A method and apparatus for concentrating pharmaceutical intermediates

Abstract

This invention relates to a method and apparatus for concentrating pharmaceutical intermediates. The apparatus includes a heat exchanger and a separator. The separator comprises a crystallization mechanism, a centrifugation mechanism, and a power supply mechanism. The crystallization mechanism crystallizes the solution under stirring. The centrifugation mechanism has a separation disc, a separator cylinder, and a heating jacket. The separation disc has a support plate, a filter section, and a guide plate. The filter section also has rotational capability as it rotates rapidly with the support plate, causing the crystals to separate from the liquid phase and fall onto the inner and outer sides of the guide plate, respectively. The heating jacket heats and liquefies the crystals, making them suitable for transport by a chemical pump. The power supply mechanism supplies cold energy to the crystallization mechanism and heat energy to the centrifugation mechanism. This invention is applicable to the crystallization and concentration of heat-sensitive, volatile, or toxic pharmaceutical intermediates, reducing the risks of deterioration, volatilization, and human poisoning.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical intermediates technology, and specifically to a method and equipment for concentrating pharmaceutical intermediates. Background Technology

[0002] Pharmaceutical intermediates are chemical raw materials or products used in the process of drug synthesis. These chemical products do not require a drug production license and can be produced in ordinary chemical plants. As long as they reach a certain level, they can be used in drug synthesis. Currently, my country needs more than 2,000 kinds of raw materials and intermediates that are used in chemical production each year, with a demand of more than 2.5 million tons.

[0003] Fluorinated pyridine intermediates are among the most sought-after products, leading to a high demand for them. The production of fluorinated pyridine pharmaceutical intermediates involves a significant amount of solvent, necessitating concentration to increase the concentration of active ingredients before refining, thus reducing unnecessary energy waste.

[0004] Common concentration methods include vacuum distillation, reverse osmosis, and extraction. Among these, vacuum distillation is energy-intensive, extraction involves many steps, and reverse osmosis has high membrane costs, short operating time, and high requirements for solution properties. In recent years, crystallization concentration has been vigorously developed due to its low energy consumption and pollution-free nature. For example, patent application number 202320091221.9 discloses a standby crystallization centrifuge device for pharmaceutical intermediates. Sodium sulfate is cooled and crystallized in a crystallizer, and then the crystals and solution are initially filtered. The solution with more crystals enters a centrifuge tank for centrifugation to separate the solid and liquid. The solid after centrifugation is collected through the crystal outlet. Fluoropyridine can cause certain harm to the human nervous system, digestive system, circulatory system, liver, and kidneys. The above-mentioned crystallization centrifuge device requires manual opening and closing of the crystal outlet for collection, which may cause operators to come into contact with pharmaceutical intermediates and affect their health. Therefore, such a device and method are not suitable for the production of fluorinated pharmaceutical intermediates. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a method and apparatus for concentrating pharmaceutical intermediates. The purpose is to provide a method and apparatus for crystallizing and concentrating pharmaceutical intermediates, particularly heat-sensitive, volatile, or toxic pharmaceutical intermediates, thereby reducing the risk of deterioration, volatilization, or poisoning to humans from contact with pharmaceutical intermediates.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows:

[0007] A method for concentrating pharmaceutical intermediates includes the following steps:

[0008] S1: Pre-cooling, the solution containing pharmaceutical intermediates is cooled by passing it through a heat exchanger using a low-temperature fluid. After cooling, the temperature is lower than the freezing point of one component in the pharmaceutical intermediate or solvent and higher than the freezing point of another component.

[0009] S2: Crystallization. The solution in S1, cooled to the freezing point, is added into the crystallization mechanism. Crystal nuclei are introduced and the solution is cooled further under stirring to crystallize. The component with a relatively high freezing point in the pharmaceutical intermediate or solvent forms crystals.

[0010] S3: Centrifugation and liquefaction. The solution containing crystals in the crystallization mechanism is transferred to the centrifugation mechanism for centrifugal separation. While the liquid phase is separated from the crystals by centrifugation, the liquid phase is stored in one storage space, and the crystals are automatically stored in another storage space and liquefied by heating.

[0011] S4: Collect and use a chemical pump to extract the two separated liquid phases. One phase contains an increased concentration of pharmaceutical intermediates and is transferred to the product packaging or refining process. The other phase is the solvent phase and is recycled back to the production system for reuse.

[0012] In step S2, the ratio of the amount of solution added to the crystallization mechanism per minute to the internal volume of the crystallization mechanism is less than 5%. In step S1, the solution is continuously transported to the crystallization mechanism. In step S2, the solution containing crystals is continuously transported to the centrifugation mechanism. In step S3, the crystals and liquid phase are continuously separated. In step S4, the two liquid phases are continuously output.

[0013] When the ratio of the solution flow rate to the internal volume of the crystallization mechanism is less than 2%, the solution containing pharmaceutical intermediates can be fed into the crystallization mechanism while being stirred and crystallized, and the solution containing crystals can be discharged into the centrifuge mechanism at the same time, forming a continuous production process. Since there are always crystals in the crystallization mechanism, there is no need to add additional crystal nuclei.

[0014] Freeze-crystallization separation offers advantages such as low temperature, high efficiency, energy saving, environmental friendliness, and minimal or no wastewater generation. It exhibits excellent separation effects for heat-sensitive and volatile pharmaceutical intermediates. Furthermore, because it avoids heating, it preserves the efficacy of the pharmaceutical intermediates. For volatile intermediates, the lower temperature reduces volatility, thus increasing yield. However, currently, freeze-crystallization separation is not suitable for fluorine-containing pharmaceutical intermediates. This is primarily because the addition of fluorine atoms significantly improves the heat resistance and stability of the intermediates, reducing their thermal decomposition. Separation is achieved through distillation and other processes. On the other hand, the addition of fluorine atoms makes pharmaceutical intermediates somewhat toxic, especially fluorinated pyridine. Pyridine itself is toxic, and the addition of fluorine atoms makes it even more toxic. Long-term exposure to fluorinated pyridine can cause certain harm to the human nervous system, digestive system, circulatory system, liver and kidneys. After freezing crystallization, the crystals are separated by centrifugal force, but the crystals remain on the inside of the filter screen and need to be cleaned manually. During the operation, it is easy to come into contact with pharmaceutical intermediates and thus cause occupational diseases. Therefore, for the health of their employees, many manufacturers usually prefer to use the more expensive reverse osmosis or distillation methods rather than freezing crystallization separation.

[0015] This invention improves the separation process, enabling pharmaceutical intermediates to be separated using a lower-cost and safer cryo-crystallization method while ensuring operator safety, thereby reducing production costs. The main improvement lies in the separation of crystals. Conventional centrifugal separation equipment typically retains crystals inside the filter screen, causing crystal accumulation that hinders centrifugal separation and requires manual cleaning. This invention, however, ejects the crystals into a separate storage space during centrifugation. This not only removes crystals promptly, preventing accumulation and ensuring effective separation, but also allows the crystals in this storage space to be heated. The heated crystals liquefy and can be transported via a chemical pump, thus avoiding the problem of manual cleaning of crystals coming into contact with pharmaceutical intermediates.

[0016] A pharmaceutical intermediate concentration device, using the aforementioned pharmaceutical intermediate concentration method, includes a heat exchanger and a separator. The separator includes a crystallization mechanism, a centrifugation mechanism, and a power supply mechanism. The crystallization mechanism has a cooling coil and a stirring paddle for crystallizing the solution under stirring conditions. The crystallization mechanism has a discharge pipe for feeding the centrifugation mechanism. The centrifugation mechanism has a separation disc, a separator cylinder, and a heating jacket. The separator cylinder has storage spaces on both its inner and outer sides. The separation disc has a support plate, a filter section, and a guide plate. The filter section also has rotational capability when it rotates rapidly with the support plate, causing the crystals to separate from the liquid phase and fall onto the inner and outer sides of the guide plate, respectively. The lower end of the guide plate is located inside the upper end of the separator cylinder. The heating jacket heats and liquefies the crystals. The power supply mechanism is a vortex tube, with its cold end supplying cold energy to the crystallization mechanism and its hot end supplying heat to the centrifugation mechanism.

[0017] An apparatus is provided for implementing the above-mentioned pharmaceutical intermediate concentration method. The apparatus can achieve continuous concentration and separation of pharmaceutical intermediates using a heat exchanger and a separator. It is low in cost, all materials are transported by chemical pumps, no manual operation is required, and it does not affect the health of operators.

[0018] Furthermore, the air outlet of the cooling coil and the air outlet of the heating jacket are connected to a common air outlet pipe, and the end of the air outlet pipe is vented.

[0019] This invention utilizes a vortex tube to supply both cooling and heating. The vortex tube itself has a cold end and a hot end. The cold end blows out cold air, with a minimum temperature reaching -50℃ to -70℃, while the hot end blows out hot air, with a maximum temperature reaching 140℃ to 170℃. Since this technical solution requires continuous cooling and heating, the vortex tube is the most suitable choice. While an industrial compressor could also achieve the same effect, it requires time and effort to modify, and it's inconvenient to adjust for the different temperatures required by various pharmaceutical intermediates, making it far less convenient than the vortex tube. Furthermore, the vortex tube primarily utilizes compressed air, which is readily available. The air outlets of the cooling coil and the heating jacket are connected to a single exhaust pipe, which is vented. Because the cooling coil blows out cold air and the heating jacket blows out hot air, the combined cold and hot air, after mixing to room temperature, can be vented without affecting the workshop environment.

[0020] Furthermore, a drive motor for rapidly rotating the support plate is connected to the center of the lower surface of the support plate. A filter section is provided on the upper surface of the support plate. The filter section is a C-shaped open ring and includes an inner filter screen and an outer filter screen. Both the inner and outer filter screens include a metal skeleton and a filter cloth connected to the metal skeleton. The inner and outer filter screens are connected end to end to form a closed ring. As the support plate rotates, the inner and outer filter screens can rotate and alternate positions. A guide plate is provided between the inner and outer filter screens. The guide plate is a curved C-shaped plate with a smaller diameter at the upper end than at the lower end. The lower end of the guide plate penetrates the support plate and is located below it. The support plate has water passage holes located inside the guide plate. A partition plate is provided on the inner side of the guide plate. The lower end of the partition plate is connected to the upper surface of the support plate and restricts the flow of liquid phase inside the guide plate.

[0021] This technical solution mainly utilizes the centrifugal mechanism of the separator, which includes a separation disc, a separator cylinder, and a heating jacket. When the separation disc rotates rapidly, it can centrifugally separate the mixture of crystals and liquid phase within the crystallization mechanism. After separation, the crystals remain inside the filtration section. However, the filtration section of this technical solution includes an inner filter screen and an outer filter screen. As the filtration section rotates with the support plate, the inner and outer filter screens can rotate and alternate positions, thereby achieving the effect of automatically removing crystals during the filtration process.

[0022] This technical solution also has various variations. For example, the filtration section is a ring composed of multiple cylindrical filter screens, and each cylindrical filter screen has two guide posts. This can also achieve filtration and transfer the crystals out. However, because multiple filter screens will form multiple openings, the crystals and liquid mixture discharged by the crystallization mechanism will easily fly out at its openings, causing raw material waste or reduced concentration efficiency. This invention has only one opening, which has the best effect.

[0023] Furthermore, the opening of the filter section is provided with an arc-shaped baffle, the circle in which the baffle is located is concentric with the circle in which the guide plate is located, and the central angle subtended by the baffle is greater than the central angle subtended by the opening of the guide plate.

[0024] Because the filtration section cannot form a perfect ring, the mixture of crystals and liquid phase discharged from the crystallization mechanism is prone to flying out at its opening, causing raw material waste or reduced concentration efficiency. Therefore, a baffle is set up to intercept it and allow it to flow onto the filtration section during rotation to achieve filtration, thus compensating for the defect of the filtration section having an opening.

[0025] Furthermore, a guide disc is provided at the center of the upper surface of the support plate. The guide disc is a spherical crown shell with an upward opening and a spherical arch facing the support plate. Guide ribs are provided on the inner surface of the spherical crown shell. The height of the spherical crown shell is less than or equal to half the height of the filter section.

[0026] The guide plate guides the mixture of crystals and liquid phase discharged from the crystallization mechanism, causing it to transfer evenly to the center of the filtration section. During the transfer process, a dispersion effect is formed, preventing the material from being too concentrated and affecting the filtration and separation effect.

[0027] Furthermore, the lower end of the discharge pipe is lower than the upper end of the filter section, and there is a drive column at the connection between the inner filter screen and the outer filter screen. The drive column is rotatably connected to the support plate, and a drive wheel higher than the filter section is fixedly connected to the upper end of the drive column. A fixed wheel is connected to the discharge pipe, and the drive wheel and the fixed wheel are connected by a belt or chain.

[0028] The drive column positions the filter section and also rotates the two layers of filter screens within the filter section, achieving self-relocation and allowing the crystals to transfer to the outside of the filter section. The drive column is primarily powered by the rotation of the support plate. When the support plate rotates, the drive column rotates with it. Because the drive wheel is connected to the upper end of the drive column and is connected to the fixed wheel on the discharge pipe via a belt or chain, the drive wheel has relative rotational power with respect to the support plate. As the drive wheel rotates, it drives the drive column to rotate, thereby achieving the interchange of positions between the inner and outer filter screens.

[0029] Furthermore, the diameter of the drive wheel is greater than the diameter of the drive column and the diameter of the fixed wheel.

[0030] The main purpose of making the diameter of the drive wheel larger than the diameter of the drive column and the fixed wheel is to slow down the rotation speed of the drive column. During centrifugal separation, the rotation speed of the bearing plate is relatively fast. Only rapid rotation can generate sufficient centrifugal force to better separate the crystals from the liquid phase. If the drive column also rotates rapidly, the crystals will be carried by the inner filter screen to the position of the outer filter screen before the liquid phase has completely separated from the crystals. This results in the crystals containing more liquid phase, incomplete separation, material waste, or low concentration efficiency. This invention reduces the rotation speed of the drive column, making the material separation more thorough and reducing the retention of liquid phase in the crystals.

[0031] Furthermore, both the inner and outer filter screens are provided with n limiting posts on their inner and outer sides, where n is greater than or equal to 5, and the limiting posts are rotatably connected to the support plate.

[0032] The function of the limiting post is to maintain the shape of the inner and outer filter screens, ensuring they remain in an arc shape and do not deform. During rotation, it also supports the inner and outer filter screens, preventing damage to them.

[0033] Furthermore, both the limiting post and the driving post are columnar bodies that are thick at both ends and thin in the middle, and the outer wall of the driving post is provided with connecting spikes that extend into the filter section.

[0034] The guide plate throws the material towards the middle of the inner filter screen, causing the liquid phase to be filtered due to centrifugal force. The crystals remain in the middle of the inner filter screen and move with it. Both the limiting column and the driving column are columnar bodies that are thick at both ends and thin in the middle. This causes the middle of the inner filter screen to bulge outward, leaving space for the crystals to move and preventing them from being blocked by the limiting column. This allows the inner filter screen to smoothly transfer the crystals and avoids them remaining on the inside of the inner filter screen due to the action of the limiting column, thus preventing them from hindering the centrifugal filtration effect.

[0035] The beneficial effects of the present invention through the above technical solution are as follows:

[0036] This invention improves the separation process of pharmaceutical intermediates, enabling the separation of pharmaceutical intermediates using a lower-cost and safer freeze crystallization method while ensuring the personal safety of operators, thereby reducing production costs.

[0037] This invention primarily improves the separation mechanism for crystals in solution. Conventional centrifugal separation equipment typically retains crystals inside the filter screen, causing crystal accumulation that hinders the centrifugal separation effect and requires manual cleaning. This invention, however, ejects the crystals into a separate storage space during centrifugation. This not only removes crystals at any time, preventing crystal accumulation from affecting the separation effect, but also allows the crystals in this storage space to be heated. The heated crystals liquefy and can be transported by a chemical pump, thus avoiding the problems of manual cleaning of crystals and contact with pharmaceutical intermediates.

[0038] The filtration unit of the present invention includes an inner filter screen and an outer filter screen. As the filtration unit rotates with the support plate, the inner filter screen and the outer filter screen can rotate and alternate positions, thereby achieving the effect of automatically removing crystals during the filtration process. Attached Figure Description

[0039] Figure 1 This is a schematic diagram of the structure of the present invention;

[0040] Figure 2 This is a schematic diagram of the separator of the present invention;

[0041] Figure 3 This is a cross-sectional front view of the separator of the present invention;

[0042] Figure 4 yes Figure 3 Sectional view along axis AA;

[0043] Figure 5 yes Figure 3 BB-direction sectional view;

[0044] Figure 6 This is a right-section cross-sectional view of the separator of the present invention;

[0045] Figure 7 This is a schematic diagram (partial cross-sectional view) of the separation disc of the present invention;

[0046] Figure 8 yes Figure 3 BB-directed sectional view (another structure of the separation disc).

[0047] The attached diagram is labeled as follows: 1. Heat exchanger; 2. Separator; 3. Crystallization mechanism; 4. Centrifugation mechanism; 5. Power supply mechanism; 6. Cooling coil; 7. Stirring paddle; 8. Discharge pipe; 9. Separation disc; 10. Separating cylinder; 11. Heating jacket; 12. Support plate; 13. Filter section; 14. Guide plate; 15. Gas outlet pipe; 16. Drive shaft; 17. Drive motor; 18. Inner filter screen; 19. Outer filter screen; 20. Frame; 21. Filter cloth; 22. Water passage hole; 23. Separating plate; 24. Baffle; 25. Guide disc; 26. Guide rib; 27. Drive column; 28. Drive wheel; 29. ​​Fixed wheel; 30. Limiting column. Detailed Implementation

[0048] The present invention will be further described below with reference to the accompanying drawings and specific embodiments:

[0049] like Figure 1 , Figure 2 , Figure 3 and Figure 6As shown, a pharmaceutical intermediate concentration device includes a heat exchanger 1 and a separator 2. The pharmaceutical intermediate solution undergoes heat exchange in the heat exchanger 1 to form a subcooled state. After cooling, the temperature is lower than the freezing point of one component in the pharmaceutical intermediate or solvent and higher than the freezing point of another component. The separator includes a crystallization mechanism 3, a centrifugation mechanism 4, and a power supply mechanism 5. The shells of the crystallization mechanism 3 and the centrifugation mechanism 4 are integrally formed, with the lower end of the crystallization mechanism 3 being the upper end of the centrifugation mechanism 4. The crystallization mechanism 3 has a cooling coil 6 and a stirring paddle 7 for crystallizing the solution under stirring. After the pharmaceutical intermediate solution enters the crystallization mechanism 3, crystal nuclei are added for stirring and continued cooling to crystallize a specific component in the solution. The crystal nuclei are crystalline powders of the pharmaceutical intermediate solute or crystalline powders of the solvent. The crystallization mechanism 3 has a function to supply power to the centrifugation mechanism. 4. The feeding discharge pipe 8. The centrifugal mechanism 4 has a separation disc 9, a separator cylinder 10 and a heating jacket 11. The separator cylinder 10 has storage space on both the inner and outer sides. The separation disc 9 has a support plate 12, a filter section 13 and a guide plate 14. The filter section 13 has its own rotational ability when it rotates rapidly with the support plate 12, so that the crystals and liquid phases are separated and fall on the inner and outer sides of the guide plate 14 respectively. The lower end of the guide plate 14 is located inside the upper end of the separator cylinder 10. The heating jacket 11 heats and liquefies the crystals. In this embodiment, the energy supply mechanism 5 is a vortex tube. The cold end of the vortex tube delivers cold energy to the crystallization mechanism 3 and the hot end delivers heat to the centrifugal mechanism 4. The vortex tube can generate hot air and cold air at the same time, which are used for the crystallization mechanism 3 and the centrifugal mechanism 4 respectively, resulting in high energy utilization.

[0050] The air outlet of the cooling coil 6 and the air outlet of the heating jacket 11 are connected to a common air outlet pipe 15, and the end of the air outlet pipe 15 is vented.

[0051] like Figure 4 , Figure 5 and Figure 7As shown, the lower surface of the support plate 12 is connected to a drive motor 17 via a drive shaft 16, which drives the support plate 12 to rotate rapidly. The upper surface of the support plate 12 has a filter section 13, which is a C-shaped open ring. The filter section 13 includes an inner filter screen 18 and an outer filter screen 19. Both the inner and outer filter screens 18 and 19 include a metal frame 20 and a filter cloth 21 connected to the metal frame, and are in an upright position. The inner and outer filter screens 18 and 19 are connected end-to-end to form a closed ring. As the support plate 12 rotates, the filter section 13... The inner filter screen 18 and the outer filter screen 19 are capable of rotating and alternating positions. There is a guide plate 14 between the inner filter screen 18 and the outer filter screen 19. The guide plate 14 is an arc-shaped plate that is curved into a "C" shape. The diameter of the upper end of the guide plate 14 is smaller than the diameter of the lower end. The lower end of the guide plate 14 passes through the support plate 12 and is located below the support plate 12. The support plate 12 is provided with a water passage hole 22 located inside the guide plate 14. A partition plate 23 is provided on the inner side of the guide plate 14. The lower end of the partition plate 23 is connected to the upper surface of the support plate 12. There is a water passage hole 22 between every two adjacent partition plates 23.

[0052] like Figure 8 As shown, this technical solution also has various variations. For example, the filtration section is a ring composed of multiple cylindrical filter screens, and each cylindrical filter screen has two guide posts. This can also achieve filtration and transfer the crystals out. However, because multiple filter screens will form multiple openings, the crystals and liquid mixture discharged by the crystallization mechanism will easily fly out at its openings, causing raw material waste or reduced concentration efficiency. This invention has only one opening, which has the best effect.

[0053] The filtration section 13 traps crystals in the pharmaceutical intermediate solution on the inner filter screen 18. The liquid phase passes through the inner filter screen 18 and is trapped on the guide plate 14. Guided by the inclined state of the guide plate 14, it moves downward, passes through the water passage 22, enters the separator 10, and is stored inside the separator 10. The crystals rotate with the inner filter screen 18. When the inner filter screen 18 rotates to become the outer filter screen 19, the crystals are thrown to the outside of the guide plate 14 and separated from the outer filter screen 19. At this time, the heating jacket 11 heats the crystals, causing them to melt and flow downward, and be stored on the outside of the separator 10. In this invention, after the pharmaceutical intermediate is concentrated, both parts are liquid phases, which can be transferred and transported by a chemical pump without the need for manual cleaning of the crystals inside the filter screen.

[0054] The filter section 13 has an arc-shaped baffle 24 at its opening. The circle containing the baffle 24 is concentric with the circle containing the guide plate 14. The central angle of the baffle 24 is greater than the central angle of the opening of the guide plate 14.

[0055] The upper surface of the support plate 12 is provided with a guide plate 25 at its center. The guide plate 25 is a spherical crown shell with an opening facing upward and arched towards the support plate 12. The inner surface of the spherical crown shell is provided with guide ribs 26. The height of the spherical crown shell is less than or equal to half the height of the filter section 13.

[0056] The guide plate 25 can have various shapes, such as an upward-opening cone, a disc with inclined side edges, or a horizontal disc corresponding to the middle of the height of the filter section. All of these can achieve the purpose of this embodiment. However, the structure with guide ribs 26 on the inner surface of the spherical cap is more practical in this embodiment, as it can reduce the splashing of the liquid phase.

[0057] The lower end of the discharge pipe 8 is lower than the upper end of the filter section 13. There is a drive column 27 at the connection between the inner filter screen 18 and the outer filter screen 19. The drive column 27 is rotatably connected to the support plate 12. The upper end of the drive column 27 is fixedly connected to a drive wheel 28 that is higher than the filter section 13. A fixed wheel 29 is connected to the discharge pipe 8. The drive wheel 28 and the fixed wheel 29 are connected by a belt or chain.

[0058] Besides the structure in this embodiment that makes the drive wheel 28 rotate with the drive column 27, there are many other structures, such as connecting a motor to the support plate 12 and using the motor to drive the drive column 27 to rotate, or providing a rack on the inner wall of the centrifugal mechanism 4 corresponding to the drive wheel 28 and using the rack to mesh with the drive wheel 28 to make the drive wheel 28 rotate, etc. This embodiment is a more feasible and more suitable structure for separation among these variations.

[0059] Both the inner and outer filter screens 18 and 19 are provided with n limiting posts 30 on their inner and outer sides, where n is greater than or equal to 5, and the limiting posts 30 are rotatably connected to the support plate 12.

[0060] The diameter of the drive wheel 28 is greater than the diameter of the drive column 27 and the diameter of the fixed wheel 29.

[0061] Both the limiting post 30 and the driving post 27 are columnar bodies that are thick at both ends and thin in the middle. The outer wall of the driving post 27 is provided with connecting spikes that extend into the filter section 13.

[0062] A method for concentrating pharmaceutical intermediates includes the following steps:

[0063] S1: Pre-cooling, the solution containing the pharmaceutical intermediate is cooled by a low-temperature fluid through heat exchanger 1. After cooling, the temperature is lower than the freezing point of one component in the pharmaceutical intermediate or solvent and higher than the freezing point of another component.

[0064] S2: Crystallization. The solution in S1, cooled to the freezing point, is added to the crystallization mechanism 3. Crystal nuclei are introduced and the solution is cooled further under stirring to crystallize. The component with a relatively high freezing point in the pharmaceutical intermediate or solvent forms crystals.

[0065] S3: Centrifugation and liquefaction. The solution containing crystals in the crystallization mechanism 3 is transferred to the centrifugation mechanism 4 for centrifugation separation. While the liquid phase is separated from the crystals by centrifugation, the liquid phase is stored inside the separator 10, and the crystals are automatically stored outside the separator 10. The crystals are liquefied by heating outside the separator 10.

[0066] S4: Collect and use a chemical pump to extract the two separated liquid phases. One phase contains an increased concentration of pharmaceutical intermediates and is transferred to the product packaging or refining process. The other phase is the solvent phase and is recycled back to the production system for reuse.

[0067] In step S2, the ratio of the amount of solution added to the crystallization mechanism 3 per minute to the internal volume of the crystallization mechanism is less than 5%. In step S1, the solution is continuously transported to the crystallization mechanism. In step S2, the solution containing crystals is continuously transported to the centrifugation mechanism. In step S3, the crystals and liquid phase are continuously separated. In step S4, the two liquid phases are continuously output.

[0068] The main objective of this invention is to achieve continuous crystallization and separation of materials, and to automatically separate and liquefy the crystals, which are then transported using a chemical pump without the need for manual cleaning of the crystals. Furthermore, this invention is applicable to the crystallization and concentration of heat-sensitive pharmaceutical intermediates, volatile pharmaceutical intermediates, or pharmaceutical intermediates that are toxic to humans.

[0069] The preferred embodiments of the present invention have been described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments. Various modifications can be made to the technical solutions of the present invention without departing from the spirit of the present invention or the scope of disclosure.

Claims

1. An apparatus for concentrating a pharmaceutical intermediate, characterized by, The system includes a heat exchanger (1) and a separator (2). The separator (2) includes a crystallization mechanism (3), a centrifugal mechanism (4), and a power supply mechanism (5). The crystallization mechanism (3) has a cooling coil (6) and a stirring paddle (7) for crystallizing the solution under stirring conditions. The crystallization mechanism (3) has a discharge pipe (8) for feeding the centrifugal mechanism (4). The centrifugal mechanism (4) has a separation disc (9), a separator cylinder (10), and a heating jacket (11). The separator cylinder (10) has storage space on both its inner and outer sides. The separation disc (9) has a support plate (12), a filter section (13), and a guide plate (14). The filter section (13) also has rotational capability when it rotates rapidly with the support plate (12), so that the crystals and liquid phases are separated and fall on the inner and outer sides of the guide plate (14). The lower end of the guide plate (14) is located inside the upper end of the separator (10). The heating jacket (11) heats and liquefies the crystals. The power supply mechanism (5) delivers cold energy to the crystallization mechanism (3) and heat energy to the centrifugal mechanism (4). A drive motor (17) for rapidly rotating the support plate (12) is connected to the center of the lower surface of the support plate (12). A filter section (13) is provided on the upper surface of the support plate (12). The filter section (13) is a C-shaped open ring. The filter section (13) includes an inner filter screen (18) and an outer filter screen (19). The inner filter screen (18) and the outer filter screen (19) are connected end to end to form a closed ring. During the rotation of the support plate (12), the inner filter screen (18) and the outer filter screen (19) can rotate and alternate positions. There is a guide plate (14) between the mesh (18) and the outer filter mesh (19). The upper diameter of the guide plate (14) is smaller than the lower diameter. The lower end of the guide plate (14) passes through the support plate (12) and is located below the support plate (12). The support plate (12) is provided with a water passage hole (22) located inside the guide plate (14). A partition plate (23) is provided on the inner side of the guide plate (14). The lower end of the partition plate (23) is connected to the upper surface of the support plate (12). The partition plate (23) restricts the flow of liquid phase in the guide plate (14). There is a water passage hole (22) between every two adjacent partition plates (23). The filter section (13) has an arc-shaped baffle (24) at its opening. The circle containing the baffle (24) is concentric with the circle containing the guide plate (14). The central angle of the baffle (24) is greater than the central angle of the opening of the guide plate (14).

2. The apparatus for concentrating a pharmaceutical intermediate according to claim 1, wherein The air outlet of the cooling coil (6) and the air outlet of the heating jacket (11) are connected to a common air outlet pipe (15), and the end of the air outlet pipe (15) is vented.

3. The equipment for concentrating pharmaceutical intermediates according to claim 1, characterized in that, The upper surface of the support plate (12) is provided with a guide plate (25). The guide plate (25) is a spherical crown shell with an opening facing upward and arched towards the support plate (12). The inner surface of the spherical crown shell is provided with guide ribs (26). The height of the spherical crown shell is less than or equal to half the height of the filter section (13).

4. The equipment for concentrating pharmaceutical intermediates according to claim 1, characterized in that, The lower end of the discharge pipe (8) is lower than the upper end of the filter section (13). There is a drive column (27) at the connection between the inner filter screen (18) and the outer filter screen (19). The drive column (27) is rotatably connected to the support plate (12). The upper end of the drive column (27) is fixedly connected to a drive wheel (28) higher than the filter section (13). A fixed wheel (29) is connected to the discharge pipe (8). The drive wheel (28) and the fixed wheel (29) are connected by a belt or chain. The diameter of the drive wheel (28) is greater than the diameter of the drive column (27) and the diameter of the fixed wheel (29).

5. The equipment for concentrating pharmaceutical intermediates according to claim 4, characterized in that, The inner filter screen (18) and the outer filter screen (19) are provided with n limiting posts (30) on both the inner and outer sides, where n is greater than or equal to 5, and the limiting posts (30) are rotatably connected to the bearing plate (12).

6. The equipment for concentrating pharmaceutical intermediates according to claim 5, characterized in that, The inner filter (18) and outer filter (19) both include a metal frame (20) and a filter cloth (21) connected to the metal frame (20), and are in an upright state. The limiting post (30) and the driving post (27) are both columnar bodies that are thick at both ends and thin in the middle. The outer wall of the driving post (27) is provided with connecting spikes that extend into the filter part (13).

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