A process and apparatus for the preparation of ofloxacin and levofloxacin

Abstract

The application relates to the technical field of medicine preparation, in particular to a method for preparing ofloxacin and levofloxacin, which comprises the following steps: S1, material preparation and feeding; S2, dissolving and decoloring; S3, pressure filtration and crystallization; and S4, elution and drying. The preset heating temperature, the preset temperature adjusting temperature, the standard solution turbidity and the standard solution gray scale are arranged in a central control unit; the central control unit compares real-time parameters with preset parameters, judges and adjusts the real-time operation state of the preparation equipment, ensures the working efficiency and precision of the preparation equipment, the central control unit can adjust the temperature of the solution, the feeding amount of the activated carbon and the stirring speed of the cooling stirring device according to the change of the working condition, accurately judges whether the crude product raw material is completely dissolved and whether the solution is decolorized, accurately controls the working time and the raw material feeding amount of each step, saves the raw material, avoids unnecessary waste, and improves the precision and efficiency of the preparation equipment.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to a method and apparatus for preparing ofloxacin and levofloxacin. Background Technology

[0002] Both levofloxacin and ofloxacin belong to the quinolone class of antibacterial drugs. Levofloxacin is the levorotatory optical isomer of ofloxacin. Levofloxacin has a stronger antibacterial potency than ofloxacin, reaching up to twice that of ofloxacin. Levofloxacin also has a broader antibacterial spectrum than ofloxacin. Clinically, ofloxacin can be used for upper respiratory tract infections, pelvic infections, skin and soft tissue infections, and genitourinary system infections caused by susceptible bacteria. Levofloxacin can be used for infections in all parts of the body, including moderate to severe lower respiratory tract infections, and even hematogenous sepsis. Therefore, the preparation of ofloxacin and levofloxacin is receiving increasing attention.

[0003] Existing equipment for preparing levofloxacin mainly consists of powder processing or capsule processing equipment. Chinese Patent Publication No. CN108554505A discloses a powder processing device for levofloxacin hydrochloride capsules, which grinds the raw material into tablets to a predetermined size using a grinding device. This demonstrates that existing pharmaceutical equipment for levofloxacin rarely includes refining equipment. However, the crude products of ofloxacin and levofloxacin obtained from starting materials through various chemical reactions have the problem of being dark in color and containing many impurities, resulting in poor quality when directly manufactured into pharmaceutical products. Summary of the Invention

[0004] Therefore, the present invention provides a method and apparatus for preparing ofloxacin and levofloxacin, in order to overcome the problem of low efficiency in the purification of crude ofloxacin and levofloxacin in the prior art while ensuring quality.

[0005] To achieve the above objectives, the present invention provides a method for preparing ofloxacin and levofloxacin, comprising,

[0006] Step S1, material preparation and feeding: The central control unit controls the powder feeding device to feed the crude product raw material to be processed into the dissolving tank according to the preset crude product raw material feeding weight, and calculates the amount of ethanol solution to be fed into the dissolving tank according to the crude product raw material feeding weight, and then controls the ethanol feeding device to feed the ethanol solution into the dissolving tank to form a raw material mixture.

[0007] Step S2, dissolution and decolorization: The raw material mixture inside the dissolution tank is stirred and heated by an electric stirring heater. The central control unit controls the set heating temperature of the electric stirring heater in real time according to the real-time solution temperature of the raw material mixture, and judges the real-time turbidity of the raw material mixture solution. The activated carbon dosing device is controlled to add activated carbon powder into the dissolution tank for decolorization. The raw material mixture in the dissolution tank is sampled by a sampling and detection device and an image is acquired. The central control unit performs grayscale processing on the image acquired by the sampling and detection device to obtain the real-time solution grayscale, and determines whether to add activated carbon powder to the dissolution tank based on the real-time solution grayscale. The central control unit determines whether the decolorization of the raw material mixture is completed based on the real-time solution grayscale.

[0008] Step S3, pressure filtration and crystallization: the decolorized raw material mixture is separated into solid and liquid by a filtration device, and the resulting filtrate is discharged into a crystallization tank. The position of the filtrate level in the crystallization tank is adjusted by controlling the lifting bottom plate in the crystallization tank. The filtrate is cooled by a cooling and stirring device and allowed to stand for crystallization. The real-time height change rate of the filtrate in the crystallization tank is determined by setting a standard height change rate in the central control unit to confirm whether crystallization has been completed.

[0009] Step S4, rinsing and drying: Separate the crystallized raw material from the filtrate and put the raw material crystal into the rinsing tank. Drain the ethanol solution into the rinsing tank to rinse the raw material crystal. Then put the rinsed raw material crystal into a vacuum chamber to dry, and obtain the purified ofloxacin or levofloxacin.

[0010] Further, in step S1, the central control unit is equipped with a crude product raw material feeding weight Mx. The central control unit controls the powder feeding device to feed the crude product raw material into the dissolving tank at a preset feeding weight Mx, and calculates the initial ethanol feeding weight My based on the preset feeding weight Mx, My = Mx × a, where a is the initial ethanol feeding ratio. The central control unit controls the ethanol feeding device to feed the ethanol solution into the dissolving tank at the initial ethanol feeding weight My, forming a raw material mixture in the dissolving tank. The central control unit controls the electric stirring heater to start heating at the initial set temperature Td and stir the raw material mixture in the dissolving tank.

[0011] Furthermore, the central control unit is equipped with a first preset heating temperature T1 and a second preset heating temperature T2, wherein T1 < T2 < Td. When the electric stirring heater heats the mixture in the dissolving tank, the first temperature detector measures the real-time solution temperature Ts of the mixture in the dissolving tank. The central control unit compares the real-time solution temperature Ts with the first preset heating temperature T1 and the second preset heating temperature T2.

[0012] When Ts < T1, the central control unit determines that the real-time solution temperature is lower than the first preset heating temperature. The central control unit will determine whether to adjust the heating temperature of the electric stirring heater based on the real-time solution temperature of the mixture.

[0013] When T1≤Ts≤T2, the central control unit determines that the real-time solution temperature is between the first preset heating temperature and the second preset heating temperature. The central control unit adjusts the initial temperature of the electric stirring heater to Td', Td'=(T1+T2) / 2, and controls the activated carbon feeding device to feed materials by judging the turbidity.

[0014] When T2 < Ts, the central control unit determines that the real-time solution temperature is higher than the second preset heating temperature, and controls the electric stirring heater to stop heating.

[0015] Furthermore, the central control unit is equipped with a preset temperature adjustment temperature Ti, where Ti < T1. When the central control unit determines that the real-time solution temperature is lower than the first preset heating temperature, the central control unit compares the real-time solution temperature Ts with the preset temperature adjustment temperature Ti.

[0016] When Ts < Ti, the central control unit determines that the real-time solution temperature has not reached the preset temperature adjustment temperature, and the central control unit does not adjust the heating temperature of the electric stirring heater.

[0017] When Ts≥Ti, the central control unit determines that the real-time solution temperature has reached the preset temperature adjustment temperature, and the central control unit adjusts the initial set temperature of the electric stirring heater to Td”, Td”=Td-[(Ts-Ti) / T1]×(Td-T2).

[0018] Furthermore, the central control unit is equipped with a standard solution turbidity F. When the central control unit determines that the real-time solution temperature is between the first preset heating temperature and the second preset heating temperature, the turbidity detector detects the real-time solution turbidity Fs of the mixture in the dissolving tank. The central control unit compares the real-time solution turbidity Fs with the standard solution turbidity F.

[0019] When Fs > F, the central control unit determines that the turbidity of the real-time solution exceeds the turbidity of the standard solution, and the central control unit controls the electric stirring heater to continue stirring;

[0020] When Fs≤F, the central control unit determines that the turbidity of the real-time solution does not exceed the turbidity of the standard solution, and the central control unit controls the activated carbon dispensing device to add activated carbon powder into the dissolving tank at an activated carbon input amount Mz.

[0021] Among them, the activated carbon input amount Mz is calculated by the central control unit based on the ratio b of the input amount of crude product raw material Mx to the input amount of activated carbon, Mz = Mx × b.

[0022] Furthermore, the central control unit is equipped with a unit detection time t and a standard grayscale change rate Vg. When the central control unit determines that the real-time solution turbidity does not exceed the standard solution turbidity, the sampling and detection device takes an initial sample and acquires an image. The central control unit performs grayscale processing on the image and obtains the initial solution grayscale Gc of the initial sample image. After the central control unit controls the activated carbon dispensing device to add activated carbon into the dissolving tank, the sampling and detection device samples every unit detection time t, centrifuges the mixed solution, and acquires an image of the separated solution. The central control unit performs grayscale processing on the image and obtains the real-time solution grayscale Gs of the real-time sample image. The central control unit calculates the real-time grayscale change rate Vs, Vs = (Gc - Gs) / t. The central control unit compares the real-time grayscale change rate Vs with the standard grayscale change rate Vg.

[0023] When Vs≥Vg, the central control unit determines that the real-time grayscale change rate has reached the standard grayscale change rate, and the central control unit does not adjust the activated carbon dosage.

[0024] When Vs < Vg, the central control unit determines that the real-time grayscale change rate has not reached the standard grayscale change rate. The central control unit will calculate the activated carbon replenishment amount Mz', Mz' = [Mz × (Vg / Vs)] - Mz, and control the activated carbon dispensing device to replenish activated carbon powder into the dissolving tank with the activated carbon replenishment amount Mz'.

[0025] Furthermore, the central control unit is equipped with a standard solution grayscale value Gb. After the sampling and detection device acquires a solution image, the central control unit extracts the real-time solution grayscale value Gs from the image and compares the real-time solution grayscale value Gs with the standard solution grayscale value Gb.

[0026] When Gs≤Gb, the central control unit determines that the real-time solution ash value does not exceed the standard solution ash value, and controls the electric stirring heater to stop stirring and transfers the mixture in the dissolving tank to the crystallizing tank;

[0027] When Gs > Gb, the central control unit determines that the real-time solution ash value exceeds the standard solution ash value, and controls the electric stirring heater to continue stirring.

[0028] Furthermore, the central control unit is equipped with a third preset solution temperature T3 and a fourth preset solution temperature T4, wherein T3 > T4. When the central control unit determines that the real-time solution ash value does not exceed the standard solution ash value, the central control unit transfers the mixture in the dissolving tank to the crystallizing tank and controls the filtration device to remove activated carbon residue from the mixture. The central control unit controls the cooling and stirring device to cool the filtrate. A second temperature detector detects the real-time solution temperature Ts' in the crystallizing tank. The central control unit compares the real-time solution temperature Ts' with the third preset solution temperature T3 and the fourth preset solution temperature T4.

[0029] When Ts' > T3, the central control unit determines that the real-time solution temperature exceeds the third preset solution temperature, and the central control unit controls the electric stirrer in the crystallization box to stir at the initial stirring speed V1.

[0030] When T4 < Ts' ≤ T3, the central control unit determines that the real-time solution temperature is between the third preset solution temperature and the fourth preset solution temperature. The central control unit will adjust the stirring speed of the cooling stirring device to V2 according to the real-time solution temperature Ts', V2 = V1 - [(T3 - Ts') / (T3 - T4)] × V1;

[0031] When Ts'≤T4, the central control unit determines that the real-time solution temperature is not higher than the fourth preset solution temperature. The central control unit controls the cooling and stirring device to stop stirring and allow it to stand, and judges the degree of crystallization based on the change in liquid level.

[0032] Furthermore, the central control unit is equipped with a standard height change rate Vh. When the cooling and stirring device stops stirring, the central control unit controls the lifting base plate to rise, increasing the real-time height of the solution in the crystallization tank until it reaches the observation range of the observation level tube. At this point, the central control unit controls the lifting base plate to stop rising. The central control unit obtains the initial liquid level height H1 of the solution through a liquid level gauge and obtains the real-time liquid level height Hs during the crystallization process. The central control unit calculates the real-time height change rate Vs' based on the real-time liquid level height, Vs' = (Hs - H1) / t. The central control unit compares the real-time height change rate Vs' with the standard height change rate Vh.

[0033] When Vs'≥Vh, the central control unit determines that the real-time height change rate is not lower than the standard height change rate, and the central control unit determines that crystallization is not complete and does not adjust the state of the preparation equipment.

[0034] When Vs' < Vh, the central control unit determines that the real-time height change rate is lower than the standard height change rate, the central control unit determines that crystallization is complete, and puts the raw material crystal into the rinsing tank, discharges the ethanol solution into the rinsing tank to rinse the raw material crystal, and puts the rinsed raw material crystal into a vacuum chamber to dry, thereby obtaining the refined product of ofloxacin or levofloxacin.

[0035] This invention also provides an apparatus for preparing ofloxacin and levofloxacin, applied to the above-described method for preparing ofloxacin and levofloxacin, comprising,

[0036] The dissolving tank is equipped with an electric stirring and heating device inside, which can stir and heat the mixture in the tank. A first temperature detector is installed inside the tank to detect the real-time temperature of the mixture. A turbidity detector is installed on the inner side wall of the tank to detect the real-time turbidity of the mixture. An activated carbon dispensing device is installed on the top wall of the tank to add activated carbon powder. A sampling and detection device is also installed on the inner side wall of the tank, which can extract a sample of the mixture from the tank, centrifuge it, and acquire an image of the separated sample. A powder dispensing device and an ethanol dispensing device are also installed at the top of the tank to add crude raw materials and ethanol solution, respectively.

[0037] A crystallization tank is connected to the dissolving tank via a filtration device to remove activated carbon residue from the mixture. An observation level tube with a height gauge is installed at the top of the crystallization tank to monitor the liquid level in real time. A lifting base plate is installed at the bottom of the crystallization tank to adjust its volume. A cooling and stirring device is installed above the lifting base plate to cool and stir the filtrate in the crystallization tank. A second temperature detector is installed on the inner wall of the crystallization tank to monitor the temperature of the solution in the crystallization tank in real time.

[0038] A rinsing tank, which is connected to the crystallization tank, is used to rinse the crystals obtained in the crystallization tank.

[0039] A vacuum chamber, which is connected to the rinsing chamber, is used to vacuum dry the rinsed crystals;

[0040] The central control unit is connected to the dissolving tank, the crystallizing tank, the rinsing tank, and the vacuum tank, respectively. The central control unit compares the real-time solution temperature with the preset heating temperature and the preset temperature adjustment temperature, and adjusts the heating temperature of the electric stirring heater according to the real-time solution temperature. The central control unit compares the real-time solution turbidity with the standard solution turbidity to determine whether the crude product raw material has completely dissolved. The central control unit compares the real-time ash value change rate with the standard ash value change rate, and adjusts the amount of activated carbon powder added according to the real-time ash value change rate. The central control unit compares the real-time solution ash value with the standard solution ash value to determine whether the solution has passed decolorization. The central control unit compares the real-time solution temperature with the preset solution temperature, and adjusts the stirring speed of the cooling stirring device according to the real-time solution temperature. The central control unit compares the real-time height change rate with the standard height change rate to determine whether the solution has completely crystallized.

[0041] Compared with existing technologies, the beneficial effects of this invention are as follows: In this invention, the central control unit compares the real-time solution temperature with the preset heating temperature and the preset temperature adjustment temperature, and adjusts the heating temperature of the electric stirring heater in real time. This avoids both the problem of insufficient dissolution of the crude product raw material due to temperature drop and the problem of prolonged high temperature damaging the molecular structure. The central control unit also compares the real-time solution turbidity with the standard solution turbidity to determine whether the crude product raw material has completely dissolved. This avoids the decrease in the yield of refined product caused by insufficient dissolution, improving the working accuracy of the preparation equipment, and also avoids the problem of excessive stirring time for complete dissolution, improving the working efficiency of the preparation equipment. Finally, the central control unit compares the real-time grayscale change rate with the standard grayscale change rate and replenishes activated carbon powder in real time according to the real-time grayscale change rate, ensuring… The purification process is completed in one step, avoiding the need for repeated decolorization in traditional technologies when the decolorization is not up to standard. The central control unit compares the real-time solution ash value with the standard solution ash value to determine whether the solution has passed decolorization. This avoids the problem of poor quality of the purified product caused by unqualified decolorization, and also avoids the problem of excessive stirring time for decolorization, thus improving the working efficiency and accuracy of the preparation equipment. In summary, the central control unit can adjust the set temperature of the electric stirring heater, the amount of activated carbon added, and the stirring speed of the cooling stirring device in real time according to the real-time solution temperature and the real-time ash value change rate. It can also accurately determine whether the crude product raw materials are completely dissolved and whether the solution has passed decolorization. Precise control of the working time and raw material addition amount at each step saves raw materials, avoids unnecessary waste, and improves the accuracy and efficiency of the preparation equipment.

[0042] Furthermore, the central control unit is equipped with a ratio of crude product raw material input weight to initial ethanol input weight. The central control unit calculates the ethanol input weight based on the crude product raw material input weight and the initial ethanol input weight ratio, which precisely controls the amount of ethanol input, avoiding the problem of waste caused by a large amount of ethanol. It also avoids the problem of insufficient dissolution of crude product raw materials when the amount of ethanol is insufficient, which is both environmentally friendly and improves the working accuracy of the preparation equipment.

[0043] Furthermore, the central control unit is equipped with a first preset heating temperature and a second preset heating temperature. When the real-time solution temperature is lower than the first preset heating temperature, the central control unit will determine whether to adjust the temperature of the electric stirring heater based on the real-time solution temperature Ts of the mixture. When the real-time solution temperature is between the preset heating temperatures, the central control unit will adjust the initial temperature of the electric stirring heater to the middle value of the preset heating temperature to keep the mixture warm, thus avoiding the problem of insufficient dissolution of the crude product raw materials due to temperature drop. When the real-time solution temperature is higher than the second preset heating temperature, the central control unit will control the electric stirring heater to stop heating, thus avoiding the problem of prolonged high temperature damaging the molecular structure. The central control unit adjusts the operating temperature of the electric stirring heater in real time according to the real-time solution temperature, which saves energy and improves the operating efficiency and working accuracy of the preparation equipment.

[0044] In particular, the central control unit is equipped with a preset temperature setting. When the solution temperature has not reached the preset temperature setting, the central control unit controls the electric stirring heater to heat at a higher temperature, which improves the working efficiency of the preparation equipment. When the real-time solution temperature reaches the preset temperature setting, the central control unit lowers the initial set temperature of the heating and stirring device, thereby reducing the heating rate of the mixture and avoiding the problem of uncontrollable temperature due to excessive heating, thus improving the working accuracy of the preparation equipment.

[0045] In particular, the central control unit is equipped with a standard solution turbidity setting and compares the real-time solution turbidity with the standard solution turbidity. When the real-time solution turbidity does not exceed the standard solution turbidity, the central control unit determines that the crude product raw material is completely dissolved in the ethanol solution and can proceed to the next step of activated carbon decolorization treatment. This avoids the decrease in the yield of refined product caused by insufficient dissolution, improves the working accuracy of the preparation equipment, and avoids the problem of excessive stirring time for sufficient dissolution, thus improving the working efficiency of the preparation equipment.

[0046] Furthermore, the central control unit is equipped with a unit detection time and a standard grayscale change rate. The central control unit calculates the real-time grayscale change rate based on the initial solution grayscale and the real-time solution grayscale. When the real-time grayscale change rate reaches the standard grayscale change rate, it indicates that the decolorization speed is normal, and the central control unit does not adjust the activated carbon dosage. When the real-time grayscale change rate does not reach the standard grayscale change rate, it indicates that the decolorization speed is too slow, and the central control unit increases the activated carbon dosage based on the real-time grayscale change rate, thereby improving the decolorization efficiency of the preparation equipment and thus improving the working efficiency of the preparation equipment.

[0047] In particular, the central control unit is equipped with a standard solution gray level. When the real-time solution gray level exceeds the standard solution gray level, it indicates that the decolorization is unqualified. The central control unit then controls the electric stirring heater to continue stirring. When the real-time solution gray level does not exceed the standard solution gray level, it indicates that the solution has been decolorized successfully. The central control unit then controls the electric stirring heater to stop stirring and transfers the solution to the crystallization box. This avoids the problem of poor quality of refined products caused by unqualified decolorization, improves the working accuracy of the preparation equipment, and avoids the problem of excessive stirring time for qualified decolorization, thus improving the working efficiency of the preparation equipment.

[0048] Furthermore, when the real-time solution temperature in the crystallization chamber exceeds the third preset solution temperature, the central control unit controls the electric stirrer in the crystallization chamber to stir at a faster speed, accelerating the cooling rate of the solution in the crystallization chamber and improving the working efficiency of the preparation equipment. When the real-time solution temperature is between the third and fourth preset solution temperatures, the central control unit will reduce the stirring speed of the electric stirrer according to the real-time solution temperature, avoiding the problem of crystals being difficult to precipitate due to excessive stirring. When the real-time solution temperature is not higher than the fourth preset solution temperature, the central control unit controls the electric stirrer in the crystallization chamber to stop stirring, avoiding the problem of crystals being difficult to precipitate due to excessive stirring, further improving the working efficiency of the preparation equipment.

[0049] Furthermore, the central control unit is equipped with a standard height change rate. When the real-time height change rate is not lower than the standard height change rate, it indicates that the solution in the crystallization box is crystallizing, and the central control unit does not adjust the operating status of the preparation equipment. When the real-time height change rate is lower than the standard height change rate, it indicates that the solution in the crystallization box has crystallized completely, and the central control unit can control other equipment to carry out the next step. This avoids the problem of low yield of refined products due to incomplete crystallization, improves the working accuracy of the preparation equipment, and avoids the problem of excessive standing time for complete crystallization, thus improving the working efficiency of the preparation equipment. Attached Figure Description

[0050] Figure 1 This is a schematic diagram of the equipment used to prepare ofloxacin and levofloxacin as described in this embodiment;

[0051] Figure 2 This is a flowchart illustrating the method for preparing ofloxacin and levofloxacin as described in this embodiment;

[0052] Figure 3 This is a schematic diagram of the route for synthesizing crude levofloxacin in this embodiment. Detailed Implementation

[0053] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0054] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0055] It should be noted that in the description of this invention, the terms "upper", "lower", "left", "right", "inner", "outer", etc., which indicate directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings. This is only for the convenience of description and is not intended to indicate or imply that the device or element must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation of this invention.

[0056] Furthermore, it should be noted that, in the description of this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0057] Please see Figure 1 As shown, where Figure 1 This is a schematic diagram of the equipment for preparing ofloxacin and levofloxacin as described in this embodiment. The present invention discloses an equipment for preparing ofloxacin and levofloxacin, comprising: a powder dispensing device 1, an ethanol dispensing device 2, a dissolving tank 3, an electric stirring heater 301, an activated carbon dispensing device 302, a first temperature detector 303, a turbidity detector 304, a sampling and detection device 305, a crystallization tank 4, a filtration device 401, a cooling and stirring device 402, a second temperature detector 403, an observation level tube 404, a liquid level gauge 405, a lifting base plate 406, a rinsing tank 5, a vacuum chamber 6, and a central control unit (not shown in the figure).

[0058] The dissolving tank 3 is equipped with an electric stirring heater 301, which can stir and heat the mixture in the dissolving tank 3. A first temperature detector 303 is installed inside the dissolving tank 3 to detect the real-time temperature of the mixture. A turbidity detector 304 is installed on the inner wall of the dissolving tank 3 to detect the turbidity of the mixture in the dissolving tank 3 in real time. An activated carbon dispensing device 302 is installed on the top wall of the dissolving tank 3 to dispense activated carbon powder into the dissolving tank 3. A sampling and detection device 305 is also installed on the inner wall of the dissolving tank 3, which can extract a sample of the mixture in the dissolving tank 3 for centrifugation and acquire an image of the separated sample. A powder dispensing device 1 and an ethanol dispensing device 2 are also installed at the top of the dissolving tank 3 to dispense crude raw materials and ethanol solution into the dissolving tank 3, respectively.

[0059] The crystallization tank 4 is connected to the dissolving tank 3 via a filter device 401, which removes activated carbon residue from the mixture. A liquid level observation tube 404 is installed at the top of the crystallization tank 4, and a liquid level gauge 405 is installed inside the observation tube 404 to monitor the liquid level in real time. A lifting base plate 406 is installed at the bottom of the crystallization tank 4 to adjust the volume of the crystallization tank 4 by lifting. A cooling and stirring device 402 is installed on the upper part of the lifting base plate 406 to stir and cool the filtrate in the crystallization tank 4. A second temperature detector 403 is installed on the inner wall of the crystallization tank 4 to monitor the temperature of the solution in the crystallization tank 4 in real time.

[0060] The rinsing tank 5 is connected to the crystallization tank 4 and is used to rinse the crystals obtained in the crystallization tank 4.

[0061] Vacuum chamber 6, which is connected to the rinsing chamber 5, is used to vacuum dry the rinsed crystals;

[0062] The central control unit is connected to the dissolving tank 3, the crystallizing tank 4, the rinsing tank 5, and the vacuum tank 6, respectively. The central control unit compares the real-time solution temperature with the preset heating temperature and the preset temperature adjustment temperature, and adjusts the heating temperature of the electric stirring heater 301 according to the real-time solution temperature. The central control unit compares the real-time solution turbidity with the standard solution turbidity to determine whether the crude product raw material has completely dissolved. The central control unit compares the real-time ash change rate with the standard ash change rate, and adjusts the amount of activated carbon powder added according to the real-time ash change rate. The central control unit compares the real-time solution ash with the standard solution ash to determine whether the solution has passed decolorization. The central control unit compares the real-time solution temperature with the preset solution temperature, and adjusts the stirring speed of the cooling stirring device 402 according to the real-time solution temperature. The central control unit compares the real-time height change rate with the standard height change rate to determine whether the solution has completely crystallized.

[0063] Please see Figure 2 As shown, Figure 2 This is a flowchart illustrating the method for preparing ofloxacin and levofloxacin as described in this embodiment. The present invention also provides a method for preparing ofloxacin and levofloxacin, applied to the aforementioned equipment for preparing ofloxacin and levofloxacin, comprising:

[0064] Step S1, material preparation and feeding: The central control unit controls the powder feeding device 1 to feed the crude product raw material to be processed into the dissolving tank 3 according to the preset crude product raw material feeding weight, and calculates the amount of ethanol solution to be fed into the dissolving tank 3 according to the crude product raw material feeding weight, and then controls the ethanol feeding device 2 to feed the ethanol solution into the dissolving tank 3 to form a raw material mixture.

[0065] Step S2, dissolution and decolorization: The raw material mixture inside the dissolution tank 3 is stirred and heated by an electric stirring heater 301. The central control unit controls the set heating temperature of the electric stirring heater 301 in real time according to the real-time solution temperature of the raw material mixture, and judges the real-time solution turbidity of the raw material mixture. The activated carbon dosing device 302 is controlled to add activated carbon powder into the dissolution tank 3 for decolorization. The raw material mixture in the dissolution tank 3 is sampled by a sampling and detection device 305 and an image is acquired. The central control unit performs grayscale processing on the image acquired by the sampling and detection device 305 to obtain the real-time solution grayscale, and determines whether to add activated carbon powder to the dissolution tank 3 based on the real-time solution grayscale. The central control unit determines whether the decolorization of the raw material mixture is completed based on the real-time solution grayscale.

[0066] Step S3, pressure filtration and crystallization: the decolorized raw material mixture is separated into solid and liquid by the filtration device 401, and the resulting filtrate is discharged into the crystallization tank 4. The position of the filtrate liquid level in the crystallization tank 4 is adjusted by controlling the lifting bottom plate 406 in the crystallization tank 4, and the filtrate is cooled by the cooling and stirring device 402 for static crystallization. The real-time height change rate of the filtrate in the crystallization tank 4 is determined by setting a standard height change rate in the central control unit to confirm whether crystallization has been completed.

[0067] Step S4, rinsing and drying: Separate the crystallized raw material from the filtrate and put the raw material crystal into the rinsing tank 5. Drain the ethanol solution into the rinsing tank 5 to rinse the raw material crystal. Then put the rinsed raw material crystal into the vacuum box 6 to dry, and obtain the purified ofloxacin or levofloxacin.

[0068] The purpose of rinsing is to clean any residual liquid that may be present on the crystals. The crystals obtained in crystallization box 4 are soluble in water but not in alcohol at 0-5℃. Therefore, rinsing with alcohol can prevent possible reactions between the crystals and water. In addition, alcohol is easy to evaporate, and the crystals after rinsing are easier to dry.

[0069] In this invention, the central control unit compares the real-time solution temperature with the preset heating temperature and the preset temperature adjustment temperature, and adjusts the heating temperature of the electric stirring heater 301 in real time. This avoids both the problem of insufficient dissolution of the crude product raw material due to temperature drop and the problem of prolonged high temperature damaging the molecular structure. The central control unit compares the real-time solution turbidity with the standard solution turbidity to determine whether the crude product raw material has completely dissolved. This avoids the decrease in the yield of refined product caused by insufficient dissolution, improving the working accuracy of the preparation equipment, and also avoids the problem of excessive stirring time for sufficient dissolution, improving the working efficiency of the preparation equipment. The central control unit compares the real-time grayscale change rate with the standard grayscale change rate, and replenishes activated carbon powder in real time according to the real-time grayscale change rate, ensuring that the refining process is completed in one step, avoiding... This eliminates the need for repeated decolorization when decolorization fails in traditional techniques. The central control unit compares the real-time solution ash value with the standard solution ash value to determine whether the solution has passed decolorization. This avoids both the poor quality of refined products caused by unqualified decolorization and the excessive stirring time required to achieve qualified decolorization, thus improving the efficiency and accuracy of the preparation equipment. In summary, the central control unit can adjust the set temperature of the electric stirring heater 301, the amount of activated carbon added, and the stirring speed of the cooling stirring device 402 in real time based on the real-time solution temperature and the rate of change of real-time ash value. It can also accurately determine whether the crude product raw materials are completely dissolved and whether the solution has passed decolorization. Precise control of the working time and raw material addition amount at each step saves raw materials, avoids unnecessary waste, and improves the accuracy and efficiency of the preparation equipment.

[0070] Specifically, in step S1, the central control unit is set with a crude product raw material feeding weight Mx. The central control unit controls the powder feeding device 1 to feed the crude product raw material into the dissolving tank 3 with a preset feeding weight Mx, and calculates the initial ethanol feeding weight My based on the preset feeding weight Mx, My = Mx × a, where a is the initial ethanol feeding ratio. The central control unit controls the ethanol feeding device 2 to feed the ethanol solution into the dissolving tank 3 with the initial ethanol feeding weight My, forming a raw material mixture in the dissolving tank 3. The central control unit controls the electric stirring heater 301 to start heating at the initial set temperature Td and stir the raw material mixture in the dissolving tank 3.

[0071] The central control unit is equipped with a setting for the weight of crude raw materials and the initial ethanol feeding ratio. The central control unit calculates the ethanol feeding weight based on the weight of crude raw materials and the initial ethanol feeding ratio, which precisely controls the amount of ethanol input, avoiding the problem of waste caused by large amounts of ethanol. It also avoids the problem of insufficient dissolution of crude raw materials when the amount of ethanol is insufficient, which is both environmentally friendly and improves the working accuracy of the preparation equipment.

[0072] Specifically, the central control unit is equipped with a first preset heating temperature T1 and a second preset heating temperature T2, wherein T1 < T2 < Td. When the electric stirring heater 301 heats the mixture in the dissolving tank 3, the first temperature detector 303 detects the real-time solution temperature Ts of the mixture in the dissolving tank 3. The central control unit compares the real-time solution temperature Ts with the first preset heating temperature T1 and the second preset heating temperature T2.

[0073] When Ts < T1, the central control unit determines that the real-time solution temperature is lower than the first preset heating temperature. The central control unit will determine whether to adjust the heating temperature of the electric stirring heater 301 based on the real-time solution temperature of the mixture.

[0074] When T1≤Ts≤T2, the central control unit determines that the real-time solution temperature is between the first preset heating temperature and the second preset heating temperature. The central control unit adjusts the initial temperature of the electric stirring heater 301 to Td', Td'=(T1+T2) / 2, and controls the feeding of activated carbon by judging the turbidity.

[0075] When T2 < Ts, the central control unit determines that the real-time solution temperature is higher than the second preset heating temperature, and the central control unit controls the electric stirring heater 301 to stop heating;

[0076] The central control unit is equipped with a first preset heating temperature and a second preset heating temperature. When the real-time solution temperature is lower than the first preset heating temperature, the central control unit will determine whether to adjust the temperature of the electric stirring heater 301 based on the real-time solution temperature Ts of the mixture. When the real-time solution temperature is between the preset heating temperatures, the central control unit will adjust the initial temperature of the electric stirring heater 301 to the middle value of the preset heating temperatures to keep the mixture warm, thus avoiding the problem of insufficient dissolution of the crude product raw materials due to temperature drop. When the real-time solution temperature is higher than the second preset heating temperature, the central control unit will control the electric stirring heater 301 to stop heating, thus avoiding the problem of prolonged high temperature damaging the molecular structure. The central control unit adjusts the working temperature of the electric stirring heater 301 in real time according to the real-time solution temperature, which saves energy and improves the operating efficiency and working accuracy of the preparation equipment.

[0077] Specifically, the central control unit is equipped with a preset temperature adjustment temperature Ti, where Ti < T1. When the central control unit determines that the real-time solution temperature is lower than the first preset heating temperature, the central control unit compares the real-time solution temperature Ts with the preset temperature adjustment temperature Ti.

[0078] When Ts < Ti, the central control unit determines that the real-time solution temperature has not reached the preset temperature adjustment temperature, and the central control unit does not adjust the heating temperature of the electric stirring heater 301.

[0079] When Ts≥Ti, the central control unit determines that the real-time solution temperature has reached the preset temperature adjustment temperature, and the central control unit adjusts the initial set temperature of the electric stirring heater 301 to Td”, Td”=Td-[(Ts-Ti) / T1]×(Td-T2);

[0080] The central control unit is equipped with a preset temperature setting. When the solution temperature has not reached the preset temperature setting, the central control unit controls the electric stirring heater 301 to heat at a higher temperature, which improves the working efficiency of the preparation equipment. When the real-time solution temperature reaches the preset temperature setting, the central control unit lowers the initial set temperature of the heating and stirring device to reduce the heating rate of the mixture, avoid the problem of uncontrollable temperature due to excessive heating, and improve the working accuracy of the preparation equipment.

[0081] Specifically, the central control unit is equipped with a standard solution turbidity F. When the central control unit determines that the real-time solution temperature is between the first preset heating temperature and the second preset heating temperature, the turbidity detector 304 detects the real-time solution turbidity Fs of the mixture in the dissolving tank 3 in real time. The central control unit compares the real-time solution turbidity Fs with the standard solution turbidity F.

[0082] When Fs > F, the central control unit determines that the turbidity of the real-time solution exceeds the turbidity of the standard solution, and the central control unit controls the electric stirring heater 301 to continue stirring;

[0083] When Fs≤F, the central control unit determines that the turbidity of the real-time solution does not exceed the turbidity of the standard solution, and the central control unit controls the activated carbon feeding box to add activated carbon powder into the dissolving box 3 at an activated carbon feeding amount Mz.

[0084] Among them, the activated carbon input amount Mz is calculated by the central control unit based on the ratio of the crude product raw material input amount Mx to the activated carbon input amount b, Mz = Mx × b;

[0085] The central control unit is equipped with a standard solution turbidity setting and compares the real-time solution turbidity with the standard solution turbidity. When the real-time solution turbidity does not exceed the standard solution turbidity, the central control unit determines that the crude product raw material is completely dissolved in the ethanol solution and can proceed to the next step of activated carbon decolorization treatment. This avoids the decrease in the yield of refined product caused by insufficient dissolution, improves the working accuracy of the preparation equipment, and avoids the problem of excessive stirring time for sufficient dissolution, thus improving the working efficiency of the preparation equipment.

[0086] Specifically, the central control unit is configured with a unit detection time t and a standard grayscale change rate Vg. When the central control unit determines that the real-time solution turbidity does not exceed the standard solution turbidity, the sampling and detection device 305 takes an initial sample and acquires an image. The central control unit performs grayscale processing on the image and obtains the initial solution grayscale Gc of the initial sample image. After the central control unit controls the activated carbon dispensing device 302 to add activated carbon into the dissolving tank 3, the sampling and detection device 305 samples every unit detection time t, centrifuges the mixed solution, and acquires an image of the separated solution. The central control unit performs grayscale processing on the image and obtains the real-time solution grayscale Gs of the real-time sample image. The central control unit calculates the real-time grayscale change rate Vs, Vs = (Gc - Gs) / t. The central control unit compares the real-time grayscale change rate Vs with the standard grayscale change rate Vg.

[0087] When Vs≥Vg, the central control unit determines that the real-time grayscale change rate has reached the standard grayscale change rate, and the central control unit does not adjust the activated carbon dosage.

[0088] When Vs < Vg, the central control unit determines that the real-time grayscale change rate has not reached the standard grayscale change rate. The central control unit adjusts the activated carbon dosage to Mz' based on the real-time grayscale change rate, Mz' = Mz × (Vg / Vs), and controls the activated carbon dispensing box to add activated carbon to the dissolving box 3 by the activated carbon dosage Mz' - Mz.

[0089] The central control unit is equipped with a unit detection time and a standard grayscale change rate. The central control unit calculates the real-time grayscale change rate based on the initial solution grayscale and the real-time solution grayscale. When the real-time grayscale change rate reaches the standard grayscale change rate, it indicates that the decolorization speed is normal, and the central control unit does not adjust the activated carbon dosage. When the real-time grayscale change rate does not reach the standard grayscale change rate, it indicates that the decolorization speed is too slow, and the central control unit increases the activated carbon dosage based on the real-time grayscale change rate, thereby improving the decolorization efficiency of the preparation equipment and thus improving the working efficiency of the preparation equipment.

[0090] Specifically, the central control unit is equipped with a standard solution grayscale value Gb. After the sampling and detection device 305 acquires a solution image, the central control unit extracts the real-time solution grayscale value Gs from the image. The central control unit then compares the real-time solution grayscale value Gs with the standard solution grayscale value Gb.

[0091] When Gs≤Gb, the central control unit determines that the real-time solution ash value does not exceed the standard solution ash value, and controls the electric stirring heater 301 to stop stirring and transfers the mixture in the dissolving tank 3 to the crystallizing tank 4;

[0092] When Gs > Gb, the central control unit determines that the real-time solution ash value exceeds the standard solution ash value, and the central control unit controls the electric stirring heater 301 to continue stirring;

[0093] The central control unit is equipped with a standard solution gray level. When the real-time solution gray level exceeds the standard solution gray level, it indicates that the decolorization is unqualified. The central control unit controls the electric stirring heater 301 to continue stirring. When the real-time solution gray level does not exceed the standard solution gray level, it indicates that the solution has been decolorized and is qualified. The central control unit controls the electric stirring heater 301 to stop stirring and transfers the solution to the crystallization box 4. This avoids the problem of poor quality of refined products caused by unqualified decolorization, improves the working accuracy of the preparation equipment, and avoids the problem of excessive stirring time for qualified decolorization, thus improving the working efficiency of the preparation equipment.

[0094] Specifically, the central control unit is equipped with a third preset solution temperature T3 and a fourth preset solution temperature T4, wherein T3 > T4. When the central control unit determines that the real-time solution ash value does not exceed the standard solution ash value, the central control unit transfers the mixture in the dissolving tank 3 to the crystallizing tank 4 and controls the filtration device 401 to remove activated carbon residue from the mixture. The central control unit controls the cooling and stirring device 402 to cool the filtrate. The second temperature detector 403 detects the real-time solution temperature Ts' in the crystallizing tank 4. The central control unit compares the real-time solution temperature Ts' with the third preset solution temperature T3 and the fourth preset solution temperature T4.

[0095] When Ts' > T3, the central control unit determines that the real-time solution temperature exceeds the third preset solution temperature, and the central control unit controls the electric stirrer in the crystallization box 4 to stir at the initial stirring speed V1.

[0096] When T4 < Ts' ≤ T3, the central control unit determines that the real-time solution temperature is between the third preset solution temperature and the fourth preset solution temperature. The central control unit will adjust the stirring speed of the electric stirrer to V2 according to the real-time solution temperature Ts', V2 = V1 - [(T3 - Ts') / (T3 - T4)] × V1;

[0097] When Ts'≤T4, the central control unit determines that the real-time solution temperature is not higher than the fourth preset solution temperature. The central control unit controls the cooling stirring device 402 to stop stirring and allow it to stand, and judges the degree of crystallization based on the change in liquid level.

[0098] When the real-time solution temperature in crystallization chamber 4 exceeds the third preset solution temperature, the central control unit controls the electric stirrer in crystallization chamber 4 to stir at a faster speed, accelerating the cooling rate of the solution in crystallization chamber 4 and improving the working efficiency of the preparation equipment. When the real-time solution temperature is between the third and fourth preset solution temperatures, the central control unit will reduce the stirring speed of the electric stirrer according to the real-time solution temperature, avoiding the problem of crystals being difficult to precipitate due to excessive stirring. When the real-time solution temperature is not higher than the fourth preset solution temperature, the central control unit controls the electric stirrer in crystallization chamber 4 to stop stirring, avoiding the problem of crystals being difficult to precipitate due to excessive stirring, further improving the working efficiency of the preparation equipment.

[0099] In this embodiment, the crystallization temperature has a significant impact on the yield. When the crystallization temperature is too high, the nucleus generation rate and crystal growth rate are too low, the target product is not fully precipitated, and the yield is not high. However, when the crystallization temperature is 0°C and 5°C, the molar yield is basically the same. Therefore, the third preset solution temperature T3 can be set to 40°C, and the fourth preset solution temperature T4 can be set to 5°C.

[0100] Specifically, the central control unit is equipped with a standard height change rate Vh. When the cooling and stirring device 402 stops stirring, the central control unit controls the lifting base plate 406 to rise, increasing the real-time height of the solution in the crystallization tank 4 until it reaches the observation range of the observation level tube 404. At this point, the central control unit controls the lifting base plate 406 to stop rising. The central control unit obtains the initial liquid level height H1 of the solution through the liquid level gauge 405 and obtains the real-time liquid level height Hs of the solution during the crystallization process. The central control unit calculates the real-time height change rate Vs' based on the real-time liquid level gauge 405, where Vs' = (Hs - H1) / t. The central control unit compares the real-time height change rate Vs' with the standard height change rate Vh.

[0101] When Vs'≥Vh, the central control unit determines that the real-time height change rate is not lower than the standard height change rate, and the central control unit determines that crystallization is not complete and does not adjust the state of the preparation equipment.

[0102] When Vs' < Vh, the central control unit determines that the real-time height change rate is lower than the standard height change rate, the central control unit determines that crystallization is complete, and puts the raw material crystal into the rinsing tank 5, discharges the ethanol solution into the rinsing tank 5 to rinse the raw material crystal, puts the rinsed raw material crystal into the vacuum box 6 to dry, and obtains the refined product of ofloxacin or levofloxacin.

[0103] Among them, the cross-sectional area of ​​the observation liquid level tube 404 is much smaller than the cross-sectional area of ​​the crystallization box 4, and the cross-sectional area of ​​the observation liquid level tube 404 is calculated based on the volume change of the solution crystallization in the crystallization box 4.

[0104] The central control unit is equipped with a standard height change rate. When the real-time height change rate is not lower than the standard height change rate, it indicates that the solution in crystallization box 4 is crystallizing, and the central control unit does not adjust the operating status of the preparation equipment. When the real-time height change rate is lower than the standard height change rate, it indicates that the solution in crystallization box 4 has crystallized completely, and the central control unit can control other equipment to carry out the next step. This avoids the problem of low yield of refined products due to incomplete crystallization, improves the working accuracy of the preparation equipment, and avoids the problem of excessive standing time for complete crystallization, thus improving the working efficiency of the preparation equipment.

[0105] Please see Figure 3 As shown, Figure 3 This is a schematic diagram of the route for synthesizing crude levofloxacin in this embodiment. In this embodiment, crude levofloxacin is prepared by stereoselective synthesis. It is prepared from 2,3,4,5-tetrafluorobenzoic acid as raw material, which is condensed with diethyl malonate after acylation, partially hydrolyzed and decarboxylated, condensed with triethyl orthoformate, replaced by S-(+)-2-aminopropanol, cyclized, hydrolyzed, and then condensed with N-methylpiperazine to obtain crude product. Since the product obtained after cyclization and condensation reactions is dark in color, it needs to be dissolved and decolorized first during purification.

[0106] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the scope of protection of the present invention.

[0107] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A process for the preparation of ofloxacin and levofloxacin, characterized in that, Comprise: Step S1, the preparation of putting, the central control unit controls the medicine powder putting device to put the rough product raw material to be handled into the dissolving box with the preset rough product raw material putting weight, and the ethanol solution putting amount is calculated according to the rough product raw material putting weight after controlling the ethanol putting device to put the ethanol solution into the dissolving box, and the raw material mixed solution is formed; Step S2, dissolving and decolorizing, the raw material mixed solution in the dissolving box is stirred and heated by the electric stirring heater, the central control unit controls the set heating temperature of the electric stirring heater according to the real-time solution temperature of the raw material mixed solution, and judges the real-time solution turbidity of the raw material mixed solution, controls the activated carbon putting device to put the activated carbon powder into the dissolving box, carries out decolorizing, carries out sampling and image acquisition to the raw material mixed solution in the dissolving box by the sampling detection device, the central control unit carries out gray processing to the image collected by the sampling detection device to obtain the real-time solution gray, and whether the activated carbon powder is supplemented and put into the dissolving box is judged according to the real-time solution gray, and whether the raw material mixed solution is decolorized is judged according to the real-time solution gray by the central control unit; Step S3, filter pressing and crystallization, the raw material mixed solution after decolorizing is separated by the filter device, and the obtained filtrate is discharged into the crystallization box, the position of the filtrate liquid level in the crystallization box is adjusted by controlling the lifting bottom plate in the crystallization box, the filtrate is cooled by the cooling stirring device, and the crystallization is carried out, the real-time height change rate of the filtrate in the crystallization box is judged by setting the standard height change rate in the central control unit, and whether the crystallization is completed is determined; Step S4, leaching and drying, the raw material crystal after crystallization is separated in the filtrate, and the raw material crystal is put into the leaching box, the ethanol solution is discharged into the leaching box to leach the raw material crystal, and the raw material crystal after leaching is put into the vacuum box for drying, to obtain the refined product of ofloxacin or levofloxacin; In the step S1, the central control unit is provided with a rough product raw material feeding weight Mx, the central control unit controls the medicine powder putting device to put the rough product raw material into the dissolving box with the preset rough product raw material feeding weight Mx, and calculates the initial ethanol feeding weight My according to the preset rough product raw material feeding weight Mx, My=Mx×a, wherein a is the initial ethanol feeding ratio, the central control unit controls the ethanol putting device to put the ethanol solution into the dissolving box with the initial ethanol feeding weight My, to form the raw material mixed solution in the dissolving box, and the central control unit controls the electric stirring heater to start heating at the initial set temperature Td and stirs the raw material mixed solution in the dissolving box; The central control unit is provided with a first preset heating temperature T1 and a second preset heating temperature T2, wherein T1 When Ts When T1≤Ts≤T2, the central control unit determines that the real-time solution temperature is between the first preset heating temperature and the second preset heating temperature, adjusts the initial temperature of the electric stirring heater to Td', Td'= (T1+T2) / 2, and controls the activated carbon feeding device to feed by determining the turbidity; When T2 The central control unit is provided with a standard solution turbidity F. When the central control unit determines that the real-time solution temperature is between the first preset heating temperature and the second preset heating temperature, the turbidity detector detects the real-time solution turbidity Fs of the mixed solution in the dissolving tank in real time, and the central control unit compares the real-time solution turbidity Fs with the standard solution turbidity F. When Fs When Fs≤F, the central control unit determines that the real-time solution turbidity does not exceed the standard solution turbidity, and controls the activated carbon feeding device to feed activated carbon powder into the dissolving tank at the activated carbon feeding amount Mz. The central control unit is provided with a unit detection time t and a standard gray scale change rate Vg. When the central control unit determines that the real-time solution turbidity does not exceed the standard solution turbidity, the sampling detection device takes an initial sample and collects images. The central control unit processes the images in gray scale and obtains the initial solution gray scale Gc of the initial sample image. After the central control unit controls the activated carbon feeding device to feed activated carbon into the dissolving tank, the sampling detection device samples every unit detection time t, centrifuges the sample liquid of the mixed solution, and collects images of the separated sample liquid. The central control unit processes the images in gray scale and obtains the real-time solution gray scale Gs of the real-time sample image. The central control unit calculates the real-time gray scale change rate Vs, Vs= (Gc-Gs) / t, and compares the real-time gray scale change rate Vs with the standard gray scale change rate Vg. When Vs≥Vg, the central control unit determines that the real-time gray scale change rate reaches the standard gray scale change rate, and the central control unit does not adjust the activated carbon feeding amount. When Vs The central control unit is provided with a unit detection time t and a standard gray scale change rate Vg. When the central control unit determines that the real-time solution turbidity does not exceed the standard solution turbidity, the sampling detection device takes an initial sample and collects images. The central control unit processes the images in gray scale and obtains the initial solution gray scale Gc of the initial sample image. After the central control unit controls the activated carbon feeding device to feed activated carbon into the dissolving tank, the sampling detection device samples every unit detection time t, centrifuges the sample liquid of the mixed solution, and collects images of the separated sample liquid. The central control unit processes the images in gray scale and obtains the real-time solution gray scale Gs of the real-time sample image. The central control unit calculates the real-time gray scale change rate Vs, Vs= (Gc-Gs) / t, and compares the real-time gray scale change rate Vs with the standard gray scale change rate Vg. When Vs≥Vg, the central control unit determines that the real-time gray scale change rate reaches the standard gray scale change rate, and the central control unit does not adjust the activated carbon feeding amount. When Vs The central control unit is provided with a unit detection time t and a standard gray scale change rate Vg. When the central control unit determines that the real-time solution turbidity does not exceed the standard solution turbidity, the sampling detection device takes an initial sample and collects images. The central control unit processes the images in gray scale and obtains the initial solution gray scale Gc of the initial sample image. After the central control unit controls the activated carbon feeding device to feed activated carbon into the dissolving tank, the sampling detection device samples every unit detection time t, centrifuges the sample liquid of the mixed solution, and collects images of the separated sample liquid. The central control unit processes the images in gray scale and obtains the real-time solution gray scale Gs of the real-time sample image. The central control unit calculates the real-time gray scale change rate Vs, Vs= (Gc-Gs) / t, and compares the real-time gray scale change rate Vs with the standard gray scale change rate Vg. When Vs≥Vg, the central control unit determines that the real-time gray scale change rate reaches the standard gray scale change rate, and the central control unit does not adjust the activated carbon feeding amount. When Vs 2. A process for the preparation of ofloxacin and levofloxacin as claimed in claim 1, wherein, The preset temperature adjusting temperature Ti is arranged in the central control unit, wherein Ti < T1, when the central control unit determines that the real-time solution temperature is lower than the first preset heating temperature, the central control unit compares the real-time solution temperature Ts with the preset temperature adjusting temperature Ti, When Ts < Ti, the central control unit determines that the real-time solution temperature does not reach the preset temperature adjusting temperature, and the central control unit does not adjust the heating temperature of the electric stirring heater; When Ts ≥ Ti, the central control unit determines that the real-time solution temperature reaches the preset temperature adjusting temperature, and the central control unit adjusts the initial setting temperature of the electric stirring heater to Td”, Td” = Td-[(Ts-Ti) / T1]×(Td-T2).

3. A process for the preparation of ofloxacin and levofloxacin as claimed in claim 1, wherein, The standard solution gray scale Gb is arranged in the central control unit, after the sampling detection device collects the solution image, the central control unit extracts the real-time solution gray scale Gs in the image, and the central control unit compares the real-time solution gray scale Gs with the standard solution gray scale Gb, When Gs ≤ Gb, the central control unit determines that the real-time solution gray scale does not exceed the standard solution gray scale, the central control unit controls the electric stirring heater to stop stirring, and the mixed liquid in the dissolving box is transmitted to the crystallization box; When Gs > Gb, the central control unit determines that the real-time solution gray scale exceeds the standard solution gray scale, and the central control unit controls the electric stirring heater to continue stirring.

4. A process for the preparation of ofloxacin and levofloxacin as claimed in claim 3, wherein The third preset solution temperature T3 and the fourth preset solution temperature T4 are arranged in the central control unit, wherein T3 > T4, when the central control unit determines that the real-time solution gray scale does not exceed the standard solution gray scale, the central control unit transmits the mixed liquid in the dissolving box to the crystallization box, controls the filter device to remove the activated carbon waste residue in the mixed liquid, controls the cooling stirring device to cool the filtrate, and the second temperature detector detects the real-time solution temperature Ts’ in the crystallization box, and the central control unit compares the real-time solution temperature Ts’ with the third preset solution temperature T3 and the fourth preset solution temperature T4, When Ts’ > T3, the central control unit determines that the real-time solution temperature exceeds the third preset solution temperature, and the central control unit controls the electric stirrer in the crystallization box to stir at the initial stirring speed V1; When T4 < Ts’ ≤ T3, the central control unit determines that the real-time solution temperature is between the third preset solution temperature and the fourth preset solution temperature, and the central control unit adjusts the stirring speed of the cooling stirring device to V2 according to the real-time solution temperature Ts’, V2 = V1-[(T3-Ts’) / (T3-T4)]×V1; When Ts’ ≤ T4, the central control unit determines that the real-time solution temperature is not higher than the fourth preset solution temperature, and the central control unit controls the cooling stirring device to stop stirring and stand still, and judges the crystallization degree according to the change of liquid level.

5. A process for the preparation of ofloxacin and levofloxacin as claimed in claim 4, wherein, The standard height change rate Vh is arranged in the central control unit. When the cooling and stirring device stops stirring, the central control unit controls the lifting bottom plate to rise, so as to increase the real-time height of the solution in the crystallization tank, until the observation range of the observation liquid level tube is reached, the central control unit controls the lifting bottom plate to stop rising, the central control unit obtains the initial liquid level height H1 of the solution through the liquid level gauge, and obtains the real-time liquid level height Hs of the solution during the crystallization process, the central control unit calculates the real-time height change rate Vs' of the liquid level according to the real-time liquid level height of the solution, Vs'= (Hs-H1) / t, the central control unit compares the real-time height change rate Vs' with the standard height change rate Vh, When Vs'≥Vh, the central control unit determines that the real-time height change rate is not lower than the standard height change rate, the central control unit determines that the crystallization is not completed, and the state of the preparation equipment is not adjusted; When Vs'<Vh, the central control unit determines that the real-time height change rate is lower than the standard height change rate, the central control unit determines that the crystallization is completed, and the raw material crystals are put into the leaching tank, the ethanol solution is discharged to the leaching tank to leach the raw material crystals, the leached raw material crystals are put into the vacuum tank for drying, and the refined product of ofloxacin or levofloxacin is obtained.

6. An apparatus for preparing ofloxacin and levofloxacin, which is applied to the method for preparing ofloxacin and levofloxacin according to any one of claims 1 to 5, characterized by, It comprises, The inside of the dissolving tank is provided with an electric stirring heater capable of stirring and heating the mixed liquid in the dissolving tank, a first temperature detector is arranged in the inside of the dissolving tank to detect the real-time temperature of the mixed liquid in the dissolving tank, a turbidity detector is arranged on the inner side wall of the dissolving tank to detect the turbidity of the mixed liquid in the dissolving tank in real time, an activated carbon feeding device is arranged on the top wall in the inside of the dissolving tank to feed activated carbon powder into the dissolving tank, and a sampling and detecting device is further arranged on the inner side wall of the dissolving tank, which can extract sample liquid of the mixed liquid in the dissolving tank for centrifugal separation and image acquisition of the separated sample liquid; a medicine powder feeding device and an ethanol feeding device are further arranged on the upper part of the dissolving tank to feed the raw material of the crude product and the ethanol solution into the dissolving tank, respectively; The crystallization tank is connected with the dissolving tank through a filtering device for removing activated carbon waste residue in the mixed liquid, an observation liquid level tube is arranged on the top of the crystallization tank, a liquid level gauge is arranged in the observation liquid level tube to detect the liquid level height in the observation liquid level tube in real time, a lifting bottom plate is arranged at the bottom of the crystallization tank to adjust the volume in the crystallization tank through lifting, a cooling and stirring device is arranged on the upper part of the lifting bottom plate to stir and cool the filtrate in the crystallization tank, and a second temperature detector is arranged on the inner side wall of the crystallization tank to detect the temperature of the solution in the crystallization tank in real time; The leaching tank is connected with the crystallization tank to leach the crystals obtained from the crystallization tank; The vacuum tank is connected with the leaching tank to vacuum dry the leached crystals. A central control unit is connected with the dissolving tank, the crystallizing tank, the elution tank and the vacuum tank respectively. The central control unit compares the real-time solution temperature with the preset heating temperature and the preset temperature adjusting temperature, and adjusts the heating temperature of the electric stirring heater according to the real-time solution temperature. The central control unit compares the real-time solution turbidity with the standard solution turbidity, and determines whether the crude product raw material is completely dissolved. The central control unit compares the real-time gray scale change rate with the standard gray scale change rate, and adjusts the amount of activated carbon powder according to the real-time gray scale change rate. The central control unit compares the real-time solution gray scale with the standard solution gray scale, and determines whether the solution is qualified for decolorization. The central control unit compares the real-time solution temperature with the preset solution temperature, and adjusts the stirring speed of the cooling stirring device according to the real-time solution temperature. The central control unit compares the real-time height change rate with the standard height change rate, and determines whether the solution is completely crystallized.

Images