Preparation method of solid refined product

Abstract

The invention belongs to the technical field of solid refined product preparation, and particularly relates to a preparation method of a solid refined product. The alcohol buffer solution is added into the filtering cavity in advance, on one hand, full coating of alcohol molecules on the surface of a solid is promoted through the dilution effect of the alcohol buffer solution on a solid-liquid mixture, and the solid forms a loose structure so as to improve the subsequent treatment efficiency; on the other hand, by means of the buffering effect of the alcohol buffer solution, blockage caused by the fact that solid particles are directly attached to the surface of the sintered filter screen can be effectively reduced, and the continuity of the filtering process is guaranteed. Furthermore, by screening the matched alcohol solvent and solid material, the selected alcohol not only can be tightly adsorbed on the solid surface through intermolecular force and replace water molecules on the surface to form a stable coating layer, but also can form an azeotropic mixture with the lowest azeotropic point with water, so that the system can realize high-efficiency removal of the solvent at a lower temperature; and finally, the residual quantity of water and ethanol in the solid refined product is obviously reduced.

Description

Technical Field

[0001] This application belongs to the field of solid refined product preparation technology, specifically relating to a method for preparing solid refined products. Background Technology

[0002] In the preparation of solid purified products, alcohol precipitation is a widely used separation and purification technique. Its core principle is to fully utilize the difference in solubility of the target active ingredient in water and ethanol. Specifically, most target active ingredients have good solubility in water, but their solubility decreases sharply in high-concentration ethanol environments, causing them to precipitate from the solution. Simultaneously, impurities such as proteins, polysaccharides, and inorganic salts in the system tend to denature or precipitate at high ethanol concentrations. However, by rationally controlling the alcohol precipitation conditions, selective precipitation of the target components can be achieved, while some impurities remain in the solution, thus achieving preliminary purification. Typically, when the ethanol content in the system reaches approximately 80%, most water-soluble impurities such as proteins and inorganic salts are almost completely removed, significantly improving the purity of the product. Subsequently, the solid-liquid mixture after alcohol precipitation needs to enter subsequent filtration and drying processes. A fixed filtration, washing, and drying machine is usually used for integrated processing to achieve solid-liquid separation, washing, and final drying, thereby obtaining a high-purity solid purified product.

[0003] Filtration and drying are crucial subsequent steps in the alcohol precipitation process, directly impacting product yield, purity, and production efficiency. In practice, the solid-liquid mixture after alcohol precipitation is typically transferred in batches to a stationary filter washing and drying unit for filtration. After each batch of material is fed, an inert gas (such as nitrogen) is introduced into the system to apply pressure and force the ethanol solvent in the mixture out through filter pressing, achieving initial solid-liquid separation. This process needs to be repeated until all material in the alcohol precipitation tank has been filtered. However, in a high-concentration ethanol environment, some solid components exhibit high viscosity due to enhanced intermolecular forces or weakened solvation effects. This makes them highly susceptible to clogging the sintered metal filter screen at the bottom of the equipment during filtration, obstructing the filtrate passage and severely affecting filtration efficiency. Furthermore, the precipitated material is often sticky and tends to form a dense filter cake layer or gel-like film on the filter plate of the filter press, further hindering the smooth filtration of ethanol. This not only significantly extends filtration time and increases operational intensity but may also lead to product loss due to incomplete filtration, thereby reducing the final yield and increasing production costs.

[0004] To address the aforementioned technical challenges, invention patent application number 201510990561.5 proposes an optimized improvement scheme for the alcohol precipitation process. This method introduces a staged addition of alcohol and supernatant replacement operation on the basis of the traditional alcohol precipitation process: First, an appropriate amount of ethanol is added to the system to initially raise the alcohol concentration to 60%–65%. At this concentration, some impurities have begun to precipitate or deactivate, but the target component has not yet precipitated in large quantities. Subsequently, 1 / 3 to 2 / 3 of the supernatant in the alcohol precipitation tank is discharged, which effectively removes some of the precipitated impurities and residual solvent. Next, a high concentration (95%) of ethanol is added to the remaining material, so that the ethanol content of the final system is precisely controlled within the range of 70%–75%. After thorough stirring and settling, the improved alcohol precipitate is obtained, which is then subjected to subsequent filtration and drying. This process, by adjusting the ethanol concentration in stages and discharging part of the supernatant, effectively reduces the adhesion between precipitated particles, making the precipitated solid particles more uniform and loose, which is beneficial for smooth passage through the filter plate during filtration and avoids filter clogging. Meanwhile, this method also has multiple advantages such as reducing production energy consumption, shortening the drying cycle, reducing ethanol residue in the product, and increasing yield. However, despite the outstanding performance of this technology in improving filtration performance and increasing production efficiency, the applicant found through further experimental research that the ethanol residue in the final product prepared by this method is still relatively high, and cannot fully meet the stringent requirements for solvent residue in some high-purity formulations. Summary of the Invention

[0005] The purpose of this application is to provide a method for preparing solid refined products with low alcohol residue, which is achieved through the following technical solution:

[0006] A method for preparing a solid purified product includes the following steps: adding a solid-liquid mixture to a filter chamber containing an alcohol buffer solution, pressure filtration, and vacuum drying to obtain a solid purified product with less than 0.1% ethanol residue; the solid-liquid mixture includes a solid and an alcohol precipitate; both the alcohol buffer solution and the alcohol precipitate contain alcohol and water, and the alcohol concentration in the alcohol buffer solution is higher than the alcohol concentration in the alcohol precipitate; the alcohol can displace water molecules on the surface of the solid to form an alcohol coating layer on at least a portion of the solid surface; the alcohol and water constitute an azeotropic mixture, and the azeotropic mixture has a minimum azeotropic point.

[0007] The lowest azeotropic point refers to the boiling point of the azeotropic mixture being lower than the boiling point of either the alcohol or the water.

[0008] Preferably, the preparation method further includes the following steps: adding an alcohol buffer solution to the filter chamber, such that the level of the alcohol buffer solution is higher than the upper surface of the sintered filter screen in the filter chamber, and the moisture content of the surface of the sintered filter screen is less than 5%.

[0009] Preferably, the preparation method further includes the following step: before adding alcohol buffer to the filter chamber, the sintered filter screen is rinsed with the alcohol to form an alcohol film on its surface.

[0010] Preferably, the contact angle of the sintered filter screen with water is greater than the contact angle with the alcohol.

[0011] Preferably, the preparation method further includes the following steps: adding a solid-liquid mixture to the filter chamber in batches, and performing a pressure filtration process before adding the next batch of solid-liquid mixture, wherein the pressure filtration process retains 30% of the liquid volume in the filter chamber before pressure filtration as mother liquor, and then adding the next batch of solid-liquid mixture.

[0012] Preferably, the preparation method further includes the following step: the volume ratio of the first batch of the solid-liquid mixture to the volume of the alcohol buffer is 2:1.

[0013] Preferably, the last batch of solid-liquid mixture is filtered without retaining the mother liquor. After all the solid mixture is filtered, the solid is dried. The filtration pressure is 0.1~0.2MPa. The vacuum drying temperature is 30~55℃ and the pressure is -0.09~-0.1MPa.

[0014] Preferably, the alcohol includes at least one of ethanol, methanol, isopropanol, ethylene glycol, or polyethylene glycol.

[0015] Preferably, the solid comprises at least one of sodium hyaluronate, sodium hyaluronate, sodium carboxymethyl cellulose, sodium alginate, chitosan, or xanthan gum.

[0016] Preferably, the alcohol is ethanol, and the solid is sodium hyaluronate; the ethanol residue of the solid refined product is less than 0.05%.

[0017] Compared with the prior art, this application has the following beneficial effects:

[0018] This application pre-adds an alcohol buffer solution to the filtration chamber. On one hand, the alcohol buffer solution dilutes the solid-liquid mixture, promoting full coating of alcohol molecules on the solid surface and creating a loose structure to improve subsequent processing efficiency. On the other hand, the buffering effect of the alcohol buffer solution effectively reduces clogging caused by solid particles directly adhering to the sintered filter screen surface, ensuring the continuity of the filtration process. Furthermore, by screening suitable alcohol solvents and solid materials, the selected alcohols not only tightly adsorb onto the solid surface through intermolecular forces, replacing surface water molecules to form a stable coating layer, but also form an azeotropic mixture with water having the lowest azeotropic point. Therefore, the system can achieve efficient solvent removal at lower temperatures, ultimately significantly reducing the residual water and ethanol content in the purified solid product.

[0019] This application precisely controls the moisture content of the sintered filter screen surface through drying or alcohol washing: drying reduces the proportion of free water on the surface, decreasing water molecule-mediated hydrogen bond adsorption between solid filter screens; alcohol washing, on the other hand, utilizes the affinity between alcohol molecules and the filter screen surface to form a uniform alcohol film, replacing surface water molecules and reducing solid-liquid interfacial tension. Both methods effectively weaken the adhesion between solid particles and the sintered filter screen, preventing the formation of a dense accumulation layer on the filter screen surface due to strong adsorption, making it easier for solid particles to detach from the filter screen surface with the filtrate, thereby reducing filtration resistance, shortening the processing cycle per unit time, and significantly improving the filtration rate and the stability of continuous equipment operation.

[0020] This application achieves a higher contact angle between the filter screen and water than with alcohol by selectively choosing the appropriate material. This characteristic means that the filter screen surface has a significantly better affinity for alcohol than for water. When rinsing with alcohol, alcohol molecules can quickly spread and cover the filter screen surface due to stronger interfacial forces, effectively displacing residual water molecules and forming a continuous and uniform alcohol film on the sintered filter screen surface. This uniform alcohol film not only acts as a physical barrier to reduce direct contact between solid particles and the filter screen surface, lowering the adhesion between them, but also ensures smoother liquid flow on the filter screen surface due to the compatibility of alcohol with subsequent alcohol buffer solutions and alcohol precipitates. This provides a stable interfacial environment for subsequent solid-liquid separation processes, further improving filtration efficiency and the purity and stability of the refined solid product.

[0021] This application introduces a solid-liquid mixture into the filter chamber in batches, retaining a certain volume of mother liquor after each batch of filtration. On one hand, the residual mother liquor buffers the newly added solid-liquid mixture, preventing solid particles from rapidly accumulating and compressing to form a dense filter cake due to concentrated feeding. This keeps the filter cake loose, reducing resistance to liquid flow through the filter cake layer. On the other hand, the alcohol component in the mother liquor interacts fully with the surface of subsequently added solids, maintaining the stability of the alcohol coating layer on the solid surface and further reducing the tendency for particle aggregation. This loose state not only shortens the liquid's permeation path in the filter cake and accelerates the filtrate flow rate but also reduces the risk of clogging on the filter screen, ensuring efficient filtration in each batch. Detailed Implementation

[0022] The present application will now be further described by way of specific embodiments. Those skilled in the art will be able to implement the present application based on these descriptions. Furthermore, the embodiments of the present application described below are generally only a part of the embodiments of the present application, and not all of the embodiments. Therefore, all other embodiments obtained by those skilled in the art based on the embodiments of the present application without inventive effort should fall within the scope of protection of the present application.

[0023] Example 1

[0024] A method for preparing a solid refined product includes the following steps:

[0025] (1) Preparation of sodium hyaluronate aqueous solution

[0026] Raw material dissolution: Add 280 kg of solid-liquid mixture (85% sodium hyaluronate, 14% ethanol, and 1% sodium chloride by mass percentage) transferred from the previous process to 1500 kg of purified water and stir to dissolve. Observe the solution state during stirring. After there are no obvious particulate substances, continue stirring until a completely transparent, homogeneous, and clear solution without suspended impurities is formed.

[0027] (2) Alcohol precipitation reaction

[0028] Solution transfer: The dissolved sodium hyaluronate aqueous solution is filtered and transferred to the alcohol precipitation tank through a sterile pipeline. Before the transfer, it is confirmed that the tank has been autoclaved and cooled to room temperature.

[0029] Ethanol addition: Turn on the stirring device of the alcohol precipitation tank and add 3600L of 95% pharmaceutical ethanol.

[0030] Settling: After turning off the agitator, maintain the temperature of the alcohol precipitation tank at 20~35℃ and allow it to settle. Observe the changes in the solid-liquid interface during the settling process. When the interface becomes clear, the alcohol precipitation operation is complete.

[0031] Washing and dehydration: Discard part of the supernatant, then add pharmaceutical ethanol equal to the weight of the solid-liquid mixture, stir, and allow to settle. Observe the changes in the solid-liquid interface during the settling process. When the interface becomes clear, discharge part of the supernatant again to obtain a solid-liquid mixture of sodium hyaluronate solid particles and ethanol solution. Stir to obtain a uniformly distributed solid-liquid mixture for later use.

[0032] (3) Filtering, washing and drying

[0033] Pretreatment: In the filter chamber of the stationary filter washing and drying machine, add 75L of 95% ethanol as an alcohol buffer, turn on the stirrer and reduce it to the minimum (6mm away from the surface of the sintered mesh), ensuring that the liquid level is 20-30cm above the top surface of the sintered metal filter mesh.

[0034] Batch feeding: The solid-liquid mixture after alcohol precipitation is transferred sequentially to the filtration chamber in batches of 150L under nitrogen pressure. After each batch is fed, the mixture is stirred, and the state inside the chamber is observed using the sight glass of the tank to ensure that the solid particles are uniformly suspended without sedimentation.

[0035] Inert gas pressure filtration: With the agitator on, introduce inert gas (nitrogen or argon) with a purity ≥99.99% into the top of the sealed chamber, slowly pressurize to 0.2 MPa (pressurization rate 0.02 MPa / min), and maintain this pressure for filtration. During the filtration process, visually inspect the filtrate discharge through the pipe sight glass and tank sight glass, retaining approximately 30% of the mother liquor in the system to ensure a loose filter cake structure.

[0036] Circulation operation and final pressure filtration: Repeat the above feeding, stirring, pressure filtration and liquid retention operation until the material in the alcohol precipitation tank is completely processed. For the final pressure filtration, turn off the stirring, raise the stirring to the highest position, increase the pressure to 0.2 MPa + 0.05 MPa, and filter for 30 minutes. When cracks appear on the solid surface, the pressure filtration is complete.

[0037] (4) Vacuum drying and finished product acquisition

[0038] The drying temperature of the fixed filter washing and drying machine was set at 25-55℃, the vacuum degree was maintained at 0.1MPa, and the drying process lasted for 30 hours. The dried solid was then removed, crushed, and sieved to obtain refined sodium hyaluronate, which was then sealed and stored in a dry container.

[0039] Example 2

[0040] Based on Example 1, this embodiment further includes using 95% ethanol to rinse the surface of the sintered metal filter screen at the bottom of the filter chamber before adding ethanol to the filter chamber of the fixed filter washing and drying machine, thereby removing moisture from the surface of the sintered screen and the inside of the mesh.

[0041] Example 3

[0042] In this embodiment, based on Example 1, no mother liquor is retained in each batch of pressure filtration.

[0043] Example 4

[0044] A method for preparing a solid refined product includes the following steps:

[0045] (1) Preparation of sodium hyaluronate aqueous solution

[0046] Raw material dissolution: Add 280 kg of solid-liquid mixture (85% sodium hyaluronate, 14% ethanol, and 1% sodium chloride by mass percentage) transferred from the previous process to 1500 kg of purified water and stir to dissolve. Observe the solution state during stirring. After there are no obvious particulate substances, continue stirring until a completely transparent, homogeneous, and clear solution without suspended impurities is formed.

[0047] (2) Alcohol precipitation reaction

[0048] Solution transfer: The prepared sodium hyaluronate aqueous solution is filtered through a sterile pipeline and transferred to the alcohol precipitation tank. Before the transfer, it is confirmed that the tank has been autoclaved (121℃, 30min) and cooled to room temperature.

[0049] Ethanol addition: Turn on the stirring device of the alcohol precipitation tank and add 3300L of 95% pharmaceutical ethanol.

[0050] Settling: After turning off the agitator, maintain the temperature of the alcohol precipitation tank at 20~45℃ and allow it to settle. Observe the changes in the solid-liquid interface during the settling process. When the interface becomes clear, the alcohol precipitation operation is complete.

[0051] Washing and dehydration: Discard part of the supernatant, then add 1.5 times the weight of the solid-liquid mixture of pharmaceutical-grade ethanol, stir, and allow to settle. Observe the changes in the solid-liquid interface during the settling process. When the interface becomes clear, discharge part of the supernatant again to obtain a solid-liquid mixture of sodium hyaluronate solid particles and ethanol solution. Stir to obtain a uniformly distributed solid-liquid mixture for later use.

[0052] (3) Filtering, washing and drying

[0053] Pretreatment: In the filter chamber of the stationary filter washing and drying machine, add 60L of 95% ethanol as an alcohol buffer, ensuring that the liquid level is 20-30cm above the surface of the sintered metal filter screen.

[0054] Batch feeding: The solid-liquid mixture after alcohol precipitation is packaged into 120L batches and transferred sequentially to the filtration chamber under pressure. After each batch is fed, the stirring device is started and the state inside the chamber is observed using the tank sight glass to ensure that the solid particles are uniformly suspended without sedimentation.

[0055] Inert gas pressure filtration: With the agitator on, introduce inert gas (nitrogen or argon) with a purity ≥99.99% into the top of the sealed chamber, slowly pressurize to 0.2 MPa (pressurization rate 0.02 MPa / min), and maintain this pressure for filtration. During the filtration process, monitor the filtrate discharge using a flow meter, retaining 30% of the mother liquor in the system to ensure a loose, non-thermal structure in the filter cake.

[0056] Circulation operation and final pressure filtration: Repeat the above feeding, stirring, pressure filtration and liquid retention operation until the material in the alcohol precipitation tank is completely processed. For the final pressure filtration, turn off the stirring, raise the stirring to the highest position, increase the pressure to 0.2 MPa + 0.05 MPa, and press for 20 minutes to complete the pressure filtration.

[0057] (4) Vacuum drying and finished product acquisition

[0058] The drying temperature of the fixed filter washing and drying machine is set at 20-55℃, the vacuum degree is maintained at 0.1MPa, and the drying process is carried out for 30 hours. The dried solid is taken out, crushed (particle size controlled at 100-200 mesh), and sieved to obtain refined sodium hyaluronate, which is then sealed and stored in a dry container.

[0059] Example 5

[0060] Based on Example 4, this embodiment further includes using 95% ethanol to rinse the surface of the sintered metal filter screen at the bottom of the filter chamber before adding ethanol to the filter chamber of the fixed filter washing and drying machine, thereby removing moisture from the surface of the sintered screen and the inside of the mesh.

[0061] Example 6

[0062] In this embodiment, based on Example 4, no mother liquor is retained in each batch of pressure filtration.

[0063] Comparative Example 1

[0064] The difference between this comparative example and Example 1 is that the preparation method of the patent cited in the background art is adopted. Specifically, after the alcohol precipitation reaction is completed, 1 / 3 to 2 / 3 of the volume of the supernatant of the solid-liquid mixture is removed; 95% ethanol is added to the remaining material so that the ethanol content of the final system is precisely controlled in the range of 70-75%; and then the obtained material is filtered, washed and dried. The step of adding alcohol buffer solution in the filtration chamber as in Example 1 is no longer included.

[0065] Comparative Example 2

[0066] The difference between this comparative example and Comparative Example 1 is that the supernatant of the solid-liquid mixture is not removed and 95% concentration ethanol of the volume of Example 1 is added directly.

[0067] Comparative Example 3

[0068] The difference between this comparative example and Example 1 is that it does not include a pretreatment process, that is, the alcohol buffer solution is not added to the filter chamber of the stationary filter washing and drying machine, and the solid-liquid mixture is directly added to the filter chamber in batches.

[0069] Performance testing

[0070] This performance test examines the loss on drying and ethanol residue of the solid refined products prepared in the examples and comparative examples. The test method for loss on drying is WS1-(X072)-2011Z, and the test method for ethanol residue is in accordance with the company's internal control inspection standards.

[0071] Test methods for ethanol residue

[0072] Chromatographic conditions: A capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane as the stationary phase was used. A programmed temperature ramp was employed: initial column temperature 40℃, held for 5 min, ramped to 150℃ at a rate of 20℃ / min, held for 3 min, and then ramped to 200℃ at a rate of 30℃ / min, held for 3 min. The injection port temperature was 200℃; a flame ionization detector (FID) was used at 250℃. The headspace vial equilibration temperature was 80℃, and the equilibration time was 30 min. The quantitative loop temperature was 100℃, the transfer line temperature was 110℃, and the split ratio was 30:1.

[0073] Preparation of blank and reference solutions: Accurately transfer 5 ml of 0.1 mol / L sodium hydroxide solution into a headspace vial, seal the vial, and let stand overnight to prepare the blank solution. Accurately weigh 0.1 g of ethanol and place it in a 100 ml volumetric flask containing an appropriate amount of water. Dissolve and dilute to the mark with water. Accurately transfer 5.0 ml of the above solution into a 50 ml volumetric flask, dilute to the mark with 0.1 mol / L sodium hydroxide solution, and mix well. Accurately measure 5 ml of this solution into a 20 ml headspace vial, seal the vial, and prepare reference solution 1. Prepare reference solution 2 by repeating the same procedure with 0.1 g of ethanol.

[0074] Accurately weigh approximately 0.1 g of this product and place it in a 20 ml headspace vial. Accurately add 5 ml of 0.1 mol / L sodium hydroxide solution, seal, and let stand overnight to allow dissolution. Prepare two parallel batches.

[0075] Inject the reference solution and the test solution separately, and calculate the ethanol content based on peak area using the external standard method. Inject the reference solution five times consecutively, record the chromatograms, and the resolution between the ethanol peak and other peaks should be greater than 2.0.

[0076] Calculation formula

[0077]

[0078] A: Peak area of ​​the test sample

[0079] A: Peak area of ​​the reference standard

[0080] m_supply: Sample weight of the test sample

[0081] C represents the concentration of the reference standard.

[0082] Result determination: Ethanol should not exceed 0.5%.

[0083] Table 1 Performance Test Results Group Loss on drying (%) Ethanol residue (%) Example 1 9.0 0.04 Example 2 8.7 0.04 Example 3 10.1 0.07 Example 4 7.79 0.05 Example 5 8.8 0.05 Example 6 11.9 0.09 Comparative Example 1 11.2 0.1 Comparative Example 2 11.5 0.2 Comparative Example 3 12.6 0.4 .

[0084] As can be seen from the table above, compared with the method of increasing the alcohol concentration of the solid mixture in the cited patent (Comparative Example 1) and the method of directly adding alcohol buffer to the solid mixture in Comparative Example 2, Example 1 of this application, by pre-adding alcohol buffer to the filter chamber and adopting the operation of retaining the mother liquor, can effectively reduce the clogging caused by solid particles directly adhering to the surface of the sintered filter screen by means of the buffering effect of alcohol buffer, and ensure the continuity of the filtration process. The performance test results show that the ethanol residue in Example 1 is only 2 / 5 of that in Comparative Example 1 and only 1 / 5 of that in Comparative Example 2, which reflects an unexpected technical effect.

Claims

1. A method for preparing a solid refined product, characterized in that, Includes the following steps: A solid-liquid mixture is added to a filter chamber containing an alcohol buffer solution, and the mixture is pressure filtered and vacuum dried to obtain a solid purified product with less than 0.1% ethanol residue. The solid-liquid mixture includes a solid and an alcohol precipitate. Both the alcohol buffer solution and the alcohol precipitate consist of alcohol and water, and the alcohol concentration in the alcohol buffer solution is higher than the alcohol concentration in the alcohol precipitate. The alcohol can displace water molecules on the surface of the solid to form an alcohol coating layer on at least a portion of the solid surface. The alcohol and water form an azeotropic mixture, and the azeotropic mixture has a minimum azeotropic point.

2. The method for preparing a solid refined product according to claim 1, characterized in that, It also includes the following steps: An alcohol buffer solution is added to the filter chamber so that the level of the alcohol buffer solution is higher than the upper surface of the sintered filter screen in the filter chamber, and the surface moisture content of the sintered filter screen is less than 5%.

3. The method for preparing a solid refined product according to claim 1 or 2, characterized in that, It also includes the following steps: Before adding the alcohol buffer solution into the filter chamber, the sintered filter screen is rinsed with the alcohol to form an alcohol film on its surface.

4. The method for preparing a solid refined product according to claim 3, characterized in that, The sintered filter screen has a larger contact angle with water than with alcohol.

5. The method for preparing a solid refined product according to claim 1, characterized in that, It also includes the following steps: The solid-liquid mixture is added to the filter chamber in batches, and a pressure filtration process is performed before adding the next batch of solid-liquid mixture. The pressure filtration process retains 30% of the liquid volume in the filter chamber before the pressure filtration as mother liquor, and then the next batch of solid-liquid mixture is added.

6. The method for preparing a solid refined product according to claim 5, characterized in that, It also includes the following steps: The first batch of the solid-liquid mixture is added in a volume ratio of 2:1 to the alcohol-buffered solution.

7. The method for preparing a solid refined product according to claim 5, characterized in that, The last batch of solid-liquid mixture is filtered to remove the mother liquor. After all the solid mixture is filtered, the solid is dried. The filtration pressure is 0.1~0.2MPa. The vacuum drying temperature is 30~55℃ and the pressure is -0.09~-0.1MPa.

8. The method for preparing a solid refined product according to claim 1, characterized in that, The alcohol includes at least one of ethanol, methanol, isopropanol, ethylene glycol, or polyethylene glycol.

9. The method for preparing a solid refined product according to claim 1, characterized in that, The solid includes at least one of sodium hyaluronate, sodium hyaluronate, sodium carboxymethyl cellulose, sodium alginate, chitosan, or xanthan gum.

10. The method for preparing a solid refined product according to claim 1, characterized in that, The alcohol is ethanol, and the solid is sodium hyaluronate; the ethanol residue of the solid refined product is less than 0.05%.

Images