An ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system and its application

Abstract

The present invention provides an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device and its application, wherein the symmetrical jet-coupled slug flow crystallization system device comprises a first feeding device, a second feeding device, a third feeding device, a cyclone crystallization device, an ultrasonic generating device, a mixing device and a reaction device. The present invention enables the raw material liquid to achieve micro-scale turbulent mixing in the cyclone crystallization device, quickly forms a high-concentration and uniformly concentrated mixed stream, and the fine crystal nuclei contained in the stream grow uniformly in the slug flow. At the same time, the slug flow can effectively inhibit the scaling or pipe clogging of the stream in the reaction device. By adjusting the residence time of the stream in the reaction device, an ultrafine particle product with uniform particle size and controllable target particle size can be obtained.

Description

Technical Field

[0001] The invention belongs to the technical field of crystallization, and relates to an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device and application thereof. Background Art

[0002] Fluid mixing is a common unit operation in chemical production and is widely used in industrial processes such as fine chemicals, pharmaceutical chemicals, polymerization processes, and biochemicals. For rapid reaction precipitation or reverse dissolution crystallization, the mixing effect between fluids directly affects the particle size distribution, yield, and quality of the final product. Therefore, a reasonably designed rapid mixing device is of great significance for enhancing the mixing effect of streams, improving reaction efficiency and product quality, and optimizing the production process.

[0003] Impinging stream reactors and cyclone crystallization devices are common reactors for enhancing fluid mixing. Studies have shown that the fluid flow rate required to achieve turbulent effects in cyclone crystallization devices is significantly lower than the fluid flow rate in impinging stream reactors, which means that cyclone crystallization devices have better transfer characteristics and excellent mixing effects. Since its introduction, cyclone crystallization devices have been widely used in industrial processes such as mixing, liquid phase extraction, absorption and desorption, preparation of ultrafine powders and nanomaterials, among which flow and mixing have an important influence on rapid precipitation and dissolution crystallization in cyclone crystallization devices.

[0004] CN108854624A proposes an efficient swirl jet type injection mixer, in which two different streams are ejected from small holes at different pipe heights into the pipe, and form a swirl three-dimensional flow in opposite directions, and an efficient turbulent effect is achieved between the two swirl fluids, thereby achieving rapid mixing between the two fluids. The mixer has very high requirements on the fluid flow rate, and the material residence time is too short, so it is impossible to obtain ultrafine particle products of the target particle size by adjusting the residence time.

[0005] In addition, introducing an ultrasonic horn to enhance local turbulent shear to further improve mass transfer performance is also a common means to improve the mixing effect between streams.

[0006] CN113413846 provides an ultrasonic reverse vortex flow impingement flow reactor, in which different reaction liquid raw material fluids achieve a molecular-scale mixing effect in the vortex reactor and the impingement structure assembly, and the ultrasound further strengthens the local turbulent shear, shortens the time for the fluid in the reactor to mix evenly, greatly improves the production efficiency, and obtains good economic benefits. However, the assembly cannot achieve fast and efficient mixing of the reaction and crystallization decoupling system and three or more fluids, especially for asymmetric fluids, and this type of equipment cannot meet the requirements of achieving good mixing between the streams.

[0007] CN113750920A provides an ultrasonic enhanced impingement flow coupled Taylor vortex crystallization system, which enhances the microscopic mixing performance of different streams through ultrasonic assisted impingement flow, and the Taylor reactor provides a higher mass transfer coefficient and a smaller shear stress, which can provide further growth of the crystal nucleus. However, this assembly also cannot provide fast and efficient mixing for asymmetric flow systems and reaction and crystallization decoupling systems. Therefore, it is urgent to develop a post-processing system for coupling mixed liquid with an enhanced turbulent cyclone crystallization device to meet the needs of fast mixing and efficient mass transfer of different streams in multiple dimensions, and further provide a place for uniform concentration of the mixed liquid in the cyclone crystallization device, so as to accurately control the particle size distribution and particle size of ultrafine particles.

[0008] In short, the existing cyclone crystallization device components and their assemblies, cyclone jet injection mixers and impact flow reactors cannot meet the following requirements: (1) For the rapid precipitation reaction process, due to the short reaction precipitation time, the residence time cannot be controlled to obtain uniform ultrafine particles with controllable particle size, and the amount of anti-solvent required is large; (2) For reaction systems with asymmetric flow rates or systems in which reaction and precipitation are decoupled, the above components cannot significantly improve the mass transfer performance between different streams and achieve efficient mixing of different streams; (3) The above components all belong to the structure of rapid mixing, and do not provide a uniform supersaturation system for the crystal nuclei precipitated by rapid mixing so that the crystal nuclei can further grow to the ultrafine particle product of the target particle size. Summary of the invention

[0009] In view of the deficiencies in the prior art, the object of the present invention is to provide an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device and its application.

[0010] To achieve this object, the present invention adopts the following technical solutions:

[0011] In a first aspect, the present invention provides an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device, the symmetrical jet-coupled slug flow crystallization system device comprising a first feeding device, a second feeding device, a third feeding device, a cyclone crystallization device, an ultrasonic generating device, a mixing device and a reaction device;

[0012] The cyclone crystallization device comprises a shell, which is divided from top to bottom into a mixing section, a contraction section and an extension section which are connected in sequence, the mixing section and the extension section are both equal-diameter cylinders, the diameter of the mixing section is larger than the diameter of the extension section, and the diameter of the contraction section gradually decreases from top to bottom;

[0013] At least two feed channels are arranged along the circumferential direction on the outer wall of the mixing section, and the feed channels are arranged obliquely in the clockwise direction or the counterclockwise direction, and the feed channels are respectively connected to the first feed device and the second feed device; the ultrasonic generating device has an ultrasonic horn, and the ultrasonic horn is inserted into the inner cavity of the contraction section from top to bottom; the extension section is externally connected to the third feed device;

[0014] The mixing device comprises an air inlet, a liquid inlet and a discharge port, the air inlet is externally connected to a high-pressure gas source, the liquid inlet is externally connected to the cyclone crystallization device, and the discharge port is externally connected to a reaction device; the cyclone flow stream formed by the cyclone crystallization device enters the mixing device, is mixed with the high-pressure gas flow introduced from the high-pressure gas source in the mixing device to form a gas-liquid slug flow and is introduced into the reaction device.

[0015] The crystallization system provided by the present invention is mainly used to solve the commonly used rapid reaction precipitation or reverse dissolution crystallization process, especially to solve the problems of low stream mixing efficiency, slow mass transfer rate, uneven distribution of system supersaturation, wide distribution of precipitation particle size, uncontrollable particle size, etc. in the reaction precipitation or reaction precipitation decoupling process with asymmetric flow rates of multiple different raw materials. Compared with the existing technology, the ultrasonic enhanced symmetrical cyclone crystallization device mainly strengthens mixing and mass transfer by intensifying the micro-scale turbulence of the surrounding flow field when the cavitation bubble vibrates (steady-state cavitation) or the cavitation bubble collapses (transient cavitation) through the ultrasonic cavitation effect. When ultrasonic action is combined with a cyclone crystallization device, the cavitation effect of ultrasound causes the micro-scale turbulence to be further intensified, thereby enhancing the interaction between different components at the molecular scale, improving the mass transfer performance and the mixing effect. It can achieve a wide spectrum of multi-scale turbulent vortex flow and micro-scale turbulent mixing for multiple streams of materials with different flow rates, thereby producing a large and uniformly distributed supersaturation within a dozen milliseconds or even a few milliseconds, promoting the precipitation of a large number of fine crystal nuclei, and enabling the raw material liquid to achieve micro-scale turbulent mixing in the cyclone crystallization device, quickly forming a high-concentration and uniformly concentrated mixed stream, and the fine crystal nuclei contained in the stream grow evenly in the slug flow. The mixing device cuts the mixed stream into a large number of fine, immiscible, uniformly concentrated solid-liquid suspension streams by introducing high-pressure airflow, and provides equal residence time to allow crystal nuclei to grow. The slug flow can effectively inhibit the scaling or pipe clogging of the stream in the reaction device. By adjusting the residence time of the stream in the reaction device, ultrafine particle products with uniform particle size, minimum agglomeration and controllable target particle size can be obtained.

[0016] It should be noted that the present invention does not make specific requirements and special restrictions on the structures and types of the first feeding device, the second feeding device and the third feeding device, as long as the purpose of conveying materials can be achieved. For example, the first feeding device, the second feeding device and the third feeding device are all injection pumps. In addition, the mixing device in the present invention can be selected as a T-shaped mixer. The high-pressure gas source can be selected as a pressure tank.

[0017] As a preferred technical solution of the present invention, the contraction section is an inverted truncated cone structure with a gradually changing diameter, the contraction section has a large end face and a small end face, the large end face of the contraction section is butt-jointed with one end of the mixing section, and the small end face of the contraction section is butt-jointed with one end of the extension section.

[0018] The ratio of the diameter of the large end surface of the contraction section to the diameter of the small end surface of the contraction section is (1-10):1, for example, it can be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0019] The ratio of the cross-sectional diameter of the feed channel to the diameter of the large end surface of the contraction section is 1:(10-40), for example, it can be 1:10, 1:15, 1:20, 1:25, 1:30, 1:35 or 1:40, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0020] As a preferred technical solution of the present invention, four feed channels are circumferentially arranged on the outer wall of the mixing section, which are respectively marked as the first feed channel, the second feed channel, the third feed channel and the fourth feed channel in the clockwise direction.

[0021] The first feed channel and the third feed channel are respectively connected to the first feed device, and the first feed device is used to pass the first material into the mixing section through the first feed channel and the third feed channel respectively.

[0022] The second feed channel and the fourth feed channel are respectively connected to the second feed device, and the second feed device is used to pass the second material into the mixing section through the second feed channel and the fourth feed channel respectively.

[0023] As a preferred technical solution of the present invention, the axis of the feed channel is perpendicular to the axis of the mixing section in a vertical plane.

[0024] The tangent line passing through the intersection of the feed channel and the mixing section is the intersection tangent line, and the angle between the axis of the feed channel and the intersection tangent line is 100 to 180°, for example, it can be 100°, 110°, 120°, 130°, 140°, 150°, 160°, 170° or 180°, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0025] The diameter at the intersection of the axis of the feed channel and the outer wall of the mixing section is recorded as the first intersection diameter, and the axes of all the feed channels are located on the same side of the extension line of the corresponding first intersection diameter.

[0026] As a preferred technical solution of the present invention, the axes of all the feed channels are located on the left side of the extension line of the corresponding first intersection diameter, and the first material and the second material are introduced into the mixing section through the feed channels to form a clockwise swirl; or,

[0027] The axes of all the feed channels are located on the right side of the extension line of the corresponding first intersection diameter, and the first material and the second material are introduced into the mixing section through the feed channels to form a counterclockwise swirl.

[0028] After being pressurized by the first feeding device and the second feeding device, two different raw material liquids are jetted at high speed from four feeding channels symmetrically distributed in the mixing section to the vortex crystallization device to form a mixed flow stream, forming a wide-spectrum multi-scale turbulent vortex. The ultrasonic cavitation effect causes the micro-scale turbulence of the mixed flow stream to be further intensified, thereby strengthening the interaction between the components at the molecular scale. The mixed flow stream is accelerated through the contraction section to enter the extension section to form a secondary turbulent vortex flow with another high-speed jet flow stream (the third material) from the jet hole, thereby realizing micro-scale turbulent mixing, improving mass transfer performance, and enhancing mixing effect.

[0029] As a preferred technical solution of the present invention, at least two jet holes are opened in the circumferential direction on the outer wall of the extension section, and a buffer chamber is arranged on the outer circumference of the extension section in the area where the jet holes are located, and the buffer chamber covers the jet holes.

[0030] The buffer chamber is connected to a feed pipe, and the third feed device introduces a third material into the buffer chamber through the feed pipe, and the third material enters the extension section through the jet hole.

[0031] As a preferred technical solution of the present invention, the diameter passing through the intersection of the jet hole and the inner wall of the extension section is recorded as the second intersection diameter, and all the jet hole axes are located on the same side of the corresponding second intersection diameter extension line and the angle between them and the corresponding second intersection diameter extension line is 0 to 45°, for example, it can be 0°, 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40° or 45°, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0032] As a preferred technical solution of the present invention, the first material and the second material form a first stream of clockwise swirling flow in the mixing section, all the jet hole axes are located on the right side of the extension line of the diameter of the second intersection, and the first stream and the third material form a counterclockwise swirling flow in the extension section; or,

[0033] The first material and the second material form a first stream of counterclockwise swirling flow in the mixing section, all the jet hole axes are located on the left side of the extension line of the second intersection diameter, and the first stream and the third material form a clockwise swirling flow in the extension section.

[0034] The present invention greatly expands the application scenarios of the device by optimizing the number and distribution of feed channels in the mixing section of the cyclone crystallizer and the structure and distribution of the jet holes in the extension chamber. No matter it is the mixing and crystallization precipitation of different streams with equal flow rates or the mixing and crystallization precipitation of different streams with non-equivalent flow rates, fast mixing and efficient mass transfer of different streams under different flow rates can be achieved. It is particularly suitable for the mixing of streams with asymmetric flow rates or multiple streams with a number of streams greater than 2 and the decoupling of reaction and precipitation to prepare a crystallization system of ultrafine particles. In addition, by changing the jet direction, the swirl direction in the mixing section and the extension section is adjusted. When the mixing section is counterclockwise swirling, the extension section is clockwise swirling; similarly, when the mixing section is counterclockwise swirling, the extension section is counterclockwise swirling, thereby achieving a good mixing effect of the streams in milliseconds. The cyclone crystallizer is connected to an external mixer, which introduces high-pressure airflow to cut the solid-liquid suspension stream into several slug streams with highly uniform concentrations and containing fine crystal nuclei. This can effectively prevent the streams from scaling or clogging in the reaction device. By adjusting the residence time of the streams in the reaction device, the precise preparation of ultrafine particles with uniform particle size, minimum agglomeration and controllable target particle size can be achieved without the need for additional grinding, crushing and other means.

[0035] Two different material systems are pressurized by an injection pump and are respectively ejected at high speed from different feed channels to the mixing section of the swirl crystallization device to form a first stream of turbulent swirl. The ultrasonic amplitude transformer further improves its mass transfer performance by strengthening the local turbulent shear of the first stream. Subsequently, the first stream flows through the contraction section and accelerates into the extension section to quickly mix with the third material from the high-speed jet of the extension section, continuously forming a second stream with crystal nuclei. The second stream is mixed with a stable gas flow from a high-pressure gas source through a mixing device and then enters the reaction device in the form of a gas-liquid plug flow. The suspension with the crystal nuclei further grows in the reaction device, and finally a suspension containing inorganic salts or organic drug particles is obtained from the outlet of the reaction device.

[0036] As a preferred technical solution of the present invention, the length of the ultrasonic horn inserted into the contraction section does not exceed 2 / 3 of the height of the contraction section.

[0037] As a preferred technical solution of the present invention, the reaction device is a tubular reactor, which includes a reaction tube, and the ratio of the inner diameter of the reaction tube to the diameter of the small end face of the contraction section is 1:(1-5), for example, it can be 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0038] The discharge port of the reaction device is connected to a collecting device.

[0039] The system refers to an equipment system, a device system or a production device.

[0040] The numerical range described in the present invention not only includes the point values ​​listed above, but also includes any point values ​​between the above numerical ranges that are not listed. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0041] The ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device provided by the present invention is used for reaction crystallization or dissolution cooling crystallization of inorganic salt or organic drug particles, wherein the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device is used for reaction crystallization or dissolution cooling crystallization of barium sulfate, cefuroxime sodium ultrafine particles or miglitol ultrafine particles.

[0042] Two different material systems (referred to as solution system A and solution system B) are pressurized by an injection pump and jetted at high speed from different feed channels to the mixing section of a swirl crystallization device to form a first stream of turbulent swirl. The ultrasonic amplitude transformer further improves its mass transfer performance by strengthening the local turbulent shear of the first stream. Subsequently, the first stream flows through the contraction section and accelerates into the extension section to quickly mix with another material system (referred to as solution system C) from the high-speed jet of the extension section, and continuously precipitates a second stream with crystal nuclei. The second stream is mixed with a stable gas flow from a high-pressure gas source through a mixing device and then enters a reaction device in the form of a gas-liquid plug flow. The suspension with the crystal nuclei further grows in the reaction device, and finally a suspension containing inorganic salts or organic drug particles (referred to as P) is obtained from the outlet of the reaction device.

[0043] If it is a reaction crystallization, the organic drug particles P are obtained by reacting raw material liquid A with raw material liquid B, and the particles P are insoluble in a poor solvent C, and the solvent C can be the same as solvent A or solvent B; if it is a dissolution cooling crystallization, the particles P are soluble in a good solvent S and insoluble in a poor solvent B, and the solvent C is a cooling liquid, which can be the same as solvent B, or an organic reagent that is immiscible with solvent A or solvent B. The solution system A is prepared by dissolving the crude particles P in a good solvent S, and the solution system A is a saturated solution or an unsaturated solution of the crude particles P.

[0044] The ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device provided by the present invention is used for quantitatively expressing the mixing effect, and the quantitative expression of the mixing effect is through calculating the separation index under different Reynolds numbers.

[0045] Compared with the prior art, the present invention has the following beneficial effects:

[0046] The crystallization system provided by the present invention is mainly used to solve the commonly used rapid reaction precipitation or reverse dissolution crystallization process, especially to solve the problems of low stream mixing efficiency, slow mass transfer rate, uneven distribution of system supersaturation, wide distribution of precipitation particle size, uncontrollable particle size, etc. in the reaction precipitation or reaction precipitation decoupling process with asymmetric flow rates of multiple different raw materials. Compared with the existing technology, the ultrasonic enhanced symmetrical cyclone crystallization device mainly strengthens mixing and mass transfer by intensifying the micro-scale turbulence of the surrounding flow field when the cavitation bubble vibrates (steady-state cavitation) or the cavitation bubble collapses (transient cavitation) through the ultrasonic cavitation effect. When ultrasonic action is combined with a cyclone crystallization device, the cavitation effect of ultrasound causes the micro-scale turbulence to be further intensified, thereby enhancing the interaction between different components at the molecular scale, improving the mass transfer performance and the mixing effect. It can achieve a wide spectrum of multi-scale turbulent vortex flow and micro-scale turbulent mixing for multiple streams of materials with different flow rates, thereby producing a large and uniformly distributed supersaturation within a dozen milliseconds or even a few milliseconds, promoting the precipitation of a large number of fine crystal nuclei, and enabling the raw material liquid to achieve micro-scale turbulent mixing in the cyclone crystallization device, quickly forming a high-concentration and uniformly concentrated mixed stream, and the fine crystal nuclei contained in the stream grow evenly in the slug flow. The mixing device cuts the mixed stream into a large number of fine, immiscible, uniformly concentrated solid-liquid suspension streams by introducing high-pressure airflow, and provides equal residence time to allow crystal nuclei to grow. The slug flow can effectively inhibit the scaling or pipe clogging of the stream in the reaction device. By adjusting the residence time of the stream in the reaction device, ultrafine particle products with uniform particle size, minimum agglomeration and controllable target particle size can be obtained. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 A schematic structural diagram of an ultrasonic-assisted jet-type swirl-coupled slug flow crystallization system device provided in a specific embodiment of the present invention;

[0048] Figure 2 Schematic diagram of the structure of the ultrasonic-assisted jet-coupled slug flow crystallization system device in Example 1 of the present invention;

[0049] Figure 3 Schematic diagram of the structure of the ultrasonic-assisted jet-coupled slug flow crystallization system device in Example 2 of the present invention;

[0050] Figure 4 Schematic diagram of the structure of the ultrasonic-assisted jet-coupled slug flow crystallization system device in Example 3 of the present invention;

[0051] Figure 5 Schematic diagram of the structure of the ultrasonic-assisted jet-coupled slug flow crystallization system device in Example 4 of the present invention;

[0052] Figure 64 is a comparison diagram of the separation index measured at different Reynolds numbers Re in Example 4 of the present invention;

[0053] Among them, 1-first feeding device; 2-second feeding device; 3-cyclone crystallization device; 4-ultrasonic generating device; 5-feeding channel; 6-third feeding device; 7-jet hole; 8-mixing device; 9-high pressure gas source; 10-reaction device; 11-collecting device. DETAILED DESCRIPTION

[0054] It should be understood that, in the description of the present invention, the terms "center", "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or positional relationship are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention. In addition, the terms "first", "second", etc. are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first", "second", etc. may explicitly or implicitly include one or more of the features. In the description of the present invention, unless otherwise specified, "multiple" means two or more.

[0055] It should be noted that in the description of the present invention, unless otherwise clearly specified and limited, the terms "disposed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood by specific circumstances.

[0056] Those skilled in the art should understand that the present invention necessarily includes necessary pipelines, conventional valves and general pump equipment for realizing a complete process, but the above content does not constitute the main innovation of the present invention. Those skilled in the art can add layouts on their own based on the process flow and equipment structure selection, and the present invention does not make special requirements or specific limitations on this.

[0057] The technical solution of the present invention is further described below with reference to the accompanying drawings and through specific implementation methods.

[0058] In a specific embodiment, the present invention provides an ultrasonically enhanced symmetrical jet coupled slug flow crystallization system device, such as Figure 1As shown, the symmetrical jet-coupled slug flow crystallization system device comprises a first feeding device 1, a second feeding device 2, a third feeding device 6, a cyclone crystallization device 3, an ultrasonic generating device 4, a mixing device 8 and a reaction device 10;

[0059] The cyclone crystallization device 3 includes a shell, which is divided from top to bottom into a mixing section, a contraction section and an extension section which are connected in sequence, the mixing section and the extension section are both equal-diameter cylinders, the diameter of the mixing section is larger than the diameter of the extension section, and the diameter of the contraction section gradually decreases from top to bottom;

[0060] At least two feed channels 5 are circumferentially arranged on the outer wall of the mixing section, and the feed channels 5 are inclined in a clockwise or counterclockwise direction, and the feed channels 5 are respectively connected to the first feed device 1 and the second feed device 2; the ultrasonic generating device 4 has an ultrasonic horn, and the ultrasonic horn is inserted into the inner cavity of the contraction section from top to bottom; the extension section is externally connected to the third feed device 6;

[0061] The mixing device 8 has an air inlet, a liquid inlet and a discharge port, the air inlet is externally connected to a high-pressure gas source 9, the liquid inlet is externally connected to the cyclone crystallization device 3, and the discharge port is externally connected to a reaction device 10; the cyclone flow stream formed by the cyclone crystallization device 3 enters the mixing device 8, and is mixed with the high-pressure gas flow introduced from the high-pressure gas source 9 in the mixing device 8 to form a gas-liquid slug flow and is introduced into the reaction device 10.

[0062] The crystallization system provided by the present invention is mainly used to solve the commonly used rapid reaction precipitation or reverse dissolution crystallization process, especially to solve the problems of low stream mixing efficiency, slow mass transfer rate, uneven distribution of system supersaturation, wide distribution of precipitation particle size, uncontrollable particle size, etc. in the reaction precipitation or reaction precipitation decoupling process with asymmetric flow rates of multiple different raw materials. Compared with the existing technology, the ultrasonic enhanced symmetrical cyclone crystallization device 3 mainly strengthens mixing and mass transfer by intensifying the micro-scale turbulence of the surrounding flow field when the cavitation bubble vibrates (steady-state cavitation) or the cavitation bubble collapses (transient cavitation) through the ultrasonic cavitation effect. When the ultrasonic action is combined with the cyclone crystallization device 3, the cavitation effect of the ultrasound causes the micro-scale turbulence to be further intensified, thereby enhancing the interaction between different components at the molecular scale, improving the mass transfer performance and the mixing effect. It can achieve a wide spectrum of multi-scale turbulent vortex flow and micro-scale turbulent mixing for multiple streams of materials with different flow rates, thereby producing a large and uniformly distributed supersaturation within a dozen milliseconds or even a few milliseconds, promoting the precipitation of a large number of fine crystal nuclei, and enabling the raw material liquid to achieve micro-scale turbulent mixing in the cyclone crystallization device 3, quickly forming a high-concentration and uniformly concentrated mixed stream, and the fine crystal nuclei contained in the stream grow evenly in the slug flow. The mixing device 8 cuts the mixed stream into a large number of fine, immiscible, uniformly concentrated solid-liquid suspension streams by introducing high-pressure airflow, and provides an equal residence time to allow the crystal nuclei to grow. The slug flow can effectively inhibit the scaling or pipe clogging of the stream in the reaction device 10. By adjusting the residence time of the stream in the reaction device 10, an ultrafine particle product with uniform particle size, minimum agglomeration and controllable target particle size can be obtained.

[0063] It should be noted that the present invention does not make specific requirements and special restrictions on the structures and types of the first feeding device 1, the second feeding device 2 and the third feeding device 6, as long as the purpose of conveying materials can be achieved. For example, the first feeding device 1, the second feeding device 2 and the third feeding device 6 are all injection pumps. In addition, the mixing device 8 in the present invention can be selected as a T-shaped mixer. The high-pressure gas source 9 can be selected as a pressure tank.

[0064] Furthermore, the contraction section is an inverted truncated cone structure with a gradually changing diameter, and has a large end face and a small end face, the large end face of the contraction section is butted against one end of the mixing section, and the small end face of the contraction section is butted against one end of the extension section.

[0065] The ratio of the diameter of the large end surface of the contraction section to the diameter of the small end surface of the contraction section is (1-10):1.

[0066] The ratio of the cross-sectional diameter of the feed channel 5 to the diameter of the large end surface of the contraction section is 1:(10-40).

[0067] Furthermore, four feed channels 5 are circumferentially arranged at the outer wall of the mixing section, which are respectively marked as the first feed channel, the second feed channel, the third feed channel and the fourth feed channel in the clockwise direction.

[0068] The first feed channel and the third feed channel are respectively connected to the first feed device 1, and the first feed device 1 is used to pass the first material into the mixing section through the first feed channel and the third feed channel respectively.

[0069] The second feed channel and the fourth feed channel are respectively connected to the second feed device 2, and the second feed device 2 is used to pass the second material into the mixing section through the second feed channel and the fourth feed channel respectively.

[0070] Furthermore, the axis of the feed channel 5 is perpendicular to the axis of the mixing section in a vertical plane.

[0071] The tangent line passing through the intersection of the feed channel 5 and the mixing section is the intersection tangent line, and the axis of the feed channel 5 is 100 to 180 degrees from the intersection tangent line.

[0072] The diameter at the intersection of the axis of the feed channel 5 and the outer wall of the mixing section is recorded as the first intersection diameter, and the axes of all the feed channels 5 are located on the same side of the extension line of the corresponding first intersection diameter.

[0073] Further, the axes of all the feed channels 5 are located on the left side of the extension line of the corresponding first intersection diameter, and the first material and the second material are introduced into the mixing section through the feed channels 5 to form a clockwise swirl; or,

[0074] The axes of all the feed channels 5 are located on the right side of the extension line of the corresponding first intersection diameter, and the first material and the second material are introduced into the mixing section through the feed channels 5 to form a counterclockwise swirl.

[0075] After being pressurized by the first feeding device 1 and the second feeding device 2, two different raw material liquids are jetted at high speed from four feeding channels 5 symmetrically distributed in the mixing section to the swirl crystallization device 3 to form a mixed flow stream, forming a broad-spectrum multi-scale turbulent swirl. The ultrasonic cavitation effect causes the microscale turbulence of the mixed flow stream to be further intensified, thereby strengthening the interaction between the components at the molecular scale. The mixed flow stream is accelerated through the contraction section to enter the extension section to form a secondary turbulent vortex flow with another high-speed jet flow stream (the third material) from the jet hole 7, thereby realizing microscale turbulent mixing, improving mass transfer performance, and enhancing mixing effect.

[0076] Furthermore, at least two jet holes 7 are circumferentially formed on the outer wall of the extension section, and a buffer chamber is provided on the outer circumference of the extension section in the area where the jet holes 7 are located, and the buffer chamber covers the jet holes 7 .

[0077] The buffer chamber is connected to a feed pipe, and the third feed device 6 introduces a third material into the buffer chamber through the feed pipe. The third material enters the extension section through the jet hole 7.

[0078] Furthermore, the diameter passing through the intersection of the jet hole 7 and the inner wall of the extension section is recorded as the second intersection diameter, and the axes of all the jet holes 7 are located on the same side of the corresponding extension line of the second intersection diameter and the angle between them and the corresponding extension line of the second intersection diameter is 0 to 45°.

[0079] Further, the first material and the second material form a first stream of clockwise swirling flow in the mixing section, the axes of all the jet holes 7 are located on the right side of the extension line of the diameter of the second intersection, and the first stream and the third material form a counterclockwise swirling flow in the extension section; or,

[0080] The first material and the second material form a first stream of counterclockwise swirling flow in the mixing section, the axes of all the jet holes 7 are located on the left side of the extension line of the diameter of the second intersection, and the first stream and the third material form a clockwise swirling flow in the extension section.

[0081] The present invention adjusts the swirl direction in the mixing section and the extension section by changing the jet direction. When the mixing section is counterclockwise swirl, the extension section is clockwise swirl; similarly, when the mixing section is counterclockwise swirl, the extension section is counterclockwise swirl, thereby further cutting the mixed stream into a number of slug streams with highly uniform concentrations and containing fine crystal nuclei, which can effectively prevent the stream from scaling or clogging in the reaction device 10. By adjusting the residence time of the stream in the reaction device 10, the precise preparation of ultrafine particles with uniform particle size, minimum agglomeration, and controllable target particle size can be achieved without adding grinding, crushing, etc. This invention is particularly suitable for the crystallization system of preparing ultrafine particles by mixing streams with asymmetric flow rates or multiple streams with a number of streams greater than 2 and decoupling reaction and precipitation.

[0082] The ultrasonically enhanced symmetrical jet coupled slug flow crystallization system device of the present invention is particularly suitable for reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles. Solution system A and solution system B are pressurized by injection pumps and jetted at high speed from different feed channels 5 to the mixing section of the swirl crystallization device 3 to form a first stream of turbulent swirl flow. The ultrasonic horn further improves its mass transfer performance by strengthening the local turbulent shear of the first stream. Then, the first stream flows through the contraction section and accelerates to enter the extension section to quickly mix with the third material from the high-speed jet of the extension section, continuously forming a second stream with crystal nuclei. The second stream is mixed with the stable gas flow from the high-pressure gas source 9 through the mixing device 8 and enters the reaction device 10 in the form of gas-liquid slug flow. The suspension with crystal nuclei further grows in the reaction device 10, and finally a suspension containing inorganic salts or organic drug particles is obtained from the outlet of the reaction device 10.

[0083] Furthermore, the length of the ultrasonic horn inserted into the contraction section does not exceed 2 / 3 of the height of the contraction section.

[0084] Furthermore, the reaction device 10 is a tubular reactor, which includes a reaction tube, and the ratio of the inner diameter of the reaction tube to the diameter of the small end surface of the contraction section is 1:(1-5).

[0085] The discharge port of the reaction device 10 is connected to the collecting device 11 .

[0086] Example 1

[0087] This embodiment provides a crystallization system device, which uses an ultrasonically enhanced symmetrical jet coupled slug flow crystallization system device to prepare barium sulfate precipitation. The structural parameters and operation steps of the crystallization system device are as follows:

[0088] like Figure 2 As shown, the inner diameter of the large end face of the contraction section is 48 mm, the inner diameter of the small end face of the contraction section is 15 mm, the inner diameter of the extension section is 20 mm, the inner diameters of the four feed channels 5 symmetrically distributed in the mixing section are all 6 mm, the angle between the axis of the feed channel 5 and the tangent of the intersection is 180°, and the length of the ultrasonic amplitude rod inserted into the contraction section is 2 / 3 of the height of the contraction section.

[0089] The frequency of the ultrasonic horn is 20KHz and the power is 100W. The distance from the center of the jet hole 7 on the extension section to the small end face of the contraction section is 5 times the diameter of the extension section. Four jet holes 7 are provided on the outer wall of the extension section. The inner diameter of the jet hole 7 is 3mm. The angle between the axis of the jet hole 7 and the extension line of the diameter of the second intersection is 30°. The inner diameter of the mixing device 8 is 15mm, and the inner diameter of the reaction tube of the reaction device 10 is 15mm.

[0090] The first material (10~300kg / m3 Barium chloride aqueous solution) is pressurized by an injection pump at 0.1-3.0 m 3 / h flow rate from the first feed channel and the third feed channel to the mixing section of the cyclone crystallization device 3, the second material (10 ~ 300kg / m 3 Sodium sulfate aqueous solution) is pressurized by an injection pump at 0.1-3.0m 3 The first material and the second material form a first stream of turbulent swirling flow in the mixing section.

[0091] The ultrasonic horn acts on the first stream, further enhancing the mixing and mass transfer effect. Then the first stream flows through the contraction section and accelerates into the extension section, where it mixes with the third material (water solution, flow rate 0.1-6.6m 3 / h) to rapidly mix, continuously forming a second stream with crystal nuclei, the second stream is mixed with the stable gas flow from the high-pressure gas source 9 through the mixing device 8 and then enters the reaction device 10 in the form of gas-liquid slug flow, the suspension with crystal nuclei further grows in the reaction device 10, and finally a suspension of barium sulfate particles is obtained from the outlet of the reaction device 10, and barium sulfate crystals are obtained after filtration, the particle size distribution of the barium sulfate crystals is 1.3-39 μm, and the average particle size D 50 =17μm.

[0092] As the preferred technical solution of this embodiment:

[0093] The first material (150kg / m 3 Barium chloride aqueous solution) is pressurized by a syringe pump to 1.5m 3 / h flow rate from the first feed channel and the third feed channel to the mixing section of the cyclone crystallization device 3, the second material (150kg / m 3 Sodium sulfate aqueous solution) is pressurized by an injection pump to 1.5m 3 The first material and the second material form a first stream of turbulent swirling flow in the mixing section.

[0094] The ultrasonic horn acts on the first stream, further enhancing the mixing and mass transfer effect. Then the first stream flows through the contraction section and accelerates into the extension section, where it mixes with the third material (water solution, flow rate 3.3m 3 / h) is quickly mixed to continuously form a second stream with crystal nuclei, and the second stream is mixed with the stable gas flow from the high-pressure gas source 9 through the mixing device 8 and enters the reaction device 10 in the form of gas-liquid slug flow. The suspension with crystal nuclei further grows in the reaction device 10, and finally a suspension of barium sulfate particles is obtained from the outlet of the reaction device 10. After filtering, barium sulfate crystals are obtained. The particle size distribution of the barium sulfate crystals is 1.7-5.9 μm, and the average particle size D 50 =2.9μm.

[0095] Example 2

[0096] This embodiment provides a crystallization system device, which uses an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system to prepare ultrafine cefuroxime sodium particles. The structural parameters and operation steps of the crystallization system device are as follows:

[0097] like Figure 3 As shown, the inner diameter of the large end face of the contraction section is 48 mm, the inner diameter of the small end face of the contraction section is 20 mm, the inner diameter of the extension section is 23 mm, the inner diameters of the four feed channels 5 symmetrically distributed in the mixing section are all 8 mm, the angle between the axis of the feed channel 5 and the tangent of the intersection is 165°, and the length of the ultrasonic amplitude rod inserted into the contraction section is 2 / 3 of the height of the contraction section.

[0098] The frequency of the ultrasonic horn is 20KHz and the power is 150W. The distance from the center of the jet hole 7 on the extension section to the small end face of the contraction section is 20 times the diameter of the extension section. Four jet holes 7 are provided on the outer wall of the extension section. The inner diameter of the jet hole 7 is 5mm. The angle between the axis of the jet hole 7 and the extension line of the diameter of the second intersection is 5°. The inner diameter of the mixing device 8 is 20mm, and the inner diameter of the reaction tube of the reaction device 10 is 20mm.

[0099] The first material (10~300kg / m 3 Cefuroxime acid acetone aqueous solution) is pressurized by a syringe pump at 0.1-7.7 m 3 / h flow rate from the first feed channel and the third feed channel to the mixing section of the cyclone crystallization device 3, the second material (10 ~ 500kg / m 3 Sodium 2-ethylhexanoate methanol aqueous solution) is pressurized by an injection pump at 0.1-3.0 m 3 The flow rate of / h is high-speed jetted from the second feed channel and the fourth feed channel to the mixing section of the cyclone crystallization device 3. The first material and the second material form a first stream of turbulent cyclone in the mixing section.

[0100] The ultrasonic horn acts on the first stream, further enhancing the mixing and mass transfer effect. Then the first stream flows through the contraction section and accelerates into the extension section and the third material (acetone solution, flow rate 0.1-6.6m 3 / h) to rapidly mix, continuously form a second stream with crystal nuclei, the second stream is mixed with the stable gas flow from the high pressure gas source 9 through the mixing device 8 and then enters the reaction device 10 in the form of gas-liquid slug flow, the suspension with crystal nuclei further grows in the reaction device 10, and finally obtains a suspension of cefuroxime sodium particles from the outlet of the reaction device 10, and obtains cefuroxime sodium crystals after filtration, the particle size distribution of the cefuroxime sodium crystals is 3-77 μm, and the average particle size D 50 =41μm.

[0101] As the preferred technical solution of this embodiment:

[0102] The first material (100kg / m 3 Cefuroxime acid acetone aqueous solution) was pressurized by a syringe pump at 2.3 m 3 / h flow rate from the first feed channel and the third feed channel to the mixing section of the cyclone crystallization device 3, the second material (220kg / m 3 Sodium 2-ethylhexanoate methanol aqueous solution) was pressurized by an injection pump to 1.1m 3 The flow rate of / h is high-speed jetted from the second feed channel and the fourth feed channel to the mixing section of the cyclone crystallization device 3. The first material and the second material form a first stream of turbulent cyclone in the mixing section.

[0103] The ultrasonic horn acts on the first stream, further enhancing the mixing and mass transfer effect. Then the first stream flows through the contraction section and accelerates into the extension section and the third material (acetone solution, flow rate of 2.5m 3 / h) to rapidly mix, continuously form a second stream with crystal nuclei, the second stream is mixed with the stable gas flow from the high pressure gas source 9 through the mixing device 8 and then enters the reaction device 10 in the form of gas-liquid slug flow, the suspension with crystal nuclei further grows in the reaction device 10, and finally obtains a suspension of cefuroxime sodium particles from the outlet of the reaction device 10, and obtains cefuroxime sodium crystals after filtration, the particle size distribution of cefuroxime sodium crystals is 7-33 μm, and the average particle size D 50 =21μm.

[0104] Example 3

[0105] This embodiment provides a crystallization system device, which uses an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system to prepare ultrafine miglitol particles. The structural parameters and operation steps of the crystallization system device are as follows:

[0106] like Figure 4As shown, the inner diameter of the large end face of the contraction section is 48 mm, the inner diameter of the small end face of the contraction section is 17 mm, the inner diameter of the extension section is 22 mm, the inner diameters of the four feed channels 5 symmetrically distributed in the mixing section are all 7 mm, the angle between the axis of the feed channel 5 and the tangent of the intersection is 150°, and the length of the ultrasonic amplitude rod inserted into the contraction section is 2 / 3 of the height of the contraction section.

[0107] The frequency of the ultrasonic horn is 20KHz and the power is 200W. The distance from the center of the jet hole 7 on the extension section to the small end face of the contraction section is 15 times the diameter of the extension section. Two jet holes 7 are provided on the outer wall of the extension section. The inner diameter of the jet hole 7 is 6mm. The angle between the axis of the jet hole 7 and the extension line of the diameter of the second intersection is 45°. The inner diameter of the mixing device 8 is 20mm, and the inner diameter of the reaction tube of the reaction device 10 is 20mm.

[0108] The first material (10~500kg / m 3 Miglitol aqueous solution) is pressurized by a syringe pump at 0.1-10 ml 3 / h flow rate from the first feed channel and the third feed channel to the mixing section of the cyclone crystallization device 3, and the second material (acetone solution) is pressurized by the injection pump at a rate of 0.1-10m 3 The flow rate of / h is high-speed jetted from the second feed channel and the fourth feed channel to the mixing section of the cyclone crystallization device 3. The first material and the second material form a first stream of turbulent cyclone in the mixing section.

[0109] The ultrasonic horn acts on the first stream, further enhancing the mixing and mass transfer effect. Then the first stream flows through the contraction section and accelerates into the extension section and the third material (kerosene at 10 to -20 ° C, used as a cooling medium, with a flow rate of 0.1 to 10 m / s) from the jet hole 7. 3 / h) to rapidly mix, continuously forming a second stream with crystal nuclei, the second stream is mixed with a stable gas flow from a high-pressure gas source 9 through a mixing device 8 and then enters a reaction device 10 in the form of a gas-liquid slug flow, the suspension with crystal nuclei further grows in the reaction device 10, and finally a suspension of miglitol particles is obtained from the outlet of the reaction device 10, and miglitol crystals are obtained after filtration, the particle size distribution of the miglitol crystals is 1 to 79 μm, and the average particle size D 50 =37μm.

[0110] As the preferred technical solution of this embodiment:

[0111] The first material (100kg / m 3 Miglitol aqueous solution) was pressurized by a syringe pump at a flow rate of 1.1m 3 / h flow rate from the first feed channel and the third feed channel to the mixing section of the cyclone crystallization device 3, and the second material (acetone solution) is pressurized by the injection pump at a rate of 1.7m 3The first material and the second material form a first stream of turbulent swirling flow in the mixing section.

[0112] The ultrasonic horn acts on the first stream, further enhancing the mixing and mass transfer effect. Then the first stream flows through the contraction section and accelerates into the extension section and the third material (-5℃ kerosene, used as cooling medium, with a flow rate of 3.8m 3 / h) to rapidly mix, continuously forming a second stream with crystal nuclei, the second stream is mixed with a stable gas flow from a high pressure gas source 9 through a mixing device 8 and then enters a reaction device 10 in the form of a gas-liquid slug flow, the suspension with crystal nuclei further grows in the reaction device 10, and finally a suspension of miglitol particles is obtained from the outlet of the reaction device 10, and miglitol crystals are obtained after filtration, the particle size distribution of the miglitol crystals is 5 to 21 μm, and the average particle size D 50 =13μm.

[0113] Example 4

[0114] This embodiment provides a crystallization system device, which uses the iodide-iodate parallel competitive reaction system proposed by Fournier to quantitatively analyze the mixing effect of the ultrasonically enhanced symmetrical jet-coupled coupled slug flow crystallization system.

[0115] The structural parameters of the crystallization system are as follows:

[0116] like Figure 5 As shown, the inner diameter of the large end face of the contraction section is 48 mm, the inner diameter of the small end face of the contraction section is 12 mm, the inner diameter of the extension section is 15 mm, the inner diameters of the four feed channels 5 symmetrically distributed in the mixing section are all 8 mm, the angle between the axis of the feed channel 5 and the tangent of the intersection is 165°, and the length of the ultrasonic amplitude rod inserted into the contraction section is 2 / 3 of the height of the contraction section.

[0117] The frequency of the ultrasonic horn is 20KHz and the power is 120W. The distance from the center of the jet hole 7 on the extension section to the small end face of the contraction section is 10 times the diameter of the extension section. Four jet holes 7 are provided on the outer wall of the extension section. The inner diameter of the jet hole 7 is 3mm. The angle between the axis of the jet hole 7 and the extension line of the diameter of the second intersection is 30°. The inner diameter of the mixing device 8 is 20mm, and the inner diameter of the reaction tube of the reaction device 10 is 20mm.

[0118] The specific steps are as follows:

[0119] (1) A sulfuric acid solution and an iodide-iodate mixed solution of a certain concentration are prepared, wherein the first material is a 0.1 mol / L H2SO4 solution, the second material is a mixed solution of 0.2424 mol / L H3BO3, 0.1212 mol / L NaOH, 0.01556 mol / L KI and 0.00311 mol / L KIO3, and the third material is a mixed solution of 0.1212 mol / L H3BO3, 0.0606 mol / L NaOH, 0.00778 mol / L KI and 0.00155 mol / L KIO3.

[0120] (2) adjusting the flow rate of the injection pump on each feed channel 5 on the cyclone crystallization device 3 according to the required Reynolds number Re;

[0121] (3) simultaneously opening the injection pumps of the various feed channels 5 on the cyclone crystallization device 3, so that the acid-base reaction liquid forms a jet and enters the cyclone crystallization device 3 to cause an acid-base reaction;

[0122] (4) adjusting the gas flow rate output by the high-pressure gas source 9 according to the required residence time of the material;

[0123] (5) After the flow rate stabilizes, the product is taken out from the collecting device 11, and the iodine concentration in the product is detected by a visible light spectrophotometer;

[0124] (6) Conduct multiple experiments according to different Reynolds numbers Re to measure the required product concentration value;

[0125] (8) Turn on the ultrasonic generator 4, set the ultrasonic output power of the ultrasonic generator 4, repeat steps (2) to (6), measure the iodine concentration in the product, and convert it to obtain the separation index. The result is as follows: Figure 5 shown.

[0126] Depend on Figure 5 It can be seen that under different Reynolds numbers Re, the separation index obtained by applying the ultrasonic field is lower than the separation index obtained without applying the ultrasonic field. It can be seen that the ultrasonic action can make the material mixing more complete, promote the interaction between molecules, and play a role in strengthening the mixing of the flow streams.

[0127] The calculation method of the outlier index is:

[0128] The reaction equation of the system is as follows:

[0129] H2BO3 - +H + →H3BO3 quasi-instantaneous reaction (1)

[0130] IO3 - +5I - +6H+ →3I2+3H2O fast reaction (2)

[0131]

[0132] Reaction (1) is an acid-base neutralization reaction, which is an instantaneous reaction. The reaction rate k1=10 11 L / (mol·s), the reaction rate of reaction (2) Among them, k2 and ionic strength I s The following relationship exists:

[0133]

[0134]

[0135] The reaction rate of reaction (3) is At 25℃,

[0136]

[0137] Define the outlier index X s To characterize the micro-mixing efficiency, its definition is:

[0138]

[0139]

[0140]

[0141] Where Y represents the H consumed in reaction (2) + The amount of H injected + The ratio of total volume, Y st Indicates the Y value when it is completely out of the set; when X s = 0, indicating that the two fluids are completely mixed and only microscopic mixing occurs; s =1, indicating that the two fluids are completely separated, and only macroscopic mixing occurs. <X s When <1, it indicates that the two fluids are partially mixed, and macroscopic mixing and microscopic mixing exist at the same time.

[0142] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. An application of an ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device in the reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The symmetrical jet-coupled slug flow crystallization system device comprises a first feeding device, a second feeding device, a third feeding device, a cyclone crystallization device, an ultrasonic generating device, a mixing device and a reaction device; The cyclone crystallization device comprises a shell, which is divided from top to bottom into a mixing section, a contraction section and an extension section which are connected in sequence, the mixing section and the extension section are both equal-diameter cylinders, the diameter of the mixing section is larger than the diameter of the extension section, and the diameter of the contraction section gradually decreases from top to bottom; At least two feed channels are arranged along the circumferential direction on the outer wall of the mixing section, and the feed channels are arranged obliquely in the clockwise direction or the counterclockwise direction, and the feed channels are respectively connected to the first feed device and the second feed device; the ultrasonic generating device has an ultrasonic horn, and the ultrasonic horn is inserted into the inner cavity of the contraction section from top to bottom; the extension section is externally connected to the third feed device; The mixing device comprises an air inlet, a liquid inlet and a discharge port, the air inlet is externally connected to a high-pressure gas source, the liquid inlet is externally connected to the cyclone crystallization device, and the discharge port is externally connected to a reaction device; the cyclone flow stream formed by the cyclone crystallization device enters the mixing device, is mixed with the high-pressure gas flow introduced from the high-pressure gas source in the mixing device to form a gas-liquid slug flow and is introduced into the reaction device.

2. The use of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 1 in the reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The contraction section is an inverted truncated cone structure with a gradually changing diameter. The contraction section has a large end face and a small end face. The large end face of the contraction section is butted against one end of the mixing section, and the small end face of the contraction section is butted against one end of the extension section.

3. The use of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 2 in the reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The ratio of the diameter of the large end surface of the contraction section to the diameter of the small end surface of the contraction section is (1-10):

1.

4. The use of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 2 in the reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles is characterized in that: The ratio of the cross-sectional diameter of the feed channel to the diameter of the large end surface of the contraction section is 1:(10-40).

5. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 1 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: Four feed channels are circumferentially arranged on the outer wall of the mixing section, which are respectively marked as the first feed channel, the second feed channel, the third feed channel and the fourth feed channel in the clockwise direction.

6. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 5 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The first feed channel and the third feed channel are respectively connected to the first feed device, and the first feed device is used to pass the first material into the mixing section through the first feed channel and the third feed channel respectively.

7. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 6 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The second feed channel and the fourth feed channel are respectively connected to the second feed device, and the second feed device is used to pass the second material into the mixing section through the second feed channel and the fourth feed channel respectively.

8. The use of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 7 in the reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The axis of the feed channel is perpendicular to the axis of the mixing section in a vertical plane.

9. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 8 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The tangent line passing through the intersection of the feed channel and the mixing section is the intersection tangent line, and the angle between the axis of the feed channel and the intersection tangent line is 100-180°.

10. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 8 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The diameter at the intersection of the axis of the feed channel and the outer wall of the mixing section is recorded as the first intersection diameter, and the axes of all the feed channels are located on the same side of the extension line of the corresponding first intersection diameter.

11. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 10 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The axes of all the feed channels are located on the left side of the extension line of the corresponding first intersection diameter, and the first material and the second material are introduced into the mixing section through the feed channels to form a clockwise swirl; or, The axes of all the feed channels are located on the right side of the extension line of the corresponding first intersection diameter, and the first material and the second material are introduced into the mixing section through the feed channels to form a counterclockwise swirl.

12. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 7 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: At least two jet holes are opened on the outer wall of the extension section along the circumferential direction, and a buffer chamber is arranged on the outer circumference of the extension section in the area where the jet holes are located, and the buffer chamber covers the jet holes; The buffer chamber is connected to a feed pipe, and the third feed device introduces a third material into the buffer chamber through the feed pipe, and the third material enters the extension section through the jet hole.

13. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 12 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The diameter passing through the intersection of the jet hole and the inner wall of the extension section is recorded as the second intersection diameter, and all the jet hole axes are located on the same side of the corresponding second intersection diameter extension line and the angle between them and the corresponding second intersection diameter extension line is 0 to 45°.

14. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 13 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The first material and the second material form a first stream of clockwise swirling flow in the mixing section, all the jet hole axes are located on the right side of the extension line of the diameter of the second intersection, and the first stream and the third material form a counterclockwise swirling flow in the extension section; or, The first material and the second material form a first stream of counterclockwise swirling flow in the mixing section, all the jet hole axes are located on the left side of the extension line of the second intersection diameter, and the first stream and the third material form a clockwise swirling flow in the extension section.

15. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 1 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The length of the ultrasonic horn inserted into the contraction section does not exceed 2 / 3 of the height of the contraction section.

16. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 1 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The reaction device is a tubular reactor, which comprises a reaction tube, and the ratio of the inner diameter of the reaction tube to the diameter of the small end surface of the contraction section is 1:(1-5).

17. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 1 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The discharge port of the reaction device is connected to a collecting device.

18. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 1 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device is used for reaction crystallization or dissolution cooling crystallization of barium sulfate, cefuroxime sodium ultrafine particles or miglitol ultrafine particles.

19. Application of the ultrasonically enhanced symmetrical jet-coupled slug flow crystallization system device according to claim 17 in reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The ultrasonically enhanced symmetrical jet coupled slug flow crystallization system device is used to quantitatively describe the mixing effect.

20. The use of the ultrasonically enhanced symmetrical jet coupled slug flow crystallization system device according to claim 19 in the reaction crystallization or dissolution cooling crystallization of inorganic salts or organic drug particles, characterized in that: The quantitative description of the mixing effect is by calculating the separation index at different Reynolds numbers.

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