Device and method for preparing hydrocortisone sodium succinate

Abstract

The invention provides a hydrocortisone sodium succinate preparation device and method.The device comprises a shell, a heat insulation plate is horizontally arranged in the middle of the shell and divides the shell into a first cavity and a second cavity, and a reaction assembly and a crystallization assembly are arranged in the first cavity and the second cavity respectively; the reaction assembly mixes and reacts the raw materials in the first chamber, and the control device controls the processes of the reaction assembly and the crystallization assembly and controls the crystallization assembly to adjust the granularity of the crystallization process in real time based on environmental data so as to adjust the crystallization degree in real time. Accurate control of the reaction conditions of the reaction assembly is optimized through the control device so as to improve the reaction efficiency, meanwhile, the crystallization assembly is controlled to dry and crystallize the reacted feed liquid so as to improve the product selectivity, and the granularity in the crystallization process is adjusted in real time based on environmental data, so that the product purity is improved. The crystallization degree in the crystallization process is adjusted in real time, so that the crystallization degree is prevented from being influenced.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical processing, and in particular to a device and method for preparing hydrocortisone sodium succinate. Background Art

[0002] Hydrocortisone sodium succinate is a salt compound of hydrocortisone, which has multiple pharmacological effects such as anti-inflammatory, anti-allergic and immunosuppressive. As a drug intermediate, the purity and quality stability of the product are crucial to the final drug quality during production and preparation. It is necessary to optimize the precise control of the reaction conditions to improve the reaction efficiency and product selectivity. At the same time, in the formation of material particles, it is necessary to strictly control the mixing process and the uniformity after mixing to avoid affecting the degree of crystallization when the environmental conditions change. Therefore, the present invention studies and designs a device and method for preparing hydrocortisone sodium succinate. Summary of the invention

[0003] Therefore, the technical problem to be solved by the present invention is to overcome the above-mentioned defects, thereby providing a device and method for preparing hydrocortisone sodium succinate.

[0004] In order to solve the above problems, the present invention provides a hydrocortisone sodium succinate preparation device, which comprises:

[0005] A shell, wherein a heat insulation board is horizontally arranged in the middle of the shell, and the heat insulation board divides the shell into a first chamber and a second chamber, and a reaction component and a crystallization component are respectively arranged in the first chamber and the second chamber, and the reaction component mixes and reacts the raw materials in the first chamber, and the crystallization component crystallizes the liquid from the first chamber to the second chamber and then discharges it from the shell;

[0006] A drying and conveying device is disposed below the shell to further dry and convey the crystals discharged from the shell after crystallization;

[0007] A screening device, connected to the drying and conveying device, for screening the dried crystals to obtain hydrocortisone sodium succinate;

[0008] The control device controls the progress of the reaction component and the crystallization component, and controls the crystallization component to adjust the particle size of the crystallization process in real time based on environmental data, so as to adjust the degree of crystallization in real time.

[0009] Preferably, the reaction component comprises a first feeding port and a second feeding port, the first feeding port and the second feeding port are respectively arranged at the top of the shell, the first feeding port and the second feeding port are respectively provided with a first feeding port cover and a second feeding port cover, a first motor is arranged at the center of the top of the shell, the first motor is connected to the control device, the first motor is connected to a stirring rod, one end of the stirring rod is connected to the output shaft of the first motor, the other end of the stirring rod rotatably penetrates the top of the shell and extends into the shell, a plurality of groups of stirring blades are arranged on the stirring rod, the lengths of the stirring blades of two adjacent groups are different, and the lengths of the stirring blades of the two separated groups are the same;

[0010] A liquid adding pipe is arranged on the side wall of the shell near the top of the heat insulation board, one end of the liquid adding pipe extends into the shell, a flow regulating valve is arranged on the liquid adding pipe, and the flow regulating valve is connected to the control device;

[0011] The first chamber is provided with a first connecting pipe, one end of the first connecting pipe passes through the shell side wall of the first chamber, and the other end of the first connecting pipe extends into the crystallization assembly;

[0012] The outer wall of the shell outside the first chamber is provided with a jacket, and the jacket is respectively provided with a liquid injection port and a liquid discharge port.

[0013] Preferably, the first connecting pipe is also connected to a second connecting pipe, the second connecting pipe passes through the side wall of the shell and extends into the first chamber, the second connecting pipe is provided with a first electric valve and a first lifting pump, and the first connecting pipe located outside the first chamber is provided with a second electric valve, and the first electric valve, the second electric valve and the first lifting pump are respectively connected to the control device.

[0014] Preferably, the crystallization assembly includes an interlayer, which is arranged on the top of the second chamber, the outer side of the interlayer is connected to the inner wall of the first chamber, an arc-shaped groove is arranged at the center of one side of the interlayer away from the heat insulation board, a first connecting pipe and a second connecting pipe are arranged on the side wall of the interlayer, the first connecting pipe and the second connecting pipe both pass through the interlayer and the shell to the outside of the shell, a discharge port is arranged at the center of the bottom of the shell, a discharge bin is arranged at the discharge port, and the outlet of the discharge bin is connected to the drying and conveying device;

[0015] A partition is provided above the discharge port, a gap is provided between the partition and the inner wall of the shell, a plurality of support rods are provided in the shell at the discharge port, the two ends of the support rods are respectively connected to the bottom of the partition and the bottom of the shell, and an L-shaped protective tube is provided between the center of the partition and the side wall of the discharge bin;

[0016] The partition is provided with an annular plate, a rotary drum is provided above the annular plate, the rotary drum is rotatably connected to the inner side of the annular plate, an arc block is provided on the rotary drum, and the center of the arc block is provided at an eccentric position of the rotary drum;

[0017] The rotary cylinder and the arc block are respectively provided with a first cavity and a second cavity, the first cavity and the second cavity are connected, the first connecting pipe is rotatably passed through the partition from the L-shaped protective tube and then extends into the first cavity, and a third annular edge is provided at one end of the first connecting pipe located in the first cavity, the third annular edge abuts against the bottom of the first cavity and is rotatably connected to the bottom of the first cavity;

[0018] The side wall of the arc block is evenly provided with a plurality of slide bars with the center of the arc block as the center of the circle, and the surface of the arc block between two adjacent slide bars and the top of the arc block are evenly provided with injection ports, and an arc scraper is also provided in the arc groove, one end of the arc scraper is located at the center of the arc groove, and the other end of the arc scraper extends along the arc groove toward the side wall of the shell, and the arc scraper is connected to the rotary drum;

[0019] The side wall of the shell below the heat insulation board is also provided with an exhaust pipe, and the exhaust pipe is provided with a third electric valve, and the third electric valve is connected to the control device;

[0020] Pressure sensors are respectively disposed in the first cavity and the second cavity, a humidity sensor is disposed on the inner wall of the second cavity below the first groove, and the pressure sensor and the humidity sensor are respectively connected to the processor.

[0021] Preferably, a first conical groove is provided at one end of the injection port close to the second cavity, and a second conical groove is provided at the other end of the injection port, the ends with smaller cross-sections of the first conical groove and the second conical groove are close to each other, and a central tube is connected between the first conical groove and the second conical groove, the central tube connects the first conical groove and the second conical groove, and an electromagnetic valve is also provided in the middle of the central tube, and the electromagnetic valve is connected to the control device.

[0022] Preferably, a protection box is provided inside the annular plate, a second motor is provided inside the protection box, the second motor is connected to a rotating shaft, one end of the rotating shaft is connected to the output shaft of the second motor, the other end of the rotating shaft rotatably passes through the top of the protection box and extends to the rotary cylinder, and the second motor is connected to the control device;

[0023] The annular plate is provided with a rotation groove adapted to the rotary drum, the rotary drum is rotatably connected to the annular plate through the rotation groove, the bottom of the rotary drum is provided with an assembly groove, the inner side of the assembly groove is provided with a gear ring, the inner side of the gear ring is meshed with a first gear, and the rotating shaft is connected to the center of the first gear;

[0024] A rotating bearing is arranged at the center of the assembly groove, and the first connecting pipe is connected to the rotating bearing;

[0025] The top of the rotor is provided with an annular support whose center is located at an eccentric position of the rotor, and the annular support connects the rotor and the arc block;

[0026] A third connecting tube is provided between the first cavity and the second cavity, one end of the third connecting tube penetrates into the first cavity and is provided with a first annular edge, the first annular edge is connected to the bottom of the first cavity, the other end of the third connecting tube penetrates into the second cavity and is provided with a second annular edge, the second annular edge is connected to the top of the second cavity;

[0027] The shape of the top and side wall of the arc-shaped block is the same as the shape of the arc-shaped groove.

[0028] Preferably, the first connecting pipe is also connected to a fourth connecting pipe, the fourth connecting pipe is externally connected to a pressurizing machine, a pressure regulating valve is arranged on the fourth connecting pipe, a fifth electric valve is arranged at one end of the first connecting pipe close to the fourth connecting pipe, a second lifting pump and a sixth electric valve are arranged between the second connecting pipe and the fourth connecting pipe, and the pressure regulating valve, the fifth electric valve, the sixth electric valve and the second lifting pump are respectively connected to the control device.

[0029] Preferably, a first connecting rod is connected between one end of the arc-shaped scraper and the rotary drum, and a second connecting rod is connected between the other end of the arc-shaped scraper and the top of the arc-shaped block;

[0030] An L-shaped connecting rod is also connected to the outer side of the rotary drum, and the L-shaped connecting rod extends toward the partition. A shovel plate is arranged on the partition, and the L-shaped connecting rod is connected to the shovel plate.

[0031] Preferably, a bell mouth is also provided under the partition, and the bell mouth is sleeved outside the L-shaped protective tube, and the end with a larger cross-section of the bell mouth is provided with a gap between the partition, and the other end of the bell mouth is connected to a blast pipe, one end of the blast pipe is connected to the bell mouth, and the other end of the blast pipe passes through the discharge bin and is connected to an external blast dryer.

[0032] The present invention also provides a method for preparing hydrocortisone sodium succinate, comprising the hydrocortisone sodium succinate preparation device described in any of the preceding items, comprising the following steps:

[0033] S1: adding hydrocortisone succinate monoester through the first feeding port, adding purified water through the second feeding port to dissolve it, passing hot water at 65°C to 75°C into the jacket to heat the first chamber, reacting for 60 minutes, adding an alkaline regulator through the liquid adding tube, adjusting the pH of the liquid in the first chamber to 8-12, and then adding acetone into the shell at 2 ml / min through the liquid adding tube. After 45 minutes, adjusting the temperature in the jacket to 25°C to 35°C and keeping it warm for 1.5 hours;

[0034] S2: nitrogen is introduced into the first connecting pipe through the fourth connecting pipe, the liquid in the first connecting pipe enters the first cavity, a pressure difference is formed between the second cavity and the first cavity, the liquid in the second cavity forms a blowout effect, and the liquid in the second cavity is sprayed out through the injection port. When the opening of the injection ports of different groups is controlled, the liquid sprayed out of the opened injection ports forms a spray layer of corresponding thickness in the arc-shaped groove in coordination with the rotation of the rotary drum. Based on the real-time adjustment of the pressure difference between the second cavity and the first cavity and the opening state of the corresponding group of injection ports, the injection layer is sprayed out of the second cavity. The layer is adjusted in real time, and crystallizes to form crystals of corresponding particle size under drying at 80°C to 100°C in the interlayer, and flows downward through the gap between the partition 24 and the shell 1 to the bottom of the shell 1 after sliding through the scraper. At the same time, the external blower dryer blows air to the bottom of the partition 24 through the blower pipe 64, and further dries the second chamber along the bottom of the partition 24, accelerating the drying of the spray layer. The gas in the second chamber is discharged through the exhaust pipe 33, and the crystallized and dried hydrocortisone sodium succinate finally flows to the drying conveying device 66;

[0035] S3: The drying and conveying device further dries and conveys the crystals discharged from the shell, and then screens them through a screening device to obtain hydrocortisone sodium succinate.

[0036] The hydrocortisone sodium succinate preparation device and method provided by the present invention have the following beneficial effects:

[0037] 1. The present invention optimizes the precise control of the reaction conditions of the reaction component by the control device to improve the reaction efficiency. At the same time, the reaction liquid is dried and crystallized by controlling the crystallization component to improve the product selectivity. The particle size of the crystallization process is adjusted in real time based on environmental data, and the degree of crystallization in the crystallization process is adjusted in real time to avoid affecting the degree of crystallization.

[0038] 2. The present invention also groups each group of injection ports between each two slide bars. When one group, two groups, or all of them are working, different modes of injection groups are formed in a single or combined state. The thickness of the injection layer corresponding to each injection group is different. When the environment in the second chamber is different, the dryness of the injection layer is also different. The injection range of the liquid sprayed from the injection port to the arc groove is different, so that the particle size of the crystals formed after crystallization is also different.

[0039] 3. The present invention also controls the pressure in the fourth connecting pipe by controlling the pressure regulating valve through the control device, so as to change the pressure difference between the first cavity and the second cavity. When the slurry is ejected through the injection port, its injection rate is changed and its injection pressure is also different. The humidity sensor signal in the second cavity is obtained by the humidity sensor, and the processor solves it to obtain its corresponding humidity data. The sensor signal is obtained in real time based on the humidity sensor in the second chamber, and the processor solves it to obtain the humidity data in the second chamber. Based on the humidity data, the crystal evaluation model is used to obtain the real-time particle size status, and then the real-time obtained particle size status is fed back. Based on this, the pressure difference between the first cavity and the second cavity is adjusted to achieve the purpose of real-time adjustment. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 It is a schematic diagram of the general assembly structure of the present invention;

[0041] Figure 2 For the present invention Figure 1 A schematic diagram of the structure enlargement in the middle;

[0042] Figure 3 For the present invention Figure 1 A magnified schematic diagram of the structure at B in the middle;

[0043] Figure 4 It is a schematic diagram of the installation of the solenoid valve structure of the present invention;

[0044] Figure 5 It is a schematic diagram of the installation of the slide structure of the present invention.

[0045] The reference numerals are:

[0046] 1. Shell; 2. Heat insulation board; 3. First feeding port; 4. Second feeding port; 5. First motor; 6. Stirring rod; 7. Stirring blade; 8. Liquid adding pipe; 9. Flow regulating valve; 10. Second connecting pipe; 11. Jacket; 12. Liquid injection port; 13. Liquid discharge port; 14. First connecting pipe; 15. Second electric valve; 16. First lifting pump; 17. First electric valve; 18. Interlayer; 19. Arc groove; 20. First connecting pipe; 21. Second connecting pipe; 22. Discharge port; 23. Discharge bin; 24. Partition; 25. Support rod; 26. L-shaped protective pipe; 27. Annular plate; 28. Rotor; 29. ​​Arc block; 30. First cavity; 31. Second cavity; 32. Injection port; 33. Exhaust pipe; 34. Arc scraper; 35 , the third electric valve; 36, the protective box; 37, the second motor; 38, the rotating shaft; 39, the rotating groove; 40, the assembly groove; 41, the gear ring; 42, the first gear; 43, the rotating bearing; 44, the annular support; 45, the first annular edge; 46, the second annular edge; 47, the third annular edge; 50, the third connecting pipe; 51, the fourth connecting pipe; 52, the pressure regulating valve; 53, the fifth electric valve; 54, the second lifting pump; 55, the sixth electric valve; 56, the first connecting rod; 57, the second connecting rod; 59, the L-shaped connecting rod; 60, the shovel plate; 61, the slide; 63, the bell mouth; 64, the blast pipe; 66, the drying and conveying device; 321, the first conical groove; 322, the second conical groove; 323, the middle pipe; 324, the solenoid valve. DETAILED DESCRIPTION

[0047] like Figure 1-5 As shown, the present invention provides a hydrocortisone sodium succinate preparation device, which comprises:

[0048] Shell 1, a heat insulation board 2 is horizontally arranged in the middle of the shell 1, the heat insulation board 2 divides the shell 1 into a first chamber and a second chamber, the first chamber and the second chamber are respectively provided with a reaction component and a crystallization component, the reaction component mixes and reacts the raw materials in the first chamber, the crystallization component crystallizes the liquid from the first chamber to the second chamber and then discharges it from the shell 1; a drying and conveying device 66 is arranged below the shell 1, and further dries and conveys the crystals discharged from the shell 1 after crystallization; a screening device is connected to the drying and conveying device 66, and screens the dried crystals to obtain hydrocortisone sodium succinate; a control device controls the progress of the reaction component and the crystallization component. Figure 1-5As shown, a preparation device of hydrocortisone sodium succinate comprises a shell 1, and a heat insulation board 2 horizontally arranged in the middle of the shell 1 divides the shell 1 into a first chamber and a second chamber, wherein the heat insulation board 2 avoids the interference of heat in the first chamber and the second chamber, and a reaction component and a crystallization component are respectively arranged in the first chamber and the second chamber, and the reaction component mixes the raw materials in the first chamber and provides reaction conditions for the reaction at the same time, so that after the reaction, the raw materials are crystallized in the second chamber by the crystallization component and then discharged to the shell 1, and then further dried by the drying and conveying device 66 and conveyed to the screening device, and the screening device screens the dried crystals to obtain the product hydrocortisone sodium succinate, wherein the control device is in the reaction component, and optimizes the precise control of the reaction conditions to improve the reaction efficiency, and at the same time, the reacted feed liquid is dried and crystallized by controlling the crystallization component to improve the product selectivity, and the particle size of the crystallization process is adjusted in real time based on the environmental data, and the crystallization degree in the crystallization process is adjusted in real time to avoid affecting the degree of crystallization.

[0049] In some embodiments, the reaction component includes a first feeding port 3 and a second feeding port 4, the first feeding port 3 and the second feeding port 4 are respectively arranged on the top of the shell 1, the first feeding port 3 and the second feeding port 4 are respectively provided with a first feeding port cover and a second feeding port cover, a first motor 5 is arranged at the center of the top of the shell 1, the first motor 5 is connected to the control device, the first motor 5 is connected to a stirring rod 6, one end of the stirring rod 6 is connected to the output shaft of the first motor 5, the other end of the stirring rod 6 rotatably passes through the top of the shell 1 and extends into the shell 1, the stirring rod 6 is provided with a plurality of groups of stirring blades 7, two adjacent The lengths of the stirring blades 7 of the two groups are different, and the lengths of the stirring blades 7 of the two separated groups are the same; a liquid adding pipe 8 is provided on the side wall of the shell 1 near the top of the insulation board 2, one end of the liquid adding pipe 8 extends into the shell 1, and a flow regulating valve 9 is provided on the liquid adding pipe 8, and the flow regulating valve 9 is connected to the control device; the first chamber is provided with a first connecting pipe 14, one end of the first connecting pipe 14 passes through the side wall of the shell 1 of the first chamber, and the other end of the first connecting pipe 14 extends into the crystallization assembly; a jacket 11 is provided on the outer wall of the shell 1 outside the first chamber, and the jacket 11 is respectively provided with a liquid injection port 12 and a liquid discharge port 13. Figure 1-5As shown, the first feeding port 3 of the reaction component is used to add hydrocortisone succinate, and the second feeding port 4 is used to add purified water, wherein the first feeding port 3 and the second feeding port 4 can be screwed or clamped with the first feeding port cover and the second feeding port cover, and the liquid adding pipe 8 is used to add an alkaline regulator and acetone to the first chamber respectively, wherein the alkaline regulator is used to adjust the pH value of the feed liquid in the first chamber, and the flow regulating valve 9 arranged on the liquid adding pipe 8 can control the amount and rate of adding the alkaline regulator and acetone to the first chamber through a control device to adapt to the progress of the reaction.

[0050] Specifically, the first motor 5 is commercially available, and the state parameters of the first motor 5 can be controlled by a control device, so that the stirring blades 7 on the stirring rod 6 can rotate at different rates, so that corresponding adjustments can be made according to the reaction needs, wherein the first motor 5 and the stirring rod 6 can be connected by a coupling; wherein the lengths of two adjacent groups of stirring blades 7 are different, and the lengths of the two separated groups of stirring blades 7 are the same, so that different stirring areas are formed between the continuous multiple groups of stirring blades 7, and another group of stirring blades 7 with different lengths sandwiched between the two stirring blades 7 with the same length cooperate to form step stirring, and the stirring blades 7 have different forces on the slurry in the first chamber in the nearby space, so that the slurry in the first chamber is stepped under the step stirring, and then the slurry in the first chamber surges, so that the slurry in the first chamber is mixed more fully, which can improve the efficiency of the slurry reaction in the first chamber, and further improve the control of the reaction process.

[0051] Specifically, the first chamber is provided with a first connecting pipe 14, so that the reacted liquid can be passed into the crystallization component for crystallization through the first connecting pipe 14, and the outer wall of the shell 1 arranged outside the reaction component is provided with a jacket 11, and the jacket 11 is used to pass hot water at 65°C to 75°C to provide conditions for the reaction in the first chamber, and the injection port 12 and the discharge port 13 of the jacket 11 are respectively used to add hot water to the jacket 11 and discharge hot water.

[0052] In some embodiments, the first connecting pipe 14 is further connected to a second connecting pipe 10, the second connecting pipe 10 penetrates the side wall of the housing 1 and extends into the first chamber, the second connecting pipe 10 is provided with a first electric valve 17 and a first lift pump 16, the first connecting pipe 14 outside the first chamber is provided with a second electric valve 15, the first electric valve 17, the second electric valve 15 and the first lift pump 16 are respectively connected to the control device. Figure 1-5As shown, the first connecting pipe 14 is below the second connecting pipe 10 relative to the first chamber. In this way, the second electric valve 15 and the first electric valve 17 are opened by the control device, so that the first connecting pipe 14 can extract the liquid in the lower layer of the first chamber out of the first chamber, and the first lifting pump 16 can be controlled to assist the liquid to be returned to the top of the first chamber through the second connecting pipe 10 for re-mixing. The advantage of this is that the liquid in the first chamber forms a layered surge, and the upper and lower liquids are fully mixed, which can further improve the efficiency of the liquid reaction in the first chamber.

[0053] In some embodiments, the crystallization assembly includes an interlayer 18, which is arranged at the top of the second chamber, the outer side of the interlayer 18 is connected to the inner wall of the first chamber, an arc-shaped groove 19 is arranged at the center of the side of the interlayer 18 away from the insulation board 2, and the side wall of the interlayer 18 is provided with a first connecting pipe 20 and a second connecting pipe 21, the first connecting pipe 20 and the second connecting pipe 21 both penetrate the interlayer 18 and the shell 1 to the outside of the shell 1, a discharge port 22 is arranged at the center of the bottom of the shell 1, a discharge bin 23 is arranged at the discharge port 22, and the outlet of the discharge bin 23 is connected to the drying conveying device 66; the discharge port 22 is arranged above A partition 24 is provided, and a gap is set between the partition 24 and the inner wall of the shell 1. A plurality of support rods 25 are provided in the shell 1 at the discharge port 22, and the two ends of the support rods 25 are respectively connected to the bottom of the partition 24 and the bottom of the shell 1, and an L-shaped protective tube 26 is provided between the center of the partition 24 and the side wall of the discharge bin 23; an annular plate 27 is provided on the partition 24, and a rotary drum 28 is provided above the annular plate 27, and the rotary drum 28 is rotatably connected to the inner side of the annular plate 27, and an arc block 29 is provided on the rotary drum 28, and the center of the arc block 29 is set at the eccentric position of the rotary drum 28; the rotary drum 28 and the arc block 29 are respectively provided with The first cavity 30 and the second cavity 31 are connected, the first cavity 30 and the second cavity 31 are connected, the first connecting pipe 14 rotates from the L-shaped protective tube 26 to penetrate the partition 24 and then extends into the first cavity 30, and the first connecting pipe 14 is provided with a third annular edge 47 at one end located in the first cavity 30, and the third annular edge 47 abuts against the bottom of the first cavity 30 and is rotatably connected to the bottom of the first cavity 30; the side wall of the arc block 29 is evenly provided with a plurality of sliding strips with the center of the arc block 29 as the center of the circle, and the surface of the arc block 29 between two adjacent sliding strips and the top of the arc block 29 are evenly provided with a plurality of injection ports 32, the An arc-shaped scraper 34 is also provided in the arc-shaped groove 19, one end of the arc-shaped scraper 34 is located at the center of the arc-shaped groove 19, and the other end of the arc-shaped scraper 34 extends along the arc-shaped groove 19 to the side wall of the shell 1, and the arc-shaped scraper 34 is connected to the rotary drum 28; an exhaust pipe 33 is also provided on the side wall of the shell 1 below the heat insulation board 2, and a third electric valve 35 is provided on the exhaust pipe 33, and the third electric valve 35 is connected to the control device; pressure sensors are respectively provided in the first cavity and the second cavity, and a humidity sensor is provided on the inner wall of the second chamber below the first groove, and the pressure sensor and the humidity sensor are respectively connected to the processor. Figure 1-5As shown, a discharge port 22 is arranged at the center of the bottom of the shell 1, and a discharge bin 23 is arranged at the discharge port 22. The outlet of the discharge bin 23 is connected to the drying and conveying device 66. A partition 24 is arranged above the discharge port 22. A gap is arranged between the outer side of the partition 24 and the inner wall of the shell 1, so that the crystallized liquid can slide toward the discharge port 22 through the gap. The partition 24 is connected above the discharge port 22 through a plurality of support rods 25. An L-shaped protective tube 26 is arranged at the center of the partition 24 and the side wall of the discharge bin 23. One end of the L-shaped protective tube 26 is connected to the side wall of the discharge bin 23, and the other end is vertically connected to the discharge bin 23. The center of the partition 24 is connected to the top of the partition 24 and the L-shaped protective tube 26, and an annular plate 27 is arranged on the partition 24, and a rotary cylinder 28 is arranged above the annular plate 27. The rotary cylinder 28 is rotatably connected to the inner side of the annular plate 27. When the rotary cylinder 28 rotates relative to the annular plate 27, its arc block 29 also rotates with the rotary cylinder 28, so that a local point on the arc block 29 makes an eccentric motion relative to the annular edge, and during the rotation of the arc block 29, the distance between the arc block 29 and the inner wall of the shell 1 is also dynamically changing, and the distance gradually increases, then decreases, and then increases.

[0054] Specifically, an interlayer 18 is arranged on the top of the second chamber above the arc block 29, and the outer side of the interlayer 18 is connected to the inner wall of the first chamber, and an arc groove 19 is arranged at the center of one side of the interlayer 18 away from the insulation board 2. The shape of the arc groove 19 can be arranged corresponding to the arc block 29. 80°C to 100°C hot water can be added to the interlayer 18 through the first connecting pipe 20 and the second connecting pipe 21, so that the material liquid sprayed into the arc groove 19 can be crystallized, and the environment in the second chamber can be dried at the same time, so that the water vapor mixed with the spray from the injection port can be dried, and the water temperature in the interlayer can be adjusted according to the environment in the second chamber.

[0055] Specifically, the first connecting pipe 14 penetrates the side wall of the discharge bin 23 and enters the L-shaped protective tube 26, and passes along the L-shaped protective tube 26 to the top of the partition 24 at the other end of the L-shaped protective tube 26, and then the first connecting pipe 14 penetrates the rotary drum 28 to the first cavity 30, and delivers the reacted liquid in the first cavity into the first cavity 30, wherein the first connecting pipe 14 is provided with a third annular edge 47 at one end located in the first cavity 30, and the third annular edge 47 abuts the bottom of the first cavity 30 and is rotatably connected to the bottom of the first cavity 30, so that when the rotary drum 28 rotates, it does not affect the addition of liquid into the first cavity 30.

[0056] Specifically, a plurality of slide bars are arranged on the side wall of the arc block 29, and a plurality of injection ports 32 are arranged between two adjacent slide bars, and the orientation of these injection ports 32 is the arc groove 19. When the injection port 32 ejects the liquid in the second cavity 31, it acts on the area corresponding to the injection port 32. The arc scraper 34 is connected to the center of the arc groove 19 and the rotary drum 28. The arc scraper 34 can be arranged at the shortest distance between the arc block 29 and the inner wall of the shell 1 relative to the arc block 29. In this way, the arc block 29 rotates one circle relative to the partition 24. When it rotates one circle, the injection layer at the relative position in the arc groove 19 is scraped off, so that it falls downward and falls toward the partition 24 between the slide bars on the side wall of the arc block 29. An exhaust pipe 33 is arranged on the side wall of the shell 1 below the heat insulation board 2, so that the gas in the second chamber is continuously circulated. After the injection port 32 is ejected, the gas can be discharged from the exhaust pipe 33. At this time, it is only necessary for the control device to control the third electric valve 35 to open.

[0057] Specifically, the pressure sensor disposed in the first cavity and the second cavity and the humidity sensor disposed on the inner wall of the second cavity under the first groove are both commercially available. The pressure sensor acquires the pressure sensing signals in the first cavity and the second cavity in real time, and the processor solves the pressure sensing signals to obtain the corresponding pressure signals in the first cavity and the second cavity. When a pressure difference is formed between the first cavity and the second cavity, the pressure causes the liquid in the first cavity to flow to the second cavity and be ejected through the set ejection port. The pressure regulating valve is controlled by the control device to adjust the pressure in the fourth connecting pipe, so as to change the pressure difference between the first cavity and the second cavity. When the liquid is ejected through the ejection port, its ejection rate is changed and its ejection pressure is also different. The humidity sensing signal in the second cavity is acquired by the humidity sensor, and the processor solves the humidity signal to obtain the corresponding humidity data. Based on the humidity sensor in the second cavity, the sensing signal is acquired in real time, and the processor solves the humidity signal to obtain the humidity data in the second cavity. Based on the humidity data, the crystal evaluation model is used to obtain the real-time particle size state, and then the real-time particle size state feedback is obtained. Based on this, the pressure difference between the first cavity and the second cavity is adjusted to achieve the purpose of real-time adjustment.

[0058] In some embodiments, the injection port 32 is provided with a first conical groove 321 at one end close to the second cavity 31, and a second conical groove 322 is provided at the other end of the injection port 32. The ends with smaller cross-sections of the first conical groove 321 and the second conical groove 322 are close to each other, and a central tube 323 is connected between the first conical groove 321 and the second conical groove 322. The central tube 323 connects the first conical groove 321 and the second conical groove 322. A solenoid valve 324 is also provided in the middle of the central tube 323, and the solenoid valve 324 is connected to the control device. Figure 1-5As shown, a first conical groove 321 is provided at one end of the injection port 32 close to the second cavity 31, and a second conical groove 322 is provided at the other end of the injection port 32. The ends of the first conical groove 321 and the second conical groove 322 with smaller cross sections are close to each other, and a central through pipe 323 is connected between the first conical groove 321 and the second conical groove 322, so that when the liquid in the second cavity 31 moves toward the injection port 32, the space of the first conical groove 321 gradually becomes smaller. At this time, the pressure on the liquid increases. As the central through pipe 323 continues to spray into the arc groove 19 from the second conical groove 322, the cross section of the second conical groove 322 gradually increases, so that the range of the spray is larger. The range gradually becomes larger, wherein each through tube 323 is provided with a solenoid valve 324, and the opening of the solenoid valve 324 is controlled by a control device, so that each group of injection ports between the control slides can be partially or completely operated, and each group of injection ports between every two slides can be grouped, when one group, two groups... or completely operated, different modes of injection groups are formed in a single or combined state, and the thickness of the injection layer corresponding to each injection group is different. When the environment in the second chamber is different, the degree of dryness of the injection layer is also different, and the injection range of the liquid sprayed from the injection port to the arc groove is different, so that the particle size of the crystals formed after crystallization is also different. In some embodiments, a protective box 36 is provided on the inner side of the annular plate 27, a second motor 37 is provided in the protective box 36, the second motor 37 is connected to a rotating shaft 38, one end of the rotating shaft 38 is connected to the output shaft of the second motor 37, the other end of the rotating shaft 38 rotatably passes through the top of the protective box 36 and extends to the rotary cylinder 28, the second motor 37 is connected to the control device; the annular plate 27 is provided with a rotating groove 39 adapted to the rotary cylinder 28, the rotary cylinder 28 is rotatably connected to the annular plate 27 through the rotating groove 39, an assembly groove 40 is provided at the bottom of the rotary cylinder 28, a gear ring 41 is provided on the inner side of the assembly groove 40, a first gear 42 is meshed on the inner side of the gear ring 41, and the rotating shaft 38 is connected to the center of the first gear 42; the assembly groove 4 0 is provided with a rotating bearing 43 at the center, and the first connecting pipe 14 is connected to the rotating bearing 43; an annular support 44 is provided at the top of the rotor 28, and the center is located at the eccentric position of the rotor 28, and the annular support 44 connects the rotor 28 and the arc block 29; a third connecting pipe 50 is provided between the first cavity 30 and the second cavity 31, and one end of the third connecting pipe 50 passes through the first cavity 30 and is provided with a first annular edge 45, and the first annular edge 45 is connected to the bottom of the first cavity 30, and the other end of the third connecting pipe 50 passes through the second cavity 31 and is provided with a second annular edge 46, and the second annular edge 46 is connected to the top of the second cavity 31; the shape of the top and side wall of the arc block 29 is the same as the shape of the arc groove 19. Figure 1-5As shown, the protection box 36 is convenient for protecting the second motor 37, which is connected to the inner side of the annular plate 27, which can be in the form of bonding or screwing. The second motor 37 is commercially available, and the working state and state parameters of the second motor 37 are controlled by the control device, wherein the rotating shaft 38 of the second motor 37 is connected to the first gear 42, and the first gear 42 drives the gear ring 41, so that the rotor 28 can rotate in the rotating groove 39; the rotating bearing 43 at the center of the assembly groove 40 supports the first connecting pipe 14. When the rotor 28 rotates, the first connecting pipe 14 is kept stationary relative to the shell 1, so as to facilitate the delivery of the slurry to the first cavity 30; wherein the rotor 28 and the arc block 29 are connected by an annular support 44 at the eccentric position of the rotor 28, and the first cavity 30 and the second cavity 31 are connected by a third connecting pipe 50, one end of the third connecting pipe 50 passes through the first cavity 30 and is provided with a first annular edge 45, and the other end passes through the second cavity 3 1 and a second annular edge 46 is provided. The first annular edge 45 and the second annular edge 46 strengthen the connection between the third connecting pipe 50 and the first cavity 30 and the second cavity 31, so as to facilitate the liquid in the first cavity 30 to further act on the second cavity 31. In this way, when there are liquid in the first cavity 30 and the second cavity 31, after adding liquid into the first cavity 30, due to the pressure difference between the first cavity 30 and the second cavity 31, the liquid in the first cavity 30 will naturally flow into the second cavity 31. When the second cavity 31 is full, a blowout effect will be formed, so that it can be sprayed out through the corresponding injection port 32. According to the control of opening different injection ports, injection layers of different thicknesses can be formed, so that after crystallization, the shape of the top and side wall of the arc block 29 is the same as the shape of the arc groove 19. In this way, when the arc scraper 34 scrapes the injection layer in the arc groove 19, it can scrape more smoothly.

[0059] In some embodiments, the first connecting pipe 14 is also connected to a fourth connecting pipe 51, the fourth connecting pipe 51 is externally connected to a pressurizing machine, a pressure regulating valve 52 is provided on the fourth connecting pipe 51, a fifth electric valve 53 is provided at one end of the first connecting pipe 14 close to the fourth connecting pipe 51, a second lift pump 54 and a sixth electric valve 55 are provided between the second connecting pipe 10 and the fourth connecting pipe 51, and the pressure regulating valve 52, the fifth electric valve 53, the sixth electric valve 55 and the second lift pump 54 are respectively connected to the control device. Figure 1-5As shown, the first connecting pipe 14 is also connected to the fourth connecting pipe 51, and the fourth connecting pipe 51 is externally connected to a pressurizer, which is commercially available. The pressurizer pressurizes the fourth connecting pipe 51, which can be in the form of introducing nitrogen, so that in the process of adding the feed liquid in the first connecting pipe to the first cavity through the pipeline, the material in the feed liquid can be stably dissolved in it, thereby promoting its dissolution effect. At the same time, it is pressurized. Due to the effect of the pressure difference, when a pressure difference is formed in the first cavity and the second cavity, the further flow of the feed liquid can be promoted, so that the feed liquid can enter the preparation stage for injection. At the same time, by controlling the pressure regulating valve, the pressure in the pipeline can be changed. , so that after the liquid in the first connecting pipe is added into the first cavity, the pressure in the first cavity is changed, so that under the action of the pressure difference between the first cavity and the second cavity, the rate of the liquid entering the second cavity is changed, so that it can be controlled and adjusted in real time according to the thickness of the spray layer and the environment in the second chamber, so as to achieve the purpose of crystal particle size adjustment, wherein the fifth electric valve 53, the sixth electric valve 55 and the second lifting pump 54 are controlled by the control device. The fifth electric valve 53 and the sixth electric valve 55 control the circulation of the pipeline, and the second lifting pump 54 acts on the liquid in the first connecting pipe 14 to flow into the first cavity 30.

[0060] In some embodiments, a first connecting rod 56 is connected between one end of the arc scraper 34 and the rotary drum 28, and a second connecting rod 57 is connected between the other end of the arc scraper 34 and the top of the arc block 29; an L-shaped connecting rod 59 is also connected to the outer side of the rotary drum 28, and the L-shaped connecting rod 59 extends toward the partition 24, and a shovel plate 60 is provided on the partition 24, and the L-shaped connecting rod 59 connects the shovel plate 60. Figure 1-5 As shown, the arc scraper 34 is connected to the rotor 28 and the arc block 29 through the first connecting rod 56 and the second connecting rod 57. The L-shaped connecting rod 59 is connected to the outer side of the rotor 28. The shovel plate 60 connected thereto is slidably connected to the partition 24. The shovel plate 60 is not arranged along the radial direction of the partition 24. In this way, as the rotor 28 rotates, the spray layer on the partition 24 can be scraped toward the gap between the partition 24 and the inner wall of the shell 1, so that it can flow to the collection bin for subsequent processing steps.

[0061] In some embodiments, a bell mouth 63 is further provided below the partition 24, and the bell mouth 63 is sleeved outside the L-shaped protective tube 26, and a gap is provided between the end of the bell mouth 63 with a larger cross section and the partition 24, and a blast pipe 64 is connected to the other end of the bell mouth 63, and one end of the blast pipe 64 is connected to the bell mouth 63, and the other end of the blast pipe 64 passes through the discharge bin 23 and is connected to an external blast dryer. Figure 1-5As shown, a bell mouth 63 is further provided below the partition 24, and the bell mouth 63 is sleeved outside the L-shaped protective tube 26. The end of the bell mouth 63 with a larger cross section is provided with a gap between the partition 24, and air is blown by an external blower dryer, and enters the bell mouth 63 through the blower pipe 64. After the bell mouth 63 acts on the bottom of the partition 24, it moves along the gap between the bell mouth 63 and the partition 24 toward the gap between the partition 24 and the inner wall of the shell 1, and then enters the space where the arc groove 19 is placed. In the process, the fallen spray layer is dried, and at the same time, the sprayed water vapor can be carried along the exhaust port to the outside of the second chamber, thereby improving the crystallization and drying rate of the crystals in the second chamber.

[0062] The present invention also provides a method for preparing hydrocortisone sodium succinate, which adopts the hydrocortisone sodium succinate preparation device described in any of the preceding items, and comprises the following steps:

[0063] S1: Hydrocortisone succinate monoester is added through the first feed port 3, purified water is added through the second feed port 4 to dissolve it, hot water at 65°C to 75°C is introduced into the jacket 11 to heat the first chamber, and after reacting for 60 minutes, an alkaline regulator is added through the liquid adding pipe 8 to adjust the pH of the liquid in the first chamber to 8-12, and acetone is added into the shell 1 at 2 ml / min through the liquid adding pipe 8. After continuing for 45 minutes, the temperature in the jacket 11 is adjusted to 25°C to 35°C and kept warm for 1.5 hours;

[0064] S2: nitrogen is introduced into the first connecting pipe through the fourth connecting pipe, the feed liquid in the first connecting pipe enters the first cavity, a pressure difference is formed between the second cavity and the first cavity, the feed liquid in the second cavity forms a blowout effect, and the feed liquid in the second cavity is sprayed out through the injection port. When the opening of the injection ports of different groups is controlled, in coordination with the rotation of the rotary drum, the feed liquid sprayed out of the opened injection port forms a spray layer of corresponding thickness in the arc-shaped groove, and crystallizes under the drying temperature of 80°C to 100°C in the interlayer to form crystals of corresponding particle size, and then flows downward through the gap between the partition 24 and the shell 1 to the bottom of the shell 1 through the sliding of the scraper. At the same time, the external blower dryer blows air toward the bottom of the partition 24 through the blower pipe 64, and further dries the second chamber along the bottom of the partition 24 to accelerate the drying of the spray layer. The gas in the second chamber is discharged through the exhaust pipe 33, and the crystallized and dried hydrocortisone sodium succinate finally flows to the drying and conveying device 66;

[0065] S3: The drying and conveying device 66 further dries and conveys the crystals discharged from the shell 1, and obtains hydrocortisone sodium succinate after screening by the screening device.

[0066] The step S2 further includes: constructing a crystal evaluation model, based on real-time acquisition of environmental data in the second chamber, importing the environmental data into the crystal evaluation model, acquiring a particle size state corresponding to the crystal, and acquiring an evaluation value under the particle size state;

[0067] The target pressure of the fourth communication pipe and the opening state of the corresponding group of injection ports are acquired based on the evaluation value to adjust the injection layer in real time.

[0068] Specifically, the crystal evaluation model is constructed as follows: during the ejection process of the ejection port, the pressure of the liquid in the second cavity per unit time and the distance between the ejection port and the arc-shaped groove are determined by taking the size of the ejection surface as the unit time;

[0069] Taking the empirical and experimental values ​​of the particle size of the crystals in the spray layer formed by the slurry as a reference, the particle size state of the crystals is estimated based on the moisture contained in the spray surface per unit time. By acquiring historical data and real-time experimental data, a neural network model is trained to obtain a crystal evaluation model.

[0070] Specifically, the environmental data is: humidity data in the second chamber, based on the real-time acquisition of the sensor signal by the humidity sensor in the second chamber, the processor solves it to obtain the humidity data in the second chamber, based on the humidity data, the real-time particle size state is obtained using the crystal evaluation model, and the evaluation value under the particle size state is obtained, and based on the evaluation value, the target pressure of the fourth connecting tube and the opening state of the injection port of the corresponding group are obtained.

[0071] Specifically, the target pressure of the fourth connecting pipe is: through the pressure sensors in the first cavity and the second cavity, the pressure in the first cavity and the pressure in the second cavity are obtained in real time, and a dynamic pressure difference is formed between the first cavity and the second cavity. The pressure in the fourth connecting pipe is adjusted by controlling the pressure regulating valve through the control device, so as to change the pressure difference between the first cavity and the second cavity. When the slurry is sprayed out through the injection port, its injection rate is changed and its injection pressure is also different.

[0072] Specifically, the opening state of the corresponding group of injection ports is: different groups of injection groups are formed between every two slides, and the injection groups can work in one group, two groups... or all of them. Since the distance from each group of injection ports to the arc-shaped groove is different, the injection surfaces formed by their injection are also different. When their corresponding opening is controlled, injection surfaces of different sizes are formed, thereby achieving the purpose of controlling the particle size.

[0073] Specifically, after the evaluation value is obtained, a first adjustment value for the target pressure of the fourth communication pipe and a second adjustment value for the opening state of the corresponding group of injection ports are respectively obtained based on the evaluation score, and an evaluation value threshold is established based on historical data and experience values;

[0074] Specifically, during the adjustment process, when the evaluation value is less than the evaluation value threshold range, the first adjustment value is mainly used. After the adjustment of the first adjustment value is completed, the second adjustment value is gradually adjusted using a segmented method to achieve the expected goal. This is because in the early stage of crystallization, the difference between the second cavity and the first cavity is large; when the evaluation value is between the evaluation thresholds, the first adjustment value and the second adjustment value are adjusted at the same time; when the evaluation value is greater than the evaluation threshold range, the second adjustment value is mainly used. After the adjustment of the second adjustment value is completed, the first adjustment value is gradually adjusted using a segmented method to achieve the expected goal. This is because after a stable blowout is formed, the pressure difference between the second cavity and the first cavity becomes smaller.

[0075] Specifically, the control device optimizes the precise control of the reaction conditions in the reaction component to improve the reaction efficiency. At the same time, the reaction liquid is dried and crystallized by controlling the crystallization component to improve product selectivity. The particle size of the crystallization process is adjusted in real time based on environmental data to avoid affecting the degree of crystallization.

[0076] Specifically, the lengths of two adjacent groups of stirring blades 7 are different, while the lengths of the two separated groups of stirring blades 7 are the same, so that different stirring areas are formed between the continuous groups of stirring blades 7. Another group of stirring blades 7 with different lengths sandwiched between the two stirring blades 7 with the same length cooperates to form step stirring. The stirring blades 7 exert different forces on the liquid in the first chamber in the nearby space, so that under the step stirring, the liquid in the first chamber is stepped and then surged, so that the liquid in the first chamber is mixed more fully, which can improve the efficiency of the liquid reaction in the first chamber and further improve the control of the reaction process.

[0077] Specifically, a jacket 11 is provided on the outer wall of the shell 1 disposed outside the reaction assembly, and hot water at 65° C. to 75° C. is introduced into the jacket 11 to provide conditions for the reaction in the first chamber.

[0078] Specifically, the control device controls the second electric valve 15 and the first electric valve 17 to open, so that the first connecting pipe 14 can extract the slurry in the lower layer of the first chamber out of the first chamber, and the first lifting pump 16 can be controlled to assist the slurry to be returned to the top of the first chamber through the second connecting pipe 10 for re-mixing. The advantage of this is that the slurry in the first chamber forms a layered surge, and the slurry above and below is fully mixed, which can further improve the efficiency of the slurry reaction in the first chamber.

[0079] Specifically, a plurality of slide bars are arranged on the side wall of the arc block 29, and a plurality of injection ports 32 are arranged between two adjacent slide bars, and the injection ports 32 are oriented toward the arc groove 19. When the injection port 32 ejects the slurry in the second cavity 31, it acts on the area corresponding to the injection port 32. The arc scraper 34 is connected to the center of the arc groove 19 and the rotary drum 28. The arc scraper 34 scrapes off the injection layer at a relative position in the arc groove 19, causing it to fall downward and fall toward the partition 24 along the slide bars on the side wall of the arc block 29. An exhaust pipe 33 is arranged on the side wall of the shell 1 below the heat insulation board 2, so that the gas in the second chamber is continuously circulated, and the gas can be discharged from the exhaust pipe 33 after the injection port 32 is ejected.

[0080] Specifically, by controlling the opening of the solenoid valve 324 through the control device, some groups of injection ports 32 can be operated and some can be closed. In this way, since the distance from each group of injection ports to the arc-shaped groove is different, the injection surface formed by the injection is also different. When the corresponding opening is controlled, injection surfaces of different sizes are formed, thereby achieving the purpose of controlling the particle size.

[0081] Specifically, an L-shaped connecting rod 59 is connected to the outside of the rotary drum 28, and the shovel plate 60 connected thereto is slidably connected to the partition 24. The shovel plate 60 is not arranged along the radial direction of the partition 24. In this way, as the rotary drum 28 rotates, the spray layer on the partition 24 can be scraped toward the gap between the partition 24 and the inner wall of the shell 1, so that it can flow to the collection bin.

[0082] Specifically, air is blown by an external blower dryer and enters the bell mouth 63 through the blower pipe 64. After the bell mouth 63 acts on the bottom of the partition 24, it moves along the gap between the bell mouth 63 and the partition 24 toward the gap between the partition 24 and the inner wall of the shell 1, and then enters the space under the arc groove 19. In the process, the fallen sprayed layer is dried. At the same time, the sprayed water vapor can be carried along the exhaust port to the outside of the second chamber, thereby increasing the crystallization and drying rate of the crystals in the second chamber.

[0083] Specifically, the dried hydrocortisone sodium succinate finally flows to the drying conveying device 66. As the drying conveying device 66 further conveys it, it fully contacts the drying conveying device 66, its shape is crushed, and the crushed shape is further dried, so that the target hydrocortisone sodium succinate can be obtained after screening by the screening device.

[0084] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention. The above description is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and variations can be made without departing from the technical principles of the present invention. These improvements and variations should also be regarded as the protection scope of the present invention.

Claims

1. A hydrocortisone sodium succinate preparation device, characterized in that, include: A shell, wherein a heat insulation board is horizontally arranged in the middle of the shell, and the heat insulation board divides the shell into a first chamber and a second chamber, and a reaction component and a crystallization component are respectively arranged in the first chamber and the second chamber, and the reaction component mixes and reacts the raw materials in the first chamber, and the crystallization component crystallizes the liquid from the first chamber to the second chamber and then discharges it from the shell; A drying and conveying device is disposed below the shell to further dry and convey the crystals discharged from the shell after crystallization; A screening device, connected to the drying and conveying device, for screening the dried crystals to obtain hydrocortisone sodium succinate; The control device controls the progress of the reaction component and the crystallization component, and controls the crystallization component to adjust the particle size of the crystallization process in real time based on environmental data, so as to adjust the degree of crystallization in real time.

2. The hydrocortisone sodium succinate preparation device according to claim 1, characterized in that: The reaction assembly comprises a first feeding port and a second feeding port, the first feeding port and the second feeding port are respectively arranged at the top of the shell, the first feeding port and the second feeding port are respectively provided with a first feeding port cover and a second feeding port cover, a first motor is arranged at the center of the top of the shell, the first motor is connected to the control device, the first motor is connected to a stirring rod, one end of the stirring rod is connected to the output shaft of the first motor, the other end of the stirring rod rotatably penetrates the top of the shell and extends into the shell, the stirring rod is provided with a plurality of stirring blades, the lengths of the stirring blades of two adjacent groups are different, and the lengths of the stirring blades of the two separated groups are the same; A liquid adding pipe is arranged on the side wall of the shell near the top of the heat insulation board, one end of the liquid adding pipe extends into the shell, a flow regulating valve is arranged on the liquid adding pipe, and the flow regulating valve is connected to the control device; The first chamber is provided with a first connecting pipe, one end of the first connecting pipe passes through the shell side wall of the first chamber, and the other end of the first connecting pipe extends into the crystallization assembly; The outer wall of the shell outside the first chamber is provided with a jacket, and the jacket is respectively provided with a liquid injection port and a liquid discharge port.

3. The hydrocortisone sodium succinate preparation device according to claim 2, characterized in that: The first connecting pipe is also connected to a second connecting pipe, which passes through the side wall of the shell and extends into the first chamber. The second connecting pipe is provided with a first electric valve and a first lifting pump. The first connecting pipe outside the first chamber is provided with a second electric valve. The first electric valve, the second electric valve and the first lifting pump are respectively connected to the control device.

4. The hydrocortisone sodium succinate preparation device according to claim 2, characterized in that: The crystallization assembly includes an interlayer, which is arranged on the top of the second chamber, the outer side of the interlayer is connected to the inner wall of the first chamber, an arc-shaped groove is arranged at the center of one side of the interlayer away from the heat insulation board, a first connecting pipe and a second connecting pipe are arranged on the side wall of the interlayer, the first connecting pipe and the second connecting pipe both pass through the interlayer and the shell to the outside of the shell, a discharge port is arranged at the center of the bottom of the shell, a discharge bin is arranged at the discharge port, and the outlet of the discharge bin is connected to the drying and conveying device; A partition is provided above the discharge port, a gap is provided between the partition and the inner wall of the shell, a plurality of support rods are provided in the shell at the discharge port, the two ends of the support rods are respectively connected to the bottom of the partition and the bottom of the shell, and an L-shaped protective tube is provided between the center of the partition and the side wall of the discharge bin; The partition is provided with an annular plate, a rotary drum is provided above the annular plate, the rotary drum is rotatably connected to the inner side of the annular plate, an arc block is provided on the rotary drum, and the center of the arc block is provided at an eccentric position of the rotary drum; The rotary cylinder and the arc block are respectively provided with a first cavity and a second cavity, the first cavity and the second cavity are connected, the first connecting pipe is rotatably passed through the partition from the L-shaped protective tube and then extends into the first cavity, and a third annular edge is provided at one end of the first connecting pipe located in the first cavity, the third annular edge abuts against the bottom of the first cavity and is rotatably connected to the bottom of the first cavity; The side wall of the arc block is evenly provided with a plurality of slide bars with the center of the arc block as the center of the circle, and the surface of the arc block between two adjacent slide bars and the top of the arc block are evenly provided with a plurality of injection ports, and an arc scraper is also arranged in the arc groove, one end of the arc scraper is located at the center of the arc groove, and the other end of the arc scraper extends along the arc groove toward the side wall of the shell, and the arc scraper is connected to the rotary drum; The side wall of the shell below the heat insulation board is also provided with an exhaust pipe, and the exhaust pipe is provided with a third electric valve, and the third electric valve is connected to the control device; Pressure sensors are respectively disposed in the first cavity and the second cavity, a humidity sensor is disposed on the inner wall of the second cavity below the first groove, and the pressure sensor and the humidity sensor are respectively connected to the processor.

5. The hydrocortisone sodium succinate preparation device according to claim 4, characterized in that: A first conical groove is provided at one end of the injection port close to the second cavity, and a second conical groove is provided at the other end of the injection port. The ends with smaller cross-sections of the first conical groove and the second conical groove are close to each other, and a central through pipe is connected between the first conical groove and the second conical groove, and the central through pipe connects the first conical groove and the second conical groove. Solenoid valves are also provided in the middle of the central through pipes, and the solenoid valves are connected to the control device.

6. The hydrocortisone sodium succinate preparation device according to claim 4, characterized in that: A protection box is arranged inside the annular plate, a second motor is arranged inside the protection box, the second motor is connected to a rotating shaft, one end of the rotating shaft is connected to the output shaft of the second motor, the other end of the rotating shaft rotatably passes through the top of the protection box and extends to the rotary cylinder, and the second motor is connected to the control device; The annular plate is provided with a rotation groove adapted to the rotary drum, the rotary drum is rotatably connected to the annular plate through the rotation groove, the bottom of the rotary drum is provided with an assembly groove, the inner side of the assembly groove is provided with a gear ring, the inner side of the gear ring is meshed with a first gear, and the rotating shaft is connected to the center of the first gear; A rotating bearing is arranged at the center of the assembly groove, and the first connecting pipe is connected to the rotating bearing; The top of the rotor is provided with an annular support whose center is located at an eccentric position of the rotor, and the annular support connects the rotor and the arc block; A third connecting tube is provided between the first cavity and the second cavity, one end of the third connecting tube penetrates into the first cavity and is provided with a first annular edge, the first annular edge is connected to the bottom of the first cavity, the other end of the third connecting tube penetrates into the second cavity and is provided with a second annular edge, the second annular edge is connected to the top of the second cavity; The shape of the top and side wall of the arc-shaped block is the same as the shape of the arc-shaped groove.

7. The hydrocortisone sodium succinate preparation device according to claim 4, characterized in that: The first connecting pipe is also connected to a fourth connecting pipe, the fourth connecting pipe is externally connected to a pressurizing machine, a pressure regulating valve is arranged on the fourth connecting pipe, a fifth electric valve is arranged at one end of the first connecting pipe close to the fourth connecting pipe, a second lifting pump and a sixth electric valve are arranged between the second connecting pipe and the fourth connecting pipe, and the pressure regulating valve, the fifth electric valve, the sixth electric valve and the second lifting pump are respectively connected to the control device.

8. The hydrocortisone sodium succinate preparation device according to claim 4, characterized in that: A first connecting rod is connected between one end of the arc scraper and the rotary drum, and a second connecting rod is connected between the other end of the arc scraper and the top of the arc block; An L-shaped connecting rod is also connected to the outer side of the rotary drum, and the L-shaped connecting rod extends toward the partition. A shovel plate is arranged on the partition, and the L-shaped connecting rod is connected to the shovel plate.

9. The hydrocortisone sodium succinate preparation device according to claim 4, characterized in that: A bell mouth is also provided below the partition, and the bell mouth is sleeved outside the L-shaped protective tube. The end of the bell mouth with a larger cross section is provided with a gap between the partition, and the other end of the bell mouth is connected to a blast pipe. One end of the blast pipe is connected to the bell mouth, and the other end of the blast pipe passes through the discharge bin and is connected to an external blast dryer.

10. A method for preparing hydrocortisone sodium succinate, characterized in that: The hydrocortisone sodium succinate preparation device according to any one of claims 1 to 9 comprises the following steps: S1: adding hydrocortisone succinate monoester through the first feeding port, adding purified water through the second feeding port to dissolve it, passing hot water at 65°C to 75°C into the jacket to heat the first chamber, reacting for 60 minutes, adding an alkaline regulator through the liquid adding tube, adjusting the pH of the liquid in the first chamber to 8-12, and then adding acetone into the shell at 2 ml / min through the liquid adding tube. After 45 minutes, adjusting the temperature in the jacket to 25°C to 35°C and keeping it warm for 1.5 hours; S2: nitrogen is introduced into the first connecting pipe through the fourth connecting pipe, the liquid in the first connecting pipe enters the first cavity, a pressure difference is formed between the second cavity and the first cavity, the liquid in the second cavity forms a blowout effect, and the liquid in the second cavity is sprayed out through the injection port. When the opening of the injection ports of different groups is controlled, the liquid sprayed out of the opened injection ports forms a spray layer of corresponding thickness in the arc-shaped groove in coordination with the rotation of the rotary drum. Based on the real-time adjustment of the pressure difference between the second cavity and the first cavity and the opening state of the corresponding group of injection ports, the injection layer is sprayed out of the second cavity. The layer is adjusted in real time, and crystallizes to form crystals of corresponding particle size under drying at 80°C to 100°C in the interlayer, and flows downward through the gap between the partition 24 and the shell 1 to the bottom of the shell 1 after sliding through the scraper. At the same time, the external blower dryer blows air to the bottom of the partition 24 through the blower pipe 64, and further dries the second chamber along the bottom of the partition 24, accelerating the drying of the spray layer. The gas in the second chamber is discharged through the exhaust pipe 33, and the crystallized and dried hydrocortisone sodium succinate finally flows to the drying conveying device 66; S3: The drying and conveying device further dries and conveys the crystals discharged from the shell, and then screens them through a screening device to obtain hydrocortisone sodium succinate.

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