A pharmaceutical intermediate production device with timed feeding

Abstract

The present invention discloses a pharmaceutical intermediate production device with timed feeding, belonging to the technical field of pharmaceutical intermediate production devices, including a production reaction kettle, on which a pressure transmitter is provided; it also includes a timed feeding device, which includes a controller for overall control, a pipe seat, a buffer pipe bin, a feeding pipe group, a pressure regulating module and a waste liquid circulation unit. Porous plates are integrally formed on the upper and lower inner sides of the pipe seat respectively, and the bottom of the pipe seat is fixed to the feed inlet of the production reaction kettle; a temperature control system is connected to the pipe seat; a U-shaped heat exchange pipe is arranged inside the pipe seat, and both ends of the heat exchange pipe extend outside the pipe seat. The pharmaceutical intermediate production device with timed feeding of the present invention can completely feed the ingredients into the kettle body, and the feeding process will not damage the pressure environment and temperature environment of the production reaction kettle; enabling the reaction system in the production reaction kettle to carry out precise reactions and ensuring the reaction yield of the pharmaceutical intermediate.

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.

[0005] 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;

[0006] Buffer pipe silo, the buffer pipe silo includes a main material pipe silo and two drip pipe silos; conduits are provided at the bottoms of both the main material pipe silo and the drip pipe silos in a communicating manner, the conduits movably penetrate through two orifice plates and extend out of the bottom of the pipe seat; the conduits are hermetically welded to the orifice plates; a bottom valve is provided between the main material pipe silo and the conduits;

[0007] Feeding pipe group, the feeding pipe group includes a mixing liquid pipe valve and a rotary valve group that communicate with the top of the main material pipe silo; the mixing liquid pipe valve is connected to a high-position mixing liquid tank; the rotary valve group is connected to a high-position additive storage tank; double valve groups are connected to the tops of both drip pipe silos; the other ends of the double valve groups are connected to high-position drip agent storage tanks;

[0008] Pressure regulating module, the pressure regulating module includes a pressure regulating valve that communicates with one end of a heat exchange pipe; the other end of the pressure regulating valve is connected to a pressure gas source; the other end of the heat exchange pipe is connected to a first three-way valve, and the other two ends of the first three-way valve are respectively connected to the middle end of a double valve group and a second three-way valve; the other two ends of the second three-way valve are respectively connected to the middle end of another double valve group and the top of the main material pipe silo; after the pressure gas sent by the pressure gas source is regulated and temperature-controlled, it is sent into the buffer pipe silo, and the pressure difference at the outlet and inside of the conduit can be eliminated through the pressure gas source, enabling the conduit to discharge materials and drip smoothly;

[0009] Waste liquid circulation unit, the waste liquid circulation unit includes a reflux pump, and also includes a high-position valve body and a low-position valve body that communicate with the upper and lower parts of the generating reaction kettle, 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 silo through a check valve; the reflux pump can pump out the waste liquid or reaction tail liquid that has completed one reaction in the generating reaction kettle through the high-position valve body or the low-position valve body and send it into the main material pipe silo for mixing and dilution of powder additives, so that powder additives can be added to the generating reaction kettle separately, and at the same time, the main material pipe silo can be flushed, so as to completely send the ingredients into the generating reaction kettle and ensure the balance of the reaction system ingredients in the generating reaction kettle.

[0010] Further, the double valve group includes an upper valve body and a lower valve body connected in series with each other, and the first three-way valve and the second three-way valve are connected to the output end of the upper valve body through check valves; the upper valve body and the lower valve body are opened alternately. When the upper valve body is opened, a certain amount of reaction drip liquid is sent between the upper valve body and the lower valve body. After the liquid delivery is completed, the upper valve body is closed. Then, the lower valve body is opened, and the certain amount of drip liquid is intermittently or continuously dripped into the generating reaction kettle through the pressure gas source.

[0011] Further, the mixing liquid tank includes a tank body, on which an electric stirring paddle is provided, and a metering valve is provided. The other end of the metering valve is connected to multiple groups of liquid dispensing pipe valves, and the other ends of the liquid dispensing pipe valves are respectively connected to the high-position liquid dispensing 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; the liquid dispensing pipe valves carry out batching in sequence. During batching, one of the batching pipe valves sends the corresponding reaction liquid into the metering valve, and after being metered by the metering valve, it is sent into the tank body, and then the next reaction liquid is dispensed through the next batching pipe valve; then, a quantitative solid powder is sent into the tank body through the rotary valve or the metering screw. Finally, the solid material and the liquid material are fully mixed by the electric stirring paddle to obtain a solid-liquid mixture.

[0012] Further, exhaust pipe valves are provided on the dropping agent storage tank and the main material pipe bin, and pressure gas can be discharged through the exhaust pipe valves to ensure smooth feeding next time.

[0013] Further, the temperature control system includes a circulating pipe group connected in series with the pipe seat. A circulating pump and a temperature control source are connected in series on the circulating 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 pumped into the inner side of the pipe seat through the circulating pump and the circulating pipe group. After heat exchange, the temperature control liquid is sent back to the temperature control source through the circulating pipe group for precise temperature adjustment.

[0014] Further, sealing packing is cast on the top surface of the orifice plate; a heat insulation and heat preservation outer sleeve is provided outside the pipe seat. On the basis of the sealed welding of the orifice plate and the conduit, the sealing packing is cast to ensure the sealing performance inside the pipe seat and prevent the temperature control liquid of the temperature control system from overflowing.

[0015] Further, a check valve is provided between the dropping pipe bin and the conduit. When the inside of the generating reaction kettle is in a high-pressure state, the check valve can be tightly closed. Until the external pressure air source opens the check valve, the dropping can proceed smoothly. By controlling the pressure difference at both ends of the check valve, the opening degree of the check valve can be controlled, so as to achieve precise dropping into the generating reaction kettle.

[0016] Further, the controller is built-in with a drip-feeding timing module, a batching timing module, and an additive timing module. The working process of the drip-feeding timing module is as follows: First, set the total drip volume, drip start time, and drip end time through the drip-feeding timing module. The controller calculates the drip duration based on the drip start time and drip end time, and calculates the drip volume per unit time by dividing the total drip volume by the drip duration. Among them, the time can be set from 0.5 to 10 minutes. Then, the controller queries the correlation table of the preset drip volume and pressure difference with the drip volume per unit time as the index to obtain the pressure difference value. Next, the controller starts timing. When the drip start time is reached, the controller triggers the opening of the first three-way valve and the second three-way valve to connect the pressure air source and the double-valve pipe group. The controller monitors the reaction kettle pressure value generated 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.

[0017] The working process of the batching timing module is as follows: First, set the batching parameters through the batching timing module. The batching parameters can be added and modified multiple times. The batching parameters include the total batching volume and the batching feeding cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is specifically as follows: The controller starts timing. When the batching feeding time is reached, the controller triggers the opening of the first three-way valve and the second three-way valve to connect the pressure air source to the main material pipe bin and disconnect the connecting pipeline between the pressure air source and the double-valve pipe group. Then, the controller controls the pressure regulating valve to output a pressure value that is the sum of the reaction kettle pressure value monitored in real time and the preset pressure value. Next, the bottom valve opens, and the controller starts timing. After the timing time is reached, the waste liquid circulation unit works, and the high-position valve body and the low-position valve body are selected to be opened. When the pharmaceutical intermediate product is a precipitate, the high-position valve body is opened. When the pharmaceutical intermediate product is a floating substance or a substance to be precipitated, the low-position valve body is opened. The liquid that has completed the reaction in the reaction kettle is used to wash the main material pipe bin, and the batching is washed into the reaction kettle. Then, the bottom valve is closed, and the exhaust valve is opened. After a batching feeding is completed, the controller returns to the working process of the drip-feeding timing module. At the same time, the controller monitors and determines whether the batching feeding cycle is reached. If it is reached, it enters the next batching timing module.

[0018] The working process of the additive timing module is as follows: First, set the batching parameters through the additive timing module. The batching parameters can be added and modified multiple times. The batching parameters include the total batching volume and the batching feeding cycle. After the controller obtains the batching parameters, it executes the timing feeding process, which is specifically as follows:

[0019] The controller times. When the additive dosing time is reached, the rotary valve group sends the set total amount of additive into the main material pipe bin. The controller adjusts the pressure of the pressure regulating module according to the process of the batching timing feeding module. Then, the bottom valve opens. At the same time, the waste liquid circulation unit works, pumping the liquid that has completed the reaction into the main material pipe bin, mixing it with the additive in the main material pipe bin, and flushing it into the reaction kettle. When the reflux pump reaches the set working duration, the reflux pump stops, the bottom valve closes, and the drain valve opens. After one additive dosing is completed, the controller returns to the working process of the drip liquid timing feeding module. At the same time, the controller monitors and determines whether the additive dosing cycle is reached. If it is reached, it enters the next additive timing feeding module. The total drip liquid amount and the total batching amount are respectively measured and obtained through the metering unit valve group on the mixing liquid pipe valve and the rotary valve group.

[0020] Further, the correlation table is obtained through theoretical calculation or actual test. During actual test, both ends of the conduit 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, drip liquid is injected into the pressure vessel at the high position. After waiting for the pressure to stabilize, the relationship between the drip liquid amount and the pressure difference can be tested. By changing the pressure of the pressure vessel at the high position, the drip liquid amount per unit time can be tested.

[0021] Compared with the prior art, the pharmaceutical intermediate generating equipment with timing feeding of the present invention can send external solid-liquid mixture, separate additives, and drip liquid into the kettle at a fixed time under the high-pressure or vacuum environment of the kettle body. Under the high-pressure state, external pressure matching is used to adjust the pressure difference so that the batching can be completely sent into the kettle. The pressure air source is temperature-controlled by the temperature control system and used as the feeding driving air source, which can preheat the batching. During the process of feeding the material into the kettle, precise temperature control is carried out through the temperature control system, and the feeding process will not damage the pressure environment and temperature environment of the reaction kettle. It enables the reaction system in the reaction kettle to react precisely. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a schematic diagram of the overall structure of the pharmaceutical intermediate generating equipment of the present invention.

[0023] Figure 2 It is a schematic diagram of the structure of the timing feeding device of the pharmaceutical intermediate generating equipment of the present invention.

[0024] Figure 3 It is a schematic diagram of the installation structure of the timing feeding device and the mixing tank of the present invention.

[0025] Figure 4 It is a schematic diagram of the working process structure of the drip liquid timing feeding module of the present invention.

[0026] Figure 5 It is a schematic diagram of the working process structure of the batching timing feeding module of the present invention.

[0027] Figure 6Schematic structural diagram of the working process of the auxiliary agent timing feeding module of the present invention.

[0028] Reference numerals: 1, 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, drip tube bin; 9, conduit; 10, bottom valve; 11, mixed 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-level valve body; 18, low-level 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 mixing pipe valve; 26, solid powder supply pipe; 27, rotary valve; 28, sealing packing. Detailed implementation manners

[0029] Example 1:

[0030] As Figures 1 to 6 shown, the pharmaceutical intermediate generation equipment with timing feeding includes a reaction kettle 1, and a pressure transmitter 2 is arranged on the reaction kettle 1; it also includes a timing feeding device, and the timing feeding device includes a controller for overall machine control.

[0031] Pipe seat 3, orifice plates 4 are integrally formed on the upper and lower parts inside the pipe seat 3 respectively, and the bottom of the pipe seat 3 is fixed to the feed inlet of the reaction kettle 1; a temperature control system 5 is connected to the pipe seat 3; a U-shaped heat exchange tube 6 is arranged inside the pipe seat 3, and both ends of the heat exchange tube 6 extend outside the pipe seat 3.

[0032] Buffer pipe bin, the buffer pipe bin includes a main material pipe bin 7 and two drip tube bins 8; conduits 9 are communicated at the bottoms of the main material pipe bin 7 and the drip tube bins 8, the conduits 9 movably penetrate through the two orifice plates 4 and extend out of the bottom of the pipe seat 3; the conduits 9 are hermetically welded to the orifice plates 4; a bottom valve 10 is arranged between the main material pipe bin 7 and the conduit 9.

[0033] Feeding pipe group, the feeding pipe group includes a mixed liquid pipe valve 11 communicated with the top of the main material pipe bin 7 and a rotary valve group 12; the mixed liquid pipe valve 11 is connected to a high-level mixed liquid tank; the rotary valve group 12 is connected to a high-level additive storage tank; double-valve pipe groups are connected to the tops of the drip tube bins 8; the other ends of the double-valve pipe groups are connected to high-level drip agent storage tanks.

[0034] Pressure regulating module, the pressure regulating module includes a pressure regulating valve 13 communicated with one end of a 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, and the other two ends of the first three-way valve 14 are respectively connected to the middle end of a double-valve tube group and a second three-way valve 15; the other two ends of the second three-way valve 15 are respectively connected to the middle end of another double-valve tube group and the top of the main material pipe bin 7; after the pressure gas sent out by the pressure gas source is regulated and temperature-controlled, it is sent into the buffer pipe bin. By the pressure gas source, the pressure difference at the outlet and inside of the conduit 9 can be eliminated, so that the conduit 9 can discharge materials and drip smoothly.

[0035] 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 communicated with 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 has completed one reaction in the generating reaction kettle 1 through the high-position valve body 17 or the low-position valve body 18 and send it into the main material pipe bin 7 for mixing and diluting the powder additives, so that the powder additives can be added into the generating reaction kettle 1 separately, and at the same time, the main material pipe bin 7 can be flushed, so as to send the ingredients completely into the generating reaction kettle 1 and ensure the ingredient balance of the reaction system in the generating reaction kettle 1.

[0036] The double-valve tube group includes an upper valve body 20 and a lower valve body 21 connected in series. The first three-way valve 14 and the second three-way valve 15 are 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. When the upper valve body 20 is opened, a quantitative reaction drip is sent 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. Then, the lower valve body 21 is opened, and the quantitative drip is intermittently or continuously dripped into the generating reaction kettle 1 through the pressure gas source.

[0037] The mixing liquid tank includes a tank body 22, an electric stirring paddle 23 is arranged on the tank body 22, a metering valve 24 is arranged on the tank body 22, the other end of the metering valve 24 is connected to a plurality of liquid distribution pipe valves 25, and the other ends of the liquid distribution pipe valves 25 are respectively connected to high-position liquid distribution storage tanks; a solid powder supply pipe 26 is also arranged on the tank body 22, and the solid powder supply pipe 26 is connected to a powder storage tank through a rotary valve 27 or a metering screw; the liquid distribution pipe valves 25 carry out batching in sequence. When batching, one of the batching pipe valves sends the corresponding reaction liquid into the metering valve 24. After being metered by the metering valve 24, it is sent into the tank body 22. Then, the next batching pipe valve is used for batching the next reaction liquid; then, a quantitative solid powder is sent into the interior of the tank body 22 through the rotary valve 27 or the metering screw. Finally, the solid material and the liquid material are fully mixed by the electric stirring paddle 23 to obtain a solid-liquid mixture.

[0038] An exhaust pipe valve is provided on the drip agent storage tank and the main material pipe bin 7. Through the exhaust pipe valve, the pressure gas can be discharged externally to ensure smooth feeding next time.

[0039] The temperature control system 5 includes a circulating pipe group connected in series with the pipe seat 3. A circulating pump and a temperature control source are connected in series on the circulating 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 pumped into the inner side of the pipe seat 3 through the circulating pump and the circulating pipe group. After heat exchange, the temperature control liquid is sent back to the temperature control source through the circulating pipe group for precise temperature adjustment.

[0040] Sealing filler 28 is cast on the top surface of the orifice plate 4; an insulating and heat-preserving jacket is provided outside the pipe seat 3. On the basis of the sealed welding of the orifice plate 4 and the conduit 9, the sealing filler 28 is cast, so as to ensure the internal sealing performance of the pipe seat 3 and prevent the temperature control liquid of the temperature control system 5 from overflowing.

[0041] A one-way valve 19 is provided between the drip pipe bin 8 and the conduit 9. When the high-pressure state exists in the reaction kettle 1, the one-way valve 19 can be tightly closed. Until the external pressure gas source opens the one-way valve 19, the drip can smoothly drop. By controlling the pressure difference at both ends of the one-way valve 19, the opening degree of the one-way valve 19 can be controlled, so as to accurately drip into the reaction kettle 1.

[0042] The controller is built-in with a drip liquid timing feeding module, a batching timing feeding module, and an auxiliary agent timing feeding module; the working process of the drip liquid timing feeding module is as follows: First, set the total drip liquid volume, the drip liquid start time, and the drip liquid end time through the drip liquid timing feeding module. The controller calculates the drip liquid duration according to the drip liquid start time and the drip liquid end time, and calculates the drip liquid volume per unit time by dividing the total drip liquid volume by the drip liquid duration. Among them, the time can be set to 0.5 - 10 min. Then, the controller uses the drip liquid volume per unit time as an index to query the associated table of the preset drip liquid volume and the pressure difference, and obtains the pressure difference value. Then, the controller starts timing. When the drip liquid start time is reached, the controller triggers the opening of the first three-way valve 14 and the second three-way valve 15 to connect the pressure gas source and the double-valve pipe group. The controller monitors the pressure value of the reaction kettle 1 in real time through the pressure transmitter 2, and superimposes the collected pressure value on the queried pressure difference value to obtain the pressure value output by the pressure regulating valve 13;

[0043] The working process of the ingredient timing feeding module is as follows: First, set ingredient parameters through the ingredient timing feeding module. The ingredient parameters can be added and modified multiple times. The ingredient parameters include the total amount of ingredients and the ingredient feeding cycle. After the controller obtains the ingredient parameters, it executes the timing feeding process, which is specifically as follows: The controller starts timing. When it reaches the ingredient feeding time, the controller triggers the opening of the first three-way valve 14 and the second three-way valve 15, connects the pressure air source to the main material pipe bin 7, and disconnects the pressure air source from the pipeline connecting the double-valve group. Then, the controller controls the pressure regulating valve 13 to output a pressure that is the sum of the pressure value of the reaction kettle 1 monitored in real time and the preset pressure value. Next, the bottom valve 10 is opened, and the controller starts timing. After reaching the timing time, the waste liquid circulation unit works, and the high-position valve body 17 and the low-position valve body 18 are selectively opened. When the pharmaceutical intermediate product is a precipitate, the high-position valve body 17 is opened. When the pharmaceutical intermediate product is a floating substance or a substance to be precipitated, the low-position valve body 18 is opened. The liquid that has completed the reaction in the reaction kettle 1 is used to wash the main material pipe bin 7, and the ingredient washing is brought into the reaction kettle 1. Then, the bottom valve 10 is closed, and the exhaust valve is opened. After completing one ingredient feeding, the controller returns to the working process of the drip feeding timing module. At the same time, the controller monitors and determines whether the ingredient feeding cycle is reached. If it is reached, it enters the next ingredient timing feeding module;

[0044] The working process of the auxiliary agent timing feeding module is as follows: First, set ingredient parameters through the auxiliary agent timing feeding module. The ingredient parameters can be added and modified multiple times. The ingredient parameters include the total amount of ingredients and the ingredient feeding cycle. After the controller obtains the ingredient parameters, it executes the timing feeding process, which is specifically as follows:

[0045] The controller starts timing. When it reaches the auxiliary agent feeding time, the rotary valve group 12 sends the set total amount of the auxiliary agent into the main material pipe bin 7. The controller adjusts the pressure of the pressure regulating module according to the process of the ingredient timing feeding module. Then, the bottom valve 10 is opened. At the same time, the waste liquid circulation unit works, pumps the liquid that has completed the reaction into the main material pipe bin 7, mixes it with the auxiliary agent in the main material pipe bin 7, and flushes it into the reaction kettle 1. When the reflux pump 16 reaches the set working duration, the reflux pump 16 stops running, the bottom valve 10 is closed, and the exhaust valve is opened. After completing one auxiliary agent feeding, the controller returns to the working process of the drip feeding timing module. At the same time, the controller monitors and determines whether the auxiliary agent feeding cycle is reached. If it is reached, it enters the next auxiliary agent timing feeding module; The total drip amount and the total amount of ingredients are respectively measured and obtained through the metering unit valve groups on the liquid mixing pipe valve 11 and the rotary valve group 12.

[0046] The correlation table is obtained through theoretical calculation or actual test. During actual test, both ends of the conduit 9 are respectively connected to two pressure vessels at high and low positions, and a rated pressure is given to the pressure vessel at the low position. Then, drip liquid is injected into the pressure vessel at the high position. After waiting for the pressure to stabilize, the relationship between the drip liquid amount and the pressure difference can be tested. By changing the pressure of the pressure vessel at the high position, the drip liquid amount per unit time can be tested.

[0047] The above embodiments are only preferred embodiments of the present invention. Therefore, all equivalent changes or modifications made according to the structures, features, and principles described in the scope of the present invention application are included in the scope of the present invention application.

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 timing 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 second 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 comprises an upper valve body and a lower valve body connected in series with each other, and the first three-way valve and the second three-way valve are 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 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, 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.

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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