A preparation system and method for the transformation crystallization of cefuroxime sodium

Abstract

The present invention belongs to the technical field of drug preparation, and specifically relates to a preparation system and method for the conversion of cefuroxime sodium crystals, which includes a reaction unit, a drying unit, and a preparation unit. The reaction unit mixes different drugs through a reaction kettle and transports them to the drying unit for drying. The dried medicine is transported to the preparation unit to prepare finished medicine; the reaction kettle includes a device main body, a feed inlet, and a discharge outlet; the reaction kettle further includes a pre-storage cylinder, which is installed at the top of the feed inlet and is located at the top of the device main body; during the process of the drug being scattered and flipped, the gas supply device transports inert gas with a preset temperature and humidity into the rotating cylinder, and the inert gas contacts the scattered drug. On the one hand, the temperature and humidity parameters of the drug are adjusted through the inert gas, and on the other hand, the contact area between the drug and the inert gas is enlarged through scattering, improving the efficiency of drug conditioning, reducing the degree of influence on the drug, and thus improving the preparation effect of the drug.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparation, and specifically relates to a preparation system and method for the transformation of cefuroxime sodium crystal form. Background Art

[0002] Cefuroxime sodium for injection is the most common antibiotic in clinical practice. Domestically produced cefuroxime sodium for injection are all imitations. Although this product has been on the market for many years, most domestic products are in multiple crystal forms, and generally have problems such as high color grade, low purity, and poor crystal form transformation, which are mainly reflected in large color changes, significant increases in related substances and polymers, and large decreases in content. The conventional preparation method of cefuroxime sodium is through steps of mixing reaction, drying, and formulation.

[0003] During the mixing reaction, the drug is put into the reaction kettle in a certain proportion and then heated to a predetermined reaction temperature. This means that the heating process is carried out after the drug is put into the reaction kettle to ensure that the drug reacts under appropriate temperature and pressure. Heating can be achieved by passing steam or other heating media through the jacket, and at the same time, the heating rate and temperature need to be controlled to ensure the safety and efficiency of the reaction. Therefore, before the drug is put into the reaction kettle, the reaction kettle is usually in an unheated or preheated state, waiting for the addition of the drug and the subsequent reaction process.

[0004] In the actual preparation process, the storage of the drug before being put in is likely to affect the quality of the drug. For example, during the transfer process of the drug, it reacts with components such as microorganisms in the air, resulting in the oxidation of the drug and even the generation of toxic substances. And during the transfer process of the drug, it is easy to come into contact with the moisture in the humid air, affecting the water content of the drug and ultimately affecting the quality of the final product. Summary of the Invention

[0005] In order to make up for the deficiencies of the prior art and solve the above technical problems, the present invention proposes a preparation system and method for the transformation of cefuroxime sodium crystal form.

[0006] The technical solution adopted by the present invention to solve its technical problems is: The present invention proposes a preparation system and method for the transformation of cefuroxime sodium crystal form, including a reaction unit, a drying unit, and a formulation unit. The reaction unit mixes and reacts different drugs through a reaction kettle and transports them to the drying unit for drying. The dried medicament is transported to the formulation unit to prepare the finished medicine. The reaction kettle includes a device main body, a feed inlet, and a discharge outlet. The reaction kettle further includes:

[0007] Pre-storage cylinder, the pre-storage cylinder is installed at the top of the feed inlet, and the pre-storage cylinder is located at the top of the reaction kettle; a rotating cylinder is rotatably connected inside the pre-storage cylinder, a sensor is installed inside the rotating cylinder for detecting temperature and humidity, and a feeding port is provided at the top of the rotating cylinder. A detector is provided at the top of the pre-storage cylinder, and the detection end of the detector detects the medicine inside the rotating cylinder through the feeding port; the rotating cylinder is connected to a driving member installed on the pre-storage cylinder to realize the rotation of the rotating cylinder; a diaphragm is provided on the inner wall of the center of the bottom of the rotating cylinder, and an electric telescopic rod is provided between the diaphragm and the inner wall of the bottom of the rotating cylinder; a lifting tube is provided at the center of the bottom of the diaphragm, a lifting rod slides inside the lifting tube, and the bottom of the lifting rod is connected to the telescopic end of the electric telescopic rod;

[0008] Vibration block, the vibration block is arranged on the inner wall of one side of the lifting tube. One side of the lifting rod is hinged to a swing block through a torsion spring, and the top of the vibration block contacts the bottom of the swing block; a first box is provided below the lifting tube, and a first plate is slidably connected inside the first box. The lifting rod passes through the center of the first plate and is connected to each other. The outer ring of the first box is respectively connected to a first tube, a second tube and a third tube through valves; one end of the first tube communicates with the rotating cylinder, one end of the second tube communicates with the feed inlet, and the third tube communicates with a gas supply device on one side of the reaction kettle, and the gas supply device supplies inert gas into the rotating cylinder.

[0009] Preferably, the inner wall of the bottom of the rotating cylinder is evenly provided with rotating plates, and one end of the rotating plate is connected to the side wall of the rotating cylinder, and the other end is close to the diaphragm. The top of the rotating plate protrudes above the rotating cylinder; both sides of the rotating plate are inclined towards the diaphragm, and the inside of the rotating plate is a hollow structure; sampling holes are evenly opened on the inner wall of the rotating plate, and a sealing plate is slidably connected to the inner wall of the rotating plate through a spring, and the sealing plate is used to block the sampling holes; a sampling tube is slidably arranged inside the rotating plate, an electric push rod is arranged at the bottom of the rotating plate, and the telescopic end of the electric push rod is connected to the bottom of the sampling tube, and the bottom of the sampling tube contacts the sealing plate.

[0010] Preferably, the sampling holes are inclined towards the electric push rod; the inner wall of the rotating plate is evenly provided with vibration grooves, and the vibration grooves are vertically arranged on one side of the sampling holes. One side of the sealing plate is slidably connected to a trapezoidal protrusion through a spring, and the protrusion extends into the vibration grooves.

[0011] Preferably, guide plates are provided on both sides of the rotating plate, and the guide plates are arc-shaped, and one end of the guide plate faces the diaphragm.

[0012] Preferably, a gas guide pipe is provided between adjacent rotating plates, and the gas guide pipe is located at the connection between the bottom wall and the side wall of the rotating cylinder. Both ends of the gas guide pipe face the guide plates of the adjacent rotating plates along the connection between the bottom wall and the side wall of the rotating cylinder, and the middle part of the gas guide pipe is connected to the first tube.

[0013] Preferably, an air tank is provided inside the pre-storage cylinder, and the air tank is connected to the second tube through an internal one-way valve and a trachea; a metering device is provided at the bottom inside the first box.

[0014] Preferably, a filter plate is provided inside the gas tank. The filter plate is located at the axial center of the gas tank, and the two side edges of the filter plate are in contact with the inner wall of the gas tank. One end of the filter plate is evenly hinged with swing plates, and the swing plates are symmetrically arranged with respect to the filter plate. One of the two swing plates swings towards the inside of the gas tank, and the other swings towards the outside of the gas tank.

[0015] Preferably, a blowing ring is provided inside the first box, and the blowing ring is close to the metering device. Blowing holes are evenly formed in the blowing ring, and the blowing holes are distributed around the connection between the first box and the metering device. The blowing holes face the connection between the first box and the metering device, and the blowing ring is connected to the third pipe.

[0016] Preferably, elastic pieces are evenly provided at the bottom of the diaphragm, and the elastic pieces are wavy. One end of the elastic piece is connected to the inner wall of the rotating cylinder, and the other end is connected to the lifting pipe.

[0017] A preparation method for the crystal transformation of cefuroxime sodium, the preparation method comprising the following steps:

[0018] S1: Before the drug is put into the reaction kettle, first put it into the rotating cylinder through the feeding port, and then seal the feeding port immediately; the driving member drives the rotating cylinder to rotate forward and backward to achieve the purpose of shaking the drug; then temper the drug, and the gas supply device conveys inert gas with a preset temperature and humidity into the rotating cylinder. The inert gas contacts the drug in a sprinkling state, and the temperature and humidity parameters of the drug are adjusted through the inert gas.

[0019] S2: Subsequently, detect the drug situation. The driving member and the rotating cylinder in the pre-storage cylinder remain static. The worker opens the feeding port at the top of the rotating cylinder, inserts the detector into the rotating cylinder, performs non-destructive detection on the drug, and analyzes the detection parameters according to the standard parameters; after determining that it is qualified, put the drug into the reaction kettle.

[0020] S3: Then, the drug is dispersed in an organic solvent which is a mixture of one or more of C1-C4 lower alcohols containing water, acetone containing water, and tetrahydrofuran containing water in a specified ratio. Stir and perform crystal transformation at 40°C - 65°C for 0.5 - 6 h, and perform filtration while maintaining a constant temperature state. After drying, a cefuroxime sodium crystal compound is obtained.

[0021] The beneficial effects of the present invention are as follows:

[0022] 1. For the preparation system and method for the crystal transformation of cefuroxime sodium described in the present invention, while driving the drug to form a tumbling by forward and reverse rotation, the electric telescopic rod is started to drive the lifting rod to lift and lower, so that the diaphragm bends and vibrates up and down to sprinkle the drug, further improving the tumbling effect of the drug; moreover, the rotation of the rotating cylinder can promote the movement of the drug at the connection between the bottom and the side wall inside the rotating cylinder, accelerate the movement of the drug towards the diaphragm, and improve the drug tumbling efficiency.

[0023] 2. In the preparation system and method for the polymorph transformation of cefuroxime sodium according to the present invention, during the process of the drug being scattered and turned over, the gas supply device conveys inert gas with a preset temperature and humidity into the rotary drum. The inert gas contacts the scattered drug. On the one hand, the temperature and humidity parameters of the drug are adjusted through the inert gas. On the other hand, the contact area between the drug and the inert gas is enlarged through scattering, improving the efficiency of drug conditioning and reducing the degree of influence on the drug, thereby improving the preparation effect of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The present invention will be further described below with reference to the accompanying drawings.

[0025] Figure 1 is a perspective view of the reaction kettle in the present invention;

[0026] Figure 2 is a perspective view of the pre-storage cylinder;

[0027] Figure 3 is an internal schematic view of the pre-storage cylinder;

[0028] Figure 4 is a state diagram of the diaphragm at rest;

[0029] Figure 5 is a state diagram when the first box supplies gas to the gas tank;

[0030] Figure 6 is an internal schematic view of the rotary drum;

[0031] Figure 7 is a cross-sectional view of the rotary drum in the top-down direction;

[0032] Figure 8 is an internal schematic view of the rotating plate;

[0033] Figure 9 is a state diagram of the protrusion passing through the vibration groove;

[0034] In the figure: reaction kettle 1, feed inlet 11, discharge outlet 12, pre-storage cylinder 13, rotary drum 14, feeding port 15, detector 16, driving member 17, diaphragm 18, electric telescopic rod 19, lifting pipe 2, lifting rod 21, vibration block 22, swinging block 23, first box 24, first plate 25, first pipe 26, second pipe 27, third pipe 28, gas supply device 29, rotating plate 3, sampling hole 31, sealing plate 32, sampling pipe 33, electric push rod 34, vibration groove 35, protrusion 36, guide plate 37, air guide pipe 38, gas tank 4, metering device 41, filter plate 42, swinging plate 43, blowing ring 44, blowing hole 45, elastic piece 46. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0035] The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention. Embodiment 1:

[0036] To effectively solve the above problems, as shown in the accompanying drawings of the specification Figures 1-9 it includes a reaction unit, a drying unit, and a preparation unit. The reaction unit mixes and reacts different drugs through a reaction kettle 1 and transports them to the drying unit for drying. The dried medicine is transported to the preparation unit to prepare finished medicine; the reaction kettle 1 includes an equipment main body, a feed inlet 11, and a discharge outlet 12; the reaction kettle 1 is a reactor commonly used for drug preparation. In the reaction kettle 1, the drugs are put into the reaction kettle 1 through the feed inlet 11, and the original drugs are mixed with specific catalytic drugs or reaction drugs and react under certain temperature, pressure, and stirring speed; these reaction conditions are usually determined according to the specific synthesis route and process requirements of cephalosporin drugs to ensure the efficient progress of the reaction and the purity of the product; after the reaction is completed, it is discharged from the reaction kettle 1 through the discharge outlet 12.

[0037] The reaction kettle 1 further includes:

[0038] A pre-storage cylinder 13, the pre-storage cylinder 13 is installed on the top of the feed inlet 11, and the pre-storage cylinder 13 is located on the top of the reaction kettle 1; a rotating cylinder 14 is rotatably connected inside the pre-storage cylinder 13. A sensor is installed inside the rotating cylinder 14 to detect temperature and humidity, and a feeding port 15 is provided at the top of the rotating cylinder 14. A detector 16 is provided at the top of the pre-storage cylinder 13, and the detection end of the detector 16 detects the drugs inside the rotating cylinder 14 through the feeding port 15; the rotating cylinder 14 is connected to a driving member 17 installed on the pre-storage cylinder 13 to realize the rotation of the rotating cylinder 14; a diaphragm 18 is provided on the inner wall of the center of the bottom of the rotating cylinder 14, and an electric telescopic rod 19 is provided between the diaphragm 18 and the inner wall of the bottom of the rotating cylinder 14; a lifting tube 2 is provided at the center of the bottom of the diaphragm 18, a lifting rod 21 slides inside the lifting tube 2, and the bottom of the lifting rod 21 is connected to the telescopic end of the electric telescopic rod 19.

[0039] The vibrating block 22 is arranged on the inner wall of one side of the lifting tube 2. One side of the lifting rod 21 is hinged to the swinging block 23 through a torsion spring, and the top of the vibrating block 22 contacts the bottom of the swinging block 23. A first box 24 is arranged below the lifting tube 2, and a first plate 25 is slidably connected in the first box 24. The lifting rod 21 penetrates through the center of the first plate 25 and is connected to each other. The outer circle of the first box 24 is respectively connected with a first pipe 26, a second pipe 27 and a third pipe 28 through valves. One end of the first pipe 26 communicates with the rotary drum 14, one end of the second pipe 27 communicates with the feeding port 11, and the third pipe 28 communicates with the gas supply device 29 on one side of the reaction kettle 1. The gas supply device 29 supplies inert gas into the rotary drum 14.

[0040] The sensor is a conventional temperature and humidity sensor for detecting the storage condition of the drug in the rotary drum 14. The detector 16 is a conventional instrument for detecting parameters such as the water content of the drug, such as a near-infrared moisture meter. Its principle is to focus near-infrared light beams of multiple wavelengths on the surface of the object to be measured, and the near-infrared light beams reflected from its surface are received and processed by a high-level infrared optical detection system to complete the detection work of the drug. The driving member 17 is a conventional electric driving device, such as a motor that can meet the forward and reverse rotation modes. The driving member 17 is connected to the rotary drum 14 through a conventional connection method to realize the cycle of the driving member 17 driving the rotary drum 14 to rotate forward and reverse. The electric telescopic rod 19 is a conventional electrically driven telescopic device, and the electric telescopic rod 19 is selected from the types with its own power supply to meet the purpose that the rotary drum 14 drives the electric telescopic rod 19 to rotate without being affected. The one-way valve is a conventional valve appliance. The gas supply device 29 is a conventional equipment equipped with the reaction kettle 1 for supplying gas to the reaction kettle 1 and other devices to meet the working requirements.

[0041] Specific working process: Before the drug is put into the reaction kettle 1, first put it into the rotary drum 14 through the feeding port 15, and then seal the feeding port 15 immediately. The driving member 17 drives the rotary drum 14 to rotate forward and reverse, that is, after the rotary drum 14 drives the stored drug inside to rotate clockwise, the rotary drum 14 rotates reversely to drive the drug to rotate counterclockwise in a short time. The rotation angles of the rotary drum 14 rotating forward and reverse are both less than 180 degrees. In this way, the drug forms a surging in the rotary drum 14 to achieve the purpose of shaking the drug, which helps to prevent caking or stratification, ensure the uniformity of the drug before being put into the reaction kettle 1, maintain the quality of the drug before the reaction, and improve the effect of drug preparation. When the first batch of drugs starts to react in the reaction kettle 1 and the process lasts for several hours, at this time, the second batch of drugs is put into the rotary drum 14 for detecting and adjusting the temperature and humidity parameters of the drug. When it is necessary to initially detect the storage condition of the drug, the driving member 17 and the rotary drum 14 in the pre-storage cylinder 1 remain static. The worker opens the feeding port 15 at the top of the rotary drum 14 and inserts the detector 16 into the rotary drum 14 to perform non-destructive detection on the drug, avoiding contamination during the drug detection process, maintaining the cleanliness of the drug, thereby improving the effect of drug preparation and further improving the finished product quality of the drug.

[0042] The rotary drum 14 drives components such as the diaphragm 18 and the electric telescopic rod 19 to rotate. When the electric telescopic rod 19 is not activated, the diaphragm 18 is in a flat state, and the top of the vibration block 22 contacts the bottom of the swing block 23. When the electric telescopic rod 19 is activated, it drives the lifting rod 21 and the swing block 23 to descend. The swing block 23 drives the lifting tube 2 to descend through the vibration block 22. The lifting tube 2 drives the diaphragm 18 to descend from the central position, and the diaphragm 18 is sunken and bent into a bowl shape. At this time, the diaphragm 18 is bent to the limit so that the lifting tube 2 no longer descends, while the electric telescopic rod 19 continuously drives the lifting rod 21 to descend. After the vibration block 22 stops descending, it squeezes the swing block 23, and the swing block 23 swings over the vibration block 22. The vibration block 22 is no longer affected by the pulling of the swing block 23, so that the sunken diaphragm 18 rebounds into an arched pot lid shape due to the characteristics of the rubber, and returns to a flat state after several rebounds, achieving the purpose of large-amplitude vibration of the diaphragm 18. When the diaphragm 18 is sunken, part of the drug converges and flows onto the diaphragm 18. When the diaphragm 18 arches, the drug is thrown upward by the diaphragm 18, realizing the effect of drug turning, avoiding the situation of caking and other problems when the drug and other auxiliary agents are placed for a long time, improving the uniformity of the drug, and thus improving the preparation effect of the drug. The inner wall of the rotary drum 14 below the diaphragm 18 is communicated with the outside, avoiding the influence of the space seal between the diaphragm 18 and the first box 24 on the bending of the diaphragm 18;

[0043] While the lifting rod 21 drives the diaphragm 18 to vibrate during its lifting and lowering, the lifting rod 21 drives the first plate 25 to lift and lower in the first box 24. Different states of the rotary drum 14 serve different purposes. For example:

[0044] When the rotary drum 14 is in the storage state, the rotary drum 14 and the first plate 25 are stationary. The gas supply device 29 transports inert gas into the first box 24 through the third pipe 28, and the first box 24 transports inert gas to the bottom of the rotary drum 14 through the first pipe 26, improving the storage environment of the drug, avoiding the situation of drug oxidation and other problems, improving the quality of the drug, and thus improving the preparation effect of the drug, and further improving the finished product quality of the drug. And because the inert gas in the rotary drum 14 is transported from bottom to top, when the worker opens the feeding port 15, the inert gas diffuses outward from the feeding port 15, preventing the outside air from entering the rotary drum 14 to contact the drug, and avoiding the situation of affecting the drug in a humid preparation environment. Moreover, the upward transport of the inert gas in the rotary drum 14 can blow the drug at the bottom of the rotary drum 14 to rise, improving the drug turning effect;

[0045] When the rotary drum 14 conditions the drug, the rotary drum 14 rotates periodically. While driving the drug to surge through forward and reverse rotation, the electric telescopic rod 19 is activated to drive the lifting rod 21 to lift and lower, causing the diaphragm 18 to bend and vibrate up and down, spraying the drug, and further improving the tumbling effect of the drug. Moreover, the rotation of the rotary drum 14 can promote the movement of the drug at the connection between the bottom and the side wall inside the rotary drum 14, accelerate the movement of the drug onto the diaphragm 18, and improve the drug tumbling efficiency. At this time, during the process of the drug being sprayed and tumbled, the gas supply device 29 conveys inert gas with a preset temperature and humidity into the rotary drum 14. The inert gas contacts the drug in the spraying state. On the one hand, the temperature and humidity parameters of the drug are adjusted through the inert gas. On the other hand, the contact area between the drug and the inert gas is enlarged through spraying, improving the efficiency of drug conditioning, reducing the degree of influence on the drug, and thus improving the preparation effect of the drug.

[0046] When the rotary drum 14 conveys the drug to the reaction kettle 1, the rotary drum 14 rotates slowly, the first plate 25 remains stationary, the gas supply device 29 stops supplying gas, and the drug in the rotary drum 14 enters the first box 24 through the first pipe 26. Until the drug in the first box 24 reaches the required amount, the first pipe 26 is closed, the second pipe 27 and the third pipe 28 are opened, the gas supply device 29 starts supplying gas, the third pipe 28 conveys gas into the first box 24, and the gas flow in the first box 24 drives the drug to enter the reaction kettle 1 through the third pipe 28 until the drug in the first box 24 and the second pipe 27 is drained completely, ensuring the dosing accuracy of the drug and improving the preparation effect of the drug. Moreover, when the drug enters the first box 24 through the first pipe 26, the slow rotation of the rotary drum 14 can promote the movement of the drug, accelerate the entry of the drug into the first box 24, and improve the dosing rate of the drug. Also, the feed inlet 11 of the reaction kettle 1 does not need to be opened throughout the process, avoiding the influence on the temperature and humidity inside the reaction kettle 1 and the resulting impact on the preparation effect of the reaction kettle 1, thereby improving the preparation effect of the drug. In addition, in order to drain the drug in the first box 24 and the second pipe 27, the electric telescopic rod 19 is activated, and the first plate 25 frequently lifts and lowers in the first box 24 to squeeze the gas in the first box 24 into the second pipe 27, causing the first box 24 to intermittently jet gas into the second pipe 27, increasing the gas flow rate, thereby improving the effect of gas scouring the second pipe 27, cleaning the second pipe 27, and avoiding the situation where the drug deteriorates after long-term residue and is mixed into the drug during subsequent feeding, ensuring the preparation safety of the drug. Finally, after the feeding is completed, the second pipe 27 is closed, and the gas supply device 29 continues to supply gas into the rotary drum 14. When the gas passes through the first pipe 26 during gas conveyance, the residual drug in the first pipe 26 is also blown into the rotary drum 14 to avoid drug residue.

[0047] Through the above description, taking the rotary drum 14 as an example, targeted measures are taken for conveying, conditioning, and storing the drug, improving the convenient use degree of the rotary drum 14, and thus enhancing the practicality. Example Two:

[0048] On the basis of the first embodiment, a rotating plate 3 is evenly arranged on the inner wall at the bottom of the rotating drum 14, and one end of the rotating plate 3 is connected to the side wall of the rotating drum 14, and the other end is close to the diaphragm 18, and the top of the rotating plate 3 is exposed above the rotating drum 14; both sides of the rotating plate 3 are inclined toward the diaphragm 18, and the interior of the rotating plate 3 is a hollow structure; sampling holes 31 are evenly opened on the inner wall of the rotating plate 3, and a sealing plate 32 is slidably connected to the inner wall of the rotating plate 3 through a spring, and the sealing plate 32 is used to block the sampling holes 31; a sampling tube 33 is slidably arranged in the rotating plate 3, and an electric push rod 34 is arranged at the bottom of the rotating plate 3, and the telescopic end of the electric push rod 34 is connected to the bottom of the sampling tube 33, and the bottom of the sampling tube 33 contacts the sealing plate 32; the electric push rod 34 is a conventional electric telescopic device;

[0049] The sampling hole 31 is arranged obliquely toward the electric push rod 34; the inner wall of the rotating plate 3 is evenly provided with vibration grooves 35, and the vibration grooves 35 are vertically arranged on one side of the sampling hole 31, and a trapezoidal protrusion 36 is slidably connected to one side of the sealing plate 32 through a spring, and the protrusion 36 extends into the vibration groove 35;

[0050] Guide plates 37 are provided on both sides of the rotating plate 3, and the guide plates 37 are arc-shaped, with one end of the guide plates 37 facing the diaphragm 18;

[0051] An air guide tube 38 is provided between adjacent rotating plates 3, and the air guide tube 38 is located at the connection between the bottom wall and the side wall of the rotating drum 14, and both ends of the air guide tube 38 are directed toward the guide plate 37 of the adjacent rotating plate 3 along the connection between the bottom wall and the side wall of the rotating drum 14, and the middle part of the air guide tube 38 is connected to the No. 1 pipe 26;

[0052] Specific working process: the rotating drum 14 drives the rotating plate 3 to rotate clockwise, and the rotating plate 3 pushes the medicine to rotate together. After the rotating drum 14 rotates to a set angle, the rotating drum 14 drives the rotating plate 3 to rotate counterclockwise. The medicine continues to move clockwise due to inertia until the medicine collides with the inclined surface on one side of the rotating plate 3. The inclined surface of the rotating plate 3 guides the medicine. After being guided, the medicine moves toward the diaphragm 18 and gathers on the diaphragm 18. With the throwing of the diaphragm 18, the movement effect of the medicine is improved, thereby improving the uniformity of the medicine, promoting the contact between the medicine and the inert gas, and accelerating the temperature and humidity parameters of the medicine to reach the required values for preparation;

[0053] After the drug is conditioned or stored for a long time, workers need to take samples of the drug at this time. If the feeding port 15 is opened for sampling, it is easy to cause the sampling vessel to contaminate the drug. Therefore, when sampling, the electric push rod 34 starts to drive the sampling tube 33 to descend. The sampling tube 33 descends to contact the sealing plate 32 and squeezes the sealing plate 32 to descend to expose the sampling hole 31. After the sampling tube 33 is located below the sampling hole 31, the electric push rod 34 remains static. Subsequently, the control drum 14 rotates forward and backward frequently. When the drug collides with the rotating plate 3, the drug contacts the sampling hole 31 on the rotating plate 3 and enters the sampling tube 33 through the sampling hole 31. After the drug sample is obtained in the sampling tube 33, the electric push rod 34 rises to drive the sampling tube 33 to reset, and the sealing plate 32 rises and resets under the influence of the spring to re-seal the sampling hole 31. Then, the worker replaces the sampling tube 33 from the top of the rotating plate 3 to take the drug sample. Sampling is carried out without contacting foreign vessels, reducing the possibility of drug contamination and improving the sampling safety of the drug, thereby improving the preparation quality of the drug.

[0054] By setting the sampling hole 31 to be inclined towards the electric push rod 34, among the two ends of the sampling hole 31, the end close to the drug is located above the end close to the sampling tube 33. The drug entering the sampling hole 31 is affected by the inclined inner wall of the sampling hole 31 and moves more smoothly into the sampling tube 33, avoiding the situation where the drug remains in the sampling hole 31 for a long time, thereby improving the preparation effect of the drug. Moreover, during the lifting and lowering process of the sealing plate 32, the protrusion 36 is driven to lift and lower together. When the protrusion 36 contacts the inner wall of the rotating plate 3, the spring on the protrusion 36 is in a compressed state. After the protrusion 36 moves close to the vibration groove 35, the protrusion 36 is no longer squeezed by the inner wall of the rotating plate 3. The protrusion 36 is driven by the stretching of the spring to enter and collide with the vibration groove 35. The collision of the protrusion 36 with the vibration groove 35 causes vibration, making the rotating plate 3 and the sampling hole 31 vibrate. Through the vibration of the sampling hole 31, the drug remaining in the sampling hole 31 is promoted to move into the rotating plate 3, avoiding the drug remaining in the sampling hole 31 and further improving the preparation effect of the drug. When not sampling, the sealing plate 32 blocks the sampling hole 31, so that the drug cannot enter the sampling hole 31 when contacting the rotating plate 3.

[0055] Furthermore, when not sampling, the drug moves to contact the guide plate 37 on the inclined surface of the rotating plate 3, and part of the drug moves onto the guide plate 37. At this time, while the drum 14 drives the guide plate 37 to reverse through the rotating plate 3, the drug is also affected by inertia and continues to move along the guide plate 37 towards one end. Since the guide plate 37 is arc-shaped, the drug is guided by the guide plate 37 to move above the diaphragm 18 until it falls from one end of the guide plate 37, achieving the purpose of spraying, further improving the movement effect of the drug, increasing the contact degree between the drug and the inert gas during drug conditioning, and thus improving the preparation effect of the drug.

[0056] When feeding the reaction kettle 1, the rotary drum 14 drives the air guide pipe 38 to rotate frequently in both forward and reverse directions. After the drug enters the air guide pipe 38, it enters the first box 24 through the first pipe 26. When tempering the drug, the first pipe 26 conveys gas into the rotary drum 14 through the air guide pipe 38. Since both ends of the air guide pipe 38 face the guide plate 37 of the adjacent rotating plate 3 along the connection between the bottom wall and the side wall of the rotary drum 14, the gas ejected from the air guide pipe 38 can be blown towards the connection between the bottom wall and the side wall of the rotary drum 14, avoiding the long-term retention of the drug at the dead corner of the rotary drum 14, which affects the tempering of the drug here due to space limitations, thereby improving the uniformity of drug tempering and further improving the preparation effect of the drug. Moreover, when the gas ejected from both ends of the air guide pipe 38 contacts the drug, it promotes the movement of the drug, enabling more drugs to produce a sprinkling effect through the guide plate 37, contributing to the tempering work of the drug and the inert gas, thereby improving the tempering efficiency of the drug and further improving the preparation efficiency of the drug. Example Three:

[0057] On the basis of Example Two, an air tank 4 is provided inside the pre-storage cylinder 13, and the air tank 4 is connected to the second pipe 27 through an internal one-way valve and a trachea. A measuring device 41 is provided at the bottom inside the first box 24.

[0058] A filter plate 42 is provided inside the air tank 4. The filter plate 42 is located at the axis position of the air tank 4, and the two side edges of the filter plate 42 contact the inner wall of the air tank 4. One end of the filter plate 42 is evenly hinged with a swing plate 43, and the swing plate 43 is symmetrically divided with the filter plate 42 as the reference. One of the two swing plates 43 swings towards the inside of the air tank 4, and the other swings towards the outside of the air tank 4.

[0059] An air blowing ring 44 is provided inside the first box 24, and the air blowing ring 44 is close to the measuring device 41. The air blowing ring 44 is evenly provided with air blowing holes 45, and the air blowing holes 45 are distributed around the connection between the first box 24 and the measuring device 41. The air blowing holes 45 face the connection between the first box 24 and the measuring device 41, and the air blowing ring 44 is connected to the third pipe 28.

[0060] Elastic pieces 46 are evenly provided at the bottom of the diaphragm 18, and the elastic pieces 46 are wavy. One end of the elastic piece 46 is connected to the inner wall of the rotary drum 14, and the other end is connected to the lifting pipe 2.

[0061] The measuring device 41 is a conventional weighing scale; the filter plate 42 is a conventional device for filtering gas.

[0062] Specific working process: Each time when feeding the first box 24, the drug entering the first box 24 accumulates on the measuring device 41, and the measuring device 41 weighs the weight of the drug. When the dosing amount is reached, the drug is then put into the reaction kettle 1, so that the entire process of drug feeding will not contact the outside world, avoiding the influence of the drug contacting air during the feeding process, thereby improving the preparation effect of the drug.

[0063] After each feeding of the first box 24, the first box 24 starts self-cleaning; the first pipe 26, the second pipe 27, and the third pipe 28 are closed, the first plate 25 descends, squeezing the gas in the first box 24 into the second pipe 27. Since one end of the second pipe 27 close to the reactor 1 is closed, the gas tank 4 is opened to communicate with the second pipe 27, so that the gas in the second pipe 27 enters the gas tank 4 through the gas pipe; when the gas just enters the gas tank 4, it contacts the swing plate 43. One of the swing plates 43 swings towards the inside of the gas tank 4 under the influence of air pressure, and the gas passes over the swing plate 43 and enters the inside of the gas tank 4 and contacts the filter plate 42; the first plate 25 rises, creating a pressure difference inside the first box 24, causing the first box 24 to inhale air from the gas tank 4 through the second pipe 27. The other one of the two swing plates 43 swings towards the outside of the gas tank 4 under the influence of the suction pressure, so that the gas in the gas tank 4 is sucked through the filter plate 42, filtering out the residual drugs carried in the gas, achieving the effect of purifying the gas, that is: the gas discharged from the first box 24 flushes the inner walls of the first box 24 and the second pipe 27, and transports the residual drugs into the gas tank 4 with the gas for filtration; the first box 24 sucks the filtered gas. At this time, the gas flows reversely in the second pipe 27, flushing the inner walls of the second pipe 27 and the first box 24 again, and the first box 24 is ready to discharge gas. This cycle is repeated, enabling the first box 24 to perform gas circulation with the remaining inert gas without wasting inert gas, thereby improving the cleaning degree of the first box 24 and the second pipe 27, avoiding drug contamination, and further improving the cleaning degree of the drugs; while the first box 24 and the third box maintain the flow of inert gas for a long time, and have a lower cleaning requirement compared to the second pipe 27;

[0064] When the first box 24 feeds the reactor 1, the third pipe 28 conveys inert gas to the blowing ring 44. The blowing ring 44 blows air through the blowing holes 45 to the dead corner where the first box 24 is connected to the metering device 41, blowing up the drugs inside and entering the reactor 1 together with the inert gas, ensuring that all the drugs on the metering device 41 can be put into the reactor 1, avoiding large errors in the input dosage and affecting the preparation of the drugs, thereby improving the preparation effect of the drugs; moreover, the surface of the blowing ring 44 is smooth-treated to prevent drugs from accumulating on the top of the blowing ring 44 when entering the first box 24; furthermore, the blowing holes 45 blow air towards the dead corner at the bottom of the first box 24, which helps to reduce the drug residue in the first box 24 and facilitates the self-cleaning work of the first box 24;

[0065] Further, by evenly providing the elastic piece 46 at the bottom of the diaphragm 18, the lifting tube 2 drives the diaphragm 18 and the elastic piece 46 to bend and descend. When the diaphragm 18 descends close to the limit position, the elastic piece 46 can serve as the support of the diaphragm 18 to stop the diaphragm 18 from being continuously pulled, avoiding the diaphragm 18 being torn by the lifting tube 2, thereby protecting the diaphragm 18; moreover, after the lifting tube 2 pulls the elastic piece 46 to bend, it can store energy for the vibration of the diaphragm 18, improve the vibration effect of the diaphragm 18, thereby improving the spraying effect of the drug, and further improving the contact effect between the drug and the inert gas during drug conditioning; furthermore, since the elastic piece 46 is wavy and one end of the elastic piece 46 is connected to the inner wall of the rotating cylinder 14, compared with the straight elastic piece 46, under the same material and length, the extended length of the wavy elastic piece 46 is greater than the length of the straight elastic piece 46, so that the wavy elastic piece 46 can improve the energy storage capacity and achieve the purpose of better vibration effect of the wavy elastic piece 46; when the wavy elastic piece 46 bends, each wavy part can bend and store energy, improving the bending uniformity of the elastic piece 46, avoiding excessive bending at a certain place of the elastic piece 46, reducing the service life, and preventing the situation that the damaged part of the elastic piece 46 pierces the diaphragm 18; in addition, since the lifting tube 2 and the elastic piece 46 are connected to the bottom of the diaphragm 18, the mass of the diaphragm 18 is increased, the inertia generated during the vibration of the diaphragm 18 is increased, thereby improving the vibration effect of the diaphragm 18; finally, since the lifting tube 2 is always sleeved on the lifting rod 21 for lifting and lowering, it is avoided that the lifting tube 2 and the lifting rod 21 are separated from each other, resulting in the situation that normal work is affected. Example 4:

[0066] A preparation method for the polymorph transformation of cefuroxime sodium, the preparation method comprising the following steps:

[0067] S1: Before the drug is put into the reaction kettle 1, first put it into the rotating cylinder 14 through the feeding port 15, and then seal the feeding port 15 immediately; the driving member 17 drives the rotating cylinder 14 to rotate forward and backward to achieve the purpose of shaking the drug; then the drug is conditioned, and the gas supply device 29 conveys the inert gas with a preset temperature and humidity into the rotating cylinder 14, and the inert gas contacts the drug in the spraying state, and the temperature and humidity parameters of the drug are adjusted through the inert gas;

[0068] S2: Subsequently, the drug situation is detected. The driving member 17 and the rotating cylinder 14 in the pre-storage cylinder 13 remain static. The worker opens the feeding port 15 at the top of the rotating cylinder 14, inserts the detector 16 into the rotating cylinder 14, and performs non-destructive detection on the drug, and analyzes the detection parameters according to the standard parameters; after determining that it is qualified, the drug is put into the reaction kettle 1.

[0069] S3: Next, the drug is dispersed in an organic solvent which is a mixture of one or more of water-containing C1-C4 lower alcohols, water-containing acetone, and water-containing tetrahydrofuran in a specified proportion, and stirred for crystal conversion at 40°C - 65°C for 0.5 - 6 h. Filtering is carried out while maintaining a constant temperature state, and a cefuroxime sodium crystal compound is obtained after drying;

[0070] Specifically: During the production process of cefuroxime sodium, it is of great importance to use a reaction kettle to conduct quality inspection on raw materials before crystal conversion. Inspect indicators such as the purity, impurity content, and moisture content of the raw materials to ensure compliance with production requirements and avoid unqualified raw materials from affecting the final crystal conversion quality; According to the results of the raw material quality inspection, adjust the crystal conversion process parameters of the reaction kettle, such as temperature, pH value, stirring speed, etc., to improve the crystal conversion efficiency of cefuroxime sodium; Early detection of problems in raw materials through inspection can avoid production interruption or unqualified crystal conversion caused by raw material quality problems; Using a reaction kettle for the crystal conversion of cefuroxime sodium can optimize the crystal form, improve the purity, improve the physical properties, and obtain a more stable product quality; This process not only improves the efficacy and formulation performance of the drug, but also reduces the production cost, meets the regulatory requirements of drug production, and through precise control of process parameters, efficient and stable large-scale production can be achieved.

[0071] The above has shown and described the basic principles, main features, and advantages of the present invention. Skilled workers in this industry should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed. The scope of protection claimed by the present invention is defined by the appended claims and their equivalents.

Claims

1. A preparation system for the conversion of cefuroxime sodium crystals, comprising a reaction unit, a drying unit and a preparation unit. The reaction unit mixes different drugs through a reaction kettle (1) for reaction and transports them to the drying unit for drying. The dried medicine is transported to the preparation unit to prepare finished medicine; the reaction kettle (1) includes a device main body, a feed inlet (11) and a discharge outlet (12); it is characterized in that, The reactor (1) further includes: A pre-storage cylinder (13), which is installed at the top of the feed inlet (11), and the pre-storage cylinder (13) is located at the top of the reactor (1); A rotating cylinder (14) is rotatably connected inside the pre-storage cylinder (13), a sensor for detecting temperature and humidity is installed inside the rotating cylinder (14), and a feeding port (15) is provided at the top of the rotating cylinder (14). A detector (16) is provided at the top of the pre-storage cylinder (13), and the detection end of the detector (16) detects the drug inside the rotating cylinder (14) through the feeding port (15); The rotating cylinder (14) is connected to a driving member (17) installed on the pre-storage cylinder (13) to realize the rotation of the rotating cylinder (14); A diaphragm (18) is provided on the inner wall of the center of the bottom of the rotating cylinder (14), and an electric telescopic rod (19) is provided between the diaphragm (18) and the inner wall of the bottom of the rotating cylinder (14); A lifting tube (2) is provided at the center of the bottom of the diaphragm (18), a lifting rod (21) slides inside the lifting tube (2), and the bottom of the lifting rod (21) is connected to the telescopic end of the electric telescopic rod (19). A vibration block (22) is provided on one inner wall of the lifting tube (2). One side of the lifting rod (21) is hinged to a swinging block (23) through a torsion spring, and the top of the vibration block (22) contacts the bottom of the swinging block (23); A first box (24) is provided below the lifting tube (2), and a first plate (25) is slidably connected inside the first box (24). The lifting rod (21) passes through the center of the first plate (25) and is connected to each other. The outer circle of the first box (24) is respectively connected to a first tube (26), a second tube (27) and a third tube (28) through valves; One end of the first tube (26) communicates with the rotating cylinder (14), one end of the second tube (27) communicates with the feed inlet (11), and the third tube (28) communicates with a gas supply device (29) on one side of the reactor (1), and the gas supply device (29) supplies inert gas into the rotating cylinder (14). The inner wall of the bottom of the rotating cylinder (14) is evenly provided with rotating plates (3), and one end of the rotating plate (3) is connected to the side wall of the rotating cylinder (14), and the other end is close to the diaphragm (18). The top of the rotating plate (3) is exposed above the rotating cylinder (14); Both sides of the rotating plate (3) are inclined towards the diaphragm (18), and the inside of the rotating plate (3) is a hollow structure; Sampling holes (31) are evenly opened on the inner wall of the rotating plate (3), and a sealing plate (32) is slidably connected to the inner wall of the rotating plate (3) through a spring, and the sealing plate (32) is used to block the sampling holes (31); A sampling tube (33) slides inside the rotating plate (3), an electric push rod (34) is provided at the bottom of the rotating plate (3), and the telescopic end of the electric push rod (34) is connected to the bottom of the sampling tube (33), and the bottom of the sampling tube (33) contacts the sealing plate (32). The sampling hole (31) is inclined towards the electric push rod (34); Vibration grooves (35) are evenly provided on the inner wall of the rotating plate (3), and the vibration grooves (35) are vertically arranged on one side of the sampling hole (31). One side of the sealing plate (32) is slidably connected to a trapezoidal protrusion (36) through a spring, and the protrusion (36) extends into the vibration groove (35).

2. The preparation system for the polymorph transformation of cefuroxime sodium according to claim 1, characterized in that: Guide plates (37) are provided on both sides of the rotating plate (3), and the guide plates (37) are arc-shaped, with one end of the guide plate (37) facing the diaphragm (18).

3. The preparation system for the conversion of cefuroxime sodium according to claim 2, characterized in that: An air duct (38) is provided between adjacent rotating plates (3), and the air duct (38) is located at the connection of the bottom wall and the side wall of the rotating cylinder (14). Both ends of the air duct (38) face the guide plates (37) of the adjacent rotating plates (3) along the connection of the bottom wall and the side wall of the rotating cylinder (14), and the middle part of the air duct (38) is connected to the first pipe (26).

4. The preparation system for the conversion of cefuroxime sodium according to claim 1, characterized in that: An air tank (4) is provided in the pre-storage cylinder (13), and the air tank (4) is connected to the second pipe (27) through a built-in one-way valve and a trachea; a metering device (41) is provided at the inner bottom of the first box (24).

5. The preparation system for the crystal transformation of cefuroxime sodium according to claim 4, characterized in that: A filter plate (42) is provided in the air tank (4), the filter plate (42) is located at the axis position of the air tank (4), and the two side edges of the filter plate (42) are in contact with the inner wall of the air tank (4); one end of the filter plate (42) is evenly hinged with a swing plate (43), and the swing plate (43) is symmetrically divided with the filter plate (42) as the reference. One of the two swing plates (43) swings towards the inside of the air tank (4), and the other swings towards the outside of the air tank (4).

6. The preparation system for the polymorph transformation of cefuroxime sodium according to claim 4, wherein: A blowing ring (44) is provided in the first box (24), and the blowing ring (44) is close to the metering device (41); uniformly distributed blowing holes (45) are provided on the blowing ring (44), and the blowing holes (45) are distributed around the connection between the first box (24) and the metering device (41), the blowing holes (45) face the connection between the first box (24) and the metering device (41), and the blowing ring (44) is connected to the third pipe (28).

7. The preparation system for the crystal transformation of cefuroxime sodium according to claim 1, wherein: Elastic pieces (46) are evenly provided at the bottom of the diaphragm (18), and the elastic pieces (46) are wavy. One end of the elastic piece (46) is connected to the inner wall of the rotating cylinder (14), and the other end is connected to the lifting pipe (2).

8. A preparation method for the polymorph transformation of cefuroxime sodium, the preparation method being applicable to the preparation system for the polymorph transformation of cefuroxime sodium according to any one of claims 1-7, characterized in that: The preparation method includes the following steps: S1: Before the drug is put into the reaction kettle (1), first put it into the rotating cylinder (14) through the feeding port (15), and then seal the feeding port (15); the driving member (17) drives the rotating cylinder (14) to rotate forward and backward to achieve the purpose of shaking the drug; then temper the drug, and the gas supply device (29) transports inert gas with preset temperature and humidity into the rotating cylinder (14). The inert gas contacts the drug in a sprinkling state, and the temperature and humidity parameters of the drug are adjusted through the inert gas. S2: Subsequently, detect the drug situation. The driving member (17) and the rotating cylinder (14) in the pre-storage cylinder (13) remain static. The worker opens the feeding port (15) at the top of the rotating cylinder (14), inserts the detector (16) into the rotating cylinder (14), performs non-destructive detection on the drug, and analyzes the detection parameters according to the standard parameters; after determining that it is qualified, put the drug into the reaction kettle (1). S3: Then, the drug is dispersed in an organic solvent prepared by mixing one or several of water-containing C1-C4 lower alcohols, water-containing acetone, and water-containing tetrahydrofuran in a specified ratio, and stirred for crystal conversion at 40°C - 65°C for 0.5 - 6 h. Filtering is carried out under a constant temperature state, and after drying, the cefuroxime sodium crystal compound is obtained.

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