A high-efficiency crystallization device for cefcapene pivoxil hydrochloride bulk drug

Abstract

The application discloses a high-efficiency crystallization device for cefcapene pivoxil hydrochloride bulk drug, wherein the upper scraping structure and the lower scraping structure respectively comprise upper scraping plates and lower scraping plates which are coaxially rotated with the stirring shaft; the upper scraping plates and the lower scraping plates swing outward and are attached to the inner wall of the crystallization tank by centrifugal force generated by the rotation of the stirring shaft, can be used for cleaning the inner wall of the crystallization tank, and simultaneously realize self-adaptive adjustment of scraping and pressing force with stirring speed; a flow guide cylinder is fixedly arranged at the middle part of the crystallization tank; a gap is formed between the flow guide cylinder and the crystallization tank; a stirring paddle is further arranged on the stirring shaft and is located in the flow guide cylinder; the stirring shaft makes the solution flow out from the bottom of the flow guide cylinder, flow upward along the gap, and wash the outer wall of the flow guide cylinder and the inner wall of the crystallization tank; through cooperation of the upper scraping structure and the lower scraping structure, the upper scraping plates and the lower scraping plates swing outward and are attached to the inner wall of the crystallization tank by centrifugal force generated by the rotation of the stirring shaft, so as to clean the inner wall of the crystallization tank and simultaneously realize self-adaptive adjustment of scraping and pressing force with stirring speed.

Description

Technical Field

[0001] This invention relates to the field of crystallization tank technology for the production of cefoperazone, and particularly to a high-efficiency crystallization device for cefoperazone raw material. Background Technology

[0002] Cefcarpine ester is a third-generation oral cephalosporin antibiotic, and its active pharmaceutical ingredient is typically purified by crystallization. Because multiple sites on the β-lactam ring in the cefacarpine ester molecule are prone to degradation, its stability is poor. Factors such as excessively high temperature and humidity can increase impurities in the finished product. Therefore, temperature control during the crystallization process has a decisive impact on product quality.

[0003] Existing cefoperazone crystallizers typically consist of a tank body, a stirring device, and a jacketed heat exchange structure. During crystallization, cefoperazone crystals easily precipitate and adhere to the inner wall of the tank (especially in the jacketed heat exchange area), forming a dense "crystal scar" layer. After crystal scars adhere, the heat exchange resistance of the jacket increases significantly, causing the actual temperature inside the tank to deviate from the set value. Since cefoperazone is extremely sensitive to crystallization temperature, temperature runaway will directly affect product purity and yield. In addition, as the crystal scars thicken, they detach and mix into the finished product, increasing product impurities. Some devices have a fixed hard-contact scraper structure inside the tank. The scraper blades are always rigidly attached to the inner wall of the tank, resulting in extremely high frictional resistance during stirring. This not only increases equipment energy consumption but also scratches the polished surface of the inner wall of the tank, compromising GMP aseptic finish. Furthermore, the constant clamping force easily causes wear and shedding of the scraper blades, contaminating the active pharmaceutical ingredient. Summary of the Invention

[0004] This invention proposes a highly efficient crystallization device for cefoperazone raw material, which solves the problems of easy scaling on the tank wall and high frictional resistance of the scraping structure during the crystallization process of cefoperazone, which easily damages the tank wall.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A high-efficiency crystallization device for cefoperazone raw material includes a crystallization tank. A stirring shaft is rotatably mounted inside the crystallization tank via bearings. A drive motor is mounted at the top of the crystallization tank. The upper end of the stirring shaft passes through the crystallization tank and is connected to the output shaft of the drive motor. An upper scraping structure and a lower scraping structure are respectively mounted at the upper and lower ends of the stirring shaft. The upper scraping structure and the lower scraping structure each include an upper scraper and a lower scraper that rotate coaxially with the stirring shaft. The upper scraper and the lower scraper swing outward and adhere to the inner wall of the crystallization tank by the centrifugal force generated by the rotation of the stirring shaft, so as to clean the inner wall of the crystallization tank. At the same time, the wall-scraping pressure is adaptively adjusted with the stirring speed. A guide tube is fixedly installed in the middle of the crystallization tank. The outer diameter of the guide tube wall gradually increases from top to bottom. An annular gap is formed between the guide tube and the crystallization tank. A stirring paddle is also installed on the stirring shaft. The stirring paddle is located inside the guide tube. The stirring shaft causes the solution to flow out from the bottom of the guide tube and flow upward along the gap, scouring the outer wall of the guide tube and the inner wall of the crystallization tank.

[0006] Preferably, the crystallization tank includes a tank body fixed on a frame, a jacket is fitted inside the tank body, a discharge valve is installed below the jacket, and a feed port is provided at the top of the tank body. A gap is left between the jacket and the tank body to form a clamping groove, and a cooling medium is introduced into the clamping groove to allow the solution on the inner wall of the jacket to crystallize.

[0007] Preferably, the guide tube is coaxially arranged with the stirring shaft. The guide tube includes an upper section, a middle section, and a lower section. The upper and lower sections are of equal diameter, and the middle section is a gradually changing section. The outer diameter of the middle section increases linearly from top to bottom, and the taper angle is 0.5°-2°. The width of the annular gap formed between the guide tube and the crystallizer gradually decreases from top to bottom. The wide gap between the upper section and the inner wall of the crystallizer has a large flow cross-sectional area, low flow velocity, low dynamic pressure, and high static pressure, forming a low-pressure slow flow zone. The narrow gap between the lower section and the inner wall of the crystallizer has a small flow cross-sectional area, high flow velocity, high dynamic pressure, and low static pressure, forming a high-pressure strong flow zone. This achieves a natural zoning of the flow velocity within the annular gap—low-pressure slow flow in the upper part and high-pressure strong flow in the lower part.

[0008] Preferably, both the upper end of the upper section and the lower end of the lower section are provided with rounded chamfers, and the radius of the rounded chamfer R is greater than or equal to 10 mm, which can eliminate the flow dead zone and eddy current stagnation zone at the sharp corners and prevent the crystal from preferentially adhering at the edges. The surface roughness Ra of the inner and outer walls of the flow guide tube is Ra≤0.4μm, which reduces the nucleation sites on the solid surface and lowers the probability of heterogeneous nucleation of crystals on the surface of the flow guide tube. At the same time, the flow guide tube only serves as a flow guiding component and does not undertake the function of heat exchange.

[0009] The upper outer edge of the upper section of the guide tube is uniformly provided with turbulence wings along the circumference. Each turbulence wing is inclined downward at 30° along the rotation direction of the stirring paddle. The thickness of the turbulence wing is the same as the thickness of the tube wall. The side of the turbulence wing facing the fluid flow is a circular arc guide surface, and the back side is a plane or micro-arc surface. When the downward flow generated by the rotating impeller reaches the upper end of the guide tube, it will be blocked by the turbulence vane. Since the turbulence vane is tilted downward at 30° along the rotation direction of the impeller, the arc-shaped guide surface of the vane will smoothly guide the main flow to the annular gap between the guide tube and the jacket, avoiding short circuits and dead zones in the fluid at the upper inlet of the guide tube, and making the circulation of the whole tank more complete.

[0010] The lower section of the guide tube is provided with a spiral turbulence bar. When the solution flows upward along the annular gap, it is simultaneously subjected to tangential impact and axial guidance from the spiral turbulence bar, generating a three-dimensional spiral turbulence containing velocity components in the radial, tangential, and axial directions. The shear stress of this turbulence on the tank wall is much higher than that generated by the two-dimensional disturbance of the vertical turbulence bar. Under narrow gap and high flow velocity conditions, the spiral turbulence strip forces the fluid to move along a spiral path, generating a local high-speed jet in the tiny gap between the top of the turbulence strip and the tank wall, which directly impacts the tank wall surface and peels off the attached loose crystalline layer.

[0011] Preferably, the upper scraping structure includes two upper rings fixed on the stirring shaft. The two upper rings are linearly distributed from top to bottom. Each upper ring has multiple sets of upper connecting parts arranged in a ring array. An upper scraper is installed between the corresponding two upper connecting parts on the upper and lower rings.

[0012] Preferably, the upper connecting member includes an upper connecting sleeve welded to the outer surface of the upper collar. The upper connecting sleeve has an insertion hole inside, and an upper connecting arm is slidably inserted into the insertion hole. The end of the upper connecting arm away from the upper collar is outside the upper connecting sleeve and fixed to the upper scraper. An upper abutment ring is fixed to the end of the upper connecting arm inside the insertion hole. An upper lifting spring is sleeved on the upper connecting arm. The two ends of the upper lifting spring are fixed to the upper abutment ring and the inner wall of the insertion hole, respectively. The upper lifting spring causes the upper scraper to always have a tendency to move towards the upper collar.

[0013] Preferably, the lower scraping structure includes a lower sleeve ring fixed on the stirring shaft, and multiple sets of lower connecting parts arranged in a ring array are fixed at both ends of the outer surface of the lower sleeve ring. A lower scraper is installed between two corresponding lower connecting parts on the lower sleeve ring.

[0014] Preferably, the lower connecting member includes a lower connecting sleeve welded to the outer surface of the lower collar. The lower connecting sleeve is designed to be inclined downwards, and the two corresponding lower connecting sleeves are arranged in parallel. The lower connecting sleeve has an insertion groove inside, and a lower connecting arm is slidably inserted into the insertion groove. The end of the lower connecting arm away from the lower collar is outside the lower connecting sleeve and fixed to the lower scraper. The end of the lower connecting arm inside the insertion groove is fixed to a lower abutment ring. A lower lifting spring is sleeved on the lower connecting arm. The two ends of the lower lifting spring are fixed to the lower abutment ring and the inner wall of the insertion groove, respectively. The lower lifting spring makes the lower scraper always tend to move towards the lower collar. The lower half of the scraper has an arc-shaped structure, which can contact the arc-shaped surface at the bottom of the jacket and scrape it clean. The upper half of the scraper has a straight plate structure, which can scrape and clean the straight section of the jacket.

[0015] Preferably, both the upper scraper and the lower scraper are made of spring steel. The thickness of the upper scraper and the lower scraper gradually decreases from the end near the stirring shaft to the end away from the stirring shaft. The thick ends of the upper scraper and the lower scraper are rigidly connected to the upper connecting arm and the lower connecting arm, respectively, forming a cantilever thin-end structure between them.

[0016] Preferably, the end of the upper scraper is cut into multiple independent scraper strips along the circumferential direction, with a small upper gap between the segments and the length of each scraper strip is different; the end of the lower scraper is cut into multiple independent scraper strips along the circumferential direction, with a small lower gap between the segments and the length of each scraper strip is different. A single scraper is divided into multiple independent scraper strips, each with slightly different lengths and widths and different natural frequencies. At the same rotation speed, each strip generates different frequency flutter, forming a wide-band composite vibration. This results in a more uniform and efficient scraping effect. Furthermore, if there are minor unevenness or crystal protrusions on the tank wall, each scraper strip can deform independently to adapt, rather than the entire scraper being lifted up together. This ensures the fit between the scraper and the tank wall. At the same time, the gaps between the strips allow a small amount of liquid to pass through, and the resulting micro-jet can wash the scraper itself, reducing the adhesion of crystals to the scraper. An upper buffer pad is provided between the upper scraper and the upper connecting arm, and a lower buffer pad is provided between the lower scraper and the lower connecting arm. The upper and lower buffer pads are made of polyurethane or rubber. They can limit the maximum vibration amplitude of the upper and lower scrapers, prevent resonance runaway from causing excessive deformation or fatigue fracture of the upper and lower scrapers, and buffer the impact force.

[0017] The beneficial effects of this invention are: 1. Through the cooperation of the upper and lower scraping structures, the upper and lower scrapers swing outward and adhere to the inner wall of the crystallization tank by the centrifugal force generated by the rotation of the stirring shaft. This can be used to clean the inner wall of the crystallization tank. At the same time, the scraping pressure can be adaptively adjusted with the stirring speed. In the low-speed crystallization stage, the scraper automatically retracts under the action of the lifting spring and disengages from the tank wall without generating any frictional resistance. In the high-speed cleaning stage, the scraper automatically unfolds under the action of centrifugal force to scrape against the wall, which greatly reduces the energy consumption of the equipment and avoids continuous scraping damage to the polished surface of the inner wall of the tank, maintaining the GMP aseptic smoothness requirements. It also effectively prevents the scraper from wearing off and chipping off the scraper and contaminating the raw materials caused by constant pressure.

[0018] 2. Through the forced circulation and annular scouring of the guide tube, the fluid self-cleaning of the intermediate tank wall is achieved. The turbulence strips on the outer wall of the guide tube generate local disturbances to the upward flow in the annular gap, enhancing the scouring effect. Together with the upper and lower mechanical scrapers, it forms a complete tank wall coverage without dead angles. The rounded chamfers at the upper and lower ends of the guide tube eliminate flow dead zones, and the mirror polishing of the inner and outer walls reduces nucleation sites. The guide tube only guides the flow and does not participate in heat exchange, effectively preventing crystals from adhering to the surface of the guide tube. At the same time, the temperature distribution throughout the tank is uniform, so that the supersaturation of the entire tank is at a uniform and relatively low stable value. Under this uniform low supersaturation, the number of nuclei is precisely controlled, and the existing crystal seeds in the solution will grow steadily and slowly, with a narrow particle size distribution and a high proportion of large particles, effectively improving the crystallization effect and quality. Attached Figure Description

[0019] Figure 1 This is a front view of a high-efficiency crystallization apparatus for cefoperazone raw material proposed in this invention; Figure 2 This is an internal schematic diagram of a high-efficiency crystallization apparatus for cefoperazone raw material proposed in this invention; Figure 3 for Figure 2 Center view; Figure 4 for Figure 2 A schematic diagram of the structure of the middle stirring shaft, the upper scraping structure, and the lower scraping structure; Figure 5 for Figure 4 A schematic diagram of the upper scraping structure; Figure 6 This is a schematic diagram of the upper scraper in the upper scraping structure; Figure 7 for Figure 4 A schematic diagram of the middle and lower scraping structure; Figure 8 This is a schematic diagram of the lower scraper in the lower scraping structure.

[0020] Numbering on the map: 1. Crystallizer; 11. Tank body; 12. Jacket; 13. Discharge valve; 2. Drive motor; 3. Flow deflector; 31. Upper section; 32. Middle section; 33. Lower section; 34. Spoiler strips; 35. Spoiler wing; 4. Stirring shaft; 5. Upper scraping structure; 51. Upper collar; 52. Upper connector; 521. Upper connecting sleeve; 522. Upper connecting arm; 523. Upper lifting spring; 524. Upper abutment ring; 53. Upper scraper; 531. Upper gap; 532. Upper buffer pad; 6. Lower scraping structure; 61. Lower collar; 62. Lower connector; 621. Lower connecting sleeve; 622. Lower connecting arm; 623. Lower lifting spring; 624. Lower abutment ring; 63. Lower scraper; 631. Lower gap; 632. Lower buffer pad; 7. Stirring paddle. Detailed Implementation

[0021] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0022] Reference Figure 1 - Figure 8 A high-efficiency crystallization device for cefoperazone raw material includes a crystallization tank 1. A stirring shaft 4 is rotatably mounted inside the crystallization tank 1 via a bearing. A drive motor 2 is mounted on the top of the crystallization tank 1. The upper end of the stirring shaft 4 passes through the crystallization tank 1 and is connected to the output shaft of the drive motor 2. An upper scraping structure 5 and a lower scraping structure 6 are respectively mounted on the upper and lower ends of the stirring shaft 4. The upper scraping structure 5 and the lower scraping structure 6 respectively include an upper scraper 53 and a lower scraper 63 that rotate coaxially with the stirring shaft 4. The upper scraper 53 and the lower scraper 63 swing outward and adhere to the inner wall of the crystallization tank 1 by the centrifugal force generated by the rotation of the stirring shaft 4, so as to clean the inner wall of the crystallization tank 1. At the same time, the wall-scraping pressure is adaptively adjusted with the stirring speed. A guide tube 3 is fixedly installed in the middle of the crystallization tank 1. The outer diameter of the guide tube 3 gradually increases from top to bottom. An annular gap is formed between the guide tube 3 and the crystallization tank 1. A stirring paddle 7 is also installed on the stirring shaft 4. The stirring paddle 7 is located inside the guide tube 3. The stirring shaft 4 causes the solution to flow out from the bottom of the guide tube 3 and flow upward along the gap, scouring the outer wall of the guide tube 3 and the inner wall of the crystallization tank 1.

[0023] Reference Figure 2 The crystallization tank 1 includes a tank body 11 fixed on the frame. A jacket 12 is fitted inside the tank body 11. A discharge valve 13 is installed below the jacket 12. A feed port is also provided at the top of the tank body 11. A gap is left between the jacket 12 and the tank body 11 to form a clamping groove. Cooling medium is introduced into the clamping groove, thereby causing the solution on the inner wall of the jacket 12 to crystallize.

[0024] Reference Figure 2 , Figure 3The guide tube 3 is coaxially arranged with the stirring shaft 4. The guide tube 3 includes an upper section 31, a middle section 32 and a lower section 33. The upper section 31 and the lower section 33 are of equal diameter, while the middle section 32 is a gradually changing section. The outer diameter of the middle section 32 increases linearly from top to bottom, and the taper angle is 0.5°-2°. The width of the annular gap formed between the guide tube 3 and the crystallizer 1 gradually decreases from top to bottom. The wide gap between the upper section 31 and the inner wall of the crystallizer 1 has a large flow cross-sectional area, low flow velocity, low dynamic pressure and high static pressure, forming a low-pressure slow flow zone. The narrow gap between the lower section 33 and the inner wall of the crystallizer 1 has a small flow cross-sectional area, high flow velocity, high dynamic pressure and low static pressure, forming a high-pressure strong flow zone. This achieves a natural zoning of the flow velocity within the annular gap—low-pressure slow flow in the upper part and high-pressure strong flow in the lower part.

[0025] When the solution flows out from the bottom of the guide tube 3, it has just entered the annular gap from the propulsion zone of the agitator 7. At this time, the solution temperature is relatively high, the temperature difference between it and the cooling medium of the jacket 12 is the largest, and the heat exchange demand is the most urgent. The narrowest annular gap and the highest flow rate are set in the bottom area. The high-speed solution washes the inner wall of the crystallizer 1 in a forced convection manner, which can quickly remove the latent heat of crystallization and cool the high-temperature solution to close to the target temperature in the shortest time. As the solution continues to flow upward along the annular gap, the solution temperature gradually decreases, and the temperature difference with the medium in jacket 12 gradually narrows, thus reducing the heat exchange demand. At this time, the gap gradually widens and the flow rate gradually slows down, which avoids excessive local supersaturation caused by overcooling and saves the stirring energy required to maintain a high flow rate. This optimal heat transfer matching principle of large temperature difference with large flow rate and small temperature difference with small flow rate ensures that the heat exchange intensity of each area of ​​the entire tank accurately corresponds to the local heat load. It effectively eliminates the drawbacks of insufficient heat exchange in the lower part and excessive cooling in the upper part caused by the uniform flow rate throughout the traditional constant diameter guide tube 3, making the temperature field in the entire crystallizing tank 1 more uniform.

[0026] Preferably, the upper end of the upper section 31 and the lower end of the lower section 33 are provided with rounded chamfers, and the radius of the rounded chamfer R is greater than or equal to 10 mm, which can eliminate the flow dead zone and eddy current stagnation zone at the sharp corners and prevent the crystal from preferentially adhering at the edge. The surface roughness Ra of the inner and outer walls of the flow guide tube 3 is Ra≤0.4μm, which reduces the nucleation sites on the solid surface and lowers the probability of heterogeneous nucleation of crystals on the surface of the flow guide tube 3. At the same time, the flow guide tube 3 only serves as a flow guide component and does not undertake the heat exchange function.

[0027] The upper outer edge of the upper section 31 of the guide tube 3 is uniformly provided with turbulence wings 35 along the circumferential direction. Each turbulence wing 35 is inclined downward at 30° along the rotation direction of the stirring paddle 7. The thickness of the turbulence wing 35 is the same as the thickness of the tube wall of the guide tube 3. The side of the turbulence wing 35 facing the fluid flow is a circular arc guide surface, and the back side is a flat or micro-arc surface. When the downward flow generated by the rotation of the agitator 7 reaches the upper end of the guide tube 3, it will be blocked by the turbulence wing 35. Since the turbulence wing 5 is tilted downward at 30° along the rotation direction of the agitator, the arc guide surface of the wing will smoothly guide the main flow to the annular gap between the guide tube 3 and the jacket 12, avoiding the short circuit and dead zone of the fluid at the upper inlet of the guide tube 3, and making the circulation of the whole tank more complete. Meanwhile, after the fluid bypasses the turbulence wing 35, weak vortices are generated on the back side of the wing (i.e. downstream side). These micro vortices continuously disturb the concentration boundary layer and temperature boundary layer of the tank wall near the liquid surface, destroying the conditions required for crystal nucleation on the tank wall surface (i.e., local supersaturation accumulation), thus preventing crystal scars from forming on the tank wall near the liquid surface from the source.

[0028] The lower section of the outer wall of the guide tube 3 is provided with a spiral turbulence bar 34. When the solution flows upward along the annular gap, it is simultaneously subjected to tangential impact and axial guidance by the spiral turbulence bar 34, generating a three-dimensional spiral turbulence containing velocity components in the radial, tangential and axial directions. The shear stress of this turbulence on the tank wall is much higher than the two-dimensional disturbance generated by the vertical turbulence bar. Under narrow gap and high flow velocity conditions, the spiral baffle 34 forces the fluid to move along the spiral path, generating a local high-speed jet in the tiny gap between the top of the baffle 34 and the tank wall, which directly impacts the surface of the tank wall and peels off the attached loose crystalline layer.

[0029] Reference Figure 4 The upper scraping structure 5 includes two upper rings 51 fixed on the stirring shaft 4. The two upper rings 51 are linearly distributed from top to bottom. Each upper ring 51 has multiple sets of upper connecting parts 52 arranged in a ring array. An upper scraper 53 is installed between the corresponding two upper connecting parts 52 on the upper and lower upper rings 51.

[0030] Reference Figure 5 , Figure 6 The upper connecting member 52 includes an upper connecting sleeve 521 welded to the outer surface of the upper collar 51. The upper connecting sleeve 521 has an insertion hole inside, and an upper connecting arm 522 is slidably inserted into the insertion hole. The end of the upper connecting arm 522 away from the upper collar 51 is outside the upper connecting sleeve 521 and fixed to the upper scraper 53. The end of the upper connecting arm 522 inside the insertion hole is fixed to an upper abutment ring 524. An upper lifting spring 523 is sleeved on the upper connecting arm 522. The two ends of the upper lifting spring 523 are fixed to the upper abutment ring 524 and the inner wall of the insertion hole, respectively. The upper lifting spring 523 makes the upper scraper 53 always have a tendency to move towards the upper collar 51. During the low-speed crystallization stage, the thrust of the upper lifting spring 523 is greater than the centrifugal force on the upper connecting arm 522 and the upper scraper 53. The upper connecting arm 522 is pushed towards the axis of the stirring shaft 4, and the upper scraper 53 maintains a certain gap with the inner wall of the jacket 12, so as not to generate additional resistance and not to interfere with the stability of the liquid surface and the crystallization environment. During the high-speed cleaning phase, the centrifugal force on the upper connecting arm 522 and the upper scraper 53 is greater than the thrust of the upper lifting spring 523. The upper connecting arm 522 slides outward along the upper connecting sleeve 521, and the upper scraper 53 rotates close to the tank wall of the jacket 12 to scrape off the crystal skin attached near the liquid surface and the upper tank wall.

[0031] Reference Figure 4 , Figure 7 The lower scraping structure 6 includes a lower sleeve ring 61 fixed on the stirring shaft 4. Multiple sets of lower connecting pieces 62 arranged in a ring array are fixed at both ends of the outer surface of the lower sleeve ring 61. A lower scraper 63 is installed between two corresponding lower connecting pieces 62 on the lower sleeve ring 61.

[0032] Reference Figure 7 , Figure 8 The lower connecting member 62 includes a lower connecting sleeve 621 welded to the outer surface of the lower collar 61. The lower connecting sleeve 621 is designed to be inclined downwards, and the two corresponding lower connecting sleeves 621 are arranged in parallel. The lower connecting sleeve 621 has an insertion groove inside, and a lower connecting arm 622 is slidably inserted into the insertion groove. The end of the lower connecting arm 622 away from the lower collar 61 is outside the lower connecting sleeve 621 and fixed to the lower scraper 63. The end of the lower connecting arm 622 inside the insertion groove is fixed to a lower abutment ring 624. A lower lifting spring 623 is sleeved on the lower connecting arm 622. The two ends of the lower lifting spring 623 are fixed to the lower abutment ring 624 and the inner wall of the insertion groove, respectively. The lower lifting spring 623 makes the lower scraper 63 always tend to move towards the lower collar 61. The lower half of the scraper 63 has an arc-shaped structure design, which can contact the arc-shaped surface at the bottom of the jacket 12 and scrape and clean it. The upper half of the scraper 63 has a straight plate structure, which can scrape and clean the straight section of the jacket 12. During the low-speed crystallization stage, the thrust of the lower lifting spring 623 is greater than the centrifugal force, the lower connecting arm 622 is pushed towards the axis of the stirring shaft 4, and the lower scraper 63 maintains a gap with the tank wall of the jacket 12. During the high-speed cleaning phase, the centrifugal force is greater than the thrust of the lower lifting spring 623, the lower connecting arm 622 slides outward along the lower connecting sleeve 621, and the lower scraper 63 rotates and scrapes against the tank wall of the jacket 12.

[0033] Reference Figure 6 , Figure 8 Both the upper scraper 53 and the lower scraper 63 are made of spring steel. The thickness of the upper scraper 53 and the lower scraper 63 gradually decreases from the end near the stirring shaft 4 to the end away from the stirring shaft 4. The thick ends of the upper scraper 53 and the lower scraper 63 are rigidly connected to the upper connecting arm 522 and the lower connecting arm 622 respectively, forming a cantilever thin-end structure between them. The upper scraper 53 and the lower scraper 63 are made of spring steel and have a cantilever thin-end structure. When they rotate at high speed and are close to the tank wall, they use friction to generate self-excited high-frequency flutter, forming a composite cleaning effect of shearing and scraping as well as high-frequency micro-vibration impact, which improves the scraping effect.

[0034] The end of the upper scraper 53 is cut into multiple independent scraper strips along the circumference, with a small upper gap 531 between the segments, and the lengths of the scraper strips vary. The end of the lower scraper 63 is cut into multiple independent scraper strips along the circumference, with a small lower gap 631 between the segments, and the lengths of the scraper strips vary. A single scraper is divided into multiple independent scraper strips, each with slightly different lengths and widths and different natural frequencies. When the stirring shaft 4 rotates at the same speed, each scraper strip generates a flutter at a different frequency, thus expanding the original single-frequency self-excited vibration into a broadband composite vibration. This broadband vibration has a better removal effect on different types of scars, including dense hard scars, loose crystal skin, and sticky deposits, overcoming the limitation that single-frequency vibration is only effective for specific types of scars. Furthermore, when there are minor unevenness or crystal protrusions on the surface of the tank wall, each section of the scraper can deform independently to adapt to the micro-morphology of the tank wall, rather than the entire scraper being lifted up. This ensures that the scraper and the tank wall are closely fitted in various local areas, avoiding scraping blind spots caused by the scraper being lifted up due to local protrusions. Meanwhile, the gaps between sections allow a small amount of liquid to pass through at high speed. These liquids form tiny jets between the scraper and the tank wall, which scour the surface of the scraper itself, effectively reducing the adhesion of crystals on the scraper, delaying the scaling of the scraper, and extending the continuous running time of the scraper. By setting a segmented structure, the flutter of the upper scraper 53 and the lower scraper 63 is expanded from a single frequency to a wide-band composite vibration, which has a better removal effect on different types of scale, such as dense hard scale, loose crystal skin, and sticky deposits. The self-flushing effect of the gaps reduces the scale buildup on the upper scraper 53 and the lower scraper 63 themselves, and extends the continuous running time of the upper scraper 53 and the lower scraper 63. An upper buffer pad 532 is provided between the upper scraper 53 and the upper connecting arm 522, and a lower buffer pad 632 is provided between the lower scraper 63 and the lower connecting arm 622. The upper buffer pad 532 and the lower buffer pad 632 are made of polyurethane or rubber buffer pads. They can limit the maximum vibration amplitude of the upper scraper 53 and the lower scraper 63, prevent resonance runaway from causing excessive deformation or fatigue fracture of the upper scraper 53 and the lower scraper 63, and at the same time buffer the impact force.

[0035] Working principle: Crude cefoperazone is dissolved in a solvent (methanol), then decolorized by activated carbon and filtered. The resulting filtrate is fed into crystallizer 1 through the feed inlet, while the liquid level is controlled to be about 200 mm above the top of the guide tube 3.

[0036] Then, the drive motor 2 is started, and the stirring shaft 4 rotates at a speed of 40 r / min. The upper connecting part 52 and the lower connecting part 62 are in a retracted state under the action of the upper lifting spring 523 and the lower lifting spring 623, respectively. There is a gap between the upper scraper 53, the lower scraper 63 and the tank wall of the jacket 12. Meanwhile, the solution inside the guide tube 3 moves downward under the push of the stirring paddle 7, flows out from the bottom of the guide tube 3 and flows upward along the annular gap, and fully exchanges heat with the jacket 12. The temperature of the whole tank is uniformly controlled between 5 and 10℃ (temperature difference ≤ ±0.5℃). Hydrochloric acid aqueous solution is added dropwise into the tank for crystallization. During the crystallization process, the stirring speed is maintained at 40 r / min and the crystal growth time is 1.5 hours.

[0037] A cleaning operation is performed every 30 minutes. The speed of the stirring shaft 4 is increased to 75 r / min and kept running for a few minutes. At this time, the upper connecting arm 522 and the lower connecting arm 622 slide outward under the action of centrifugal force, overcoming the thrust of the upper lifting spring 523 and the lower lifting spring 623 respectively. The upper scraper 53 adheres to the upper tank wall and generates self-excited vibration, scraping off the crystal skin attached to the liquid surface and the upper tank wall. The lower scraper 63 adheres to the tank wall and generates self-excited vibration, scraping off the crystal layer accumulated and compacted in the lower part of the straight section and the arc section. The middle section of the tank wall is continuously flushed by the annular gap upward flow induced by the guide tube 3. After a period of time, the speed is reduced to 40 r / min, and all components automatically reset, restoring the crystallization state.

[0038] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0039] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0040] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A high-efficiency crystallization apparatus for cefoperazone raw material, characterized in that, The system includes a crystallization tank (1), inside which a stirring shaft (4) is rotatably mounted via bearings. A drive motor (2) is mounted on the top of the crystallization tank (1). The upper end of the stirring shaft (4) passes through the crystallization tank (1) and is connected to the output shaft of the drive motor (2). An upper scraping structure (5) and a lower scraping structure (6) are respectively mounted on the upper and lower ends of the stirring shaft (4). The upper scraping structure (5) and the lower scraping structure (6) respectively include an upper scraper (53) and a lower scraper (63) that rotate coaxially with the stirring shaft (4). The upper scraper (53) and the lower scraper (63) swing outward and adhere to the inner wall of the crystallization tank (1) by the centrifugal force generated by the rotation of the stirring shaft (4) to clean the inner wall of the crystallization tank (1) and at the same time realize the adaptive adjustment of the wall scraping pressure with the stirring speed. A guide tube (3) is fixedly installed in the middle of the crystallization tank (1). The outer diameter of the guide tube (3) gradually increases from top to bottom. An annular gap is formed between the guide tube (3) and the crystallization tank (1). A stirring paddle (7) is also installed on the stirring shaft (4). The stirring paddle (7) is located inside the guide tube (3). The stirring shaft (4) causes the solution to flow out from the bottom of the guide tube (3) and flow upward along the gap, scouring the outer wall of the guide tube (3) and the inner wall of the crystallization tank (1).

2. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 1, characterized in that, The crystallization tank (1) includes a tank body (11) fixed on the frame. A jacket (12) is sleeved inside the tank body (11). A discharge valve (13) is installed below the jacket (12). A gap is left between the jacket (12) and the tank body (11) to form a clamping groove.

3. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 1, characterized in that, The guide tube (3) is coaxially arranged with the stirring shaft (4). The guide tube (3) includes an upper section (31), a middle section (32) and a lower section (33). The upper section (31) and the lower section (33) are equal diameter sections, the middle section (32) is a gradually changing section, the outer diameter of the middle section (32) increases linearly from top to bottom, and the taper angle is 0.5°-2°. The width of the annular gap formed between the guide tube (3) and the crystallizer (1) gradually decreases from top to bottom. The upper end of the upper section (31) and the lower end of the lower section (33) are both provided with rounded chamfers, and the radius of the rounded chamfer R≥10mm. The surface roughness Ra of the inner and outer walls of the guide tube (3) is ≤0.4μm.

4. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 1, characterized in that, The upper outer edge of the upper section (31) of the guide tube (3) is uniformly provided with turbulence wings (35) along the circumferential direction. Each turbulence wing (35) is inclined downward at 30° along the rotation direction of the stirring paddle (7). The thickness of the turbulence wing (32) is consistent with the thickness of the tube wall of the guide tube (3). The lower section of the guide tube (3) is provided with a spiral turbulence strip (34).

5. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 1, characterized in that, The upper scraping structure (5) includes two upper rings (51) fixed on the stirring shaft (4). The two upper rings (51) are linearly distributed from top to bottom. Each upper ring (51) has multiple sets of upper connectors (52) arranged in a ring array. An upper scraper (53) is installed between the two corresponding upper connectors (52) on the upper and lower upper rings (51).

6. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 5, characterized in that, The upper connector (52) includes an upper connecting sleeve (521) welded to the outer surface of the upper collar (51). The upper connecting sleeve (521) has an insertion hole inside, and an upper connecting arm (522) is slidably inserted into the insertion hole. One end of the upper connecting arm (522) away from the upper collar (51) is outside the upper connecting sleeve (521) and fixed to the upper scraper (53). One end of the upper connecting arm (522) inside the insertion hole is fixed with an upper abutment ring (524). An upper lifting spring (523) is sleeved on the upper connecting arm (522). The two ends of the upper lifting spring (523) are fixed to the upper abutment ring (524) and the inner wall of the insertion hole, respectively.

7. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 6, characterized in that, The lower scraping structure (6) includes a lower collar (61) fixed on the stirring shaft (4). Multiple sets of lower connecting pieces (62) arranged in a ring array are fixed at both ends of the outer surface of the lower collar (61). A lower scraper (63) is installed between two corresponding lower connecting pieces (62) on the lower collar (61).

8. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 7, characterized in that, The lower connector (62) includes a lower connecting sleeve (621) welded to the outer surface of the lower collar (61). The lower connecting sleeve (621) is designed to be inclined downwards, and the two corresponding lower connecting sleeves (621) are arranged in parallel. The lower connecting sleeve (621) has an insertion groove inside, and a lower connecting arm (622) is slidably inserted into the insertion groove. The end of the lower connecting arm (622) away from the lower collar (61) is outside the lower connecting sleeve (621) and fixed to the lower scraper (63). The lower connecting arm (622) is fixed to a lower abutment ring (624) at one end inside the insertion groove. A lower lifting spring (623) is sleeved on the lower connecting arm (622). The two ends of the lower lifting spring (623) are fixed to the lower abutment ring (624) and the inner wall of the insertion groove, respectively.

9. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 8, characterized in that, The upper scraper (53) and the lower scraper (63) are both made of spring steel. The thickness of the upper scraper (53) and the lower scraper (63) gradually decreases from the end near the stirring shaft (4) to the end away from the stirring shaft (4). The thick ends of the upper scraper (53) and the lower scraper (63) are rigidly connected to the upper connecting arm (522) and the lower connecting arm (622), respectively.

10. The high-efficiency crystallization apparatus for cefoperazone raw material according to claim 9, characterized in that, The end of the upper scraper (53) is cut into multiple independent scraper strips along the circumferential direction, with a small upper gap (531) between the segments. The lengths of the scraper strips are different. The end of the lower scraper (63) is cut into multiple independent scraper strips along the circumferential direction, with a small lower gap (631) between the segments. The lengths of the scraper strips are different. An upper buffer pad (532) is provided between the upper scraper (53) and the upper connecting arm (522), and a lower buffer pad (632) is provided between the lower scraper (63) and the lower connecting arm (622).

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