A rapid cooling crystallization device for nicotinamide riboside

Abstract

The application discloses a nicotinamide nucleoside rapid cooling crystallization device, and relates to the technical field of crystallization equipment for biological medicine intermediates. The device comprises a crystallization kettle, the outer surface of the crystallization kettle is provided with a spiral flow guide jacket, the bottom of the spiral flow guide jacket is provided with a nitrogen inlet pipe for conveying liquid nitrogen refrigerant into the jacket. Each circle of the spiral flow guide jacket is provided with an isolation seat, an adjusting cylinder is rotatably installed on the inner side of the isolation seat, the surface of the adjusting cylinder is provided with a through hole and a flow interception hole, and the flow direction of the liquid nitrogen in the single-circle spiral flow guide jacket is switched through the rotation of the adjusting cylinder. The outer side of the crystallization kettle is provided with a nitrogen collecting pipe, the adjusting cylinder is communicated with the nitrogen collecting pipe through an eccentric hole structure, and the cut-off liquid nitrogen is discharged. Through the above structure, the spiral rising range of the liquid nitrogen can be selectively controlled according to the liquid level height of the raw material in the crystallization kettle, so that the liquid nitrogen only cools the corresponding crystallization area, the invalid cooling of the area above the liquid level is avoided, and the consumption of the cold source is reduced.

Description

Technical Field

[0001] This invention belongs to the field of nicotinamide glycoside production technology, specifically relating to a rapid cooling crystallization device for nicotinamide nucleoside. Background Technology

[0002] Nicotinamide nucleoside, as an important pharmaceutical and nutritional functional raw material, typically requires dissolution, cooling, and crystallization processes during its preparation. The crystallization process, in particular, demands precise temperature control. In current production, nicotinamide nucleoside crystallization is usually carried out inside a crystallization vessel. Cooling is achieved by installing a cooling jacket or introducing a low-temperature refrigerant to the outside of the vessel, thus promoting supersaturation of the solution and crystal formation.

[0003] In existing technologies, crystallization reactors typically employ an integral cooling jacket structure on the outside. The cooling medium flows along a fixed path within the jacket to cool the entire reactor. While this structure effectively cools the reactor body, the cooling medium's effective range usually covers the entire height of the crystallization reactor, resulting in a lack of targeted cooling. When the raw material level inside the crystallization reactor is low, the cooling medium still needs to cool the areas of the reactor body above the liquid level, leading to low utilization of the cold source. This is especially problematic when using cryogenic refrigerants such as liquid nitrogen, which can easily result in wasted cooling capacity and increased production costs.

[0004] Furthermore, the flow path and effective height of the cooling medium in existing crystallization devices are typically fixed, making dynamic adjustment difficult based on the actual liquid level in the crystallizer. When the raw material feed rate changes, the cooling method remains unchanged, affecting both energy efficiency and stability control of the crystallization process. In rapid cooling crystallization processes, if the cooling zone does not match the actual crystallization zone, localized overcooling or insufficient cooling can easily occur, impacting crystal formation and product quality. Summary of the Invention

[0005] To address the problems existing in the prior art, the present invention aims to provide a rapid cooling crystallization device for nicotinamide nucleoside, which can adjust the effective height of the cooling medium outside the crystallization vessel and match the cooling process with the crystallization liquid level.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A rapid cooling crystallization device for nicotinamide nucleoside includes a crystallization vessel, the crystallization vessel having a hollow interior with a sealed end cap hinged to the top, a spiral flow guide jacket provided on the outer surface of the crystallization vessel, and a nitrogen inlet pipe provided at the bottom of the spiral flow guide jacket; Each turn of the spiral guide jacket is provided with an isolation seat, and multiple isolation seats are on the same vertical line. An adjusting cylinder is rotatably installed inside the isolation seat. The adjusting cylinder extends beyond the end of the isolation seat. The adjusting cylinder is hollow inside. Through holes are symmetrically opened on the end of the surface of the adjusting cylinder. Cut-off holes are opened on the end of the surface of the adjusting cylinder. The cut-off holes and through holes are vertically distributed. The flow direction of liquid nitrogen inside the single-turn spiral guide jacket is controlled by controlling the direction of the through holes and the cut-off holes.

[0007] Furthermore, a nitrogen collecting tube is vertically fixed to the outside of the crystallization vessel. The nitrogen collecting tube is hollow inside, and docking cylinders are evenly arranged on the surface of the nitrogen collecting tube. The end of the adjusting cylinder that is away from the isolation seat is rotated inside the docking cylinder.

[0008] Furthermore, the outer end face of the regulating cylinder is provided with a first eccentric hole, the inner side of the docking cylinder is provided with an isolation plate, the surface of the isolation plate is provided with a second eccentric hole, and the first eccentric hole and the second eccentric hole coincide when the flow interception hole is connected to the internal flow channel of the spiral guide jacket.

[0009] Furthermore, a corrugated knob is fixed on the outer surface of the adjusting cylinder, and the corrugated knob is positioned between the docking cylinder and the isolation seat.

[0010] Furthermore, an extension plate is provided on one side of the docking cylinder, and positioning bolts penetrate the surface of the extension plate.

[0011] Furthermore, the surface of the regulating cylinder has two positioning holes, which are distributed at an angle. The end of the positioning bolt is adapted to the internal size of the positioning hole, and the two positioning holes correspond to the through hole and the intercepting hole, respectively.

[0012] Furthermore, a stirring motor is fixed at the center of the top of the sealing end cap, and a stirring rod is provided downward at the output end of the stirring motor, with the stirring rod placed inside the crystallization vessel.

[0013] Furthermore, a base is provided at the bottom of the crystallization vessel, and the crystallization vessel is connected to a discharge pipe, with a control valve installed inside the discharge pipe.

[0014] Compared with the prior art, the beneficial effects of the present invention are: This technical solution involves setting a spiral flow guide jacket on the outer surface of the crystallization vessel and introducing liquid nitrogen as a cooling medium at the bottom of the spiral flow guide jacket. The liquid nitrogen flows from bottom to top along the spiral path, thereby rapidly cooling the crystallization vessel. Compared with the traditional integral cooling jacket structure, this spiral flow guide method can shorten the heat transfer path of the cooling medium, allowing the raw materials in the crystallization vessel to enter the temperature range required for crystallization more quickly, thus meeting the cooling rate requirements during the crystallization of nicotinamide nucleoside.

[0015] By setting an isolation seat in each turn of the spiral guide jacket and rotating an adjusting cylinder inside the isolation seat, the spiral guide jacket forms multiple independently controllable cooling units in the height direction. When the raw material liquid level in the crystallizer is low, the single turn of the spiral guide jacket above the liquid level can be closed to prevent liquid nitrogen from continuing to flow upward and to cool the area without raw material. This solves the problem of fixed cooling range and inability of cooling height to match the liquid level in existing crystallization devices.

[0016] By setting through holes and choke holes on the surface of the regulating cylinder, and using the rotation of the regulating cylinder to switch the orientation of the through holes and choke holes, the liquid nitrogen inside the single-turn spiral guide jacket can switch between continuing to spiral upward or being guided to discharge. When it is necessary to stop cooling above a certain height, the liquid nitrogen enters the regulating cylinder through the choke hole and is guided to the nitrogen collection pipe for discharge through the eccentric hole structure. The structure effectively controls the rising height of the liquid nitrogen, thereby reducing the amount of liquid nitrogen used and reducing the waste of cold source.

[0017] By setting the regulating cylinders at each height position to correspond with the nitrogen collection pipe, and using the eccentric hole connecting structure to centrally discharge the intercepted liquid nitrogen, the liquid nitrogen flow path is clear and orderly, avoiding turbulence or stagnation of liquid nitrogen in the jacket, thereby ensuring the stability of the cooling process and facilitating the controllability of the temperature field during crystallization.

[0018] By setting a corrugated knob on the outside of the regulating cylinder, and using a limiting structure with positioning bolts and positioning holes, the regulating cylinder can stably maintain the corresponding angle under different working conditions, avoiding accidental rotation during liquid nitrogen flow. This ensures the reliability of the single-turn spiral guide jacket in the open or closed state, and improves the operability and safety of the liquid nitrogen height adjustment process.

[0019] By installing a stirring motor and stirring rod inside the crystallization vessel, the raw materials inside the vessel are kept fully mixed during the cooling process, avoiding uneven cooling in some areas that could affect the crystallization effect. This, combined with the external adjustable-height spiral guide jacket structure, enables balanced control of the temperature distribution inside the crystallization vessel, which is beneficial to the stable crystallization process of nicotinamide nucleoside. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the formal structure of the present invention; Figure 2 This is a schematic diagram of the rear view structure of the present invention; Figure 3 This is a schematic diagram of the isolation seat structure of the present invention; Figure 4 For the present invention Figure 1 A schematic diagram of the cross-sectional structure; Figure 5 This is a schematic diagram of the three-dimensional structure of the nitrogen collecting tube of the present invention; Figure 6 This is a schematic diagram of the three-dimensional structure of the regulating cylinder of the present invention.

[0021] The attached diagram lists the components represented by each number as follows: 1. Crystallization vessel; 11. Base; 12. Discharge pipe; 13. Sealing end cap; 2. Stirring motor; 21. Stirring rod; 3. Spiral guide jacket; 31. Nitrogen inlet pipe; 32. Isolation seat; 4. Adjusting cylinder; 41. Through hole; 42. Cut-off hole; 43. Corrugated knob; 44. Positioning hole; 45. First eccentric hole; 5. Nitrogen collecting pipe; 51. Connecting cylinder; 52. Isolation plate; 53. Second eccentric hole; 54. Extension plate; 6. Positioning bolt. Detailed Implementation

[0022] To make the objectives and advantages of this invention clearer, the invention will be specifically described below with reference to embodiments. It should be understood that the following text is merely used to describe one or more specific embodiments of the invention and does not strictly limit the scope of protection specifically claimed by the invention. Example

[0023] refer to Figures 1 to 6 As shown, a rapid cooling crystallization device for nicotinamide nucleoside includes a crystallization vessel 1. The crystallization vessel 1 serves as the main container for the crystallization reaction of nicotinamide nucleoside. During the crystallization process, the raw materials inside the vessel need to be rapidly and controlled to avoid the waste of cold source caused by the fixed cooling range in traditional overall cooling methods. The interior of the crystallization vessel 1 is hollow to form a crystallization space for containing the raw material solution. The top of the crystallization vessel 1 is provided with a sealing end cap 13 by a hinge to achieve sealing control during the crystallization process and facilitate opening and maintenance. A spiral flow guide jacket 3 is provided on the outer surface of the crystallization vessel 1 along the height direction. The spiral flow guide jacket 3 is used as a flow channel for low-temperature refrigerant. It cools and exchanges heat on the crystallization vessel 1 by adhering to the outer wall of the crystallization vessel 1. A nitrogen inlet pipe 31 is provided at the bottom of the spiral flow guide jacket 3. The nitrogen inlet pipe 31 is used to transport liquid nitrogen refrigerant into the spiral flow guide jacket 3 to achieve a bottom-up spiral cooling process.

[0024] Each turn of the spiral guide jacket 3 is equipped with an isolation seat 32. The isolation seat 32 is used to divide the spiral guide jacket 3 into multiple independent single-turn cooling units in the height direction to solve the problem that the existing integral jacket cannot adjust the cooling range according to the liquid level. Multiple isolation seats 32 are arranged on the same vertical line to form a unified adjustment structure. An adjustment cylinder 4 is rotatably installed inside the isolation seat 32. The adjustment cylinder 4 is used to control the flow state of liquid nitrogen in the corresponding single-turn spiral guide jacket 3. The adjustment cylinder 4 extends beyond the end of the isolation seat 32 for external operation. The interior of the adjustment cylinder 4 is hollow to form a liquid nitrogen guide channel. Through holes 41 are symmetrically opened on the surface end of the adjustment cylinder 4. The through holes 41 are used to form a through channel between adjacent single-turn spiral guide jackets 3 when the open state is achieved. A flow-blocking hole 42 is opened on the surface end of the adjustment cylinder 4. The flow-blocking hole 42 is used to guide liquid nitrogen to the discharge path when the upward flow channel is closed. The flow-blocking hole 42 and the through hole 41 are vertically distributed to realize the switching control of the two flow directions.

[0025] By controlling the direction of the through hole 41 and the cut-off hole 42, the flow direction of liquid nitrogen inside the single-turn spiral guide jacket 3 is controlled. Thus, the spiral guide jacket 3 at the corresponding height is selectively opened or closed according to the height of the raw material liquid level inside the crystallizer 1, so that the liquid nitrogen only spirals upward in the crystallization area that needs to be cooled, avoiding the waste of cold source caused by the liquid nitrogen still ineffectively cooling the area above the liquid level when the raw material liquid level is low.

[0026] refer to Figure 4 and Figure 5 As shown, a nitrogen collecting pipe 5 is vertically fixed on the outside of the crystallization vessel 1. The nitrogen collecting pipe 5 is used to centrally discharge the intercepted liquid nitrogen to ensure the orderly flow of the refrigerant. The inside of the nitrogen collecting pipe 5 is hollow to form a discharge channel. The surface of the nitrogen collecting pipe 5 is uniformly provided with docking cylinders 51. The docking cylinders 51 are used to provide rotational installation space for the adjusting cylinders 4 at various height positions. The end of the adjusting cylinder 4 away from the isolation seat 32 is rotatably installed inside the docking cylinder 51 so that the adjusting cylinder 4 can maintain a stable docking relationship with the nitrogen collecting pipe 5 during rotation.

[0027] refer to Figures 4 to 6 As shown, the outer end face of the regulating cylinder 4 is provided with a first eccentric hole 45. The first eccentric hole 45 is used as a transition channel for liquid nitrogen to enter the nitrogen collecting pipe 5 from the regulating cylinder 4. An isolation plate 52 is provided on the inner side of the docking cylinder 51. The isolation plate 52 is used to divide the internal space of the nitrogen collecting pipe 5 and limit the flow path of liquid nitrogen. A second eccentric hole 53 is provided on the surface of the isolation plate 52. The second eccentric hole 53 is used to form a communication channel with the first eccentric hole 45. When the intercepting hole 42 is connected to the internal flow channel of the spiral guide jacket 3, the first eccentric hole 45 and the second eccentric hole 53 coincide, so as to realize the guidance and discharge of liquid nitrogen from the single-turn spiral guide jacket 3 to the nitrogen collecting pipe 5.

[0028] refer to Figure 4 and Figure 6As shown, a corrugated knob 43 is fixed on the outer surface of the adjusting cylinder 4. The corrugated knob 43 is used to provide a force-bearing part for manual rotation operation so as to switch the angle of the adjusting cylinder 4. The corrugated knob 43 is placed between the docking cylinder 51 and the isolation seat 32 to limit the axial position of the adjusting cylinder 4 and ensure the stability of the rotation operation.

[0029] refer to Figure 5 and Figure 6 As shown, an extension plate 54 is provided on one side of the docking cylinder 51. The extension plate 54 is used as the installation base of the positioning structure. A positioning bolt 6 passes through the surface of the extension plate 54. The positioning bolt 6 is used to limit and fix the angle position of the adjusting cylinder 4 under different working conditions.

[0030] refer to Figure 5 and Figure 6 As shown, the surface of the regulating cylinder 4 has two positioning holes 44, which are distributed at a 90-degree angle to correspond to the open state of the through hole 41 and the open state of the throttling hole 42, respectively. The end of the positioning bolt 6 is adapted to the internal size of the positioning hole 44 to achieve reliable positioning. The two positioning holes 44 correspond to the through hole 41 and the throttling hole 42, respectively, so as to ensure that the regulating cylinder 4 can be stably maintained under different liquid nitrogen flow direction control states.

[0031] refer to Figures 1 to 4 As shown, a stirring motor 2 is fixed at the top center of the sealed end cap 13. The stirring motor 2 is used to drive the raw material solution to generate uniform flow during the crystallization process, so as to avoid the local temperature difference from affecting the crystallization effect. A stirring rod 21 is set downward at the output end of the stirring motor 2. The stirring rod 21 is placed inside the crystallization vessel 1 to stir and mix the raw materials in the vessel, thereby cooperating with the external spiral guide jacket 3 to achieve uniform cooling and crystallization.

[0032] refer to Figure 1 and Figure 3 As shown, a base 11 is provided at the bottom of the crystallization vessel 1. The base 11 is used to support and fix the crystallization vessel 1 to ensure the overall stability of the device. The crystallization vessel 1 is connected to a discharge pipe 12. The discharge pipe 12 is used to discharge the crystallized product after crystallization. A control valve is installed inside the discharge pipe 12 to control the opening and closing of the discharge process. Example

[0033] See Figures 1 to 6As shown, in this embodiment, a rapid cooling crystallization device for nicotinamide nucleoside includes a crystallization vessel 1, which is made of 316L stainless steel and has a volume of 500L, used to hold the nicotinamide nucleoside crystallization mother liquor; a spiral guide jacket 3 is provided on the outer surface of the crystallization vessel 1, which is a double-layer stainless steel welded structure, forming a liquid nitrogen flow channel inside; a nitrogen inlet pipe 31 is provided at the bottom of the spiral guide jacket 3, which is made of low-temperature resistant stainless steel pipe with a nominal diameter of DN15, and is connected to a liquid nitrogen storage tank through a low-temperature valve; At the beginning of crystallization, liquid nitrogen enters the spiral guide jacket 3 through the nitrogen inlet pipe 31 and flows from bottom to top along the spiral structure of the jacket. Through the heat exchange between the jacket and the outer wall of the crystallization vessel 1, the temperature of the mother liquor inside the crystallization vessel 1 drops rapidly. At the same time, the stirring motor 2 fixed at the top center of the sealed end cover 13 drives the stirring rod 21 to rotate. The stirring motor 2 is a variable frequency motor with a rated power of 1.5kW, which keeps the mother liquor flowing evenly during the cooling process, thereby avoiding the influence of local temperature gradients on the crystallization process.

[0034] In the comparative case, a traditional integral cooling jacket crystallizer was used, with circulating ethylene glycol aqueous solution as the cooling medium, and the cooling rate was about 0.5℃ / min. In this embodiment, a liquid nitrogen spiral flow jacket structure was used, and the measured cooling rate could reach 2.5℃ / min, verifying the feasibility of the spiral flow jacket combined with liquid nitrogen cooling in rapid cooling crystallization. Example

[0035] See Figures 1 to 6 As shown, in this embodiment, each turn of the spiral guide jacket 3 is provided with an isolation seat 32. The isolation seat 32 is made of integral stainless steel and is arranged at equal intervals along the height direction of the crystallizer 1. An adjusting cylinder 4 is rotatably installed inside each isolation seat 32. The adjusting cylinder 4 adopts a stainless steel cylinder structure with a low-temperature resistant polytetrafluoroethylene lining to reduce rotational resistance and improve reliability under low-temperature conditions. When the liquid level of the nicotinamide nucleoside mother liquor in the crystallization vessel 1 is 60% of the height of the crystallization vessel 1, only the regulating cylinder 4 corresponding to the liquid level height range is opened to keep the spiral guide jacket 3 in the range in a continuous state; the regulating cylinder 4 located above the liquid level is closed by rotation, so that the corresponding single-turn spiral guide jacket 3 stops the upward flow of liquid nitrogen, so that the liquid nitrogen only acts on the actual crystallization area and avoids ineffective cooling of the area above the liquid level.

[0036] In the comparative case, without the isolation seat 32 and the regulating cylinder 4, liquid nitrogen always flows through the entire spiral guide jacket 3, increasing liquid nitrogen consumption by about 35% under low liquid level conditions. This embodiment effectively reduces liquid nitrogen consumption by adjusting the cooling height in stages, verifying the engineering feasibility of the staged cooling structure. Example

[0037] See Figures 4 to 6As shown, in this embodiment, the end of the surface of the regulating cylinder 4 is provided with a through hole 41 and a flow-stopping hole 42, and the through hole 41 and the flow-stopping hole 42 are distributed perpendicularly at 90 degrees. When the regulating cylinder 4 is rotated until the through hole 41 is aligned with the internal flow channel of the spiral guide jacket 3, the liquid nitrogen can continue to flow upward. When the regulating cylinder 4 is rotated until the flow-stopping hole 42 is connected with the internal flow channel of the spiral guide jacket 3, the liquid nitrogen is guided into the interior of the regulating cylinder 4. Liquid nitrogen then passes through the first eccentric hole 45 on the outer end face of the regulating cylinder 4, through the second eccentric hole 53 on the inner isolation plate 52 of the docking cylinder 51, and finally enters the nitrogen collection pipe 5 and is discharged from the system. The nitrogen collection pipe 5 adopts a DN25 stainless steel riser structure to ensure smooth discharge.

[0038] In the comparative case, the liquid nitrogen was directly retained in the jacket after being intercepted, which easily formed low-temperature liquid accumulation and affected the subsequent cooling stability. In this embodiment, the liquid nitrogen is guided to the nitrogen collection pipe 5 through the eccentric hole for centralized discharge. The liquid nitrogen flow path is clear, which verifies the reliability of the interception and discharge structure. Example

[0039] See Figures 4 to 6 As shown, in this embodiment, a corrugated knob 43 is fixedly provided on the outer surface of the adjusting cylinder 4. The corrugated knob 43 adopts a low-temperature resistant rubber-coated stainless steel frame structure, which is convenient for manual operation. An extension plate 54 is provided on one side of the docking cylinder 51. A positioning bolt 6 is provided through the surface of the extension plate 54. The positioning bolt 6 is an M8 stainless steel set bolt. The surface of the regulating cylinder 4 is provided with two positioning holes 44, which are distributed at a 90-degree angle and correspond to the opening positions of the through hole 41 and the throttling hole 42, respectively. The regulating cylinder 4 can be reliably locked in two working states by the cooperation of the positioning bolt 6 with the positioning hole 44.

[0040] In the comparison case, the positioning bolt 6 and positioning hole 44 were not provided, and the adjusting cylinder 4 was prone to angular displacement under the impact of liquid nitrogen flow; this embodiment ensures the stability of the adjustment state through a mechanical limiting structure, verifying the feasibility of the structural design. Example

[0041] See Figures 1 to 4 As shown, in this embodiment, a stirring motor 2 is fixed at the top center of the sealing end cap 13. The stirring motor 2 is an explosion-proof variable frequency motor. The output shaft is connected to the stirring rod 21. The stirring rod 21 adopts a multi-segment blade structure and is made of stainless steel. While liquid nitrogen cools the outer wall of the crystallizer 1 in stages through the spiral guide jacket 3, the stirring rod 21 continuously stirs the mother liquor inside the crystallizer 1, making the temperature distribution inside the vessel more uniform and avoiding local overcooling areas from affecting the crystal precipitation process, thus forming a synergistic effect with the adjustable height cooling structure.

[0042] In the comparison case, when the stirring motor 2 was not turned on, there was obvious temperature stratification in the crystallizing vessel 1; in this embodiment, a uniform crystallization environment was achieved by combining the stirring structure with external cooling, thus verifying the feasibility of this synergistic solution. Example

[0043] See Figures 1 to 6 As shown in this embodiment, in actual operation, a nicotinamide nucleoside rapid cooling crystallization device uses a crystallization vessel 1 as the core reaction container. The crystallization vessel 1 is fixedly installed on the ground foundation by a base 11. A sealing end cap 13 is installed on the top of the crystallization vessel 1 by a hinge. The sealing end cap 13 is in a closed state before operation to ensure the sealing of the inside of the crystallization vessel 1 during the crystallization process. Before crystallization begins, the nicotinamide nucleoside solution is added into the crystallization vessel 1 through the top or side feed port to form a stable raw material liquid level in the crystallization vessel 1. Then the control valve inside the discharge pipe 12 is closed to prevent the material from being discharged prematurely during the crystallization process. Start the stirring motor 2 fixed at the top center of the sealed end cover 13. The stirring motor 2 drives the stirring rod 21 to rotate inside the crystallization vessel 1 through the output shaft. The stirring rod 21 continuously stirs the nicotinamide nucleoside solution, so that the solution inside the crystallization vessel 1 forms a circulating flow in the axial and radial directions, thereby providing uniform heat transfer conditions for subsequent cooling and crystallization. After the stirring state stabilizes, liquid nitrogen is introduced into the spiral guide jacket 3 through the nitrogen inlet pipe 31. Under the action of gravity and nitrogen inlet pressure, the liquid nitrogen enters the bottom of the spiral guide jacket 3 and flows from bottom to top along the spiral flow channel formed by the spiral guide jacket 3. During the flow, the liquid nitrogen exchanges heat with the outer wall of the crystallization vessel 1, thereby rapidly cooling the solution inside the crystallization vessel 1. During the liquid nitrogen rise process, according to the raw material liquid level height inside the crystallizer 1, the regulating cylinder 4 within the corresponding liquid level height range is adjusted to the state where the through hole 41 is connected to the internal flow channel of the spiral guide jacket 3, so that the single-turn spiral guide jacket 3 within the corresponding height range is kept in the state of liquid nitrogen penetration, while the regulating cylinder 4 located above the liquid level is rotated to the state where the cut-off hole 42 is connected to the internal flow channel of the spiral guide jacket 3 by the corrugated knob 43. When the liquid nitrogen flows to the single-turn spiral guide jacket 3 at the interception height, the liquid nitrogen enters the regulating cylinder 4 through the interception hole 42, and then flows through the first eccentric hole 45 on the outer end face of the regulating cylinder 4 and the second eccentric hole 53 on the inner isolation plate 52 of the docking cylinder 51 in sequence, and finally flows into the nitrogen collecting pipe 5, and is discharged downward by the nitrogen collecting pipe 5, thereby preventing the liquid nitrogen from continuing to spiral upward to a higher position. After the regulating cylinder 4 completes the rotation adjustment, the regulating cylinder 4 is mechanically limited in the state of the through hole 41 or the cut-off hole 42 by the cooperation of the positioning bolt 6 and the corresponding positioning hole 44, so as to prevent the regulating cylinder 4 from shifting at an angle under the impact of liquid nitrogen flow and to ensure the stability of liquid nitrogen flow direction control. Throughout the cooling and crystallization process, the spiral guide jacket 3 only participates in heat exchange within the range corresponding to the raw material liquid level. Liquid nitrogen is no longer introduced into the spiral guide jacket 3 above the liquid level, so that the cooling capacity of liquid nitrogen is concentrated on the actual crystallization area, avoiding ineffective cooling. Once the solution temperature inside the crystallization vessel 1 reaches the set crystallization temperature and crystal precipitation is completed, the supply of liquid nitrogen to the nitrogen inlet pipe 31 is stopped. After the residual liquid nitrogen in the spiral guide jacket 3 is discharged, the stirring motor 2 is turned off, the control valve inside the discharge pipe 12 is opened, and the crystallized product is discharged from the bottom of the crystallization vessel 1, thus completing a complete rapid cooling crystallization process of nicotinamide nucleoside.

[0044] The working principle of this invention is as follows: the raw material is placed inside the crystallization kettle 1 and the control valve of the discharge pipe 12 is closed. The stirring motor 2 is started to control the stirring rod 21 to rotate. Liquid nitrogen is delivered into the spiral guide jacket 3 through the nitrogen inlet pipe 31 at the bottom. The liquid nitrogen will gradually rise with the spiral guide jacket 3 to cool the spiral guide jacket 3, thereby enabling the crystallization reaction to take place inside the crystallization kettle 1. Adjust the liquid nitrogen coverage area according to the height of the raw material liquid level inside the crystallizer 1. When the through hole 41 is horizontally connected to the flow channel of the spiral guide jacket 3, the first eccentric hole 45 and the second eccentric hole 53 are misaligned. At this time, the inside of the single-turn spiral guide jacket 3 is in a through state, and liquid nitrogen can flow through and spiral upward. The cooperation between the positioning bolt 6 and the positioning hole 44 can ensure the stability of the flow of the single-turn spiral guide jacket 3. Close the adjusting cylinder 4 at the appropriate position according to the height of the internal liquid level. At this time, the adjusting cylinder 4 can be adjusted by the corrugated knob 43. The control causes the regulating cylinder 4 to rotate 90 degrees, and the intercepting hole 42 is connected to the inflow direction side of the single-turn nitrogen inlet pipe 31. The through hole 41 is in a vertical state to maintain a seal. At this time, the first eccentric hole 45 and the second eccentric hole 53 coincide. The liquid nitrogen inside this turn of the nitrogen inlet pipe 31 will enter the regulating cylinder 4 through the intercepting hole 42, and then enter the nitrogen collecting pipe 5 through the first eccentric hole 45 and the second eccentric hole 53 in sequence to achieve discharge. The regulating cylinder 4 above the liquid level is completely closed so that the liquid nitrogen cannot continue to move upward. This structure allows for adjustment of the height of the liquid nitrogen spiral as it rises, based on the height of the liquid level inside the crystallizer 1. This prevents the liquid nitrogen from still needing to cool the entire device when there is a small amount of raw material, thus avoiding a waste of the cold source.

[0045] The above description is merely a preferred embodiment of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention. Structures, devices, and operating methods not specifically described or explained in this invention are implemented according to conventional methods in the art unless otherwise specified or limited.

Claims

1. A rapid cooling crystallization apparatus for nicotinamide nucleoside, comprising a crystallization vessel (1), characterized in that: The crystallizer (1) has a hollow interior with a sealed end cap (13) hinged to the top. The crystallizer (1) has a spiral flow guide jacket (3) on its outer surface and a nitrogen inlet pipe (31) at the bottom of the spiral flow guide jacket (3). Each turn of the spiral guide jacket (3) is provided with an isolation seat (32), and multiple isolation seats (32) are on the same vertical line. An adjusting cylinder (4) is rotatably installed inside the isolation seat (32). The adjusting cylinder (4) extends beyond the end of the isolation seat (32). The adjusting cylinder (4) is hollow inside. Through holes (41) are symmetrically opened on the surface end of the adjusting cylinder (4). A flow-blocking hole (42) is opened on the surface end of the adjusting cylinder (4). The flow-blocking hole (42) and the through hole (41) are vertically distributed. The direction of liquid nitrogen inside the single-turn spiral guide jacket (3) is controlled by controlling the direction of the through hole (41) and the cut-off hole (42).

2. The nicotinamide nucleoside rapid cooling crystallization device according to claim 1, characterized in that: A nitrogen collecting tube (5) is vertically fixed on the outside of the crystallization vessel (1). The nitrogen collecting tube (5) is hollow inside. A docking cylinder (51) is evenly arranged on the surface of the nitrogen collecting tube (5). The end of the adjusting cylinder (4) that is away from the isolation seat (32) is rotated inside the docking cylinder (51).

3. The nicotinamide nucleoside rapid cooling crystallization device according to claim 2, characterized in that: The outer end face of the regulating cylinder (4) is provided with a first eccentric hole (45), the inner side of the docking cylinder (51) is provided with an isolation plate (52), the surface of the isolation plate (52) is provided with a second eccentric hole (53), and the first eccentric hole (45) and the second eccentric hole (53) coincide when the flow interception hole (42) is connected to the internal flow channel of the spiral guide jacket (3).

4. The nicotinamide nucleoside rapid cooling crystallization device according to claim 2, characterized in that: A corrugated knob (43) is fixed on the outer surface of the adjusting cylinder (4), and the corrugated knob (43) is placed between the docking cylinder (51) and the isolation seat (32).

5. The nicotinamide nucleoside rapid cooling crystallization device according to claim 2, characterized in that: An extension plate (54) is provided on one side of the docking cylinder (51), and a positioning bolt (6) passes through the surface of the extension plate (54).

6. The nicotinamide nucleoside rapid cooling crystallization device according to claim 5, characterized in that: The regulating cylinder (4) has two positioning holes (44) on its surface. The two positioning holes (44) are distributed at a 90-degree angle. The end of the positioning bolt (6) is adapted to the internal size of the positioning hole (44). The two positioning holes (44) correspond to the through hole (41) and the intercepting hole (42) respectively.

7. The nicotinamide nucleoside rapid cooling crystallization device according to claim 1, characterized in that: The sealing end cap (13) is fixed with a stirring motor (2) at the top center. The stirring motor (2) has a stirring rod (21) at the output end facing downwards. The stirring rod (21) is placed inside the crystallization vessel (1).

8. The nicotinamide nucleoside rapid cooling crystallization device according to claim 1, characterized in that: The crystallization vessel (1) is provided with a base (11) at the bottom, and the crystallization vessel (1) is connected to a discharge pipe (12), with a control valve installed inside the discharge pipe (12).

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