Purification method of glucosamine hydrochloride

Abstract

The invention relates to the technical field of chemical engineering, in particular to a purification method of glucosamine hydrochloride, which adopts a composite decolorizing agent and a gradient dissolution process to remarkably improve decolorizing stability and efficiency. In the purification stage, the ion exchange process is dynamically regulated and controlled by monitoring the conductivity and the pH value in real time, impurities are efficiently removed, and the product purity is improved; in the crystallization process, a multi-modal data fusion algorithm is introduced, a crystallization path is dynamically optimized according to multi-dimensional parameters such as images, temperature, pH and turbidity, generation of a target crystal form is promoted, and the consistency of the yield and the crystal form is improved; a mother liquor reflux enrichment process is combined, so that resource recycling is realized, and consumption and three-waste emission are reduced; and finally, performing program temperature control vacuum drying to ensure stable physicochemical properties of the product. According to the method, accurate control over the whole process is achieved, high-purity and high-yield glucosamine hydrochloride can be stably prepared, and the high-end application requirement is met.

Description

Technical Field

[0001] This invention relates to the field of chemical engineering technology, and in particular to a method for purifying glucosamine hydrochloride. Background Technology

[0002] Glucosamine hydrochloride, as an important bioactive substance, has wide applications in various fields such as medicine, health products, and food additives. It is not only a key component of proteoglycans in the articular cartilage matrix, significantly contributing to joint health and promoting cartilage repair, but it is also used as a nutritional supplement to help improve bone and joint function. With increasing market demand, the requirements for the purity and quality of glucosamine hydrochloride are also rising. Therefore, how to efficiently and environmentally achieve its high-purity preparation has become a current research hotspot.

[0003] Existing purification methods for glucosamine hydrochloride suffer from unstable decolorization, imprecise purification process control leading to incomplete impurity removal, and difficulty in precisely controlling the crystallization process, making it difficult to meet the demand for high-purity products. Summary of the Invention

[0004] The purpose of this invention is to provide a purification method for glucosamine hydrochloride, which solves the technical problems in the prior art, such as unstable decolorization effect, insufficient precision in purification process control leading to incomplete removal of impurities, and difficulty in precisely controlling the crystallization process, making it difficult to meet the demand for high-purity products.

[0005] To achieve the above objectives, the present invention provides a method for purifying glucosamine hydrochloride, comprising the following: First, crude glucosamine hydrochloride is placed in a polar solvent and dissolved in a gradient at a set temperature. Then, a composite decolorizing agent is added for adsorption and decolorization. Subsequently, the decolorized solution was purified by using a dynamic control algorithm based on real-time monitoring of conductivity and pH to regulate the adsorption-desorption cycle of the ion exchange resin column in order to remove impurities and improve purity. Then, the purified solution is transferred to the crystallization reactor, and an adaptive crystallization control algorithm based on multimodal data fusion is started. By analyzing the high-definition image, temperature, pH and turbidity parameters of the solution in real time, the crystallization kinetic path is dynamically adjusted to induce the formation of a specific crystal form with high purity and high yield. After crystallization, the mother liquor is separated to obtain wet crystals of glucosamine hydrochloride. Finally, the wet crystals of glucosamine hydrochloride were subjected to temperature-controlled vacuum drying to obtain the purified high-purity glucosamine hydrochloride product.

[0006] The polar solvent used is water, or at least two of the following: water, methanol, and ethanol, mixed in any proportion. The specific process of gradient dissolution is as follows: first, preheat the solvent to 40-45℃, add the crude product, and stir at a rate of 100-200 rpm for 5-10 minutes; then, heat the system to 60-65℃ and continue stirring until completely dissolved.

[0007] The composite decolorizing agent used consists of activated carbon and diatomaceous earth in a mass ratio of 3-5:1, and its total addition amount is 1%-5% of the dry weight of the crude product; the decolorization process is carried out at 55-60℃, and the adsorption time is 30-60 minutes.

[0008] The purification process of the decolorized solution includes ion exchange resin column purification and solvent selective crystallization. The ion exchange resin column purification uses a strong acidic cation exchange resin and is controlled by a dynamic adsorption-desorption cycle algorithm. The solution flow rate and resin regeneration frequency are dynamically adjusted according to the real-time monitoring of the effluent conductivity, pH value and glucosamine concentration. Solvent-selective crystallization treatment uses an aqueous mixed solvent, including a reversible ionic liquid, and introduces a pulsed CO2 / N2 gas flow to trigger a reversible protonation-deprotonation cycle of DRIL, inducing selective crystallization of glucosamine hydrochloride. The pulsed gas flow is adjusted in real time by a reinforcement learning-model prediction control coupled algorithm.

[0009] The dynamic adsorption-desorption cycle algorithm is as follows: During the adsorption stage, when the conductivity of the effluent rises to 1.2 times the initial value, it is considered that the resin adsorption is saturated. At this time, the feeding is stopped and the desorption process is started. During the desorption stage, a hydrochloric acid solution with a mass concentration of 2%-5% is used as the desorbent, and backwashing is performed at 0.5 times the initial flow rate until the conductivity of the effluent drops to less than 0.8 times the initial value, at which point desorption is complete. The resin column was then rinsed with deionized water until neutral, in preparation for the next round of adsorption.

[0010] During processing breaks or product switching, a standard online cleaning procedure is performed, using cleaning agents to thoroughly clean the dissolving tank, crystallization reactor, pipelines, and valves to prevent cross-contamination and ensure the purity and consistency of each batch of products.

[0011] The adaptive crystallization control algorithm based on multimodal data fusion is executed according to the following steps: The image sequence of the crystallization solution is captured in real time by a high-definition camera, and the physicochemical parameters of the solution are collected simultaneously by online temperature sensor, pH sensor and turbidity sensor; The image sequence is input into a pre-trained convolutional neural network model, which outputs the crystal morphology distribution, average size, and size dispersion. Physicochemical parameters are integrated with crystal morphology characteristics to form a multidimensional feature vector; The multidimensional feature vector is input into the reinforcement learning decision model. Based on the deviation between the current crystallization state and the preset optimal crystallization path, the decision model outputs real-time control commands to adjust the cooling rate, stirring speed, or antisolvent addition rate during the crystallization process, so that the crystallization process always converges toward the goal of high purity, large particles, and narrow distribution.

[0012] The purified product was further validated by online 1H NMR spectroscopy for loop closure, as detailed below: A 1.7T miniature benchtop NMR spectroscopy system was used to acquire end-cell proton signals at δ 5.2 ppm with a resolution of 0.1 Hz. Purity was predicted using a partial least squares (PLS) model, with a root mean square error (RMSEP) ≤ 0.15%. When the predicted purity is below 99.5%, the automatic reflux pipeline is triggered to return the product to the secondary crystallization unit, achieving 100% release control.

[0013] This invention discloses a purification method for glucosamine hydrochloride. By employing a composite decolorizing agent combined with a gradient dissolution process, the method significantly improves decolorization stability and efficiency, effectively solving problems such as uneven decolorization and high residual color in traditional methods. During the purification stage, a dynamic control algorithm based on real-time monitoring of conductivity and pH value enables precise regulation of the adsorption-desorption process of the ion exchange resin column, thereby efficiently removing various impurities and significantly improving product purity. In the crystallization stage, an adaptive control algorithm based on multimodal data fusion is introduced. By analyzing multi-dimensional parameters such as image, temperature, pH, and turbidity in real time, the crystallization path is dynamically optimized, effectively guiding the formation of the target crystal form and significantly improving crystal yield and product crystal form consistency. Simultaneously, the mother liquor reflux enrichment process achieves resource recycling, reducing raw material loss and waste generation. Finally, programmed temperature-controlled vacuum drying ensures the stability of the finished product's physicochemical properties. The overall process achieves precise control throughout the entire process from decolorization and purification to crystallization, effectively overcoming the shortcomings of traditional processes such as extensive control and low product purity. It can stably prepare high-purity, high-yield glucosamine hydrochloride products, meeting the needs of high-end applications. Attached Figure Description

[0014] 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.

[0015] Figure 1 This is a flowchart of the purification method for glucosamine hydrochloride of the present invention. Detailed Implementation

[0016] The embodiments of the present invention are described in detail below. Examples of the embodiments are shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain the present invention, but should not be construed as limiting the present invention.

[0017] Please see Figure 1 , Figure 1 This is a flowchart of the purification method for glucosamine hydrochloride of the present invention.

[0018] This invention provides a method for purifying glucosamine hydrochloride, comprising the following: S1. First, place the crude glucosamine hydrochloride in a polar solvent and perform gradient dissolution at a set temperature. Then, add a composite decolorizing agent for adsorption and decolorization. In this specific embodiment, the polar solvent used is water, or at least two of the following polar solvents, namely water, methanol, and ethanol, mixed in any proportion; The specific process of gradient dissolution is as follows: first, preheat the solvent to 40-45℃, add the crude product, and stir at a rate of 100-200 rpm for 5-10 minutes; then, heat the system to 60-65℃ and continue stirring until completely dissolved.

[0019] The composite decolorizing agent used consists of activated carbon and diatomaceous earth in a mass ratio of 3-5:1, and its total addition amount is 1%-5% of the dry weight of the crude product; the decolorization process is carried out at 55-60℃ and the adsorption time is 30-60 minutes.

[0020] S2. Subsequently, the decolorized solution is purified by using a dynamic control algorithm based on real-time monitoring of conductivity and pH to regulate the adsorption-desorption cycle of the ion exchange resin column in order to remove impurities and improve purity. In this specific embodiment, the decolorized solution is purified by ion exchange resin column purification and solvent selective crystallization. The ion exchange resin column purification uses a strong acidic cation exchange resin and is controlled by a dynamic adsorption-desorption cycle algorithm. The solution flow rate and resin regeneration frequency are dynamically adjusted according to the real-time monitoring of the effluent conductivity, pH value and glucosamine concentration. Solvent-selective crystallization treatment uses an aqueous mixed solvent, including a reversible ionic liquid, and introduces a pulsed CO2 / N2 gas flow to trigger a reversible protonation-deprotonation cycle of DRIL, inducing selective crystallization of glucosamine hydrochloride. The pulsed gas flow is adjusted in real time by a reinforcement learning-model prediction control coupled algorithm.

[0021] The dynamic adsorption-desorption cycle algorithm is as follows: During the adsorption stage, when the conductivity of the effluent rises to 1.2 times the initial value, it is considered that the resin adsorption is saturated. At this time, the feeding is stopped and the desorption process is started. During the desorption stage, a hydrochloric acid solution with a mass concentration of 2%-5% is used as the desorbent, and backwashing is performed at 0.5 times the initial flow rate until the conductivity of the effluent drops to less than 0.8 times the initial value, at which point desorption is complete. The resin column was then rinsed with deionized water until neutral, in preparation for the next round of adsorption.

[0022] S3. Then, the purified solution is transferred to the crystallization reactor, and the adaptive crystallization control algorithm based on multimodal data fusion is started. By analyzing the high-definition image, temperature, pH and turbidity parameters of the solution in real time, the crystallization kinetic path is dynamically adjusted to induce the formation of a specific crystal form with high purity and high yield. In this specific implementation, the adaptive crystallization control algorithm based on multimodal data fusion is executed according to the following steps: The image sequence of the crystallization solution is captured in real time by a high-definition camera, and the physicochemical parameters of the solution are collected simultaneously by online temperature sensor, pH sensor and turbidity sensor; The image sequence is input into a pre-trained convolutional neural network model, which outputs the crystal morphology distribution, average size, and size dispersion. Physicochemical parameters are integrated with crystal morphology characteristics to form a multidimensional feature vector; The multidimensional feature vector is input into the reinforcement learning decision model. Based on the deviation between the current crystallization state and the preset optimal crystallization path, the decision model outputs real-time control commands to adjust the cooling rate, stirring speed, or antisolvent addition rate during the crystallization process, so that the crystallization process always converges toward the goal of high purity, large particles, and narrow distribution.

[0023] S4. After crystallization is complete, separate the mother liquor to obtain glucosamine hydrochloride wet crystals; In this specific embodiment, the separated mother liquor is collected and concentrated through a mother liquor enrichment and recovery unit (such as a vacuum concentrator).

[0024] The concentrated mother liquor can be returned to the gradient dissolution process in step one at a specified ratio (e.g., 5%-10%) to dissolve new crude product.

[0025] S5. Finally, the wet crystals of glucosamine hydrochloride are subjected to programmed temperature-controlled vacuum drying to obtain the purified high-purity glucosamine hydrochloride product.

[0026] In this specific implementation method, the purified product was further verified by online 1H NMR loop spectroscopy, as follows: A 1.7T miniature benchtop NMR spectroscopy system was used to acquire end-cell proton signals at δ 5.2 ppm with a resolution of 0.1 Hz. Purity was predicted using a partial least squares (PLS) model, with a root mean square error (RMSEP) ≤ 0.15%. When the predicted purity is below 99.5%, the automatic reflux pipeline is triggered to return the product to the secondary crystallization unit, achieving 100% release control.

[0027] The final high-purity glucosamine hydrochloride product is packaged under specific environmental conditions (such as low temperature and low humidity), moisture-proof and light-proof packaging materials are selected, and storage conditions are clearly specified to ensure the stability of the product during its shelf life.

[0028] When handling gaps or switching products, perform standard online cleaning procedures, using cleaning agents to thoroughly clean the dissolving tank, crystallization reactor, pipelines, and valves to prevent cross-contamination and ensure the purity and consistency of each batch of products.

[0029] Before or after decolorization, use filter bags, candle filters, or plate and frame filters to remove insoluble particulate impurities, residual decolorizing agent powder, or colloidal substances from the solution, providing a cleaner feed for subsequent purification and crystallization.

[0030] After ion exchange resin column purification is completed, an intermediate monitoring step is added: the absorbance of the effluent at a wavelength of 260-280 nm is monitored in real time using an online ultraviolet spectrometer, and this absorbance is used as a feedback signal to dynamically adjust the parameters of the CO2 / N2 pulsed gas flow in the subsequent solvent-selective crystallization treatment.

[0031] After adaptive crystallization and before separation, a polishing purification step is added: 1%-3% of the volume of pretreated pharmaceutical-grade activated carbon is added to the crystallization system, and the mixture is slowly stirred at 50-100 rpm for 15-30 minutes at 25-35℃. Then, the mixture is allowed to stand and the activated carbon is removed.

[0032] The purification method for glucosamine hydrochloride in this embodiment firstly removes pigments and macromolecular impurities from the crude product efficiently through gradient dissolution combined with a composite decolorizing agent, laying a solid foundation for further purification. Its core innovation lies in the introduction of a dynamic control algorithm based on real-time monitoring. This algorithm precisely regulates the adsorption-desorption cycle and crystallization process of the ion exchange resin, achieving intelligent and optimized operation across the entire chain from impurity removal to crystal formation. This not only significantly improves product purity (≥99.5%) and yield but also effectively ensures that the crystals possess excellent characteristics such as uniform particle size and regular morphology. Furthermore, this method constructs a complete resource recycling and quality assurance closed loop: the reflux of the mother liquor significantly reduces raw material consumption and waste emissions, reflecting the concept of green production; while the closed-loop verification system combining online 1H NMR spectroscopy with an automatic reflux mechanism achieves 100% online monitoring and assurance of finished product quality, preventing the outflow of substandard products and ensuring batch-to-batch stability and consistency. In summary, this method demonstrates outstanding advantages in terms of efficiency, quality, cost control, and environmental protection, providing a stable, reliable, and advanced technical path suitable for large-scale industrial production of high-purity, high-quality glucosamine hydrochloride.

[0033] The above-disclosed embodiments are merely one or more preferred embodiments of this application and should not be construed as limiting the scope of this application. Those skilled in the art can understand that all or part of the processes for implementing the above embodiments and equivalent changes made in accordance with the claims of this application still fall within the scope of this application.

Claims

1. A method for purifying glucosamine hydrochloride, characterized in that, comprising the following steps: First, the crude glucosamine hydrochloride is dissolved in a polar solvent at a set temperature, and then a composite decolorizing agent is added for adsorption and decolorization; Then, the decolorized solution is purified by using a dynamic control algorithm based on real-time monitoring of conductivity and pH to regulate the adsorption-desorption cycle of the ion exchange resin column, to remove impurities and improve purity; Then, the purified solution is transferred to a crystallization reactor, and an adaptive crystallization control algorithm based on multi-modal data fusion is started to dynamically regulate the crystallization kinetics by real-time analysis of high-definition images, temperature, pH and turbidity parameters of the solution, to induce the formation of specific crystal forms with high purity and high yield; After crystallization is complete, the mother liquor is separated to obtain wet glucosamine hydrochloride crystals; Finally, the wet glucosamine hydrochloride crystals are subjected to programmed temperature vacuum drying to obtain high-purity glucosamine hydrochloride.

2. The method for purifying glucosamine hydrochloride according to claim 1, characterized in that, the polar solvent used is water, and the polar solvent used is a solvent mixed in any proportion from at least two of water, methanol and ethanol; The specific process of gradient dissolution is: first, preheat the solvent to 40-45℃, add the crude product, and stir at a speed of 100-200 rpm for 5-10 minutes; then, increase the temperature of the system to 60-65℃, and continue to stir until complete dissolution.

3. The method for purifying glucosamine hydrochloride according to claim 2, characterized in that, the composite decolorizing agent used is composed of activated carbon and diatomite in a mass ratio of 3-5:1, and the total amount of addition is 1%-5% of the dry weight of the crude product; the decolorization process is carried out at 55-60℃, and the adsorption time is 30-60 minutes.

4. The method for purifying glucosamine hydrochloride according to claim 3, characterized in that, the purification of the decolorized solution includes ion exchange resin column purification and solvent selective crystallization treatment; The ion exchange resin column purification uses strong acid cation exchange resin and is controlled based on a dynamic adsorption-desorption cycle algorithm, and the solution flow rate and resin regeneration frequency are dynamically adjusted according to the real-time monitoring of the effluent conductivity, pH and glucosamine concentration; The solvent selective crystallization treatment uses a mixed solvent containing water, including a reversible ionic liquid, and a pulse gas flow of CO2 / N2 is introduced to trigger the reversible protonation-deprotonation cycle of DRIL, to induce the selective crystallization of glucosamine hydrochloride, and the pulse gas flow is adjusted in real time by a reinforcement learning-model predictive control coupling algorithm.

5. The method for purifying glucosamine hydrochloride according to claim 4, characterized in that, the dynamic adsorption-desorption cycle algorithm is as follows: In the adsorption stage, when the effluent conductivity rises to 1.2 times the initial value, it is considered that the resin adsorption is saturated, at which time the feeding is paused and the desorption program is started; In the desorption stage, a hydrochloric acid solution with a mass concentration of 2%-5% is used as a desorbent, and a reverse flush is performed at 0.5 times the initial flow rate until the effluent conductivity decreases to less than 0.8 times the initial value, i.e., desorption is complete; Subsequently, the resin column is washed with deionized water until it is neutral, preparing for the next round of adsorption.

6. The method for purifying glucosamine hydrochloride according to claim 5, characterized in that, During the processing gap or switching products, a standard online cleaning program is performed, and a cleaning agent is used to thoroughly clean the dissolving tank, crystallization reactor, pipelines, and valves to prevent cross-contamination and ensure the purity and consistency of each batch of products.

7. The method for purifying glucosamine hydrochloride according to claim 6, characterized in that, The adaptive crystallization control algorithm based on multi-modal data fusion is executed according to the following steps: Real-time image sequences of the crystallization solution are captured by a high-definition camera, and physical and chemical parameters of the solution are synchronously collected by online temperature sensors, pH sensors, and turbidity sensors; The image sequences are input into a pre-trained convolutional neural network model, and the crystal morphology distribution, average size, and size dispersion are output; The physical and chemical parameters are fused with the crystal morphology characteristics to form a multi-dimensional feature vector; The multi-dimensional feature vector is input into a reinforcement learning decision model, which outputs real-time control instructions based on the deviation of the current crystallization state from the preset optimal crystallization path, to adjust the cooling rate, stirring speed, or anti-solvent addition rate during the crystallization process, so that the crystallization process always converges towards the target of high purity, large particles, and narrow distribution.

8. The method for purifying glucosamine hydrochloride according to claim 7, characterized in that, The purified product is further verified by online nuclear magnetic resonance spectroscopy, as follows: A 1.7T small desktop NMR is used to collect end group proton signals at 0.1 Hz resolution at δ5.2 ppm, and a partial least squares (PLS) model is used to predict purity with a root mean square error RMSEP≤0.15%; When the predicted purity is less than 99.5%, an automatic reflux pipeline is triggered to return the product to the secondary crystallization unit, achieving 100% release control.

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