Crystallization equipment for producing penicillin 6-APA

Abstract

A crystallization device for producing penicillin 6-APA comprises a crystallizer, the top of the crystallizer is communicated with a penicillin saline solution inlet pipe and a butanol inlet pipe, the upper portion of the crystallizer is communicated with a vacuum pipe, the penicillin saline solution inlet pipe and the butanol inlet pipe are respectively provided with a liquid inlet valve, the vacuum pipe is provided with a vacuum pump, and the top of the crystallizer is provided with a motor. An output shaft of the motor is fixedly connected with the top of a vertically-arranged rotating rod, the rotating rod is rotationally connected with the middle of the top of the crystallizer through a first bearing, the bottom of the rotating rod is located on the lower portion in the crystallizer, and a plurality of sets of stirring blades are arranged on the portion, located in the crystallizer, of the rotating rod from top to bottom. A heating device is arranged in the crystallizer; the bottom of the crystallizer is communicated with a liquid outlet pipe. According to the utility model, large crystal particles can be avoided to a great extent in the production process of penicillin 6-APA, so that the impurity removal efficiency in the washing process is ensured, and the production efficiency can be improved while the purity is ensured.

Description

Technical Field

[0001] This utility model belongs to the field of penicillin 6-APA production, specifically a crystallization device for penicillin 6-APA production. Background Technology

[0002] Penicillin 6-APA is a relatively common pharmaceutical intermediate. Its preparation typically involves producing penicillin through biological culture to obtain a fermentation broth. This broth is then filtered, acidified, extracted with butyl ester, and alkalized back-extracted to obtain an aqueous solution of penicillin salt. This solution is then azeotropically crystallized with butanol, filtered, washed, and dried to obtain industrial penicillin salt. The industrial penicillin salt is then dissolved, enzymatically converted, crystallized, filtered, washed, and dried to obtain penicillin 6-APA. Therefore, the purity of the obtained industrial penicillin salt affects the purity of the final penicillin 6-APA. Current crystallization procedures for industrial penicillin salt... The process involves adding butanol solvent to an aqueous solution of penicillin salt and performing azeotropic crystallization under vacuum. After crystallization, the solution is filtered, and then washed with butanol before proceeding to the next step. However, in the current production process, large crystal particles may be generated during crystallization, which may contain other substances. Therefore, simple washing cannot remove these substances, leading to a decrease in the purity of the penicillin industrial salt. This also results in a decrease in the purity of the subsequent pharmaceutical intermediate penicillin 6-APA. Therefore, it is necessary to crush the penicillin industrial salt before washing, which increases production time and reduces production efficiency. Utility Model Content

[0003] This invention provides a crystallization device for the production of penicillin 6-APA, which addresses the deficiencies in the prior art.

[0004] This utility model is achieved through the following technical solution:

[0005] A crystallization device for penicillin 6-APA production includes a crystallizer. The top of the crystallizer is connected to a penicillin saline solution inlet pipe and a butanol inlet pipe. The upper part of the crystallizer is connected to a vacuum tube. An inlet valve is installed on each of the penicillin saline solution inlet pipe and the butanol inlet pipe. A vacuum pump and a one-way valve are installed on the vacuum tube. A motor is installed on the top of the crystallizer. The output shaft of the motor is fixedly connected to the top of a vertically arranged rotating rod. The rotating rod is rotatably connected to the middle of the top of the crystallizer via a first bearing. The bottom of the rotating rod is located in the lower part of the crystallizer. An array of stirring blades is arranged from top to bottom on the portion of the rotating rod inside the crystallizer. Several through-grooves are formed on the stirring blades. Grinding balls are placed in the through-grooves. Grinding ball blocking devices are installed at the openings on both sides of the through-grooves. A heating device is installed inside the crystallizer. The bottom of the crystallizer is connected to an outlet pipe. An outlet valve and an outlet pump are installed on the outlet pipe. A filter screen is installed at the connection between the outlet pipe and the crystallizer. The bottom of the crystallizer is connected to a discharge pipe. A discharge valve and a discharge pump are installed on the discharge pipe.

[0006] As described above, in a crystallization device for penicillin 6-APA production, a horizontally arranged fixed frame is connected to each side of the bottom of the rotating rod. A roller is horizontally arranged at the bottom of the fixed frame, and the middle of both ends of the roller is fixedly connected to one end of a horizontally arranged rotating shaft through a second bearing. The rotating shaft is fixedly connected to the fixed frame.

[0007] As described above, in a crystallization apparatus for penicillin 6-APA production, the grinding ball blocking device includes a horizontally arranged blocking bar, which is fixedly connected to the two ends of the opening of the corresponding side through groove.

[0008] The crystallization equipment for penicillin 6-APA production described above includes an electric heating plate disposed inside the lower part of both sides of the crystallizer.

[0009] The crystallization equipment for penicillin 6-APA production described above has a temperature sensor installed in the lower part of the crystallizer.

[0010] The advantages of this invention are: it can largely avoid the formation of large crystal particles during the azeotropic crystallization process of penicillin salt solution and butanol, thereby ensuring the efficiency of impurity removal during the washing process, thus ensuring the purity of penicillin industrial salt, and thus improving production efficiency while ensuring the purity of the pharmaceutical intermediate penicillin 6-APA obtained in subsequent production. Attached Figure Description

[0011] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0012] Figure 1 This is a schematic diagram of the structure of this utility model;

[0013] Figure 2 yes Figure 1 A magnified view of part I;

[0014] Figure 3 yes Figure 1 A magnified view of part II.

[0015] Reference numerals: 1. Crystallizer; 2. Penicillin saline solution inlet pipe; 3. Butanol inlet pipe; 4. Vacuum pipe; 5. Inlet valve; 6. Vacuum pump; 7. Check valve; 8. Motor; 9. Rotary rod; 10. First bearing; 11. Stirring blade; 12. Through groove; 13. Grinding ball; 14. Outlet pipe; 15. Outlet valve; 16. Outlet pump; 17. Filter screen; 18. Outlet pipe; 19. Outlet valve; 20. Outlet pump; 21. Fixing frame; 22. Roller; 23. Second bearing; 24. Rotating shaft; 25. Barrier rod; 26. Electric heating plate; 27. Temperature sensor. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, not all embodiments. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of this utility model.

[0017] A crystallization device for producing penicillin 6-APA includes a crystallizer 1. The top of the crystallizer 1 is connected to a penicillin saline solution inlet pipe 2 and a butanol inlet pipe 3. The upper part of the crystallizer 1 is connected to a vacuum tube 4. An inlet valve 5 is respectively installed on the penicillin saline solution inlet pipe 2 and the butanol inlet pipe 3. A vacuum pump 6 and a one-way valve 7 are installed on the vacuum tube 4. A motor 8 is installed on the top of the crystallizer 1. The output shaft of the motor 8 is fixedly connected to the top of a vertically arranged rotating rod 9. The rotating rod 9 is rotatably connected to the middle of the top of the crystallizer 1 through a first bearing 10. The bottom of the rotating rod 9 is located at the top of the crystallizer 1. In the lower inner part, the portion of the rotating rod 9 located inside the crystallizer 1 is provided with an array of stirring blades 11 from top to bottom. Several through grooves 12 are opened on the stirring blades 11. Grinding balls 13 are placed in the through grooves 12. Grinding ball blocking devices are set at the openings on both sides of the through grooves 12. A heating device is set inside the crystallizer 1. The bottom of the crystallizer 1 is connected to the liquid outlet pipe 14. A liquid outlet valve 15 and a liquid outlet pump 16 are set on the liquid outlet pipe 14. A filter screen 17 is set at the connection between the liquid outlet pipe 14 and the crystallizer 1. The bottom of the crystallizer 1 is connected to the discharge pipe 18. A discharge valve 19 and a discharge pump 20 are set on the discharge pipe 18. In this invention, a penicillin saline solution is injected into the crystallizer 1 through the penicillin saline solution inlet pipe 2. Then, a measured amount of butanol solvent is added through the butanol inlet pipe 3, and the two inlet valves 5 are closed. The vacuum pump 6, motor 8, and heating device are then activated. The vacuum pump 6 evacuates the crystallizer 1, while the heating device raises the temperature to a specified range and maintains it, thus achieving azeotropic crystallization under vacuum. Simultaneously, the motor 8 drives the rotating rod 9 and stirring blade 11 to accelerate solvent evaporation and improve crystallization efficiency. Furthermore, the crystallized particles pass through the through-groove 12 on the stirring blade 11 and collide with the grinding balls 13, causing the crystallized particles to break down, thereby reducing the probability of large-diameter crystallized particles during crystallization and ensuring the purity of the crystals after subsequent washing. After 90% of the solvent has evaporated, the vacuum pump 6 and the heating device are turned off. The outlet valve 15 and outlet pump 16 on the outlet pipe 14 are opened to discharge the remaining solvent, and then the outlet valve 15 and outlet pump 16 are closed. The filter screen 17 can prevent the crystals from being discharged. Then, the inlet valve 5 on the butanol inlet pipe 3 is opened to add a certain amount of butanol solvent. At the same time, the mixture is quickly washed under the stirring action of the rotor 9 and the stirring blade 11. During the washing process, if there are large crystal particles, they will still collide with the grinding balls 13, thereby further ensuring the purity of the crystals after washing. If multiple washing is required, the butanol solvent after washing can be discharged through the outlet pipe 14. The above washing operation is repeated. After the last washing, the outlet valve 19 and outlet pump 20 on the outlet pipe 18 are opened to discharge the crystals and butanol solvent. After filtration, the mixture can be dried.

[0018] Specifically, in this embodiment, a horizontally arranged fixing frame 21 is connected to each of the two sides of the bottom of the rotating rod 9. A roller 22 is horizontally arranged at the lower part of the fixing frame 21. The middle of both ends of the roller 22 is fixedly connected to one end of a horizontally arranged rotating shaft 24 via a second bearing 23. The rotating shaft 24 is fixedly connected to the fixing frame 21. This invention, through the roller 22, can crush and break up the crystals accumulated at the bottom of the crystallizer 1 as the solvent continuously flows out, thereby further reducing the probability of larger crystal formation.

[0019] Specifically, the grinding ball blocking device described in this embodiment includes a horizontally arranged blocking bar 25, which is fixedly connected to both ends of the opening of the corresponding side through groove 12. In this utility model, the blocking bar 25 can prevent the grinding ball 13 from falling out of the through groove 12 during rotation, ensuring its long-term stable use.

[0020] Furthermore, the heating device described in this embodiment includes electric heating plates 26 disposed inside the lower part of both sides of the crystallizer 1. This utility model can conveniently complete heating through the electric heating plates 26, making it easy to use.

[0021] Furthermore, a temperature sensor 27 is installed in the lower part of the crystallizer 1 described in this embodiment. This invention uses the temperature sensor 27 to obtain the temperature inside the crystallizer 1 in real time, thereby conveniently adjusting the power of the electric heating plate 26 based on the obtained temperature to achieve temperature control.

[0022] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this utility model, and not to limit it. Although this utility model has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this utility model.

Claims

1. A crystallization apparatus for the production of penicillin 6-APA, characterized in that: The crystallizer (1) is connected to a penicillin saline solution inlet pipe (2) and a butanol inlet pipe (3) at its top. The upper part of the crystallizer (1) is connected to a vacuum tube (4). An inlet valve (5) is installed on each of the penicillin saline solution inlet pipe (2) and the butanol inlet pipe (3). A vacuum pump (6) and a one-way valve (7) are installed on the vacuum tube (4). A motor (8) is installed on the top of the crystallizer (1). The output shaft of the motor (8) is fixedly connected to the top of a vertically arranged rotating rod (9). The rotating rod (9) is rotatably connected to the middle of the top of the crystallizer (1) via a first bearing (10). The bottom of the rotating rod (9) is located in the lower part of the crystallizer (1). 9) The part located inside the crystallizer (1) is provided with an array of stirring blades (11) from top to bottom. Several through grooves (12) are opened on the stirring blades (11). Grinding balls (13) are provided in the through grooves (12). Grinding ball blocking devices are provided at the openings on both sides of the through grooves (12). A heating device is provided inside the crystallizer (1). The bottom of the crystallizer (1) is connected to the liquid outlet pipe (14). A liquid outlet valve (15) and a liquid outlet pump (16) are provided on the liquid outlet pipe (14). A filter screen (17) is provided at the connection between the liquid outlet pipe (14) and the crystallizer (1). The bottom of the crystallizer (1) is connected to the discharge pipe (18). A discharge valve (19) and a discharge pump (20) are provided on the discharge pipe (18).

2. The crystallization apparatus for producing penicillin 6-APA according to claim 1, characterized by: The bottom sides of the rotating rod (9) are respectively connected to a horizontally arranged fixed frame (21). The lower part of the fixed frame (21) is horizontally arranged with a roller (22). The middle of both ends of the roller (22) is fixedly connected to one end of the horizontally arranged rotating shaft (24) through a second bearing (23). The rotating shaft (24) is fixedly connected to the fixed frame (21).

3. The crystallization apparatus for producing penicillin 6-APA according to claim 1, characterized in that: The grinding ball blocking device includes a horizontally arranged blocking bar (25), which is fixedly connected to the two ends of the opening of the corresponding side through groove (12).

4. The crystallization apparatus for producing penicillin 6-APA according to claim 1, characterized by: The heating device includes electric heating plates (26) disposed inside the lower part on both sides of the crystallizer (1).

5. The crystallization apparatus for producing penicillin 6-APA according to claim 1, characterized in that: A temperature sensor (27) is installed in the lower part of the crystallizer (1).

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