the compound produced in the first step, the third step PR(3) incorporates a concentration step to concentrate the solution containing the compound extracted in the second step, and the fourth step PR(4) incorporates a crystallization step to crystallize the compound from the concentrated solution prepared in the third step. This allows the entire process from synthesis to crystallization to be constructed as a continuous flow production system.

[0061] This flow continuous production system can be easily configured by connecting the piping that discharges the processed material from the agitation and mixing unit to the piping that supplies the material to the agitation and mixing unit of the next process. Furthermore, if the processing speeds of each process differ, a tank for temporarily storing the processed material can be inserted in between. Additionally, to adjust the processing capacity of each process, it is possible to divide the material discharge route from a single storage tank into multiple routes and parallelize the processing steps.

[0062] Figure 16 is a flow diagram detailing an example of the continuous flow production system shown in Figure 15. In the synthesis step of the first step PR(1), a solution a1 containing the raw materials for the compound (Solution A, e.g., aqueous solution) and a solution a2 containing other raw materials (Solution B, e.g., oily solution) are placed in the stirring and mixing unit VM1. The solutions are stirred and mixed in the stirring and mixing unit VM1 to promote the chemical reaction and produce the compound. The solution a3 containing the compound is placed in the separator tank SP1, and the lower solution a4 containing the compound is sent to the extraction step of the second step PR(2). The upper solution (for example, oily solution B (solvent)) a5 in the separator tank SP1 can be returned to the solution B tank and reused as needed.

[0063] In the extraction step of the second step PR(2), the extraction solvent (Solution C, for example, an oily solvent) a6 and the solution a4 containing the compound are placed in the stirring and mixing unit VM2 and stirred and mixed to dissolve the compound contained in solution a4 into solvent a6. The processed material a7 discharged from the stirring and mixing unit VM2 is introduced into the separator tank SP2, where it is separated into the solvent a9 containing the compound and the other solution a8.

[0064] In the concentration step of the third step PR(3), solvent a9 containing the compound obtained in the extraction step is placed in the stirring and mixing unit VM3 and heated to vaporize a portion of the solvent and concentrate the solvent containing the compound. Solvent a9 containing the compound may be directly introduced into the stirring and mixing unit VM3, but it is also possible to configure the system to temporarily store it in a storage tank RT as needed and supply the required amount. In addition, a heat transfer medium for heating is supplied to the stirring and mixing unit VM3.

[0065] The processed material a10 discharged from the stirring and mixing unit VM3 is placed in the separator tank SP3 to separate the vaporized solvent. The vaporized solvent a12 is sent to the stirring and mixing unit VM4 using a vacuum pump or the like, cooled and liquefied, and may then be returned to the tank containing the extraction solvent (solution C). The stirring and mixing unit VM4 is supplied with a heat transfer medium to cool the vaporized solvent.

[0066] The solvent a11 containing the concentrated compound is sent to the crystallization step of the fourth step PR(4). Solvent a11 is sent to a stirring and mixing unit VM5, which is cooled by a heat transfer medium. In the stirring and mixing unit VM5, solvent a11 is cooled, the compound is crystallized, and the resulting product a13 is discharged. The crystallized compound can be dried and powdered as needed.

[0067] Figures 17 to 20 illustrate examples of multi-stage processing steps. Figure 17 shows an example of a multi-stage synthesis process, in which the compound produced in the first synthesis step PR(11) is introduced into the next second synthesis step PR12 to synthesize another compound. Naturally, each step is provided with its own stirring and mixing unit. Of course, if a stirring and mixing unit is not required in some synthesis steps, it is possible to omit the stirring and mixing unit in those steps.

[0068] Figure 18 is a flow chart illustrating an example of using a single stirring and mixing unit in multiple processes (e.g., a synthesis process). In the stirring and mixing unit used in this invention, the mixture inside the casing is sequentially replaced as long as the supply of materials continues. For this reason, material α1 from tank T1 and material α2 from tank T2 are supplied to the stirring and mixing unit VM, and the solution β1 containing the first compound is stored in the storage tank RT1.

[0069] Next, if the supply of material α2 is stopped and only material α1 is supplied to the stirring and mixing unit VM for a while, the material inside the stirring and mixing unit will be completely filled with material α1. Next, material α3 is supplied from tank T3 to stirring and mixing unit VM, where material α1 and material α3 are stirred and mixed to produce solution β2 containing the second compound, which is then stored in storage tank RT2.

[0070] Furthermore, it is also possible to configure the system to stop supplying material α3, replace the contents of the stirring and mixing unit VM with material α1, and then supply material α2 again. The supply and cessation of these materials α1-3 can be easily achieved by controlling valves VA1-3 and switching valve V. The above explanation described an example where a single stirring and mixing unit is used in the synthesis process. However, if a common solution (solvent) is used in different processes, it is also possible to incorporate a configuration like that shown in Figure 18.

[0071] Figure 19 shows a multi-stage extraction process. By further processing the liquid treated in the first extraction step PR(21) with the second extraction step PR(22), the purity of the compounds contained in the treated liquid (solvent) can be further increased. For example, by adjusting the pH concentration in the first and second extraction steps, it is possible to change the types of compounds and impurities that are separated.

[0072] Figure 20 shows a multi-stage concentration process. The liquid treated in the first concentration step PR(31) can be further treated in the second concentration step PR(32) to increase the concentration of the compound. It is also possible to change the type of impurities removed from the compound-containing liquid by changing the set temperature used in each step.

[0073] As described above, by adjusting the form of the stirring and mixing unit used in the present invention, the operating environment of the stirring and mixing unit (temperature, pH concentration, vibration frequency, etc.), and the combination of each processing step, a flow continuous production system for a wide variety of compounds can be constructed. Moreover, the stirring and mixing unit used in the present invention allows for easy adjustment of the processing speed (residence time in each step) within each step by adjusting the amount of material supplied to the stirring and mixing unit (pressure and flow rate), thereby enabling the realization of an optimal processing step. Furthermore, it is possible to connect the processing steps while continuously flowing the processed material through different processing steps, making it possible to construct a flow continuous production system capable of mass production. [Industrial applicability]

[0074] As described above, the present invention makes it possible to provide a flow continuous production method and apparatus that enables mass production. [Explanation of symbols]

[0075] CA casing SH shaft PA, PA1~2 Partition Plate (Partition Member) DU drive unit S, S1~3 stirring plates JA Jacket HM Heat Transfer Medium P Pump

Claims

1. In a continuous flow production method for compounds, which utilizes multiple stirring and mixing units, each comprising a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, A synthesis step comprising: continuously introducing two or more different materials containing at least one solution into at least one stirring and mixing unit (A), stirring and mixing the mixture containing the materials with the stirring plate to react the materials and produce a compound, and continuously discharging the solution (a) containing the compound from the stirring and mixing unit (A); An extraction step is performed by continuously introducing a solution (a) containing the compound discharged in the synthesis step and a solvent for selectively extracting the compound into at least one stirring and mixing unit (B), and by stirring and mixing the solution (a) and the solvent with the stirring plate, thereby continuously discharging a solution (b) in which the compound has been dissolved in the solvent from the stirring and mixing unit (B), and separating the solvent (b') containing the compound from other materials from the solution (b), A crystallization step comprising: continuously introducing either the solution (a) discharged from the synthesis step or the solvent (b') containing the compound discharged from the extraction step into at least one stirring and mixing unit (C); cooling the solution (a) or the solvent (b') while stirring and mixing with the stirring plate to crystallize the compound; and continuously discharging the crystallized solution (c) containing the compound from the stirring and mixing unit (C); A flow continuous production method that combines these elements.

2. In the flow continuous production method described in claim 1, A continuous flow production method characterized by separating materials not used in the synthesis reaction from the solution (a) containing the compound discharged in the synthesis step, and introducing them back into the stirring and mixing unit (A).

3. In the flow continuous production method described in claim 1, A flow continuous production method characterized in that the solution (a) containing the compound or the solvent (b') containing the compound, to be introduced into the crystallization step, is concentrated before being introduced.

4. In the flow continuous production method described in claim 3, In the crystallization step, the solvent (b') containing the compound obtained in the extraction step is introduced. A flow continuous production method characterized by introducing the solvent separated from the solvent (b') in the concentration step back into the stirring and mixing unit (B).

5. In the flow continuous production method according to any one of claims 1 to 4, A continuous flow production method characterized in that the stirring and mixing unit (A) to (C) heats or cools the material inside the casing to control the material to a predetermined temperature.

6. In the flow continuous production method according to any one of claims 1 to 4, A continuous flow production method characterized in that the vibration frequency of the stirring plate that performs the reciprocating motion is individually adjusted in the stirring and mixing units (A) to (C).

7. In the flow continuous production method according to any one of claims 1 to 4, A continuous flow production method characterized in that, in the stirring and mixing units (A) to (C), the processing amount processed by each stirring and mixing unit is controlled by the amount of material supplied to each stirring and mixing unit.

8. In a continuous flow production apparatus for compounds, which utilizes multiple stirring and mixing units, each comprising a stirring plate attached to a reciprocating shaft, a casing housing the shaft and the stirring plate, an inlet for introducing material into the casing, and an outlet for discharging material from the casing, A synthesis means comprising: continuously introducing two or more different materials containing at least one solution into at least one stirring and mixing unit (A); stirring and mixing the mixture containing the materials with the stirring plate to react the materials and produce a compound; and continuously discharging the solution (a) containing the compound from the stirring and mixing unit (A); An extraction means is provided which, at least one stirring and mixing unit (B) is continuously supplied with a solution (a) containing the compound discharged by the synthesis means and a solvent for selectively extracting the compound, and the solution (a) and the solvent are stirred and mixed with the stirring plate to continuously discharge a solution (b) in which the compound has been dissolved in the solvent from the stirring and mixing unit (B), thereby separating the solvent (b') containing the compound from other materials from the solution (b), A crystallization means that continuously introduces either the solution (a) discharged from the synthesis means or the solvent (b') containing the compound discharged from the extraction means into at least one stirring and mixing unit (C), cools the solution (a) or the solvent (b') while stirring and mixing with a stirring plate to crystallize the compound, and continuously discharges the crystallized solution (c) containing the compound from the stirring and mixing unit (C), A flow continuous production system composed of a combination of elements.

9. In the flow continuous production apparatus according to claim 8, A flow continuous production apparatus characterized by having a circulation line (La) that separates materials not used in the synthesis reaction from the solution (a) containing the compound discharged by the synthesis means and reintroduces them to the stirring and mixing unit (A).

10. In the flow continuous production apparatus according to claim 8, A flow continuous production apparatus characterized by having a concentration means for concentrating the solution (a) containing the compound or the solvent (b') containing the compound before introducing it into the crystallization means.

11. In the flow continuous production apparatus according to claim 10, The crystallization means is introduced with the solvent (b') containing the compound obtained by the extraction means, A flow continuous production apparatus characterized by having a circulation line (Lb) for introducing the solvent separated from the solvent (b') by the concentration means back into the stirring and mixing unit (B).

12. In the flow continuous production apparatus according to claim 8, A flow continuous production apparatus characterized in that, when introducing material into the synthesis means, extraction means, or crystallization means, two or more linear pumps are piped in parallel and the linear pumps are selectively driven to continuously supply the material.

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