Preparation method of mannitol

Abstract

The invention provides a mannitol preparation method, which comprises: using glucose as a raw material, carrying out differential isomerization on glucose isomerase to obtain high fructose corn syrup, carrying out chromatographic separation on the high fructose corn syrup to obtain fructose, and carrying out hydrogenation reduction on the fructose under the action of a catalyst to obtain mannitol and sorbitol, finally, mannitol and sorbitol are purified in a cooling crystallization mode, and a mannitol product is obtained. The finished product prepared by the method provided by the invention is less in fine powder and not easy to cake; all indexes of the product meet the requirements of Chinese pharmacopoeia.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis pharmaceuticals, and more specifically relates to a method for preparing mannitol. Background Technology

[0002] Mannitol is an important hexose alcohol with wide and crucial applications in many fields, including medicine, food, and chemicals. In the pharmaceutical field, mannitol, due to its unique physicochemical properties, is often used as a dehydrating agent to reduce intracranial and intraocular pressure, treating diseases such as cerebral edema and glaucoma; it is also a good diuretic, promoting the excretion of excess water from the body. Furthermore, in pharmaceutical preparations, mannitol can be used as a filler and lyophilization protectant to improve drug stability and quality. In the food industry, mannitol, due to its low sweetness, low calorie content, and non-hygroscopic properties, is widely used in the production of sugar-free foods, low-calorie foods, and various health foods, meeting consumers' demands for healthy eating. In the chemical field, mannitol can be used in the production of synthetic resins, plastics, and explosives, and it can also be used as a raw material in cosmetics, providing moisturizing and hydrating effects.

[0003] Currently, the main industrial methods for preparing mannitol are kelp extraction and chemical synthesis. Kelp extraction uses kelp and other seaweed as raw materials, extracting mannitol through a series of complex steps including soaking, alkaline hydrolysis, acidification, and crystallization. However, this method has several limitations. First, the source of raw materials is greatly limited by season and region. The growth and harvesting of kelp and other seaweed are distinctly seasonal, and not all regions are suitable for seaweed cultivation, leading to unstable raw material supply and difficulty in meeting the needs of large-scale industrial production. Second, the kelp extraction process is cumbersome, has a long production cycle, and consumes large amounts of energy and chemical reagents, increasing production costs and causing environmental pollution. Furthermore, the mannitol product obtained by this method has relatively low purity, requiring further complex purification steps, further increasing production costs and difficulty.

[0004] Chemical synthesis methods mainly include catalytic hydrogenation using glucose as a raw material. When preparing mannitol from glucose, glucose is typically first converted to fructose, then the fructose is hydrogenated and reduced under a catalyst to obtain a mixture of mannitol and sorbitol. Finally, the mannitol product is obtained through separation and purification. Although chemical synthesis methods overcome the limitations of raw materials in kelp extraction to some extent, existing chemical synthesis processes still have some problems that urgently need to be solved.

[0005] In the glucose isomerization stage, controlling the reaction conditions is crucial for the amount and quality of fructose produced. Improper control of factors such as pH, temperature, and metal ion concentration in the reaction system can affect the activity of glucose isomerase, leading to low isomerization efficiency, reduced fructose production, and potentially more impurities, impacting subsequent reactions and product quality. In the hydrogenation reduction stage, the selection and application conditions of the catalyst significantly influence the selectivity and yield of the reaction. Currently used catalysts may have issues such as low activity and poor selectivity, resulting in an undesirable ratio of mannitol and sorbitol produced, and potentially generating byproducts that reduce product purity. Furthermore, improper control of conditions such as temperature and pressure in the hydrogenation reaction can also affect the reaction's progress and product quality.

[0006] In the subsequent separation and purification stages, existing methods are not ideal for separating mixtures of mannitol and sorbitol. Cooling crystallization is a commonly used separation method, but controlling the crystallization process is difficult. Factors such as crystallization temperature and cooling rate affect the crystal morphology, particle size distribution, and purity. Improper crystallization conditions may lead to the inclusion of numerous impurities in the crystals or uneven crystal size, affecting subsequent centrifugation, drying, and other operations, thereby reducing product quality and yield. Furthermore, existing separation and purification processes are cumbersome, requiring multiple decolorization, filtration, and crystallization operations, which not only increases production costs and time but may also result in the loss of some mannitol, further reducing product yield.

[0007] In summary, existing mannitol preparation methods suffer from numerous problems in raw material supply, reaction condition control, and separation and purification, resulting in low product purity, low yield, and high production costs, making it difficult to meet the growing market demand for high-quality mannitol. Therefore, developing an efficient, environmentally friendly method for preparing high-purity mannitol is of significant practical importance. Summary of the Invention

[0008] In view of this, the present invention provides a method for preparing mannitol, which can effectively improve the total yield and reduce energy consumption.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing mannitol includes: using glucose as raw material, performing differential isomerization with glucose isomerase to obtain fructose syrup, then separating the fructose syrup by chromatography to obtain fructose, purifying the fructose, hydrogenating and reducing the fructose to mannitol and sorbitol under the action of a catalyst, and finally purifying the mannitol and sorbitol by cooling crystallization to obtain the mannitol product.

[0010] Preferably, the above preparation method specifically includes the following steps: (1) Ingredients: Add deionized water or glucose solution to the sugar dissolving tank, then pour glucose into the sugar dissolving tank for sugar dissolving treatment; (2) First decolorization: The dissolved sugar is put into the decolorization tank, activated carbon is added for decolorization, and after decolorization, it is filtered and then put into the isomerization heating tank. (3) Isomerization: Add magnesium sulfate and sodium metabisulfite, then adjust the pH to 7.0-8.5, heat and then enter the isomerization column for isomerization treatment; (4) First exchange: The isomerized feed solution enters the ion exchange column for desalination; (5) Separation: The exchanged liquid enters the chromatographic separation to obtain glucose solution and high fructose (fructose content ≥95%); the high fructose is evaporated and enters the next process; (6) Evaporation: The high fructose after separation is increased in concentration by vacuum evaporation at 70-80℃, and the high fructose concentration index is ≥30%; (7) Hydrogenation: High fructose is pumped into a high-pressure reactor, nickel catalyst is added, the temperature is controlled at 125-150℃, the pressure is 4-10MPa, and the hydrogenation control indicators are: mannitol content ≥58%, residual sugar ≤1.5%; (8) Secondary exchange: After hydrogenation, the feed solution enters the ion exchange column for desalting treatment. The conductivity of the feed solution after exchange is ≤50us / cm; (9) Secondary decolorization: After the exchange, the liquid is pumped into the decolorization tank, then plant activated carbon is added for decolorization treatment, and then filtered by a filter. (10) Evaporation: The decolorized liquid is evaporated in a multi-effect evaporator, and the concentration is controlled at 50-65%. (11) Primary crystallization: The steamed liquid is injected into the primary crystallizer and crystallization is achieved by continuous cooling. When the temperature drops below 20°C, the liquid is discharged and centrifuged. (12) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation; the time is controlled to be more than 10 seconds, and the mannitol content of the filter cake is ≥80%; (13) Three-stage decolorization and filtration: Dissolve the filter cake, inject the alcohol solution into the decolorization tank, add 0.5-5 kg / t of pharmaceutical activated carbon (dry weight) for decolorization and filtration; filtration is carried out by plate and frame filter cloth. (14) Secondary crystallization: The filtered liquid is injected into the crystallizer and the crystallization is achieved by cooling. When the temperature is below 25°C, the liquid is discharged and then mannitol is obtained by centrifugation, drying and screening.

[0011] Preferably, the sugar treatment temperature in step (1) is 55-65℃ and the glucose concentration is 40-50%.

[0012] Preferably, in step (2), the ratio of activated carbon to precipitated sugar is 2-4 kg / m³. 3The decolorization time is 25-35 minutes.

[0013] Preferably, in step (4), the amount of magnesium sulfate added is 0-0.5 g / L; the amount of sodium metabisulfite added is 0-0.3 g / L; sodium hydroxide is used to adjust the pH, the heating temperature is 50-60℃, and the fructose content after isomerization is controlled at 40-50%.

[0014] Preferably, the nickel catalyst in step (8) is a quaternary nickel catalyst; Preferably, in step (10), the ratio of activated carbon to the exchanged liquid is 0-5 kg / T, and the decolorization time is 25-35 minutes.

[0015] Preferably, in step (13), 0.5-5 kg / t of pharmaceutical activated carbon (dry weight) is added for decolorization, and the decolorization time is 25-35 minutes.

[0016] Preferably, in step (14), the moisture content of the centrifuged filter cake is controlled below 9%, the drying temperature is ≥55℃, and the material moisture content is ≤0.5%.

[0017] As can be seen from the above technical solution, compared with the prior art, the present invention has the following technical effects: 1. The crystals are large and uniform, easy to centrifuge, and the product has high purity.

[0018] 2. The finished product contains less fine powder and is less prone to clumping.

[0019] 3. All product indicators meet the requirements of the Chinese Pharmacopoeia. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0021] Figure 1 The attached figure is a flowchart of the present invention. Detailed Implementation

[0022] 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.

[0023] Example 1 This embodiment provides a method for preparing mannitol, including the following steps: (1) Preparation: First, add deionized water or separated glucose solution to the sugar dissolving tank, then pour glucose into the sugar dissolving tank. The sugar dissolving temperature is controlled at 60℃ and the concentration is controlled at 42%. The volume of the prepared glucose solution is about 4600L.

[0024] (2) Decolorization: The dissolved sugar is put into the decolorization tank, and 2.5KG of activated carbon is added to each tank. After decolorization for 30 minutes, the sugar is filtered and then put into the isomer heating tank.

[0025] (3) Isomerization: Add magnesium sulfate (0.3 g / L) and sodium metabisulfite (0.2 g / L), adjust the pH of the feed solution to 7.8 with sodium hydroxide, heat the feed solution to 56°C, and enter the isomerization column. The fructose content after isomerization is controlled at 43%.

[0026] (4) Exchange: The isomerized feed solution enters the ion exchange column for desalting.

[0027] (5) Separation: The exchanged feed solution enters the chromatographic separation to obtain glucose solution and high fructose (fructose content 95.5%) at both ends. The high fructose is evaporated and enters the next process.

[0028] (6) Evaporation: The high fructose after separation is evaporated at 70°C to increase the concentration, and the high fructose concentration index is 35%.

[0029] (7) Hydrogenation: High fructose is fed into a high pressure reactor, a quaternary nickel catalyst is added, the temperature is controlled at 130℃ and the pressure at 6MPa. Hydrogenation control indicators: mannitol content 61%, residual sugar 1.2%.

[0030] (8) Exchange: After hydrogenation, the feed solution enters the ion exchange column for desalting. After exchange, the conductivity of the feed solution is 35 μS / cm.

[0031] (9) Decolorization: After the exchange, the liquid is pumped into the decolorization tank, and 0-5 kg ​​of activated carbon is added to each tank. The decolorization time is 30 minutes, and the liquid is filtered by a filter.

[0032] (10) Evaporation: The decolorized liquid is evaporated by a multi-effect evaporator and the concentration is controlled at 58%.

[0033] (11) Primary crystallization: After steaming, the liquid is injected into the primary crystallizer and crystallization is achieved by continuous cooling. When the temperature drops to 18°C, the liquid is discharged and centrifuged.

[0034] (12) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation. The time is controlled at 15 seconds, and the mannitol content of the filter cake is 82%.

[0035] (13) Decolorization and filtration: Dissolve the filter cake, inject the alcohol solution into the decolorization tank, add 3 kg / t of medicinal activated carbon (dry weight) for decolorization, and decolorize for 30 minutes.

[0036] (14) Secondary crystallization: The filtered liquid is injected into the crystallizer and the crystallization is achieved by cooling. When the temperature is below 22°C, the liquid is discharged and centrifuged.

[0037] (15) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation, and the moisture content of the centrifuged filter cake is controlled at 8%.

[0038] (16) Drying: The centrifuged material enters the microwave dryer, the drying temperature is 60℃, and the moisture content of the material is 0.3%.

[0039] (17) Screening: Start the screening machine and transport the screened material to the packaging station.

[0040] (18) Packaging: The materials are transported to a quantitative packaging scale for packaging.

[0041] Example 2 This embodiment provides a method for preparing mannitol, including the following steps: (1) Preparation: First, add deionized water or separated glucose solution to the sugar dissolving tank, then pour glucose into the sugar dissolving tank. The sugar dissolving temperature is controlled at 58℃ and the concentration is controlled at 45%. The volume of the prepared glucose solution is about 4600L.

[0042] (2) Decolorization: The dissolved sugar is put into a decolorization tank, and 4KG of plant activated carbon is added to each tank. After decolorization for 30 minutes, the sugar is filtered and then put into a heterogeneous heating tank.

[0043] (3) Isomerization: Add magnesium sulfate (0.3 g / L) and sodium metabisulfite (0.2 g / L), adjust the pH of the feed solution to 8.0 with sodium hydroxide, heat the feed solution to 58°C, and enter the isomerization column. The fructose content after isomerization is controlled at 42%.

[0044] (4) Exchange: The isomerized feed solution enters the ion exchange column for desalting.

[0045] (5) Separation: The exchanged feed solution enters the chromatographic separation to obtain glucose solution and high fructose (fructose content 96%) at both ends. The high fructose is evaporated and enters the next process.

[0046] (6) Evaporation: The high fructose after separation is evaporated at 80℃ to increase the concentration, and the high fructose concentration index is 33%.

[0047] (7) Hydrogenation: High fructose is fed into a high pressure vessel, nickel catalyst is added, temperature is controlled at 132℃, pressure is 6.5MPa, hydrogenation control indicators: mannitol content 60%, residual sugar 1.0%.

[0048] (8) Exchange: After hydrogenation, the feed solution enters the ion exchange column for desalting. After exchange, the conductivity of the feed solution is 40 μS / cm.

[0049] (9) Decolorization: After the exchange, the liquid is pumped into the decolorization tank, and 4 kg of plant activated carbon is added to each tank. The decolorization time is 30 minutes, and the liquid is filtered by a filter.

[0050] (10) Evaporation: The decolorized liquid is evaporated by a multi-effect evaporator, and the concentration is controlled at 60%.

[0051] (11) Primary crystallization: After steaming, the liquid is injected into the primary crystallizer and crystallization is achieved by continuous cooling. When the temperature drops to 20°C, the liquid is discharged and centrifuged.

[0052] (12) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation. The time is controlled at 12 seconds, and the mannitol content of the filter cake is 81%.

[0053] (13) Decolorization and filtration: Dissolve the filter cake, inject the alcohol solution into the decolorization tank, add 3 kg / t of medicinal activated carbon (dry weight) for decolorization, and decolorize for 30 minutes.

[0054] (14) Secondary crystallization: The filtered liquid is injected into the crystallizer and the crystallization is achieved by cooling. When the temperature is 23°C, the liquid is discharged and centrifuged.

[0055] (15) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation, and the moisture content of the centrifuged filter cake is controlled at 9%.

[0056] (16) Drying: The centrifuged material enters the microwave dryer, the drying temperature is 58℃, and the moisture content of the material is 0.2%.

[0057] (17) Screening: Start the screening machine and transport the screened material to the packaging station.

[0058] (18) Packaging: The materials are transported to a quantitative packaging scale for packaging.

[0059] Example 3 This embodiment provides a method for preparing mannitol, including the following steps: (1) Preparation: First, add deionized water or separated glucose solution to the sugar dissolving tank, then pour glucose into the sugar dissolving tank. The sugar dissolving temperature is controlled at 60℃ and the concentration is controlled at 42%. The volume of the prepared glucose solution is about 4600L.

[0060] (2) Decolorization: The dissolved sugar is put into a decolorization tank, and 3KG of plant activated carbon is added to each tank. After decolorization for 30 minutes, the sugar is filtered and then put into a heterogeneous heating tank.

[0061] (3) Isomerization: Add magnesium sulfate (0.3 g / L) and sodium metabisulfite (0.2 g / L), adjust the pH of the feed solution to 8.2 with sodium hydroxide, heat the feed solution to 55°C, and enter the isomerization column. The fructose content after isomerization is controlled at 42%.

[0062] (4) Exchange: The isomerized feed solution enters the ion exchange column for desalting.

[0063] (5) Separation: The exchanged feed solution enters the chromatographic separation to obtain glucose solution and high fructose (fructose content 95.8%) at both ends. The high fructose is evaporated and enters the next process.

[0064] (6) Evaporation: The high fructose after separation is evaporated at 75°C to increase the concentration, and the high fructose concentration index is 36%.

[0065] (7) Hydrogenation: High fructose is fed into a high pressure reactor, a quaternary nickel catalyst is added, the temperature is controlled at 128℃ and the pressure at 6.3MPa. Hydrogenation control indicators: mannitol content 62% and residual sugar 1.1%.

[0066] (8) Exchange: After hydrogenation, the feed solution enters the ion exchange column for desalting. After exchange, the conductivity of the feed solution is 25 μS / cm.

[0067] (9) Decolorization: After the exchange, the liquid is pumped into the decolorization tank, and 3 kg of plant activated carbon is added to each tank. The decolorization time is 30 minutes, and the liquid is filtered by a filter.

[0068] (10) Evaporation: The decolorized liquid is evaporated by a multi-effect evaporator and the concentration is controlled at 61%.

[0069] (11) Primary crystallization: After steaming, the liquid is injected into the primary crystallizer and crystallization is achieved by continuous cooling. When the temperature drops to 17°C, the liquid is discharged and centrifuged.

[0070] (12) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation. The time is controlled at 15 seconds, and the mannitol content of the filter cake is 85%.

[0071] (13) Decolorization and filtration: Dissolve the filter cake, inject the alcohol solution into the decolorization tank, add 2.5 kg / t of medicinal activated carbon (dry weight) for decolorization, and decolorize for 30 minutes.

[0072] (14) Secondary crystallization: The filtered liquid is injected into the crystallizer and the crystallization is achieved by cooling. When the temperature is 24℃, the liquid is discharged and centrifuged.

[0073] (15) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation, and the moisture content of the centrifuged filter cake is controlled at 7%.

[0074] (16) Drying: The centrifuged material enters the microwave dryer, the drying temperature is 62℃, and the moisture content of the material is 0.4%.

[0075] (17) Screening: Start the screening machine and transport the screened material to the packaging station.

[0076] (18) Packaging: The materials are transported to a quantitative packaging scale for packaging.

[0077] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since they correspond to the methods disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to the method section.

[0078] 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. A method for preparing mannitol, characterized in that, include: Glucose is used as a raw material and is converted into fructose syrup by glucose isomerase. Then, fructose is separated by chromatography from the fructose syrup. Fructose is then hydrogenated and reduced to mannitol and sorbitol under the action of a catalyst. Finally, mannitol and sorbitol are purified by cooling crystallization to obtain mannitol product.

2. The method for preparing mannitol according to claim 1, characterized in that, Specifically, the following steps are included: (1) Ingredients: Add deionized water or glucose solution to the sugar dissolving tank, then pour glucose into the sugar dissolving tank for sugar dissolving treatment; (2) First decolorization: The dissolved sugar is put into the decolorization tank, activated carbon is added for decolorization, and after decolorization, it is filtered and then put into the isomerization heating tank. (3) Isomerization: Add magnesium sulfate and sodium metabisulfite, then adjust the pH to 7.0-8.5, heat up and then enter the isomerization column for isomerization treatment; (4) First exchange: The isomerized feed solution enters the ion exchange column for desalination; (5) Separation: The exchanged feed solution enters the chromatographic separation to obtain glucose solution and high fructose. The high fructose is evaporated and enters the next process. (6) Evaporation: After separation, the high fructose concentration is increased by vacuum evaporation at 70-80℃, and the high fructose concentration index is ≥30%; (7) Hydrogenation: High fructose is fed into a high-pressure reactor, a quaternary nickel catalyst is added, the temperature is controlled at 125-150℃, and the pressure is 4-10MPa. Hydrogenation control indicators: mannitol content ≥58%, residual sugar ≤1.5%; (8) Secondary exchange: After hydrogenation, the feed solution enters the ion exchange column for desalting treatment. The conductivity of the feed solution after exchange is ≤50us / cm; (9) Secondary decolorization: After the exchange, the liquid is pumped into the decolorization tank, activated carbon is added for decolorization treatment, and then filtered by a filter. (10) Evaporation: The decolorized liquid is evaporated in an evaporator at 70-90℃, and the concentration is controlled at 50-65%; (11) Primary crystallization: After steaming, the liquid is injected into the primary crystallizer and cooled by cooling water to achieve crystallization. When the temperature drops below 20°C, the liquid is discharged and centrifuged. (12) Centrifugation: The crystallized liquid is injected into a centrifuge for mother liquor separation; the time is controlled at about 10 seconds, and the mannitol content of the filter cake is ≥80%; (13) Three-stage decolorization and filtration: Dissolve the filter cake, convert it to alcohol, and then inject it into the decolorization tank. Add 0.5-5 kg / t of pharmaceutical activated carbon (dry weight) for decolorization and filtration. The filtration is carried out by plate and frame filter cloth. (14) Secondary crystallization: The filtered liquid is injected into the crystallizer and the crystallization is achieved by cooling. When the temperature is below 25°C, the liquid is discharged and then mannitol is obtained by centrifugation, drying and screening.

3. The method for preparing mannitol according to claim 2, characterized in that, In step (1), the sugar treatment temperature is 55-65℃ and the glucose mass percentage concentration is 40-50%.

4. The method for preparing mannitol according to claim 2, characterized in that, In step (2), the ratio of activated carbon to precipitated sugar is 2-4 kg / m³. 3 The decolorization time is 25-35 minutes.

5. The method for preparing mannitol according to claim 2, characterized in that, In step (4), the amount of magnesium sulfate added is 0-0.5 g / L; the amount of sodium metabisulfite added is 0-0.3 g / L; sodium hydroxide is used to adjust the pH, the temperature is raised to 50-60℃, and the fructose content after isomerization is controlled at 40-50%.

6. The method for preparing mannitol according to claim 2, characterized in that, In step (8), the nickel catalyst is a quaternary catalyst.

7. The method for preparing mannitol according to claim 2, characterized in that, In step (10), the ratio of activated carbon to the exchanged liquid is 0-5 kg / T, and the decolorization time is 25-35 minutes.

8. The method for preparing mannitol according to claim 2, characterized in that, The concentration of mannitol after dissolution in step (13) is 40±5%.

9. The method for preparing mannitol according to claim 2, characterized in that, Step (13) Use 0.5-5 kg / T of activated carbon for Chinese medicine, and decolorize for 25-35 minutes.

10. A method for preparing mannitol according to claim 2, characterized in that, In step (15), the moisture content of the centrifuged filter cake is controlled below 9%, the drying temperature is ≥55℃, and the material moisture content is ≤0.5%.

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