Method for preparing high-purity lactulose solution by continuous circulation using sodium metaaluminate

Abstract

The application discloses a method for preparing a high-purity lactulose solution by continuously circulating sodium metaaluminate, and belongs to the technical field of oligosaccharide preparation. The preparation method of the application can reduce the reaction temperature, improve the lactulose conversion rate and purity, use food-grade activated carbon to adsorb lactulose clear liquid, remove 96.0% of aluminum ions at most, greatly reduce the cost of aluminum ion removal, and recycle sodium metaaluminate prepared by calcining aluminum hydroxide precipitation, thereby reducing the catalyst consumption. The process optimization method provided by the application is simple and feasible, meets the production demand of resource-saving and environment-friendly, and provides beneficial reference for promoting the industrialized production of lactulose prepared by using sodium metaaluminate / alkaline substance as an alkaline complex catalyst.

Description

Technical Field

[0001] This invention relates to a method for preparing high-purity lactulose solution using sodium aluminate in a continuous cycle, belonging to the field of oligosaccharide preparation technology. Background Technology

[0002] Lactulose (β-D-Galactopyranosyl-(1→4)-D-furctofuranose) is a non-digestible oligosaccharide with unique functional properties. It can inhibit the growth of various pathogenic bacteria while promoting the proliferation of beneficial intestinal bacteria, and has wide applications in health foods and clinical medicine.

[0003] Industrially, lactulose is mainly prepared using chemical methods, employing alkaline catalysts to isomerize lactose. This method suffers from strong thermodynamic equilibrium inhibition and product inhibition effects. Lactulose produced under high temperature and strongly alkaline conditions undergoes further degradation, resulting in a final product with low lactulose content and containing large amounts of residual lactose, sugar acids, monosaccharides, and pigments as byproducts. Furthermore, the presence of homogeneous alkaline catalysts makes the purification of high-purity lactulose extremely difficult, severely hindering the further development of chemical isomerization in the industrial production of lactulose.

[0004] Benefiting from the stronger affinity between the complexing catalyst and lactulose, in a strongly alkaline environment, the complexing catalyst preferentially complexes with the lactulose generated during isomerization, forming anionic complexes such as lactulose-boric acid, lactulose-aluminate, and lactulose-organogermanium. This reduces the inhibitory effect on the lactulose product and promotes the isomerization reaction to continue in the positive direction of lactulose production. The formed lactulose complexes also help prevent the degradation of lactulose in a strongly alkaline environment. Acidification treatment can cause the lactulose complexes to dissociate, releasing free lactulose and the complexing catalyst. The complexing catalyst can greatly improve the isomerization reaction efficiency to 70-85%, and the isomerization temperature is lower (60-70℃), the required reaction time is shorter, and the yield of lactulose is higher. In China, a continuous recycling method for preparing high-purity lactulose solution has been proposed using sodium aluminate / alkaline substances as alkaline catalysts (e.g., Chinese invention patent application CN201611103063.5, 2016). This method isomerizes lactose to form isomerized lactulose syrup. The isomerized lactulose syrup is then subjected to acidity adjustment, dilution, dispersion and residue-liquid separation to obtain lactulose clear liquid and precipitate respectively. The lactulose clear liquid is desalted and demonosaccharified to obtain a high-concentration lactulose solution. The precipitate is directly converted into aluminate after alkaline treatment, realizing the recycling of catalyst.

[0005] However, this invention has the following problems in the process of recycling precipitation: the reaction of the recycled batch is not complete, and the lactose residue in the mixed syrup after the reaction is too high, resulting in a low purity of the final syrup solution (66%). It is difficult to purify the lactulose solution produced in the recycled batch to obtain high-purity lactulose that meets the standards; the residual aluminum content in the lactulose clear liquid of the second round of recycling is ten to twenty times higher than that of the first reaction, and the residual aluminum content in the lactulose clear liquid of the third round of recycling is thirty to fifty times higher than that of the first reaction, which greatly increases the resin consumption for ion exchange dealuminization in the lactulose refining process; precipitation cannot be generated in the third round of isomerization, that is, as the number of reactions increases, it is difficult to precipitate the subsequent aluminum hydroxide by adjusting the pH.

[0006] Existing research on aluminum adsorption by unmodified activated carbon mainly focuses on aluminum residues during water purification processes in water plants. There is currently no domestic research specifically addressing the simultaneous decolorization and aluminum removal by activated carbon during sugar refining. In the paper "Experimental Study on Adsorption and Desorption of Aluminum by Activated Carbon," researchers used columnar activated carbon to adsorb polyaluminum chloride. 1 g of activated carbon was added to 100 mL of a solution with an aluminum concentration of 0.3 ppm. After vortexing at 20°C for 12–120 h, the aluminum removal rate reached 64.43% at 12 h and 95.83% at 120 h under pH 10.5 conditions. Under pH 6.5 conditions, the aluminum removal rate decreased, reaching 50.6% at 12 h and 83.63% at 120 h. Although this study achieved a high aluminum removal rate, the adsorption time was too long and the initial aluminum concentration in the solution was too low.

[0007] Currently, there are no patents in China addressing or optimizing methods for the problems arising in the continuous recycling process of sodium aluminate to prepare high-purity lactulose solution. There are few reports in China on the isomerization preparation of lactulose using a sodium aluminate / sodium hydroxide catalytic system, and only a few domestic lactulose producers, such as Dalian Chemical Research and Design Institute and Dandong Kangfu Pharmaceutical Co., Ltd., mean that almost all pharmaceutical-grade high-purity lactulose in China is imported. These three problems in the recycling precipitation process are bottlenecks hindering the industrial-scale production of high-purity lactulose using sodium aluminate. Solving these problems is urgently needed for the development of China's lactulose industry. Summary of the Invention

[0008] This paper addresses the problems in existing continuous recycling processes for preparing high-purity lactulose solutions using sodium aluminate as a catalyst, such as incomplete reaction in each batch, high residual aluminum content in the lactulose solution of each batch, and the inability to produce precipitation after multiple cycles.

[0009] The purpose of this invention is to provide a method for preparing high-purity lactulose solution using sodium aluminate in a continuous cycle, thereby filling the gap in domestic research on the isomerization process of lactulose preparation using a sodium aluminate / sodium hydroxide catalytic system, and at the same time making up for and overcoming the shortcomings of the current sodium aluminate / sodium hydroxide cycle catalytic preparation technology for lactulose.

[0010] The purpose of this invention is to provide a method for preparing a high-purity lactulose solution using sodium aluminate as a catalyst, the steps of which include:

[0011] (1) Dissolve lactose and sodium aluminate in water at concentrations of 10-50% w / v and 5-10% w / v, respectively, and adjust the pH of the system to 11.5-12.5. React at 50-70℃ for 1-2 hours. After the reaction is complete, dilute with water and cool. Adjust the pH to 5.0-7.0 until no more precipitate is formed in the system. Separate and wash to obtain the first lactulose clear solution and the first aluminum hydroxide precipitate.

[0012] (2) Dissolve lactose in water at a concentration of 35% w / v to obtain a lactose solution. Add the first aluminum hydroxide precipitate obtained in step (1) to the lactose solution, and add sodium aluminate to the lactose solution at a mass of 0% to 18% of the sodium aluminate mass in step (1). Adjust the pH of the system to 11.8 to 12.4, and react at 50 to 70°C for 1 to 2 hours. After the reaction is completed, dilute with water and cool. Adjust the pH to 5.0 to 7.0. No more precipitates are produced in the system. Separate and wash to obtain the second lactulose solution and the second aluminum hydroxide precipitate.

[0013] (3) Add activated carbon to the second lactulose solution obtained in step (2) to remove aluminum. After removal of aluminum, separate and wash to obtain the third lactulose solution and activated carbon adsorbed with aluminum. Add sodium hydroxide to the second aluminum hydroxide precipitate obtained in step (2) and calcine to prepare sodium aluminate.

[0014] (4) Add the sodium aluminate prepared in step (3) to step (1) and repeat steps (1) to (3) to prepare lactulose.

[0015] Optionally, the reaction temperature in step (1) is 60°C.

[0016] Optionally, in step (1), the amount of lactose added is 35% w / v and the amount of sodium aluminate added is 8.5% w / v.

[0017] In one embodiment, in step (1), sodium aluminate and lactose substrate are added to the solution at a molar ratio of 1:1.

[0018] In one embodiment, after the reaction in steps (1) and (2) is completed, the temperature is cooled to 20-30°C.

[0019] Optionally, the pH of the reaction system in step (1) is 12.2.

[0020] In one embodiment, sodium hydroxide is added in steps (1) and (2) to adjust the pH of the reaction system to 11.8 to 12.4.

[0021] In one embodiment, hydrochloric acid is used in steps (1) and (2) to adjust the pH until the system no longer produces precipitation.

[0022] Preferably, the amount of sodium aluminate added in step (2) is 12% of the amount of sodium aluminate added in step (1).

[0023] In one embodiment, step (2) involves washing for 60 minutes to obtain a second aluminum hydroxide precipitate.

[0024] Optionally, the reaction temperature described in step (2) is 55°C.

[0025] Optionally, the reaction time in step (2) is 60 min.

[0026] In one embodiment, the activated carbon powder in step (3) is food-grade powdered activated carbon.

[0027] Preferably, the activated carbon powder in step (3) is food-grade activated carbon powder of type 303.

[0028] In one embodiment, the activated carbon in step (3) is 0.1% to 5% of the supernatant.

[0029] Optionally, in step (3), the mass of activated carbon is 1% of the mass of the supernatant.

[0030] In one embodiment, activated carbon dealuminate adsorption is performed for 60 min in step (3).

[0031] In one embodiment, the sodium hydroxide concentration in step (3) is 40% w / w.

[0032] In one embodiment, aluminum hydroxide is calcined at 650°C in step (3).

[0033] In one embodiment, the sodium aluminate prepared in step (3) can normally catalyze both rounds of reactions.

[0034] Beneficial effects

[0035] Compared with the prior art, the present invention, which adopts the above technical solution, has the following beneficial effects:

[0036] (1) This invention optimizes the cyclic reaction conditions using sodium aluminate / sodium hydroxide as an alkaline complexing catalyst. In the second round of cyclic reaction, lactulose is prepared under the conditions of 55°C, 12% sodium aluminate supplementation and pH 12.2. The conversion rate reaches 79.5% and the purity reaches 91.5%. The conversion rate and purity are much higher than those of the unoptimized cyclic reaction system. This solves the problem that the cyclic batch reaction is incomplete, the mixed syrup after the reaction has too much lactose residue, resulting in low purity of the final syrup solution and difficulty in purifying the lactulose solution produced in the cyclic batch to obtain high-purity lactulose that meets the standards.

[0037] (2) This invention proposes and solves the problem of a significant increase in the residual aluminum content in the lactulose solution obtained by the cyclic reaction. Up to 96.0% of aluminum ions are removed by activated carbon adsorption, which greatly reduces the amount of ion exchange resin used and effectively reduces production costs.

[0038] (3) This invention improves the recovery rate of lactulose by washing and separating the lactulose encapsulated in the flocculation precipitate, and burns off the organic matter contained therein by adding alkali and calcining, so that the catalyst aluminum hydroxide is decomposed and recycled as sodium aluminate in the reaction.

[0039] (4) The optimized solution of the present invention meets the production requirements of resource conservation and environmental friendliness, and provides useful reference for promoting the clean, efficient and environmentally friendly industrial production of lactulose. Attached Figure Description

[0040] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0041] Figure 1 XRD patterns of the calcined recycled catalyst and pure sodium aluminate of the present invention;

[0042] Figure 2 Optimize for temperature conditions;

[0043] Figure 3 Optimize the amount of sodium aluminate added;

[0044] Figure 4 Optimize pH conditions;

[0045] Figure 5 This is a process flow diagram of the preparation method of the present invention;

[0046] Figure 6The three-round reaction dilution acid precipitation mixture prepared for this invention is compared with the lactulose clear solution and aluminum hydroxide precipitate obtained by centrifugation. Detailed Implementation

[0047] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0048] The technical solution of the present invention will be further described below with reference to specific embodiments. Unless otherwise stated, the instruments, materials, reagents, etc. used in the following embodiments can all be obtained through conventional commercial means.

[0049] The detection method used in the example: The specific operation process of determining the purity of lactulose by HPLC is as follows: After sampling, centrifuge (8000~12000rpm, 15~20min), filter the supernatant through a 0.22μm microporous membrane, and perform HPLC detection and analysis on the filtrate.

[0050] In the above preparation method, the specific detection conditions for determining the purity of lactulose by HPLC are as follows: Chromatograph: Waters 209; Column: Shodex HILICpak VG-50 4E, 4.6×250mm; Mobile phase: 75% (v / v) acetonitrile / water solution; Mobile phase flow rate: 1mL / min; Temperature: 25℃; Detector: R401 differential refractive index detector; Injection volume: 10μL.

[0051] The aluminum content was determined by spectrophotometry according to the first method of spectrophotometry in GB 5009.182—2017 "National Food Safety Standard - Determination of Aluminum in Food".

[0052] The continuous circulation process for preparing high-purity lactulose solution using sodium aluminate catalysis in this invention is shown in the figure below. Figure 5 As shown.

[0053] Example 1: A method for preparing high-purity lactulose solution using sodium aluminate catalysis

[0054] (1) Preparation of high-purity lactulose

[0055] (a) Preparation of the first round of lactulose solution

[0056] Under mechanical stirring, 7 kg of food-grade lactose and 1.7 kg of sodium aluminate were added to 20 L of water and dissolved. Sodium hydroxide was then added to adjust the pH to 12.0, and the mixture was stirred at 60 °C for 1 h. After the reaction, 80 L of deionized water was added to dilute the mixture, and the system was cooled to room temperature. Hydrochloric acid was then added to adjust the pH to 6.5. Lactulose supernatant and aluminum hydroxide precipitate were obtained by centrifugation.

[0057] 20 L of water was added to the precipitate and stirred to disperse the lactulose entrained in the precipitate into the solution. The washed lactulose solution and 6 kg of the first aluminum hydroxide precipitate were obtained by vacuum filtration. The lactulose solution obtained by centrifugation and washing were then mixed to obtain the first lactulose solution. The results are as follows: Figure 6 As shown, the first round of preparation is now complete.

[0058] (b) Preparation of the second round of lactulose solution

[0059] The second round of isomerization was carried out under mechanical stirring. 6 kg of the first aluminum hydroxide precipitate was added to 8 L of deionized water, and 12% (204 g) of sodium aluminate was added to replenish the initial catalyst. 7 kg of lactose substrate was added to the solution and stirred until dissolved. The pH of the reaction system was adjusted to 12.2 with sodium hydroxide, and water was added to bring the total reaction volume to 20 L. The reaction was then stirred at 55 °C for 60 minutes.

[0060] After the reaction, 2 L of hydrochloric acid and 78 L of deionized water were added to the isomerized lactulose syrup, and hydrochloric acid was added dropwise until the pH of the system reached 6.5, forming a mixture containing lactulose and a flocculated precipitate. The lactulose supernatant and aluminum hydroxide precipitate were obtained by centrifugation. 20 L of deionized water was added to the aluminum hydroxide precipitate, and the mixture was stirred for 60 minutes to disperse the lactulose entrained in the precipitate into the solution. The second aluminum hydroxide precipitate was separated by vacuum filtration, and the lactulose entrained in the precipitate was recovered. The lactulose supernatant obtained by centrifugation and washing was mixed to obtain the second lactulose supernatant. The results are as follows. Figure 6 As shown, the second round of preparation is now complete.

[0061] (2) Precipitate calcination and reuse

[0062] The second aluminum hydroxide precipitate from step (1) was dissolved using 2.5 L of 40% (w / w) concentrated sodium hydroxide. After drying, it was calcined at 650 °C in a muffle furnace to obtain 1.5 kg of sodium aluminate for subsequent reactions. The obtained precipitate could also catalyze the reaction normally. The XRD pattern of the calcined catalyst is shown in the figure. Figure 1 As shown, the crystal form and structure of the calcined sodium aluminate are basically consistent with those of the sodium aluminate reagent in the initial reaction, and the subsequent catalytic effect will not be affected by the change in crystal form. The calcined sodium aluminate was used in a new round of reaction according to step (1), and the separated lactulose ether was as follows... Figure 6 As shown in the table below, the conversion rate and purity of each cycle reaction are as follows:

[0063]

[0064] (3) Activated carbon adsorption for aluminum removal

[0065] Add 1% (w / v) of food-grade 303 powdered activated carbon (from the supernatant) to the second lactulose supernatant obtained by centrifugation in step (1), stir mechanically for 60 minutes, and then separate by vacuum filtration. Spectrophotometric determination showed that the aluminum concentration in the lactulose supernatant decreased from 128.0 ppm to 3.8 ppm, with an aluminum ion removal rate of 97.0%.

[0066] After filtration, the activated carbon was rinsed with a small amount of deionized water to recover the residual lactulose, yielding a lactulose-containing clear solution after decolorization and dealuminization by activated carbon. Spectrophotometric analysis showed that the aluminum concentration in the recovered lactulose-containing clear solution after rinsing the activated carbon was 0.5 ppm.

[0067] The lactulose supernatant obtained by vacuum filtration and the lactulose supernatant recovered after rinsing activated carbon were mixed, and the total lactulose and aluminum content were detected and calculated. HPLC and spectrophotometry showed that 96.9% of the aluminum in 100 mL of the lactulose supernatant obtained by centrifugation in step (1) was removed after activated carbon treatment, while the lactulose loss rate was only 1.6%.

[0068] Example 2: Effect of reaction temperature on lactulose conversion rate and purity

[0069] Based on Example 1, temperature optimization was performed for "(b) the preparation of the second round of lactulose solution". The second round of isomerization cycle reaction was carried out under mechanical stirring, with a 1L system used throughout the optimization process. 0.3 kg of aluminum hydroxide precipitate obtained in the first round of reaction in Example 1 was added to 0.4 L of deionized water, and 12% (10.2 g) of sodium aluminate was added to supplement the initial reaction. 350 g of lactose substrate was added to the solution, stirred to dissolve, and the pH of the reaction system was adjusted to 12.0 with sodium hydroxide. The volume was then brought to 1 L, and the reaction was stirred at 50°C, 55°C, 60°C, 65°C, and 70°C for 120–180 minutes. The results are as follows: Figure 2 As shown, HPLC analysis revealed that the conversion rates under the five conditions reached their maximum values ​​at 180 min, 80 min, 40 min, 30 min, and 15 min, respectively, at 73.0%, 81.2%, 79.3%, 78.0%, and 74.6%. At 50℃ and 55℃, the purity gradually increased with increasing reaction time, while at 60℃, 65℃, and 70℃, the purity gradually decreased after reaching its maximum value. The purity under all five conditions was less than 90%. To ensure a mild and controllable reaction, a reaction temperature of 55℃ was determined after comprehensive consideration.

[0070] Example 3: Effect of sodium aluminate addition on lactulose conversion rate and purity in the second cycle

[0071] Based on Example 1, the amount of sodium aluminate added was optimized for "(b) Preparation of the second round of lactulose solution". Under mechanical stirring, 0.5 kg of aluminum hydroxide precipitate was added to 0.3 L of deionized water, and sodium aluminate was added at initial concentrations of 0% (0 g), 6% (5.1 g), 12% (10.2 g), and 18% (15.3 g) by mass, respectively. 350 g of lactose substrate was added to the solution, stirred until dissolved, and the pH of the reaction system was adjusted to 12.0 with sodium hydroxide. The reaction was then stirred at 55 °C for 120 minutes. The results are as follows: Figure 3 As shown, HPLC analysis revealed that the conversion rates reached their maximum values ​​at 85 min under all four conditions, specifically 78.5%, 78.6%, 81.5%, and 81.0%, respectively. Under the same reaction time, the purity increased with increasing amounts of added sodium aluminate, but remained below 90%. Considering all factors, the recommended addition of sodium aluminate was 12% of the initial mass.

[0072] Example 4: Effect of pH on lactulose conversion rate and purity in the second round of reaction

[0073] Based on Example 1, the amount of sodium aluminate added was optimized for "(b) Preparation of the second round of lactulose solution". Under mechanical stirring, 0.5 kg of aluminum hydroxide precipitate was added to 0.3 L of deionized water, and 12% (10.2 g) of sodium aluminate was added to supplement the initial reaction. 350 g of lactose substrate was added to the solution, stirred until dissolved, and the pH of the reaction system was adjusted to 11.8, 12.0, 12.2, and 12.4 with sodium hydroxide. The reaction was then stirred at 55 °C for 120 minutes. The results are as follows: Figure 4 As shown, HPLC analysis revealed that the conversion rates reached their maximum values ​​of 81.5%, 77.7%, 79.5%, and 82.6% at 85 min, 75 min, 65 min, and 50 min, respectively. At pH 12.2, the purity reached 91.2% after 60 min, and at pH 12.4, the purity reached 91.6% after 60 min. While pH 12.2 and 12.4 achieved high purity (>90%) while maintaining a high conversion rate (>75%), the reaction solution at pH 12.4 was too dark, indicating a higher proportion of colored byproducts and making subsequent processing more difficult. Therefore, the optimal reaction conditions were determined to be 55℃, supplemented with 12% sodium aluminate, and a reaction pH of 12.2. Under these conditions, the lactulose conversion rate was 79.5%, the purity was 91.5%, and the lactulose concentration was 278.3 g / L.

[0074] Some steps in the embodiments of the present invention can be implemented using software, and the corresponding software program can be stored in a readable storage medium, such as an optical disc or a hard disk.

[0075] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for continuously cycling to prepare high-purity lactulose, characterized in that the steps include... include: (1) Dissolve lactose and sodium aluminate in water at concentrations of 10-50% w / v and 5-10% w / v, respectively, and adjust the pH of the system to 11.5-12.

5. React at 50-70℃ for 1-2 hours. After the reaction is completed, dilute with water and cool, then adjust the pH to 5.0-7.

0. Separate and wash to obtain the first lactulose clear solution and the first aluminum hydroxide precipitate. (2) Dissolve lactose in water at a concentration of 10-50% w / v to obtain a lactose solution. Add the first aluminum hydroxide precipitate obtained in step (1) to the lactose solution, and add sodium aluminate to the lactose solution at a mass of 12%-18% of the sodium aluminate mass in step (1). Adjust the pH of the system to 11.8-12.4, react at 50-70℃ for 1-2 hours, dilute with water and cool after the reaction, and then adjust the pH to 5.0-7.

0. Separate and wash to obtain the second lactulose solution and the second aluminum hydroxide precipitate. (3) Add activated carbon to the second lactulose solution obtained in step (2) to remove aluminum. After removal of aluminum, separate and wash to obtain the third lactulose solution and activated carbon adsorbed with aluminum. Add sodium hydroxide to the second aluminum hydroxide precipitate obtained in step (2) and calcine to prepare sodium aluminate. (4) Add the sodium aluminate prepared in step (3) to step (1) and repeat steps (1) to (3) to prepare lactulose. In step (3), the amount of activated carbon added is 0.1% to 5% w / v of the supernatant; Activated carbon dealuminization adsorption for 10~600 min.

2. The method according to claim 1, characterized in that, After the reaction in steps (1) and (2) is completed, cool to 20~30℃.

3. The method according to claim 1, characterized in that, In steps (1) and (2), hydrochloric acid is used to adjust the pH until no more precipitation occurs in the system.

4. The method according to claim 1, characterized in that, In steps (1) and (2), sodium hydroxide is added to adjust the pH to 11.8~12.

4.

5. The method according to claim 1, characterized in that, In steps (1) and (2), washing for 5 to 300 minutes is required to obtain aluminum hydroxide precipitate.

6. The method according to claim 1, characterized in that, In step (3), the activated carbon powder is food-grade powdered activated carbon.

7. The method according to claim 1, characterized in that, The sodium hydroxide aqueous solution is added in step (3).

8. The method according to claim 1, characterized in that, In step (3), aluminum hydroxide is calcined at 600~800℃.

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