Preparation method of glucosamine sulfate double salt
The method of preparing glucosamine sulfate compound salts by chitin in one step solves the existing glucosamine sulfate problems that are easy to absorb moisture and unstable oxidation, and achieves industrial production with simple process and low cost. The quality of the prepared products is controllable and complies with national standards.
Patent Information
- Application Number
- CN202411739069.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-29
- Publication Date
- 2025-03-04
AI Technical Summary
The existing glucosamine sulfates are prone to moisture absorption and unstable oxidation, making it difficult to meet the needs of industrial production.
The method of preparing glucosamine sulfate compound salts is directly prepared by chitin in one step. By mixing hydrolysis of hydrochloric acid and sulfuric acid, and adding carbonate for ion exchange, the glucosamine sulfate compound salts that meet the national standards are directly prepared.
This method is simple in process, has low energy consumption and low cost, and is suitable for industrial production. The prepared glucosamine sulfuric acid compound salt has controllable quality, high yield, and meets national standards.
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Figure CN119552203A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of double salt preparation, and particularly relates to a method for preparing glucosamine sulfate double salt. Background Art
[0002] Glucosamine is a synthetic substance in the human body. It is an important raw material for glycoproteins, glycolipids and other large-scale drugs. It is an important nutrient for the formation of cartilage cells and a natural tissue component of chondroitin, a key to health. It participates in the formation of organs such as tendons, ligaments, skin, bones and heart valves. Studies have shown that glucosamine can help repair and maintain cartilage and stimulate the growth of chondrocytes.
[0003] Glucosamine compounds mainly exist in the form of N-acetylglucosamine. Its hydrochloride and sulfate can significantly relieve the pain caused by arthritis and rheumatism and improve walking conditions. It can prevent, treat and repair connective tissue damage, and has a certain effect on bone and joint inflammation. It also helps to heal acute and chronic wounds. In addition, important components of human joints contain "sulfate", which will be easier to absorb for glucosamine that also contains "sulfate". However, glucosamine sulfate is very easy to absorb moisture, easy to oxidize, and unstable in nature, which is not conducive to practical application.
[0004] Considering that glucosamine sulfate double salt has stable properties and can better meet the actual needs of the market, developing an industrial production method with simple process flow, low cost and energy saving has become a technical problem that technical personnel in this field urgently need to solve. Summary of the invention
[0005] In view of this, the purpose of the present invention is to provide a method for preparing glucosamine sulfate double salt from chitosan in one step, in view of the problems existing in the prior art. The method has a simple process flow, can save energy consumption, reduce costs, and is suitable for the industrial production of glucosamine sulfate double salt.
[0006] In order to achieve the above object, the present invention adopts the following technical solution:
[0007] The invention discloses a method for preparing glucosamine sulfate double salt, which comprises the steps of using hydrochloric acid and sulfuric acid to hydrolyze chitosan, and then adding carbonate to prepare glucosamine sulfate double salt in one step.
[0008] In order to overcome the problems of complicated process, high cost, unstable quality, easy moisture absorption and discoloration of finished products in the prior art, the present invention provides a method for preparing glucosamine sulfate double salt from chitin in one step. The method uses hydrochloric acid and sulfuric acid to mix and hydrolyze chitin, and adds potassium and sodium carbonates. The prepared glucosamine sulfate double salt meets national standards, and the process is simple and easy to operate, the reaction is complete, the yield is high, the cost is low, and it is convenient for industrial production.
[0009] Further, the following steps are included:
[0010] S1. Chitosan pretreatment: First, remove the impurities in the raw material, add 1.5 mol / L hydrochloric acid and soak at room temperature for 12 hours, then use 1 mol / L sodium hydroxide to reflux and boil for 3 hours, dry and crush, pass through a 20-mesh sieve, and set aside;
[0011] S2, adding a mixed acid of hydrochloric acid and sulfuric acid to the chitosan pretreated in step S1, and hydrolyzing for 2 to 6 hours to obtain a mixed solution of D-glucosamine hydrochloride and D-glucosamine sulfate;
[0012] S3. Take the mixed solution obtained in step S2, add an appropriate amount of carbonate, stir until completely dissolved, concentrate by rotary evaporator, let stand at room temperature, filter, and obtain a crude product of glucosamine sulfate double salt.
[0013] S4. Take the crude product and add water in a mass ratio of 1.0:(2.0-5.0), stir until completely dissolved, add activated carbon at 55°C-70°C for decolorization for 0.5h-2h, concentrate the decolorized solution, wash the solid with an organic solvent, and dry to constant weight to obtain the glucosamine sulfate double salt.
[0014] In the present invention, in step S1, hydrochloric acid is used to soak the chitosan raw material at room temperature to remove inorganic salt components, and sodium hydroxide is used to reflux and boil to remove protein.
[0015] It is worth noting that the present invention performs acid-base pretreatment on the chitosan raw material to remove excess inorganic salts and proteins, which has the effect of reducing the generation of by-products in the reaction system and helps to improve product quality.
[0016] Furthermore, in step S2, the molar ratio of chitosan to hydrochloric acid is 1.0:(1.0-3.0), the molar ratio of chitosan to sulfuric acid is 1.0:(0.5-1.5), and the hydrolysis temperature is 80°C-95°C.
[0017] Furthermore, in step S2, the mass concentration of hydrochloric acid is 25% to 37%, and the mass concentration of sulfuric acid is 60% to 98%.
[0018] Furthermore, in step S3, the molar ratio of D-glucosamine to carbonate is 1.0:(0.5-1.2), and the carbonate is one of sodium bicarbonate, sodium carbonate, potassium bicarbonate, and potassium carbonate.
[0019] It is worth noting that the process of directly preparing glucosamine sulfate double salt by ion exchange by adding carbonate to hydrolyzate in the present invention has a faster reaction speed and a more complete reaction than ion exchange resin, and has the characteristics of saving energy consumption, reducing costs and simple process.
[0020] Furthermore, in step S4, the organic solvent is one or more of methanol, ethanol and acetone.
[0021] Furthermore, in step S4, the amount of organic solvent added is 0.2 to 6.0 times the amount of the remaining substance after concentration.
[0022] Compared with the prior art, the method for preparing glucosamine sulfate double salt from chitosan in one step provided by the present invention has the following beneficial effects:
[0023] 1. The present invention uses chitosan as a raw material, and prepares glucosamine sulfate double salt by co-hydrolysis with two acids and ion exchange. Compared with the multi-step preparation method of preparing glucosamine hydrochloride from chitosan and then preparing glucosamine sulfate double salt, the process is reduced, the process is simpler and more direct, the product yield is improved, and the production cost is effectively reduced.
[0024] 2. The present invention adopts a process of directly preparing glucosamine sulfate double salt by ion exchange by adding carbonate to hydrolyzate. Compared with ion exchange resin, the ion exchange reaction speed is faster and the reaction is more complete. It has the characteristics of saving energy consumption, reducing costs and simple process.
[0025] 3. The preparation process of glucosamine sulfate double salt disclosed in the present invention has controllable quality and high yield; the prepared glucosamine content (98% to 102%), specific rotation (+47° to 53°), sulfate content (15.5% to 16.5%), pH value (3.0 to 5.0), impurity limit, etc. all meet national standards. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.
[0028] Figure 1 The HPLC spectrum of D-glucosamine prepared in Example 1 of the present invention.
[0029] Figure 2 The HPLC spectrum of the glucosamine sulfate double salt obtained in Example 1 of the present invention.
[0030] Figure 3 The HPLC spectrum of D-glucosamine prepared in Example 2 of the present invention.
[0031] Figure 4The HPLC spectrum of the glucosamine sulfate double salt obtained in Example 2 of the present invention. DETAILED DESCRIPTION
[0032] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0033] The word "embodiment" used here as an "exemplary" does not necessarily mean that any embodiment described is superior to or better than other embodiments. Unless otherwise specified, the performance index tests in the embodiments of this application are performed using conventional test methods in the art. It should be understood that the terms described in this application are only used to describe specific implementation methods and are not used to limit the content disclosed in this application.
[0034] Unless otherwise specified, the technical and scientific terms used in this document have the same meanings as commonly understood by ordinary technicians in the technical field to which this application belongs; other experimental methods and technical means not specifically specified in this application refer to experimental methods and technical means commonly used by ordinary technicians in this field.
[0035] In order to better illustrate the content of the present application, numerous specific details are provided in the specific examples below. It should be understood by those skilled in the art that the present application can also be implemented without certain specific details. In the embodiments, some methods, means, instruments, equipment, etc. well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present application.
[0036] Under the premise of no conflict, the technical features disclosed in the embodiments of the present application can be combined arbitrarily, and the resulting technical solutions belong to the contents disclosed in the embodiments of the present application.
[0037] The invention discloses a method for preparing glucosamine sulfate double salt, and belongs to the technical field of double salt preparation. The invention uses chitosan as a raw material, hydrolyzes it with two acids, and adopts ion exchange to prepare glucosamine sulfate double salt. Compared with the method of preparing glucosamine hydrochloride from chitosan and then preparing glucosamine sulfate double salt, the one-step method for preparing glucosamine sulfate double salt meets national standards, and the process is simple and easy to operate, the reaction is complete, the yield is high, the cost is low, and it is convenient for industrial production.
[0038] In order to better understand the present invention, the present invention is further specifically described below through the following examples, but it should not be understood as a limitation of the present invention. Some non-essential improvements and adjustments made by technicians in this field based on the above invention content are also considered to fall within the protection scope of the present invention.
[0039] Example 1
[0040] A preparation method of glucosamine sulfate double salt:
[0041] S1. Remove the impurities in the raw materials, add 1.5mol / L hydrochloric acid and soak at room temperature for 12 hours to remove inorganic salt components, then reflux and boil with 1mol / L sodium hydroxide for 3 hours to remove protein. Dry and crush, and pass through a 20-mesh sieve for later use.
[0042] S2. Add 158 g of pretreated chitosan to a 1000 mL beaker, slowly add 100 mL of 31% hydrochloric acid and 107 mL of 60% sulfuric acid, stir evenly at 300 rpm, place in a water bath and slowly heat to 85°C to stir and hydrolyze. D-glucosamine ( Figure 1 ) content no longer increased, and the hydrolysis was stopped after 5 hours of reaction to obtain a mixed solution of D-glucosamine hydrochloride and D-glucosamine sulfate.
[0043] S3. Reduce the stirring speed, add potassium carbonate aqueous solution (dissolve 68 g potassium carbonate in 50 mL water), prevent bubbles from forming during the process, stir for 1 h after complete addition, transfer to a 1000 mL rotary evaporator and concentrate 150 mL of water at 65 ° C using a rotary evaporator, let stand at room temperature for 3 h, filter with a Buchner funnel to obtain 224.82 g of a crude product of glucosamine sulfate double salt.
[0044] S4. Add 224.82 g of crude product, 517 mL of water, and 6.7 g of activated carbon to a 500 mL beaker, stir evenly, place in a water bath at 65 ° C for 1 h, filter out the decolorized solution with a Buchner funnel, transfer the decolorized solution to a 1000 mL rotary evaporator, and concentrate 421 mL of water at 65 ° C with a rotary evaporator, wash with 230 mL of ethanol, filter out the solid with a Buchner funnel, and place the solid in a vacuum drying oven at 55 ° C for 5 h to obtain D-glucosamine sulfate potassium chloride double salt ( Figure 2 )149.04g, yield 94.33%.
[0045] HPLC determination of glucosamine sulfate potassium chloride content is 98.66% (national standard, content: 98.0% ~ 102.0%), sulfate content is 15.61% (national standard, barium sulfate weight method, sulfate: 15.5% ~ 16.5%), specific rotation (solvent, water): +50.2 ° (national standard, specific rotation: +47 ° ~ +53 °), pH = 4.02 (national standard, pH: 3.0 ~ 5.0), which is in line with national standards.
[0046] Example 2
[0047] A preparation method of glucosamine sulfate double salt:
[0048] S1. Remove the impurities in the raw materials, add 1.5mol / L hydrochloric acid and soak at room temperature for 12 hours to remove inorganic salt components, then reflux and boil with 1mol / L sodium hydroxide for 3 hours to remove protein. Dry and crush, and pass through a 20-mesh sieve for later use.
[0049] S2. Add 158 g of chitosan pretreated in step S1 into a 1000 mL beaker, slowly add 100 mL of 31% hydrochloric acid and 107 mL of 60% sulfuric acid, stir evenly at 300 rpm, place in a water bath and slowly heat to 85° C. to stir and hydrolyze. D-glucosamine ( Figure 3 ) content no longer increased, and the hydrolysis stopped after 5 hours to obtain a mixed solution of D-glucosamine hydrochloride and D-glucosamine sulfate.
[0050] S3. Reduce the stirring speed, add potassium bicarbonate aqueous solution (take 99g potassium bicarbonate and dissolve it in 100mL water), prevent bubbles from forming and overflowing during the process, stir for 1h after complete addition, transfer to a 1000mL rotary evaporator and concentrate 200mL of water at 65℃ using a rotary evaporator, let stand at room temperature for 3h, filter with a Buchner funnel, and obtain 229.81g of a crude product of glucosamine sulfate double salt.
[0051] S4. Add 229.81 g of crude product, 529 mL of water, and 6.9 g of activated carbon to a 500 mL beaker, stir evenly, place in a water bath at 65 ° C for 1 hour, filter out the decolorized solution with a Buchner funnel, transfer the decolorized solution to a 1000 mL rotary evaporator, and concentrate 419 mL of water at 65 ° C with a rotary evaporator, wash with 230 mL of ethanol, filter out the solid with a Buchner funnel, and place the solid in a vacuum drying oven at 55 ° C for 5 hours to obtain D-glucosamine sulfate potassium chloride double salt ( Figure 4 )145.02g, yield 91.78%.
[0052] HPLC determination of glucosamine sulfate potassium chloride content is 99.0% (national standard, content: 98.0% ~ 102.0%), sulfate content is 16.44% (national standard, barium sulfate weight method, sulfate: 15.5% ~ 16.5%), specific rotation (solvent, water): +49.6 ° (national standard, specific rotation: +47 ° ~ +53 °), pH = 3.95 (national standard, pH: 3.0 ~ 5.0), which is in line with national standards.
[0053] From Examples 1 to 2 and the attached Figures 1 to 4 It can be seen that the double salt prepared by the preparation method of glucosamine sulfate double salt disclosed in the present invention has controllable quality and high yield.
[0054] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one 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 present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. A method for preparing glucosamine sulfate double salt, characterized in that: The chitosan is hydrolyzed by mixing hydrochloric acid and sulfuric acid, and then carbonate is added to prepare glucosamine sulfate double salt in one step.
2. The one-step preparation method of glucosamine sulfate double salt according to claim 1, characterized in that: The steps include: S1. Chitosan pretreatment: First, remove the impurities in the raw material, add 1.5 mol / L hydrochloric acid and soak at room temperature for 12 hours, then use 1 mol / L sodium hydroxide to reflux and boil for 3 hours, dry and crush, pass through a 20-mesh sieve, and set aside; S2, adding a mixed acid of hydrochloric acid and sulfuric acid to the chitosan pretreated in step S1, and hydrolyzing for 2 to 6 hours to obtain a mixed solution of D-glucosamine hydrochloride and D-glucosamine sulfate; S3. Take the mixed solution obtained in step S2, add an appropriate amount of carbonate, stir until completely dissolved, concentrate by rotary evaporator, let stand at room temperature, filter, and obtain a crude product of glucosamine sulfate double salt. S4. Take the crude product and add water in a mass ratio of 1.0:(2.0-5.0), stir until completely dissolved, add activated carbon at 55°C-70°C for decolorization for 0.5h-2h, concentrate the decolorized solution, wash the solid with an organic solvent, and dry to constant weight to obtain the glucosamine sulfate double salt.
3. The preparation method according to claim 2, characterized in that: In the step S2, the molar ratio of chitosan to hydrochloric acid is 1.0:(1.0-3.0), the molar ratio of chitosan to sulfuric acid is 1.0:(0.5-1.5), and the hydrolysis temperature is 80°C-95°C.
4. The preparation method according to claim 3, characterized in that: In the step S2, the mass concentration of the hydrochloric acid is 25% to 37%, and the mass concentration of the sulfuric acid is 60% to 98%.
5. The preparation method according to claim 2, characterized in that: In the step S3, the molar ratio of D-glucosamine to carbonate is 1.0:(0.5-1.2), and the carbonate is one of sodium bicarbonate, sodium carbonate, potassium bicarbonate, and potassium carbonate.
6. The preparation method according to claim 2, characterized in that: In step S4, the organic solvent is one or more of methanol, ethanol and acetone.
7. The preparation method according to claim 6, characterized in that: In the step S4, the amount of organic solvent added is 0.2 to 6.0 times the amount of the remaining substance after concentration.