Crystallization method of large-particle D-chiro-inositol

Abstract

The invention discloses a crystallization method of large-particle D-chiro-inositol, and relates to the technical field of D-chiro-inositol production.The crystallization method comprises the steps that after a D-chiro-inositol crude product is dissolved and decolored, methyl alcohol and seed crystals are added, the temperature is lowered to 40-45 DEG C for crystallization, then the rotating speed is lowered, methyl alcohol continues to be added, nitrogen is added, airflow stirring is increased, the temperature is lowered to 20-25 DEG C, crystallization is conducted, and the large-particle D-chiro-inositol is obtained. The crystallization tank is heated to 25-30 DEG C and then cooled to 10-15 DEG C, an obtained filter cake is washed and dried, D-chiro-inositol crystals are obtained, 20-mesh oversize products are smaller than 3%, 25-mesh undersize products are smaller than 3%, more than 94% of crystal particles are 20-25 meshes, and the uniformity of the particles is high.

Description

Technical Field

[0001] This invention relates to the field of D-chiral inositol production technology, and specifically to a method for crystallizing large-particle D-chiral inositol. Background Technology

[0002] D-Chiral Inositol is one of the nine isomers of inositol that is optically active. It is also the bioactive isomer of vitamin B8. It exists in relatively high levels in buckwheat seeds, soybeans, and some insects, mostly in the form of methylated or glycosylated derivatives. It is a biodegradation product of buckwheat sugar alcohol. It has insulin-sensitizing effects and promotes liver fat metabolism. It can significantly reduce blood sugar levels and has a significant therapeutic effect on diabetes.

[0003] Chinese patent CN104961628A discloses a method for converting D-pinel to D-chiral inositol. It uses D-pinel, a widely found substance in nature, as a raw material and employs acid hydrolysis to demethylate it, converting it into D-chiral inositol. The acid solution is then deacidified. Compared to other methods using chemical synthesis of D-chiral inositol, this method offers advantages such as greater safety, higher efficiency, and less pollution. Under optimized experimental conditions, the purity of D-chiral inositol is 94.2%, which is low. Furthermore, the low room temperature crystallization temperature results in fine crystals with a non-concentrated mesh size distribution. D-chiral inositol is highly hygroscopic and prone to caking during storage; this phenomenon is more likely to occur when the product particles are uneven and fine. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a method for crystallizing large-particle D-chiral inositol, which addresses the shortcomings of the existing technology and yields large-particle D-chiral inositol crystals with high uniformity.

[0005] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0006] A method for crystallizing large-particle D-chiral inositol, comprising the following steps:

[0007] A: Dissolve crude D-chiral inositol with a mass content greater than 95% in purified water to obtain a solution;

[0008] B: After decolorizing the solution, filter it and collect the decolorized solution;

[0009] C: Add the decolorizing solution into the crystallization tank and heat it to 50-55℃. First add methanol, then add 0.1-0.5% of the weight of crude D-chiral inositol seed crystals. Maintain the stirring speed at 20-30 rpm and cool the solution to 40-45℃.

[0010] D: Adjust the stirring speed of the crystallizer to 10-20 rpm, continue to add methanol into the crystallizer, and introduce nitrogen into the bottom of the tank to increase airflow and stirring, and cool down to 20-25℃;

[0011] E: After the liquid in the crystallizer is heated to 25-30℃, it is stirred for 1 hour (at this time, the fine powder in the crystallizer will dissolve into the solution), then cooled to 10-15℃, filtered, and the filter cake and filtrate are collected;

[0012] F: Wash the filter cake with methanol 2-3 times by stirring. The amount of methanol should be enough to cover the crystals. After washing, filter to obtain wet powder.

[0013] G: The wet powder is dried at a temperature of 50-60℃ and a vacuum degree of <-0.09MPa for 5-6 hours to obtain D-chiral inositol crystals.

[0014] Preferably, in step A, the amount of purified water added is 1-1.2 times the weight of crude D-chiral inositol, and the dissolution temperature is 60-70℃.

[0015] Preferably, in step B, 1-3% w / w of activated carbon and 0.5-1% w / w of diatomaceous earth based on the weight of crude D-chiral inositol are added respectively, and the color is decolorized for 30-60 minutes.

[0016] Preferably, in step C, the amount of methanol added is 0.3-0.5 times the volume of the decolorizing liquid.

[0017] Preferably, in step C, the D-chiral inositol seed crystals are first washed with a 50% v / v methanol-water solution for 10-30 minutes to dissolve the fine particles, leaving uniformly sized crystals to avoid uneven seed crystal size affecting crystallization, and then added to the decolorizing solution.

[0018] Preferably, in step C, the liquid is cooled to 40-45°C at a cooling rate of 2-3°C / h, and after cooling, it is stirred at 40-45°C for 1 hour.

[0019] Preferably, in step D, the amount of methanol added is 0.2-0.3 times the volume of the decolorizing liquid.

[0020] Preferably, the nitrogen addition rate in step D is 0.5-1.0 L / min. · L of crystallization liquid (i.e., 0.5-1.0 liters of nitrogen gas are introduced per minute per liter of crystallization liquid).

[0021] Preferably, in step D, the liquid is cooled to 20-25°C at a rate of 3-5°C / h, and in step E, the liquid is cooled to 10-15°C at a rate of 2-3°C / h.

[0022] Preferably, the filtrate from step E is used to recover methanol via membrane separation (such as nanofiltration) or distillation for crystallization in steps C and D, and washing in step F.

[0023] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0024] 1. By precisely controlling the crystallization process, uniform, coarse-grained D-chiral inositol crystals with a highly concentrated mesh size (over 94% of the particles are distributed between 20-25 mesh) were obtained. The large and uniform particles significantly reduce the specific surface area and the contact points between crystals, thereby fundamentally reducing the tendency for moisture absorption and caking during storage, and greatly improving the physical stability and storage performance of the product.

[0025] 2. The innovative crystallization process design ensures uniform crystal growth:

[0026] Solvent optimization: Methanol, which has higher polarity, is used instead of traditional ethanol for crystallization. This not only effectively removes impurities such as inositol and improves product purity, but also facilitates the formation of regular, large-particle crystals.

[0027] Segmented crystallization and precise temperature control: A segmented strategy of "induced crystallization-growth-ripening" is adopted. First, some methanol is added at a relatively high temperature, followed by pretreated homogeneous seed crystals. Slow cooling induces ordered nucleation and initial growth of the crystals. Subsequently, methanol is added again, and the temperature is further slowed down to promote continuous crystal growth.

[0028] Shear force control: During the critical period of crystal growth, the mechanical stirring speed is reduced to a low range, and nitrogen gas is introduced from the bottom of the tank for gentle airflow agitation to compensate for the insufficient mechanical stirring speed. This combination ensures uniform mixing of the system and prevents crystal sedimentation, while greatly reducing the impact and breakage of the crystals by mechanical shear force, creating an ideal environment for the complete growth of large crystal particles.

[0029] Fine crystal elimination technology: A heating and ripening step is set in the later stage of crystallization to redissolve the fine powder that hinders the uniformity of the product. Then, the temperature is slowly lowered again to allow it to precipitate on the existing large crystal particles, thereby further optimizing the crystal particle size distribution and ensuring the particle uniformity of the final product.

[0030] 3. The combined decolorization and purification effect of activated carbon and diatomaceous earth is significant. Combined with the impurity removal ability of methanol crystallization, the purity of the product is further improved. The large and uniform crystal structure enables high solid-liquid separation efficiency, thorough washing of the filter cake, and easy drying. It can be rapidly dehydrated under mild vacuum drying conditions, avoiding surface melting or agglomeration that may occur during prolonged drying.

[0031] 4. The final D-chiral inositol product was sieved through a 20-mesh sieve with less than 3% of the material passing through it and a 25-mesh sieve with less than 3% of the material passing through it. More than 94% of the crystal particles were between 20 and 25 mesh, and the particle uniformity was high. Attached Figure Description

[0032] Figure 1 This is a crystallization diagram of the D-chiral inositol product in Example 2 of the present invention;

[0033] Figure 2 This is the liquid chromatography chromatogram of the D-chiral inositol product in Example 2 of the present invention. Detailed Implementation

[0034] The present invention will be further illustrated below with reference to the embodiments. Example 1

[0035] 1. Take 1000g of crude D-chiral inositol (D-chiral inositol content is 95%), add pure water equal to the weight of the crude product, heat to 60℃ and dissolve completely to obtain a solution;

[0036] 2. Add 1% w / w activated carbon and 0.5% w / w diatomaceous earth by weight of crude product to the solution, decolorize for 60 min, filter, and collect 1.6 L of decolorized solution;

[0037] 3. Maintain the decolorizing solution temperature at 50°C, add methanol at 0.3 times the volume of the decolorizing solution, and then add D-chiral inositol seed crystals at 0.1% w / w of the crude product weight (the D-chiral inositol seed crystals were pre-washed with 50% methanol-water solution for 10 min). Stir at 20 rpm and cool down to 40°C at a rate of 3°C / h. Maintain the temperature and stir for 1 h. At this time, a large number of crystals are produced.

[0038] 4. Add methanol at a volume of 0.2 times that of the decolorizing liquid, stir at 10 rpm, and introduce nitrogen gas into the bottom of the tank to increase airflow and stirring. The nitrogen gas is added at a rate of 0.5 L / min·L crystallization liquid (i.e., 0.5 liters of nitrogen gas are introduced per minute per liter of crystallization liquid). Then, cool down to 20℃ at a rate of 5℃ / h. At this point, a small amount of fine powder will be produced.

[0039] 5. The crystallization liquid is heated to 25°C and stirred for 1 hour. At this time, the fine powder in the crystallization liquid will dissolve into the solution. Then, the temperature is lowered to 15°C at a rate of 3°C / h, filtered, and the filter cake is collected.

[0040] 6. Wash the filter cake twice with methanol, stirring. The amount of methanol should be enough to cover the crystals. After washing, filter to obtain wet powder.

[0041] 7. The wet powder was dried at 50℃ and vacuum degree < -0.09MPa for 6h to obtain 786g of uniformly crystalline D-chiral inositol, with a yield of 78.6% and a purity of 99.6%. The residue was 2% on a 20-mesh sieve and 1.4% on a 25-mesh sieve. More than 96.6% of the crystal particles were between 20 and 25 mesh. Example 2

[0042] 1. Take 1000g of crude D-chiral inositol (D-chiral inositol content is 95%), add 1.1 times the weight of the crude product in pure water, heat to 65℃ and dissolve completely to obtain a solution;

[0043] 2. Add 2% w / w activated carbon and 0.8% w / w diatomaceous earth by weight of crude product to the solution, decolorize for 45 min, filter, and collect 1.7 L of decolorized solution;

[0044] 3. Maintain the decolorizing solution temperature at 52℃, add methanol at 0.4 times the volume of the decolorizing solution, and then add D-chiral inositol seed crystals at 0.3% w / w of the crude product (the D-chiral inositol seed crystals were pre-washed with 50% methanol-water solution for 20 min). Stir at 25 rpm and cool down to 42℃ at a cooling rate of 2.5℃ / h. Maintain the temperature and stir for 1 h. At this time, a large number of crystals are produced.

[0045] 4. Add methanol at a volume of 0.25 times that of the decolorizing liquid, stir at 15 rpm, and introduce nitrogen gas into the bottom of the tank to increase airflow and stirring. The nitrogen gas is added at a rate of 0.8 L / min·L crystallization liquid (i.e., 0.8 liters of nitrogen gas are introduced per minute per liter of crystallization liquid). Then, cool down to 22°C at a rate of 4°C / h. At this point, a small amount of fine powder will be produced.

[0046] 5. The crystallization liquid is heated to 28℃ and stirred for 1 hour. At this time, the fine powder in the crystallization liquid will dissolve into the solution. Then, the temperature is lowered to 12℃ at a rate of 2.5℃ / h, filtered, and the filter cake is collected.

[0047] 6. Wash the filter cake twice with methanol, stirring. The amount of methanol should be enough to cover the crystals. After washing, filter to obtain wet powder.

[0048] 7. The wet powder was dried at 55℃ and vacuum degree < -0.09MPa for 5.5h to obtain 804g of uniformly crystalline D-chiral inositol, with a yield of 80.4% and a purity of 99.7%. The residue was 1.2% above a 20-mesh sieve and 1.1% below a 25-mesh sieve. More than 97.7% of the crystal particles were between 20 and 25 mesh. Example 3

[0049] 1. Take 1000g of crude D-chiral inositol (D-chiral inositol content is 95%), add 1.2 times the weight of the crude product in pure water, heat to 70℃ and dissolve completely to obtain a solution;

[0050] 2. Add 3% w / w activated carbon and 1% w / w diatomaceous earth by weight of crude product to the solution, decolorize for 30 min, filter, and collect 1.8 L of decolorized solution;

[0051] 3. Maintain the decolorizing solution temperature at 55℃, add methanol at 0.5 times the volume of the decolorizing solution, and then add D-chiral inositol seed crystals at 0.5% w / w of the crude product (the D-chiral inositol seed crystals were pre-washed with 50% methanol-water solution for 10 min). Stir at 30 rpm and cool down to 45℃ at a rate of 2℃ / h. Maintain the temperature and stir for 1 h. At this time, a large number of crystals are produced.

[0052] 4. Add methanol at a volume of 0.3 times that of the decolorizing liquid, stir at 20 rpm, and introduce nitrogen gas into the bottom of the tank to increase airflow and stirring. The nitrogen gas is added at a rate of 1.0 L / min·L crystallization liquid (i.e., 1.0 liter of nitrogen gas is introduced per minute per liter of crystallization liquid). Then, cool down to 25°C at a rate of 3°C / h. At this point, a small amount of fine powder will be produced.

[0053] 5. The crystallization liquid is heated to 30℃ and stirred for 1 hour. At this time, the fine powder in the crystallization liquid will dissolve into the solution. Then, the temperature is lowered to 10℃ at a rate of 2℃ / h, filtered, and the filter cake is collected.

[0054] 6. The filter cake is washed three times with methanol, the amount of methanol being enough to cover the crystals. After washing, it is filtered to obtain wet powder.

[0055] 7. The wet powder was dried at 60℃ and under a vacuum of <-0.09MPa for 5h to obtain 823g of uniformly crystalline D-chiral inositol, with a yield of 82.3% and a purity of 99.6%. The residue was 0.9% on a 20-mesh sieve and 1.1% on a 25-mesh sieve. More than 98% of the crystal particles were between 20 and 25 mesh.

[0056] It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for crystallizing large-particle D-chiral inositol, characterized in that... Includes the following steps: A: Dissolve crude D-chiral inositol with a mass content greater than 95% in purified water to obtain a solution; B: After decolorizing the solution, filter it and collect the decolorized solution; C: Add the decolorizing solution into the crystallization tank and heat it to 50-55℃. First add methanol, then add 0.1-0.5% of the weight of crude D-chiral inositol seed crystals. Maintain the stirring speed at 20-30 rpm and cool the solution to 40-45℃. D: Adjust the stirring speed of the crystallizer to 10-20 rpm, continue to add methanol into the crystallizer, and introduce nitrogen into the bottom of the tank to increase airflow and stirring, and cool down to 20-25℃; E: After the liquid in the crystallizer is heated to 25-30℃, it is stirred for 1 hour, then cooled to 10-15℃, filtered, and the filter cake and filtrate are collected. F: The filter cake is washed with methanol 2-3 times by stirring, and then filtered to obtain wet powder; G: The wet powder is dried at a temperature of 50-60℃ and a vacuum degree of <-0.09MPa for 5-6 hours to obtain D-chiral inositol crystals.

2. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step A, the amount of purified water added is 1-1.2 times the weight of crude D-chiral inositol, and the dissolution temperature is 60-70℃.

3. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step B, add 1-3% w / w of activated carbon and 0.5-1% w / w of diatomaceous earth of crude D-chiral inositol and decolorize for 30-60 minutes.

4. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step C, the amount of methanol added is 0.3-0.5 times the volume of the decolorizing liquid.

5. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step C, the D-chiral inositol seed crystals are first washed with a 50% v / v methanol-water solution for 10-30 min, and then added to the decolorizing solution.

6. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step C, the liquid is cooled to 40-45℃ at a cooling rate of 2-3℃ / h, and after cooling, it is stirred at 40-45℃ for 1h.

7. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step D, the amount of methanol added is 0.2-0.3 times the volume of the decolorizing liquid.

8. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step D, the nitrogen gas is added at a rate of 0.5-1.0 L / min·L of crystallization liquid.

9. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: In step D, the liquid is cooled to 20-25℃ at a rate of 3-5℃ / h, and in step E, the liquid is cooled to 10-15℃ at a rate of 2-3℃ / h.

10. The crystallization method for large-particle D-chiral inositol as described in claim 1, characterized in that: The filtrate from step E is used to recover methanol via membrane separation or distillation, which is then used for crystallization in steps C and D, as well as washing in step F.

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