Temperature control method and system for preparing bilirubin
Through the multi-stage temperature control method, the problem of inaccurate temperature control during bilirubin synthesis in the prior art is solved, and efficient conversion from bilirubin to bilirubin and high-purity bilirubin preparation are achieved.
Patent Information
- Application Number
- CN202510176702.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-18
- Publication Date
- 2025-05-27
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
When the temperature control is inaccurate and fluctuates greatly, the existing chemical synthesis methods lead to unstable bilirubin reaction process, the resulting bilirubin has low purity and often produces by-products, which requires a complex post-processing process.
A multi-stage temperature control method is adopted, including heating pretreatment, dynamic temperature progressive loading and uniform temperature transition. The temperature is accurately controlled by the temperature-controlled reactor to ensure that the bile verulin is completely dissolved and converted into bilerubin, and a high-purity bilerubin is obtained.
The efficient conversion from biliverin to bilirubin is achieved, and high-purity bilirubin is obtained, reducing the complexity of by-product generation and post-processing.
Smart Images
Figure CN120037853A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of bilirubin preparation, and particularly relates to a temperature control method and system for preparing bilirubin. Background Art
[0002] Bilirubin is one of the products of hemoglobin decomposition and is widely present in the livers and blood of mammals. Its main function is to protect cells from damage by free radicals through antioxidant effects. In addition, bilirubin has important applications in medicine, such as for diagnosing liver diseases, biliary obstruction, and neonatal jaundice. Therefore, the preparation of high-purity bilirubin is of great significance for medical testing, drug research and development, and scientific research.
[0003] Currently, existing chemical synthesis methods usually require complex reaction conditions and strict temperature control. However, inaccurate temperature control and large temperature fluctuations can lead to unstable reaction processes, low purity of the generated bilirubin, and often the generation of by-products, requiring complex post-treatment processes. Summary of the Invention
[0004] The purpose of the present invention is to provide a temperature control method and system for preparing bilirubin to solve the deficiencies in the prior art, and to achieve efficient conversion from biliverdin to bilirubin through precise multi-stage temperature control, thereby obtaining high-purity bilirubin.
[0005] An embodiment of the present application provides a temperature control method for preparing bilirubin, the method comprising: Obtaining a precursor substance of bilirubin, wherein the precursor substance is biliverdin; Dissolving the biliverdin in a physiological buffer solution to form a homogeneous solution; Placing the homogeneous solution in a temperature-controlled reactor for a first-stage duration of heating pretreatment to ensure complete dissolution of the precursor substance and the start of a preliminary reaction; wherein, the temperature change during the heating pretreatment is:
[0006] wherein, is the reaction temperature at time is the initial reaction temperature, is the temperature fluctuation amplitude, is the frequency constant; is the frequency constant;
[0007] Performing dynamic temperature progressive loading for an intermediate reaction of a second-stage duration on the temperature of the temperature-controlled reactor to partially convert biliverdin into bilirubin;
[0008] The temperature in the temperature-controlled reactor is uniformly transitioned for a third-stage duration, and after the reaction ends, the solution is cooled to room temperature to terminate the reaction. Then, the obtained product is centrifuged, and the supernatant is collected to obtain a bilirubin solution.
[0009] Optionally, the temperature change during the dynamic temperature progressive loading process is as follows:
[0010] Among them, is the temperature of the i-th temperature progressive time period, , is the temperature difference range of each step.
[0011] Optionally, the temperature change during the temperature uniform transition process is as follows:
[0012] Among them, is the temperature at time after the uniform transition starts, is the initial adjustment amplitude, is the exponential decay coefficient, is the start time of the uniform transition, is the cosine fluctuation amplitude, is the cosine frequency.
[0013] Another embodiment of the present application provides a temperature control system for preparing bilirubin. The system includes:
[0014] An acquisition module for acquiring a precursor substance of bilirubin, where the precursor substance is biliverdin;
[0015] A dissolution module for dissolving the biliverdin in a physiological buffer solution to form a uniform solution;
[0016] A heating module for placing the uniform solution in a temperature-controlled reactor for a first-stage duration of heating pretreatment to ensure that the precursor substance is completely dissolved and the preliminary reaction starts. Among them, the temperature change during the heating pretreatment process is as follows:
[0017] Among them, is the reaction temperature at time , is the initial reaction temperature, is the temperature fluctuation amplitude, is the frequency constant.
[0018] A progressive module for dynamically loading the temperature of the temperature-controlled reactor for an intermediate reaction of a second-stage duration, so that part of the biliverdin is converted into bilirubin;
[0019] A transition module is used to uniformly transition the temperature in the temperature-controlled reactor for a third-stage duration, and after the reaction ends, cool the solution to room temperature to terminate the reaction, so as to centrifuge the obtained product, collect the supernatant, and obtain a bilirubin solution.
[0020] Another embodiment of the present application provides a storage medium in which a computer program is stored. Wherein, the computer program is set to execute the method described in any one of the above when running.
[0021] Another embodiment of the present application provides an electronic device, including a memory and a processor. A computer program is stored in the memory, and the processor is set to run the computer program to execute the method described in any one of the above.
[0022] Compared with the prior art, a temperature control method for preparing bilirubin provided by the present invention includes obtaining a precursor substance of bilirubin, wherein the precursor substance is biliverdin; dissolving the biliverdin in a physiological buffer to form a uniform solution; placing the uniform solution in a temperature-controlled reactor for a first-stage duration of heating pretreatment to ensure that the precursor substance is completely dissolved and the preliminary reaction starts; performing dynamic temperature progressive loading of an intermediate reaction with a second-stage duration on the temperature of the temperature-controlled reactor to partially convert biliverdin into bilirubin; performing a third-stage duration of temperature uniform transition on the temperature in the temperature-controlled reactor, and after the reaction ends, cooling the solution to room temperature to terminate the reaction, so as to centrifuge the obtained product, collect the supernatant, and obtain a bilirubin solution. Thus, through precise multi-stage temperature control, efficient conversion from biliverdin to bilirubin can be achieved, and high-purity bilirubin can be obtained. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] Figure 1 It is a hardware structure block diagram of a computer terminal for a temperature control method for preparing bilirubin provided by an embodiment of the present invention.
[0024] Figure 2 It is a flow schematic diagram of a temperature control method for preparing bilirubin provided by an embodiment of the present invention.
[0025] Figure 3 It is a structural schematic diagram of a temperature control system for preparing bilirubin provided by an embodiment of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS
[0026] The embodiments described below by referring to the drawings are exemplary and are only used to explain the present invention, and cannot be construed as limiting the present invention.
[0027] An embodiment of the present invention first provides a temperature control method for preparing bilirubin. This method can be applied to an electronic device, such as a computer terminal, specifically, an ordinary computer, etc.
[0028] The following takes running on a computer terminal as an example to elaborate on it in detail. Figure 1 The hardware structure block diagram of a computer terminal for a temperature control method for preparing bilirubin provided by an embodiment of the present invention. As Figure 1 shown, the computer terminal may include one or more ( Figure 1 only one is shown in Figure 1 the figure) processors 102 (the processors 102 may include, but are not limited to, processing devices such as microprocessor MCUs or programmable logic devices FPGAs) and a memory 104 for storing data. Optionally, the above computer terminal may further include a transmission device 106 for communication functions and an input / output device 108. Those of ordinary skill in the art can understand that Figure 1 the structure shown in Figure 1 the figure is only schematic and does not limit the structure of the above computer terminal. For example, the computer terminal may further include more or fewer components than
[0029] shown in
[0030] the figure, or have a different configuration from
[0031] Refer to Figure 2 , an embodiment of the present invention provides a temperature control method for preparing bilirubin, which may include the following steps:
[0032] S201, Obtain the precursor substance of bilirubin, where the precursor substance is biliverdin;
[0033] Specifically, obtaining the precursor substance of bilirubin is one of the important steps in preparing high-purity bilirubin. As the direct precursor of bilirubin, biliverdin needs to undergo precise chemical treatment and purification to ensure the high purity and high efficiency of the ultimately prepared bilirubin. One implementation method may include:
[0034] Step 1: Raw material selection and preparation
[0035] 1. Select suitable raw materials: Generally, biliverdin can be isolated from the decomposition products of animal hemoglobin. Therefore, it is very important to select suitable animal blood as the raw material. The blood of mammals such as pigs or cows is a common choice because their blood contains a relatively high concentration of hemoglobin.
[0036] 2. Collect blood samples: Collect fresh blood samples from the selected animals. It is necessary to ensure that the samples are not contaminated, and it is best to collect them through aseptic operation.
[0037] Step 2: Separation of hemoglobin
[0038] 1. Centrifuge to separate blood cells: Place the collected blood samples in a centrifuge and centrifuge at a speed of 3000 revolutions per minute (rpm) for 10 minutes. After centrifugation, the plasma and blood cells are separated. Collect the blood cell part and discard the supernatant (plasma).
[0039] 2. Rupture of red blood cells: Suspend the separated blood cells in physiological saline and rupture the cells using an ultrasonic crusher. The parameters for ultrasonic crushing are set as follows: frequency 20 kHz, power 150 W, and treatment time 10 minutes.
[0040] 3. Hemoglobin extraction: The broken cell suspension is centrifuged again at a speed of 5000 revolutions per minute (rpm) for 15 minutes. Collect the supernatant, which is the solution containing hemoglobin.
[0041] Step 3: Chemical conversion of biliverdin
[0042] 1. Hemoglobin oxidation: Place the solution containing hemoglobin in an ice bath and gradually add dilute hydrochloric acid (concentration 1M) to acidify the solution to pH 3.5 to 4.0. At this time, hemoglobin is gradually oxidized to methemoglobin.
[0043] 2. Generation of biliverdin: Slowly add hydrogen peroxide (H2O2, concentration 3%) dropwise to the above acidified solution while keeping the solution in an ice bath. The dropping rate of hydrogen peroxide should be controlled at 1 drop per minute, and the whole process lasts for 30 minutes. During the oxidation reaction, hemoglobin is further oxidized and finally converted into biliverdin.
[0044] Step 4: Extraction and purification of biliverdin
[0045] 1. Preliminary separation: After the reaction is completed, add an equal volume of ether and stir to extract biliverdin. Biliverdin dissolves in ether and separates from the aqueous phase. After standing, the ether layer of biliverdin will float on the upper layer, and the ether layer is separated through a separatory funnel.
[0046] 2. Purification of biliverdin: Purify the separated ether solution by silica gel column chromatography. The eluent for silica gel column chromatography can use a mixed solvent of ether and n-hexane (volume ratio 1:1). During the chromatography process, collect the green eluent part.
[0047] 3. Solvent evaporation: Remove the ether and n-hexane solvents from the collected eluent through a rotary evaporator, and finally obtain purified biliverdin solid.
[0048] Step 5: Dissolution and storage of biliverdin
[0049] 1. Dissolution of biliverdin: Dissolve the purified biliverdin solid in a physiological buffer solution (such as phosphate buffer solution, PBS) to form a uniform biliverdin solution. The dissolution process should be carried out under light-proof conditions to prevent the photodegradation of biliverdin.
[0050] 2. Storage of the solution: Store the prepared biliverdin solution in a refrigerator at 4°C for further reactions and use.
[0051] Through the above steps, biliverdin, the precursor of bilirubin, can be obtained efficiently and purely. By adopting these strict experimental steps and condition controls, the high purity and high activity of biliverdin can be ensured, providing a reliable raw material basis for the efficient synthesis of bilirubin in the follow-up.
[0052] S202, dissolve the biliverdin in a physiological buffer solution to form a uniform solution.
[0053] Specifically, effectively dissolving biliverdin in a physiological buffer solution and forming a uniform solution is an important step to ensure the smooth progress of subsequent conversion reactions. Due to the lipophilicity of biliverdin and its instability in aqueous solution, appropriate techniques and steps are required to achieve this process. The following are the detailed implementation steps:
[0054] Step 1: Prepare the physiological buffer solution
[0055] 1. Select buffer type: Select a physiological buffer suitable for the dissolution of biliverdin, such as phosphate buffer (PBS), as it can provide a stable pH environment and reduce the degradation of biliverdin.
[0056] 2. Prepare the buffer: - PBS buffer (pH 7.4) can be prepared in the following ratio: - NaCl: 8.0 g - KCl: 0.2 g - Na2HPO4: 1.44 g - KH2PO4: 0.24 g - Dissolve the above components in 800 mL of deionized water, adjust the pH to 7.4, and then make up to 1 L with deionized water.
[0057] 3. Degas the buffer: Degas the prepared buffer to avoid the influence of oxygen in the solution on the stability of biliverdin. Degassing can be achieved by purging with nitrogen for 20 minutes or by ultrasonic oscillation for 10 minutes.
[0058] Step 2: Pretreatment of biliverdin
[0059] 1. Dry biliverdin: Dry the purified biliverdin obtained from the previous step to remove residual organic solvents. Drying can be carried out in a vacuum drying oven at a temperature of 20 - 25°C for 2 hours.
[0060] 2. Grind biliverdin: To increase the dissolution rate of biliverdin, the dried biliverdin can be ground into a fine powder. Use a mortar or a mechanical grinder for grinding until the biliverdin particles are uniformly fine.
[0061] Step 3: Dissolution operation
[0062] 1. Weigh biliverdin: Accurately weigh the required amount of biliverdin powder, usually at a final concentration of 10 mg / mL. For example, if a final 100 mL biliverdin solution is required, 1 g of biliverdin powder needs to be weighed.
[0063] 2. Dissolve step by step: Add the weighed biliverdin powder to the PBS buffer gradually, rather than all at once, to avoid agglomeration of biliverdin in the solution. Add a small amount of biliverdin each time and stir well until completely dissolved before continuing to add.
[0064] Step 4: Promote dissolution
[0065] 1. Magnetic stirring: During the dissolution process, use a magnetic stirrer for stirring. The stirring speed should be set at 300 - 400 rpm and stir continuously for 30 minutes until the biliverdin is completely and uniformly dissolved.
[0066] 2. Gentle heating: To accelerate the dissolution process, the solution can be placed in a water bath at a temperature controlled at 37 ± 0.5 °C and continuously heated and stirred for 20 minutes. Note that the temperature should not be too high to prevent the decomposition of biliverdin.
[0067] Step 5: Solution homogenization and filtration
[0068] 1. Ultrasonic treatment: If the dissolution is incomplete, ultrasonic treatment can be used for homogenization. Place the solution in an ultrasonic cleaner, set the frequency to 40 kHz, and the treatment time to 10 minutes to ensure the uniformity of the solution.
[0069] 2. Filtration to remove impurities: Filter the dissolved biliverdin solution through a 0.22 μm sterile filter membrane to remove undissolved particles and impurities, ensuring the purity and uniformity of the solution.
[0070] Step 6: Solution storage
[0071] 1. Light protection: Since biliverdin is sensitive to light, the solution should be stored in the dark. Place the filtered biliverdin solution in a brown glass bottle and ensure that the bottle mouth is sealed.
[0072] 2. Low-temperature storage: Store the glass bottle containing the solution in a refrigerator at 4 °C to avoid the degradation of biliverdin caused by high temperature and reduce possible chemical changes in the solution.
[0073] Through the above detailed steps, biliverdin can be effectively dissolved in the physiological buffer to form a uniform solution. These steps include the whole process from preparing the buffer, pre-treating biliverdin to promoting dissolution and storage, ensuring the high purity and stability of the biliverdin solution, and providing a reliable basis for the subsequent preparation of bilirubin. This method not only has clear operating steps but also ensures the uniformity and purity of the solution through multiple means, making it suitable for large-scale industrial production and fine experimental research.
[0074] S203, place the uniform solution in a temperature-controlled reactor for heat pre-treatment for the first-stage duration to ensure that the precursor substances are completely dissolved and the preliminary reaction starts.
[0075] Specifically, a temperature change during the heat pre-treatment can be:
[0076] where is the reaction temperature at time is the initial reaction temperature, is the temperature fluctuation amplitude, is the frequency constant.
[0077] This temperature change formula is used to describe the dynamic change of temperature during the heating pretreatment process. By introducing the form of sinusoidal fluctuation, the temperature can gradually increase in the initial stage, accompanied by periodic fluctuations, so as to avoid the severe stress that the sudden temperature rise may cause to biliverdin or the solution system. This gentle and rhythmic temperature rise helps the complete dissolution and preliminary reaction of biliverdin. The significance and determination method of parameter design.
[0078] 1. Initial reaction temperature:
[0079] - Design significance: As the starting temperature of the reaction, ensure that the temperature environment at the beginning of the experiment is controllable and stable, so as to avoid the adverse effects caused by sudden temperature changes on the system.
[0080] - Determination method: Usually determined according to the physical properties and solubility of biliverdin. For example, if biliverdin has good solubility at 25°C, it can be set to 25°C.
[0081] 2. Temperature fluctuation amplitude:
[0082] - Design significance: Control the temperature fluctuation amplitude , which can ensure that the temperature fluctuates within a suitable range, promote the uniform dissolution of biliverdin and prevent local overheating.
[0083] - Determination method: Determined through experiments. Usually, it can be set to 5 - 10°C to observe the effect in preliminary experiments and adjust according to the reaction requirements.
[0084] 3. Frequency constant:
[0085] - Design significance: Control the frequency of temperature fluctuation, make the temperature change during the heating process smoother and more regular, and help balance the solution thermodynamic environment.
[0086] - Determination method: The appropriate frequency can be determined through experiments. For example, 1 - 2 cycles per minute (the corresponding angular frequency is approximately 0.105 - 0.21 rad / s) to ensure that the frequency of temperature regulation matches the heat balance time of the system.
[0087] Specifically, the heating pretreatment is to place the biliverdin solution in a temperature-controlled reactor, and perform temperature control and adjustment at this stage to ensure the complete dissolution, uniform distribution and start of the preliminary reaction of biliverdin. The temperature control at this stage lays the foundation for the subsequent reaction, and avoids incomplete reactions or the generation of by-products due to insufficient dissolution or local overheating. One implementation method may include:
[0088] Step 1: Pretreatment preparation
[0089] 1. Prepare the temperature-controlled reactor: Select a suitable temperature-controlled reactor and confirm that the reactor has precise temperature control capabilities and a uniform temperature distribution system. Clean and preheat the inner wall of the reactor in advance to ensure no impurity interference.
[0090] 2. Place the biliverdin solution into the reactor: Carefully pour the well-dissolved biliverdin physiological buffer solution into the reactor, ensuring that the liquid is stable and no bubbles are formed. Seal the reactor lid and perform a preliminary vacuum evacuation to remove the bubbles in the solution.
[0091] Step 2: Temperature control settings
[0092] 1. Set the initial temperature: Set the initial reaction temperature (e.g., 25 °C) on the control panel of the reactor, start the temperature-controlled reactor and stabilize it at the set temperature so that the system reaches thermal equilibrium.
[0093] 2. Set the temperature fluctuation parameters: Input the temperature fluctuation amplitude and frequency constant into the control system. For example, , ensure that the control system has loaded the relevant algorithms to adjust the temperature in real time.
[0094] Step 3: Start the heating pretreatment
[0095] 1. Start the reaction program: Start the pretreatment program of the temperature-controlled reactor, so that the heating system dynamically adjusts the temperature according to the above formula. During this process, continuously monitor the temperature and solution state inside the reactor.
[0096] 2. Real-time monitoring and adjustment: Use a temperature sensor and the control system to monitor the temperature inside the reactor in real time. If the detected temperature deviates from the set value, the system will automatically adjust the heating or cooling power. Ensure that the temperature fluctuation is within the set range and changes at a predetermined frequency.
[0097] Step 4: End the first-stage heating pretreatment
[0098] 1. Confirm the dissolution state: At the end of the predetermined heating pretreatment time (e.g., the first-stage duration is 30 minutes), check the uniformity and dissolution state of the solution to ensure that the biliverdin is completely dissolved and evenly distributed.
[0099] 2. Enter the next stage: If it is confirmed that the precursor substance is completely dissolved and the reaction has initially proceeded, prepare to enter the next stage of temperature progressive loading process. Among them, the initial reaction includes the complete dissolution of biliverdin, the formation of a complex with the buffer solution, and the redox reaction.
[0100] Through the above detailed steps, the heating pretreatment for the first-stage duration can be effectively carried out in the temperature-controlled reactor to ensure the complete dissolution of biliverdin and the initiation of the preliminary reaction. These steps include the whole process from preparing the temperature-controlled reactor, setting the temperature control parameters to executing the heating process, ensuring the accuracy and consistency of the operation. This method combines a dynamic temperature regulation algorithm and can achieve efficient dissolution of biliverdin under mild and stable conditions, laying a reliable foundation for the subsequent preparation of bilirubin. This scientific and meticulous operation method helps to improve the reaction efficiency and product quality.
[0101] S204. Perform a dynamic temperature progressive loading for the intermediate reaction with the second-stage duration on the temperature of the temperature-controlled reactor to partially convert biliverdin into bilirubin.
[0102] Specifically, the temperature change during a dynamic temperature progressive loading process can be as follows:
[0103] Among them, is the temperature of the i-th temperature progressive time period, is the temperature difference range of each step.
[0104] This temperature change formula is used to describe the dynamic temperature progressive loading of the intermediate reaction in the second stage. The formula gradually increases the reaction temperature by means of step-by-step temperature, enabling biliverdin to be gradually converted into bilirubin under stable temperature conditions. This way of temperature progression helps to control the reaction rate, minimize the generation of side reactions and by-products, and improve the yield and purity of bilirubin.
[0105] 1. The temperature at the end of the first stage:
[0106] - Design significance: As the initial temperature at the start of the second stage, it ensures a smooth transition from the temperature at the end of the first stage to the second stage, avoiding sudden temperature changes.
[0107] - Determination method: It is determined by the final temperature of the heating pretreatment in the first stage, usually recording the actual temperature at the end of the first stage.
[0108] 2. The temperature difference range of each step:
[0109] - Design significance: Control the temperature difference of each temperature progressive stage to gradually and steadily increase the temperature so that biliverdin can be gradually converted into bilirubin.
[0110] - Determination method: Through experimental optimization, it is usually set to 3 - 5 °C and gradually increased within the temperature range allowed by the system.
[0111] Specifically, the temperature progressive loading in the second stage is to gradually increase the reaction temperature in the temperature-controlled reactor, so that biliverdin is partially converted into bilirubin at a relatively stable but gradually increasing temperature. In this stage, by increasing the temperature in stages, the reaction rate can be effectively controlled, side reactions caused by rapid temperature increase can be prevented, and the yield and purity of bilirubin can be improved. One implementation method may include:
[0112] Step 1: Preparation for temperature progressive loading:
[0113] 1. Set the initial temperature Confirm the temperature at the end of the first stage , and ensure that the temperature-controlled reactor accurately records this temperature as the initial temperature.
[0114] 2. Determine the temperature difference : According to experimental data and literature, set the temperature difference range for each stage For example, the experimentally determined is 3°C.
[0115] 3. Determine the number of progressive stages n: Determine how many temperature progressive stages n are required, for example, 7 stages. The total temperature progressive time needs to match the reaction time, for example, each stage lasts for 10 minutes.
[0116] Step 2: Temperature progressive loading process:
[0117] 1. Start the progressive loading program: Select and start the progressive loading program on the control panel of the temperature-controlled reactor, and set the initial temperature , temperature difference , number of stages n and stage time.
[0118] 2. Conduct the first-stage progressive loading: At the moment of the initial temperature , the temperature-controlled reactor automatically increases the temperature by the first step , that is, . The system monitors and records the temperature in real time.
[0119] 3. Gradually conduct subsequent-stage progressive loading: At the end of the first stage, the system automatically increases the temperature from to . This process continues until all stages are iterated.
[0120] - Example: If , , the temperature in the second stage is , the temperature in the third stage is , and so on until the 7th stage .
[0121] Step 3: Dynamic Adjustment and Monitoring:
[0122] 1. Real-time temperature monitoring and regulation: Use temperature sensors to monitor the temperature inside the reactor in real time. If the detected temperature deviates from the progressive loading value, the control system automatically adjusts the heating or cooling power to ensure that the temperature is stable at the set value.
[0123] 2. Record reaction data: The system continuously records temperature data, stage time, reaction solution status, etc. during the reaction process to ensure the integrity of the entire process data for subsequent analysis and optimization.
[0124] Step 4: End the second-stage progressive loading:
[0125] 1. Confirm the partial conversion status: When all the progressive loading in the second stage is completed, check the reaction product to confirm the status of the partial conversion of biliverdin to bilirubin, and record the key reaction data.
[0126] 2. Prepare for the next stage: According to the experimental design, decide whether further temperature adjustment is required or enter the reaction treatment link of the next stage. If necessary, gradually cool down to room temperature and prepare for the temperature uniform transition in the third stage.
[0127] Through the above detailed steps, the dynamic temperature progressive loading of the intermediate reaction with the duration of the second stage can be effectively carried out in the temperature-controlled reactor to promote the partial conversion of biliverdin to bilirubin. These steps include the whole process of preparation, execution, and monitoring of the temperature progressive loading, ensuring the accuracy and consistency of the operation. Combining with the staged temperature progressive algorithm, the reaction system can operate safely and efficiently under stable and gradually increasing temperature conditions, ultimately achieving the ideal reaction effect and product quality.
[0128] S205, perform a temperature uniform transition for the duration of the third stage on the temperature inside the temperature-controlled reactor, and cool the solution to room temperature after the reaction ends to terminate the reaction, then centrifuge the obtained product to collect the supernatant to obtain a bilirubin solution.
[0129] Specifically, a temperature change during the temperature uniform transition can be:
[0130] Among them, is the temperature at time after the start of the uniform transition, is the initial adjustment amplitude, is the exponential decay coefficient, is the start time of the uniform transition, is the cosine fluctuation amplitude, is the cosine frequency.
[0131] This temperature change formula aims to describe the dynamic temperature change during the uniform temperature transition in the third stage. By combining exponential decay and cosine fluctuations, the formula achieves a smooth temperature transition, effectively avoiding the impact of sudden temperature changes on the reaction system, ensuring the stability and uniformity of the reaction, and providing optimal conditions for the formation of the final product. The design significance and determination method of the parameters are as follows:
[0132] 1. The temperature in the nth temperature progression time period:
[0133] - Design significance: As the initial temperature in the third stage, it ensures a smooth transition from the second stage to the third stage and avoids the impact of excessive temperature changes on the reaction system.
[0134] - Determination method: It is determined by the final temperature of the progressive loading in the second stage and confirmed by the recorded actual data.
[0135] 2. Initial adjustment amplitude:
[0136] - Design significance: Controls the temperature adjustment amplitude at the beginning of the uniform temperature transition, enabling the temperature to quickly enter the smooth transition process.
[0137] - Determination method: Through experimental optimization, it is usually set as an appropriate multiple of the temperature fluctuation amplitude in the first stage, such as 5 - 10 °C.
[0138] 3. Exponential decay coefficient:
[0139] - Design significance: Controls the decay rate during the uniform temperature transition to ensure that the temperature gradually and smoothly drops to the target value.
[0140] - Determination method: It is determined according to the thermodynamic characteristics of the reaction system and the required transition time, such as 0.1 - 0.5, and the specific value is adjusted by experiments.
[0141] 4. Start time of uniform transition:
[0142] - Design significance: Defines the start time of the uniform transition process to ensure that the uniform transition starts immediately after the temperature progressive loading ends.
[0143] - Determination method: It is determined by the end time of the second stage and usually starts immediately after the progressive loading ends.
[0144] 5. Cosine fluctuation amplitude:
[0145] - Design significance: Controls the cosine fluctuations during the uniform temperature transition, enabling the temperature to maintain small periodic changes during the transition and ensuring the dynamic balance of the reaction system.
[0146] - Determination method: Determined according to experimental data and reaction requirements, usually set to 1 - 3 °C.
[0147] 6. Cosine frequency:
[0148] - Design significance: Control the frequency of cosine fluctuations to make the temperature change smoother and more rhythmic.
[0149] - Determination method: Determine the appropriate frequency through experiments, such as one cycle per minute (the corresponding angular frequency is approximately 0.105 rad / s), to ensure that the frequency of temperature regulation matches the thermal equilibrium time of the system.
[0150] Specifically, the temperature uniform transition in the third stage aims to smoothly transition the temperature in the temperature-controlled reactor from the final temperature of the progressive loading in the second stage to a lower stable temperature and finally cool it to room temperature in order to terminate the reaction and stabilize the product. This process can prevent the impact of sudden temperature changes on the product structure and ensure the product quality and stability of bilirubin. In addition, the design of uniform transition can also effectively reduce the stress on the solution system caused by temperature fluctuations and maintain the dynamic balance of the system. One implementation method may include:
[0151] Step 1: Prepare for temperature uniform transition:
[0152] 1. Set the initial temperature : Confirm the temperature at the end of the progressive loading in the second stage , and ensure that the temperature-controlled reactor accurately records this temperature as the initial temperature of the uniform transition.
[0153] 2. Set the transition parameters: The temperature uniform transition parameters can be determined according to test data: - Set to 7 °C; - Set to 0.3; - Set to 2 °C; - Set to 0.105 rad / s.
[0154] Step 2: Start the uniform transition program:
[0155] 1. Set the uniform transition formula: Input the temperature formula for uniform transition into the control system of the temperature-controlled reactor and confirm the start time as the end time of the second stage.
[0156] 2. Start the uniform transition process: Start the temperature control system to dynamically adjust the reactor temperature according to the set uniform transition formula, ensuring that the temperature gradually changes from Smooth transition.
[0157] Step 3: Real-time monitoring and adjustment:
[0158] 1. Real-time temperature monitoring: Use a high-precision temperature sensor to monitor the temperature changes in the reactor in real time to ensure that it conforms to the change curve of the uniform transition formula.
[0159] 2. Automatic temperature adjustment: If the detected temperature deviates from the set value, the temperature control system automatically adjusts the heating or cooling power to ensure that the temperature changes according to the formula changes.
[0160] 3. Record reaction data: Real-time record the temperature change data, time, solution state, etc. during the reaction process to ensure the integrity and traceability of the data.
[0161] Step 4: End the uniform transition and cool to room temperature:
[0162] 1. End of the uniform transition process: When the duration of the uniform transition reaches the set time, the system automatically stops the temperature progression and begins to gradually cool to room temperature.
[0163] 2. Terminate the reaction: Cool the solution in the temperature-controlled reactor to room temperature, confirm that the reaction has been completely terminated, and record the final reaction data.
[0164] Step 5: Centrifugal separation and collection:
[0165] 1. Transfer the solution: Carefully transfer the reaction solution to a centrifuge tube to prepare for centrifugal separation.
[0166] 2. Centrifugal separation: Place the centrifuge tube in a centrifuge and set appropriate centrifugation speed and time according to the solution characteristics (for example, 3000 rpm, 10 minutes) to separate the bilirubin precipitate from the solution.
[0167] 3. Collect the supernatant: After centrifugation, carefully remove the centrifuge tube and use tools such as a pipette to collect the supernatant, ensuring that the bilirubin in the supernatant is not disturbed.
[0168] 4. Obtain bilirubin solution: Transfer the collected supernatant to a clean storage bottle, seal it, and obtain a pure bilirubin solution.
[0169] Through the above detailed steps, the temperature can be effectively and uniformly transitioned within the temperature-controlled reactor during the third stage duration, and the solution can be cooled to room temperature after the reaction to terminate the reaction and perform centrifugal separation. Combining with the dynamic temperature regulation algorithm for uniform transition, this method can ensure a smooth temperature transition, avoid the impact of sudden temperature changes on the reaction system, and improve the quality and stability of the product. Finally, through the cooling and centrifugal separation steps, a pure bilirubin solution is obtained, realizing the optimization and control of the bilirubin preparation process.
[0170] It can be seen that the precursor of bilirubin is obtained, where the precursor is biliverdin; the biliverdin is dissolved in a physiological buffer to form a uniform solution; the uniform solution is placed in a temperature-controlled reactor for a first-stage duration of heating pretreatment to ensure that the precursor is completely dissolved and the preliminary reaction starts; the temperature of the temperature-controlled reactor is dynamically increased in a second-stage duration of intermediate reaction to partially convert biliverdin into bilirubin; the temperature in the temperature-controlled reactor is uniformly transitioned for a third-stage duration, and the solution is cooled to room temperature after the reaction to terminate the reaction, and the resulting product is centrifuged to collect the supernatant to obtain a bilirubin solution, so that through precise multi-stage temperature control, the efficient conversion from biliverdin to bilirubin can be achieved, and high-purity bilirubin can be obtained.
[0171] Another embodiment of the present invention provides a temperature control system for preparing bilirubin. Refer to Figure 3 , the system may include:
[0172] An acquisition module 301, configured to acquire the precursor of bilirubin, where the precursor is biliverdin.
[0173] A dissolution module 302, configured to dissolve the biliverdin in a physiological buffer to form a uniform solution.
[0174] A heating module 303, configured to place the uniform solution in a temperature-controlled reactor for a first-stage duration of heating pretreatment to ensure that the precursor is completely dissolved and the preliminary reaction starts.
[0175] A progressive module 304, configured to dynamically increase the temperature of the temperature-controlled reactor in a second-stage duration of intermediate reaction to partially convert biliverdin into bilirubin.
[0176] A transition module 305, configured to uniformly transition the temperature in the temperature-controlled reactor for a third-stage duration, and cool the solution to room temperature after the reaction to terminate the reaction, and centrifuge the resulting product to collect the supernatant to obtain a bilirubin solution.
[0177] It can be seen that a precursor substance of bilirubin is obtained, wherein the precursor substance is biliverdin; the biliverdin is dissolved in a physiological buffer solution to form a homogeneous solution; the homogeneous solution is placed in a temperature-controlled reactor for heat pretreatment for a first-stage duration to ensure that the precursor substance is completely dissolved and a preliminary reaction starts; the temperature of the temperature-controlled reactor is dynamically increased in a progressive manner for an intermediate reaction for a second-stage duration to partially convert biliverdin into bilirubin; the temperature in the temperature-controlled reactor is uniformly transitioned for a third-stage duration, and after the reaction ends, the solution is cooled to room temperature to terminate the reaction, and the obtained product is centrifuged to collect the supernatant to obtain a bilirubin solution, so that through precise multi-stage temperature control, the efficient conversion from biliverdin to bilirubin can be achieved, and high-purity bilirubin can be obtained.
[0178] An embodiment of the present invention further provides a storage medium, in which a computer program is stored, wherein the computer program is set to execute the steps in any one of the above method embodiments when running:
[0179] Specifically, in this embodiment, the above storage medium can be set to store a computer program for executing the following steps: S201, obtain a precursor substance of bilirubin, wherein the precursor substance is biliverdin; S202, dissolve the biliverdin in a physiological buffer solution to form a homogeneous solution; S203, place the homogeneous solution in a temperature-controlled reactor for heat pretreatment for a first-stage duration to ensure that the precursor substance is completely dissolved and a preliminary reaction starts; S204, dynamically increase the temperature of the temperature-controlled reactor in a progressive manner for an intermediate reaction for a second-stage duration to partially convert biliverdin into bilirubin; S205, uniformly transition the temperature in the temperature-controlled reactor for a third-stage duration, and after the reaction ends, cool the solution to room temperature to terminate the reaction, and centrifuge the obtained product to collect the supernatant to obtain a bilirubin solution.
[0180] It can be seen that a precursor substance of bilirubin is obtained, where the precursor substance is biliverdin; the biliverdin is dissolved in a physiological buffer solution to form a homogeneous solution; the homogeneous solution is placed in a temperature-controlled reactor for heat pretreatment for a first-stage duration to ensure that the precursor substance is completely dissolved and the preliminary reaction starts; the temperature of the temperature-controlled reactor is dynamically increased in a progressive manner for an intermediate reaction for a second-stage duration to partially convert biliverdin into bilirubin; the temperature in the temperature-controlled reactor is uniformly transitioned for a third-stage duration, and after the reaction ends, the solution is cooled to room temperature to terminate the reaction, and the obtained product is centrifuged to collect the supernatant to obtain a bilirubin solution, so that through precise multi-stage temperature control, the efficient conversion from biliverdin to bilirubin can be achieved, and high-purity bilirubin can be obtained.
[0181] An embodiment of the present invention further provides an electronic device, including a memory and a processor, where a computer program is stored in the memory, and the processor is configured to run the computer program to execute the steps in any one of the above method embodiments.
[0182] Specifically, the above electronic device may further include a transmission device and an input / output device, where the transmission device is connected to the above processor, and the input / output device is connected to the above processor.
[0183] Specifically, in this embodiment, the above processor may be configured to execute the following steps through a computer program: S201, obtain a precursor substance of bilirubin, where the precursor substance is biliverdin; S202, dissolve the biliverdin in a physiological buffer solution to form a homogeneous solution; S203, place the homogeneous solution in a temperature-controlled reactor for heat pretreatment for a first-stage duration to ensure that the precursor substance is completely dissolved and the preliminary reaction starts; S204, dynamically increase the temperature of the temperature-controlled reactor in a progressive manner for an intermediate reaction for a second-stage duration to partially convert biliverdin into bilirubin; S205, uniformly transition the temperature in the temperature-controlled reactor for a third-stage duration, and after the reaction ends, cool the solution to room temperature to terminate the reaction, and centrifuge the obtained product to collect the supernatant to obtain a bilirubin solution.
[0184] It can be seen that a precursor substance of bilirubin is obtained, wherein the precursor substance is biliverdin; the biliverdin is dissolved in a physiological buffer solution to form a uniform solution; the uniform solution is placed in a temperature-controlled reactor for a first-stage heating pretreatment to ensure that the precursor substance is completely dissolved and a preliminary reaction starts; the temperature of the temperature-controlled reactor is dynamically increased in a second-stage intermediate reaction to partially convert biliverdin into bilirubin; the temperature in the temperature-controlled reactor is uniformly transitioned in a third-stage duration, and after the reaction is completed, the solution is cooled to room temperature to terminate the reaction, and the obtained product is centrifuged to collect the supernatant to obtain a bilirubin solution, so that through precise multi-stage temperature control, the efficient conversion from biliverdin to bilirubin can be achieved, and high-purity bilirubin can be obtained.
[0185] The structure, features and effects of the present invention have been described in detail based on the embodiments shown in the drawings. The above is only the preferred embodiment of the present invention, but the present invention is not limited to the scope shown in the drawings. Any changes made according to the concept of the present invention, or equivalent embodiments modified into equivalent changes, should still be within the protection scope of the present invention as long as they do not exceed the spirit covered by the specification and the drawings.
Claims
1. A temperature control method for preparing bilirubin, characterized in that: The method comprises: Obtaining a precursor substance of bilirubin, wherein the precursor substance is biliverdin; dissolving the biliverdin in a physiological buffer to form a uniform solution; The uniform solution is placed in a temperature-controlled reactor for a first-stage heating pretreatment to ensure that the precursor material is completely dissolved and a preliminary reaction begins; wherein the temperature change during the heating pretreatment is: , in, For time The reaction temperature, is the initial reaction temperature, is the temperature fluctuation amplitude, is the frequency constant; The temperature of the temperature-controlled reactor is subjected to a dynamic temperature progressive loading of the intermediate reaction for the duration of the second stage, so that biliverdin is partially converted into bilirubin; The temperature in the temperature-controlled reactor is uniformly transitioned for the duration of the third stage, and after the reaction is completed, the solution is cooled to room temperature to terminate the reaction, and the obtained product is centrifuged and the supernatant is collected to obtain a bilirubin solution.
2. The method according to claim 1, characterized in that: The temperature change during the dynamic temperature progressive loading process is: , in, is the temperature of the ith temperature progression time period, , The temperature difference range for each step.
3. The method according to claim 2, characterized in that The temperature change during the uniform temperature transition process is: , in, The time after the uniform transition starts The temperature at is the initial adjustment range, is the exponential decay coefficient, is the start time of uniform transition, is the cosine fluctuation amplitude, is the cosine frequency.
4. A temperature control system for preparing bilirubin, characterized in that: The system comprises: An acquisition module, used for acquiring a precursor substance of bilirubin, wherein the precursor substance is biliverdin; A dissolving module, used for dissolving the biliverdin in a physiological buffer to form a uniform solution; The heating module is used to place the uniform solution in a temperature-controlled reactor for a first-stage heating pretreatment to ensure that the precursor material is completely dissolved and a preliminary reaction begins; wherein the temperature change during the heating pretreatment is: , in, For time The reaction temperature, is the initial reaction temperature, is the temperature fluctuation amplitude, is the frequency constant; A progressive module, used for progressively loading the temperature of the temperature-controlled reactor with a dynamic temperature of the intermediate reaction of the second stage duration, so as to partially convert biliverdin into bilirubin; The transition module is used to uniformly transition the temperature in the temperature-controlled reactor to the third stage, and to cool the solution to room temperature after the reaction to terminate the reaction, so as to centrifuge the obtained product and collect the supernatant to obtain a bilirubin solution.
5. The system according to claim 4, wherein the temperature change during the dynamic temperature progressive loading process is: , in, is the temperature of the ith temperature progression time period, , The temperature difference range for each step.
6. The system according to claim 5, characterized in that The temperature change during the uniform temperature transition process is: , in, The time after the uniform transition starts The temperature at is the initial adjustment range, is the exponential decay coefficient, is the start time of uniform transition, is the cosine fluctuation amplitude, is the cosine frequency.
7. A storage medium, characterized in that: The storage medium stores a computer program, wherein the computer program is configured to execute the method according to any one of claims 1 to 3 when executed.
8. An electronic device, comprising a memory and a processor, characterized in that: A computer program is stored in the memory, and the processor is configured to run the computer program to perform the method according to any one of claims 1 to 3.