Device and method for preparing high-purity landiolol hydrochloride

Abstract

The invention relates to the technical field of medicine preparation, in particular to a high-purity landiolol hydrochloride preparation device and method.The high-purity landiolol hydrochloride preparation device comprises a water bath heating tank and a filtering structure communicated to the lower portion of the water bath heating tank through a valve assembly, the lower portion of the filtering structure is communicated with a cooling liquid storage tank, and a semiconductor refrigeration device is installed on the outer side of the cooling liquid storage tank; a first heat exchange unit is mounted on the outer side of the water bath heating tank; a second heat exchange unit communicated with the first heat exchange unit is mounted on the outer side of the semiconductor refrigeration device; a coherent production process is formed from crude solution adding, heating, filtering, cooling crystallization and equipment resetting, when one batch of purification is finished, a heating tank is communicated with a cooling liquid storage tank and a filtering assembly is reset, the next batch of production can be immediately put into use, long-time waiting for equipment adjustment is not needed, the production period is greatly shortened, and the production efficiency is improved. And compared with a traditional intermittent production mode, the method has the advantage that the yield is remarkably improved.

Description

Technical Field

[0001] The present invention relates to the technical field of drug preparation, and particularly relates to a preparation device and method for high-purity landiolol hydrochloride. Background Art

[0002] Landiolol hydrochloride is a ultra-short-acting β1-receptor blocker, which is mainly used for treating tachyarrhythmia, can effectively reduce heart rate, relieve heart load, and plays a key role in the emergency treatment of cardiovascular diseases such as acute myocardial infarction and unstable angina; At present, in the preparation process of landiolol hydrochloride, the purification stage is a key link determining product quality and production efficiency. The traditional purification process often adopts the recrystallization method, which usually includes steps such as preparing a hot saturated solution, hot filtration, and cooling crystallization. The traditional purification method has low efficiency, occupies a large amount of running time of production equipment during the purification process, resulting in difficulty in improving production efficiency and being unable to meet the urgent need of large-scale industrial production for highly efficient and continuous preparation of high-purity landiolol hydrochloride. Therefore, a preparation device and method for high-purity landiolol hydrochloride are proposed to improve the purification efficiency of landiolol hydrochloride and achieve continuous production. Summary of the Invention

[0003] Aiming at the problems in the prior art, the present invention provides a preparation device and method for high-purity landiolol hydrochloride, which improve the purification efficiency of landiolol hydrochloride and achieve continuous production.

[0004] The technical solution adopted by the present invention to solve its technical problems is a preparation device and method for high-purity landiolol hydrochloride, including a water bath heating tank, and a filtration structure connected to the lower part of the water bath heating tank through a valve assembly. The lower part of the filtration structure is connected to a cooling liquid storage tank. A semiconductor refrigeration device is installed on the outer side of the cooling liquid storage tank, a first heat exchange unit is installed on the outer side of the water bath heating tank, and a second heat exchange unit connected to the first heat exchange unit is installed on the outer side of the semiconductor refrigeration device.

[0005] Specifically, the filtration assembly includes a frame connected between the valve assembly and the cooling liquid storage tank. Both sides of the frame are connected to a protective shell through chutes. Filter frames with upward openings are hermetically slidably connected inside the protective shells respectively. Filter holes are provided at the bottom of the filter frames. The front and rear sides of the filter frames are hermetically slidably connected to the inner wall of the frame. Springs are connected between the sides of the two filter frames away from each other and the protective shell; filter plates are inserted into the sides of the filter frames.

[0006] Specifically, an installation groove for slidably connecting with the filter plate is provided on one side of the filter frame. The filter plate is located at the inner bottom of the filter frame, and an opening corresponding to the installation groove is provided on the side of the protective shell.

[0007] Specifically, an embedding groove is provided above the filter plate and is opened at the inner bottom of the filter frame. An expansion pad that squeezes the upper edge of the filter plate after expansion is provided in the embedding groove.

[0008] Specifically, the valve assembly includes a valve with its upper end flange-connected to the water bath heating tank. The lower end of the valve is fixedly connected to the upper surface of the frame body through a flange connecting piece.

[0009] Specifically, a first driving motor is fixedly connected to the bottom of the cooling liquid storage tank. A plurality of groups of first stirring blades distributed circumferentially are provided on the output shaft of the first driving motor. A discharge pipe is connected to the lower part of the cooling liquid storage tank. The semiconductor refrigeration device includes a plurality of groups of semiconductor refrigeration chips connected to the outside of the cooling liquid storage tank; a negative pressure pump is connected to the cooling liquid storage tank.

[0010] Specifically, the first heat exchange unit includes a plurality of groups of arc-shaped heat exchange plates arranged on the outside of the water bath heating tank. A first circulation channel is provided in each arc-shaped heat exchange plate. A first liquid inlet joint communicated with the upper end of the first circulation channel and a first liquid outlet joint communicated with the lower end of the first circulation channel are provided; The second heat exchange unit includes a plurality of groups of flat heat exchange plates arranged on one side of the semiconductor refrigeration chips. The flat heat exchange plates correspond to the arc-shaped heat exchange plates. A second circulation channel is provided in each flat heat exchange plate. A second liquid outlet joint communicated with the upper end of the second circulation channel is provided; the second liquid outlet joint is communicated with the first liquid inlet joint through a pipeline. The lower end of the second circulation channel is communicated with a second liquid inlet joint, and the first liquid outlet joint is communicated with the second liquid inlet joint through a pipeline.

[0011] Specifically, a first joint and a second joint are communicated with the upper surface of the water bath heating tank. A second driving motor is installed on the upper part of the water bath heating tank. A plurality of groups of second stirring blades distributed circumferentially are provided on the output shaft of the second driving motor. A pressure relief valve is communicated with the upper surface of the water bath heating tank.

[0012] Specifically, a reinforced support structure member is fixedly connected between the upper surfaces of the water bath heating tank and the cooling liquid storage tank 2; a plurality of groups of vertically arranged legs are fixedly connected to the lower end of the cooling liquid storage tank.

[0013] Advantages of the present invention: For the preparation device of high-purity landiolol hydrochloride of the present invention, a coherent production process is formed from adding the crude solution, heating, filtering, cooling crystallization to resetting the equipment. When the purification of one batch is completed, the heating tank is communicated with the cooling liquid storage tank, and the filtering assembly is reset, and the next batch of production can be immediately started without waiting for a long time for equipment adjustment, greatly shortening the production cycle, meeting the demand for continuity in large-scale industrial production, and significantly increasing the output compared with the traditional batch production method.

[0014] For the preparation device of high-purity landiolol hydrochloride described in the present invention, the negative pressure generated by the refrigeration of the cooling storage tank, combined with the gravity, accelerates the speed of the hot saturated solution passing through the filtration structure. The negative pressure generates suction force and forms a resultant force with the gravity, enhancing the driving force of the hot saturated solution. At the same time, it changes the pressure distribution of the solution on the filter plate, making the solution more evenly distributed on the surface of the filter plate, reducing the filtration time and improving the overall production efficiency.

[0015] For the preparation device of high-purity landiolol hydrochloride described in the present invention, the first heat exchange unit and the second heat exchange unit are interconnected to form a liquid circulation system. When the semiconductor refrigeration device refrigerates, it drives the liquid circulation to achieve the heating effect on the water bath heating tank.

[0016] For the preparation device of high-purity landiolol hydrochloride described in the present invention, the opening on the side of the protective shell not only facilitates the installation and disassembly of the filter plate, but also can indirectly detect the liquid delivery situation in the water bath heating tank by observing the moving state of the filter frame. Under normal circumstances, when there is hot saturated solution in the water bath heating tank, the negative pressure of the cooling storage tank keeps the filter frame in the moved position for filtration operation; once the solution delivery is completed, the filter frame resets under the action of the spring, and the operator can timely judge the production progress based on this and perform subsequent operations such as cleaning the filter plate and preparing the solution for the next batch, improving the convenience and accuracy of production management. Brief Description of the Drawings

[0017] The present invention will be further described below with reference to the drawings and embodiments.

[0018] Figure 1 is the axonometric drawing of the present invention; Figure 2 is the partial cross-sectional schematic diagram of the arc-shaped heat exchange plate and the flat heat exchange plate of the present invention; Figure 3 is Figure 2 the enlarged view of area A of Figure 4 is Figure 2 the enlarged view of area B of Figure 5 is the internal structure schematic diagram of the water bath heating tank of the present invention; Figure 6 is the internal structure schematic diagram of the cooling storage tank of the present invention; Figure 7 is the internal structure schematic diagram of the frame body of the present invention; Figure 8 is the cross-sectional structure schematic diagram of the frame body of the present invention; Figure 9 is Figure 8 the enlarged view of area D of Figure 10 is Figure 8 the enlarged view of area E of In the figure: 1, water bath heating tank; 2, cooling liquid storage tank; 3, frame; 4, chute; 5, protective shell; 6, filter frame; 7, filter hole; 8, spring; 9, filter plate; 10, installation groove; 11, opening; 12, embedding groove; 13, expansion pad; 14, valve; 15, first driving motor; 16, first-stage stirring paddle; 17, discharge pipe; 18, semiconductor refrigeration sheet; 19, arc-shaped heat exchange plate; 20, first circulation channel; 21, first liquid inlet joint; 22, first liquid outlet joint; 23, flat heat exchange plate; 24, second circulation channel; 25, second liquid outlet joint; 26, second liquid inlet joint; 27, first joint; 28, second joint; 29, second driving motor; 30, second-stage stirring paddle; 31, pressure relief valve; 32, reinforced support structure member; 33, leg; 34, negative pressure pump. Specific embodiments

[0019] In order to make the technical means, creative features, achieved purposes and effects of the present invention easy to understand, the present invention will be further described below in conjunction with specific embodiments.

[0020] In order to improve the purification efficiency of landiolol hydrochloride and realize continuous production, as an embodiment of the present invention, as Figure 1 、 Figure 2 shown, a preparation device and method for high-purity landiolol hydrochloride according to the present invention includes a water bath heating tank 1, and a filtering structure connected to the lower part of the water bath heating tank 1 through a valve assembly. The lower part of the filtering structure is connected to a cooling liquid storage tank 2. A semiconductor refrigeration device is installed on the outside of the cooling liquid storage tank 2, a first heat exchange unit is installed on the outside of the water bath heating tank 1, and a second heat exchange unit connected to the first heat exchange unit is installed on the outside of the semiconductor refrigeration device.

[0021] When using this device to prepare high-purity landiolol hydrochloride, first, a crude solution containing landiolol hydrochloride and a recrystallization solvent are transported into the water bath heating tank 1 in a certain proportion; After the semiconductor refrigeration device works, the semiconductor refrigeration device transports the heat of the cooling liquid storage tank 2 to the second heat exchange unit, realizing the cooling of the cooling liquid storage tank 2 and the heating of the second heat exchange unit; after the second heat exchange unit is heated, the liquid inside expands and drives the liquid to move upward, thereby promoting the liquid circulation; at the same time, after the liquid moves upward, it enters the first heat exchange unit, and the first heat exchange unit heats the water bath heating tank 1. The temperature of the liquid passing through the first heat exchange unit drops, so that the liquid starts to move downward, further facilitating the liquid circulation; After the water bath heating tank 1 is heated, the crude solution of landiolol hydrochloride and the recrystallization solvent in the tank are heated. When preparing high-purity landiolol hydrochloride, there are various impurities in the crude solution. Heating increases the solubility of landiolol hydrochloride in the solution, providing convenience for subsequent filtration and crystallization separation; As the semiconductor refrigeration device continuously refrigerates the cooling liquid storage tank 2, the temperature inside the cooling liquid storage tank 2 continuously drops, and the air in the tank contracts when cooled, thereby generating negative pressure. Since the lower part of the filtering structure is connected to the cooling liquid storage tank 2, under the action of negative pressure, the components in the filtering structure will move. After the filtering structure moves to a certain position, it is convenient for subsequent filtering operations on the hot saturated solution after heating in the water bath heating tank 1; Open the valve assembly. The hot saturated solution in the water bath heating tank 1 flows into the filtering structure through the valve assembly under the dual action of gravity and the negative pressure of the cooling liquid storage tank 2. The filtering structure is relied on to filter the hot saturated solution, reducing the time required for filtering and improving the overall production efficiency; The filtered solution then smoothly flows into the cooling liquid storage tank 2 through the lower part of the filtering structure; the filtrate entering the cooling liquid storage tank 2 starts to cool and crystallize in the low-temperature environment formed by the continuous refrigeration of the semiconductor refrigeration device. The solubility of landiolol hydrochloride decreases at low temperature and gradually precipitates from the solution in the form of crystals. After the crystallization process is completed, the mixed liquid containing crystals in the cooling liquid storage tank 2 is discharged; after discharge, through the separation equipment, the crystals are separated from the mother liquor, and then the crystals are dried. After the treatment is completed, dry high-purity landiolol hydrochloride crystals are obtained; When the liquid in the heating tank is completely discharged, the air in the heating tank enters the cooling liquid storage tank 2, and the air pressure in the cooling liquid storage tank 2 rises rapidly. At this time, the filtering component automatically resets and moves to the initial state, and the filtering component can be cleaned, which is convenient for subsequent filtering of the next group of hot saturated solutions; after a batch of purification is completed, the filtering component resets, the valve assembly can be closed, and then the next batch of production can be quickly started. From adding the crude solution, heating, filtering, cooling and crystallization to the equipment reset, a continuous production process is formed, meeting the requirements of large-scale industrial production for continuity and improving production efficiency and output.

[0022] To improve the filtering speed, exemplarily, as Figure 1 、 Figure 2 、 Figure 7 、 Figure 8 、 Figure 9 、 Figure 10 shown, the present invention further includes that the filtering component includes a frame body 3 connected between the valve assembly and the cooling liquid storage tank 2. Both sides of the frame body 3 are connected to a protective shell 5 through a chute 4. Inside the protective shell 5, a filtering frame 6 with an upward opening is hermetically and slidably connected. The bottom of the filtering frame 6 is provided with filtering holes 7. The front and rear sides of the filtering frame 6 are hermetically and slidably connected to the inner wall of the frame body 3. A spring 8 is connected between the sides of the two filtering frames 6 away from each other and the protective shell 5; a filter plate 9 is inserted into the side of the filtering frame 6.

[0023] During use, before the filtering component is enabled, the filter plate 9 is inserted into the side of the filtering frame 6 first to ensure the overall sealing of the filtering frame 6. When the cooling liquid storage tank 2 generates negative pressure during refrigeration, since the lower part of the filtering component is connected to the cooling liquid storage tank 2, under the action of the negative pressure, the filtering frame 6 will overcome the elastic force of the spring 8 and slide along the sliding grooves 4 on both sides of the frame body 3 towards the direction close to the cooling liquid storage tank 2, making the two groups of filtering frames 6 approach each other, facilitating the subsequent filtration of the heated saturated solution; When the valve component is opened, the saturated solution in the water bath heating tank 1 will flow downward naturally under the action of gravity, while the cooling liquid storage tank 2 generates negative pressure under the continuous refrigeration of the semiconductor refrigeration device. Since the lower part of the filtering structure is connected to the cooling liquid storage tank 2, under the combined action of gravity and negative pressure, the saturated solution is subjected to a stronger driving force, accelerating the flow towards the filtering structure and improving the blanking speed; When the saturated solution flows from the valve component into the frame body 3, when the saturated solution passes through the filter plate 9, various impurities in the solution will be intercepted by the filter plate 9, thus initially realizing solid-liquid separation; during normal gravity filtration, the filtration of the solution by the filter plate 9 will generate a certain resistance, affecting the blanking speed, while the existence of negative pressure causes the pressure distribution of the solution on the filter plate 9 to change, and the suction force generated by the negative pressure makes the solution more evenly distributed on the surface of the filter plate 9, further improving the filtration speed.

[0024] For the convenience of cleaning the filter plate 9, by way of example, as Figure 7 、 Figure 8 、 Figure 9 、 Figure 10 shown, the present invention further includes that an installation groove 10 slidably connected to the filter plate 9 is provided on one side of the filtering frame 6, the filter plate 9 is located at the inner bottom of the filtering frame 6, and an opening 11 corresponding to the installation groove 10 is provided on the side of the protective shell 5.

[0025] During use, the filter plate 9 can be inserted along the installation groove 10 on one side of the filtering frame 6. When the device operates and the cooling liquid storage tank 2 generates negative pressure, driving the movement of the filtering frame 6, it is convenient for subsequent filtration of the solution; When the solution in the water bath heating tank 1 is completely delivered, the cooling liquid storage tank 2 is connected to the water bath heating tank 1. At this time, the air pressure in the cooling liquid storage tank 2 rises rapidly, and the filtering frame 6 is driven to reset and move to the initial state by the spring 8 rebounding. At this time, the filter plate 9 can be slid out reversely along the installation groove 10 from the opening 11 on the side of the protective shell 5 to clean the filter plate 9; The opening 11 on the side of the protective shell 5 is not only used for the installation and disassembly of the filter plate 9, but also facilitates observing the state of the filter frame 6. The liquid conveyance situation in the water bath heating tank 1 can be indirectly detected through the movement state of the filter frame 6. Under normal circumstances, when there is a hot saturated solution in the water bath heating tank 1, the negative pressure of the cooling liquid storage tank 2 will keep the filter frame 6 in the moved position for filtering operation; once the solution conveyance in the water bath heating tank 1 is completed, the cooling liquid storage tank 2 is communicated with the water bath heating tank 1, and the filter frame 6 will reset and move to the initial state under the action of the spring 8. Therefore, the operator can judge whether the liquid in the water bath heating tank 1 has been completely conveyed by observing whether the filter frame 6 is reset. This method provides an intuitive reference index for the monitoring of the entire preparation process, helps the operator to perform subsequent operations in a timely manner, such as cleaning the filter plate 9, preparing the solution for the next batch, etc., and improves production efficiency.

[0026] To ensure the stability of the filter plate 9 during the filtering process, exemplarily, as Figure 8 , Figure 10 shown, the present invention further includes an embedding groove 12 opened at the inner bottom of the filter frame 6 above the filter plate 9, and an expansion pad 13 that expands and presses the upper edge of the filter plate 9 is provided in the embedding groove 12.

[0027] During use, the filter plate 9 is inserted into the installation groove 10 on the side of the filter frame 6. At this time, the expansion pad 13 is in an unexpanded state. When the cooling liquid storage tank 2 generates negative pressure due to refrigeration and the filter frame 6 slides along the two side chutes 4 of the frame body 3 under the action of the negative pressure, the expansion pad 13 expands in the negative pressure environment. The expanded expansion pad 13 will press the upper edge of the filter plate 9, tightly fixing the filter plate 9 in the filter frame 6. This not only ensures the stability of the filter plate 9 during the filtering process, but also enhances the sealing performance between the filter plate 9 and the filter frame 6, preventing the hot saturated solution from directly entering the cooling liquid storage tank 2 through the gap without passing through the filter plate 9, ensuring the filtering accuracy and effect, and helping to obtain a higher purity landiolol hydrochloride product.

[0028] Exemplarily, as Figure 2 shown, the present invention further includes that the valve assembly includes a valve 14 whose upper end is flange-connected to the water bath heating tank 1, and the lower end of the valve 14 is fixedly connected to the upper surface of the frame body 3 through a flange connecting member.

[0029] When in use, the valve 14 is opened, and the hot saturated solution flows into the frame body 3 for filtering under the action of gravity and the negative pressure of the cooling liquid storage tank 2 through the valve assembly.

[0030] To improve the quality and purity of crystallization, exemplarily, as Figure 1 , Figure 3 , Figure 6As shown in the figure, the present invention further includes that a first driving motor 15 is fixedly connected to the bottom of the cooling liquid storage tank 2. A plurality of groups of first stirring blades 16 distributed circularly are provided on the output shaft of the first driving motor 15. A discharge pipe 17 is communicated with the lower part of the cooling liquid storage tank 2. The semiconductor refrigeration device includes a plurality of groups of semiconductor refrigeration chips 18 connected to the outer side of the cooling liquid storage tank 2. A negative pressure pump 34 is communicated with the cooling liquid storage tank 2.

[0031] During use, when the solution containing landiolol hydrochloride flows into the cooling liquid storage tank 2 after being filtered, the first driving motor 15 is started. The output shaft of the first driving motor 15 starts to rotate, driving the first stirring blades 16 to rotate synchronously. At the same time, the semiconductor refrigeration chips 18 cool down the cooling liquid storage tank 2. After the solution cooling crystallization is completed, the discharge pipe 17 is opened to discharge the mixed liquid containing crystals. The first stirring blades 16 rotate driven by the first driving motor 15, which can evenly mix the solution in the cooling liquid storage tank 2. During the cooling crystallization process, stirring can make the landiolol hydrochloride molecules in the solution contact the low-temperature environment more evenly, avoid local overcooling or overheating, and promote the crystals to precipitate more evenly, improving the quality and purity of the crystallization. The negative pressure pump 34 can quickly extract the gas in the cooling liquid storage tank 2, quickly form a stronger negative pressure, and further provide a stable and strong negative pressure environment to ensure the negative pressure effect of the cooling liquid storage tank 2.

[0032] To improve the energy utilization rate, for example, Figure 1 、 Figure 2 、 Figure 3 、 Figure 4 As shown in the figure, the present invention further includes that the first heat exchange unit includes a plurality of groups of arc-shaped heat exchange plates 19 arranged on the outer side of the water bath heating tank 1. A first circulation channel 20 is provided in each of the arc-shaped heat exchange plates 19. A first liquid inlet joint 21 communicated with the upper end of the first circulation channel 20, and a first liquid outlet joint 22 communicated with the lower end of the first circulation channel 20. The second heat exchange unit includes a plurality of groups of flat heat exchange plates 23 arranged on one side of the semiconductor refrigeration chips 18. The flat heat exchange plates 23 correspond to the arc-shaped heat exchange plates 19. A second circulation channel 24 is provided in each of the flat heat exchange plates 23. A second liquid outlet joint 25 communicated with the upper end of the second circulation channel 24. The second liquid outlet joint 25 is communicated with the first liquid inlet joint 21 through a pipeline. The lower end of the second circulation channel 24 is communicated with a second liquid inlet joint 26, and the first liquid outlet joint 22 is communicated with the second liquid inlet joint 26 through a pipeline.

[0033] During use, in the preparation process, as the semiconductor refrigeration sheet 18 works, the cooling liquid storage tank 2 is cooled, while the flat heat exchange plate 23 is heated by the semiconductor refrigeration sheet 18. The liquid in the flat heat exchange plate 23 automatically moves upward after being heated, and enters the first liquid inlet joint 21 of the arc heat exchange plate 19 through the second liquid outlet joint 25. Thus, it can pass through the arc heat exchange plate 19 and rely on the arc heat exchange plate 19 to heat the water bath heating tank 1. And the temperature of the liquid drops after passing through the arc heat exchange plate 19, which further facilitates the downward movement of the liquid. After the liquid in the arc heat exchange plate 19 moves downward, it is discharged through the first liquid outlet joint 22 and enters the second liquid inlet joint 26, thereby promoting the cyclic movement of the liquid between the first heat exchange unit and the second heat exchange unit; Through the connected design of the first circulation channel 20 and the second circulation channel 24, the cyclic flow of the liquid between the two heat exchange units is realized. On the one hand, the heat transported by the semiconductor refrigeration sheet 18 is used to make the liquid in the second heat exchange unit flow, ensuring that the heat can be continuously transferred to the first heat exchange unit; on the other hand, after the liquid in the first heat exchange unit cools down, the liquid flows back to the second heat unit, enabling the heat to be recycled and improving the energy utilization rate; It should be noted that the first circulation channel 20 described in the present invention includes several groups of arc channels that are distributed vertically and horizontally, and adjacent first channels are connected through arc channels. The second circulation channel 24 includes several groups of heat exchange tubes that are distributed vertically and horizontally, and adjacent heat exchange tubes are connected through elbows.

[0034] Exemplarily, as Figure 1 、 Figure 5 shown, the present invention further includes that the upper surface of the water bath heating tank 1 is connected with a first joint 27 and a second joint 28. A second driving motor 29 is installed on the upper part of the water bath heating tank 1. Several groups of secondary stirring blades 30 distributed circumferentially are provided on the output shaft of the second driving motor 29. A pressure relief valve 31 is connected to the upper surface of the water bath heating tank 1.

[0035] During use, when preparing high-purity landiolol hydrochloride, raw materials such as crude solution and recrystallization solvent are added into the water bath heating tank 1 through the first joint 27 and the second joint 28. The second driving motor 29 is started, and the output shaft drives the secondary stirring blades 30 to rotate to stir the added solution, so that various solutions added into the water bath heating tank 1 are fully mixed. The uniform solution helps to improve the subsequent reaction and crystallization effects and make the solution mix evenly; After the solution is mixed well, the water bath heating tank 1 is heated to make the solution rise to form a hot saturated solution. During the heating process, the second driving motor 29 is continuously turned on to ensure that the secondary stirring blades 30 keep stirring to maintain the uniformity of the solution; During the heating process, the pressure in the water bath heating tank 1 will rise as the temperature increases. When the pressure in the tank exceeds the set safety value, the pressure relief valve 31 will automatically open to release the excess pressure, ensuring that the pressure in the tank is within the safe range; when the pressure drops below the safety value, the pressure relief valve 31 will automatically close.

[0036] Exemplarily, as Figure 1 、 Figure 2 shown, the present invention further includes that a reinforced support structure member 32 is fixedly connected between the upper surfaces of the water bath heating tank 1 and the cooling liquid storage tank 2; several groups of vertically arranged legs 33 are fixedly connected to the lower end of the cooling liquid storage tank 2.

[0037] During use, the reinforced support structure member 32 connects the water bath heating tank 1 and the cooling liquid storage tank 2, effectively enhancing the connection stability between the two; several groups of vertical legs 33 at the lower end of the cooling liquid storage tank 2 provide stable support for the cooling liquid storage tank 2.

[0038] When the present invention is in use, through the first joint 27 and the second joint 28 of the water bath heating tank 1, the crude solution containing landiolol hydrochloride and the recrystallization solvent are transported into the water bath heating tank 1 in a certain proportion. The second drive motor 29 at the upper part of the water bath heating tank 1 is started, and its output shaft drives the secondary stirring paddle 30 to rotate, stirring the added solution to make various solutions fully mixed and uniform; The semiconductor refrigeration device is turned on, and the semiconductor refrigeration chip 18 starts to work. As the semiconductor refrigeration chip 18 works, the cooling liquid storage tank 2 is cooled, while the planar heat exchange plate 23 is heated by the semiconductor refrigeration chip 18. The liquid in the planar heat exchange plate 23 automatically moves upward after being heated and enters the first liquid inlet joint 21 of the arc-shaped heat exchange plate 19 through the second liquid outlet joint 25, and then can pass through the arc-shaped heat exchange plate 19. Relying on the arc-shaped heat exchange plate 19 to heat the water bath heating tank 1, and the temperature of the liquid drops after passing through the arc-shaped heat exchange plate 19, which further facilitates the downward movement of the liquid. After the liquid in the arc-shaped heat exchange plate 19 moves downward, it is discharged through the first liquid outlet joint 22 and enters the second liquid inlet joint 26, thereby promoting the cyclic movement of the liquid between the first heat exchange unit and the second heat exchange unit; During the heating process, as the temperature rises, the pressure in the water bath heating tank 1 will gradually increase. When the pressure exceeds the preset safety value, the pressure relief valve 31 automatically opens to release the excess pressure, ensuring the safety of the equipment; when the pressure drops below the safety value, the pressure relief valve 31 automatically closes to maintain a stable pressure environment in the tank; The semiconductor refrigeration device continuously refrigerates the cooling liquid storage tank 2. The air in the tank cools and contracts to form a negative pressure. This negative pressure acts on the filtering component, causing the filter frame 6 to overcome the elastic force of the spring 8 and slide along the sliding grooves 4 on both sides of the frame body 3 towards the direction close to the cooling liquid storage tank 2. The two groups of filter frames 6 approach each other to prepare for filtering. At the same time, the expansion pad 13 expands in the negative pressure environment. After expansion, the expansion pad 13 presses against the upper edge of the filter plate 9, firmly fixing the filter plate 9 inside the filter frame 6. This not only ensures the stability of the filter plate 9 during the filtering process but also enhances the sealing between the filter plate 9 and the filter frame 6, preventing the hot saturated solution from directly entering the cooling liquid storage tank 2 through the gap without passing through the filter plate 9, ensuring the filtering accuracy and effect, and contributing to obtaining a higher purity landiolol hydrochloride product. When the valve assembly is opened, the hot saturated solution in the water bath heating tank 1 will flow downward naturally under the action of gravity. The cooling liquid storage tank 2 generates a negative pressure under the continuous refrigeration of the semiconductor refrigeration device. Since the lower part of the filtering structure is connected to the cooling liquid storage tank 2, under the combined action of gravity and negative pressure, the hot saturated solution is subjected to a stronger driving force, accelerating its flow towards the filtering structure and improving the feeding speed. When the hot saturated solution flows from the valve assembly into the frame body 3, when the hot saturated solution passes through the filter plate 9, various impurities in the solution will be intercepted by the filter plate 9, thus initially realizing solid-liquid separation. During normal gravity filtration, the filtration of the solution by the filter plate 9 will generate a certain resistance, affecting the feeding speed. However, the existence of the negative pressure causes the pressure distribution of the solution on the filter plate 9 to change. The suction force generated by the negative pressure makes the solution more evenly distributed on the surface of the filter plate 9, further improving the filtration speed. When the solution containing landiolol hydrochloride flows into the cooling liquid storage tank 2 after filtration, start the first driving motor 15. The output shaft of the first driving motor 15 starts to rotate, driving the primary stirring paddle 16 to rotate synchronously, which can evenly mix the solution in the cooling liquid storage tank 2, avoid local overcooling or overheating, and promote more uniform precipitation of crystals. At the same time, the semiconductor refrigeration chip 18 refrigerates and cools the cooling liquid storage tank 2. After the solution cooling and crystallization are completed, open the discharge pipe 17 to discharge the mixed liquid containing crystals. After discharge, through the separation equipment, the crystals are separated from the mother liquor, and then the crystals are dried. After the treatment is completed, dry high-purity landiolol hydrochloride crystals are obtained. When the solution in the water bath heating tank 1 is completely delivered, the cooling liquid storage tank 2 is connected to the water bath heating tank 1. At this time, the air pressure in the cooling liquid storage tank 2 rises rapidly. Driven by the spring 8 to rebound, the filter frame 6 moves back to the initial state. At this time, the filter plate 9 can be slid out along the installation groove 10 in the reverse direction from the opening 11 on the side of the protective shell 5 to clean the filter plate 9. Meanwhile, the conveying condition of the liquid in the water bath heating tank 1 can be indirectly detected through the moving state of the filter box 6. Under normal circumstances, when there is a hot saturated solution in the water bath heating tank 1, the negative pressure in the cooling liquid storage tank 2 will keep the filter box 6 at the moved position for filtering operation; once the solution in the water bath heating tank 1 is conveyed completely, the cooling liquid storage tank 2 is communicated with the water bath heating tank 1, and the filter box 6 will be reset and moved to the initial state under the action of the spring 8. Therefore, the operator can judge whether the liquid in the water bath heating tank 1 is conveyed completely by observing whether the filter box 6 is reset. This method provides an intuitive reference index for the monitoring of the whole preparation process, helps the operator to perform subsequent operations in time, such as cleaning the filter plate 9, preparing the solution for the next batch, etc., and improves the production efficiency.

[0039] The foregoing has shown and described the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. The above-described embodiments and the descriptions in the specification are only used to illustrate 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 all these changes and improvements fall within the scope of the present invention claimed. The scope of the present invention claimed is defined by the appended claims and their equivalents.

Claims

1. An apparatus for preparing high-purity landiolol hydrochloride, characterized in that, It includes a water bath heating tank (1), and a filtering structure connected to the lower part of the water bath heating tank (1) through a valve (14) assembly. The lower part of the filtering structure is connected to a cooling liquid storage tank (2). A semiconductor refrigeration device is installed on the outside of the cooling liquid storage tank (2). A first heat exchange unit is installed on the outside of the water bath heating tank (1). A second heat exchange unit connected to the first heat exchange unit is installed on the outside of the semiconductor refrigeration device.

2. The preparation device of a highly pure landiolol hydrochloride according to claim 1, wherein The filtering assembly includes a frame body (3) connected between the valve (14) assembly and the cooling liquid storage tank (2). Both sides of the frame body (3) are connected to a protective shell (5) through sliding grooves (4). Filter frames (6) with upward openings are hermetically and slidably connected inside the protective shell (5). Filter holes (7) are provided at the bottom of the filter frames (6). The front and rear sides of the filter frames (6) are hermetically and slidably connected to the inner wall of the frame body (3). Springs (8) are connected between the sides of the two groups of filter frames (6) away from each other and the protective shell (5); filter plates (9) are inserted into the sides of the filter frames (6).

3. The preparation device of high-purity landiolol hydrochloride according to claim 2, characterized in that, An installation groove (10) for slidably connecting with the filter plate (9) is provided on one side of the filter frame (6). The filter plate (9) is located at the inner bottom of the filter frame (6). An opening (11) corresponding to the installation groove (10) is provided on the side of the protective shell (5).

4. The preparation device of high-purity landiolol hydrochloride according to claim 3, characterized in that, An embedding groove (12) is provided at the inner bottom of the filter frame (6) above the filter plate (9). An expansion pad (13) that expands and presses the upper edge of the filter plate (9) is provided in the embedding groove (12).

5. The preparation device of high-purity landiolol hydrochloride according to claim 4, characterized in that, The valve (14) assembly includes a valve (14) whose upper end is flange-connected to the water bath heating tank (1). The lower end of the valve (14) is fixedly connected to the upper surface of the frame body (3) through a flange connecting piece.

6. The preparation device of high-purity landiolol hydrochloride according to claim 5, characterized in that, A first driving motor (15) is fixedly connected to the bottom of the cooling liquid storage tank (2). A number of groups of first stirring blades (16) distributed circumferentially are provided on the output shaft of the first driving motor (15). A discharge pipe (17) is connected to the lower part of the cooling liquid storage tank (2). The semiconductor refrigeration device includes a number of groups of semiconductor refrigeration chips (18) connected to the outside of the cooling liquid storage tank (2); a negative pressure pump (34) is connected to the cooling liquid storage tank (2).

7. The preparation device of high-purity landiolol hydrochloride according to claim 6, characterized in that, The first heat exchange unit includes a number of groups of arc-shaped heat exchange plates (19) provided on the outside of the water bath heating tank (1). A first circulation channel (20) is provided in each of the arc-shaped heat exchange plates (19). A first liquid inlet joint (21) connected to the upper end of the first circulation channel (20) and a first liquid outlet joint (22) connected to the lower end of the first circulation channel (20) are provided. The second heat exchange unit includes a number of groups of planar heat exchange plates (23) provided on one side of the semiconductor refrigeration chips (18). The planar heat exchange plates (23) correspond to the arc-shaped heat exchange plates (19). A second circulation channel (24) is provided in each of the planar heat exchange plates (23). A second liquid outlet joint (25) connected to the upper end of the second circulation channel (24) is provided; the second liquid outlet joint (25) is connected to the first liquid inlet joint (21) through a pipeline. The lower end of the second circulation channel (24) is connected to a second liquid inlet joint (26), and the first liquid outlet joint (22) is connected to the second liquid inlet joint (26) through a pipeline.

8. The preparation device of high-purity landiolol hydrochloride according to claim 7, characterized in that, The upper surface of the water bath heating tank (1) is communicated with a first joint (27) and a second joint (28). A second driving motor (29) is installed on the upper part of the water bath heating tank (1). A plurality of groups of second-stage stirring blades (30) distributed circumferentially are arranged on the output shaft of the second driving motor (29). A pressure relief valve (31) is communicated with the upper surface of the water bath heating tank (1).

9. The preparation device of high-purity landiolol hydrochloride according to claim 8, characterized in that, A reinforced support structure member (32) is fixedly connected between the upper surfaces of the water bath heating tank (1) and the cooling liquid storage tank (2); a plurality of groups of vertically arranged legs (33) are fixedly connected to the lower end of the cooling liquid storage tank (2).

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