Medical intermediate generation equipment with timed feeding function

Abstract

The invention discloses medical intermediate generation equipment capable of feeding at regular time, and belongs to the technical field of medical intermediate generation equipment, the medical intermediate generation equipment comprises a generation reaction kettle, and a pressure transmitter is arranged on the generation reaction kettle; the device further comprises a timing feeding device, the timing feeding device comprises a controller for complete machine control, a pipe base, a buffer pipe bin, a feeding pipe set, a pressure regulating module and a waste liquid circulating unit, pore plates are integrally manufactured on the upper portion and the lower portion of the inner side of the pipe base respectively, and the bottom of the pipe base is fixed to a feeding port of the generation reaction kettle. The tube seat is connected with a temperature control system; a U-shaped heat exchange tube is arranged on the inner side of the tube seat, and the two ends of the heat exchange tube extend out of the tube seat; according to the medical intermediate generation equipment capable of feeding at fixed time, ingredients can be completely fed into the kettle body, and the pressure environment and the temperature environment of the reaction kettle cannot be damaged in the feeding process; and a reaction system in the reaction kettle is subjected to accurate reaction, so that the reaction yield of the medical intermediate is ensured.

Description

Technical Field

[0001] The invention specifically relates to a pharmaceutical intermediate production device with timed feeding, belonging to the technical field of pharmaceutical intermediate production devices. Background Art

[0002] Pharmaceutical intermediates refer to intermediate compounds used to synthesize the final drugs in the pharmaceutical process. These intermediates are usually compounds formed in the intermediate steps of drug synthesis, rather than the final drug products. In the process of synthesizing drugs, chemical reactions usually require multiple steps, and each step involves a series of reactions and transformations. In the process of generating pharmaceutical intermediates, it is necessary to add materials regularly. Existing pharmaceutical intermediate production equipment with feeding, such as China Patent Authorization Announcement No.: CN114534628B, discloses a pharmaceutical intermediate production equipment with timed feeding. The pharmaceutical intermediate is evenly sprinkled into the reactor through the feeding mechanism, and the feeding mechanism and the feeding mechanism work at staggered time to achieve the control of feeding amount, speed and time. However, the existing pharmaceutical intermediate production equipment has a feeding mechanism, which is a kind of pharmaceutical intermediate production equipment with timed feeding. During the dosing process of the intermediate generating equipment, when external ingredients are added, there is a large temperature difference between the reaction system inside the kettle body, which can easily interfere with the normal reaction of the internal materials, thereby affecting the yield of the pharmaceutical intermediates. In addition, when the existing powder additives are added, they cannot be intercepted by the dosing equipment and are all sent to the kettle body; and in the synthesis process of some pharmaceutical intermediates, high-pressure reaction is required. During the intermediate dosing process, the materials cannot be fully driven into the kettle body due to the influence of high pressure, thereby causing an imbalance in the ingredients of the reaction system and affecting the yield of the pharmaceutical intermediates. In addition, during the synthesis process of some pharmaceutical intermediates, in order to avoid excessively violent reactions or excessive consumption of the reaction liquid, it is necessary to use a dripping method to supply liquid, but during the dripping process, the liquid is also affected by the high pressure inside the kettle body and cannot be delivered into the kettle body. Summary of the invention

[0003] In order to solve the above problems, the present invention proposes a pharmaceutical intermediate production equipment with timed feeding, which can completely feed the ingredients into the kettle body, and the feeding process will not destroy the pressure environment and temperature environment of the generating reaction kettle; the reaction system in the generating reaction kettle can react accurately, thereby ensuring the reaction yield of the pharmaceutical intermediate.

[0004] The pharmaceutical intermediate production equipment with timed feeding of the present invention comprises a production reaction kettle, on which a pressure transmitter is arranged; and a timed feeding device, which comprises a controller for whole machine control; A tube seat, wherein the upper and lower parts of the inner side of the tube seat are respectively integrally formed into perforated plates, and the bottom of the tube seat is fixed to the feed port of the generating reactor; the tube seat is connected to a temperature control system; a U-shaped heat exchange tube is arranged inside the tube seat, and both ends of the heat exchange tube extend out of the tube seat; The buffer tube bin includes a main material tube bin and two dripping tube bins; the main material tube bin and the dripping tube bin are both connected at the bottom with a conduit, the conduit movably penetrates the two orifice plates and extends out of the bottom of the tube seat; the conduit is sealed and welded with the orifice plates; a bottom valve is provided between the main material tube bin and the conduit; A feeding pipe group, the feeding pipe group includes a mixing pipe valve and a rotary valve group connected to the top of the main material pipe bin; the mixing pipe valve is connected to a high-position mixing tank; the rotary valve group is connected to a high-position additive storage tank; the top of the dripping pipe bin is connected to a double-valve pipe group; the other end of the double-valve pipe group is connected to a high-position dripping agent storage tank; A pressure regulating module, the pressure regulating module comprising a pressure regulating valve connected to one end of the heat exchange tube; the other end of the pressure regulating valve is connected to a pressure gas source; the other end of the heat exchange tube is connected to a first three-way valve, the other two ends of the first three-way valve are respectively connected to the middle end of a double-valve pipe group and the second three-way valve; the other two ends of the first three-way valve are respectively connected to the middle end of another double-valve pipe group and the top of the main material pipe bin; the pressure gas sent by the pressure gas source is sent to the buffer pipe bin after pressure regulation and temperature control, and the pressure difference between the outlet of the conduit and the inside of the conduit can be eliminated through the pressure gas source, so that the conduit can be smoothly discharged and dripped; A waste liquid circulation unit, which includes a reflux pump and a high-position valve body and a low-position valve body connected to the upper and lower parts of the generating reaction kettle, wherein the other ends of the high-position valve body and the low-position valve body are connected to the input end of the reflux pump, and the output end of the reflux pump is connected to the top of the main material pipe bin through a one-way valve; the reflux pump can pump out the waste liquid or reaction tail liquid that has completed a reaction in the generating reaction kettle through the high-position valve body or the low-position valve body, and send it to the main material pipe bin for mixing and diluting the powder additive, thereby realizing the addition of the powder additive to the generating reaction kettle separately, and at the same time, the main material pipe bin can be flushed, so that the ingredients are completely sent to the generating reaction kettle, ensuring the balanced ingredients of the reaction system in the generating reaction kettle.

[0005] Furthermore, the double-valve tube group includes an upper valve body and a lower valve body connected in series with each other, and the first three-way valve or the second three-way valve is connected to the output end of the upper valve body through a one-way valve; the upper valve body and the lower valve body are opened alternately, and when the upper valve body is opened, a certain amount of reaction droplets are delivered between the upper valve body and the lower valve body. After the liquid delivery is completed, the upper valve body is closed, and then the lower valve body is opened, and a certain amount of droplets are intermittently or continuously dripped into the generating reaction kettle through a pressure gas source.

[0006] Furthermore, the mixing tank includes a tank body, an electric stirring paddle is provided on the tank body, a metering valve is provided on the tank body, the other end of the metering valve is connected to multiple groups of liquid distribution pipe valves, and the other ends of the liquid distribution pipe valves are respectively connected to high-level liquid distribution storage tanks; the tank body is also provided with a solid powder supply pipe, and the solid powder supply pipe is connected to the powder storage tank through a rotary valve or a metering screw; the liquid distribution pipe valves perform batching in sequence, and during batching, one of the batching pipe valves sends the corresponding reaction liquid to the metering valve, which is metered by the metering valve and then sent to the tank body, and then the next reaction liquid is dosed through the next batching pipe valve; then, a certain amount of solid powder is sent into the tank body through the rotary valve or the metering screw, and finally, the solid material and the liquid material are fully mixed by the electric stirring paddle to obtain a solid-liquid mixture.

[0007] Furthermore, the dripping agent storage tank and the main material pipe bin are provided with exhaust pipe valves, through which the pressurized gas can be discharged to ensure smooth material discharge next time.

[0008] Furthermore, the temperature control system includes a circulation pipe group connected in series with the tube seat, and a circulation pump and a temperature control source are connected in series to the circulation pipe group. The temperature control source is a heating source or a cooling source. The temperature control liquid inside the temperature control source is heated or cooled to a set temperature. Then, the temperature control liquid is pumped into the inside of the tube seat through the circulation pump and the circulation pipe group. After the heat exchange is completed, the temperature control liquid is sent to the temperature control source through the circulation pipe group for precise temperature adjustment.

[0009] Furthermore, a sealing filler is poured on the top surface of the orifice plate; a heat-insulating jacket is provided on the outside of the pipe seat, and the sealing filler is poured on the basis of the sealing welding of the orifice plate and the conduit, thereby ensuring the sealing performance inside the pipe seat and avoiding overflow of the temperature control liquid of the temperature control system.

[0010] Furthermore, a one-way valve is arranged between the drip tube bin and the conduit. When the high pressure state is generated in the reaction kettle, the one-way valve can be tightened until the external pressure gas source pushes the one-way valve open, and the dripping liquid can drip in smoothly. By controlling the pressure difference at both ends of the one-way valve, the opening of the one-way valve can be controlled, thereby realizing accurate dripping into the reaction kettle.

[0011] Furthermore, the controller is built with a dripping timing feeding module, an ingredient timing feeding module and an auxiliary agent timing feeding module; the working process of the dripping timing feeding module is as follows: first, the total amount of dripping, the dripping start time and the dripping cut-off time are set through the dripping timing feeding module, the controller calculates the dripping time according to the dripping start time and the dripping cut-off time, and calculates the dripping amount per unit time according to the total amount of dripping divided by the dripping time, wherein the time can be set to 0.5~10min as a measurement unit, then, the controller uses the dripping amount per unit time as an index to query the preset association table of dripping amount and pressure difference to obtain the pressure difference value, then the controller times, when the dripping start time is reached, the controller triggers the first three-way valve and the second three-way valve to open, connects the pressure gas source and the double-valve pipe group, the controller monitors the pressure value of the reactor in real time through the pressure transmitter, and superimposes the collected pressure value with the queried pressure difference value to obtain the pressure value output by the pressure regulating valve; The working process of the batching timing feeding module is as follows: first, the batching parameters are set through the batching timing feeding module. The batching parameters can be added and modified multiple times. The batching parameters include the total amount of batching and the batching feeding cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is as follows: the controller starts timing. When the batching feeding time is reached, the controller triggers the first three-way valve and the second three-way valve to open, connect the pressure gas source with the main material pipe bin, disconnect the pressure gas source and the double-valve pipe group connection pipeline, and then the controller controls the pressure regulating valve to output the pressure of the real-time monitored reactor pressure value and the preset pressure value; then, the bottom valve is opened , the controller starts timing, and when the timing time is reached, the waste liquid circulation unit works, and the high-level valve body and the low-level valve body are selected to be opened. When the pharmaceutical intermediate product is a precipitate, the high-level valve body is opened, and when the pharmaceutical intermediate product is a floating object or a precipitate, the low-level valve body is opened, and the main material pipe bin is flushed with the liquid that has completed the reaction in the generation reaction kettle, and the ingredients are flushed into the generation reaction kettle; then, the bottom valve is closed and the drain valve is opened; after completing one batching addition, the controller returns to the drip timing feeding module workflow, and at the same time, the controller monitors and determines whether the batching addition cycle has been reached. If it has been reached, it enters the next batching timing feeding module; The working process of the additive timing feeding module is as follows: First, the batching parameters are set through the additive timing feeding module. The batching parameters can be added and modified multiple times. The batching parameters include the total amount of ingredients and the batching cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is as follows: The controller starts timing, and when the additive addition time is reached, the rotary valve group delivers the set total amount of additives to the main material pipe bin, and the controller adjusts the pressure of the pressure regulating module according to the process of the batching timing feeding module. Then, the bottom valve is opened, and at the same time, the waste liquid circulation unit works to pump the liquid that has completed the reaction into the main material pipe bin, mix it with the additive in the main material pipe bin, and flush it into the generating reaction kettle; when the reflux pump reaches the set working time, the reflux pump is shut down, the bottom valve is closed, and the drain valve is opened; after completing one additive addition, the controller returns to the drip timing feeding module workflow, and at the same time, the controller monitors and determines whether the additive addition cycle has been reached. If reached, it enters the next additive timing feeding module; the total amount of dripping and the total amount of ingredients are respectively measured and obtained by the metering unit valve group on the mixing pipe valve and the rotary valve group.

[0012] Furthermore, the association table is obtained through theoretical calculation or actual test. During the actual test, the two ends of the catheter are respectively connected to two pressure vessels at high and low positions, and the rated pressure is given to the pressure vessel at the low position. Then, dripping liquid is injected into the pressure vessel at the high position. After the pressure is stabilized, the relationship between the dripping amount and the pressure difference can be tested. The pressure of the high pressure vessel is changed to test the dripping amount per unit time.

[0013] Compared with the prior art, the pharmaceutical intermediate production equipment with timed feeding of the present invention can feed external solid-liquid mixture, separate auxiliary agent and dripping into the kettle body in a timed manner under the high pressure or vacuum environment of the kettle body. Under the high pressure state, the pressure difference is adjusted by external pressure distribution so that all the ingredients can be fed into the kettle body. The pressure gas source is used as the material discharge driving gas source after the temperature is controlled by the temperature control system, and the ingredients can be preheated. During the process of feeding the materials into the kettle body, the temperature is accurately controlled by the temperature control system. The feeding process will not destroy the pressure environment and temperature environment of the generating reaction kettle; the reaction system in the generating reaction kettle can react accurately. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 It is a schematic diagram of the overall structure of the pharmaceutical intermediate production equipment of the present invention.

[0015] Figure 2 This is a schematic structural diagram of the timing feeding device of the pharmaceutical intermediate production equipment of the present invention.

[0016] Figure 3 It is a schematic diagram of the installation structure of the timing feeding device and the mixing tank of the present invention.

[0017] Figure 4 It is a schematic diagram of the working process structure of the dripping timing feeding module of the present invention.

[0018] Figure 5 It is a schematic diagram of the working process structure of the batching and timing feeding module of the present invention.

[0019] Figure 6This is a schematic diagram of the working process structure of the auxiliary agent timing feeding module of the present invention.

[0020] Figure numerals: 1. generating reaction kettle, 2. pressure transmitter, 3. pipe seat, 4. orifice plate, 5. temperature control system, 6. heat exchange tube, 7. main material pipe bin, 8. dripping pipe bin, 9. conduit, 10. bottom valve, 11. mixing liquid pipe valve, 12. rotary valve group, 13. pressure regulating valve, 14. first three-way valve, 15. second three-way valve, 16. reflux pump, 17. high-position valve body, 18. low-position valve body, 19. one-way valve, 20. upper valve body, 21. lower valve body, 22. tank body, 23. electric stirring paddle, 24. metering valve, 25. liquid distribution pipe valve, 26. solid powder supply pipe, 27. rotary valve, 28. sealing packing. DETAILED DESCRIPTION

[0021] Example: like Figures 1 to 6 The pharmaceutical intermediate production equipment with timed feeding shown includes a production reaction kettle 1, on which a pressure transmitter 2 is provided; and a timed feeding device, which includes a controller for controlling the whole machine; A tube seat 3, wherein the upper and lower parts of the inner side of the tube seat 3 are respectively integrally formed with a perforated plate 4, and the bottom of the tube seat 3 is fixed to the feed port of the generating reactor 1; a temperature control system 5 is connected to the tube seat 3; a U-shaped heat exchange tube 6 is arranged inside the tube seat 3, and both ends of the heat exchange tube 6 extend out of the tube seat 3; The buffer pipe bin includes a main material pipe bin 7 and two dripping pipe bins 8; the main material pipe bin 7 and the dripping pipe bin 8 are both connected at the bottom with a conduit 9, the conduit 9 movably penetrates the two orifice plates 4 and extends out of the bottom of the pipe seat 3; the conduit 9 is sealed and welded with the orifice plate 4; a bottom valve 10 is provided between the main material pipe bin 7 and the conduit 9; A feeding pipe group, the feeding pipe group includes a mixing pipe valve 11 and a rotary valve group 12 connected to the top of the main material pipe bin 7; the mixing pipe valve 11 is connected to a high-position mixing tank; the rotary valve group 12 is connected to a high-position additive storage tank; the top of the dripping pipe bin 8 is connected to a double-valve pipe group; the other end of the double-valve pipe group is connected to a high-position dripping agent storage tank; A pressure regulating module, the pressure regulating module comprises a pressure regulating valve 13 connected to one end of the heat exchange tube 6; the other end of the pressure regulating valve 13 is connected to a pressure gas source; the other end of the heat exchange tube 6 is connected to a first three-way valve 14, the other two ends of the first three-way valve 14 are respectively connected to the middle end of a double-valve pipe group and a second three-way valve 15; the other two ends of the first three-way valve 14 are respectively connected to the middle end of another double-valve pipe group and the top of the main material pipe bin 7; the pressure gas sent by the pressure gas source is sent to the buffer pipe bin after pressure regulation and temperature control, and the pressure difference between the outlet of the conduit 9 and the inside of the conduit 9 can be eliminated through the pressure gas source, so that the conduit 9 can be smoothly discharged and dripped; A waste liquid circulation unit, the waste liquid circulation unit includes a reflux pump 16, and also includes a high-position valve body 17 and a low-position valve body 18 connected to the upper and lower parts of the generating reaction kettle 1, the other ends of the high-position valve body 17 and the low-position valve body 18 are connected to the input end of the reflux pump 16, and the output end of the reflux pump 16 is connected to the top of the main material pipe bin 7 through a one-way valve 19; the reflux pump 16 can pump out the waste liquid or reaction tail liquid that completes a reaction in the generating reaction kettle 1 through the high-position valve body 17 or the low-position valve body 18, and send it to the main material pipe bin 7 for mixing and diluting the powder additive, so that the powder additive can be added to the generating reaction kettle 1 separately, and the main material pipe bin 7 can be flushed at the same time, so that the ingredients are completely sent to the generating reaction kettle 1, ensuring the balanced ingredients of the reaction system in the generating reaction kettle 1.

[0022] The double-valve pipe group includes an upper valve body 20 and a lower valve body 21 connected in series with each other, and the first three-way valve 14 or the second three-way valve 15 is connected to the output end of the upper valve body 20 through a one-way valve 19; the upper valve body 20 and the lower valve body 21 are opened alternately, and when the upper valve body 20 is opened, a certain amount of reaction droplets are delivered between the upper valve body 20 and the lower valve body 21. After the liquid delivery is completed, the upper valve body 20 is closed, and then the lower valve body 21 is opened, and a certain amount of droplets are intermittently or continuously dripped into the generating reaction kettle 1 through a pressure gas source.

[0023] The mixing tank includes a tank body 22, on which an electric stirring paddle 23 is provided, and on which a metering valve 24 is provided. The other end of the metering valve 24 is connected to a plurality of groups of liquid dispensing pipe valves 25, and the other ends of the liquid dispensing pipe valves 25 are respectively connected to high-position liquid dispensing storage tanks; the tank body 22 is also provided with a solid powder supply pipe 26, and the solid powder supply pipe 26 is connected to the powder storage tank through a rotary valve 27 or a metering screw; the liquid dispensing pipe valves 25 perform dispensing in sequence, and during dispensing, one of the dispensing pipe valves sends the corresponding reaction liquid to the metering valve 24, which is metered by the metering valve 24 and then sent to the tank body 22, and then the next reaction liquid is dispensed through the next dispensing pipe valve; then, a certain amount of solid powder is sent into the tank body 22 through the rotary valve 27 or the metering screw, and finally, the solid material and the liquid material are fully mixed by the electric stirring paddle 23 to obtain a solid-liquid mixture.

[0024] The dripping agent storage tank and the main material pipe bin 7 are provided with exhaust pipe valves, through which the pressurized gas can be discharged to ensure smooth material discharge next time.

[0025] The temperature control system 5 includes a circulation pipe group connected in series with the tube seat 3, and a circulation pump and a temperature control source are connected in series to the circulation pipe group. The temperature control source is a heating source or a cooling source. The temperature control liquid is heated or cooled to a set temperature inside the temperature control source. Then, the temperature control liquid is injected into the inner side of the tube seat 3 through the circulation pump and the circulation pipe group. After the heat exchange is completed, the temperature control liquid is sent to the temperature control source through the circulation pipe group for precise temperature adjustment.

[0026] The top surface of the orifice plate 4 is cast with a sealing filler 28; the outside of the pipe seat 3 is provided with a heat-insulating jacket, and the orifice plate 4 and the conduit 9 are sealed and welded, and then the sealing filler 28 is cast, thereby ensuring the internal sealing performance of the pipe seat 3 and preventing the temperature control liquid of the temperature control system 5 from overflowing.

[0027] A one-way valve 19 is provided between the dropper bin 8 and the conduit 9. When the reaction kettle 1 is in a high-pressure state, the one-way valve 19 can be tightened until the one-way valve 19 is pushed open by an external pressure gas source, and the liquid can drip smoothly. By controlling the pressure difference at both ends of the one-way valve 19, the opening of the one-way valve 19 can be controlled, thereby achieving accurate dripping into the reaction kettle 1.

[0028] The controller is built with a dripping timing feeding module, a batching timing feeding module and an auxiliary agent timing feeding module; the working process of the dripping timing feeding module is as follows: first, the total amount of dripping, the dripping start time and the dripping cut-off time are set through the dripping timing feeding module, the controller calculates the dripping time according to the dripping start time and the dripping cut-off time, and calculates the dripping amount per unit time according to the total amount of dripping divided by the dripping time, wherein the time can be set to 0.5~10min as a measurement unit, then, the controller uses the dripping amount per unit time as an index to query the preset association table of dripping amount and pressure difference to obtain the pressure difference value, then the controller times, when the dripping start time is reached, the controller triggers the first three-way valve 14 and the second three-way valve 15 to open, connects the pressure gas source and the double-valve pipe group, the controller monitors the pressure value of the reactor 1 in real time through the pressure transmitter 2, and superimposes the collected pressure value with the queried pressure difference value to obtain the pressure value output by the pressure regulating valve 13; The working process of the batching timing feeding module is as follows: first, the batching parameters are set through the batching timing feeding module. The batching parameters can be added and modified multiple times. The batching parameters include the total amount of batching and the batching feeding cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is as follows: the controller starts timing. When the batching feeding time is reached, the controller triggers the first three-way valve 14 and the second three-way valve 15 to open, connect the pressure gas source with the main material pipe bin 7, disconnect the pressure gas source and the double valve pipe group connection pipeline, and then the controller controls the pressure regulating valve 13 to output the pressure that is the sum of the real-time monitored pressure value of the reactor 1 and the preset pressure value; then, the bottom valve 10 is opened, The controller starts timing, and when the timing time is reached, the waste liquid circulation unit works, and the high-level valve body 17 and the low-level valve body 18 are opened. When the pharmaceutical intermediate product is a precipitate, the high-level valve body 17 is opened, and when the pharmaceutical intermediate product is a floating object or a precipitate, the low-level valve body 18 is opened, and the main material pipe bin 7 is flushed with the liquid that has completed the reaction in the generation reaction kettle 1, and the ingredients are flushed into the generation reaction kettle 1; then, the bottom valve 10 is closed, and the drain valve is opened; after completing one batching addition, the controller returns to the dripping timing feeding module working process, and at the same time, the controller monitors and determines whether the batching addition cycle has been reached. If it has been reached, the next batching timing feeding module is entered; The working process of the additive timing feeding module is as follows: First, the batching parameters are set through the additive timing feeding module. The batching parameters can be added and modified multiple times. The batching parameters include the total amount of ingredients and the batching cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is as follows: The controller starts timing, and when the time for adding the auxiliary agent is reached, the rotary valve group 12 delivers the set total amount of auxiliary agent to the main material pipe bin 7, and the controller adjusts the pressure of the pressure regulating module according to the process of the batching timing feeding module. Then, the bottom valve 10 is opened, and at the same time, the waste liquid circulation unit works to pump the liquid that has completed the reaction into the main material pipe bin 7, mix it with the auxiliary agent in the main material pipe bin 7, and flush it into the generating reaction kettle 1; when the reflux pump 16 reaches the set working time, the reflux pump 16 is shut down, the bottom valve 10 is closed, and the drain valve is opened; after completing one auxiliary agent addition, the controller returns to the working process of the dripping timing feeding module, and at the same time, the controller monitors and determines whether the auxiliary agent addition cycle is reached. If it is reached, it enters the next auxiliary agent timing feeding module; the total amount of dripping and the total amount of batching are respectively measured and obtained by the metering unit valve group on the mixing pipe valve 11 and the rotary valve group 12.

[0029] The association table is obtained through theoretical calculation or actual test. During the actual test, the two ends of the conduit 9 are respectively connected to two pressure vessels at high and low positions, and the rated pressure is given to the pressure vessel at the low position. Then, dripping liquid is injected into the pressure vessel at the high position. After the pressure is stabilized, the relationship between the dripping amount and the pressure difference can be tested. The pressure of the high pressure vessel is changed to test the dripping amount per unit time.

[0030] The above embodiments are only preferred implementations of the present invention, so any equivalent changes or modifications made according to the structures, features and principles described in the scope of application of the present invention are included in the scope of application of the present invention.

Claims

1. A pharmaceutical intermediate production device with timed feeding, comprising a production reactor, wherein a pressure transmitter is provided on the production reactor; characterized in that: It also includes a timed feeding device, which includes a controller for controlling the entire machine; A tube seat, wherein the upper and lower parts of the inner side of the tube seat are respectively integrally formed into perforated plates, and the bottom of the tube seat is fixed to the feed port of the generating reactor; the tube seat is connected to a temperature control system; a U-shaped heat exchange tube is arranged inside the tube seat, and both ends of the heat exchange tube extend out of the tube seat; The buffer tube bin includes a main material tube bin and two dripping tube bins; the main material tube bin and the dripping tube bin are both connected at the bottom with a conduit, the conduit movably penetrates the two orifice plates and extends out of the bottom of the tube seat; the conduit is sealed and welded with the orifice plates; a bottom valve is provided between the main material tube bin and the conduit; A feeding pipe group, the feeding pipe group includes a mixing pipe valve and a rotary valve group connected to the top of the main material pipe bin; the mixing pipe valve is connected to a high-position mixing tank; the rotary valve group is connected to a high-position additive storage tank; the top of the dripping pipe bin is connected to a double-valve pipe group; the other end of the double-valve pipe group is connected to a high-position dripping agent storage tank; A pressure regulating module, the pressure regulating module comprising a pressure regulating valve connected to one end of the heat exchange tube; the other end of the pressure regulating valve is connected to a pressure gas source; the other end of the heat exchange tube is connected to a first three-way valve, the other two ends of the first three-way valve are respectively connected to the middle end of a double-valve pipe group and the second three-way valve; the other two ends of the first three-way valve are respectively connected to the middle end of another double-valve pipe group and the top of the main material pipe bin; A waste liquid circulation unit, which includes a reflux pump, and also includes a high-position valve body and a low-position valve body connected to the upper and lower parts of the generating reactor, the other ends of the high-position valve body and the low-position valve body are connected to the input end of the reflux pump, and the output end of the reflux pump is connected to the top of the main material pipe bin through a one-way valve.

2. The pharmaceutical intermediate production equipment with timed feeding according to claim 1, characterized in that: The double-valve pipe set includes an upper valve body and a lower valve body connected in series with each other, and the first three-way valve or the second three-way valve is connected to the output end of the upper valve body through a one-way valve.

3. The pharmaceutical intermediate production equipment with timed feeding according to claim 1 is characterized in that: The mixing tank includes a tank body, an electric stirring paddle is provided on the tank body, a metering valve is provided on the tank body, the other end of the metering valve is connected to multiple groups of liquid distribution pipe valves, and the other ends of the liquid distribution pipe valves are respectively connected to high-position liquid distribution storage tanks; a solid powder supply pipe is also provided on the tank body, and the solid powder supply pipe is connected to the powder storage tank through a rotary valve or a metering screw.

4. The pharmaceutical intermediate production equipment with timed feeding according to claim 1 is characterized in that: The dripping agent storage tank and the main material pipe bin are provided with exhaust pipe valves.

5. The pharmaceutical intermediate production equipment with timed feeding according to claim 1 is characterized in that: The temperature control system comprises a circulation pipe group connected in series with the pipe seat, and a circulation pump and a temperature control source are connected in series to the circulation pipe group.

6. The pharmaceutical intermediate production equipment with timed feeding according to claim 1 is characterized in that: The top surface of the orifice plate is cast with sealing filler; the outside of the pipe seat is provided with a heat-insulating jacket.

7. The pharmaceutical intermediate production equipment with timed feeding according to claim 1 is characterized in that: A one-way valve is arranged between the drip tube bin and the conduit.

8. The pharmaceutical intermediate production equipment with timed feeding according to claim 1 is characterized in that: The controller is built with a dripping timing feeding module, an ingredient timing feeding module and an auxiliary agent timing feeding module; the working process of the dripping timing feeding module is as follows: first, the total amount of dripping, the dripping start time and the dripping cut-off time are set through the dripping timing feeding module, the controller calculates the dripping duration according to the dripping start time and the dripping cut-off time, and calculates the dripping amount per unit time according to the total amount of dripping divided by the dripping duration, wherein the time can be set to 0.5~10min as a measurement unit, then, the controller uses the dripping amount per unit time as an index, queries the preset association table of dripping amount and pressure difference, and obtains the pressure difference value, then the controller times, when the dripping start time is reached, the controller triggers the first three-way valve and the second three-way valve to open, connects the pressure gas source and the double-valve pipe group, the controller monitors the pressure value of the reactor in real time through the pressure transmitter, and superimposes the collected pressure value with the queried pressure difference value to obtain the pressure value output by the pressure regulating valve; The working process of the batching timing feeding module is as follows: first, the batching parameters are set through the batching timing feeding module. The batching parameters can be added and modified multiple times. The batching parameters include the total amount of batching and the batching feeding cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is as follows: the controller starts timing. When the batching feeding time is reached, the controller triggers the first three-way valve and the second three-way valve to open, connect the pressure gas source with the main material pipe bin, disconnect the pressure gas source and the double-valve pipe group connection pipeline, and then the controller controls the pressure regulating valve to output the pressure of the real-time monitored reactor pressure value and the preset pressure value; then, the bottom valve is opened , the controller starts timing, and when the timing time is reached, the waste liquid circulation unit works, and the high-level valve body and the low-level valve body are selected to be opened. When the pharmaceutical intermediate product is a precipitate, the high-level valve body is opened, and when the pharmaceutical intermediate product is a floating object or a precipitate, the low-level valve body is opened, and the main material pipe bin is flushed with the liquid that has completed the reaction in the generation reaction kettle, and the ingredients are flushed into the generation reaction kettle; then, the bottom valve is closed and the drain valve is opened; after completing one batching addition, the controller returns to the drip timing feeding module workflow, and at the same time, the controller monitors and determines whether the batching addition cycle has been reached. If it has been reached, it enters the next batching timing feeding module; The working process of the additive timing feeding module is as follows: First, the batching parameters are set through the additive timing feeding module. The batching parameters can be added and modified multiple times. The batching parameters include the total amount of ingredients and the batching cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is as follows: The controller starts timing, and when the additive addition time is reached, the rotary valve group delivers the set total amount of additives to the main material pipe bin, and the controller adjusts the pressure of the pressure regulating module according to the process of the batching timing feeding module. Then, the bottom valve is opened, and at the same time, the waste liquid circulation unit works to pump the liquid that has completed the reaction into the main material pipe bin, mix it with the additive in the main material pipe bin, and flush it into the generating reaction kettle; when the reflux pump reaches the set working time, the reflux pump is shut down, the bottom valve is closed, and the drain valve is opened; after completing one additive addition, the controller returns to the drip timing feeding module workflow, and at the same time, the controller monitors and determines whether the additive addition cycle has been reached. If reached, it enters the next additive timing feeding module; the total amount of dripping and the total amount of ingredients are respectively measured and obtained by the metering unit valve group on the mixing pipe valve and the rotary valve group.

9. The pharmaceutical intermediate production equipment with timed feeding according to claim 8, characterized in that: The association table is obtained through theoretical calculation or actual test. During the actual test, the two ends of the catheter are respectively connected to two pressure vessels at high and low positions, and the rated pressure is given to the pressure vessel at the low position. Then, dripping liquid is injected into the pressure vessel at the high position. After the pressure is stabilized, the relationship between the dripping amount and the pressure difference can be tested. The pressure of the high pressure vessel is changed to test the dripping amount per unit time.

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