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CN-121988267-A - Reaction kettle for synthesizing medical intermediate and method thereof

CN121988267ACN 121988267 ACN121988267 ACN 121988267ACN-121988267-A

Abstract

The invention relates to the field of pharmaceutical engineering and automatic control, in particular to a reaction kettle for synthesizing a medical intermediate and an intelligent control method thereof; the system comprises a reaction kettle main body, a stirring component integrating a dynamic torque sensor and a thermal pipeline component, wherein the system firstly performs no-load calibration to draw a mechanical friction loss curve and a heat transfer coefficient map, utilizes real-time torque to deduct friction reference to invert apparent viscosity in operation and combine a reaction heat rate to judge a reaction stage, further performs dynamic heat balance control, and selectively performs medium temperature change compensation or rotational speed shearing strategy according to heat transfer deviation.

Inventors

  • WANG PENGHUI
  • CHEN CAIJIE
  • ZHAO WEIHUA
  • WANG DAN
  • WANG LIBIN

Assignees

  • 陕西蒲城万德科技有限公司

Dates

Publication Date
20260508
Application Date
20260408

Claims (10)

  1. 1. An intelligent control method for a medical intermediate synthesis process is characterized by comprising the following steps: S1, a reaction kettle main body (100), a stirring assembly (200) and a thermal pipeline assembly (300) are arranged, wherein the stirring assembly (200) comprises a servo motor (210), a dynamic torque sensor (220) and a double-layer screw propeller (240), the dynamic torque sensor (220) is connected in series between the servo motor (210) and the double-layer screw propeller (240), the reaction kettle main body (100) is provided with a liquid level detection assembly (130), and the thermal pipeline assembly (300) is connected to a jacket of the reaction kettle main body (100); S2, performing no-load calibration and thermodynamic reference construction, driving the servo motor (210) to step up to draw a no-load mechanical friction loss curve, adding an inert solvent for thermal circulation, and reversely deducing comprehensive heat transfer coefficient maps under different liquid levels based on the data of the liquid level detection assembly (130); S3, starting feeding and executing state soft measurement, deducting a reference value corresponding to the friction loss curve by utilizing real-time torque to invert real-time apparent viscosity, calculating real-time reaction heat rate based on a thermodynamic pipeline parameter and temperature change in a kettle, and judging a reaction stage according to the real-time reaction heat rate and the change rate of the real-time apparent viscosity; S4, executing dynamic heat balance control, comparing the theoretical heat transfer coefficient and the actual heat transfer coefficient in real time in a stable reaction increasing period, judging the reason of heat transfer decline according to the difference value of the theoretical heat transfer coefficient and the actual heat transfer coefficient and the real-time apparent viscosity and the Reynolds number, and selecting one of the overdrive compensation strategy for regulating the temperature of the medium and the physical shearing strategy for regulating the rotating speed until the reaction reaches a preset end point.
  2. 2. The method according to claim 1, wherein in the step S3, the inversion process of the real-time apparent viscosity comprises: -reading a real-time torque value of the dynamic torque sensor (220); Subtracting the friction torque corresponding to the friction loss curve of the no-load machine at the current rotating speed to obtain the net fluid torque; Establishing a physical relationship between the net fluid torque, the stirring rotating speed and a preset blade power standard number; The real-time apparent viscosity characterizing the polymerization degree or crystallization state of the medical intermediate is calculated.
  3. 3. The intelligent control method for a pharmaceutical intermediate synthesis process according to claim 1, wherein in the step S3, the calculation of the real-time reaction heat rate includes: Calculating the product of the inlet and outlet temperature difference, the real-time flow and the specific heat capacity of the medium of the thermal pipeline assembly (300) to obtain the jacket exchange heat power; calculating the product of the total mass of the materials in the kettle, the specific heat capacity of the materials under the current working condition and the temperature change rate in the kettle to obtain the sensible heat change power of the materials; and superposing the jacket heat exchange power and the material sensible heat change power, and subtracting the mechanical heat input by stirring to obtain the real-time reaction heat rate.
  4. 4. The method according to claim 1, wherein in the step S3, the decision logic of the reaction stage comprises: When the first derivative of the real-time reaction heat rate is positive and exceeds a set positive threshold value, and the real-time apparent viscosity keeps low-order stable, judging a reaction initiation period; Judging a stable increase period when the first derivative of the real-time reaction heat rate falls back to be fluctuating near zero and the real-time apparent viscosity shows linear or exponential rise; A reaction decay period is determined when the first derivative of the real-time heat of reaction rate is negative and the real-time apparent viscosity tends to be constant.
  5. 5. The intelligent control method for synthesizing process of pharmaceutical intermediate according to claim 1, wherein in step S4, the calculation of the theoretical heat transfer coefficient and the actual heat transfer coefficient comprises: Calculating a Reynolds number based on the real-time apparent viscosity, the stirring rotation speed and the geometric parameters of the reaction kettle main body (100); Deducing a theoretical liquid side heat transfer film coefficient under the smooth wall surface condition according to the Noval rule correlation; Calculating the current actual heat transfer coefficient by combining the real-time reaction heat rate and Newton's law of cooling; And calculating the difference between the theoretical liquid side heat transfer film coefficient and the actual heat transfer coefficient, and defining the difference as additional thermal resistance equivalent.
  6. 6. The intelligent control method for pharmaceutical intermediate synthesis process according to claim 5, wherein in step S4, the specific strategy of dynamic heat balance control comprises: If the actual heat transfer coefficient is obviously lower than the theoretical liquid side heat transfer film coefficient and the difference value exceeds a preset threshold value, judging that the heat resistance caused by inner wall scaling is increased, and controlling the thermodynamic pipeline assembly (300) to enlarge the temperature difference between a medium and a material so as to perform overdrive temperature compensation; and if the difference value between the actual heat transfer coefficient and the theoretical liquid side heat transfer film coefficient is in the allowable range, judging that the high-viscosity laminar flow thermal boundary layer is too thick, controlling the servo motor (210) to increase the rotating speed, and enhancing the wall turbulence degree by using the double-layer propeller (240).
  7. 7. The intelligent control method for synthesizing a pharmaceutical intermediate according to claim 4, wherein the step of S4 further comprises: Executing feed-forward temperature control when the reaction initiation period is determined; predicting the heat accumulation amount at the future moment according to the rising trend of the real-time reaction heat rate; Before the reaction heat peak value reaches, the thermodynamic pipeline assembly (300) is controlled to reduce the medium input opening degree in advance or switch the low-temperature medium.
  8. 8. The intelligent control method for the synthesis process of the pharmaceutical intermediate according to claim 1, wherein in the step of S1, the liquid level detection assembly (130) adopts a non-contact radar liquid level sensor, a probe of the non-contact radar liquid level sensor is vertically and downwardly aligned with the liquid level in the kettle, the dynamic torque sensor (220) is connected through a rigid coupling, and the double-layer screw belt propeller (240) comprises an outer layer lifting screw belt and an inner layer pressing screw belt.
  9. 9. A reaction kettle device for synthesizing a pharmaceutical intermediate, comprising: The reaction kettle main body (100) comprises an inner container (110) and a diversion jacket (120) coated outside the inner container (110); The stirring assembly (200) is arranged on the reaction kettle main body (100) and comprises a servo motor (210), a dynamic torque sensor (220) and a double-layer screw propeller (240); a thermal conduit assembly (300) in communication with the diversion jacket (120); A controller (400); The dynamic torque sensor (220) is arranged between the output end of the servo motor (210) and the stirring shaft (230) of the double-layer propeller (240); The controller (400) is electrically connected to the servo motor (210), the dynamic torque sensor (220) and the thermal pipeline assembly (300), respectively, for controlling the above mechanisms based on sensor feedback to perform the method steps of any one of claims 1 to 8.
  10. 10. The reaction kettle device for synthesizing pharmaceutical intermediates according to claim 9, wherein a radar liquid level detecting assembly (130) is mounted on a kettle cover (115) of the reaction kettle main body (100), a spiral guide plate is arranged in the guide jacket (120), and a flowmeter and a thermometer are arranged on the thermal pipeline assembly (300).

Description

Reaction kettle for synthesizing medical intermediate and method thereof Technical Field The invention relates to the technical field of pharmaceutical engineering and industrial automation control, in particular to a reaction kettle for synthesizing a medical intermediate and a method thereof. Background In the synthesis process of the medical intermediate, the reaction process is usually carried out in a closed reaction kettle, and is accompanied by dynamic changes of rheological characteristics such as material viscosity, density and the like and complicated heat absorption and release effects. The existing control scheme generally adopts a static heat transfer model and mainly depends on a temperature sensor to monitor the temperature in a kettle to infer the reaction progress, although the scheme has certain monitoring capability under the conventional working condition, the scheme cannot effectively strip the interference of mechanical friction of equipment and basic thermal resistance to measured data, and cannot distinguish whether the heat transfer efficiency is reduced due to the increase of thermal resistance caused by scaling of an inner wall or the thickening of a boundary layer caused by the increase of viscosity of materials, so that the reaction progress is invisible, and in addition, the method only depends on the obvious hysteresis of temperature monitoring, cannot timely sense the mutation of the reaction heat rate, and is difficult to support the accurate prediction and feedforward control of a large-inertia thermodynamic system. Therefore, how to eliminate measurement interference to get insight into the real reaction process in the kettle and realize accurate heat balance self-adaptive control based on dynamic sensing becomes a technical problem to be solved. Disclosure of Invention In view of the above shortcomings of the prior art, an object of the present invention is to provide a reaction kettle for synthesizing a pharmaceutical intermediate and a method thereof, which can solve the technical problems existing in the prior art, and specifically, the technical scheme of the present invention is as follows: an intelligent control method for a medical intermediate synthesis process comprises the following steps: S1, arranging a reaction kettle main body, a stirring assembly and a thermal pipeline assembly, wherein the stirring assembly comprises a servo motor, a dynamic torque sensor and a double-layer screw propeller, the dynamic torque sensor is connected in series between the servo motor and the double-layer screw propeller, the reaction kettle main body is provided with a liquid level detection assembly, and the thermal pipeline assembly is connected to a jacket of the reaction kettle main body; S2, performing no-load calibration and thermodynamic reference construction, driving the servo motor to step up to draw a no-load mechanical friction loss curve, adding an inert solvent for thermal circulation, and reversely deducing comprehensive heat transfer coefficient maps under different liquid levels based on the data of the liquid level detection assembly; S3, starting feeding and executing state soft measurement, deducting a reference value corresponding to the friction loss curve by utilizing real-time torque to invert real-time apparent viscosity, calculating real-time reaction heat rate based on a thermodynamic pipeline parameter and temperature change in a kettle, and judging a reaction stage according to the real-time reaction heat rate and the change rate of the real-time apparent viscosity; S4, executing dynamic heat balance control, comparing the theoretical heat transfer coefficient and the actual heat transfer coefficient in real time in a stable reaction increasing period, judging the reason of heat transfer decline according to the difference value of the theoretical heat transfer coefficient and the actual heat transfer coefficient and the real-time apparent viscosity and the Reynolds number, and selecting one of the overdrive compensation strategy for regulating the temperature of the medium and the physical shearing strategy for regulating the rotating speed until the reaction reaches a preset end point. Preferably, in the step of S3, the inversion process of the real-time apparent viscosity includes: Reading a real-time torque value of the dynamic torque sensor; Subtracting the friction torque corresponding to the friction loss curve of the no-load machine at the current rotating speed to obtain the net fluid torque; Establishing a physical relationship between the net fluid torque, the stirring rotating speed and a preset blade power standard number; The real-time apparent viscosity characterizing the polymerization degree or crystallization state of the medical intermediate is calculated. Preferably, in the step of S3, the calculation of the real-time reaction heat rate includes: Calculating the product of the inlet and outlet temperature difference, the real-tim