Preparation method of anhydrous beta-lactose with high yield and low color value

Abstract

The invention relates to the technical field of saccharide purification, in particular to a high-yield and low-color-value anhydrous beta-lactose preparation method which comprises the following steps: preparing a lactose solution by taking food-grade lactose as a raw material, adding activated carbon for adsorption, then carrying out column treatment to remove nitrogen-containing inorganic salt and organic acid, and finally carrying out film evaporation concentration to separate out beta-lactose crystals. The method comprises the following steps of: adding anhydrous beta-lactose into a reaction kettle, automatically scraping off crystals, and collecting to obtain anhydrous beta-lactose, the yield of the anhydrous beta-lactose is at least 90wt%, and the color value is lower than 25. According to the method, the yield of the beta-lactose can be improved, and the produced beta-lactose is uniform in particle size, normal in color and few in impurities.

Description

Technical Field

[0001] The invention relates to the technical field of sugar purification, and in particular to a method for preparing anhydrous beta-lactose with high yield and low color value. Background Art

[0002] Anhydrous β-lactose has good flowability and excellent tableting and recompaction properties, making it useful for direct compression. In addition, due to the absence of free water and water of crystallization, anhydrous lactose is used in water-sensitive formulations. Anhydrous lactose with a moisture content of <0.5% can provide greater stability to the API, and therefore, anhydrous β-lactose is considered the preferred excipient for dry granulation tableting.

[0003] Crystallization of lactose solution above 93.5°C will form β-lactose crystals. However, rapid high-temperature drying of lactose solution will produce a mixture of monohydrated α-lactose and amorphous lactose, such as spray drying. Amorphous lactose is the most unstable and is more susceptible to Maillard condensation reaction with primary amine compounds than crystalline lactose to produce a brown product. α-lactose has low solubility and can precipitate crystals at low temperatures, dissolving α-lactose and separating β-lactose at appropriate temperatures. At present, drum drying is used in industry to prepare β-lactose: β-lactose can be obtained by drying a 30% lactose solution in a drum at a temperature above 93.5°C. The drum speed is usually set to 5-7 rpm and the heating steam pressure is above 490.5 kPa. However, due to the high surface humidity of the drum, the lactose will lose its flavor or have an abnormal color due to overheating, and the yield is not high.

[0004] Color value is a numerical value that indicates the color depth of sugar products and is one of the most important indicators of edible sugar. The color value indicates the quality of the color of sugar products and reflects the technical level of the sugar-making process. Generally speaking, the higher the color value, the higher the content of impurities in the sugar. In the production process, too strict control of the color value index will increase production costs and affect sugar recovery; too wide control will lead to substandard product quality. Therefore, whether in the production field or the circulation field, the color value indicator is particularly important. Summary of the invention

[0005] In order to solve the technical problem of low yield and high color value of β-lactose, a method for preparing anhydrous β-lactose with high yield and low color value is provided. The method of the invention can improve the yield of β-lactose, and the produced β-lactose has uniform particle size, normal color and less impurities.

[0006] In order to achieve the above objectives, the present invention is implemented by the following technical solutions:

[0007] A method for preparing anhydrous β-lactose with high yield and low color value comprises the following steps:

[0008] S1. Using food-grade lactose as raw material, preparing lactose solution, adding activated carbon for adsorption, and filtering to obtain the first intermediate sugar solution;

[0009] S2, treating the first intermediate sugar solution through a column to remove nitrogen-containing inorganic salts and organic acids to obtain a second intermediate sugar solution;

[0010] S3. Pumping the second intermediate sugar liquid into a feeding tank of a thin film evaporator, wherein the heating temperature of the feeding tank is 85-95° C., setting the temperature of the evaporating cylinder to be in the range of 95-140° C., and simultaneously evacuating the liquid, with the scraper rotating speed being 15-60 rpm. The second intermediate sugar liquid evaporates and concentrates to precipitate β-lactose crystals in the process of being pushed downward on the evaporating cylinder of the thin film evaporator, and the crystals are automatically scraped off and collected in a bottom collector to obtain anhydrous β-lactose, wherein the yield of the anhydrous β-lactose is at least 90 wt % and the color value thereof is lower than 25.

[0011] Furthermore, the mass fraction of the lactose solution is 20%-50%; the activated carbon is added under the condition of 30-60°C insulation, and the amount of the activated carbon is 0.5%-1.5% of the weight of the lactose solution.

[0012] Furthermore, the column treatment is carried out using a strongly basic anion exchange resin column, the height-to-diameter ratio of the column is 1-10:1, the feed liquid temperature during the column treatment is 30-60°C, and the feed liquid flow rate is 5-20BV / h.

[0013] Furthermore, the method for obtaining the strong alkaline anion exchange resin column is as follows: using a macroporous or gel-type alkaline anion exchange resin, soaking the resin in a saturated NaCl aqueous solution for 24 hours to fully wash away the NaCl, washing with pure water at a flow rate of 4-6 BV / h until the resin effluent is colorless and transparent; then washing with a 4-6wt% HCl solution at a flow rate of 4 BV / h for 4-6 hours to completely convert the resin into Cl － Type, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral; then rinse with 4-6wt% NaOH solution at a flow rate of 3-4BV / h for 2-4h to completely convert the resin into OH － The resin is washed with pure water at a flow rate of 4-6 BV / h until the resin effluent is neutral for later use. After treatment with a strong alkaline anion exchange resin column, the removal rate of nitrogen-containing inorganic salts and organic acids in the sugar solution can reach more than 99%.

[0014] Furthermore, the vacuum degree during thin film evaporation is -0.06 to -0.098 MPa. The thin film evaporator used in the present invention is made of glass lining or borosilicate glass to avoid material retention, and the scraper is made of polytetrafluoroethylene.

[0015] Furthermore, the vacuum degree during thin film evaporation is set to -0.098 MPa, the heating temperature of the feeding tank is set to 90-95°C, the temperature of the evaporating cylinder is set to 100-130°C, and the scraper speed is 20-60rpm. The yield of the obtained anhydrous β-lactose is at least 94wt% and its color value is less than 25.

[0016] More preferably, the vacuum degree during thin film evaporation is set to -0.098 MPa, the heating temperature of the feeding tank is 95°C, the temperature of the evaporating cylinder is 100-120°C, the scraper speed is 20-60rpm, and the yield of the obtained anhydrous β-lactose is at least 94wt% and its color value is less than 16.

[0017] Beneficial technical effects:

[0018] The microenvironment in the β-lactose crystallization process is controlled by thin-film evaporation treatment, thereby ensuring the high uniformity of the quality of the β-lactose crystals and the stability of the crystallization process, and realizing continuous feeding and continuous discharging of β-lactose production; the method of the present invention can improve the evaporation crystallization efficiency, reduce the production cost, and solve the problem that the lactose is abnormally colored due to overheating due to the high surface humidity of the drum during the drum drying process;

[0019] The present invention adopts a thin film evaporator for continuous feeding and continuous discharging. The lactose solution enters the thin film evaporator, and the residence time of the lactose in the high temperature section is regulated to achieve the concentration of the solution. The problems of low evaporation intensity and low stability existing in the traditional evaporator are solved, and the formation of β-lactose crystals is ensured. The generated β-lactose has a uniform particle size. The thin film evaporation is used for concentration and crystallization, and the crystallization process is stable, energy-saving and environmentally friendly, and the yield of β-lactose can be improved to achieve large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is the particle size distribution diagram of anhydrous β-lactose obtained when the evaporation cylinder temperature is 120° C. in Example 1;

[0021] Figure 2 The effect of scraper speed on the particle size of β-lactose during thin film evaporation crystallization;

[0022] Figure 3 The effect of temperature change on the color value of β-lactose during thin film evaporation crystallization under vacuum degree -0.098MPa. DETAILED DESCRIPTION

[0023] The technical solutions in the embodiments of the present invention will be described clearly and completely below in combination with the embodiments of the present invention and the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. All other embodiments obtained by ordinary technicians in this field without creative work based on the embodiments of the present invention are within the scope of protection of the present invention.

[0024] Unless otherwise specifically stated, the numerical value set forth in these embodiments does not limit the scope of the present invention. The technology and method known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the technology and method should be considered as a part of the specification. In all examples shown and discussed here, any specific value should be interpreted as being merely exemplary, rather than as a limitation. Therefore, other examples of exemplary embodiments may have different values.

[0025] In addition, it should be noted that the use of words such as "first" and "second" to limit the sugar solution is only to facilitate the distinction between the sugar solutions obtained in each step. Unless otherwise stated, the above words have no special meaning and therefore cannot be understood as limiting the scope of protection of the present invention.

[0026] The experimental methods in the following examples without specifying specific conditions are usually measured in accordance with national standards; if there is no corresponding national standard, the method is carried out in accordance with the general standard requirements or general methods.

[0027] Example 1

[0028] A method for preparing anhydrous β-lactose with high yield and low color value comprises the following steps:

[0029] S1. Using food-grade lactose as raw material, add water to prepare 2 kg of 50 wt% lactose solution, keep warm at 60°C, add 10 g of activated carbon under stirring conditions, and filter with a filter element to obtain a clear first intermediate sugar solution;

[0030] S2. Treatment of strong alkaline anion exchange resin column: Use gel-type alkaline anion exchange resin (quaternary ammonium group), soak the resin in saturated NaCl aqueous solution for 24 hours, fully wash away NaCl, wash with pure water at a flow rate of 4-6 BV / h until the resin effluent is colorless and transparent; then rinse with 4-6wt% HCl solution at a flow rate of 4 BV / h for 4-6 hours to completely convert the resin into Cl － Type, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral; then rinse with 4-6wt% NaOH solution at a flow rate of 3-4BV / h for 2-4h to completely convert the resin into OH －Finally, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral for standby use;

[0031] The first intermediate sugar solution was passed through a strong alkaline anion exchange resin column with a height-to-diameter ratio of 6:1, a liquid temperature of 60°C, and a liquid flow rate of 8 BV / h to remove nitrogen-containing inorganic salts and organic acids, NO3 - / NO2 - , and the lactic acid removal rates are both greater than 99%, to obtain a second intermediate sugar solution;

[0032] S3. Pump the second intermediate sugar liquid into the feeding tank of the thin film evaporator, set the oil bath temperature of the feeding tank to 95°C, set the temperatures of the evaporating cylinder to 100°C, 110°C, 120°C, 130°C, and 140°C (parallel experiments were carried out at each temperature condition), the vacuum degree was -0.098MPa, the scraper speed was 20rpm, and the second intermediate sugar liquid was evaporated and concentrated to precipitate β-lactose crystals during the process of being pushed downward on the thin film. The scraper quickly hung down the precipitated crystals, and the anhydrous β-lactose with uniform particle size distribution was collected in the bottom collector.

[0033] The effect of different evaporation cylinder temperatures on the anhydrous β-lactose produced in this case is shown in Table 1 below.

[0034] The particle size distribution of anhydrous β-lactose prepared at an evaporation cylinder temperature of 120°C in this case was tested using a laser particle size analyzer. The results are as follows: Figure 1 As shown, it can be seen that the particle size D10 value of anhydrous β-lactose is 115 μm, the D50 value is 307 μm, and the D90 value is 532 μm.

[0035] The anhydrous β-lactose produced at various evaporation cylinder temperatures in this case was tested for color value according to GB / T 35887-2018. The results are as follows: Figure 3 And as shown in Table 1.

[0036] Table 1 Effect of different evaporation cylinder temperatures on the anhydrous β-lactose obtained

[0037]

[0038] As shown in Table 1, as the temperature of the evaporation cylinder of the thin film evaporator increases, the color value of β-lactose increases continuously, and the D50 particle size increases slightly. In the present invention, food-grade lactose is first adsorbed by activated carbon, then treated by a column, and finally evaporated by thin film. Under the conditions of a scraper speed of 20rpm and a vacuum degree of -0.098MPa, the evaporation cylinder temperature is preferably 100-130°C, and β-lactose with a D50 particle size of less than 315μm and a color value of less than 25IU can be obtained, and the preparation yield of β-lactose is high, the purity is high, and continuous production is possible.

[0039] Example 2

[0040] A method for preparing anhydrous β-lactose with high yield and low color value comprises the following steps:

[0041] S1. Using food-grade lactose as raw material, add water to prepare 4 kg of 50 wt% lactose solution, keep warm at 60°C, add 20 g of activated carbon under stirring conditions, and filter with a filter element to obtain a clear first intermediate sugar solution;

[0042] S2. Treatment of strong alkaline anion exchange resin column: Use macroporous alkaline anion exchange resin (quaternary ammonium group), soak the resin in saturated NaCl aqueous solution for 24 hours, fully wash away NaCl, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is colorless and transparent; then rinse with 4-6wt% HCl solution at a flow rate of 4BV / h for 4-6 hours to completely convert the resin into Cl － Type, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral; then rinse with 4-6wt% NaOH solution at a flow rate of 3-4BV / h for 2-4h to completely convert the resin into OH － Finally, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral for standby use;

[0043] The first intermediate sugar solution was passed through a strong alkaline anion exchange resin column with a height-to-diameter ratio of 6:1, a liquid temperature of 60°C, and a liquid flow rate of 8 BV / h to remove nitrogen-containing inorganic salts and organic acids, NO3 - / NO2 - , and the lactic acid removal rates are both greater than 99%, to obtain a second intermediate sugar solution;

[0044] S3. Pump the second intermediate sugar liquid into the feeding tank of the thin film evaporator, set the oil bath temperature of the feeding tank to 95°C, set the temperature of the evaporating cylinder to 120°C, the vacuum degree to -0.098MPa, and the scraper speeds to 20rpm, 30rpm, 40rpm, 50rpm, and 60rpm (parallel experiments were carried out for each scraper speed). The second intermediate sugar liquid evaporates and concentrates to precipitate β-lactose crystals in the process of being pushed downward on the thin film. The scraper quickly hangs down the precipitated crystals, and collects anhydrous β-lactose with uniform particle size distribution in the bottom collector.

[0045] The effect of different scraper speeds on the anhydrous β-lactose produced in this case is shown in Table 2 below.

[0046] In this case, the effect of different scraper speeds on the particle size of the anhydrous β-lactose produced is as follows: Figure 2 shown.

[0047] Table 2 Effect of different scraper speeds on the prepared anhydrous β-lactose

[0048]

[0049] From Table 2 and Figure 2 It can be seen that as the scraper speed of the thin film evaporator increases, the color value and D50 particle size of β-lactose both show a downward trend. The present invention firstly adsorbs food-grade lactose with activated carbon, then processes it through a column, and finally evaporates it with a thin film. Under the conditions of an evaporation cylinder temperature of 120°C and a vacuum degree of -0.098MPa, the scraper speed is preferably 20-60rpm, and β-lactose with a D50 particle size of less than 310μm and a color value of less than 20IU can be obtained. The preparation yield of β-lactose is high, the purity is high, and continuous production is possible.

[0050] Comparative Example 1

[0051] The preparation process of anhydrous β-lactose in this case is the same as that in Example 1 (the evaporation cylinder temperature is set to 120° C. in Example 1), except that no activated carbon is added to S1.

[0052] Comparative Example 2

[0053] The preparation process of anhydrous β-lactose in this case is the same as that in Example 1 (the evaporation cylinder temperature is set to 120° C. in Example 1), except that it is not treated with S2 gel-type strong alkaline anion exchange resin.

[0054] Comparative Example 3

[0055] The anhydrous β-lactose preparation process of this case is the same as that of Example 1 (the evaporation cylinder temperature is set to 120°C in Example 1). The difference is that S3 does not use a thin film evaporator, but instead uses a drum drying in the prior art: the second intermediate sugar solution is dried in a drum at a temperature of 100°C, and the drum speed is 6 rpm.

[0056] Comparative Example 4

[0057] The preparation process of anhydrous β-lactose in this case is the same as that in Example 1 (the evaporation cylinder temperature is set to 120° C. in Example 1), except that the 50 wt % lactose solution is directly subjected to the thin film evaporation operation in step S3.

[0058] The effects of the different methods of Example 1 and Comparative Examples 1-4 on the prepared anhydrous β-lactose are shown in Table 3.

[0059] Table 3 Effect of different methods of Example 1 and Comparative Examples 1-4 on anhydrous β-lactose

[0060]

[0061] As shown in Table 3, the color value of β-lactose prepared in Comparative Example 1 without activated carbon adsorption is slightly larger than that in Example 1, which indicates that the activated carbon adsorption step does not play a decisive role in reducing the color value of β-lactose. The color value of β-lactose prepared in Comparative Example 2 without column treatment is slightly larger than that in Example 1, which indicates that the column treatment step does not play a decisive role in reducing the color value of β-lactose, but has a greater impact on the purity of the β-lactose product, and the product without column treatment has a higher impurity content. The color value of β-lactose prepared in Comparative Example 3 without film evaporation and using conventional drum drying is much larger than that in Example 1, which indicates that the temperature and scraper speed during film evaporation play a decisive role in the color value of β-lactose, and drum drying cannot effectively reduce the color value of β-lactose. During the drum drying process, the slow speed increases the crystallization time of β-lactose on the drum, resulting in its conversion to produce pigments, which in turn affects the color value and purity of the final product. Since the color of food-grade lactose after dissolution is yellowish, with a color value of 45 IU, thin film evaporation crystallization (Comparative Example 4) is directly performed without preliminary activated carbon treatment and column treatment. Due to the high temperature of thin film evaporation, the color of the product deepens. The color change indicates that the lactose has slightly deteriorated (converted to produce pigment substances) and increased the impurity content, thus affecting the purity of the final product. It is inevitable that the color of lactose will deepen at high temperature, but the effect of thin film evaporation on the deepening of the color of lactose is much smaller than that of drum drying.

[0062] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing anhydrous β-lactose with high yield and low color value, characterized in that: The steps include: S1. Using food-grade lactose as raw material, preparing lactose solution, adding activated carbon for adsorption, and filtering to obtain the first intermediate sugar solution; S2, treating the first intermediate sugar solution through a column to remove nitrogen-containing inorganic salts and organic acids to obtain a second intermediate sugar solution; S3. Pump the second intermediate sugar liquid into the feeding tank of the thin film evaporator, the heating temperature of the feeding tank is 85-95°C, the temperature of the evaporating cylinder is set in the range of 95-140°C, and vacuum is drawn at the same time. The scraper speed is 15-60rpm, and the second intermediate sugar liquid is evaporated and concentrated on the evaporating cylinder to precipitate β-lactose crystals, and the crystals are automatically scraped off and collected in the bottom collector to obtain anhydrous β-lactose, wherein the yield of anhydrous β-lactose is at least 90wt% and its color value is less than 25.

2. The method for preparing anhydrous β-lactose with high yield and low color value according to claim 1, characterized in that: The mass fraction of the lactose solution is 20%-50%; The activated carbon is added under the condition of keeping warm at 30-60° C., and the amount of the activated carbon is 0.5%-1.5% of the weight of the lactose solution.

3. The method for preparing anhydrous β-lactose with high yield and low color value according to claim 1, characterized in that: The column treatment is carried out by using a strong alkaline anion exchange resin column, the height-to-diameter ratio of the column is 1-10:1, the feed liquid temperature during the column treatment is 30-60°C, and the feed liquid flow rate is 5-20BV / h.

4. The method for preparing anhydrous β-lactose with high yield and low color value according to claim 3, characterized in that: The method for obtaining the strong basic anion exchange resin column is: Use macroporous or gel-type alkaline anion exchange resin, soak the resin in saturated NaCl aqueous solution for 24 hours, fully wash away NaCl, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is colorless and transparent; then rinse with 4-6wt% HCl solution at a flow rate of 4BV / h for 4-6 hours to completely convert the resin into Cl － Type, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral; then rinse with 4-6wt% NaOH solution at a flow rate of 3-4BV / h for 2-4h to completely convert the resin into OH － Finally, wash with pure water at a flow rate of 4-6BV / h until the resin effluent is neutral for standby use.

5. A method for preparing anhydrous β-lactose with high yield and low color value according to any one of claims 1 to 4, characterized in that: The vacuum degree during thin film evaporation is -0.06 to -0.098 MPa.

6. A method for preparing anhydrous β-lactose with high yield and low color value according to any one of claims 1 to 4, characterized in that: The vacuum degree during thin film evaporation is set to -0.098MPa, the heating temperature of the feeding tank is set to 90-95°C, the temperature of the evaporating cylinder is set to 100-130°C, and the scraper speed is 20-60rpm. The yield of the obtained anhydrous β-lactose is at least 94wt% and its color value is less than 25.

7. A method for preparing anhydrous β-lactose with high yield and low color value according to any one of claims 1 to 4, characterized in that: The vacuum degree during thin film evaporation is set to -0.098MPa, the heating temperature of the feed tank is set to 95°C, the temperature of the evaporation cylinder is set to 100-120°C, and the scraper speed is set to 20-60rpm. The yield of the obtained anhydrous β-lactose is at least 94wt% and its color value is lower than 16.

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