Synthesis control method and system of ceramide compound based on long-chain fatty acid

Abstract

The invention relates to the technical field of automatic control, in particular to a synthesis control method and system of a ceramide compound based on long-chain fatty acid, and the method comprises the steps: carrying out the dynamic weighing monitoring of a raw material based on a set synthesis instruction, judging the received currently collected multi-source data and a preset reaction stage, and if the received multi-source data belongs to the first stage, stopping the reaction; if yes, controlling the reaction kettle to be heated to a set reaction temperature based on the synthesis instruction; if the reaction belongs to the second stage, controlling the reaction system to carry out amine-ester exchange reaction under a constant temperature condition until the reaction is confirmed to be complete through TLC detection; if the synthesis instruction belongs to the third stage, adding a quenching agent to terminate the reaction based on the synthesis instruction, and carrying out a cooling crystallization process; if the reaction process belongs to the fourth stage, an air blower is controlled to work, a product in the third stage is dried for 10-12 h, and the ceramide compound based on the long-chain fatty acid is obtained, the problem that a traditional method lacks real-time monitoring and accurate control over the reaction process is solved, and the product quality consistency is guaranteed.

Description

Technical Field

[0001] This invention relates to the field of automation control technology, and in particular to a method and system for controlling the synthesis of ceramide compounds based on long-chain fatty acids. Background Technology

[0002] Ceramides are a class of bioactive substances composed of the base of sphingosine and various fatty acids. Studies have shown that ceramides have been applied to varying degrees in the daily chemical, medical, and food industries, with their application in the daily chemical sector being particularly widespread and widely accepted by the market. Ceramides possess powerful skin-benefiting effects, such as moisturizing, skin barrier function, adhesion, anti-aging, and inflammation reduction. Due to the aforementioned importance of ceramides, many cosmetic and pharmaceutical companies are currently researching and developing related products. However, the large-scale production of natural ceramides is difficult due to factors such as the difficulty in extraction and high cost, making commercialization impractical. In the synthesis of ceramides based on the aminoester exchange reaction of long-chain fatty acid esters and sphingosine compounds, traditional methods lack real-time monitoring and precise control of the reaction process, making it difficult to guarantee product quality consistency. Summary of the Invention

[0003] The purpose of this invention is to provide a method and system for controlling the synthesis of ceramide compounds based on long-chain fatty acids, which solves the problem of the lack of real-time monitoring and precise control of the reaction process in traditional methods, thus ensuring consistent product quality.

[0004] To achieve the above objectives, in a first aspect, the present invention provides a method for controlling the synthesis of ceramide compounds based on long-chain fatty acids, comprising the following steps: Based on the set synthesis instructions, the raw materials are dynamically weighed and monitored, and the currently collected multi-source data is compared with the preset reaction stage. If it is determined that the currently collected multi-source data belongs to the first stage, then the reactor temperature is controlled to rise to the set reaction temperature based on the synthesis command; If it is determined that the currently collected multi-source data belongs to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under isothermal conditions until TLC detection confirms that the reaction is complete. If it is determined that the currently collected multi-source data belongs to the third stage, a quencher is added based on the synthesis instruction to terminate the reaction, and a cooling and crystallization process is carried out. If it is determined that the currently collected multi-source data belongs to the fourth stage, then the blower is controlled to work, and the product of the third stage is dried for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids.

[0005] This includes dynamically weighing and monitoring raw materials based on set synthesis instructions, and comparing the currently collected multi-source data with preset reaction stages, including: Based on the received synthesis instructions, the system outputs the types and amounts of sphingosine compounds, long-chain fatty acid esters, organic bases, and lower alcohols, and outputs a feeding completion signal when the feeding is completed. Based on the received feeding completion signal, control multiple data acquisition devices to collect data at a set sampling frequency; The collected multi-source data is transmitted to the control system and compared with the preset reaction stage for judgment.

[0006] The method further includes, between the first and second stages: Calculate the average temperature within the set temperature range and the fluctuation of the current temperature. If both the average temperature and the fluctuation of the current temperature are less than or equal to the set tolerance threshold, proceed to the second stage.

[0007] If the currently collected multi-source data is determined to belong to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under isothermal conditions until TLC detection confirms the reaction is complete, including: When the currently collected multi-source data belongs to the second stage, the temperature of the reactor is controlled to be maintained within 55~65℃, and the stirring equipment is controlled to stir the reaction for 2~3 hours to carry out the amine ester exchange reaction. Simultaneously, TLC is activated based on the received periodic monitoring signal to perform detection until a complete response signal is output.

[0008] This includes simultaneously initiating TLC detection based on the received periodic monitoring signal until a complete response signal is output, including: The timer is controlled to automatically sample and precisely spot samples within a set interval based on the received periodic monitoring signal; The TLC plate after spotting is transferred, and a developing solvent is added for automatic development until the set height is reached, after which it is dried. After drying, the TLC board is developed and images are acquired. The acquired images are then processed for image recognition and preprocessing. The reaction progress is determined based on the calculated spot shift value. Once the spot pixels reach the set endpoint determination condition, a complete reaction signal is output.

[0009] If the currently collected multi-source data is determined to belong to the third stage, a quencher is added based on the synthesis command to terminate the reaction, and a cooling and crystallization process is performed, including: The received complete response signal is verified multiple times until successful verification is achieved, then proceed to the third stage; The reaction rate is adjusted based on the set stirring rate, and the feeding of glacial acetic acid is controlled according to the set synthesis instructions. The pH value of the reactor is monitored simultaneously until the pH value drops to neutral. The reactor is controlled to undergo a cooling and crystallization process according to the synthesis instructions.

[0010] The process of controlling the reactor to undergo cooling and crystallization according to the synthesis instructions includes: The temperature of the reactor is controlled according to the set cooling rate, and data collected by the turbidity sensor and image sensor are acquired in real time. After determining that crystal nuclei have been generated, the reactor is kept at the temperature for 1-2 hours, then filtered and cleaned once with low alcohol. The cooling rate is adjusted according to the real-time crystal growth rate until the temperature drops to the preset crystallization endpoint temperature. When the real-time crystal growth rate is zero and the holding time is reached, a crystallization completion signal is output.

[0011] In a second aspect, the present invention provides a synthesis control system for ceramide compounds based on long-chain fatty acids, which is applied to a synthesis control method for ceramide compounds based on long-chain fatty acids as provided in the first aspect. The synthesis control system for ceramide compounds based on long-chain fatty acids includes a multi-source data acquisition module and a control judgment module. The multi-source data acquisition module is used to dynamically weigh and monitor the raw materials based on the set synthesis instructions, and to acquire the current reaction data through various acquisition devices, and transmit the obtained multi-source data to the control and judgment module. The control and judgment module is used to judge the currently collected multi-source data with the preset reaction stage. If the currently collected multi-source data is judged to belong to the first stage, the reactor is heated to the set reaction temperature based on the synthesis command. If the currently collected multi-source data is judged to belong to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under constant temperature conditions until TLC detection confirms that the reaction is complete. If the currently collected multi-source data is judged to belong to the third stage, a quencher is added to terminate the reaction based on the synthesis command, and a cooling and crystallization process is carried out. If the currently collected multi-source data is judged to belong to the fourth stage, the blower is controlled to work to dry the product of the third stage for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids.

[0012] This invention discloses a method and system for controlling the synthesis of ceramide compounds based on long-chain fatty acids. The synthesis control system for ceramide compounds based on long-chain fatty acids includes a multi-source data acquisition module and a control judgment module. Based on a set synthesis command, the system dynamically monitors the weighing of raw materials and acquires current reaction data through various acquisition devices. The acquired multi-source data is transmitted to the control judgment module, which compares the received multi-source data with a preset reaction stage. If the acquired multi-source data is determined to belong to the first stage, the system controls the reactor temperature to rise to the set reaction temperature based on the synthesis command. If the currently collected multi-source data is determined to belong to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under isothermal conditions until TLC detection confirms the completeness of the reaction; if the currently collected multi-source data is determined to belong to the third stage, a quencher is added based on the synthesis instruction to terminate the reaction, and a cooling crystallization process is carried out; if the currently collected multi-source data is determined to belong to the fourth stage, the blower is controlled to work, and the product of the third stage is dried for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids. This solves the problem of the lack of real-time monitoring and precise control of the reaction process in traditional methods, ensuring the consistency of product quality. Attached Figure Description

[0013] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0014] Figure 1 This is a schematic diagram of the steps in a method for controlling the synthesis of a ceramide compound based on long-chain fatty acids according to the first embodiment of the present invention.

[0015] Figure 2 This is a schematic diagram of the steps in a method for synthesizing a ceramide compound based on long-chain fatty acids provided by the present invention.

[0016] Figure 3 This is a schematic diagram of the synthesis process of ceramide compounds based on long-chain fatty acids provided by the present invention.

[0017] Figure 4 This is a schematic diagram illustrating the preparation principle of Embodiment 1 of the present invention.

[0018] Figure 5 This is a schematic diagram illustrating the preparation principle of Embodiment 2 of the present invention.

[0019] Figure 6 This is a schematic diagram illustrating the preparation principle of Embodiment 3 of the present invention.

[0020] Figure 7 This is the HPLC chromatogram of Example 1 of the present invention.

[0021] Figure 8This is the HPLC chromatogram of Example 2 of the present invention.

[0022] Figure 9 This is the HPLC chromatogram of Example 3 of the present invention.

[0023] Figure 10 This is a schematic diagram of the structure of a synthesis control system for a ceramide compound based on long-chain fatty acids according to the second embodiment of the present invention.

[0024] Figure 11 This is a schematic diagram of the electronic device of the present invention.

[0025] In the diagram: 101 - Multi-source data acquisition module, 102 - Control and judgment module. Detailed Implementation

[0026] Exemplary embodiments will now be described in detail, examples of which are illustrated in the accompanying drawings. When the following description relates to the drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with this application.

[0027] The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The singular forms “a,” “the,” and “the” used in this application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and includes any or all possible combinations of one or more of the associated listed items.

[0028] It should be understood that although the terms first, second, third, etc., may be used in this application to describe various information, such information should not be limited to these terms. These terms are only used to distinguish information of the same type from one another. For example, without departing from the scope of this application, first information may also be referred to as second information, and similarly, second information may also be referred to as first information. Depending on the context, the word "if" as used herein may be interpreted as "when," "when," or "in response to determination."

[0029] The first embodiment of this application is as follows: Please see Figures 1-3 This invention provides a method for controlling the synthesis of ceramide compounds based on long-chain fatty acids, comprising the following steps: S101. Based on the set synthesis instructions, the raw materials are dynamically weighed and monitored, and the currently collected multi-source data is compared with the preset reaction stage.

[0030] Specifically, based on the received synthesis instruction, the system outputs the types and amounts of sphingosine compound, long-chain fatty acid ester, organic base, and lower alcohol. Upon completion of feeding, a feeding completion signal is output. The synthesis instruction includes the complete steps of the synthesis method for ceramide compounds based on long-chain fatty acids. When the synthesis instruction is issued, a corresponding synthesis instruction is generated based on the order. The MES system automatically pushes the synthesis formula to the weighing station, displaying the types and amounts of sphingosine compound, long-chain fatty acid ester, organic base, and lower alcohol. The long-chain fatty acid ester is methyl stearate. The compound is selected from the following: methyl linoleate, methyl palmitate, ethyl oleate, ethyl stearate, and ethyl linoleate; the sphingosine compound is selected from the following: phytosphingosine, neurosphingosine, dihydrosphingosine, and 6-hydroxysphingosine; the organic base is selected from one or more of sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; the lower alcohol is selected from one or more of methanol, ethanol, or isopropanol; the molar ratio of the long-chain fatty acid ester to the sphingosine compound is (1.1~1.5):1; the molar ratio of the organic base to the sphingosine compound is (0.5~2.0):1.

[0031] The synthesis instructions include the following synthesis methods: S1. Add the sphingosine compound, long-chain fatty acid ester, organic base and lower alcohol into the reaction flask in sequence according to the set weight; S2. Increase the temperature to 55-70℃ in 0.5-1h, stir and react for 2-3h until the substrate reaction is complete as detected by TLC; S3. Add acetic acid to quench the precipitate, then add lower alcohol and stir to cool to 15-20°C, controlling the speed at 10-15°C / h, keep warm for 1-2h, then filter. Wash the filter cake once with lower alcohol, then add lower alcohol to recrystallize the filter cake at 35-65°C. After dissolving, cool to 10-20°C, controlling the speed at 10-15°C / h, keep warm for 1-2h, then filter, and wash the filter cake again with lower alcohol. S4. After drying in a forced-air environment at 50~60℃ for 10~12h, a ceramide compound based on long-chain fatty acids is obtained.

[0032] Synthesis methods such as Figure 3 The diagram illustrates a method for synthesizing ceramides via amine transesterification under alkaline conditions. This method effectively avoids esterification byproducts that occur when using condensing agents such as EDCI, thereby improving reaction purity and yield, and enhancing the quality of ceramides. R3 can be a carbon chain with fewer than 10 carbon atoms, such as methyl, ethyl, or propyl.

[0033] The ceramide synthesis process of this invention eliminates the need for complex and lengthy post-processing after the reaction is complete. High-purity ceramide can be obtained simply by cooling and crystallizing. This not only improves the quality of ceramide but also significantly shortens the production cycle and reduces production costs, giving it a clear competitive advantage in the market.

[0034] The following three examples illustrate the specific preparation process in detail: Example 1: Preparation of ceramide NS like Figure 4 As shown, 20.0 g of sphingosine, 24.0 g of ethyl stearate, 2.0 g of sodium methoxide, and 160.0 g of methanol were sequentially added to a 1 L reactor. The temperature was raised to 55-65 °C over 0.5-1 h, and the reaction was stirred for 2-3 h until the substrate reaction was complete as detected by TLC. 2.2 g of glacial acetic acid was added to quench the reaction, followed by the addition of 160.0 g of methanol. The temperature was lowered to 10-20 °C, and the reaction rate was controlled at 10-15 °C / h. After holding at this temperature for 1-2 h, the mixture was filtered, and the filter cake was washed once with 40.0 g of methanol. The obtained filter cake was then recrystallized at 55-65℃ with 200.0 g of methanol. After dissolution, the temperature was lowered to 10-20℃, and the temperature was maintained at 10-15℃ / h for 1-2 hours. The mixture was then filtered, and the filter cake was washed once with 40.0 g of methanol. The resulting filter cake was dried at 50-60℃ for 10-12 hours to obtain 30.1 g of a white solid with an HPLC purity of 96.9% and a yield of 75-85%. MS [M+H] + C 36 H 73 NO3566.54.

[0035] Example 2: Preparation of Ceramide NDS like Figure 5 As shown, 20.0 g of dihydrosphingosine, 26.0 g of ethyl stearate, 4.0 g of sodium ethoxide, and 320.0 g of ethanol were sequentially added to a 1 L reactor. The mixture was heated to 55-65 °C over 0.5-1 h, stirred for 2-3 h, and the reaction was continued until TLC analysis showed complete substrate reaction. 3.5 g of glacial acetic acid was added to quench the reaction, and then the temperature was lowered to 10-20 °C. The reaction rate was controlled at 10-15 °C / h, and the mixture was held at this temperature for 1-2 h before filtration. The filter cake was washed once with 60.0 g of ethanol. The obtained filter cake was then mixed with 200.0 g of ethanol and stirred at 35-45°C for 1-2 hours. The mixture was then cooled to 10-20°C, and the stirring speed was controlled at 10-15°C / h. After holding at this temperature for 1-2 hours, the mixture was filtered. The filter cake was washed once with 60.0 g of ethanol and then dried at 50-60°C for 10-12 hours to obtain 31.2 g of a white solid with an HPLC purity of 95.4% and a yield of 75-85%. MS [M+H] + C 36 H 71 NO3568.56.

[0036] Example 3: Preparation of Ceramide NP like Figure 6 As shown, 28g of ethyl oleate, 20g of phytosphoprotein, 2.0g of sodium methoxide, and 30g of ethanol were sequentially added to a 1L reactor. The temperature was raised to 60-70℃ over 0.5-1h, and the reaction was stirred for 2-3h until the substrate reaction was complete as detected by TLC. 2.2g of glacial acetic acid was added to quench the reaction, followed by the addition of 160.0g of methanol for cooling and crystallization. The temperature was lowered to 10-20℃, and the reaction rate was controlled at 10-15℃ / h. After holding at this temperature for 1-2h, the mixture was filtered, and the filter cake was washed once with 40.0g of methanol. The resulting filter cake was then slurried with 80.0g of methanol at 0-10℃ for 1-2h, filtered, and washed once with 40.0g of methanol. The resulting filter cake was dried in a forced-air environment at 50-60℃ for 10-12h to obtain 33.0g of a white powdery solid with an HPLC purity of 94.8% and a yield of 80-90%. MS [M+H] + C 36 H 71 NO4 582.54.

[0037] The 1L reactor used in the examples is a laboratory-scale device, but it can also be a three-necked flask or other sizes of industrial reactor.

[0038] The three embodiments described above were subjected to liquid chromatography analysis to obtain the corresponding spectra, as follows: Figures 7-9 As shown, where, Figures 7-9 In the chromatogram, the vertical axis represents the HPLC peak height, the horizontal axis represents the HPLC retention time, and the peak area represents the relative content. Figures 7-9 The value indicates the HPLC purity of the ceramide synthesized in the corresponding example.

[0039] The method for synthesizing ceramide compounds with long-chain fatty acids as the upper chain is low-cost and has controllable quality. The operation steps are simple. After the reaction is complete, only quenching, cooling and crystallization are required to obtain the finished product, which reduces the post-processing steps and improves the yield. The prepared ceramides NS, NG, NP and Ⅲ are of stable quality and have been commercialized with high market acceptance.

[0040] The dynamic weighing monitoring process involves the weighing equipment integrating a high-precision electronic scale (accuracy 0.01g) and RFID tag identification. Each raw material container (such as sphingosine, fatty acid esters, organic bases, and solvents) is affixed with an RFID tag containing the material ID, theoretical feed quantity, and tolerance range (e.g., ±1%). When the operator places the raw material container on the weighing platform, the RFID reader automatically reads the material information, and the system retrieves the corresponding theoretical feed quantity from the synthesis instruction. During the weighing process, the system reads the weight data in real time and compares it with the theoretical value. If the actual feed quantity exceeds the tolerance range, the system issues an audible and visual alarm and suspends the subsequent process until manual confirmation or re-weighing. After all raw materials are weighed, the system automatically generates an electronic batch record and outputs a "feeding complete" digital signal to the control judgment module 102.

[0041] Then, based on the received feeding completion signal, multiple acquisition devices are controlled to collect data at a set sampling frequency. The acquired multi-source data is transmitted to the control system and compared with the preset reaction stage. The acquisition devices include: a reaction temperature sensor to monitor the temperature inside the reactor in real time; a feeding completion signal receiver to receive a feeding completion signal from the automated feeding system or operator confirmation that "all raw materials (sphingosine, fatty acid esters, catalyst, solvent) have been fed"; and a TLC sampling and analysis unit, which includes: an automatic sampler to extract trace samples from the reactor at preset time intervals or according to instructions; a sample pretreatment subunit to automatically perform rapid pretreatment such as dilution and TLC spotting; a TLC plate imager to acquire high-resolution images of the processed TLC plate; and an image recognition subunit to analyze the TLC images in real time, intelligently determining whether the reaction is complete by comparing the size and intensity of the spots of reactants and products, and transmitting the result ("in reaction" or "reaction complete") to the main controller. It can be seen that the multi-source data actually includes: temperature, pH value, stirring current, pressure, TLC image, crystal image, and turbidity.

[0042] The aforementioned data acquisition equipment starts and operates according to the control and judgment module 102, and acquires data at the set sampling frequency. At the same time, it transmits the acquired multi-source data to the control and judgment module 102 for judgment and processing. All sensors support Modbus-TCP or OPC UA protocols and are connected to the workshop LAN through an industrial switch. The data is uniformly uploaded to a real-time database (such as OSIsoft PI or Ignition), and the control and judgment module 102 subscribes to the required data points. The acquisition frequency can be dynamically adjusted according to the stage (e.g., the TLC sampling period is 30 minutes in stage two, and the image sampling frequency is increased to 10 Hz in stage three).

[0043] S102. If it is determined that the currently collected multi-source data belongs to the first stage, then the reactor is heated to the set reaction temperature based on the synthesis command.

[0044] Specifically, if the control judgment module 102 determines, based on the received multi-source data, that it is currently in the first stage (i.e., it has just received the material feeding completion signal) and the temperature inside the reactor collected by the reaction temperature sensor is still at room temperature, then the control judgment module 102 controls the reactor temperature to be heated uniformly from room temperature to the target reaction temperature of 55-70℃ within 0.5-1 hour. The first stage ends when the temperature inside the reactor reaches the preset lower limit of the reaction temperature, i.e., 55℃, within 0.5-1 hour. During the first stage, the sampling frequency is controlled at 1 time / second.

[0045] After the system reaches the preset target temperature (e.g., 60℃), it does not immediately switch stages. Instead, it initiates a process called "Constant Temperature Stability Judgment Algorithm." This algorithm continuously analyzes the temperature data sequence over a recent period (e.g., the last 5 minutes), calculates the corresponding average temperature and the degree of fluctuation of the current temperature. If both the average temperature and the degree of fluctuation of the current temperature are less than or equal to the set tolerance thresholds, it enters the second stage. During this process, a stability signal is output to the control judgment module 102. In other words, the first stage ends when the average temperature reaches the set range (55-70℃) and stabilizes, the fluctuation is less than or equal to ±0.5℃, and a stability signal is output.

[0046] S103. If it is determined that the currently collected multi-source data belongs to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under constant temperature conditions until TLC detection confirms that the reaction is complete.

[0047] Specifically, when the control judgment module 102 receives the stable signal and the temperature collected by the reaction temperature sensor is within the set range, it is determined that it belongs to the second stage. The second stage is to control the temperature of the reactor to be maintained within 55~65℃, and control the stirring equipment to stir the reaction for 2~3 hours to carry out the amine ester exchange reaction. At the same time, TLC is started to detect according to the received periodic monitoring signal until the reaction is complete and the signal is output.

[0048] The TLC sampling and analysis unit controls a timer based on received periodic monitoring signals to automatically sample, perform online dilution, and perform precise spotting at set intervals (e.g., 30 minutes). Automatic sampling involves controlling a miniature corrosion-resistant pump to extract a trace amount (typically a microliter) of the reaction solution sample from the reactor. Online dilution involves automatically injecting the sample into a flow path, precisely mixing and diluting it with a preset ratio of developing solvent (or diluent) to prevent over-concentration and spot tailing. Precise spotting uses a high-precision robotic arm or pneumatically controlled spotting needle to aspirate the diluted sample and spot it quantitatively and precisely onto a preset starting line on the TLC plate. The spotting process is completely reproducible, eliminating the uncertainties of manual operation.

[0049] After spotting, the TLC plate is transferred by a robotic arm to a sealed automated developing tank. The tank is pre-filled with a suitable developing solvent (e.g., dichloromethane:methanol:acetic acid = 80:4:1) and has reached vapor pressure equilibrium. The developing tank lid is closed, and the developing process is carried out under controlled conditions. Sensors monitor the position of the developing solvent front; when it reaches a preset height (e.g., 8 cm), the robotic arm automatically removes the TLC plate. The TLC plate is then moved to a station equipped with gentle heating (e.g., 50°C) and a blower for rapid drying to remove the developing solvent.

[0050] After drying, the TLC plate passes through an automated spray developing station. A precision spray valve, under program control, uniformly and quantitatively sprays a developing agent (such as phosphomolybdic acid-ethanol solution) onto the plate surface. The sprayed TLC plate is then transferred to a precisely temperature-controlled heating plate and heated at a specific temperature (e.g., 120°C) for a certain time, causing organic substances such as ceramides to form spots. A CCD camera equipped with a specific light source (e.g., a 365nm UV lamp for fluorescent spots, or white light for carbonized spots) acquires high-resolution images of the complete TLC plate, and the image data is transmitted to the TLC sampling and analysis unit. First, the acquired image data undergoes noise reduction, background correction, and contrast enhancement. Then, using edge detection and contour finding algorithms, all spots are automatically identified, and their pixel area and optical density integral are calculated. The positions of the developing solvent front and the starting line are also automatically identified, and the specific displacement value for each spot is calculated. The specific displacement value is equal to the distance from the spot center to the starting point divided by the distance from the developing solvent front to the starting point.

[0051] The reaction progress is determined by comparing the intensity trends of reactant (sphingosine) spots and product (ceramide) spots. The judgment logic is as follows: calculate the area decay rate of reactant spots or the area growth rate of product spots in each round of TLC analysis. When reactant spots become extremely blurry (their pixel area is below a set threshold) or disappear completely, while product spots are strong and concentrated, the image analysis algorithm outputs a "reaction complete" deterministic signal to the control judgment module 102. The second stage ends when TLC detection shows that reactant spots have disappeared or product spot intensity has reached the threshold and outputs a reaction complete signal. If the image quality is poor, such as blurriness or uneven brightness, the system automatically triggers a re-image mechanism. If two consecutive TLC analyses fail, the system triggers an alarm and suggests manual intervention or initiating a backup analysis strategy, such as near-infrared spectroscopy bypass analysis.

[0052] S104. If it is determined that the currently collected multi-source data belongs to the third stage, then a quencher is added based on the synthesis instruction to terminate the reaction, and a cooling and crystallization process is carried out.

[0053] Specifically, during the second-stage synthesis process, the TLC sampling and analysis unit operates according to a preset cycle, such as 10 minutes. After each analysis, it sends a status signal to the judgment and control module, including a reaction in progress signal, a reaction complete signal, and an analysis failure signal. However, upon receiving the reaction complete signal, it does not immediately and unconditionally switch stages. To prevent misjudgments that may occur in a single analysis, such as abnormal spotting or uneven color development, a process called "reaction endpoint confirmation logic" is initiated: Condition 1: The latest TLC analysis result must be "reaction complete"; Condition 2: Check the result of the previous TLC analysis. If the previous result was "reaction in progress" and the current result is "reaction complete," this constitutes a strong trend confirmation signal, indicating that the reaction has just reached its endpoint. This is the most ideal and reliable data sequence; Condition 3: Verify whether the current reaction temperature is still stable within the preset isothermal range (e.g., 60±0.5℃). If the temperature has already run out of control, the TLC results may be unreliable.

[0054] If the latest TLC result is "complete reaction", but the previous result was not "reaction in progress" (such as the first test after the device restarts), the system will start "emergency confirmation mode": immediately trigger an additional TLC test. If both results are "complete reaction" and the temperature is within the allowable range, the endpoint will be confirmed; otherwise, the system will alarm "endpoint confirmation abnormal" and wait for manual decision-making.

[0055] Therefore, only when a reaction completion signal is received, the judgment conditions are met, and the reaction temperature is maintained within the preset constant temperature range, is it determined to be in the third stage. The reaction rate is adjusted based on the set stirring rate, and the feeding of glacial acetic acid is controlled according to the set synthesis command. The pH value of the reactor is monitored synchronously until the pH value drops to neutral. The reactor is then controlled to carry out a cooling and crystallization process according to the synthesis command. Specifically, acetic acid is added to quench the reaction, and then lower alcohol is added and the temperature is lowered to 15~20℃, controlled at a speed of 10~15℃ / h. After holding at this temperature for 1~2h, the mixture is filtered. The filter cake is washed once with lower alcohol, and then lower alcohol is added to recrystallize the filter cake at 35~65℃. After dissolution, the temperature is lowered to 10~20℃, controlled at a speed of 10~15℃ / h, and held at this temperature for 1~2h. After filtration, the filter cake is washed again with lower alcohol.

[0056] The feeding process is dynamically monitored and weighed in S101 based on the set synthesis instructions. Once the third stage is determined, a command is sent to the stirring controller to reduce the stirring rate from the reaction rate (e.g., 300 rpm) to a lower speed (e.g., 100 rpm). This is to prevent material splashing or side reactions due to localized over-acidity or intense exothermic reactions at the moment of adding the quencher (glacial acetic acid). After the speed is reduced to a low level, a command is sent to the controller connected to the glacial acetic acid metering pump. The metering pump precisely adds the calculated volume (e.g., 2.2g) of quencher according to the preset molar amount (equivalent to the molar amount of catalyst) and concentration, maintaining a stable feeding rate. During acid addition, the system reads data from the pH sensor at high speed, verifying in real time whether the pH value drops from strongly alkaline to near neutral as expected. After the quencher is added, the system waits for a short mixing time (e.g., 30 seconds) before restoring the stirring rate to normal to ensure system homogeneity. Thus, the "quenching" operation is complete.

[0057] Then the cooling and crystallization process begins. The control process is dynamically optimized based on real-time feedback. First, the temperature of the reactor is controlled according to the set cooling rate, such as starting the cooling from the reaction temperature (60℃) at a relatively fast preset rate (e.g., 15℃ / h). Simultaneously, data collected by turbidity and image sensors are acquired in real time. When the image sensor detects the appearance of the first microcrystal, or when the turbidity value shows a sharp inflection point, it is determined that "crystal nuclei have begun to form." Once a nucleation event is detected, cooling is immediately paused, and even a small temperature rebound (e.g., 0.5-1℃) is performed, maintaining this temperature for 1-2 hours. The purpose of this operation is to dissolve some of the submicron-sized, unstable crystal nuclei, retaining only the most stable nuclei, thereby effectively controlling the final crystal quantity and laying the foundation for the growth of large and uniform crystals. After continuing cooling and maintaining the temperature for 1-2 hours, the mixture is filtered, and the filter cake is washed once with a low-grade alcohol.

[0058] Then, lower alcohols are added to recrystallize the filter cake at 35-65°C. After dissolution, the temperature is lowered to 10-20°C, with a controlled rate of 10-15°C / h. During this process, the cooling rate is dynamically adjusted based on the real-time crystal growth rate. The real-time crystal growth rate is calculated from the average crystal size D50 of the yellow surface based on the acquired crystal image. The real-time crystal growth rate is the ratio of the difference in crystal size between two adjacent time intervals to the time difference. The dynamic adjustment strategy is as follows: If the real-time growth rate is higher than the ideal value (e.g., 0.5~1.2 μm / min), it indicates that the cooling is too fast, which may cause impurities to be encapsulated in the crystal or uneven growth. The system will automatically reduce the cooling rate by 10%, for example, from 15℃ / h to 13℃ / h. If the real-time growth rate is lower than the ideal value, it indicates that the cooling is too slow and the production efficiency is low. The system will automatically increase the cooling rate by 10%, for example, from 15℃ / h to 17℃ / h, but within an allowable safety limit. If the growth rate is within the ideal range, the current cooling rate will be maintained. Through this closed-loop feedback control, the system can automatically optimize the crystallization process on the best path to ensure robust crystal growth.

[0059] After the temperature drops to the preset crystallization endpoint temperature (e.g., 15℃), maintain this temperature for 1-2 hours, continuously monitoring the crystal particle size during this process. When the rate of change of D50 approaches zero for a continuous period (e.g., 30 minutes) and the holding time is reached, it indicates that crystal growth is essentially complete. Then, filter the mixture and wash the filter cake with a low-grade alcohol. At this point, a crystallization completion signal is output. The third stage ends when the pH value drops to neutral and crystallization is complete, and the crystal growth rate approaches zero.

[0060] S105. If it is determined that the currently collected multi-source data belongs to the fourth stage, then control the blower to work and dry the product of the third stage for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids.

[0061] Specifically, upon receiving a signal indicating crystallization completion, the process is considered to be in the fourth stage. At this point, the blower is activated, and the product is dried at 50-60°C for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids. The drying endpoint is determined by integrating an online moisture detector, such as a near-infrared or resistive moisture sensor, within the drying chamber to monitor the product's moisture content in real time. A moisture content threshold is set for the drying endpoint, such as ≤0.5%. During the drying process, the system collects moisture data in real time. If the moisture content is ≤0.5% within 10-12 hours, the drying process is terminated early to save energy. The end condition for the fourth stage is a moisture content ≤0.5% after drying. If the moisture content remains above the threshold after 12 hours, the system alarms "drying abnormality" and suggests checking the drying chamber temperature, airflow, or extending the drying time.

[0062] The process transforms the original experience-based operation into a data-driven process throughout the entire workflow. Every state change is recorded with data and logical judgments. Quality checks (such as whether the reaction is complete, whether the crystals are qualified, etc.) are moved from offline testing of the final product to real-time online judgment and proactive control during the production process. This fundamentally ensures the high purity and high yield of the product and realizes intelligent decision-making throughout the entire chain, from judging the reaction endpoint and optimizing crystallization to handling anomalies. This significantly reduces the reliance on the personal experience of operators and improves production efficiency and batch consistency.

[0063] The second embodiment of this application is as follows: Please see Figure 10 The present invention provides a synthesis control system for ceramide compounds based on long-chain fatty acids, which is applied to a synthesis control method for ceramide compounds based on long-chain fatty acids as provided in the first embodiment. The synthesis control system for ceramide compounds based on long-chain fatty acids includes a multi-source data acquisition module and a control judgment module 102. The multi-source data acquisition module is used to dynamically weigh and monitor the raw materials based on the set synthesis instructions, and to acquire the current reaction data through various acquisition devices, and transmit the obtained multi-source data to the control judgment module 102. The control and judgment module 102 is used to judge the currently collected multi-source data with the preset reaction stage. If the currently collected multi-source data is judged to belong to the first stage, the reactor is controlled to heat up to the set reaction temperature based on the synthesis command. If the currently collected multi-source data is judged to belong to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under constant temperature conditions until TLC detection confirms that the reaction is complete. If the currently collected multi-source data is judged to belong to the third stage, a quencher is added to terminate the reaction based on the synthesis command, and a cooling and crystallization process is carried out. If the currently collected multi-source data is judged to belong to the fourth stage, the blower is controlled to work to dry the product of the third stage for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids.

[0064] Regarding the system in the above embodiments, the specific ways in which each module performs operations have been described in detail in the embodiments related to the method, and will not be elaborated here.

[0065] For the system embodiments, since they basically correspond to the method embodiments, the relevant parts can be referred to in the description of the method embodiments. The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separate, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this application according to actual needs. Those skilled in the art can understand and implement this without creative effort.

[0066] Accordingly, this application also provides an electronic device, comprising: one or more processors; a memory for storing one or more programs; and, when the one or more programs are executed by the one or more processors, causing the one or more processors to implement the above-described method for controlling the synthesis of ceramide compounds based on long-chain fatty acids. Figure 11 The diagram shown is a hardware structure diagram of any device with data processing capabilities, which is part of a synthesis control system for ceramide compounds based on long-chain fatty acids provided in an embodiment of the present invention. Except for... Figure 11 In addition to the processor, memory, and network interface shown, any data processing device in the embodiment may also include other hardware depending on the actual function of the data processing device, which will not be described in detail here.

[0067] Accordingly, this application also provides a computer-readable storage medium storing computer instructions that, when executed by a processor, implement the above-described method for controlling the synthesis of ceramide compounds based on long-chain fatty acids. The computer-readable storage medium can be an internal storage unit of any data-processing device as described in any of the foregoing embodiments, such as a hard disk or memory. The computer-readable storage medium can also be an external storage device, such as a plug-in hard disk, smart media card (SMC), SD card, flash card, etc., equipped on the device. Furthermore, the computer-readable storage medium can include both internal storage units of any data-processing device and external storage devices. The computer-readable storage medium is used to store the computer program and other programs and data required by the data-processing device, and can also be used to temporarily store data that has been output or will be output.

[0068] Other embodiments of this application will readily occur to those skilled in the art upon consideration of the specification and practice of the disclosure herein. This application is intended to cover any variations, uses, or adaptations of this application that follow the general principles of this application and include common knowledge or customary techniques in the art not disclosed herein.

[0069] It should be understood that this application is not limited to the precise structure described above and shown in the accompanying drawings, and various modifications and changes can be made without departing from its scope.

Claims

1. A method for controlling the synthesis of ceramide compounds based on long-chain fatty acids, characterized in that, Includes the following steps: Based on the set synthesis instructions, the raw materials are dynamically weighed and monitored, and the currently collected multi-source data is compared with the preset reaction stage. If it is determined that the currently collected multi-source data belongs to the first stage, then the reactor temperature is controlled to rise to the set reaction temperature based on the synthesis command; If it is determined that the currently collected multi-source data belongs to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under isothermal conditions until TLC detection confirms that the reaction is complete. If it is determined that the currently collected multi-source data belongs to the third stage, a quencher is added based on the synthesis instruction to terminate the reaction, and a cooling and crystallization process is carried out. If it is determined that the currently collected multi-source data belongs to the fourth stage, then the blower is controlled to work, and the product of the third stage is dried for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids. If the currently collected multi-source data is determined to belong to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under isothermal conditions until TLC detection confirms the reaction is complete, including: When the currently collected multi-source data belongs to the second stage, the temperature of the reactor is controlled to be maintained within 55~65℃, and the stirring equipment is controlled to stir the reaction for 2~3 hours to carry out the amine ester exchange reaction. The timer is controlled to automatically sample and precisely spot samples within a set interval based on the received periodic monitoring signal; The TLC plate after spotting is transferred, and a developing solvent is added for automatic development until the set height is reached, after which it is dried. After drying, the TLC board is developed and images are acquired. The acquired images are then processed for image recognition and preprocessing. The reaction progress is determined based on the calculated spot shift value. Once the spot pixels reach the set endpoint determination condition, a complete reaction signal is output.

2. The method for controlling the synthesis of ceramide compounds based on long-chain fatty acids as described in claim 1, characterized in that, Based on the set synthesis instructions, the raw materials are dynamically weighed and monitored, and the currently collected multi-source data is compared with the preset reaction stages, including: Based on the received synthesis instructions, the system outputs the types and amounts of sphingosine compounds, long-chain fatty acid esters, organic bases, and lower alcohols, and outputs a feeding completion signal when the feeding is completed. Based on the received feeding completion signal, control multiple data acquisition devices to collect data at a set sampling frequency; The collected multi-source data is transmitted to the control system and compared with the preset reaction stage for judgment.

3. The method for controlling the synthesis of ceramide compounds based on long-chain fatty acids as described in claim 1, characterized in that, Between the first and second phases, the method further includes: Calculate the average temperature within the set temperature range and the fluctuation of the current temperature. If both the average temperature and the fluctuation of the current temperature are less than or equal to the set tolerance threshold, proceed to the second stage.

4. The method for controlling the synthesis of ceramide compounds based on long-chain fatty acids as described in claim 1, characterized in that, If the currently collected multi-source data is determined to belong to the third stage, a quencher is added based on the synthesis command to terminate the reaction, and a cooling and crystallization process is performed, including: The received complete response signal is verified multiple times until successful verification is achieved, then proceed to the third stage; The reaction rate is adjusted based on the set stirring rate, and the feeding of glacial acetic acid is controlled according to the set synthesis instructions. The pH value of the reactor is monitored simultaneously until the pH value drops to neutral. The reactor is controlled to undergo a cooling and crystallization process according to the synthesis instructions.

5. The method for controlling the synthesis of ceramide compounds based on long-chain fatty acids as described in claim 4, characterized in that, The reaction vessel is controlled to undergo a cooling and crystallization process according to the synthesis instructions, including: The temperature of the reactor is controlled according to the set cooling rate, and data collected by the turbidity sensor and image sensor are acquired in real time. After determining that crystal nuclei have been generated, the reactor is kept at the temperature for 1-2 hours, then filtered and cleaned once with low alcohol. The cooling rate is adjusted according to the real-time crystal growth rate until the temperature drops to the preset crystallization endpoint temperature. When the real-time crystal growth rate is zero and the holding time is reached, a crystallization completion signal is output.

6. A synthesis control system for ceramide compounds based on long-chain fatty acids, applied to the synthesis control method for ceramide compounds based on long-chain fatty acids as described in claim 1, characterized in that, The synthesis control system for the ceramide compound based on long-chain fatty acids includes a multi-source data acquisition module and a control judgment module. The multi-source data acquisition module is used to dynamically weigh and monitor the raw materials based on the set synthesis instructions, and to acquire the current reaction data through various acquisition devices, and transmit the obtained multi-source data to the control and judgment module. The control and judgment module is used to judge the currently collected multi-source data with the preset reaction stage. If the currently collected multi-source data is judged to belong to the first stage, the reactor is heated to the set reaction temperature based on the synthesis command. If the currently collected multi-source data is judged to belong to the second stage, the reaction system is controlled to carry out the amine-ester exchange reaction under constant temperature conditions until TLC detection confirms that the reaction is complete. If the currently collected multi-source data is judged to belong to the third stage, a quencher is added to terminate the reaction based on the synthesis command, and a cooling and crystallization process is carried out. If the currently collected multi-source data is judged to belong to the fourth stage, the blower is controlled to work to dry the product of the third stage for 10-12 hours to obtain a ceramide compound based on long-chain fatty acids.

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