Process and equipment for purifying vildagliptin

Abstract

The invention belongs to the technical field of purification processes, and discloses a vildagliptin purification process and equipment thereof.The vildagliptin purification process comprises a box body, a control panel is fixedly connected to the rear side of the top of the box body, a cabinet door is rotatably connected to the front end of the box body, two reaction tanks are fixedly connected to the top of the box body in a penetrating mode, and tank covers abut against the tops of the reaction tanks; a pushing device is fixedly connected to the top of the inner wall of the reaction tank, a servo motor is fixedly connected to the bottom of the reaction tank, a rotating rod is fixedly connected to an output shaft of the servo motor, and a vertical moving device is arranged on the surface of the rotating rod; the height of a collecting ring plate can be adjusted through a vertical moving device, a solution can be discharged, the collecting ring plate can also vibrate up and down, precipitates are dried through a heater, a servo motor rotates reversely subsequently, a supporting ring plate is driven to move upwards, and the inner wall of the tank body is scraped and collected in the upward moving process; and the user can collect the precipitate in the purification process more conveniently and comprehensively.

Description

Technical Field

[0001] The invention belongs to the technical field of purification processes, and in particular relates to a purification process and equipment for vildagliptin. Background Art

[0002] Vildagliptin, English name: Vil dagliptin, chemical name: (2S)-1-{[(3-hydroxytricyclo[3.3.1.13,7]decane-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile, is an oral dipeptidyl peptidase-IV (DPP-IV) inhibitor used to treat type II diabetes. On September 28, 2007, it was launched in 27 EU countries, Norway and Ireland. On August 16, 2011, "Gavila" (vildagliptin) was approved for marketing in China.

[0003] At present, when preparing small and medium doses of drugs, adhesion occurs when collecting the precipitate of the solution drug, making it difficult to collect, resulting in low work efficiency and slow preparation speed. Summary of the invention

[0004] The present invention aims at the problem of low efficiency of collecting medicines in the prior art and proposes the following technical solutions:

[0005] A purification device for vildagliptin comprises a box body, a control panel is fixedly connected to the rear side of the top of the box body, a cabinet door is rotatably connected to the front end of the box body, two reaction tanks are fixedly connected to the top of the box body, a tank cover abuts against the top of the reaction tank, a locking assembly is fixedly connected to the front end of the tank cover, a pushing device is fixedly connected to the top of the inner wall of the reaction tank, a servo motor is fixedly connected to the bottom of the reaction tank, a rotating rod is fixedly connected to the output shaft of the servo motor, a threaded groove is provided on the surface of the rotating rod, and a vertical movement device is provided on the surface of the rotating rod.

[0006] As a preferred embodiment of the above technical solution, the pushing device includes an annular fixed plate, the bottom of the annular fixed plate is evenly distributed and fixedly connected with electric push rods, the output end of the electric push rod is fixedly connected with an annular movable plate, the bottom of the annular movable plate is slidably connected with a connecting column, the bottom of the connecting column is fixedly connected with a stirring device, and the inner wall of the annular movable plate is provided with an auxiliary component.

[0007] As a preferred embodiment of the above technical solution, the stirring device includes a connecting plate, a plurality of sliding grooves are evenly arranged on the surface of the rotating rod, the connecting plate is slidably connected to the inner wall of the sliding groove, a primary stirring rod is rotatably connected to one side of the bottom of the connecting plate, a secondary stirring rod is rotatably connected to the bottom of the primary stirring rod, the bottom of the secondary stirring rod is rotatably connected to the bottom of the movable groove, and a protrusion is fixedly connected to the middle of the sliding groove at the connection between the primary stirring rod and the secondary stirring rod.

[0008] As a preferred embodiment of the above technical solution, the auxiliary component includes a ring tooth, which is fixedly connected to the inner wall of the annular movable plate, and the ring tooth is meshingly connected to a plurality of gears, and the top and bottom of the gear are fixedly connected to auxiliary stirring rods, and the bottom of the auxiliary stirring rod is rotatably connected to the top of the connecting plate.

[0009] As a preferred embodiment of the above technical solution, the vertical movement device includes a support ring plate, the inner wall of the support ring plate is fixedly connected to a one-way bearing, the top of the support ring plate is fixedly connected to a spring rod, and the top of the spring rod is fixedly connected to a collecting ring plate.

[0010] As a preferred embodiment of the above technical solution, a drainage column is fixedly connected to the top of the support ring plate, a water outlet is opened at the bottom of the surface of the drainage column, and a water leakage port is opened at the upper surface of the drainage column.

[0011] As a preferred embodiment of the above technical solution, the top of the support ring plate is fixedly connected to a base, the inner wall of the base is fixedly connected to a motor, and the motor output shaft is fixedly connected to an elliptical plate.

[0012] As a preferred embodiment of the above technical solution, the locking assembly includes a locking fixing plate, a threaded rod is fixedly connected to the top of the locking fixing plate, a rotating handle is threadedly connected to the upper surface of the threaded rod, and a lower pressure ring is fixedly connected to the front end of the tank cover.

[0013] As a preferred embodiment of the above technical solution, a loading port is fixedly connected to the top of the tank cover, a collecting tube is plugged into the front end of the reaction tank, and a heater is arranged inside the bottom of the reaction tank.

[0014] The present invention provides a purification process using the above-mentioned vildagliptin device, and the purification process comprises the following steps:

[0015] S1, adding (2S)-N-chloroacetyl-2-cyanopyrrole and 3-amino-1-adamantanol into a reaction tank for condensation reaction to obtain a crude product of vildagliptin;

[0016] S2, dissolving the crude product in S1 with 20 times the amount of acidic aqueous solution, and then adding an equal volume of organic solvent for extraction and separation, so that the vildagliptin disubstituted impurities are retained in the organic phase, and the vildagliptin is transferred to the aqueous phase, and the aqueous phase is collected;

[0017] S3, adjusting the pH value of the liquid vildagliptin obtained in S2 with an alkaline reagent, adding an organic solvent for extraction, and collecting the obtained solid precipitate by a vertical movement device;

[0018] S4. Finally, the pure product of vildagliptin is obtained by drying and compression.

[0019] The beneficial effects of the present invention are:

[0020] (1) The height of the collecting ring plate can be adjusted by the motor and the elliptical plate in the vertical moving device, so that the solution can be discharged well. After the liquid is completely discharged, the motor is started again to make the collecting ring plate vibrate up and down, and then the precipitate is dried by the heater at the bottom of the reaction tank. The subsequent servo motor reverses to drive the supporting ring plate to move up. During the upward movement, the inner wall of the tank is also scraped and collected, making it more convenient and comprehensive for users to collect the precipitate during the purification process;

[0021] (2) The stirring height can be controlled by the stirring device, so that when preparing medicines with different dosages, the stirring can be performed well. At the same time, the auxiliary component can assist in stirring the areas above the stirring device that cannot be stirred. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Shown is a perspective view of a purification apparatus for vildagliptin;

[0023] Figure 2 Shown is a schematic diagram of the interior of a box of a purification device for vildagliptin;

[0024] Figure 3 Shown is a schematic diagram of the interior of a reaction tank of a purification device for vildagliptin;

[0025] Figure 4 Shown is a schematic diagram of a driving device of a purification device for vildagliptin;

[0026] Figure 5 Shown is a schematic diagram of auxiliary components of a purification apparatus for vildagliptin;

[0027] Figure 6 Shown is a schematic diagram of a stirring device portion of a purification device for vildagliptin;

[0028] Figure 7 Shown is a schematic diagram of a stirring device portion of a purification device for vildagliptin;

[0029] Figure 8 Shown is an enlarged schematic diagram of A of a purification device for vildagliptin;

[0030] Fig. 9 Shown is an overall schematic diagram of a vertical transfer device of a purification device for vildagliptin;

[0031] Fig.10 Shown is a schematic diagram of the interior of a vertical transfer device of a purification device for vildagliptin;

[0032] Fig.11 Shown is a partially enlarged schematic diagram of a vertical transfer device of a purification device for vildagliptin;

[0033] Fig.12 Shown is a schematic diagram of a locking device of a purification device for vildagliptin.

[0034] In the figure: 1, box body; 2, control panel; 3, cabinet door; 4, reaction tank; 5, tank cover; 6, locking assembly; 601, locking fixing plate; 602, threaded rod; 603, rotating handle; 604, lower pressure ring; 7, pushing device; 701, annular fixing plate; 702, electric push rod; 703, annular moving plate; 704, connecting column; 8, servo motor; 9, rotating rod; 10, stirring device; 1001, connecting plate; 1002, sliding groove; 1003, primary stirring rod; 1004 , secondary stirring rod; 1005, bump; 11, vertical movement device; 1101, supporting ring plate; 1102, one-way bearing; 1103, spring rod; 1104, collecting ring plate; 1105, drainage column; 1106, water outlet; 1107, water leakage outlet; 1108, base; 1109, motor; 1110, elliptical plate; 12, auxiliary components; 1201, ring gear; 1202, gear; 1203, auxiliary stirring rod; 13, threaded groove; 14, collecting pipe; 15, delivery port. DETAILED DESCRIPTION

[0035] In order to make the purpose, technical solution and advantages of the embodiments of the present invention more clear, the technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments.

[0036] Embodiment 1

[0037] like Figures 1 to 9 As shown, a purification device for vildagliptin comprises a box body 1, a control panel 2 is fixedly connected to the rear side of the top of the box body 1, a cabinet door 3 is rotatably connected to the front end of the box body 1, two reaction tanks 4 are fixedly connected to the top of the box body 1, a tank cover 5 is abutted on the top of the reaction tank 4, a locking assembly 6 is fixedly connected to the front end of the tank cover 5, a pushing device 7 is fixedly connected to the top of the inner wall of the reaction tank 4, a servo motor 8 is fixedly connected to the bottom of the reaction tank 4, a rotating rod 9 is fixedly connected to the output shaft of the servo motor 8, a threaded groove 13 is provided on the surface of the rotating rod 9, and a vertical moving device 11 is provided on the surface of the rotating rod 9; when the user uses the device, firstly, the prepared reagent solution is poured into the interior of the reaction tank 4, and then the tank cover 5 is covered, and the tank cover 5 and the reaction tank 4 can be kept in a sealed state by the locking device, and then the stirring device 10 can be adjusted to a certain height by the pushing device 7, and can be adjusted according to different liquid level heights, and finally after the reaction is completed, the precipitation is collected by the vertical moving device 11.

[0038] like Figure 3 to Figure 4As shown, the pushing device 7 includes an annular fixed plate 701, and the bottom of the annular fixed plate 701 is evenly distributed and fixedly connected with electric push rods 702, the output end of the electric push rod 702 is fixedly connected with an annular movable plate 703, the bottom of the annular movable plate 703 is slidably connected with a connecting column 704, the bottom of the connecting column 704 is fixedly connected with a stirring device 10, and the inner wall of the annular movable plate 703 is provided with an auxiliary component 12; the user can control the electric push rod 702 to push the annular movable plate 703 downward according to the height of the solution inside the reaction tank 4, so that it reaches a certain position. When the annular movable plate 703 is pushed downward, the connecting plate 1001 will also move downward, and the connecting plate 1001 will move downward on the sliding groove 1002, so that the solution on the upper part of the stirring device 10 can be stirred, so that the stirring is more sufficient.

[0039] like Figures 6 to 8 As shown, the stirring device 10 includes a connecting plate 1001, and a plurality of sliding grooves 1002 are evenly arranged on the surface of the rotating rod 9, the connecting plate 1001 is slidably connected to the inner wall of the sliding groove 1002, a primary stirring rod 1003 is rotatably connected to one side of the bottom of the connecting plate 1001, a secondary stirring rod 1004 is rotatably connected to the bottom of the primary stirring rod 1003, the bottom of the secondary stirring rod 1004 is rotatably connected to the bottom of the movable groove, and a protrusion 1005 is fixedly connected to the middle part of the sliding groove 1002 at the connection between the primary stirring rod 1003 and the secondary stirring rod 1004; when the connecting plate 1001 moves downward, under the action of the protrusion 1005, the middle parts of the primary stirring rod 1003 and the secondary stirring rod 1004 are pushed out, so that the primary stirring rod 1003 and the secondary stirring rod 1004 can be bent to form a horizontal V-shape, so that the stirring rods can stir the solution at the edge well.

[0040] like Figure 5 As shown, the auxiliary component 12 includes a ring tooth 1201, which is fixedly connected to the inner wall of the annular movable plate 703, and the ring tooth 1201 is meshed with a plurality of gears 1202. The top and bottom of the gear 1202 are fixedly connected with an auxiliary stirring rod 1203, and the bottom of the auxiliary stirring rod 1203 is rotatably connected to the top of the connecting plate 1001; when the connecting plate 1001 rotates, it drives the gear 1202 to make a circular motion together, and when the gear 1202 rotates on the ring tooth 1201, it drives the auxiliary stirring rod 1203 to rotate on the connecting plate 1001, so that the solution on the upper part of the stirring device 10 can be stirred, so that the stirring is more sufficient.

[0041] like Figures 9 and 10As shown, the vertical movement device 11 includes a supporting ring plate 1101, a one-way bearing 1102 is fixedly connected to the inner wall of the supporting ring plate 1101, a spring rod 1103 is fixedly connected to the top of the supporting ring plate 1101, and a collecting ring plate 1104 is fixedly connected to the top of the spring rod 1103; when the collecting ring plate 1104 moves up and down, the spring rod 1103 will limit the collecting ring plate 1104.

[0042] like Fig.10 As shown, a drainage column 1105 is fixedly connected to the top of the support ring plate 1101, a water outlet 1106 is provided on the bottom of the surface of the drainage column 1105, and a leakage port 1107 is provided on the upper surface of the drainage column 1105; after the collecting ring plate 1104 moves down a certain distance, the leakage port 1107 on the drainage column 1105 will leak out for drainage, and filter paper is provided at the leakage port 1107 to prevent the precipitate from being retained along the leakage port 1107, and the flowing solution can be collected and processed through the collecting tube 14.

[0043] like Figure 10 to Figure 11 As shown, the top of the support ring plate 1101 is fixedly connected to a base 1108, the inner wall of the base 1108 is fixedly connected to a motor 1109, and the output shaft of the motor 1109 is fixedly connected to an elliptical plate 1110; when the reaction is completed, the rotating rod 9 stops rotating and is left to stand for a period of time, so that the precipitate accumulates at the bottom. Since the precipitate will flow with the solution, the precipitate is difficult to collect. At this time, the motor 1109 can be started, and the motor 1109 can drive the elliptical plate 1110 to rotate, thereby driving the collecting ring plate 1104 to move up and down.

[0044] like Fig.12 As shown, the locking assembly 6 includes a locking fixing plate 601, a threaded rod 602 is fixedly connected to the top of the locking fixing plate 601, a rotating handle 603 is threadedly connected to the upper surface of the threaded rod 602, and a lower pressure ring 604 is fixedly connected to the front end of the tank cover 5; after the tank cover 5 is closed, the handle 603 is rotated on the threaded rod 602 and moved downward at the same time, so that the lower pressure ring 604 is pressed down to compress the tank cover 5 and the reaction tank 4, so as to maintain a sealed state.

[0045] like Figures 2 to 12 As shown, the top of the tank cover 5 is fixedly connected with a delivery port 15, the front end of the reaction tank 4 is plugged with a collection tube 14, and a heater is arranged inside the bottom of the reaction tank 4; the inside of the reaction tank 4 is monitored by the control board 2, and when any reagent needs to be added for adjustment, the internal solution can be adjusted through the delivery port 15 on the upper part of the tank cover 5, and the heater can dry the precipitate for easy collection.

[0046] Working principle:

[0047] When the user uses the device, first pour the prepared reagent solution into the reaction tank 4, then cover the tank cover 5, rotate the handle 603 on the threaded rod 602, and move downward at the same time to press the lower pressure ring 604 downward to compress the tank cover 5 and the reaction tank 4 to maintain a sealed state, and then monitor the inside of the reaction tank 4 through the control board 2. When any reagent needs to be added for adjustment, the internal solution can be adjusted through the injection port 15 on the upper part of the tank cover 5. The solution needs to be constantly stirred during the reaction so that multiple solutions are fully mixed and reacted. The user can control the electric push rod 702 according to the height of the solution inside the reaction tank 4 to push the annular moving plate 703 downward so that When the connecting plate 1001 reaches a certain position and pushes the annular movable plate 703 to move downward, the connecting plate 1001 will also move downward. The connecting plate 1001 will move downward on the sliding groove 1002. Under the action of the protrusion 1005, the middle parts of the primary stirring rod 1003 and the secondary stirring rod 1004 are pushed out, so that the primary stirring rod 1003 and the secondary stirring rod 1004 can be bent to form a horizontal V shape, so that the two stirring rods can stir the solution at the edge well. At the same time, when the connecting plate 1001 rotates, it will drive the gear 1202 to make a circular motion together. When the gear 1202 rotates on the ring gear 1201, it will drive the auxiliary stirring rod 1203 on the connecting plate 1001. Rotate, so that the solution on the upper part of the stirring device 10 can be stirred, making the stirring more sufficient. When the reaction is completed, the rotating rod 9 stops rotating and stands for a period of time, so that the precipitate accumulates in the lower part. Since the precipitate will flow with the solution, it is difficult to collect the precipitate. At this time, the motor 1109 can be started, and the collecting ring plate 1104 can be moved down a distance to make the leaking port 1107 on the drainage column 1105 leak out for drainage. Filter paper is provided at the leaking port 1107, so that the precipitate will not be retained with the leaking port 1107. The flowing solution can be collected and processed through the collecting pipe 14. After the solution is almost all flowed away, a moist precipitate is obtained. At this time, the motor 1109 can be started again. 09, drives the elliptical plate 1110 to rotate, thereby drives the collecting ring plate 1104 to vibrate up and down, the spring rod 1103 will limit the collecting ring plate 1104, and at the same time start the bottom heater of the reaction tank 4 to dry the precipitate. After the precipitate is dried, the servo motor 8 can be reversed to drive the supporting ring plate 1101 to move upward, and at the same time, the precipitate adhering to the side wall can be scraped off, so that the collection is more complete and efficient, and it is also more convenient to clean the device later. At the same time, under the action of the one-way bearing 1102, when the rotating rod 9 stirs the solution, when the one-way bearing 1102 reaches the bottom, the rotating rod 9 will only drive the one-way bearing 1102 to rotate and will not continue to squeeze downward.

[0048] Embodiment 2

[0049] The present invention provides a purification process using the above-mentioned vildagliptin device, and the purification process comprises the following steps:

[0050] S1, adding (2S)-N-chloroacetyl-2-cyanopyrrole and 3-amino-1-adamantanol into reaction tank 4 for condensation reaction to obtain crude vildagliptin;

[0051] S2, dissolving the crude product in S1 with 20 times the amount of acidic aqueous solution, and then adding an equal volume of organic solvent for extraction and separation, so that the vildagliptin disubstituted impurities are retained in the organic phase, and the vildagliptin is transferred to the aqueous phase, and the aqueous phase is collected;

[0052] S3, adjusting the pH value of the liquid vildagliptin obtained in S2 with an alkaline reagent, adding an organic solvent for extraction, and collecting the obtained solid precipitate through a vertical moving device 11;

[0053] S4. Finally, the pure product of vildagliptin is obtained by drying and compression.

[0054] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them.

Claims

1. A purification device for vildagliptin, characterized in that, The invention comprises a box body (1), a control panel (2) is fixedly connected to the rear side of the top of the box body (1), a cabinet door (3) is rotatably connected to the front end of the box body (1), two reaction tanks (4) are fixedly connected to the top of the box body (1), a tank cover (5) is abutted on the top of the reaction tank (4), a locking assembly (6) is fixedly connected to the front end of the tank cover (5), a pushing device (7) is fixedly connected to the top of the inner wall of the reaction tank (4), a servo motor (8) is fixedly connected to the bottom of the reaction tank (4), a rotating rod (9) is fixedly connected to the output shaft of the servo motor (8), a threaded groove (13) is provided on the surface of the rotating rod (9), and a vertical movement device (11) is provided on the surface of the rotating rod (9).

2. A purification device for vildagliptin according to claim 1, characterized in that, The pushing device (7) comprises an annular fixed plate (701), the bottom of the annular fixed plate (701) is evenly distributed and fixedly connected with electric push rods (702), the output end of the electric push rod (702) is fixedly connected with an annular movable plate (703), the bottom of the annular movable plate (703) is slidably connected with a connecting column (704), the bottom of the connecting column (704) is fixedly connected with a stirring device (10), and the inner wall of the annular movable plate (703) is provided with an auxiliary component (12).

3. A purification device for vildagliptin according to claim 2, characterized in that, The stirring device (10) comprises a connecting plate (1001), a plurality of sliding grooves (1002) are evenly arranged on the surface of the rotating rod (9), the connecting plate (1001) is slidingly connected to the inner wall of the sliding groove (1002), a primary stirring rod (1003) is rotatably connected to one side of the bottom of the connecting plate (1001), a secondary stirring rod (1004) is rotatably connected to the bottom of the primary stirring rod (1003), the bottom of the secondary stirring rod (1004) is rotatably connected to the bottom of the movable groove, and a protrusion (1005) is fixedly connected to the middle of the sliding groove (1002) at the connection between the primary stirring rod (1003) and the secondary stirring rod (1004).

4. A purification device for vildagliptin according to claim 2, characterized in that, The auxiliary component (12) comprises a ring tooth (1201), wherein the ring tooth (1201) is fixedly connected to the inner wall of the annular movable plate (703), and the ring tooth (1201) is meshingly connected to a plurality of gears (1202), and the top and bottom of the gears (1202) are fixedly connected to auxiliary stirring rods (1203), and the bottom of the auxiliary stirring rod (1203) is rotatably connected to the top of the connecting plate (1001).

5. A purification device for vildagliptin according to claim 1, characterized in that, The vertical movement device (11) comprises a support ring plate (1101), the inner wall of the support ring plate (1101) is fixedly connected to a one-way bearing (1102), the top of the support ring plate (1101) is fixedly connected to a spring rod (1103), and the top of the spring rod (1103) is fixedly connected to a collection ring plate (1104).

6. A purification device for vildagliptin according to claim 5, characterized in that, A drainage column (1105) is fixedly connected to the top of the support ring plate (1101), a water outlet (1106) is provided at the bottom of the surface of the drainage column (1105), and a water leakage port (1107) is provided at the upper part of the surface of the drainage column (1105).

7. A purification device for vildagliptin according to claim 5, characterized in that: The top of the support ring plate (1101) is fixedly connected to a base (1108), the inner wall of the base (1108) is fixedly connected to a motor (1109), and the output shaft of the motor (1109) is fixedly connected to an elliptical plate (1110).

8. A purification device for vildagliptin according to claim 1, characterized in that: The locking assembly (6) comprises a locking fixing plate (601), the top of the locking fixing plate (601) is fixedly connected to a threaded rod (602), the upper surface of the threaded rod (602) is threadedly connected to a rotating handle (603), and the front end of the tank cover (5) is fixedly connected to a lower pressure ring (604).

9. A purification device for vildagliptin according to claim 8, characterized in that: The top of the tank cover (5) is fixedly connected with a delivery port (15), the front end of the reaction tank (4) is plugged with a collecting pipe (14), and the bottom of the reaction tank (4) is internally provided with a heater.

10. A process using the purification device of vildagliptin according to any one of claims 1 to 9, characterized in that: The purification process comprises the following steps: S1, adding (2S)-N-chloroacetyl-2-cyanopyrrole and 3-amino-1-adamantanol into a reaction tank (4) for condensation reaction to obtain a crude product of vildagliptin; S2, dissolving the crude product in S1 with 20 times the amount of acidic aqueous solution, and then adding an equal volume of organic solvent for extraction and separation, so that the vildagliptin disubstituted impurities are retained in the organic phase, and the vildagliptin is transferred to the aqueous phase, and the aqueous phase is collected; S3, adjusting the pH value of the liquid vildagliptin obtained in S2 with an alkaline reagent, adding an organic solvent for extraction, and collecting the obtained solid precipitate through a vertical moving device (11); S4. Finally, the pure product of vildagliptin is obtained by drying and compression.

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