A preparation process of glucosamine hydrochloride product

Abstract

The present invention discloses a preparation process for a glucosamine hydrochloride product, comprising the following steps: (1) adding concentrated hydrochloric acid to a fermentation broth and hydrolyzing N-acetylglucosamine under heating conditions; after the hydrolysis is completed, adding a neutralizer to the obtained hydrolyzate to neutralize excess hydrochloric acid; and then concentrating the obtained hydrolyzate to form a concentrated solution. (2) adding a chloride ion remover prepared by the present invention to the concentrated solution, and then irradiating the solution with visible light; after the hydrolysis is completed, separating the chloride ion remover and collecting the liquid phase. (3) adding ethanol to the liquid phase for alcohol precipitation, and then separating the solid product, and drying to obtain the glucosamine hydrochloride product. The above-mentioned preparation process for the glucosamine hydrochloride product can not only reduce the chloride ion content in the glucosamine hydrochloride, but also can use visible light for decolorization, thereby improving the purity of the glucosamine hydrochloride.

Description

Technical Field

[0001] The present invention relates to the technical field of glucosamine production, in particular to a preparation process of a glucosamine hydrochloride product. Background Art

[0002] Glucosamine hydrochloride, scientifically known as 2-amino-2-deoxy-glucose hydrochloride, is a drug used to treat and prevent osteoarthritis. It stimulates the biochemical synthesis of mucopolysaccharides and increases bone calcium uptake, improving the metabolic function and nutrition of bone and cartilage tissue. It also improves and enhances the viscosity of synovial fluid, increasing synovial fluid synthesis and providing joint lubrication. Glucosamine hydrochloride is a derivative of glucosamine and, compared to glucosamine, is less hygroscopic and less hygroscopic, making it easier to store. The main preparation processes for glucosamine hydrochloride include acid hydrolysis, enzymatic hydrolysis, and microbial fermentation. Compared to acid hydrolysis and enzymatic hydrolysis, microbial fermentation eliminates regional and seasonal constraints on raw material sourcing. The resulting glucosamine hydrochloride is free of fishy odor and does not produce allergic reactions. It also offers technical advantages such as a short production cycle, high production efficiency, and minimal environmental impact. However, the glucosamine hydrochloride prepared by this method contains a large amount of chloride ions, making it unsuitable for long-term use by patients with cardiovascular disease, kidney disease, and hypertension, limiting its application in these patients. Summary of the Invention

[0003] The present invention provides a preparation process for a glucosamine hydrochloride product, which can not only reduce the chloride ion content in glucosamine hydrochloride, but also utilize visible light for decolorization, thereby increasing the purity of glucosamine hydrochloride. To achieve the above-mentioned object, the present invention discloses the following technical solution.

[0004] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0005] (1) Add tetraethyl titanate to the mixture containing Fe 3+ The modified titanium hydroxide is obtained by adding an alkali solution to an aqueous solution of the source, and then hydrolyzing the solution under stirring. After completion, the solid product is separated and dried to obtain the modified titanium hydroxide for later use.

[0006] (2) The modified titanium hydroxide, glass powder and adhesive are mixed and granulated, and then calcined at a high temperature to obtain a chloride ion remover.

[0007] (3) Concentrated hydrochloric acid is added to the fermentation broth, and N-acetylglucosamine is hydrolyzed under heating conditions. After completion, a neutralizer is added to the obtained hydrolyzate to neutralize excess hydrochloric acid, and then the obtained hydrolyzate is concentrated to form a concentrated solution.

[0008] (4) Adding the chloride ion removing agent to the concentrated solution, and then irradiating the solution with visible light. After the irradiation is completed, the chloride ion removing agent is separated, and the liquid phase is collected for standby use.

[0009] (5) adding ethanol to the liquid phase for alcohol precipitation, then separating the solid product, and drying to obtain the glucosamine hydrochloride product.

[0010] Furthermore, in step (1), the Fe 3+ The concentration of the Fe source is 5-8%. 3+ The source includes any one of ferric chloride, ferric sulfate, ferric nitrate, and the like.

[0011] Furthermore, in step (1), the tetraethyl titanate is mixed with Fe 3+ The volume ratio of the aqueous solution is 1:1.5~2.2.

[0012] Furthermore, in step (1), the OH provided by the alkali solution - with Fe 3+ The molar ratio of Fe is 3.1~3.5:1, so that the Fe 3+ All of the precipitates are formed. Optionally, the alkali solution includes any one of sodium hydroxide solution, ammonia water, etc.

[0013] Furthermore, in step (1), the hydrolysis reaction time is 20 to 35 minutes, so that the tetraethyl titanate is hydrolyzed to form titanium dioxide.

[0014] Furthermore, in step (2), the ratio of the modified titanium hydroxide, glass powder, and adhesive is 10 parts by weight: 1.2-1.8 parts by weight: 2.5-3.5 parts by weight. Optionally, the adhesive includes any one of starch, cyclodextrin, animal glue, shellac, etc.

[0015] Furthermore, in step (2), the calcination temperature is 850-1020°C and the calcination time is 1-1.5 hours, thereby melting the glass powder and bonding the modified titanium hydroxide together. At the same time, the iron hydroxide in the modified titanium hydroxide is graded into iron oxide and loaded in the porous titanium dioxide matrix.

[0016] Furthermore, in step (3), the mass fraction of hydrochloric acid in the fermentation broth is 30-35%, the heating temperature is 80-90° C., and the hydrolysis time is 4-5.5 hours, so that the N-acetylglucosamine is converted into glucosamine.

[0017] Furthermore, in step (3), the neutralizing agent includes any one of sodium hydroxide, sodium carbonate, sodium bicarbonate, etc., so as to form glucosamine hydrochloride while removing excess hydrochloric acid.

[0018] Furthermore, in step (3), the hydrolyzate is heated and concentrated to 40-55% of the initial volume.

[0019] Furthermore, in step (4), the amount of the chloride ion remover added is 6-11 g / L.

[0020] Furthermore, in step (4), the power of the visible light is 60-100W, and the illumination time is 45-60 minutes. Thus, the pigment components in the concentrated solution are removed by the photocatalytic decolorization effect of the chloride ion remover, thereby improving the purity of the product.

[0021] Furthermore, in step (5), the amount of ethanol added is 3 to 5 times the volume of the liquid phase, and the standing time is 30 to 40 minutes, so that the glucosamine hydrochloride in the concentrated solution is crystallized and precipitated.

[0022] Furthermore, in step (5), the drying method includes any one of freeze-drying, vacuum drying, etc.

[0023] Compared with the prior art, the present invention has the following beneficial technical effects: the chloride ion remover prepared by the present invention can not only reduce the chloride ion content in glucosamine hydrochloride, but also can be decolorized by visible light to improve the purity of glucosamine hydrochloride. This is because: in the preparation of the chloride ion remover, the present invention first uses Fe 3+ The aqueous solution promotes the hydrolysis of tetraethyl titanate to form titanium hydroxide, and at the same time, alkali solution is added to dope the titanium hydroxide with iron hydroxide when it is formed to form modified titanium hydroxide. Further, the present invention granulates the modified titanium hydroxide with glass powder and an adhesive and then calcines it at a high temperature. During this process, the glass powder melts and bonds the titanium dioxide formed by the decomposition of titanium hydroxide together to form a matrix. The adhesive carbonizes and decomposes the matrix to form a porous structure. After the decomposition of the iron hydroxide, it is converted into iron oxide and loaded in the porous matrix. At the same time, part of the iron oxide is immersed in the crystal structure of the titanium dioxide to form doping, which can effectively improve the catalytic activity of the titanium dioxide in the visible light range, thereby being able to be decolorized in the visible light range. At the same time, the matrix / chloride ion remover of the porous structure can achieve adsorption of chloride ions, and the iron oxide can also promote the adsorption of chloride ions by the chloride ion remover. Therefore, the glucosamine hydrochloride can be mechanically decolorized while reducing the content of chloride ions in glucosamine hydrochloride, thereby improving the purity of glucosamine hydrochloride. DETAILED DESCRIPTION

[0024] It should be noted that the following detailed description is illustrative and is intended to provide further illustration of the present invention. The present invention will now be further illustrated through specific implementations. Example 1

[0025] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0026] (1) Mix tetraethyl titanate and 7% ferric chloride aqueous solution in a volume ratio of 1:2 and stir evenly, then - with Fe 3+ Then, sodium hydroxide solution was added at a molar ratio of 3.2:1 and stirred for 30 minutes to carry out the hydrolysis reaction. After completion, the solid product was separated by centrifugation and vacuum dried at 50°C for 1 hour to obtain modified titanium hydroxide for later use.

[0027] (2) The modified titanium hydroxide, glass powder and starch are mixed uniformly in a mass ratio of 10:1.5:3 and then wet granulated. The obtained particles with a particle size distribution between 2 and 5 mm are then calcined at 930° C. for 75 min in an air atmosphere. After completion, the mixture is cooled to room temperature to obtain a chloride ion remover for standby use.

[0028] (3) Concentrated hydrochloric acid was added to the fermentation broth to make the initial mass fraction of hydrochloric acid in the fermentation broth 30%, and then heated to 85°C in a water bath for 5 hours to hydrolyze N-acetylglucosamine. After completion, sodium hydroxide was added to the obtained hydrolyzate to neutralize the excess hydrochloric acid, and then the obtained hydrolyzate was heated and concentrated to 50% of the initial volume to obtain a concentrated solution.

[0029] (4) The chloride ion remover prepared in this example was added to the concentrated solution at a material-liquid ratio of 8 g / L, stirred evenly, and irradiated with a 70W xenon lamp for 50 minutes. After completion, the chloride ion remover was separated by filtration, and the liquid phase was collected for later use.

[0030] (5) Add 4 times the volume of ethanol (95% by mass) to the liquid phase and perform alcohol precipitation for 30 minutes. After the precipitation, the solid product is separated by centrifugation and vacuum dried at 50°C for 1 hour to obtain glucosamine hydrochloride product. Example 2

[0031] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0032] (1) Mix tetraethyl titanate and 5% ferric nitrate aqueous solution in a volume ratio of 1:1.5 and stir evenly, then - with Fe 3+ Then, sodium hydroxide solution was added at a molar ratio of 3.1:1 and stirred for 20 minutes to carry out the hydrolysis reaction. After completion, the solid product was separated by centrifugation and vacuum dried at 50°C for 1 hour to obtain modified titanium hydroxide for later use.

[0033] (2) The modified titanium hydroxide, glass powder and cyclodextrin are mixed uniformly in a mass ratio of 10:1.8:3.5 and then wet granulated. The obtained particles with a particle size distribution between 2 and 5 mm are then calcined at 850° C. for 90 min in an air atmosphere. After completion, the mixture is cooled to room temperature to obtain a chloride ion remover for standby use.

[0034] (3) Concentrated hydrochloric acid was added to the fermentation broth to make the initial mass fraction of hydrochloric acid in the fermentation broth 35%, and then heated to 90°C in a water bath for 4 hours to hydrolyze N-acetylglucosamine. After completion, sodium carbonate was added to the obtained hydrolyzate to neutralize the excess hydrochloric acid, and then the obtained hydrolyzate was heated and concentrated to 40% of the initial volume to obtain a concentrated solution.

[0035] (4) The chloride ion remover prepared in this example was added to the concentrated solution at a material-liquid ratio of 11 g / L, stirred evenly, and irradiated with a 60 W xenon lamp for 60 min. After completion, the chloride ion remover was separated by filtration, and the liquid phase was collected for later use.

[0036] (5) Add ethanol (95% by mass) in an amount three times the volume of the liquid phase and perform alcohol precipitation for 40 minutes. After the precipitation, the solid product is separated by centrifugation and vacuum dried at 50°C for 1.5 hours to obtain glucosamine hydrochloride product. Example 3

[0037] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0038] (1) Mix tetraethyl titanate and 8% ferric sulfate aqueous solution in a volume ratio of 1:2.2 and stir evenly, then - with Fe 3+ Ammonia water was added at a molar ratio of 3.5:1 and stirred for 35 minutes to carry out the hydrolysis reaction. After completion, the solid product was separated by centrifugation and vacuum dried at 50°C for 1 hour to obtain modified titanium hydroxide, which was then set aside.

[0039] (2) The modified titanium hydroxide, glass powder and starch are mixed uniformly in a mass ratio of 10:1.2:2.5 and then wet granulated. The obtained particles with a particle size distribution between 2 and 5 mm are then calcined at 1020° C. for 60 min in an air atmosphere. After completion, the mixture is cooled to room temperature to obtain a chloride ion remover for standby use.

[0040] (3) Concentrated hydrochloric acid was added to the fermentation broth to make the initial mass fraction of hydrochloric acid in the fermentation broth 32%, and then heated to 80°C in a water bath for 5.5 hours to hydrolyze N-acetylglucosamine. After completion, sodium bicarbonate was added to the resulting hydrolyzate to neutralize the excess hydrochloric acid, and then the resulting hydrolyzate was heated and concentrated to 55% of the initial volume to obtain a concentrated solution.

[0041] (4) The chloride ion remover prepared in this example was added to the concentrated solution at a material-liquid ratio of 6 g / L, stirred evenly, and irradiated with a 100 W xenon lamp for 45 minutes. After completion, the chloride ion remover was separated by filtration, and the liquid phase was collected for later use.

[0042] (5) Add 5 times the volume of ethanol (95% by mass) to the liquid phase and perform alcohol precipitation for 35 minutes. After the precipitation, the solid product is separated by centrifugation and vacuum dried at 50°C for 1.5 hours to obtain glucosamine hydrochloride product. Example 4

[0043] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0044] (1) Mix tetraethyl titanate and water in a volume ratio of 1:2 and stir evenly. Then stir continuously for 30 minutes to carry out the hydrolysis reaction. After completion, centrifuge to separate the solid product, vacuum dry it at 50°C for 1 hour to obtain titanium hydroxide, which is then set aside.

[0045] (2) The titanium hydroxide, glass powder and starch are mixed uniformly in a mass ratio of 10:1.5:3 and then wet granulated. The obtained particles with a particle size distribution between 2 and 5 mm are then calcined at 930° C. for 75 min in an air atmosphere. After completion, the mixture is cooled to room temperature to obtain a chloride ion remover for standby use.

[0046] (3) Concentrated hydrochloric acid was added to the fermentation broth to make the initial mass fraction of hydrochloric acid in the fermentation broth 30%, and then heated to 85°C in a water bath for 5 hours to hydrolyze N-acetylglucosamine. After completion, sodium hydroxide was added to the obtained hydrolyzate to neutralize the excess hydrochloric acid, and then the obtained hydrolyzate was heated and concentrated to 50% of the initial volume to obtain a concentrated solution.

[0047] (4) The chloride ion remover prepared in this example was added to the concentrated solution at a material-liquid ratio of 8 g / L, stirred evenly, and irradiated with a 70W xenon lamp for 50 minutes. After completion, the chloride ion remover was separated by filtration, and the liquid phase was collected for later use.

[0048] (5) Add 4 times the volume of ethanol (95% by mass) to the liquid phase and perform alcohol precipitation for 30 minutes. After the precipitation, the solid product is separated by centrifugation and vacuum dried at 50°C for 1 hour to obtain glucosamine hydrochloride product. Example 5

[0049] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0050] (1) Mix tetraethyl titanate and 5% ferric nitrate aqueous solution in a volume ratio of 1:1.5 and stir evenly, then - with Fe 3+ Then, sodium hydroxide solution was added at a molar ratio of 3.1:1 and stirred for 20 minutes to carry out the hydrolysis reaction. After completion, the solid product was separated by centrifugation and vacuum dried at 50°C for 1 hour to obtain modified titanium hydroxide for later use.

[0051] (2) The modified titanium hydroxide and glass powder are mixed uniformly in a mass ratio of 10:1.8 and then wet granulated. The obtained particles with a particle size distribution between 2 and 5 mm are then calcined at 850° C. for 90 min in an air atmosphere. After completion, the mixture is cooled to room temperature to obtain a chloride ion remover for standby use.

[0052] (3) Concentrated hydrochloric acid was added to the fermentation broth to make the initial mass fraction of hydrochloric acid in the fermentation broth 35%, and then heated to 90°C in a water bath for 4 hours to hydrolyze N-acetylglucosamine. After completion, sodium carbonate was added to the obtained hydrolyzate to neutralize the excess hydrochloric acid, and then the obtained hydrolyzate was heated and concentrated to 40% of the initial volume to obtain a concentrated solution.

[0053] (4) The chloride ion remover prepared in this example was added to the concentrated solution at a material-liquid ratio of 11 g / L, stirred evenly, and irradiated with a 60 W xenon lamp for 60 min. After completion, the chloride ion remover was separated by filtration, and the liquid phase was collected for later use.

[0054] (5) Add ethanol (95% by mass) in an amount three times the volume of the liquid phase and perform alcohol precipitation for 40 minutes. After the precipitation, the solid product is separated by centrifugation and vacuum dried at 50°C for 1.5 hours to obtain glucosamine hydrochloride product. Example 6

[0055] A preparation process for a glucosamine hydrochloride product comprises the following steps:

[0056] (1) Concentrated hydrochloric acid was added to the fermentation broth to make the initial mass fraction of hydrochloric acid in the fermentation broth 32%, and then heated to 80°C in a water bath for 5.5 hours to hydrolyze N-acetylglucosamine. After completion, sodium bicarbonate was added to the obtained hydrolyzate to neutralize the excess hydrochloric acid, and then the obtained hydrolyzate was heated and concentrated to 55% of the initial volume to obtain a concentrated solution.

[0057] (2) Add 5 times the volume of ethanol (95% by mass) to the concentrated solution and perform alcohol precipitation for 35 minutes. After the precipitation, the solid product is separated by centrifugation and vacuum dried at 50°C for 1.5 hours to obtain glucosamine hydrochloride product.

[0058] The purity and sodium chloride content of the glucosamine hydrochloride products prepared in Examples 1 to 6 above were tested, and the results are shown in the following table. Compared with Examples 4 to 6, the chloride ion removal agent prepared in Examples 1 to 3 can effectively reduce the chloride ion content in glucosamine hydrochloride and can also be decolorized using visible light, thereby improving the purity of glucosamine hydrochloride.

[0059] Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 purity / % 99.41 99.29 99.56 96.73 97.31 94.62 Sodium chloride content / % 9.26 9.07 9.38 11.52 13.16 16.95

[0060] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A preparation process for a glucosamine hydrochloride product, characterized in that: The steps include: (1) Add tetraethyl titanate to the mixture containing Fe 3+ The aqueous solution of the source is then added with alkali solution and hydrolyzed under stirring; after completion, the solid product is separated and dried to obtain modified titanium hydroxide; in step (1), the aqueous solution of Fe 3+ The concentration of the source is 5-8%; the tetraethyl titanate and the Fe 3+ The volume ratio of the aqueous solution is 1:1.5~2.2; the OH provided by the alkali solution - with Fe 3+ The molar ratio of Fe is 3.1~3.5:1, so that the Fe 3+ All formed precipitates; (2) The modified titanium hydroxide, glass powder and adhesive are mixed and granulated, and then calcined at a high temperature to obtain a chloride ion remover; the ratio of the modified titanium hydroxide, glass powder and adhesive is 10 parts by weight: 1.2-1.8 parts by weight: 2.5-3.5 parts by weight; the adhesive is selected from any one of starch and cyclodextrin; (3) adding concentrated hydrochloric acid to the fermentation broth and hydrolyzing the N-acetylglucosamine under heating conditions, adding a neutralizing agent to the obtained hydrolyzate to neutralize excess hydrochloric acid, and then concentrating the obtained hydrolyzate to form a concentrated solution; (4) adding the chloride ion remover to the concentrated solution, and then irradiating the solution with visible light. After the irradiation is completed, the chloride ion remover is separated, and the liquid phase is collected for standby use; the amount of the chloride ion remover added is 6-11 g / L; (5) adding ethanol to the liquid phase for alcohol precipitation, then separating the solid product and drying it to obtain the glucosamine hydrochloride product.

2. The preparation process of the glucosamine hydrochloride product according to claim 1, wherein: In step (1), the Fe 3+ The source is selected from any one of ferric chloride, ferric sulfate, and ferric nitrate.

3. The preparation process of the glucosamine hydrochloride product according to claim 1, wherein: In step (1), the alkali solution is selected from any one of sodium hydroxide solution and ammonia water.

4. The preparation process of the glucosamine hydrochloride product according to claim 1, wherein: In step (1), the hydrolysis reaction time is 20 to 35 minutes.

5. The preparation process of the glucosamine hydrochloride product according to claim 1, wherein: In step (2), the calcination temperature is 850-1020° C., and the calcination time is 1-1.5 hours.

6. The preparation process of the glucosamine hydrochloride product according to any one of claims 1 to 5, characterized in that: In step (3), the mass fraction of hydrochloric acid in the fermentation broth is 30-35%, the heating temperature is 80-90° C., and the hydrolysis time is 4-5.5 hours.

7. The preparation process of the glucosamine hydrochloride product according to any one of claims 1 to 5, characterized in that: In step (3), the neutralizing agent is selected from any one of sodium hydroxide, sodium carbonate, and sodium bicarbonate.

8. The preparation process of the glucosamine hydrochloride product according to any one of claims 1 to 5, characterized in that: In step (3), the hydrolyzate is heated and concentrated to 40-55% of the initial volume.

9. The preparation process of the glucosamine hydrochloride product according to any one of claims 1 to 5, characterized in that: In step (4), the power of the visible light is 60-100 W, and the irradiation time is 45-60 min.

10. The preparation process of the glucosamine hydrochloride product according to any one of claims 1 to 5, characterized in that: In step (5), the amount of ethanol added is 3 to 5 times the volume of the liquid phase, and the alcohol precipitation time is 30 to 40 minutes.

11. The process for preparing the glucosamine hydrochloride product according to any one of claims 1 to 5, wherein: In step (5), the drying method includes any one of freeze-drying and vacuum drying.