Crystallization process of cefazolin acid

Abstract

The invention provides a crystallization process of cefazolin acid, and relates to the technical field of medicine production. The crystallization process comprises the following steps: arranging a cefazolin acid seed crystal on the surface of a rotary drum; heating the feed liquid to a preset temperature, and keeping the temperature; the rotary drum is placed above the feed liquid, and a seed crystal layer on the surface of the rotary drum is immersed into the liquid level of the feed liquid by a preset depth; wherein the feed liquid comprises excessive cefazolin acid, and saturated cefazolin acid is dissolved in the feed liquid; water with the preset water temperature is introduced into the rotary drum, so that the temperature of the rotary drum is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature; and rotating the rotary drum to crystallize the cefazolin acid on the seed crystal layer of the rotary drum. The invention provides a crystallization process of cefazolin acid, which can be used for obtaining large-size cefazolin acid crystals.

Description

Technical Field

[0001] The invention relates to the technical field of drug production, and in particular to a crystallization process of cefazolin acid. Background Art

[0002] Cefazolin sodium is an anti-inflammatory drug widely used in inflammation. Cefazolin acid is an important raw material for the synthesis of cefazolin sodium.

[0003] In the related art, the crystal size of cefazolin acid is relatively small, which can easily cause equipment damage and crystal yield loss when centrifuged.

[0004] Therefore, in view of the above problems, a crystallization process of cefazolin acid is urgently needed to obtain large-sized cefazolin acid crystals. Summary of the invention

[0005] The present invention provides a crystallization process of cefazolin acid, which can obtain large-sized cefazolin acid crystals. The technical scheme of the present invention is as follows:

[0006] A crystallization process of cefazolin acid, comprising:

[0007] placing cefazolin acid seed crystals on the surface of the drum to form a seed crystal layer;

[0008] Heat the liquid to a preset temperature and keep it warm;

[0009] The drum is placed above the feed liquid, so that the seed layer on the surface of the drum is immersed in the feed liquid to a preset depth; wherein the feed liquid includes an excess of cefazolin acid, so that the feed liquid is saturated with cefazolin acid;

[0010] Passing water of a preset water temperature into the drum so that the temperature of the drum is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature;

[0011] The drum was rotated to allow cefazolin acid to crystallize on the seed layer of the drum.

[0012] Preferably, the preset depth is 0-3 mm.

[0013] Preferably, the solid cefazolin acid in the liquid is contained in a container with a filter, and the filter provided in the container is used to prevent the solid cefazolin acid from escaping from the container.

[0014] Preferably, it also includes:

[0015] The container containing cefazolin acid is spirally lifted and lowered in the liquid.

[0016] Preferably, the preset temperature is 10-30°C, and the preset water temperature is 1-5°C lower than the preset temperature.

[0017] Preferably, the step of heating the liquid to a preset temperature and keeping the temperature constant comprises:

[0018] A plurality of heating devices are installed in the vertical direction around the barrel where the liquid is located;

[0019] Installing a plurality of temperature sensors at different depths of the barrel;

[0020] The power of each of the heating devices is dynamically adjusted according to the temperature of the temperature sensor so that the temperature of the slurry is maintained at the preset temperature.

[0021] Preferably, in the process of rotating the drum to allow cefazolin acid to crystallize on the seed layer of the drum, the method further comprises:

[0022] Monitoring the liquid level of the feed liquid, and dynamically replenishing the feed liquid according to the liquid level of the feed liquid, so that the liquid level of the feed liquid remains unchanged;

[0023] The depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid is monitored, and the height position of the rotating drum is adjusted according to the depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid, so that the depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid is maintained at a preset depth.

[0024] Preferably, the step of monitoring the liquid level of the feed liquid and dynamically replenishing the feed liquid according to the liquid level of the feed liquid comprises:

[0025] Monitoring the liquid level of the feed liquid, and replenishing the feed liquid using a feed replenishment bin filled with saturated cefazolin acid feed liquid at a preset temperature, so that the liquid level of the feed liquid reaches a preset height; wherein the output port of the feed replenishment bin is strip-shaped, and the height is the preset height;

[0026] A material receiving bin is provided and an input port of the bin is provided at a preset height, and the input port of the material receiving bin is strip-shaped.

[0027] Preferably, it also includes:

[0028] The preset water temperature is adjusted according to the thickness of the crystal layer; wherein, the thicker the thickness, the lower the preset water temperature.

[0029] Preferably, adjusting the preset water temperature according to the thickness of the crystal layer comprises:

[0030] Calculate the vertical projection area of ​​the portion of the drum immersed in the liquid;

[0031] The heat flow is calculated using the Fourier conduction formula Q = -kA (ΔT / Δx);

[0032] Wherein, Q is the heat flow, Δx is the crystal layer thickness, A is the vertical projection area, k is the thermal conductivity of cefazolin acid, and ΔT is the temperature difference between the preset water temperature and the preset temperature;

[0033] As the thickness of the crystal layer increases, Δx changes. Substitute the new Δx into the above formula, keep other parameters unchanged, and obtain a new ΔT. Keep the preset temperature unchanged, and adjust the preset water temperature to make the above formula valid.

[0034] Compared with the prior art, the present invention has at least the following beneficial effects:

[0035] In the present embodiment, the cefazolin acid seed is first arranged on the surface of the drum, and then the drum is placed above the feed liquid, so that the seed layer covered on the drum is contacted with the feed liquid surface. The feed liquid includes dissolving saturated cefazolin acid, and the seed on the drum, when contacting the saturated feed liquid, crystallizes to obtain large-sized cefazolin acid crystals at the easy crystallization place of the solid-liquid interface, under the growth site provided by the seed. Before crystallization, it is necessary to heat the feed liquid to a preset temperature. After reaching the preset temperature, the feed liquid has a higher cefazolin acid solubility, and is easy to drop in temperature when being cooled, which is convenient for crystal precipitation. For the convenience of crystallization, water with a preset water temperature is introduced into the drum, and then the temperature of the drum is controlled to be the preset water temperature, and the preset water temperature is lower than the preset temperature so that the saturated state in the feed liquid is destroyed, and cefazolin acid is separated out under the promotion of the seed. In the process of crystallization, it is necessary to rotate the drum to prevent a certain position from being in a state of contact with the feed liquid for a long time, causing the feed liquid and the crystal contacting therewith to reduce the temperature difference, and inhibiting crystal growth. The rotating drum can prevent the crystals from contacting with the liquid for a long time, and can also grow crystals around the drum, so that a larger crystal surface can be obtained in a smaller space. In addition, the rotation of the drum can also make the liquid on the surface of the liquid flow. A certain fluidity can not only replenish the saturated or supersaturated liquid near the crystal layer, but also provide a certain vibration to promote crystallization. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0037] Figure 1 This is a crystallization process flow chart of cefazolin acid provided in an embodiment of the present invention;

[0038] Figure 2 It is a schematic diagram of the structure of a device for achieving crystallization of cefazolin acid provided in an embodiment of the present invention;

[0039] Figure 3 It is a schematic structural diagram of a container provided by an embodiment of the present invention.

[0040] In the figure:

[0041] 1- Rotating drum;

[0042] 2- liquid;

[0043] 3-Container;

[0044] 31-through-tube;

[0045] 32- curved panel;

[0046] 4- Heating device;

[0047] 5- Feeding silo;

[0048] 6- Material collection bin. DETAILED DESCRIPTION

[0049] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0050] like Figure 1 to Figure 2 As shown, the embodiment of the present invention provides a crystallization process of cefazolin acid, comprising:

[0051] placing cefazolin acid seed crystals on the surface of the drum 1 to form a seed crystal layer;

[0052] Heat the liquid 2 to a preset temperature and keep it warm;

[0053] The drum 1 is placed above the feed liquid 2, so that the seed layer on the surface of the drum 1 is immersed in the feed liquid 2 to a preset depth; wherein the feed liquid 2 includes an excess of cefazolin acid, so that the feed liquid 2 is saturated with cefazolin acid;

[0054] Water of a preset water temperature is introduced into the drum 1 so that the temperature of the drum 1 is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature;

[0055] The drum 1 is rotated to allow cefazolin acid to crystallize on the seed crystal layer of the drum 1 .

[0056] In the present embodiment, the cefazolin acid seed crystal is first arranged on the surface of the drum 1, specifically, it can be glued and bonded on the surface of the drum 1, or it can be pressed on the surface of the drum 1. Then the drum 1 is placed above the feed liquid 2, so that the seed crystal layer covered on the drum 1 is in contact with the liquid surface of the feed liquid 2. The feed liquid 2 includes cefazolin acid dissolved to saturation, and the seed crystal on the drum 1, when contacting the saturated feed liquid 2, crystallizes to obtain large-sized cefazolin acid crystals at the easy crystallization place of the solid-liquid interface, under the growth site provided by the seed crystal. Before crystallization, the feed liquid 2 needs to be heated to a preset temperature. After reaching the preset temperature, the feed liquid 2 has a higher solubility of cefazolin acid, and is easy to drop in temperature when it is cold. In order to facilitate crystallization, water with a preset water temperature is introduced into the drum 1, and then the temperature of the drum 1 is controlled to be the preset water temperature. The preset water temperature is lower than the preset temperature so that the saturated state in the feed liquid 2 is destroyed, and the cefazolin acid is precipitated under the promotion of the seed crystal. The water introduced into the drum 1 can be recycled through a circulation pipeline. During the crystallization process, it is necessary to rotate the drum 1 to prevent a certain position from being in contact with the liquid 2 for a long time, which will reduce the temperature difference between the liquid 2 and the crystals in contact with it and inhibit the growth of crystals. The rotating drum 1 can prevent the crystals from being in contact with the liquid 2 for a long time, and can also grow crystals all around the drum 1, so that a larger crystallization surface can be obtained in a smaller space. In addition, the rotation of the drum 1 can also make the liquid on the surface of the liquid 2 flow. A certain fluidity can not only replenish the saturated or supersaturated liquid 2 near the crystal layer, but also provide a certain vibration to promote crystal crystallization. It should be noted that whether it is promoting liquid flow or a certain liquid vibration, it needs to be kept in a lower range, otherwise, the crystallization environment is too unstable and the resulting crystal size is small.

[0057] It should be noted that the rotation speed of the drum 1 is relatively slow, and the vibration it provides is extremely small, which is conducive to crystallization but will not cause large-scale disturbance to the liquid surface.

[0058] In this embodiment, the drum 1 can be a polygonal prism composed of multiple planes, or can be a cylindrical shape.

[0059] In this embodiment, the slurry 2 may include acids, alcohols, esters and water.

[0060] In some embodiments of the present invention, the preset depth is 0-3 mm.

[0061] In this embodiment, the optimal depth of the cefazolin acid crystal layer immersed in the liquid surface is 0 to 3 mm. If it is too deep, the temperature difference will be too small, the hydraulic pressure will be too large, and the crystal quality will be reduced.

[0062] It should be noted that the rotation speed of the drum 1 is relatively slow. In the process of its bottom part slowly rotating away from the liquid surface, due to the surface tension of the liquid surface, the part of the drum 1 that has just left the liquid surface will pull the liquid surface in contact with it to a certain height. At this height, the seed crystal can contact the liquid and has sufficient material basis to form recrystallized crystals. At the same time, at the force balance between the rising liquid level and the gravity of the liquid, the force is very weak and approaches zero, which will not affect the precipitation of the recrystallized crystals, allowing the crystals to fully crystallize and obtain larger crystals. If the drum 1 penetrates deeper below the liquid surface, the hydraulic pressure will be larger, which greatly affects the size of the recrystallized crystals.

[0063] In some embodiments of the present invention, the solid cefazolin acid in the liquid 2 is contained in a container 3 with a filter screen, and the filter screen provided in the container 3 is used to prevent the solid cefazolin acid from escaping from the container 3 .

[0064] In this embodiment, the solid cefazolin acid contained in the container 3 can be quickly dissolved in the liquid 2 after part of the cefazolin acid is crystallized, thereby maintaining the saturation state of the cefazolin acid in the liquid 2, and at the same time prevent the solid cefazolin acid particles from flowing into the liquid 2 and then flowing onto the seed crystals and covering the seed crystals, resulting in the inability to obtain uniform, high-quality large crystals.

[0065] In some embodiments of the present invention, it further comprises:

[0066] A container 3 containing cefazolin acid is spirally lifted and lowered in the liquid 2, preferably a streamlined container 3.

[0067] In order to make the concentration of cefazolin acid in the liquid 2 uniform, the container 3 containing the cefazolin acid solid needs to be moved. It should be noted that a stirrer cannot be used for stirring. If a stirrer is used, although the concentration of cefazolin acid can be made uniform, the liquid level cannot be guaranteed to be stable. If the liquid level oscillates, the crystallization environment at the drum 1 will be affected, and large-sized cefazolin acid crystals cannot be obtained.

[0068] Please refer to Figure 3 In some embodiments of the present invention, the container 3 is an ellipsoid, and the container 3 is provided with a plurality of through holes toward the center thereof, and the through holes are penetrated by through tubes 31 whose apertures match the through holes and whose lengths are longer than the through holes. The two ends of the through tubes 31 are respectively connected with curved panels 32 matching the curvatures of the inner and outer walls of the container 3, and a filter is installed inside the through tubes 31.

[0069] Since it is not possible to cause a large fluctuation in the state of the liquid surface, an ellipsoidal container with a pointed head and a smooth external curved surface is selected to ensure movement without causing a large disturbance to the liquid.

[0070] In this embodiment, the container 3 can be composed of a whole metal filter screen, but in order to prevent a large disturbance to the liquid surface, the container 3 still needs to be controlled to have a reasonable moving speed. Therefore, the dissolution rate of the solid recrystallized material in the container 3 will be affected to a certain extent. In order to solve this problem, a plurality of through-tubes 31 inclined toward the center of the container 3 are designed. During the forward process of the through-tube 31 in the forward direction, the curved plate 32 at the outer end will push the through-tube 31 into the container 3 under the action of the liquid. The curved plate 32 fits with the tip of the container 3, which will not affect the liquid separation function of the tip of the forward end. At the same time, the liquid flowing into the container through the through-tube 31 has a faster flow rate, forming a fast flow rate in the container 3, accelerating dissolution, and small disturbance outside the container 3. The liquid in the container 3 flows out from the through-tube 31 at the rear end of the container 3, and the liquid pushes the curved plate 32 located inside the container 3 of the through-tube 31, so that the curved plate 32 is attached to the inner wall of the container 3. The through-tube 31 is mainly located outside the container 3, and the liquid dissolving the solute inside the container 3 is discharged from the through-tube 31 to the outside of the container 3. Since the through-tube 31 extends out of the container 3, the curved plate 32 outside the through-tube 31 partially disperses the liquid in the tail area of ​​the container 3, so that the liquid with solute discharged from the through-tube 31 is dispersed in multiple directions, achieving a rapid dispersion effect.

[0071] In some embodiments of the present invention, the preset temperature is 10-30°C, and the preset water temperature is 1-5°C lower than the preset temperature.

[0072] In this embodiment, the preset temperature is 10-30°C, at which the feed liquid 2 has a high solubility of cefazolin acid and is easy to drop in temperature when cooled. The preset water temperature is 1-5°C lower than the preset temperature, and the temperature difference should not be too large. If the temperature difference is greater than the above range, the crystallization speed is too fast and large-sized cefazolin acid crystals cannot be grown.

[0073] In some embodiments of the present invention, heating the feed liquid 2 to a preset temperature and keeping the temperature constant comprises:

[0074] A plurality of heating devices 4 are installed in the vertical direction around the barrel where the liquid 2 is located;

[0075] Install multiple temperature sensors at different depths of the barrel;

[0076] The power of each heating device 4 is dynamically adjusted according to the temperature of the temperature sensor to keep the temperature in the slurry 2 at a preset temperature.

[0077] In this embodiment, temperature stability is the basis for the growth of cefazolin acid crystals. In order to stabilize the temperature of the slurry 2, multiple heating devices 4 are arranged at different positions of the barrel where the slurry 2 is located, and multiple temperature sensors are arranged in the barrel. Through the cooperation of the heating device 4 and the temperature sensor, the temperature of the slurry 2 reaches a dynamic balance and is always maintained at a preset temperature.

[0078] In some embodiments of the present invention, during the process of rotating the drum 1 to crystallize cefazolin acid on the seed layer of the drum 1, the method further comprises:

[0079] Monitor the liquid level of the feed liquid 2, and dynamically replenish the feed liquid 2 according to the liquid level of the feed liquid 2 so that the liquid level of the feed liquid 2 remains unchanged;

[0080] Monitor the depth of the outer surface of the crystal layer formed on the surface of the drum 1 immersed in the liquid 2, and adjust the height position of the drum 1 according to the depth of the outer surface of the crystal layer formed on the surface of the drum 1 immersed in the liquid 2, so that the depth of the outer surface of the crystal layer formed on the surface of the drum 1 immersed in the liquid 2 is maintained at a preset depth.

[0081] In the present embodiment, as the crystals in the feed liquid 2 are precipitated and the solid cefazolin acid is dissolved, the volume of the feed liquid 2 will change, which will cause the liquid level to change. Therefore, it is necessary to monitor the liquid level. In addition, as the crystals are continuously precipitated on the surface of the drum 1, the thickness of the crystal layer on the drum 1 will also change. Therefore, in order to ensure the immersion depth, the immersion depth of the crystal layer outside the drum 1 must also be monitored. Specifically, a laser rangefinder sensor can be used. By arranging multiple laser rangefinder sensors at the bottom of the feed liquid 2, the laser is reflected when it is incident on the liquid surface. The liquid level can be obtained by the time difference between the emission and reception of the laser. Similarly, the height position of the crystal layer can also be obtained. Of course, other sensors that can measure position can also be selected, such as visual sensors and acoustic wave sensors.

[0082] In one embodiment of the present invention, monitoring the liquid level of the feed liquid and dynamically replenishing the feed liquid according to the liquid level of the feed liquid includes:

[0083] Monitor the liquid level of the feed liquid, and use the feed replenishment bin 5 filled with saturated cefazolin acid feed liquid at a preset temperature to replenish the feed liquid so that the liquid level of the feed liquid reaches a preset height; wherein the output port of the feed replenishment bin 5 is strip-shaped and has a preset height;

[0084] A material receiving bin 6 is provided and an input port of the bin 6 is provided at a preset height, and the input port of the material receiving bin 6 is strip-shaped.

[0085] In this embodiment, a feeding bin 5 and a receiving bin 6 are used, and the output port of the feeding bin 5 and the input port of the receiving bin 6 are set at preset heights, so that the balance of the liquid level can be dynamically adjusted. The output port of the feeding bin 5 and the input port of the receiving bin 6 are both flat strips, and the length of the strips can be the same as the width of the side wall of the barrel. With such a design, the flow rate per unit time is large, forming a laminar flow that flattens the liquid surface, and the disturbance to the liquid surface is small. In addition, the grains that have not grown on the drum 1 can enter the receiving bin 6 through the flow of the laminar flow to prevent them from affecting the crystallization of the drum 1, and these grains can be recovered. In addition, the laminar flow at a preset temperature can also ensure the stability of the liquid surface temperature.

[0086] It is understandable that both the feeding bin 5 and the receiving bin 6 can be provided with flow regulating valves to achieve the purpose of dynamic regulation.

[0087] In one embodiment of the present invention, it also includes:

[0088] The preset water temperature is adjusted according to the thickness of the crystal layer; wherein, the thicker the thickness, the lower the preset water temperature.

[0089] In one embodiment of the present invention, adjusting the preset water temperature according to the thickness of the crystal layer includes:

[0090] Calculate the vertical projection area of ​​the portion of the drum 1 immersed in the liquid 2;

[0091] The heat flow is calculated using the Fourier conduction formula Q = -kA (ΔT / Δx);

[0092] Wherein, Q is the heat flow, Δx is the seed layer thickness, A is the vertical projection area, k is the thermal conductivity of cefazolin acid, and ΔT is the temperature difference between the preset water temperature and the preset temperature;

[0093] As the thickness of the crystal layer increases, Δx changes. Substitute the new Δx into the above formula, keep other parameters unchanged, and get a new ΔT. Keep the preset temperature unchanged and adjust the preset water temperature to make the above formula valid.

[0094] In this embodiment, as the thickness of the crystal layer increases, its heat flow will change, which will in turn have a certain impact on the crystal quality. In order to obtain uniform and stable crystals, the stability of the heat flow can be ensured by adjusting the preset water temperature.

[0095] It will be appreciated that the adjustment of the preset water temperature may be controlled by the source of the water.

[0096] In some embodiments of the present invention, it further comprises:

[0097] After the rotating drum 1 is raised to a preset height from the initial crystal growth position, the rotating drum 1 is taken out and the crystal layer attached to its surface is collected;

[0098] A new rotating drum 1 with a seed layer attached thereto is replaced, and its height is adjusted so that the seed layer is immersed in the feed liquid 2 to a preset depth, and then crystal growth continues.

[0099] In this embodiment, if the crystal layer is too thick, it will affect the temperature of the outermost crystal layer, and the temperature difference between the surface of the crystal layer and the liquid 2 will be uncontrollable. Therefore, after a certain thickness, the drum 1 is taken out, and a new drum 1 is replaced. The crystals deposited with a certain thickness are taken out, and the inner layer of seeds are retained and used again. Of course, a brand new drum 1 covered with seeds can also be used.

[0100] In some embodiments of the present invention, rotating drum 1 to crystallize cefazolin acid on the seed layer of drum 1 comprises:

[0101] The drum 1 is rotated at a rotation speed of 0.1 to 0.03 r / min to allow cefazolin acid to crystallize on the seed crystal layer of the drum 1 .

[0102] In this embodiment, rotating the drum 1 at the above rotation speed can not only slightly stir the liquid flow, but also keep the liquid surface calm and leave sufficient time and space for crystallization.

[0103] In some embodiments of the present invention, the drum 1 is made of a heat-conducting material, which can keep the temperature of the drum 1 consistent with the temperature of the water passing through it in a timely manner.

[0104] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A crystallization process for cefazolin acid, characterized in that: include: placing cefazolin acid seed crystals on the surface of the drum to form a seed crystal layer; Heat the liquid to a preset temperature and keep it warm; The drum is placed above the feed liquid, so that the seed layer on the surface of the drum is immersed in the feed liquid to a preset depth; wherein the feed liquid includes an excess of cefazolin acid, so that the feed liquid is saturated with cefazolin acid; Passing water of a preset water temperature into the drum so that the temperature of the drum is the preset water temperature; wherein the temperature of the preset water temperature is lower than the preset temperature; The drum was rotated to allow cefazolin acid to crystallize on the seed layer of the drum.

2. A crystallization process for cefazolin acid according to claim 1, characterized in that: The preset depth is 0-3 mm.

3. A crystallization process for cefazolin acid according to claim 1, characterized in that: The cefazolin acid solid in the liquid is contained in a container with a filter screen, and the filter screen provided in the container is used to prevent the solid cefazolin acid from escaping from the container.

4. A crystallization process for cefazolin acid according to claim 3, characterized in that: Also includes: The container containing cefazolin acid is spirally lifted and lowered in the liquid.

5. A crystallization process for cefazolin acid according to claim 1, characterized in that: The preset temperature is 10-30°C, and the preset water temperature is 1-5°C lower than the preset temperature.

6. The crystallization process of cefazolin acid according to claim 1, characterized in that: The step of heating the liquid to a preset temperature and keeping the temperature constant comprises: A plurality of heating devices are installed in the vertical direction around the barrel where the liquid is located; Installing a plurality of temperature sensors at different depths of the barrel; The power of each of the heating devices is dynamically adjusted according to the temperature of the temperature sensor so that the temperature of the slurry is maintained at the preset temperature.

7. The crystallization process of cefazolin acid according to claim 1, characterized in that: In the process of rotating the drum to allow cefazolin acid to crystallize on the seed layer of the drum, the method further comprises: Monitoring the liquid level of the feed liquid, and dynamically replenishing the feed liquid according to the liquid level of the feed liquid, so that the liquid level of the feed liquid remains unchanged; The depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid is monitored, and the height position of the rotating drum is adjusted according to the depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid, so that the depth of the outer surface of the crystal layer formed on the surface of the rotating drum immersed in the liquid surface of the feed liquid is maintained at a preset depth.

8. The crystallization process of cefazolin acid according to claim 7, characterized in that: The step of monitoring the liquid level of the feed liquid and dynamically replenishing the feed liquid according to the liquid level of the feed liquid comprises: Monitoring the liquid level of the feed liquid, and replenishing the feed liquid using a feed replenishment bin filled with saturated cefazolin acid feed liquid at a preset temperature, so that the liquid level of the feed liquid reaches a preset height; wherein the output port of the feed replenishment bin is strip-shaped, and the height is the preset height; A material receiving bin is provided and an input port of the bin is provided at a preset height, and the input port of the material receiving bin is strip-shaped.

9. The crystallization process of cefazolin acid according to claim 7, characterized in that: Also includes: The preset water temperature is adjusted according to the thickness of the crystal layer; wherein, the thicker the thickness, the lower the preset water temperature.

10. The crystallization process of cefazolin acid according to claim 9, characterized in that: The step of adjusting the preset water temperature according to the thickness of the crystal layer comprises: Calculate the vertical projection area of ​​the portion of the drum immersed in the liquid; The heat flow is calculated using the Fourier conduction formula Q = -kA (ΔT / Δx); Wherein, Q is the heat flow, Δx is the crystal layer thickness, A is the vertical projection area, k is the thermal conductivity of cefazolin acid, and ΔT is the temperature difference between the preset water temperature and the preset temperature; As the thickness of the crystal layer increases, Δx changes. Substitute the new Δx into the above formula, keep other parameters unchanged, and obtain a new ΔT. Keep the preset temperature unchanged, and adjust the preset water temperature to make the above formula valid.

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