Device and method for preparing 7-aminoceftriazine

Abstract

The preparation device comprises a support, a reaction tank used for mixing raw materials is fixedly connected to the support, a stirring rod is rotatably connected to the interior of the reaction tank, the stirring rod is fixedly connected to an output shaft of a servo motor, and the servo motor is fixedly connected to the support. A differential mechanism used for limiting the speed is further arranged between the servo motor and the stirring rod, and the stirring rod is fixedly connected with a stirring disc and a mixing disc which are used for stirring and mixing materials; a special collecting module is arranged in the crystal growing mechanism, the important function of effectively introducing seed crystals in the crystal growing process is achieved, and meanwhile liquid is discharged through a drainage hole. Under the acting force of the solution, the crystals cannot fall off due to gravity when entering the collecting module. According to the design, in the next crystallization, the precipitation of the crystal can be promoted by introducing the previously retained crystal, a core is provided for the formation of the crystal, and the crystal is guided to grow orderly, so that the quality and yield of the crystal are remarkably improved.

Description

Technical Field

[0001] The invention relates to the technical field of medicine preparation, in particular to a preparation device and method of 7-aminoceftriaxone. Background Art

[0002] The chemical name of ceftriaxone sodium is (6R,7R)-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazine-3-yl)thio[methyl]-5-thio-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt triplicate hemihydrate. Ceftriaxone sodium is a third-generation cephalosporin antibiotic with a broad spectrum and high efficacy. It is used for urinary tract infections, biliary tract infections, lower respiratory tract infections, pelvic infections, abdominal infections, bone and joint infections, skin and soft tissue infections, sepsis, meningitis and other diseases caused by sensitive pathogens.

[0003] Ceftriaxone sodium was successfully developed by Roche in Switzerland in 1978. After its patent expired in 1996, ceftriaxone sodium began to grow at an astonishing rate in China. In recent years, ceftriaxone sodium has the largest market share among cephalosporins. Both raw materials and preparations have been in a state of fierce competition. Therefore, reducing the production cost of ceftriaxone sodium is an important measure for various manufacturers to remain invincible. 7-ACT (7-aminoceftazidime) is an intermediate for the synthesis of ceftriaxone sodium. Optimizing its process and reducing its production cost is very conducive to enhancing the market competitiveness of ceftriaxone sodium.

[0004] In the current preparation process of 7-aminoceftazidime using existing devices, there are some obvious problems. On the one hand, it is impossible to effectively promote the precipitation of crystals by introducing crystals. In the process of crystal growth, the introduction of seed crystals can often provide a core for the formation of crystals and guide the orderly growth of crystals, thereby improving the quality and yield of crystals. However, the existing preparation devices are insufficient in this regard, resulting in a lack of effective guidance in the crystal precipitation process, making it difficult to achieve efficient crystallization. On the other hand, during the preparation process, the separation equipment is mainly used to separate the solid product from the mother liquor, while the crystal growing equipment is used for the further growth and stabilization of the crystals. If the equipment in these two key links does not achieve good consistency, it will cause many inconveniences during the operation. In the process of transferring the separated product to the crystal growing equipment, there may be risks of leakage, loss and external contamination of the raw materials, which will not only lead to waste of raw materials and increase production costs, but also reduce the efficiency of the entire preparation process due to the complexity and inconsistency of the operation. At the same time, due to the inconsistency between the equipment, it may also affect the stability and consistency of the crystal growth, further reducing the efficiency and quality of the output 7-aminoceftazidime crystals.

[0005] Therefore, a preparation device and method of 7-aminoceftriaxone are proposed. Summary of the invention

[0006] The object of the present invention is to provide a preparation device and method for 7-aminoceftazidime, so as to solve the problems that the crystal precipitation process proposed in the above background technology lacks effective guidance, it is difficult to achieve efficient crystallization and the incoherence between equipments, and it may also affect the stability and consistency of crystal growth, further reducing the efficiency and quality of the output 7-aminoceftazidime crystals.

[0007] To achieve the above-mentioned purpose, the present invention provides the following technical solutions: a preparation device and method of 7-aminoceftazidime, comprising a bracket, a reaction tank for mixing raw materials is fixedly connected to the bracket, a stirring rod is rotatably connected inside the reaction tank, and the stirring rod is fixedly connected to the output shaft of a servo motor, a differential for limiting speed is also provided between the servo motor and the stirring rod, and a stirring disk and a mixing disk for stirring and mixing are fixedly connected to the stirring rod, the reaction tank is fixedly connected to a crystal growing mechanism for precipitating crystals through a connecting pipe, and a feed valve for controlling the flow of liquid is provided at the connection between the connecting pipe and the crystal growing mechanism; The crystal growing mechanism includes a mechanism base and a crystal growing tank fixed on the mechanism base, the crystal growing tank is rotatably connected to the inside of the output main shaft, and the inside of the output main shaft is connected to the connecting pipe, so that the liquid in the reaction tank can flow out from the feed port opened on the output main shaft, the output main shaft is fixedly connected to a small thread and a large thread, and the output main shaft is movably connected to a compression plate for squeezing the liquid and a collection plate for collecting part of the crystals, the compression plate and the collection plate are both provided with a small thread sleeve and a large thread sleeve meshing with the small thread and the large thread, and the connection between the small thread and the small thread sleeve and between the large thread and the large thread sleeve are connected by a ball nut pair, so that the compression plate and the collection plate are driven to move when the output main shaft rotates, and the compression plate and the collection plate are fixedly connected by a telescopic rod, so that the compression plate pushes the collection plate when the output main shaft rotates forward. The collecting plate moves until the collecting plate is engaged with the large thread. When the output spindle is reversed, the collecting plate pushes the pressing plate to move until the pressing plate is engaged with the small thread. The collecting plate is fixedly connected to a connecting piston through a connecting rod, and a connecting pipe for liquid outflow is provided on the connecting piston, so that the connecting piston is driven to move when the collecting plate moves. The crystal growing mechanism is fixedly connected to a separation mechanism through a connecting valve. The connecting piston is movably connected to the inside of the connecting valve, and a limit block matching the internal slide groove of the connecting valve is fixedly connected to the connecting piston, so that when the connecting piston moves inside the connecting valve, the liquid flows to the inside of the separation mechanism through the connecting pipe. A hole groove matching the output spindle is also provided on the connecting piston. A plurality of collection modules for collecting partial crystals in the solution are movably connected to the collecting plate, and the telescopic rod is fixedly connected to the collection module. The separation mechanism includes a separation base, a separation tank fixed on the separation base, and a rotating motor, and the output main shaft is fixedly connected to the output shaft of the rotating motor. The side of the output main shaft close to the rotating motor is also provided with a rotating bone for separating solution and solid, and the rotating bone is also fixed on the output shaft of the rotating motor, so that when the rotating motor rotates, the liquid enters the interior of the rotating bone through the connecting tube, the radius of the rotating bone is greater than the radius of the connecting piston, so that the connecting piston can move to the interior of the rotating bone to allow the liquid to enter the rotating bone through the connecting tube, and a separation chamber for throwing out the mixed liquid is also provided on the rotating bone, and the bottom of the separation base is provided with a liquid outlet pipe and a crystal outlet for interconnecting with the separation tank.

[0008] Preferably: a preheating tube for preheating the reaction tank is arranged outside the reaction tank, and a cooling tube for dissipating heat inside the crystal growing mechanism is also fixedly connected to the outside of the crystal growing mechanism, the cooling tube and the preheating tube are interconnected, and a water pump for circulating water inside the preheating tube and the cooling tube is arranged on the water inlet at one end of the cooling tube.

[0009] Preferably: the collecting module comprises a piston tube, a side of which is provided with a plurality of feed holes for crystals to enter, so that when the pressing plate pushes the collecting plate, the collecting module is ejected from the inside of the collecting plate, and the piston tube is also provided with a plurality of drainage holes for liquid to pass through.

[0010] Preferably: a sampling device is also provided on the side of the reaction tank to detect whether the reaction of the liquid inside the reaction tank is complete through TCL, and a pH meter for displaying the pH value of the solution in the reaction tank is fixedly connected to the outer side of the crystal growing mechanism, and an alkali solution input port for titrating the solution is also opened on the top of the crystal growing tank.

[0011] Preferably: a fixer and a bearing seat for reducing the rotational friction of the output spindle are provided at both ends of the separation tank, and the connecting piston fits tightly against the inner wall of the bearing seat to prevent the liquid from overflowing.

[0012] Preferably, a liquid outlet is provided at the bottom of the bearing seat, and the liquid outlet is communicated with a waste liquid treatment device through liquid outlet pipes on both sides to treat the separated waste liquid.

[0013] Preferably, the crystal outlet is fixedly connected to a washing device for washing crystals, and a drying mechanism for drying crystals is provided inside the washing device to obtain purer crystals.

[0014] Preferably: the compression plate fits tightly against the interior of the crystal growing tank so that no liquid overflows to the other side of the compression plate when the compression plate moves, and a one-way valve is provided inside the feed port so that the liquid does not flow back into the interior of the output spindle.

[0015] S1. Raw material mixing reaction: Add 7-ACA, triazine ring, EDTA and sodium metabisulfite into a reaction tank, stir evenly in dimethyl carbonate, heat to about 24°C, add boron trifluoride dimethyl carbonate complex, and react at 30°C for 20 minutes; S2, titration crystal cultivation: open the feed valve to let the solution flow into the crystal cultivation tank from the feed port through the connecting pipe, add water as a terminator to terminate the reaction, and add ammonia water until the pH is 2. Stir the rod to crystallize, and cultivate the crystal at ℃ for 30 minutes. During the first reaction, some crystals will be retained in the collection module and released to guide the growth of crystals during the next crystallization; S3, centrifugal filtration: The output main shaft rotates to drive the compression plate to squeeze the mixed solution with formed crystals into the bone, and separate the solid and liquid through the bone and separation cavity; S4, washing and drying: The separated crystals are discharged from the collection plate, washed with water and ethanol, and finally dried to obtain the dry product of 7-ACT.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The present invention realizes the important function of effectively introducing crystal seeds during the crystal growth process by providing a special collection module in the crystal growing mechanism. Specifically, in the process of the compression plate pushing the collection plate, the collection module is pushed out from the inside of the collection plate, and the feed holes on its side can collect part of the crystals in the solution, while the liquid is discharged through the drainage holes. Under the force of the solution, the crystals will not fall due to gravity when entering the collection module. This design makes it possible to promote the precipitation of crystals by introducing previously retained crystals during the next crystallization, provide a core for the formation of crystals, guide the orderly growth of crystals, and thus significantly improve the quality and yield of crystals; The present invention drives the movement of the compression plate and the collection plate through the forward and reverse rotation of the output spindle, accurately realizing the key function of squeezing the solution into the rotating bone for efficient solid-liquid separation. When the output spindle rotates forward, the compression plate pushes the collection plate to move, squeezing the liquid to the other side of the crystal growing tank, and the collection module collects the crystals at the same time. Subsequently, the solution is squeezed into the rotating bone, and the separation chamber on the rotating bone uses centrifugal force to throw out the mixed liquid to achieve effective separation of solid and liquid. This process not only has a coherent operation, reducing the risk of leakage, loss and contamination of raw materials during the transfer process, but also improves the efficiency of the entire preparation process, ensures the stability and consistency of crystal growth, and further improves the efficiency and quality of the output of 7-aminoceftazidime crystals; The present invention cleverly realizes the important functions of rationally utilizing energy and reducing energy consumption by interconnecting the preheating tube outside the reaction tank and the cooling tube outside the crystal growing mechanism, and arranging a water pump to circulate water inside the preheating tube and the cooling tube. The large amount of heat generated by the crystal growing mechanism during operation heats up the water in the cooling tube, and the heated water flows to the outer wall of the reaction tank through the water circulation to preheat the reaction tank. Such a heat exchange system makes full use of energy, reduces energy waste, greatly improves energy utilization efficiency, effectively reduces energy consumption in multiple preparation processes, and achieves the dual goals of energy conservation and environmental protection and cost reduction. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a schematic diagram of the overall structure of the present invention; Figure 2 It is a disassembled stereogram of the reaction tank of the present invention; Figure 3 It is a disassembled stereoscopic diagram of the crystal growing mechanism and the separation mechanism of the present invention; Figure 4 A side perspective view of the separation mechanism of the present invention; Figure 5 It is an overall stereogram of the output spindle of the present invention; Figure 6 It is a linkage relationship diagram of the compression plate and the collection plate of the present invention; Figure 7It is a position relationship diagram of the collecting plate and the connecting piston of the present invention; Figure 8 For the present invention Figure 7 A magnified image of A.

[0018] In the figure: 1. Bracket; 2. Reactor; 3. Servo motor; 4. Differential; 5. Stirring rod; 6. Stirring plate; 7. Mixing plate; 8. Connecting pipe; 9. Feeding valve; 10. Preheating pipe; 11. Cooling pipe; 12. Crystal growing mechanism; 121. Mechanism base; 122. Crystal growing tank; 123. Output spindle; 124. Small thread; 125. Large thread; 126. Feeding port; 127. Compression plate; 128. Small thread sleeve; 129. Telescopic rod; 1210. Collecting plate; 1211. Large thread sleeve; 1212. Connecting rod; 1213. Connecting piston; 1214. Limiting block; 1215. Connecting pipe; 1216. Hole groove; 1217. Collecting module; 12171. Piston tube; 12172. Drain hole; 12173. Feeding hole; 13. Separation mechanism; 131. Separation base; 132. Separation tank; 133. Rotation motor; 134. Fixer; 135. Rotation bone; 136. Separation chamber; 137. Liquid outlet device; 138. Liquid outlet pipe; 139. Waste liquid treatment device; 1310. Crystal outlet; 14. Connecting valve. DETAILED DESCRIPTION

[0019] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0020] See also Figures 1 to 8 The present invention provides a technical solution of a device and method for preparing 7-aminoceftazidime: The preparation device and method of 7-aminoceftazidime include a support 1, a reaction tank 2 for mixing raw materials is fixedly connected to the support 1, a stirring rod 5 is rotatably connected inside the reaction tank 2, and the stirring rod 5 is fixedly connected to the output shaft of a servo motor 3, a differential 4 for limiting speed is also provided between the servo motor 3 and the stirring rod 5, and a stirring plate 6 and a mixing plate 7 for stirring and mixing are fixedly connected to the stirring rod 5, the reaction tank 2 is fixedly connected to a crystal growing mechanism 12 for precipitating crystals through a connecting pipe 8, and a feed valve 9 for controlling the flow of liquid is provided at the connection between the connecting pipe 8 and the crystal growing mechanism 12; The crystal growing mechanism 12 includes a mechanism base 121 and a crystal growing tank 122 fixed on the mechanism base 121. The interior of the crystal growing tank 122 is rotatably connected to an output spindle 123, and the interior of the output spindle 123 is connected to the connecting pipe 8, so that the liquid in the reaction tank 2 flows out from the feed port 126 opened on the output spindle 123. The output spindle 123 is fixedly connected to a small thread 124 and a large thread 125, and the output spindle 123 is movably connected to a compression plate 127 for squeezing liquid and a collection plate 1210 for collecting part of the crystals. The compression plate 12 The interior of the collecting plate 1210 is provided with a small thread sleeve 128 and a large thread sleeve 1211 meshed with the small thread 124 and the large thread 125, and the connection between the small thread 124 and the small thread sleeve 128 and between the large thread 125 and the large thread sleeve 1211 are connected by a ball nut pair, so that when the output spindle 123 rotates, the pressure plate 127 and the collecting plate 1210 are driven to move, and the pressure plate 127 and the collecting plate 1210 are fixedly connected by a telescopic rod 129, so that when the output spindle 123 rotates forward, the pressure plate 127 pushes the collecting plate 1210 moves until the collecting plate 1210 is meshed with the large thread 125. When the output spindle 123 is reversed, the collecting plate 1210 pushes the pressing plate 127 to move until the pressing plate 127 is meshed with the small thread 124. The collecting plate 1210 is fixedly connected to the connecting piston 1213 through the connecting rod 1212, and the connecting piston 1213 is provided with a connecting pipe 1215 for liquid outflow, so that when the collecting plate 1210 moves, the connecting piston 1213 is driven to move. The crystal growing mechanism 12 is fixedly connected to the separation mechanism 13 through the connecting valve 14. The connecting piston 12 13 is movably connected to the inside of the connecting valve 14, and a limit block 1214 matching the internal slide groove of the connecting valve 14 is fixedly connected to the connecting piston 1213, so that when the connecting piston 1213 moves inside the connecting valve 14, the liquid flows to the inside of the separation mechanism 13 through the connecting pipe 1215, and a hole groove 1216 matching the output main shaft 123 is also opened on the connecting piston 1213, and a plurality of collecting modules 1217 for collecting partial crystals in the solution are movably connected to the collecting plate 1210, and the telescopic rod 129 is fixedly connected to the collecting module 1217; The separation mechanism 13 includes a separation base 131, a separation tank 132 fixed on the separation base 131, and a rotating motor 133, and the output main shaft 123 is fixedly connected to the output shaft of the rotating motor 133, and a rotating bone 135 for separating solution and solid is also sleeved on the side of the output main shaft 123 close to the rotating motor 133, and the rotating bone 135 is also fixed on the output shaft of the rotating motor 133, so that when the rotating motor 133 rotates, the liquid enters the inside of the rotating bone 135 through the connecting pipe 1215, and the radius of the rotating bone 135 is greater than the radius of the connecting piston 1213, so that the connecting piston 1213 can move to the inside of the rotating bone 135 so that the liquid enters the rotating bone 135 through the connecting pipe 1215, and the rotating bone 135 is also provided with a separation chamber 136 for throwing out the mixed liquid, and the bottom of the separation base 131 is provided with a liquid outlet pipe 138 and a crystal outlet 1310 for communicating with the separation tank 132; The collecting module 1217 includes a piston tube 12171, on the side of which a plurality of feed holes 12173 for crystals to enter are provided, so that when the pressing plate 127 pushes the collecting plate 1210, the collecting module 1217 is pushed out from the inside of the collecting plate 1210, and the piston tube 12171 is also provided with a plurality of drainage holes 12172 for liquid to pass through.

[0021] During operation, in the reaction tank 2, the servo motor 3 drives the stirring rod 5 to rotate through the differential 4, and the stirring plate 6 and the mixing plate 7 on the stirring rod 5 stir and mix the added raw materials such as 7-ACA, triazine ring, EDTA and sodium metabisulfite. The preheating tube 10 outside the reaction tank 2 preheats the reaction tank 2 to about 24° C., which is conducive to the reaction. The dimethyl boron trifluoride carbonate complex is added and reacted at 30° C. for 20 minutes; After the mixing reaction is completed, the feed valve 9 is opened, and the reacted liquid flows into the crystal growing tank 122 from the feed port 126 on the output spindle 123 through the connecting pipe 8. Water is added as a terminator to terminate the reaction, and ammonia water is added dropwise until the pH value is 2.5 for crystallization, and the crystal is grown at 8°C for 30 minutes. After the reaction is completed, the output spindle 123 in the crystal growing tank 122 rotates. When the output spindle 123 rotates forward, the compression plate 127 pushes the collecting plate 1210 to move, so that the liquid squeezes the other side of the crystal growing tank 122 when the compression plate 127 moves, and when the collecting plate 1210 is pushed by the telescopic rod 129, the collecting module 1217 is first removed from the collecting plate 1210. The part is ejected, and the feed hole 12173 on the side of the piston tube 12171 collects part of the crystals in the solution, and the liquid is discharged through the drainage hole 12172. Under the force of the solution, the crystals will not fall due to gravity when entering the collection module 1217, until the collection plate 1210 is engaged with the large thread 125. At this time, when the output spindle 123 rotates, the collection plate 1210 drives the compression plate 127 to move, and 1217 is received inside 1210, so that when the solution is discharged, part of the crystals are collected inside the collection module 1217. At this time, the compression plate 127 squeezes the mixed solution that has generated the crystals into the rotating bone 135. In the embodiment, the radius of the rotating bone 135 is larger than the radius of the connecting piston 1213, so that the connecting piston 1213 can accurately move to the inside of the rotating bone 135, so that the liquid can smoothly enter the rotating bone 135 through the connecting tube 1215, and the separation chamber 136 on the rotating bone 135 throws out the mixed liquid, and uses centrifugal force to achieve efficient separation of solid and liquid. The separated liquid enters the waste liquid treatment device 139 through the liquid outlet pipe 138 for proper treatment, ensuring that the waste liquid is treated in an environmentally friendly manner. The separated crystals will be discharged from the collecting plate 1210 and enter the washing device for washing with water and ethanol to remove impurities, and finally dried by the drying mechanism to obtain a purer 7-ACT dry product. When it is dried again When the preparation is carried out for the first time, when the output spindle 123 reverses, the collecting plate 1210 pushes the pressing plate 127 to move until the pressing plate 127 engages with the small thread 124, so that the collecting module 1217 is pulled out from the collecting plate 1210 again, and the crystals inside it fall on the inner wall of the crystal growing tank 122 under the action of gravity, so that when the preparation is carried out next time, the crystal precipitation can be promoted by introducing crystals, thereby achieving efficient crystallization. The pressing plate 127 fits tightly with the inside of the crystal growing tank 122 to prevent the liquid from overflowing to the other side when the pressing plate 127 moves. The one-way valve inside the feed port 126 ensures that the liquid will not flow back into the output spindle 123.

[0022] As an embodiment of the present invention, Figure 1 , Figure 2 and Figure 3As shown, a preheating tube 10 for preheating the reaction tank 2 is arranged outside the reaction tank 2, and a cooling tube 11 for dissipating heat inside the crystal growing mechanism 12 is also fixedly connected to the outside of the crystal growing mechanism 12, the cooling tube 11 and the preheating tube 10 are interconnected, and a water pump for circulating water inside the preheating tube 10 and the cooling tube 11 is arranged on the water inlet at one end of the cooling tube 11.

[0023] During operation, the cooling tube 11 on the outside of the crystal growing mechanism 12 effectively dissipates heat from the inside of the crystal growing mechanism 12 to ensure that the crystal growing process is carried out under suitable temperature conditions. The cooling tube 11 is interconnected with the preheating tube 10, and the water pump on the water inlet of the cooling tube 11 circulates water inside the preheating tube 10 and the cooling tube 11 to form an efficient heat exchange system. In this way, the water heated by the large amount of heat generated by the neutralization titration of the cooling tube 11 can circulate on the outer wall of the middle reaction tank 2, thereby preheating the reaction tank 2, realizing the rational use of energy, improving energy utilization efficiency, and reducing energy consumption, so as to achieve a reduction in energy consumption during multiple preparations.

[0024] As an embodiment of the present invention, Figure 5 and Figure 6 As shown, a sampling device is also provided on the side of the reaction tank 2 to detect whether the reaction is complete through TCL of the liquid inside the reaction tank 2, and a pH meter for displaying the pH value of the solution in the reaction tank 2 is fixedly connected to the outer side of the crystal growing mechanism 12. An alkali solution input port for titrating the solution is also provided above the crystal growing tank 122. The compression plate 127 fits tightly with the interior of the crystal growing tank 122 so that no liquid will overflow to the other side of the compression plate 127 when the compression plate 127 moves, and a one-way valve is provided inside the feed port 126 to prevent the liquid from flowing back into the interior of the output spindle 123.

[0025] During operation, the sampling device on the side of the reaction tank 2 is used to perform TCL detection on the liquid inside the reaction tank 2, so as to determine whether the solution has reacted completely to ensure that the reaction reaches the expected level. The pH meter on the outside of the crystal growing mechanism 12 is used to accurately display the pH value of the solution in the reaction tank 2, providing accurate pH parameters for the crystal growing process. The alkali solution input port above the crystal growing tank 122 is used to titrate the solution to adjust the pH value of the solution and create an environment suitable for crystal precipitation. During the crystal growing process, the feed valve 9 is opened to allow the solution to flow into the crystal growing tank 122, and water is added as a terminator to terminate the reaction. Ammonia water is added dropwise to a pH of 2.5 for crystallization, and the crystal is grown at 8°C for 30 minutes to ensure that the crystal can fully grow and stabilize. During the first reaction, some crystals are retained in the collection module 1217. These crystals act as seeds during the next crystallization, guiding the orderly growth of the crystals and improving the quality and yield of the crystals.

[0026] As an embodiment of the present invention, Figure 3 and Figure 4As shown, the two ends of the separation tank 132 are provided with a fixer 134 and a bearing seat 137 for reducing the rotation friction of the output main shaft 123, and the connecting piston 1213 is tightly fitted on the inner wall of the bearing seat 137 to prevent the liquid from overflowing. The bottom of the bearing seat 137 is provided with a liquid outlet, and the liquid outlet is interconnected with the waste liquid treatment device 139 through the liquid outlet pipes 138 on both sides to treat the separated waste liquid. The crystal outlet 1310 is fixedly connected to the washing device for washing crystals, and a drying mechanism for drying crystals is provided inside the washing device to obtain purer crystals.

[0027] During operation, the fixers 134 and the bearing seats 137 at both ends of the separation tank 132 effectively reduce the friction of the rotation of the output main shaft 123, ensuring the smooth rotation process, and the connecting piston 1213 fits tightly against the inner wall of the bearing seat 137, strictly preventing liquid from overflowing, thereby ensuring the stability and safety of the separation process. The liquid outlet at the bottom of the bearing seat 137 is connected to the waste liquid treatment device 139 through the liquid outlet pipe 138, ensuring that the waste liquid can be treated in a timely and effective manner to avoid pollution to the environment.

[0028] S1, raw material mixing reaction: add 7-ACA, triazine ring, EDTA and sodium metabisulfite into reaction tank 2, stir evenly in dimethyl carbonate, heat to about 24°C, add boron trifluoride dimethyl carbonate complex, and react at 30°C for 20 minutes; S2, titration crystal growth: open the feed valve 9 to let the solution flow into the crystal growth tank 122 from the feed port 126 through the connecting pipe 8, add water as a terminator to terminate the reaction, and drop ammonia water until the pH is 2. Stir the rod 5 for crystallization, and grow the crystal at 8°C for 30 minutes. During the first reaction, some crystals are retained in the collection module 1217 and released to guide the growth of crystals during the next crystallization; S3, centrifugal filtration: The output main shaft 123 rotates to drive the compression plate 127 to squeeze the mixed solution with formed crystals into the bone transfer chamber 135, and the solid and liquid are separated through the bone transfer chamber 135 and the separation chamber 136; S4, washing and drying: the separated crystals are discharged from the collecting plate 1210, washed with water and ethanol, and finally dried to obtain a dry 7-ACT product.

[0029] Working principle: During operation, in the reaction tank 2, the servo motor 3 drives the stirring rod 5 to rotate through the differential 4, and the stirring plate 6 and the mixing plate 7 on the stirring rod 5 stir and mix the added raw materials such as 7-ACA, triazine ring, EDTA and sodium metabisulfite. The preheating tube 10 outside the reaction tank 2 preheats the reaction tank 2 to about 24°C, which is conducive to the reaction. The dimethyl boron trifluoride carbonate complex is added and reacted at 30°C for 20 minutes; After the mixing reaction is completed, the feed valve 9 is opened, and the reacted liquid flows into the crystal growing tank 122 from the feed port 126 on the output spindle 123 through the connecting pipe 8. Water is added as a terminator to terminate the reaction, and ammonia water is added dropwise until the pH value is 2.5 for crystallization, and the crystal is grown at 8°C for 30 minutes. After the reaction is completed, the output spindle 123 in the crystal growing tank 122 rotates. When the output spindle 123 rotates forward, the compression plate 127 pushes the collecting plate 1210 to move, so that the liquid squeezes the other side of the crystal growing tank 122 when the compression plate 127 moves, and when the collecting plate 1210 is pushed by the telescopic rod 129, the collecting module 1217 is first removed from the collecting plate 1210. The part is ejected, and the feed hole 12173 on the side of the piston tube 12171 collects part of the crystals in the solution, and the liquid is discharged through the drainage hole 12172. Under the force of the solution, the crystals will not fall due to gravity when entering the collection module 1217, until the collection plate 1210 is engaged with the large thread 125. At this time, when the output spindle 123 rotates, the collection plate 1210 drives the compression plate 127 to move, and 1217 is received inside 1210, so that when the solution is discharged, part of the crystals are collected inside the collection module 1217. At this time, the compression plate 127 squeezes the mixed solution that has generated the crystals into the rotating bone 135. In the embodiment, the radius of the rotating bone 135 is larger than the radius of the connecting piston 1213, so that the connecting piston 1213 can accurately move to the inside of the rotating bone 135, so that the liquid can smoothly enter the rotating bone 135 through the connecting tube 1215, and the separation chamber 136 on the rotating bone 135 throws out the mixed liquid, and uses centrifugal force to achieve efficient separation of solid and liquid. The separated liquid enters the waste liquid treatment device 139 through the liquid outlet pipe 138 for proper treatment, ensuring that the waste liquid is treated in an environmentally friendly manner. The separated crystals will be discharged from the collecting plate 1210 and enter the washing device for washing with water and ethanol to remove impurities, and finally dried by the drying mechanism to obtain a purer 7-ACT dry product. When it is dried again When the preparation is carried out for the first time, when the output spindle 123 reverses, the collecting plate 1210 pushes the pressing plate 127 to move until the pressing plate 127 engages with the small thread 124, so that the collecting module 1217 is pulled out from the collecting plate 1210 again, and the crystals inside it fall on the inner wall of the crystal growing tank 122 under the action of gravity, so that when the preparation is carried out next time, the crystal precipitation can be promoted by introducing crystals, thereby achieving efficient crystallization. The pressing plate 127 fits tightly with the inside of the crystal growing tank 122 to prevent the liquid from overflowing to the other side when the pressing plate 127 moves. The one-way valve inside the feed port 126 ensures that the liquid will not flow back into the output spindle 123.

[0030] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A device for preparing 7-aminoceftazidime, comprising a support (1), characterized in that: The support (1) is fixedly connected to a reaction tank (2) for mixing raw materials, the reaction tank (2) is rotatably connected to a stirring rod (5) inside, and the stirring rod (5) is fixedly connected to an output shaft of a servo motor (3), a differential (4) for limiting speed is further provided between the servo motor (3) and the stirring rod (5), and a stirring disk (6) and a mixing disk (7) for stirring and mixing are fixedly connected to the stirring rod (5), the reaction tank (2) is fixedly connected to a crystal growing mechanism (12) for precipitating crystals via a connecting pipe (8), and a feed valve (9) for controlling the flow of liquid is provided at the connection between the connecting pipe (8) and the crystal growing mechanism (12); The crystal growing mechanism (12) comprises a mechanism base (121) and a crystal growing tank (122) fixed on the mechanism base (121); an output spindle (123) is rotatably connected to the interior of the crystal growing tank (122); and the interior of the output spindle (123) is connected to a connecting pipe (8) so that the liquid in the reaction tank (2) flows out from a feed port (126) provided on the output spindle (123); a small thread (124) and a large thread (125) are fixedly connected to the output spindle (123); and a compression plate (127) for squeezing the liquid and a collection plate (1210) for collecting part of the crystals are movably connected to the output spindle (123); The interiors of the forced plate (127) and the collecting plate (1210) are provided with a small thread sleeve (128) and a large thread sleeve (1211) meshing with the small thread (124) and the large thread (125), and the connection points between the small thread (124) and the small thread sleeve (128) and between the large thread (125) and the large thread sleeve (1211) are connected by a ball nut pair, so that when the output main shaft (123) rotates, the forced plate (127) and the collecting plate (1210) are driven to move, and the forced plate (127) and the collecting plate (1210) are fixedly connected by a telescopic rod (129), so that when the output main shaft (123) rotates forward, the forced plate (127) pushes the collecting plate (1210) to move. 1210) moves until the collecting plate (1210) meshes with the large thread (125); when the output spindle (123) reverses, the collecting plate (1210) pushes the pressing plate (127) to move until the pressing plate (127) meshes with the small thread (124); the collecting plate (1210) is fixedly connected to a connecting piston (1213) via a connecting rod (1212); and a connecting pipe (1215) for liquid outflow is provided on the connecting piston (1213), so that when the collecting plate (1210) moves, the connecting piston (1213) is driven to move; the crystal growing mechanism (12) is fixedly connected to a separation mechanism (13) via a connecting valve (14); and the connecting piston (1213) is movably connected to the interior of the connecting valve (14), and a limit block (1214) matching the internal slide groove of the connecting valve (14) is fixedly connected to the connecting piston (1213), so that when the connecting piston (1213) moves inside the connecting valve (14), the liquid flows to the interior of the separation mechanism (13) through the connecting pipe (1215), and a hole groove (1216) matching the output main shaft (123) is also formed on the connecting piston (1213). A plurality of collection modules (1217) for collecting partial crystals in the solution are movably connected to the collecting plate (1210), and the telescopic rod (129) is fixedly connected to the collection module (1217); The separation mechanism (13) comprises a separation base (131), a separation tank (132) fixed on the separation base (131), and a rotating motor (133), and the output main shaft (123) is fixedly connected to the output shaft of the rotating motor (133), and a rotating bone (135) for separating solution and solid is also sleeved on the side of the output main shaft (123) close to the rotating motor (133), and the rotating bone (135) is also fixed on the output shaft of the rotating motor (133), so that when the rotating motor (133) rotates, the liquid passes through the connecting tube (1215) enters the interior of the rotating bone (135), and the radius of the rotating bone (135) is greater than the radius of the connecting piston (1213), so that the connecting piston (1213) can move to the interior of the rotating bone (135) to allow the liquid to enter the rotating bone (135) through the connecting tube (1215), and the rotating bone (135) is also provided with a separation chamber (136) for throwing out the mixed liquid, and the bottom of the separation base (131) is provided with a liquid outlet pipe (138) and a crystal outlet (1310) for communicating with the separation tank (132).

2. The preparation device of 7-aminoceftriaxone according to claim 1, characterized in that: A preheating tube (10) for preheating the reaction tank (2) is arranged outside the reaction tank (2), and a cooling tube (11) for dissipating heat inside the crystal growing mechanism (12) is also fixedly connected to the outside of the crystal growing mechanism (12), the cooling tube (11) and the preheating tube (10) are communicated with each other, and a water pump for circulating water inside the preheating tube (10) and the cooling tube (11) is arranged on a water inlet at one end of the cooling tube (11).

3. The preparation device of 7-aminoceftriaxone according to claim 1, characterized in that: The collecting module (1217) comprises a piston tube (12171), and a plurality of feeding holes (12173) for crystals to enter are provided on the side of the piston tube (12171), so that when the pressing plate (127) pushes the collecting plate (1210), the collecting module (1217) is pushed out from the inside of the collecting plate (1210), and a plurality of drainage holes (12172) for liquid to pass through are also provided on the piston tube (12171).

4. The preparation device of 7-aminoceftriaxone according to claim 1, characterized in that: A sampling device is also provided on the side of the reaction tank (2) to detect whether the reaction is complete by TCL of the liquid inside the reaction tank (2), and a pH meter for displaying the pH value of the solution in the reaction tank (2) is fixedly connected to the outer side of the crystal growing mechanism (12), and an alkali solution input port for titrating the solution is also provided on the top of the crystal growing tank (122).

5. The preparation device of 7-aminoceftriaxone according to claim 1, characterized in that: A fixer (134) and a bearing seat (137) for reducing the rotational friction of the output main shaft (123) are provided at both ends of the separation tank (132), and the connecting piston (1213) is tightly fitted on the inner wall of the bearing seat (137) to prevent liquid from overflowing.

6. The preparation device of 7-aminoceftriaxone according to claim 5, characterized in that: The bottom of the bearing seat (137) is provided with a liquid outlet, and the liquid outlet is connected to a waste liquid treatment device (139) via liquid outlet pipes (138) on both sides to treat the separated waste liquid.

7. The preparation device of 7-aminoceftriaxone according to claim 1, characterized in that: The crystal outlet (1310) is fixedly connected to a washing device for washing crystals, and a drying mechanism for drying crystals is provided inside the washing device to obtain purer crystals.

8. The preparation device of 7-aminoceftriaxone according to claim 1, characterized in that: The compression plate (127) fits tightly against the interior of the crystal growing tank (122) so that when the compression plate (127) moves, no liquid will overflow to the other side of the compression plate (127), and a one-way valve is provided inside the feed port (126) so that the liquid will not flow back into the interior of the output spindle (123).

9. A method for using the preparation device of 7-aminoceftriaxone according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1, raw material mixing reaction: add 7-ACA, triazine ring, EDTA and sodium metabisulfite into the reaction tank (2), stir evenly in dimethyl carbonate, raise the temperature to about 24°C, add boron trifluoride dimethyl carbonate complex, and react at 30°C for 20 minutes; S2, titration crystal growth: open the feed valve (9) and let the solution flow into the crystal growth tank (122) from the feed port (126) through the connecting pipe (8), add water as a stopper to terminate the reaction, and add ammonia water until the pH is 2. Stir the rod (5) to crystallize, and grow the crystal at (8) ° C for 30 minutes. During the first reaction, some crystals are retained in the collection module (1217) and released to guide the growth of crystals during the next crystallization; S3, centrifugal filtration: the output main shaft (123) rotates to drive the compression plate (127) to squeeze the mixed solution with the generated crystals into the rotating bone (135), and the solid and liquid are separated through the rotating bone (135) and the separation chamber (136); S4, washing and drying: The separated crystals are discharged from the collecting plate (1210), washed with water and ethanol, and finally dried to obtain a dry 7-ACT product.

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