A highly efficient and stable inositol crystallization process

Abstract

This invention discloses an efficient and stable inositol crystallization process, comprising the following steps: (1) mixing a gel polysaccharide and an inositol solution uniformly to obtain a gel polysaccharide aqueous suspension, then adding seed crystals and mixing thoroughly before vacuum evaporation and crystallization to form a gel; (2) heating the gel to 65-70°C to obtain the precipitate, which is the inositol crystal. The method of this invention has a short crystallization cycle, low energy consumption, and improves the uniformity of the crystals.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical manufacturing technology, and in particular relates to an efficient and stable inositol crystallization process. Background Technology

[0002] Inositol, also known as cyclohexanehexol, is a growth factor for animals and microorganisms, belonging to the vitamin class, and is widely found in animals and plants. Visually, inositol appears as white crystals or crystalline powder, odorless, and with a sweet taste. This alcohol possesses various physiological and pharmacological activities, making it highly valuable for treating diseases such as cirrhosis and hepatitis, and also showing good efficacy in treating depression and obsessive-compulsive disorder. As a healthcare product, its crystallization requirements are relatively high, ensuring high purity and uniformity while maintaining easy solubility. Besides the above uses, inositol is also an important pharmaceutical intermediate. However, currently, domestically produced inositol crystal products have poor crystal morphology, with small, needle-like crystals, causing inconvenience in storage and use.

[0003] Since the solubility of inositol in water does not change much with temperature (0.15g of inositol dissolves per gram of water at 20℃; 0.38g of inositol dissolves per gram of water at 60℃), the industrial production of crystalline inositol mostly adopts the method of adding seed crystals and applying pressure to evaporate and remove part of the solvent to achieve supersaturation of the solution, thereby precipitating crystals. This traditional process has the following main problems: (1) Evaporation crystallization without seed crystals makes it difficult to control the morphology of the seed crystals; (2) Crystal precipitation occurs during the evaporation process, and scaling easily forms on the heating surface, which can easily cause equipment blockage; (3) High energy consumption, failure to control the amount and rate of water evaporation, inability to ensure that the solution concentration is in the metastable region during solvent loss, difficulty in controlling the supersaturation of the mother liquor, and serious impact on crystal growth.

[0004] Therefore, providing an efficient and stable inositol crystallization process is a problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0005] In view of this, the present invention provides an efficient and stable inositol crystallization process. The method has a short crystallization cycle, low energy consumption, and improves the uniformity of crystals.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A highly efficient and stable inositol crystallization process, wherein the process employs a gel crystallization process, and the raw material for the gel is a gel polysaccharide.

[0008] Preferably, the process includes the following steps:

[0009] (1) After mixing the gel polysaccharide and inositol solution evenly, a gel polysaccharide aqueous suspension is obtained. Then, seed crystals are added, mixed evenly, and vacuum evaporated to crystallize until a gel is formed.

[0010] (2) The precipitate obtained after heating the gel to 65-70℃ is inositol crystal.

[0011] This invention utilizes the initial crystallization product of inositol fermentation broth as the main raw material. The crystallization process requires no solvents such as ethanol, making it natural and environmentally friendly. By adding a certain amount of condensing polysaccharide, and heating the condensing polysaccharide aqueous dispersion (above 2%) to 54-80℃, followed by cooling to 40℃, a thermally reversible low-strength gel is formed. Reheating to 70℃ causes the gel to dissolve again, thus fixing the inositol solution within a cross-linked network at approximately 40℃. This provides a static environment with spatial constraints for crystal growth, avoiding direct crystallization in the liquid, which can lead to uneven stirring, precipitation, and excessive radial crystal growth. It also facilitates the removal of polysaccharides at high temperatures. The low concentration of the inositol solution in the crystallization vessel, combined with controlled evaporation, shortens the inositol solution concentration and crystallization cycle, improves crystal uniformity, and results in high-purity, stable-quality products suitable for wide application in food, pharmaceuticals, and daily chemical industries.

[0012] Preferably, the concentration of gel polysaccharide in the gel polysaccharide aqueous suspension in step (1) is 0.2-3.0 wt%, more preferably 0.5-1.5 wt%.

[0013] Controlling the concentration of gel polysaccharides within this range achieves the gelation effect while facilitating subsequent impurity removal and cost savings.

[0014] Preferably, the size of the seed crystal in step (1) is 100-250 mesh, and more preferably 180-200 mesh.

[0015] Selecting this size of seed crystal facilitates subsequent crystal growth and control of crystal morphology, ensuring crystal uniformity.

[0016] Preferably, the temperature for mixing the seed crystals in step (1) is 40-45°C, and the vacuum degree is 45-60 kPa.

[0017] Low-temperature evaporation of water causes the gel polysaccharide suspension to solidify, increasing the water evaporation rate and ensuring that the gelation process is reversible solidification at 80℃.

[0018] Preferably, the method for preparing the seed crystal in step (1) is as follows: take a small seed crystal and place it in a seed inositol solution, stir and cool it to 40-45°C, and pre-grow the seed crystal to 180-200 mesh.

[0019] The temperature of the suspension containing seed crystals is the same as that of the gel polysaccharide solution to avoid crystal bursting or dissolution due to temperature changes.

[0020] Preferably, the small-sized seed crystals are 300-325 mesh in size, and the amount of small-sized seed crystals added is 0.5-1‰ of the dry matter weight of the seed crystal inositol solution;

[0021] The addition of seed crystals of this size reduces the mass of added crystals, increases their quantity and dispersion, and ensures sufficient growth space to provide conditions for later growth into uniform crystals.

[0022] The mass concentration of the seed inositol solution is 30-33%, and the temperature of the seed inositol solution is 58-70℃.

[0023] The saturated inositol solution at this temperature ensures that the concentration will not exceed the gel capacity during the later evaporation and crystallization process, while also reducing thermal costs.

[0024] Preferably, the mass concentration of the seed inositol solution is 1.5-4% higher than the mass concentration of the inositol solution.

[0025] Ensure that the seed crystals have a sufficient concentration to grow to the target size at the appropriate temperature, and ensure that the solution concentration is basically consistent during mixing.

[0026] Preferably, the mixing method in step (1) is as follows: the mixture of the gel polysaccharide and the inositol solution is stirred evenly at 150-180 rpm, and then 0.1-0.5‰ of the volume of the inositol solution and steel balls with a diameter of 5-6 mm are added. The high-pressure air nozzle mixing device is started, and the high-pressure air nozzle sprays air at a high speed of 250-300 m / s from the bottom.

[0027] Adding small steel balls in advance and mixing them evenly in the gel facilitates energy transfer and ensures uniform temperature changes.

[0028] Preferably, the heating in step (2) is a gradient heating;

[0029] The precipitate needs to be washed and dried. The washing water temperature is 7-15℃, and the water volume is 0.5-0.75 times the mass of the precipitate. The drying temperature is 35-60℃.

[0030] To avoid product dissolution due to excessively high water temperature or excessive water volume, this drying temperature achieves the desired drying effect while avoiding heat waste.

[0031] Inositol crystals were prepared using an efficient and stable inositol crystallization process as described above.

[0032] As can be seen from the above technical solution, compared with the prior art, the beneficial effects of the present invention are as follows:

[0033] This invention provides an efficient and stable inositol crystallization process. The method has a short crystallization cycle, low energy consumption, and improves the uniformity of the crystals. Detailed Implementation

[0034] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] Inositol solution is obtained by fermenting glucose and glycerol with laboratory engineered bacteria to produce inositol, followed by treatment methods such as ceramic membrane filtration and activated carbon decolorization.

[0036] All the above reagents are commercially available. The engineered bacteria are obtained by genetically modifying Pichia pastoris GS115 by knocking out the key glycolysis gene pgi and the negative regulatory gene PAS chr-10033 of inositol biosynthesis, and by overexpressing the inositol-3 phosphate synthase (ino1) gene. There are no requirements for their source or brand, as long as they meet the experimental requirements.

[0037] Example 1

[0038] An efficient and stable inositol crystallization process, the specific steps of which are as follows:

[0039] (1) Take 0.66g of inositol particles with a particle size of about 47um as seed crystals and place them in a seed crystal container with a total mass of 2kg, a temperature of 70℃ and a concentration of 33% inositol solution. Stir and slowly cool down to the same temperature as the main crystallizer and pre-grow the seed crystals to 200 mesh.

[0040] (2) Add 1.52% of the mass of the condensed polysaccharide in the crystallization vessel to the 30% inositol solution in the crystallization vessel. Mix the mixture with a stirrer at 60 r / min and then stop stirring. Add small steel balls with a diameter of 6 mm and a quantity equal to 0.5‰ of the volume of the inositol solution. Start the high-pressure air nozzle of the mixing equipment to spray air at a high speed of 300 m / s from the bottom.

[0041] (3) Add the seed crystals from the seed tank to the crystallization vessel. First, cool and crystallize to 45°C, then stop stirring and carry out evaporation crystallization under a vacuum of 45KPa. Control the amount of water evaporated until a gel is formed in the crystallization vessel.

[0042] (4) The gel gradient obtained above is heated to 70°C, then centrifuged, washed with 0.75 times the mass of inositol at 15°C water, and dried at 60°C to obtain inositol crystals.

[0043] In this embodiment, inositol crystals were sieved using 30-mesh and 60-mesh sieves. Based on the total mass of the sieved products, the mass percentage of crystals of different particle sizes in each sieve interval (above 30-mesh, 30-60-mesh, and below 60-mesh) was calculated. The particle size of inositol in the finished product was approximately 5% above 30-mesh, 80% between 30-60-mesh, and 15% below 60-mesh, with an inositol purity of 99.7%.

[0044] Example 2

[0045] An efficient and stable inositol crystallization process, the specific steps of which are as follows:

[0046] (1) Take 0.48g of inositol particles with a particle size of about 48um as seed crystals and place them in a seed crystal tank with a total mass of 2kg, a temperature of 58℃ and a concentration of 30% inositol solution. Stir and slowly cool down to the same temperature as the main crystallizer and pre-grow the seed crystals to 180 mesh.

[0047] (2) Add 0.50% of the mass of the condensed polysaccharide in the crystallization vessel to the 28.5% inositol solution in the crystallization vessel. Mix the mixture with a stirrer at 60 r / min, then stop stirring. Add small steel balls with a diameter of 5 mm and a quantity equal to 0.1 times the volume of the inositol solution. Start the high-pressure air nozzle of the mixing equipment to spray high-speed air at 250 m / s from the bottom.

[0048] (3) Add the seed crystals from the seed crystal tank to the crystallization vessel. First, cool the crystals to 40°C, then stop stirring and carry out evaporation crystallization under a vacuum of 60KPa. Control the amount of water evaporation to form a gel in the crystallization vessel.

[0049] (4) The gel gradient obtained above is heated to 65°C, then centrifuged, washed with 0.5 times the mass of inositol in 7°C water, and dried at 35°C to obtain inositol crystals.

[0050] In this embodiment, inositol crystals were sieved using 30-mesh and 60-mesh sieves. Based on the total mass of the sieved product, the mass percentage of crystals of different particle sizes in each sieve interval (above 30-mesh, 30-60-mesh, and below 60-mesh) was calculated. In the finished inositol product, the particle size of inositol was approximately 8% above 30-mesh, 85% between 30-60-mesh, and about 7% below 60-mesh, with an inositol purity of 99.6%.

[0051] Example 3

[0052] An efficient and stable inositol crystallization process, the specific steps of which are as follows:

[0053] (1) Take 0.64g of inositol particles with a particle size of about 45um as seed crystals and place them in a seed crystal container with a total mass of 2kg, a temperature of 60℃ and a concentration of 32% inositol solution. Stir and slowly cool down to the same temperature as the main crystallizer and pre-grow the seed crystals to 195 mesh.

[0054] (2) Add 1.3% of the mass of the condensed polysaccharide in the crystallization vessel to the 29% inositol solution in the crystallization vessel. Mix the mixture with a stirrer at 60 r / min, then stop stirring. Add small steel balls with a diameter of 5 mm and a quantity equal to 0.3‰ of the volume of the inositol solution. Start the high-pressure air nozzle of the mixing equipment to spray high-speed air at 270 m / s from the bottom.

[0055] (3) Add the seed crystals from the seed tank to the crystallization vessel and first cool and crystallize to 43°C. Then stop stirring and carry out evaporation crystallization under a vacuum of 55KPa, controlling the amount of water evaporation until a gel is formed in the crystallization vessel.

[0056] (4) The gel gradient obtained above is heated to 68°C, then centrifuged, washed with 0.6 times the mass of inositol in 8°C water, and dried at 40°C to obtain inositol crystals.

[0057] In this embodiment, inositol crystals were sieved using 30-mesh and 60-mesh sieves. Based on the total mass of the sieved products, the mass percentage of crystals of different particle sizes in each sieve interval (above 30-mesh, 30-60-mesh, and below 60-mesh) was calculated. In the finished inositol product, the particle size of inositol was approximately 12% above 30-mesh, 75% between 30-60-mesh, and 13% below 60-mesh, with an inositol purity of 99.5%.

[0058] Example 4

[0059] An efficient and stable inositol crystallization process, the specific steps of which are as follows:

[0060] (1) Take 0.60g of inositol particles with a particle size of about 46um as seed crystals and place them in a seed crystal container with a total mass of 2kg, a temperature of 65℃ and a concentration of 31% inositol solution. Stir and slowly cool down to the same temperature as the main crystallizer and pre-grow the seed crystals to 190 mesh.

[0061] (2) Add 1.49% of the mass of the condensed polysaccharide in the crystallization vessel to the 27.5% inositol solution in the crystallization vessel. Mix the mixture with a stirrer at 60 r / min, then stop stirring. Add small steel balls with a diameter of 6 mm and a quantity equal to 0.4‰ of the volume of the inositol solution. Start the high-pressure air nozzle of the mixing equipment to spray high-speed air at 280 m / s from the bottom.

[0062] (3) Add the seed crystals from the seed crystal tank to the crystallization vessel. First, cool the crystallization to 44°C, then stop stirring and carry out evaporation crystallization under a vacuum of 50KPa. Use vacuum pressure to control the amount of water evaporation in the crystallization vessel until a gel is formed inside the crystallization vessel.

[0063] (4) The gel gradient obtained above is heated to 68°C, then centrifuged, washed with 0.65 times the mass of inositol at 10°C water, and dried at 55°C to obtain inositol crystals.

[0064] In this embodiment, inositol crystals were sieved using 30-mesh and 60-mesh sieves. Based on the total mass of the sieved product, the mass percentage of crystals of different particle sizes in each sieve interval (above 30-mesh, 30-60-mesh, below 60-mesh) was calculated. In the finished inositol product, the particle size of inositol was approximately 10% above 30-mesh, 82% between 30-60-mesh, and about 8% below 30-mesh, with an inositol purity of 99.4%.

[0065] Comparative Example 1

[0066] Take a 30% inositol solution, add 1‰ 180-200 mesh seed crystals at 60℃, cool to 25℃ at a rate of 1℃ / h while stirring at 200rpm, then centrifuge, wash with 1 times the mass of inositol at 15℃ water, and dry at 40℃ to obtain inositol crystals.

[0067] In this embodiment, inositol crystals were sieved using 30-mesh and 60-mesh sieves. Based on the total mass of the sieved product, the mass percentage of crystals of different particle sizes in each sieve interval (above 30-mesh, 30-60-mesh, and below 60-mesh) was calculated. In the finished inositol product, the particle size of inositol was approximately 7% above 30-mesh, 66% between 30-60-mesh, and about 25% below 60-mesh, with an inositol purity of 98.6%.

[0068] Comparative Example 2

[0069] Take a 30% inositol solution, add 1‰ 300-325 mesh seed crystals at 55℃, and cool to 25℃ at a rate of 0.5℃ / h while stirring at 170rpm. Then, centrifuge, wash with 1 times the mass of inositol at 10℃ water, and dry at 40℃ to obtain inositol crystals.

[0070] In this embodiment, 77% of the inositol in the finished product has a particle size of 60 mesh or larger. The inositol crystals were sieved using 30-mesh and 60-mesh sieves. Based on the total mass of the sieved product, the mass percentage of crystals of different particle sizes in each sieve interval (above 30 mesh, 30-60 mesh, below 60 mesh) was calculated. Above 30 mesh accounted for 10%, 30-60 mesh for 68%, and below 60 mesh for approximately 22%, resulting in an inositol purity of 98.4%.

[0071] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An inositol crystallization process, characterized in that, The process employs a gel crystallization process, wherein the raw material for the gel is gel polysaccharide; The process includes the following steps: (1) After mixing the gel polysaccharide and inositol solution evenly, a gel polysaccharide aqueous suspension is obtained. Then, seed crystals are added, mixed evenly, and vacuum evaporated to crystallize until a gel is formed. (2) The precipitate obtained after heating the gel to 65-70℃ is inositol crystals; The concentration of the gel polysaccharide in the aqueous suspension of the gel polysaccharide in step (1) is 0.2-3.0 wt%; The seed crystals mentioned in step (1) are 100-250 mesh in size; The temperature for seed mixing in step (1) is 40-45℃, and the vacuum degree for vacuum evaporation is 45-60KPa.

2. The inositol crystallization process according to claim 1, characterized in that, The method for preparing the seed crystal in step (1) is as follows: take a small seed crystal and place it in a seed inositol solution, stir and cool it to 40-45℃, and pre-grow the seed crystal to 100-250 mesh.

3. The inositol crystallization process according to claim 2, characterized in that, The small-sized seed crystals are 300-325 mesh in size, and the amount of small-sized seed crystals added is 0.5-1‰ of the solid content of the seed crystal inositol solution. The mass concentration of the seed inositol solution is 30-33%, and the temperature of the seed inositol solution is 58-70℃.

4. The inositol crystallization process according to claim 3, characterized in that, The mass concentration of the seed inositol solution is 1.5-4% higher than that of the inositol solution.

5. The inositol crystallization process according to claim 1, characterized in that, The mixing method in step (1) is as follows: the mixture of the gel polysaccharide and the inositol solution is stirred evenly at 150-180 rpm, and then 0.1-0.5‰ of the volume of the inositol solution and steel balls with a diameter of 5-6 mm are added. The high-pressure air nozzle mixing device is started, and the high-pressure air nozzle sprays air at a high speed of 250-300 m / s from the bottom.

6. The inositol crystallization process according to claim 1, characterized in that, The heating in step (2) is a gradient heating, with heating rates of: 1℃ / h for 45-50℃, 2℃ / h for 50-60℃, and 3℃ / h for 60-70℃; The precipitate needs to be washed and dried. The washing water temperature is 7-15℃, and the water volume is 0.5-0.75 times the mass of the precipitate. The drying temperature is 35-60℃.