High-stability glass pigment and preparation method thereof

Abstract

The invention relates to the technical field of crystallization, and particularly provides a high-stability glassine and a preparation method thereof. According to the technical scheme, the method comprises the following steps: firstly, dissolving a glassy solid in a mixed solvent of alcohols and ketones at the dissolving temperature of 50-65 DEG C, filtering out insoluble substances, cooling the system to 25-35 DEG C, adding a seed crystal, and introducing nitrogen for bubbling; and slowly cooling the system to 0-10 DEG C, growing crystals, filtering, leaching with a mixed solvent of alcohol and water, and carrying out vacuum drying at 40-50 DEG C to obtain the product. The glass color prepared by the method has the advantages that the crystal particle size is greater than 300 microns, the surface is smooth and flat, the specific surface area is less than 150 m < 3 > / kg, the chemical purity is higher than 99.9%, the physicochemical properties are stable, and particularly, the hygroscopicity is far lower than that of a conventional product. The characteristics are more beneficial to storage and transportation, the downstream product quality is improved, and the overall cost is reduced. Meanwhile, the preparation method disclosed by the invention is high in granularity controllability, good in batch-to-batch reproducibility, high in yield, high in production efficiency, green and environment-friendly in solvent system and suitable for large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of crystallization, and in particular relates to a high-stability boson and a preparation method thereof. Background Art

[0002] Bosin, also known as hydroxypropyl tetrahydropyrantriol, has a CAS number of 439685-79-7 and is a type of C-glycoside derivative. It can assist the human body in synthesizing mucopolysaccharides, thereby promoting the production of hyaluronic acid and collagen, and is mainly used to delay skin aging. Its structural formula is as follows:

[0003] This ingredient was originally extracted from natural xylose by L'Oreal, France, and its chemical structure, preparation method and application field are protected in patent WO2002051828. In recent years, there have been more and more studies on the synthesis of pro-xylane. For example, Alexandre Cavezza et al. reported in the academic paper Synthesis of Pro-XylaneTM: A new biologically active C-glycoside in aqueous media in 2009 that the chemical synthesis process of pro-xylane with D-xylose as substrate; patents CN113735811 and CN110467591 used metal complexes to catalyze the synthesis of pro-xylane; patent CN111876452 used enzyme catalysis to synthesize pro-xylane in a green way, etc.

[0004] With the continuous development of the Bose synthesis process, its storage and processing performance have also become crucial. Bose itself has the characteristic of being hygroscopic, and its wet stability has a significant impact on the processing difficulty and cost of its downstream processes, so it has become a key technical indicator. Patent CN114105923 improves the wet stability of Bose by changing the crystal form, but changing the crystal form will affect the water absorption and moisturizing effect of Bose, and there may be risks in biosafety, which requires a lot of research and confirmation, which will greatly increase the cost.

[0005] As we all know, large-particle products have smaller specific surface areas, fewer active sites, and are less likely to absorb moisture. In addition, a complete and smooth crystal surface will further reduce the specific surface area, thereby improving the wet stability of the crystal. Improving the wet stability of boson by increasing the particle size and modifying the surface is of great practical significance.

[0006] The inventors found in relevant research that the preparation method of the present invention can control the crystal size of boson to be above 300 μm, and the surface is smooth and flat, with a specific surface area of ​​less than 150 m 3 / kg. Its chemical purity is as high as 99.9%. It has been verified by experiments that the hygroscopicity of the boson product is much lower than that of commercially available products, and its stability is extremely high. These characteristics are more conducive to storage and transportation, improving the quality of downstream products and reducing overall costs. At the same time, the preparation method of the present invention has high controllability of particle size, good batch-to-batch reproducibility, high yield, high production efficiency, and a green and environmentally friendly solvent system, which is suitable for large-scale production. Summary of the invention

[0007] Purpose of the invention: To address the many deficiencies of existing boson in terms of hygroscopicity and stability, a method for preparing boson crystals with high stability is provided.

[0008] The technical scheme of the present invention is as follows: the first step is to dissolve the crude solid product of bosaicin in a mixed solvent of alcohol and ketone, with a liquid-to-solid ratio of 0.8:1-2:1 and a dissolution temperature of 50°C to 65°C. After stirring for 30 minutes to equilibrium, mechanical impurities are filtered out, and the filtrate is kept warm at the dissolution temperature.

[0009] Step 2: Cool the system to 25℃~35℃. Add seed crystals and bubble nitrogen into the solution for 1~2 hours. Stir continuously and keep the temperature constant.

[0010] Step 3: Stop bubbling, slowly cool the system to 0℃~10℃ while stirring, and grow the crystal at a constant temperature for 1~3 hours at the end of the cooling process.

[0011] Step 4: Filter and rinse the filter cake with 0.2~0.5 volume of a mixed solvent of alcohol and water.

[0012] Step 5: Dry the sample at 40℃~50℃ and vacuum degree -0.1MPa for 4~6 hours until constant weight is obtained.

[0013] More specifically: the alcohol solvent in the first step is one of methanol, ethanol, n-propanol, and isopropanol, and the ketone solvent is one of acetone, methyl ethyl ketone, methyl propyl ketone, and methyl isopropyl ketone. The ratio of alcohol to ketone is 90:10-98:2.

[0014] The cooling rate described in the second step is 3~5 min / ℃.

[0015] The bubbling gas flow rate described in the second step is 1~3 V / min, and V represents the volume of the solvent.

[0016] The cooling rate described in the third step is 20~30 min / ℃.

[0017] The eluting alcohol used in the fourth step is one of methanol, ethanol, n-propanol and isopropanol, and the ratio of alcohol to water is 9:1~1:1.

[0018] In the technical solution of the present invention, the bubbling gas flow rate in the second step is the key parameter A: if the bubbling speed is too slow, the crystal surface is rough and the specific surface area increases; if the bubbling speed is too fast, the particle size decreases, which also leads to an increase in the specific surface area. Both are not conducive to the wet stability of the product. The cooling speed in the third step is the key parameter B: when the cooling speed is too fast, the crystallization driving force is too high, the particle size is small, and crystal agglomeration, impurity inclusion and other phenomena are prone to occur; if the cooling speed is too slow, the time cost is too high and the productivity is reduced.

[0019] Beneficial effects: The present invention specifically provides a method for preparing a crystal of high-stability boson. The boson crystal prepared by the method has a particle size greater than 300 μm, a smooth surface, and a specific surface area less than 150 m 3 / kg, chemical purity is higher than 99.9%, physical and chemical properties are stable, especially its hygroscopicity is much lower than conventional products. These characteristics are more conducive to storage and transportation, improve the quality of downstream products, and reduce overall costs. At the same time, the preparation method of the present invention has high controllability of particle size, good batch reproducibility, high yield, high production efficiency, green solvent system, and is suitable for scale-up production. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 : 100x microscope view of Example 1.

[0021] Figure 2 : Particle size distribution diagram of Example 1. DETAILED DESCRIPTION Example

[0023] 100 g of boson, 90 ml of methanol, and 10 ml of acetone were placed in a crystallizer. The temperature of the system was raised to 65°C and stirred to dissolve. After 30 min, undissolved mechanical impurities were filtered out, and the filtrate was kept at 65°C. Then the system was cooled to 30°C at a cooling rate of 4 min / °C. After reaching 30°C, seed crystals were added, and nitrogen was bubbled at the same time with a nitrogen flow rate of 200 ml / min, and then stirring was continued for 2 h. Stop nitrogen bubbling, cool the system to 0°C at a rate of 25 min / °C, and grow crystals at 0°C for 2 h. Filter, rinse the filter cake with 20 ml of 80% methanol, and then dry the filter cake at 40°C under -0.1 MPa vacuum for 4 h. The product yield was 92.6%, Dv(90) was 387.2 μm, and the specific surface area was 101.3 m 3 / kg, HPLC purity is 99.90%.

[0024] Embodiment 2: 100 g of boson, 85 ml of ethanol, and 5 ml of methyl ethyl ketone were placed in a crystallizer. The system was heated to 60°C and stirred to dissolve. After 30 min, undissolved mechanical impurities were filtered out, and the filtrate was kept at 60°C. Then the system was cooled to 25°C at a cooling rate of 5 min / °C. After reaching 30°C, seed crystals were added, and nitrogen was bubbled at the same time. The nitrogen flow rate was 270 ml / min, and then stirring was continued for 1 h. Stop nitrogen bubbling, cool the system to 5°C at a rate of 30 min / °C, and grow crystals at 5°C for 3 h. Filter, rinse the filter cake with 40 ml of 90% ethanol, and then dry the filter cake at 45°C under -0.1 MPa vacuum for 5 h. The product yield was 92.1%, Dv(90) was 432.5 μm, and the specific surface area was 100.6 m 3 / kg, HPLC purity is 99.92%.

[0025] Embodiment 3: 100 g of bosylamine, 108 ml of isopropanol, and 12 ml of methyl propyl ketone were placed in a crystallizer, and the temperature of the system was raised to 55 ° C, stirred and dissolved. After 30 min, undissolved mechanical impurities were filtered out, and the filtrate was kept at 55 ° C. Then the system was cooled to 30 ° C, and the cooling rate was 3 min / ° C. After reaching 30 ° C, seed crystals were added, and nitrogen was bubbled at the same time, with a nitrogen flow rate of 240 ml / min, and then stirred for 2 h. Stop nitrogen bubbling, cool the system to 10 ° C at a rate of 20 min / ° C, and grow crystals at 10 ° C for 2 h. Filter, rinse the filter cake with 20 ml, 50% isopropanol, and then dry the filter cake at 50 ° C at -0.1 MPa vacuum for 4 h. The product yield was 91.9%, Dv (90) was 315.7 μm, and the specific surface area was 143.1 m 3 / kg, HPLC purity is 99.93%.

[0026] Embodiment 4: 100 g of boson, 73 ml of n-propanol, and 7 ml of acetone were put into the crystallizer, and the temperature of the system was raised to 60 ° C, stirred and dissolved. After 30 min, the undissolved mechanical impurities were filtered out, and the filtrate was kept at 60 ° C. Then the system was cooled to 35 ° C, and the cooling rate was 4 min / ° C. After reaching 35 ° C, seed crystals were added, and nitrogen was bubbled at the same time, with a nitrogen flow rate of 80 ml / min, and then stirred for 2 h. Stop nitrogen bubbling, cool the system to 5 ° C at a rate of 30 min / ° C, and grow crystals at 5 ° C for 2 h. Filter, rinse the filter cake with 30 ml, 60% n-propanol, and then dry the filter cake at 50 ° C at -0.1 MPa vacuum for 6 h. The product yield was 93.4%, Dv (90) was 388.6 μm, and the specific surface area was 109.6m 3 / kg, HPLC purity is 99.90%.

[0027] Embodiment 5: 100 g of boson, 115 ml of ethanol, and 5 ml of methyl isopropyl ketone were placed in a crystallizer, and the temperature of the system was raised to 50 °C, and the mixture was stirred and dissolved. After 30 min, the undissolved mechanical impurities were filtered out, and the filtrate was kept at 50 °C. Then the system was cooled to 25 °C at a rate of 5 min / °C. After reaching 25 °C, a seed crystal was added, and nitrogen was bubbled at the same time, with a nitrogen flow rate of 240 ml / min, and then the mixture was stirred for 1 h. The nitrogen bubbling was stopped, and the system was cooled to 5 °C at a rate of 25 min / °C, and the crystals were grown at 5 °C for 3 h. Filter, rinse the filter cake with 40 ml of 70% ethanol, and then dry the filter cake at 40 °C under -0.1 MPa vacuum for 4 h. The product yield was 91.0%, Dv(90) was 412.4 μm, and the specific surface area was 98.5 m 3 / kg, HPLC purity is 99.93%.

[0028] Embodiment 6: 100 g of boson, 95 ml of isopropanol, and 5 ml of methyl ethyl ketone were placed in a crystallizer, and the temperature of the system was raised to 55°C, and the mixture was stirred and dissolved. After 30 min, the undissolved mechanical impurities were filtered out, and the filtrate was kept at 55°C. Then the system was cooled to 30°C at a rate of 4 min / °C. After reaching 30°C, a seed crystal was added, and nitrogen was bubbled at the same time, with a nitrogen flow rate of 300 ml / min, and then the mixture was stirred for 2 h. The nitrogen bubbling was stopped, and the system was cooled to 0°C at a rate of 30 min / °C, and the crystals were grown at 0°C for 2 h. Filter, rinse the filter cake with 50 ml of 90% isopropanol, and then dry the filter cake at 45°C under -0.1 MPa vacuum for 5 h. The product yield was 93.5%, Dv(90) was 401.8 μm, and the specific surface area was 111.5 m 3 / kg, HPLC purity is 99.92%.

[0029] Test Example 1: Hygroscopicity test using DVS The wet stability of the boson obtained in the embodiment of the present invention was evaluated using DVS and compared with commercially available samples. The results are as follows:

[0030] The test results show that: The moisture gain of the bosogen prepared by the method of the present invention under the conditions of RH of 65%, 80% and 95% is significantly lower than that of the commercially available product.

[0031] Test Example 2: Long-term moisture absorption stability study The wet stability of the boson obtained in the present invention was investigated using a constant temperature and humidity chamber and compared with commercially available samples. The results of the wet weight gain investigation are as follows:

[0032] The test results show that: The moisture absorption stability of the boson described in the present invention at different humidity levels is much higher than that of commercially available products, and has obvious advantages over the prior art.

[0033] It can be understood that the above specific description of the present invention is only used to illustrate the present invention and is not limited to the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that the present invention can still be partially modified or replaced by equivalents to achieve the same technical effects; as long as the use requirements are met, they are within the protection scope of the present invention.

Claims

1. A high-stability boson and a preparation method thereof, characterized in that Preparation method The method comprises the following steps: Step 1: dissolving the crude solid product of Bose in a mixed solvent of alcohols and ketones, with a liquid-solid ratio of 0.8:1-2:1 and a dissolution temperature of 50°C to 65°C. After stirring for 30 minutes to equilibrium, filter out the mechanical impurities, and keep the filtrate warm at the dissolution temperature. Step 2: cool the system to 25°C-35°C. Add seed crystals, and bubble nitrogen into the solution for 1-2 hours. Stir continuously during this period and keep the temperature constant. Step 3: stop bubbling, slowly cool the system to 0°C-10°C under stirring, and keep the crystal at a constant temperature for 1-3 hours at the end of the cooling. Step 4: filter, and rinse the filter cake with 0.2-0.5 volumes of a mixed solvent of alcohols and water. Step 5: dry the sample at 40°C-50°C and a vacuum degree of -0.1MPa for 4-6 hours to constant weight.

2. The method for preparing the highly stable boson according to claim 1, characterized in that In the first step, the alcohol solvent is one of methanol, ethanol, n-propanol, and isopropanol, and the ketone solvent is one of acetone, methyl ethyl ketone, methyl propyl ketone, and methyl isopropyl ketone. The ratio of alcohol to ketone is 90:10-98:

2.

3. The method for preparing the highly stable boson according to claim 1, characterized in that The cooling rate described in the second step is 3~5 min / ℃.

4. The method for preparing high-stability boson according to claim 1, characterized in that The bubbling gas flow rate described in the second step is 1~3 v / min.

5. The method for preparing high-stability boson according to claim 1, characterized in that The cooling rate described in the third step is 20~30 min / ℃.

6. The method for preparing high-stability boson according to claim 1, characterized in that The eluting alcohol used in the fourth step is one of methanol, ethanol, n-propanol and isopropanol, and the ratio of alcohol to water is 9:1~1:1.

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