Preparation method and preparation device of pharmaceutical grade tris (hydroxymethyl) aminomethane

Abstract

The invention belongs to the technical field of compound preparation, and particularly relates to a preparation method and a preparation device of pharmaceutical-grade tris (hydroxymethyl) aminomethane. S1, adding the raw materials into a reaction kettle, heating, stirring and mixing; s2, dropwise adding nitromethane to carry out condensation reaction; s3, adding the solution into a reaction tank and carrying out atomization treatment; s4, introducing hydrogen, mixing the hydrogen with the atomized solution, contacting with a catalyst, and carrying out a reduction reaction; s4, after the reaction is completed, stopping atomizing the solution; s5, adding activated carbon into the solution, and filtering, cooling and crystallizing the solution to obtain crude product particles; s6, dissolving the crude product particles with deionized water, and adding activated carbon to remove impurities; s7, the solution is filtered, cooled and crystallized; and S8, carrying out drying treatment on the separated crystals. According to the invention, trihydroxymethyl nitromethane is atomized and uniformly mixed with hydrogen, and the mixed fluid is fully contacted and reacted with the catalyst, so that the utilization rate of discharged hydrogen is increased, and the production efficiency is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of compound preparation, and particularly to a preparation method and a preparation device for pharmaceutical-grade tris(hydroxymethyl)aminomethane. Background Art

[0002] Tris(hydroxymethyl)aminomethane is an important organic compound. In the pharmaceutical field, since it can absorb hydrogen ions to correct acidosis, it is commonly used in acute metabolic and respiratory acidemia. It is an ideal drug and also an important pharmaceutical intermediate. When the existing tris(hydroxymethyl)aminomethane is prepared, it is mostly through the condensation reaction of nitromethane and excessive paraformaldehyde to generate the intermediate tris(hydroxymethyl)nitromethane, and then hydrogen is used to carry out a reduction reaction on the intermediate to obtain tris(hydroxymethyl)aminomethane. After the reduction reaction is completed, the catalyst is removed by neutralization and filtration, and then purified by crystallization and recrystallization, and finally dried to obtain solid tris(hydroxymethyl)aminomethane.

[0003] In the above reduction reaction, since the reaction between hydrogen and tris(hydroxymethyl)nitromethane needs to contact with the catalyst, and in the existing device during the preparation process, the catalyst is mostly directly added to the tris(hydroxymethyl)nitromethane solution, and then hydrogen is gradually introduced into the tris(hydroxymethyl)nitromethane solution, and stirring is used to make tris(hydroxymethyl)nitromethane and hydrogen contact with the catalyst at the same time. However, in this process, since the solubility of hydrogen in the solution is low, and gaseous hydrogen needs to be dissolved in the solution first, and then can contact and react with tris(hydroxymethyl)nitromethane and the catalyst together. At the same time, the existing method uses a powder catalyst directly dispersed in the solution, and hydrogen is introduced in the form of bubbles, and the contact efficiency of the gas-liquid-solid three phases is low, and the unreacted hydrogen is easily escaped from the solution, resulting in low hydrogen utilization rate per unit time and affecting the production efficiency. Summary of the Invention

[0004] The present invention provides a preparation method and a preparation device for pharmaceutical-grade tris(hydroxymethyl)aminomethane, which are used to solve the defect that hydrogen cannot be uniformly mixed with tris(hydroxymethyl)aminomethane and then contact with the catalyst in the existing reaction device.

[0005] The technical implementation scheme of the present invention is: a preparation method of pharmaceutical-grade trishydroxymethylaminomethane, comprising the following steps: S1: adding nitromethane and polyformaldehyde in a certain molar ratio of 1:3.3 and a catalyst into a reactor, heating and stirring until the polyformaldehyde is completely dissolved; S2: slowly dropping nitromethane into the solution for condensation reaction, and keeping the temperature of the solution between 40 and 55°C; S3: adding the solution after the reaction into a reaction tank, and atomizing the solution, and the temperature in the reaction tank is between 40 and 50°C; S4: introducing hydrogen into the reaction tank, and the hydrogen is mixed with the atomized solution and then mixed with the catalyst. Contact to carry out reduction reaction to obtain trishydroxymethylaminomethane; S4: after the reduction reaction is completed, stop atomizing the solution and keep the temperature of the solution in the reaction tank at 60°C; S5: add activated carbon to the solution and slowly stir it to allow the activated carbon to adsorb impurities in the solution, then filter the solution and cool it for crystallization to obtain crude particles; S6: use deionized water to dissolve the crude particles and add activated carbon again to remove impurities, keeping the solution temperature at 80°C; S7: filter the above-mentioned secondary impurity removal solution again, and then cool it for crystallization again; S8: dry the precipitated crystals to obtain finished trishydroxymethylaminomethane particles.

[0006] A preparation device for pharmaceutical-grade tris(hydroxymethyl)aminomethane, which is applied to the above-mentioned preparation method for pharmaceutical-grade tris(hydroxymethyl)aminomethane, comprises: a reaction tank, wherein the upper and lower sides of the reaction tank are respectively provided with a feed port and a discharge port, and the lower part of the reaction tank is provided with a circulation port; a motor, which is fixedly connected to the reaction tank; an air intake pipe, which is fixedly connected to the output shaft of the motor, the air intake pipe is externally connected to a hydrogen tank, the air intake pipe is provided with a sliding shell, and the air intake pipe is connected to the sliding shell through an air delivery pipe; there are multiple exhaust pipes, which are all provided on the sliding shell, and the exhaust pipe is connected to the sliding shell; A stirring frame, fixedly connected to the air inlet pipe; a liquid inlet pipe, fixedly connected to the air inlet pipe, the liquid inlet pipe is rotatably connected to the reaction tank, the liquid inlet pipe and the circulation port are commonly connected to a circulation pump through a hose; an atomizing shell, fixedly connected to and communicated with the liquid inlet pipe; a fixed ring, fixedly connected to the reaction tank, the fixed ring is fixedly connected to a fixed frame through a connecting rod, the fixed ring and the fixed frame are rotatably connected to an annular filter screen, and the annular filter screen is filled with a catalyst; a power assembly is arranged in the reaction tank, and is used to adjust the position of the annular filter screen to disperse the catalyst after the catalyst is agglomerated in the annular filter screen.

[0007] Furthermore, the fixing ring is located below the fixing frame.

[0008] Furthermore, the power assembly includes: a first electric push rod, fixedly connected in the reaction tank, a sliding frame fixedly connected to the telescopic end of the first electric push rod, the sliding frame is slidably connected to the liquid inlet pipe, the sliding frame is slidably connected to the fixed frame, and an air pressure sensor is arranged on the fixed ring, and the air pressure sensor is used to detect the pressure of the gas in the reaction tank; a transmission plate, which has a plurality of transmission plates, which are evenly hinged to the sliding frame in a circumferential direction, and a torsion spring is fixedly connected between the transmission plate and the sliding frame; annular soft strips, the number of which is the same as the number of the transmission plates, are evenly fixed to the annular filter screen in a circumferential direction, the fixed frame and the fixed ring are both slidably connected to the annular soft strips, the annular soft strips are fixedly connected with evenly distributed limit plates, and the limit plates are located on the moving path of the adjacent transmission plates; a smoothing assembly, which is arranged on the sliding frame, and is used to slap the catalyst in the annular filter screen in the process of driving the annular filter screen to rotate.

[0009] Furthermore, the limiting plate is an L-shaped plate.

[0010] Furthermore, the smoothing component includes: a rotating ring, slidably connected to the liquid inlet pipe, and the rotating ring is rotatably connected to the sliding frame; an annular plate, rotatably and slidably connected to the rotating ring, and the annular plate is fixed with a circumferentially distributed smoothing plate, and the smoothing plate is used to squeeze the annular filter; a vibration component is arranged on the annular plate, and is used to drive the annular plate to move up and down, so that the smoothing plate hits the annular filter.

[0011] Furthermore, the vibration assembly includes: a first spring fixed between the rotating ring and the annular plate, the annular plate and the fixed frame are fixed with circumferentially distributed extrusion blocks on the facing sides, and the extrusion blocks at different heights squeeze each other to drive the annular plate to move.

[0012] Furthermore, it also includes: a sliding component, which is arranged on the air intake pipe and is used to adjust the distance between the exhaust pipe and the atomization shell, and the sliding component includes: a second electric push rod, which is fixed to the fixed ring, and the air intake pipe and the sliding shell are slidably connected, and the telescopic end of the second electric push rod is fixed to a limiting ring, and the limiting ring is slidably connected to the reaction tank; elastic rods, the number of which is the same as the number of the exhaust pipes, are respectively fixed to adjacent exhaust pipes, and the elastic rods are slidably and rotatably connected to the limiting rings.

[0013] Furthermore, a second spring is fixedly connected between the air intake pipe and the sliding shell, and the exhaust pipe is hinged to the sliding shell.

[0014] Furthermore, the included angle between the exhaust pipe and the horizontal plane is less than 30°, and one end of the exhaust pipe away from the air inlet pipe is higher than the other end thereof.

[0015] Compared with the prior art, the present invention has the following advantages: 1. In the process of producing trishydroxymethylaminomethane, the present invention improves the utilization rate of the discharged hydrogen by atomizing trishydroxymethylnitromethane and uniformly mixing it with hydrogen, and then fully contacts and reacts the mixed fluid with a catalyst, thereby improving the production efficiency of trishydroxymethylaminomethane.

[0016] 2. When the catalyst in the annular filter screen agglomerates, the annular filter screen is driven to move by the annular soft strip, so that the annular filter screen drives the catalyst to move, and the catalyst in the annular filter screen remains loose, thereby ensuring the contact area between trihydroxymethylnitromethane and the catalyst, thereby ensuring the production efficiency of trihydroxymethylaminomethane.

[0017] 3. When adjusting the position of the annular filter, the present invention reduces the impact force of the gas on the atomized solution and the amount of contact between the atomized solution and the annular filter by adjusting the angle and position of the exhaust pipe. At the same time, the gas discharged from the exhaust pipe blows the catalyst particles in the annular filter to speed up the flow rate of the solution between the catalyst particles, thereby quickly dealing with the catalyst agglomeration and ensuring the normal progress of the reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a schematic diagram of the three-dimensional structure of the present invention;

[0019] Figure 2 It is a schematic diagram of the three-dimensional structure of the motor, the air inlet pipe and the liquid inlet pipe of the present invention;

[0020] Figure 3 It is a schematic diagram of the three-dimensional structure of the liquid inlet pipe, the sliding frame and the fixed frame of the present invention;

[0021] Figure 4 It is a three-dimensional structural schematic diagram of the transmission plate, the annular soft strip and the smoothing plate of the present invention;

[0022] Figure 5 It is a schematic diagram of the three-dimensional structure of the rotating ring, the annular plate and the second spring of the present invention;

[0023] Figure 6 It is a three-dimensional structural cross-sectional view of the sliding frame, the fixed frame and the rotating ring of the present invention;

[0024] Figure 7 It is a three-dimensional structural schematic diagram of the transmission plate, the annular soft strip and the limit plate of the present invention;

[0025] Figure 8 It is a schematic diagram of the three-dimensional structure of the intake pipe, the exhaust pipe and the second spring of the present invention;

[0026] Figure 9 It is a three-dimensional structural cross-sectional view of the air intake pipe, the sliding shell and the exhaust pipe of the present invention.

[0027] In the accompanying drawings: 1-reaction tank, 101-circulation port, 2-motor, 3-inlet pipe, 4-sliding shell, 5-exhaust pipe, 6-stirring frame, 7-liquid inlet pipe, 8-atomizing shell, 9-fixed ring, 10-sliding frame, 11-fixed frame, 12-annular filter, 13-first electric push rod, 14-transmission plate, 15-torsion spring, 16-annular soft strip, 17-limiting plate, 1101-rotating ring, 18-annular plate, 19-smoothing plate, 20-first spring, 21-extrusion block, 24-second spring, 25-second electric push rod, 26-limiting ring, 27-elastic rod. DETAILED DESCRIPTION

[0028] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] A method for preparing pharmaceutical grade trishydroxymethylaminomethane, such as Figures 1-9 As shown, the method comprises the following steps: S1: adding nitromethane and paraformaldehyde in a certain molar ratio of 1:3.3 and a catalyst into a reaction kettle, heating and stirring until the paraformaldehyde is completely dissolved; S2: slowly dropping nitromethane into the solution for condensation reaction, and maintaining the temperature of the solution between 40 and 55°C; S3: adding the solution after the reaction into a reaction tank, and atomizing the solution, and the temperature in the reaction tank is between 40 and 50°C; S4: introducing hydrogen into the reaction tank, and the hydrogen is mixed with the atomized solution and then contacts with the catalyst for reduction reaction to obtain trihydroxy Methylaminomethane; S4: after the reduction reaction is completed, stop atomizing the solution and keep the temperature of the solution in the reaction tank at 60°C; S5: add activated carbon to the solution and stir slowly to allow the activated carbon to adsorb impurities in the solution, then filter the solution and cool it to crystallize to obtain crude particles; S6: use deionized water to dissolve the crude particles and add activated carbon again to remove impurities, keeping the solution temperature at 80°C; S7: filter the above-mentioned secondary impurity removal solution again, and then cool it to crystallize again; S8: dry the precipitated crystals to obtain finished trishydroxymethylaminomethane particles.

[0030] like Figures 1-5As shown, a preparation device of pharmaceutical-grade tris(hydroxymethyl)aminomethane described in the present invention is applied to the preparation method of pharmaceutical-grade tris(hydroxymethyl)aminomethane described above, comprising: a reaction tank 1, wherein the upper and lower sides of the reaction tank 1 are respectively provided with a feed port and a discharge port, and the lower part of the reaction tank 1 is provided with a circulation port 101; a motor 2, which is fixedly connected to the reaction tank 1; an air intake pipe 3, which is fixedly connected to the output shaft of the motor 2, the air intake pipe 3 is externally connected to a hydrogen tank, the air intake pipe 3 is provided with a sliding shell 4, and the air intake pipe 3 is connected to the sliding shell 4 through an air delivery pipe; a plurality of exhaust pipes 5, which are all provided on the sliding shell 4, and the exhaust pipe 5 is connected to the sliding shell 4 The invention relates to a mixing frame 6, which is fixedly connected to the air inlet pipe 3; a liquid inlet pipe 7, which is fixedly connected to the air inlet pipe 3, the liquid inlet pipe 7 is rotatably connected to the reaction tank 1, and the liquid inlet pipe 7 and the circulation port 101 are connected to a circulation pump through a hose; an atomizing shell 8, which is fixedly connected to and communicated with the liquid inlet pipe 7; a fixing ring 9, which is fixedly connected to the reaction tank 1, the fixing ring 9 is fixedly connected to a fixing frame 11 through a connecting rod, the fixing ring 9 and the fixing frame 11 are rotatably connected to an annular filter screen 12, and the annular filter screen 12 is filled with a catalyst; a power assembly, which is arranged in the reaction tank 1, and is used to adjust the position of the annular filter screen 12 to disperse the catalyst after the catalyst is agglomerated in the annular filter screen 12.

[0031] Further, such as Figure 4 and Figure 5 As shown, the fixing ring 9 is located below the fixing frame 11 .

[0032] The above scheme provides a method for atomizing the solution and mixing it with hydrogen to directly contact and react with the catalyst during the reduction reaction, thereby improving the utilization rate of hydrogen and accelerating the reaction speed of the material; the circulation port 101 is used to extract the solution in the reaction tank 1 during the reaction of the solution in the reaction tank 1. In the following, the electrical components located in the reaction tank 1 are all installed with a protective shell to prevent the electrical components from contacting the reactants. The upper part of the reaction tank 1 is provided with an air outlet, which is connected to an external vacuum pump. The vacuum pump is used to extract the solution in the reaction tank 1 through a ring. The unreacted hydrogen behind the filter 12 allows the hydrogen in the reaction tank 1 to circulate normally; a rotating shell is provided at the upper end of the intake pipe 3, and the intake pipe 3 is connected to the hydrogen tank through the rotating shell. In this embodiment, the intake pipe 3 and the sliding shell 4 are fixedly connected; the number of exhaust pipes 5 is five, which are evenly distributed on the side of the sliding shell 4. In this embodiment, the relative position between the exhaust pipe 5 and the sliding shell 4 is fixed, and the upper side of the exhaust pipe 5 is provided with axially distributed exhaust holes, which are used to discharge hydrogen into the reaction tank 1, so that part of the hydrogen contacts with the solution, and at the same time The atomized solution is blown to move upward and contact the catalyst; the stirring frame 6 is used to stir the solution gathered at the bottom of the reaction tank 1; the liquid inlet pipe 7 is located on the outside of the air inlet pipe 3, and a rotating shell is also provided on the upper part of the liquid inlet pipe 7. The rotating shell of the liquid inlet pipe 7 and the circulation port 101 are connected to a circulation pump through a hose. The circulation pump is an existing device and is not shown in the figure. The circulation pump is used to extract the solution in the reaction tank 1 and transport it to the liquid inlet pipe 7; the atomizing shell 8 is located on the upper side of the sliding shell 4, and the atomizing shell 8 is provided with uniformly distributed atomizing nozzles; the annular filter 1 2 is an elastic filter screen or elastic filter cloth, which is used to make the annular filter screen 12 adapt to the changes in the shapes of the fixing ring 9 and the fixing frame 11 during movement. The annular filter screen 12 is filled with a catalyst. In actual use, a fixing ring can be added at the position where the annular filter screen 12 contacts the fixing ring 9 and the fixing frame 11 according to the situation to stabilize the shape of the annular filter screen 12. The catalyst in the annular filter screen 12 is a nickel catalyst, and the nickel catalyst is granular, which is used to increase the contact area between the nickel catalyst and the solution and hydrogen. The particle size of the nickel catalyst can be adjusted according to the situation.

[0033] Further, such as Figures 2-7As shown, the power assembly includes: a first electric push rod 13, which is fixed in the reaction tank 1, and a sliding frame 10 is fixed to the telescopic end of the first electric push rod 13, and the sliding frame 10 is slidably connected to the liquid inlet pipe 7, and the sliding frame 10 is slidably connected to the fixed frame 11, and an air pressure sensor is arranged on the fixed ring 9, and the air pressure sensor is used to detect the pressure of the gas in the reaction tank 1; there are multiple transmission plates 14, which are evenly hinged to the sliding frame 10 in the circumferential direction, and a torsion spring 15 is fixed between the transmission plate 14 and the sliding frame 10; annular soft strips 16, the number of which is the same as the number of transmission plates 14, and are evenly fixed to the annular filter screen 12 in the circumferential direction, and the fixed frame 11 and the fixed ring 9 are both slidably connected to the annular soft strips 16, and the annular soft strips 16 are fixed with uniformly distributed limit plates 17, and the limit plates 17 are located on the moving path of the adjacent transmission plates 14; a smoothing assembly is arranged on the sliding frame 10, and is used to beat the catalyst in the annular filter screen 12 in the process of driving the annular filter screen 12 to rotate.

[0034] Further, such as Figure 6 and Figure 7 As shown, the limiting plate 17 is an L-shaped plate.

[0035] The above scheme provides a method for driving the annular filter 12 to rotate and adjusting the position of the catalyst in the annular filter 12 to loosen it after the solution in the catalyst on the annular filter 12 is excessive and agglomerated; initially, the telescopic end of the first electric push rod 13 is in an extended state, and the telescopic end of the first electric push rod 13 is fixedly connected to the sliding frame 10, and the air pressure sensor on the fixing ring 9 is used to detect the pressure of the gas under the annular filter 12 in the reaction tank 1; in this embodiment, the number of the transmission plates 14 is six, and the transmission plate 14 has a barb on the side away from the liquid inlet pipe 7, and the barb It is used to hook the limit plate 17 and drive the sliding frame 10 to move when the sliding frame 10 moves upward. Initially, the barb of the transmission plate 14 has hooked the adjacent limit plate 17, and the torsion spring 15 is used to drive the transmission plate 14 to rotate and reset, and the torsion spring 15 is always in a state of storing force; the fixed ring 9 and the fixed frame 11 are both provided with an arc groove, and the arc groove is used to enable the annular soft strip 16 to drive the limit plate 17 to move, so that the limit plate 17 can pass through the fixed ring 9 and the fixed frame 11, and the transmission plate 14 and the limit plate 17 are both provided with rounded corners to prevent the transmission plate 14 from being stuck by the limit plate 17 when it is reset.

[0036] Further, such as Figures 3-6 As shown, the smoothing component includes: a rotating ring 1101, which is slidably connected to the liquid inlet pipe 7, and the rotating ring 1101 is rotatably connected to the sliding frame 10; an annular plate 18, which is rotatably and slidably connected to the rotating ring 1101, and the annular plate 18 is fixed with a circumferentially distributed smoothing plate 19, and the smoothing plate 19 is used to squeeze the annular filter 12; a vibration component, which is arranged on the annular plate 18, and is used to drive the annular plate 18 to move up and down, so that the smoothing plate 19 hits the annular filter 12.

[0037] Further, such as Figures 3-6 As shown, the vibration assembly includes: a first spring 20, which is fixed between the rotating ring 1101 and the annular plate 18, and the facing sides of the annular plate 18 and the fixed frame 11 are fixed with circumferentially distributed extrusion blocks 21, and the extrusion blocks 21 at different heights squeeze each other to drive the annular plate 18 to move.

[0038] The above scheme provides a method for preliminarily loosening the catalyst in the annular filter 12 and reducing the resistance encountered by the annular filter 12 when rotating during the adjustment of the annular filter 12; the rotating ring 1101 is located at the lower part of the sliding frame 10; initially, the extrusion block 21 on the annular plate 18 does not contact the extrusion block 21 on the sliding frame 10. In this embodiment, the annular plate 18 has six caressing plates 19. When the annular plate 18 does not move upward, the caressing plates 19 rotate with the annular plate 18 and mix the atomized solution and hydrogen. After the annular plate 18 moves upward, the caressing plates 19 squeeze the lower side of the annular filter 12 to disperse the agglomerated catalyst in the annular filter 12. The caressing plates 19 can be provided with protrusions to improve the effect of loosening the catalyst in the annular filter 12; the first spring 20 is used to push the annular plate 18 to move and reset, and the extrusion blocks 21 are provided with rounded corners, so that when the extrusion blocks 21 of different heights are squeezed against each other, the annular plate 18 moves downward under the drive of the extrusion blocks 21 thereon, thereby driving the caressing plates 19 to move up and down.

[0039] Working process: when it is necessary to carry out reduction reaction on the generated trihydroxymethylnitromethane solution, the staff adds the solution to be reacted into the reaction tank 1 through the feed port. When the liquid level of the solution approaches the lower end of the air inlet pipe 3, the staff seals the feed port after the solution is added, then starts the motor 2, the circulation pump and activates the air pressure sensor on the fixed ring 9. The circulation pump draws the solution in the reaction tank 1 from the circulation port 101 and transports it to the liquid inlet pipe 7 through a hose. Then the solution enters the atomizing shell 8 and is discharged through the atomizing nozzle to realize circulation. The output shaft of the motor 2 drives the air inlet pipe 3 to rotate, the air inlet pipe 3 drives the sliding shell 4, the stirring frame 6 and the liquid inlet pipe 7 to rotate, the sliding shell 4 drives the exhaust pipe 5 to rotate, the stirring frame 6 rotates to stir the solution in the reaction tank 1, the liquid inlet pipe 7 drives the atomizing shell 8 and the rotating ring 1101 to rotate synchronously, the atomizing shell 8 rotates so that the atomized solution sprayed out covers the exhaust pipe 5, and the rotating ring 1101 drives the smoothing plate 19 to rotate through the annular plate 18.

[0040] After the above solution starts to circulate, the staff opens the hydrogen tank to transport hydrogen into the air inlet pipe 3. The hydrogen enters the sliding shell 4 through the air inlet pipe 3 and the air delivery pipe, and then enters the exhaust pipe 5 and is discharged through the exhaust hole thereon. The discharged hydrogen pushes the atomized solution sprayed from the atomizing shell 8 to move upward, so that the atomized solution gradually approaches the annular filter screen 12 (hereinafter, the mixture of hydrogen and atomized solution is collectively referred to as fluid). In the process of the fluid moving upward, when the fluid moves to the vicinity of the caressing plate 19, the rotating caressing plate 19 further mixes the hydrogen in the fluid with the atomized solution, so that the hydrogen in the fluid and the atomized solution are distributed more evenly, so as to promote the reaction between the two and improve the utilization of hydrogen. rate. After the fluid contacts the catalyst in the annular filter 12, the substances in the fluid react under the action of the catalyst in the annular filter 12 to generate trishydroxymethylaminomethane, and the generated trishydroxymethylaminomethane is located in the atomized solution. At the same time, the atomized solution in the fluid adheres to the surface of the catalyst and forms liquid droplets separated from the hydrogen. As the reaction proceeds, the number of liquid droplets gradually increases, and under the action of gravity, they gather into droplets separated from the annular filter 12 and then fall into the solution in the reaction tank 1. At the same time, the incompletely reacted hydrogen passes through the annular filter 12 and gathers above the reaction tank 1. At this time, the staff starts the vacuum pump to collect and reuse the hydrogen gathered on the upper part of the reaction tank 1.

[0041] During the above reaction, when the liquid content between the catalyst particles in the annular filter 12 is too much and agglomerates appear, the rate at which the fluid passes through the annular filter 12 decreases, causing the air pressure between the annular filter 12 and the liquid surface in the reaction tank 1 to increase, and the value of the air pressure sensor increases and sends a signal to the first electric push rod 13. The telescopic end of the first electric push rod 13 is retracted and drives the sliding frame 10 to move upward. During this process, the air intake pipe 3 continues to drive the parts thereon to rotate, and the sliding frame 10 drives the transmission plate 14 and the rotating ring 1101 to move upward. Since the transmission plate 14 hooks the limit plate 17, the transmission plate 14 drives the annular soft strip 16 to move through the limit plate 17. During this process, under the action of the limit plate 17, the lower end of the transmission plate 14 gradually deflects toward the axial direction of the liquid inlet pipe 7 and reduces the force storage degree of the torsion spring 15, and the annular soft strip 16 drives the annular filter 12 to move synchronously, thereby completing the flipping of the inner and outer edges of the annular filter 12, so that the annular filter 12 rubs the catalyst particles therein during the movement, so that the catalyst particles are active and separated, and then the position of the annular filter 12 is adjusted and the catalyst particles are loosened, which facilitates the passage and reaction of the fluid, until the telescopic end of the first electric push rod 13 is completely retracted, the transmission plate 14 stops moving, and the position of the annular filter 12 is flipped.

[0042] During the upward movement of the rotating ring 1101, the rotating ring 1101 drives the annular plate 18 to move upward through the first spring 20. The annular plate 18 drives the ironing plate 19 and the extrusion block 21 thereon to move upward. When the ironing plate 19 contacts the annular filter screen 12, the ironing plate 19 loosens the catalyst inside the annular filter screen 12, facilitating the flow of the liquid between the catalyst particles. Until the extrusion block 21 on the annular plate 18 contacts the fixed frame 11, the annular plate 18 and the parts thereon stop moving. The sliding frame 10 continues to drive the rotating ring 1101 to move upward. The rotating ring 1101 moves upward relative to the annular plate 18 and compresses the first spring 20. Until the sliding frame 10 stops moving, the rotating ring 1101 stops moving. During this process, as the annular plate 18 drives the parts thereon to rotate, when the extrusion block 21 on the annular plate 18 contacts the extrusion block 21 on the fixed frame 11, the annular plate 18 moves downward under the extrusion of the two corresponding upper and lower extrusion blocks 21 and compresses the first spring 20 again, separating the ironing plate 19 from the annular filter screen 12. When the two corresponding upper and lower extrusion blocks 21 are separated, the first spring 20 pushes the annular plate 18 upward to strike the annular filter screen 12 again, thereby completing the loosening of the catalyst at different positions inside the annular filter screen 12, improving the loosening degree of the catalyst inside the annular filter screen 12, and facilitating the movement of the annular filter screen 12.

[0043] After the telescopic end of the first electric push rod 13 retracts and waits for a period of time, the telescopic end of the first electric push rod 13 extends and drives the parts thereon to move backward and reset. The sliding frame 10 drives the rotating ring 1101 and the transmission plate 14 to move downward and reset. The transmission plate 14 is reversely rotated by the extrusion of the annular soft strip 16 and the torsion spring 15 is wound again to store energy. When the transmission plate 14 passes through the limit plate 17, the transmission plate 14 crosses the limit plate 17 by extrusion. The first spring 20 extends and pushes the annular plate 18 to reset. Until the telescopic end of the first electric push rod 13 is fully extended, the sliding frame 10 stops moving downward. At this time, the position of the telescopic end of the sliding frame 10 is lower than its initial position. Then, the telescopic end of the first electric push rod 13 drives the sliding frame 10 to move upward again. Until the telescopic end of the first electric push rod 13 is reset, the sliding frame 10 is reset, and the transmission plate 14 catches the limit plate 17 again. The device is reset. When encountering the situation of catalyst caking again, repeat the above process to adjust the position of the annular filter screen 12 to loosen the catalyst inside the annular filter screen 12. When the flow rate of hydrogen entering the intake pipe 3 is the same as the flow rate of the vacuum pump extracting the upper gas in the reaction tank 1, the solution of tris(hydroxymethyl)nitromethane completely reacts. The staff turns off the opened electrical components, and then discharges and collects the reacted solution through the discharge port of the reaction tank 1. After the collection of the reacted solution is completed, repeat the above process to prepare tris(hydroxymethyl)aminomethane again.

[0044] Further, as Figure 2 andFigure 3 As shown, it further includes: a sliding component, which is arranged on the intake pipe 3 and is used to adjust the distance between the exhaust pipe 5 and the atomizing shell 8. The sliding component includes: a second electric push rod 25, which is fixedly connected to the fixed ring 9. The intake pipe 3 and the sliding shell 4 are slidably connected. The telescopic end of the second electric push rod 25 is fixedly connected with a limiting ring 26, and the limiting ring 26 is slidably connected with the reaction tank 1; elastic rods 27, the number of which is the same as that of the exhaust pipes 5, are respectively fixedly connected to adjacent exhaust pipes 5, and the elastic rods 27 are slidably and rotatably connected with the limiting ring 26.

[0045] Further, as Figure 2 and Figure 3 shown, a second spring 24 is fixedly connected between the intake pipe 3 and the sliding shell 4, and the exhaust pipe 5 is hinged to the sliding shell 4.

[0046] Further, as Figure 2 、 Figure 3 、 Figure 5 、 Figure 8 and Figure 9 shown, the included angle between the exhaust pipe 5 and the horizontal plane is less than 30°, and the end of the exhaust pipe 5 far from the intake pipe 3 is higher than the other end.

[0047] The above solution provides a way to increase the distance between the exhaust pipe 5 and the atomizing shell 8, reduce the impact force of hydrogen on the atomizing solution ejected from the atomizing shell 8, and reduce the subsequent atomizing solution adhering to the surface of the catalyst in the annular filter 12 during the process of adjusting the position of the annular filter 12. In this embodiment, the exhaust pipe 5 can only swing around the sliding shell 4 in the vertical plane to adjust the direction of the airflow discharged from the exhaust pipe 5. The second electric push rod 25 is used to drive the limiting ring 26 to move, so that the limiting ring 26 drives the exhaust pipe 5 to move through the elastic rod 27. The elastic rod 27 can be compressed. During the downward movement of the limiting ring 26, the included angle between the exhaust pipe 5 and the horizontal plane is adjusted by compressing the elastic rod 27. The elastic coefficient of the elastic rod 27 is greater than that of the second spring 24, which is used to synchronously move the sliding shell 4 downward during the process of driving the limiting ring 26 to move downward. The initial angle of the exhaust pipe 5 is used to make the gas blown out by the exhaust pipe 5 have an impact force on the atomizing solution discharged from the atomizing shell 8, so that the atomizing solution discharged from the atomizing shell 8 can normally contact the catalyst in the annular filter 12.

[0048] Workflow: After the above-mentioned air pressure sensor detects an increase in the air pressure between the annular filter screen 12 and the solution, the air pressure sensor transmits a signal to the first electric push rod 13 and the second electric push rod 25. The telescopic end of the first electric push rod 13 retracts to drive the sliding frame 10 to move upward, and the telescopic end of the second electric push rod 25 extends to drive the limiting ring 26 to move downward. The limiting ring 26 drives the exhaust pipe 5 to move downward through the elastic rod 27, reducing the impact force of the gas discharged from the exhaust pipe 5 on the atomized solution blown out by the atomizing shell 8. (The circulation pump can also be turned off at this time). The exhaust pipe 5 drives the sliding shell 4 to move downward and compress the second spring 24 until the second spring 24 cannot be compressed, and then the sliding shell 4 stops moving downward. The limiting ring 26 continues to move downward and compress the elastic rod 27. The elastic rod 27 drives the exhaust pipe 5 to rotate, causing the end of the exhaust pipe 5 away from the intake pipe 3 to move downward, thereby adjusting the orientation of the air outlet of the exhaust pipe 5, further reducing the impact force of the gas on the atomized solution, and at the same time increasing the impact force on the annular filter screen 12. By blowing air flow into the catalyst particles in the annular filter screen 12, the flow of the solution between the catalyst particles in the annular filter screen 12 is accelerated, further accelerating the treatment speed of the agglomerated catalyst and ensuring the normal progress of the reaction. Until the telescopic end of the second electric push rod 25 is fully extended, the limiting ring 26 stops moving. Taking the left limiting ring 26 in Figure 3 as an example, at this time, the limiting ring 26 is close to horizontal, and the left end of the limiting ring 26 is higher than its right end.

[0049] With the adjustment of the position of the annular filter screen 12, when the telescopic end of the first electric push rod 13 drives the sliding frame 10 to move in the reverse direction and reset, the telescopic end of the second electric push rod 25 retracts and drives the limiting ring 26 to move in the reverse direction and reset. The extrusion force of the limiting ring 26 on the elastic rod 27 decreases, and the elastic rod 27 extends and resets to drive the exhaust pipe 5 to swing in the reverse direction and reset. Until the elastic rod 27 is reset, as the limiting ring 26 continues to move upward, the second spring 24 pushes the sliding shell 4 to move upward and reset.

[0050] The above is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention.

Claims

1. A method for preparing pharmaceutical grade trishydroxymethylaminomethane, characterized in that: The steps include: S1: Add nitromethane and paraformaldehyde in a certain molar ratio of 1:3.3 and a catalyst into a reaction kettle, and heat and stir until the paraformaldehyde is completely dissolved; S2: Slowly add nitromethane to the solution to carry out condensation reaction, and keep the temperature of the solution between 40 and 55°C; S3: adding the reacted solution into a reaction tank and atomizing the solution, wherein the temperature in the reaction tank is between 40° C. and 50° C.; S4: introducing hydrogen into the reaction tank, mixing the hydrogen with the atomized solution and contacting with the catalyst to perform a reduction reaction, thereby obtaining trishydroxymethylaminomethane; S4: After the reduction reaction is completed, the atomizing solution is stopped and the temperature of the solution in the reaction tank is maintained at 60°C; S5: Add activated carbon into the solution and stir slowly to allow the activated carbon to absorb impurities in the solution, and then filter and cool the solution to crystallize to obtain crude particles; S6: Use deionized water to dissolve the crude particles and add activated carbon again to remove impurities, keeping the solution temperature at 80°C; S7: filtering the secondary impurity-removing solution again, and then cooling and crystallizing it again; S8: Drying the precipitated crystals to obtain finished trishydroxymethylaminomethane particles.

2. A preparation device for pharmaceutical-grade tris(hydroxymethyl)aminomethane, applied to the preparation method for pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 1, characterized in that: Included are: A reaction tank (1), wherein the upper and lower sides of the reaction tank (1) are respectively provided with a feed port and a discharge port, and the lower part of the reaction tank (1) is provided with a circulation port (101); A motor (2) is fixedly connected to the reaction tank (1); An air intake pipe (3) is fixedly connected to the output shaft of the motor (2), the air intake pipe (3) is externally connected to a hydrogen tank, the air intake pipe (3) is provided with a sliding shell (4), and the air intake pipe (3) is connected to the sliding shell (4) through an air delivery pipe; A plurality of exhaust pipes (5) are provided on the sliding shell (4), and the exhaust pipes (5) are in communication with the sliding shell (4); A stirring frame (6) fixedly connected to the air inlet pipe (3); A liquid inlet pipe (7) is fixedly connected to the air inlet pipe (3), the liquid inlet pipe (7) is rotatably connected to the reaction tank (1), and the liquid inlet pipe (7) and the circulation port (101) are connected to a circulation pump via a hose; An atomizing shell (8) is fixedly connected to and communicated with the liquid inlet pipe (7); A fixing ring (9) is fixedly connected to the reaction tank (1); the fixing ring (9) is fixedly connected to a fixing frame (11) via a connecting rod; the fixing ring (9) and the fixing frame (11) are rotatably connected to an annular filter screen (12); and the annular filter screen (12) is filled with a catalyst; A power component is arranged in the reaction tank (1) and is used to adjust the position of the annular filter (12) to disperse the catalyst after the catalyst is agglomerated in the annular filter (12).

3. A preparation device for pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 2, characterized in that: The fixing ring (9) is located below the fixing frame (11).

4. The preparation device of pharmaceutical grade tris(hydroxymethyl)aminomethane according to claim 3, characterized in that: The power assembly includes: A first electric push rod (13) is fixedly connected in the reaction tank (1); a sliding frame (10) is fixedly connected to the telescopic end of the first electric push rod (13); the sliding frame (10) is slidably connected to the liquid inlet pipe (7); the sliding frame (10) is slidably connected to the fixed frame (11); an air pressure sensor is arranged on the fixed ring (9); the air pressure sensor is used to detect the pressure of the gas in the reaction tank (1); a plurality of transmission plates (14) are evenly hinged to the sliding frame (10) in the circumferential direction; a torsion spring (15) is fixedly connected between the transmission plate (14) and the sliding frame (10); annular soft strips (16), the number of which is the same as the number of the transmission plates (14), and are evenly fixed to the annular filter screen (12) in the circumferential direction; the fixing frame (11) and the fixing ring (9) are both slidably connected to the annular soft strips (16); the annular soft strips (16) are fixedly connected with evenly distributed limiting plates (17), and the limiting plates (17) are located on the moving path of the adjacent transmission plates (14); A smoothing component is arranged on the sliding frame (10) and is used to beat the catalyst in the annular filter screen (12) in the process of driving the annular filter screen (12) to rotate.

5. The device for preparing pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 4, characterized in that: The limiting plate (17) is an L-shaped plate.

6. The device for preparing pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 5, characterized in that: The smoothing component includes: A rotating ring (1101) is slidably connected to the liquid inlet pipe (7), and the rotating ring (1101) is rotatably connected to the sliding frame (10); an annular plate (18) rotatably and slidably connected to the rotating ring (1101); the annular plate (18) is fixedly connected with circumferentially distributed caressing plates (19); the caressing plates (19) are used to squeeze the annular filter screen (12); A vibration component is arranged on the annular plate (18) and is used to drive the annular plate (18) to move up and down, so that the smoothing plate (19) hits the annular filter (12).

7. The device for preparing pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 6, characterized in that: The vibration component includes: The first spring (20) is fixed between the rotating ring (1101) and the annular plate (18). The annular plate (18) and the fixed frame (11) are fixedly connected to the facing sides thereof with circumferentially distributed extrusion blocks (21). The extrusion blocks (21) at different heights squeeze each other to drive the annular plate (18) to move.

8. The device for preparing pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 7, characterized in that: Also included are: A sliding assembly is arranged on the air inlet pipe (3) and is used to adjust the distance between the exhaust pipe (5) and the atomizing shell (8), and the sliding assembly comprises: The second electric push rod (25) is fixedly connected to the fixing ring (9), the air intake pipe (3) and the sliding shell (4) are slidably connected, and the telescopic end of the second electric push rod (25) is fixedly connected to the limiting ring (26). The limiting ring (26) is slidably connected to the reaction tank (1); The number of the elastic rods (27) is the same as the number of the exhaust pipes (5), and they are respectively fixed to adjacent exhaust pipes (5). The elastic rods (27) are slidably and rotatably connected to the limiting rings (26).

9. The device for preparing pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 8, characterized in that: A second spring (24) is fixedly connected between the air intake pipe (3) and the sliding shell (4), and the exhaust pipe (5) is hinged to the sliding shell (4).

10. The device for preparing pharmaceutical-grade tris(hydroxymethyl)aminomethane according to claim 9, characterized in that: The included angle between the exhaust pipe (5) and the horizontal plane is less than 30°, and one end of the exhaust pipe (5) away from the air inlet pipe (3) is higher than the other end.

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