Preparation method of acetylated sodium hyaluronate

Abstract

The invention relates to the field of organic chemical synthesis, and provides a preparation method of acetylated sodium hyaluronate, which comprises the following steps: reacting sodium hyaluronate with acetyl chloride under the catalytic action of a recoverable catalyst, adding reaction liquid into water to separate out precipitate after the reaction is finished, filtering and washing to obtain acetylated hyaluronic acid, and drying to obtain the acetylated sodium hyaluronate. Adding alkali liquor to adjust the pH value of the solution to be neutral, filtering, and spray-drying to obtain acetylated sodium hyaluronate. The prepared acetylated sodium hyaluronate has the advantages that the preparation method is simple, the catalyst can be recycled, and the acetylated sodium hyaluronate is high in substitution degree, high in yield and high in safety.

Description

Technical Field

[0001] The present invention relates to the field of organic chemical synthesis, and particularly relates to an acetylated sodium hyaluronate, a preparation method thereof, and an application thereof. Background Art

[0002] Acetylated sodium hyaluronate is a derivative generated by the acetylation reaction of sodium hyaluronate. Some of the hydrogen on the hydroxyl group of acetylated sodium hyaluronate is replaced by acetyl groups, enhancing its lipophilicity while retaining its hydrophilicity. In the field of cosmetics, acetylated sodium hyaluronate has excellent moisturizing effects, can also repair the skin barrier, improve skin elasticity, and keep the skin smooth. In the medical field, acetylated sodium hyaluronate can be used to prepare drug carriers, injections, and also has functions such as cellular immune activation, promoting bone formation, and drug targeting. Therefore, with the increasing demand for acetylated sodium hyaluronate, the preparation methods of acetylated sodium hyaluronate have gradually attracted attention.

[0003] Patent CN113121721B provides a preparation method of acetylated sodium hyaluronate, including the following steps: under the protection of an inert gas, reacting a hyaluronate and acetic anhydride in toluene with a catalyst, adding a water absorbent during the reaction, and obtaining the product after the reaction solution is post-treated, separated and purified, and dried; this invention can effectively avoid too high or too low substitution degrees, thereby obtaining a product with an acetyl substitution degree of 2.7 - 3.2, and the reaction raw materials and conditions are mild, and the separation and purification steps are simple. However, toluene has acute toxicity and may endanger the health of experimental personnel.

[0004] Patent CN113150184B provides a method for preparing acetylated sodium hyaluronate. The key point of using this method is to dissolve sodium hyaluronate in a formamide solvent, then add acetic anhydride together with cyclohexylamine for acetylation reaction. After the reaction ends, add a 5% sodium bicarbonate solution, and finally wash the acetylated sodium hyaluronate with water until it is neutral, and then collect the precipitate and dry it to obtain the product. Using this method to prepare sodium hyaluronate avoids the use of organic reagents in the water washing step, reduces costs while protecting the environment, and is suitable for industrial production. However, the water washing method is difficult to remove cyclohexylamine, making it remain in the acetylated sodium hyaluronate and affecting its safety.

[0005] Therefore, there is an urgent need in the market to develop a preparation method of acetylated sodium hyaluronate with good safety. Summary of the Invention

[0006] Aiming at the problems existing in the prior art, the purpose of the present invention is to develop a preparation method of acetylated sodium hyaluronate with good safety, recyclable catalyst, high yield, and high substitution degree.

[0007] In order to achieve the above purpose, the technical solutions adopted by the present invention are as follows:

[0008] The present invention provides a preparation method of acetylated sodium hyaluronate, comprising the following steps:

[0009] S1. Sodium hyaluronate is added to DMF to obtain a suspension. Acetyl chloride is added to DMF and stirred at room temperature for 20 - 30 min to obtain a solution. The solution is added dropwise to the suspension, a recyclable catalyst is added, and the reaction is carried out at 60 - 80 °C for 7 - 9 h, then the temperature is lowered to 25 - 35 °C and the reaction is carried out for 14 - 18 h to obtain a reaction solution. Water is added to the reaction solution until a large amount of precipitate precipitates, and the filtrate and the precipitate are obtained by filtration. The precipitate part is washed and dried to obtain acetylated hyaluronic acid, and the filtrate is dried to obtain the recyclable catalyst;

[0010] S2. The acetylated hyaluronic acid obtained in step S1 is dissolved in an aqueous sodium hydroxide solution until there is just no precipitate, then the pH is adjusted to alkaline, a decolorizing agent is added for decolorization. After the decolorization is completed, the pH is adjusted to neutral. After filtration, the filtrate is spray-dried to obtain acetylated sodium hyaluronate.

[0011] The applicant has disclosed a preparation method of acetylated sodium hyaluronate in Patent CN110724171A: Under a protective gas, a hyaluronate and acetyl chloride react in an organic solvent, and the product is separated and purified and then salted with a base to obtain the product. The preparation method of this invention does not require corrosive substances such as concentrated sulfuric acid or pyridine-based catalysts that are difficult to purify. The reaction is mild, the steps are simple, and the separation and purification steps are simple. However, in this preparation process, due to the lack of pyridine-based catalysts, the catalytic efficiency in the reaction process is low, resulting in a low yield of the product. Based on the above defects, through a large number of research experiments, the present application has developed a new preparation method of acetylated sodium hyaluronate. First, sodium hyaluronate reacts with acetyl chloride under the catalytic action of a recyclable catalyst. After the reaction is completed, the reaction solution is added to water to precipitate a precipitate. After filtration and washing, acetylated hyaluronic acid is obtained. An alkaline solution is added to adjust the pH value of the solution to neutral, and after filtration, it is spray-dried to obtain acetylated sodium hyaluronate. The prepared acetylated sodium hyaluronate has the advantages of simple preparation method, recyclable catalyst, high degree of substitution, high yield, and high safety.

[0012] In some embodiments, the preparation method of the recyclable catalyst comprises the following steps:

[0013] A1. Oxalic acid is added to polyethylene glycol, concentrated sulfuric acid is added, and the temperature is raised to 70 - 80 °C, and the reaction is carried out for 2 - 4 h to obtain polyethylene glycol oxalate;

[0014] A2. Add 1-formylpiperazine to absolute ethanol, stir and sonicate until clear, then dropwise add an aqueous sodium hydroxide solution of 8-12 wt%, stir for 5-10 min, add 3-acetylpyridine, stir at room temperature for 4-6 h, then add 25-28 wt% ammonia water and continue stirring for 4-6 h. Then heat under reflux at 70-80 °C for 9-11 h, let it stand and cool to room temperature, rotary evaporate at 60-80 °C until viscous, wash 3-5 times each with absolute ethanol and deionized water at 0-5 °C, dry and recrystallize with absolute ethanol, and obtain the terpyridine compound after drying.

[0015] A3. Add the terpyridine compound obtained in step A2 and dicyclohexylcarbodiimide to the polyethylene glycol oxalate obtained in step A1, heat to 60-80 °C and stir for 2-3 h to obtain a recyclable catalyst.

[0016] Preferably, the mass ratio of the 1-formylpiperazine to the 3-acetylpyridine is (0.4-0.7):1.

[0017] Preferably, the mass ratio of the terpyridine compound to the dicyclohexylcarbodiimide is 1:(0.004-0.009).

[0018] In this application, polyethylene glycol oxalate is prepared by reacting polyethylene glycol with oxalic acid, and then reacting it with a terpyridine compound containing a secondary amino group and a tertiary amino group to obtain a catalyst containing polyethylene glycol segments, pyridine groups and tertiary amino groups at the same time. It has water solubility and can be separated in the step of separating acetyl hyaluronic acid with water in step S1, thereby improving the safety of sodium acetylated hyaluronate.

[0019] In the synthesis process of the recyclable catalyst, the nitrogen atom in the tertiary amino group on the terpyridine compound contains a lone pair of electrons, which can act as a nucleophile to attack the carbonyl carbon of the carboxyl group to generate an activated intermediate, thereby reducing the activation energy of the reaction, accelerating the reaction rate, being beneficial to improving the production efficiency of the recyclable catalyst, further reducing the dosage of the catalyst and the reaction temperature, and thus reducing the production cost of the recyclable catalyst.

[0020] In the preparation process of sodium acetylated hyaluronate, two tertiary amino groups and three pyridine groups play a catalytic role at the same time, which can accelerate the reaction rate, reduce the generation of side reactions, and be beneficial to improving the substitution degree and yield of sodium acetylated hyaluronate.

[0021] In some embodiments, the number average molecular weight of the polyethylene glycol is 400-600.

[0022] In some embodiments, the mass ratio of the polyethylene glycol to the oxalic acid is 1:(0.12-0.2).

[0023] By limiting the molecular weight of polyethylene glycol and the ratio of polyethylene glycol to oxalic acid, the substitution degree and yield of sodium acetylated hyaluronate can be increased in this application. This may be because the molecular weight and hydroxyl content of the recyclable catalyst affect the reaction rate between sodium hyaluronate and acetyl chloride, thereby affecting the substitution degree and yield of sodium acetylated hyaluronate.

[0024] In some embodiments, the mass ratio of the polyethylene glycol oxalate to the terpyridine compound in step A3 is 1:(0.6 - 1).

[0025] By limiting the ratio of polyethylene glycol oxalate to the terpyridine compound in this application, the yield and substitution degree of sodium acetylated hyaluronate can be improved. This may be because only a small amount of terpyridine compound is grafted onto the recyclable catalyst chain segment under this ratio, which can then improve the water solubility of the recyclable catalyst and is conducive to enhancing the dispersibility of the recyclable catalyst. And each terpyridine compound is only connected to one polyethylene glycol oxalate chain segment, which can expose the tertiary amine group and pyridine group on the recyclable catalyst, facilitating the improvement of the catalytic rate and further enhancing the yield and substitution degree of sodium acetylated hyaluronate.

[0026] In some embodiments, the mass ratio of the sodium hyaluronate to acetyl chloride is 1:(1.6 - 3).

[0027] In some embodiments, the mass ratio of the sodium hyaluronate to the recyclable catalyst is 1:(0.01 - 0.05).

[0028] By limiting the ratio of sodium hyaluronate to acetyl chloride and the ratio of sodium hyaluronate to the recyclable catalyst in this application, the hydroxyl groups carried on the recyclable catalyst are less likely to snatch the acetyl groups in the system, which is conducive to enhancing the yield and substitution degree of sodium acetylated hyaluronate.

[0029] In some embodiments, the average molecular weight of the sodium hyaluronate is 800KDa - 2000KDa.

[0030] In some embodiments, the decolorizing agent is an aqueous hydrogen peroxide solution.

[0031] Preferably, the hydrogen peroxide in the aqueous hydrogen peroxide solution is 0.5 - 1% of the total volume of the aqueous hydrogen peroxide solution.

[0032] In some embodiments, the decolorizing temperature in step S2 is 40 - 50°C, and the temperature for spray drying is 70 - 90°C.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] 1. The present invention develops a preparation method of acetylated sodium hyaluronate. First, sodium hyaluronate reacts with acetyl chloride under the catalysis of a recyclable catalyst. After the reaction, the reaction solution is added to water to precipitate a solid, which is filtered and washed to obtain acetylated hyaluronic acid. Then, an alkaline solution is added to adjust the pH value of the solution to neutral, and after filtration, it is spray-dried to obtain acetylated sodium hyaluronate. The prepared acetylated sodium hyaluronate has the advantages of simple preparation method, recyclable catalyst, high degree of substitution, high yield, and high safety.

[0035] 2. The present invention prepares polyethylene glycol oxalate by reacting polyethylene glycol with oxalic acid, and then reacts it with a terpyridine compound containing secondary and tertiary amine groups to obtain a water-soluble catalyst, which can be separated in the step of separating acetyl hyaluronic acid with water in step S1, thereby improving the safety of acetylated sodium hyaluronate.

[0036] 3. The recyclable catalyst prepared by the present invention contains two tertiary amine groups and three pyridine groups, which can simultaneously play a catalytic role in the preparation process of acetylated sodium hyaluronate, accelerate the reaction rate, reduce the generation of side reactions, and are beneficial to improving the degree of substitution and yield of acetylated sodium hyaluronate. Specific Embodiments

[0037] The following will illustrate the present invention in conjunction with specific implementation examples. It should be noted that the following examples are examples of the present invention, only used to illustrate the present invention, and not to limit the present invention. Without departing from the gist or scope of the present invention, other combinations and various improvements within the concept of the present invention can be made.

[0038] In the following examples, the compounds and related reagents used can be purchased from the market. The number-average molecular weight of polyethylene glycol-1 is 400, the number-average molecular weight of polyethylene glycol-2 is 1000, purchased from Jinan Xinke Chemical Co., Ltd.; the average molecular weight of sodium hyaluronate is 800KDa; hydrogen peroxide in the hydrogen peroxide aqueous solution is 0.7% of the total volume of the hydrogen peroxide aqueous solution.

[0039] Preparation Example 1

[0040] A preparation method of recyclable catalyst-1, comprising the following steps:

[0041] A1. Add 1.6 g of oxalic acid to 10 g of polyethylene glycol-1, add 0.5 g of 89 wt% sulfuric acid, heat up to 75 °C, and react for 3 h to obtain polyethylene glycol oxalate;

[0042] A2. Add 10 g of 1 - formylpiperazine to absolute ethanol, stir and sonicate until clear, then dropwise add 25 g of 10 wt% aqueous sodium hydroxide solution within 3 min. After stirring for 7 min, add 20 g of 3 - acetylpyridine. Stir at room temperature for 5 h, then add 70 g of 26 wt% ammonia water and continue to stir for 5 h. Then heat under reflux at 75 °C for 10 h, let it stand and cool to room temperature. Rotary evaporate at 70 °C until it becomes viscous, wash 4 times each with absolute ethanol and deionized water at 3 °C, dry and recrystallize with absolute ethanol. After drying, a terpyridine compound is obtained;

[0043] A3. Add 8 g of the terpyridine compound obtained in step A2 and 0.05 g of dicyclohexylcarbodiimide to 10 g of the polyethylene glycol oxalate obtained in step A1, heat up to 70 °C and stir for 2.5 h to obtain recyclable catalyst - 1.

[0044] Preparation Example 2

[0045] A preparation method of recyclable catalyst - 2, the specific implementation manner is the same as that of Preparation Example 1, the difference is that polyethylene glycol - 1 is replaced with polyethylene glycol - 2 in equal amount.

[0046] Preparation Example 3

[0047] A preparation method of recyclable catalyst - 3, the specific implementation manner is the same as that of Preparation Example 1, the difference is that the addition amount of oxalic acid is 2.5 g.

[0048] Preparation Example 4

[0049] A preparation method of recyclable catalyst - 4, the specific implementation manner is the same as that of Preparation Example 1, the difference is that the addition amount of the terpyridine compound is 12 g.

[0050] Example 1

[0051] A preparation method of acetylated sodium hyaluronate, comprising the following steps:

[0052] S1. Add 10 g of sodium hyaluronate to 30 g of DMF to obtain a suspension. Add 23 g of acetyl chloride to 50 g of DMF and stir at room temperature for 25 min to obtain a solution. Drop the solution into the suspension, add 0.3 g of recyclable catalyst - 1, react at 70 °C for 8 h, then cool down to 30 °C and react for 16 h to obtain a reaction solution. Add water to the reaction solution until a large amount of precipitate precipitates, filter to obtain a filtrate and a precipitate. Wash and dry the precipitate part to obtain acetylated hyaluronic acid, and dry the filtrate to obtain a recyclable catalyst;

[0053] S2. Dissolve 10 g of the acetylated hyaluronic acid obtained in step S1 in an aqueous sodium hydroxide solution with a pH of 12 until there is just no precipitate, then adjust the pH to 12, add 30 g of an aqueous hydrogen peroxide solution, and perform decolorization at 45°C. After the decolorization is completed, adjust the pH to 7. After filtration, spray-dry the filtrate at 80°C to obtain sodium acetylated hyaluronate.

[0054] Example 2

[0055] A method for preparing sodium acetylated hyaluronate, comprising the following steps:

[0056] S1. Add 10 g of sodium hyaluronate to 30 g of DMF to obtain a suspension. Add 16 g of acetyl chloride to 50 g of DMF and stir at room temperature for 20 min to obtain a solution. Drop the solution into the suspension, add 0.1 g of recyclable catalyst -1, react at 60°C for 9 h, then cool down to 25°C and react for 18 h to obtain a reaction solution. Add water to the reaction solution until a large amount of precipitate precipitates out. Filter to obtain a filtrate and a precipitate. Wash and dry the precipitate to obtain acetylated hyaluronic acid, and dry the filtrate to obtain the recyclable catalyst;

[0057] S2. Dissolve 10 g of the acetylated hyaluronic acid obtained in step S1 in an aqueous sodium hydroxide solution with a pH of 12 until there is just no precipitate, then adjust the pH to 12, add 30 g of an aqueous hydrogen peroxide solution, and perform decolorization at 40°C. After the decolorization is completed, adjust the pH to 7. After filtration, spray-dry the filtrate at 70°C to obtain sodium acetylated hyaluronate.

[0058] Example 3

[0059] A method for preparing sodium acetylated hyaluronate, comprising the following steps:

[0060] S1. Add 10 g of sodium hyaluronate to 30 g of DMF to obtain a suspension. Add 30 g of acetyl chloride to 50 g of DMF and stir at room temperature for 25 min to obtain a solution. Drop the solution into the suspension, add 0.5 g of recyclable catalyst -1, react at 80°C for 7 h, then cool down to 35°C and react for 14 h to obtain a reaction solution. Add water to the reaction solution until a large amount of precipitate precipitates out. Filter to obtain a filtrate and a precipitate. Wash and dry the precipitate to obtain acetylated hyaluronic acid, and dry the filtrate to obtain the recyclable catalyst;

[0061] S2. Dissolve 10 g of the acetylated hyaluronic acid obtained in step S1 in an aqueous sodium hydroxide solution with a pH of 12 until there is just no precipitate, then adjust the pH to 12, add 30 g of an aqueous hydrogen peroxide solution, and perform decolorization at 50°C. After the decolorization is completed, adjust the pH to 7. After filtration, spray-dry the filtrate at 90°C to obtain sodium acetylated hyaluronate.

[0062] Example 4

[0063] A preparation method of sodium acetylated hyaluronate, the specific implementation manner is the same as that of Example 1, the difference is that the addition amount of acetyl chloride is 13 g.

[0064] Example 5

[0065] A preparation method of sodium acetylated hyaluronate, the specific implementation manner is the same as that of Example 1, the difference is that the addition amount of recyclable catalyst-1 is 0.7 g.

[0066] Example 6

[0067] A preparation method of sodium acetylated hyaluronate, the specific implementation manner is the same as that of Example 1, the difference is that recyclable catalyst-1 is replaced with recyclable catalyst-2 in equal amount.

[0068] Example 7

[0069] A preparation method of sodium acetylated hyaluronate, the specific implementation manner is the same as that of Example 1, the difference is that recyclable catalyst-1 is replaced with recyclable catalyst-3 in equal amount.

[0070] Example 8

[0071] A preparation method of sodium acetylated hyaluronate, the specific implementation manner is the same as that of Example 1, the difference is that recyclable catalyst-1 is replaced with recyclable catalyst-4 in equal amount.

[0072] Comparative Example 1

[0073] A preparation method of sodium acetylated hyaluronate, the specific implementation manner is the same as that of Example 1, the difference is that recyclable catalyst-1 is replaced with 4-dimethylaminopyridine in equal amount.

[0074] Performance test

[0075] The following performance tests were carried out on the sodium acetylated hyaluronate obtained in the above examples and comparative examples:

[0076] (1) Degree of substitution: The degree of acetyl substitution of each sample was detected by hydroxylamine colorimetry.

[0077] (2) Yield: The yield was calculated according to the following formula:

[0078] μ = 401.3 * m 2 / m 1 *(401.3﹢(43﹣1)*DS);

[0079] m 1 is the mass of the fed sodium hyaluronate, m 2 is the mass of the obtained sodium acetylated hyaluronate, and DS is the degree of acetyl substitution.

[0080] The test results are shown in Table 1 as follows:

[0081] Table 1

[0082] Group Degree of substitution Yield % Example 1 3.5 65.37 Example 2 3.4 64.57 Example 3 3.4 64.31 Example 4 3.2 62.62 Example 5 3.0 61.28 Example 6 3.1 61.71 Example 7 3.2 62.83 Example 8 2.9 60.35 Comparative Example 1 2.7 58.49

[0083] It can be seen from the data in Table 1 that the sodium acetylated hyaluronate prepared in Examples 1-3 has a high yield and degree of substitution. By comparing Examples 4 and 5 with Example 1, it can be seen that after changing the ratio of sodium hyaluronate to acetyl chloride or the ratio of sodium hyaluronate to the recyclable catalyst, the hydroxyl groups carried on the recyclable catalyst are prone to snatch the acetyl groups in the system, which is conducive to reducing the yield and degree of substitution of sodium acetylated hyaluronate; by comparing Examples 6 and 7 with Example 1, it can be seen that after changing the number average molecular weight of polyethylene glycol or the ratio of polyethylene glycol to oxalic acid, the molecular weight and hydroxyl group content of polyethylene glycol affect the reaction rate of sodium hyaluronate with acetyl chloride, thereby reducing the degree of substitution and yield of sodium acetylated hyaluronate; by comparing Example 8 with Example 1, it can be seen that after changing the ratio of polyethylene glycol oxalate to terpyridine compound, the water solubility of the recyclable catalyst decreases, resulting in a decrease in the reaction rate of sodium hyaluronate with acetyl chloride, and thus reducing the degree of substitution and yield of sodium acetylated hyaluronate; by comparing Comparative Example 1 with Example 1, it can be seen that the degree of substitution and yield of sodium acetylated hyaluronate prepared directly using a conventional catalyst are reduced.

[0084] The above embodiments are only used to illustrate the technical concept and characteristics of the present invention, and the purpose is to enable those who are familiar with this technology to understand the content of the present invention and implement it. However, the protection scope of the present invention cannot be limited by this. Any equivalent changes or modifications made according to the spirit and essence of the present invention should be covered by the protection scope of the present invention.

Claims

1. A method for preparing acetylated sodium hyaluronate, characterized in that: The following steps are involved: S1. Sodium hyaluronate is added to DMF to obtain a suspension, acetyl chloride is added to DMF and stirred at room temperature for 20-30 minutes to obtain a solution, the solution is added dropwise to the suspension, a recyclable catalyst is added, the reaction is carried out at 60-80° C. for 7-9 hours, and then the temperature is lowered to 25-35° C. to react for 14-18 hours to obtain a reaction solution, water is added to the reaction solution until a large amount of precipitate is precipitated, and a filtrate and a precipitate are obtained by filtering, the precipitate is partially washed and dried to obtain acetylated hyaluronic acid, and the filtrate is dried to obtain a recyclable catalyst; S2. Dissolve the acetylated hyaluronic acid obtained in step S1 with an aqueous sodium hydroxide solution until there is no precipitation, then adjust the pH to alkaline, add a decolorizing agent to decolorize, and after the decolorization is completed, adjust the pH to neutral. After filtering, the filtrate is spray-dried to obtain acetylated sodium hyaluronate.

2. The method for preparing acetylated sodium hyaluronate according to claim 1, characterized in that: The method for preparing the recyclable catalyst comprises the following steps: A1. Add oxalic acid to polyethylene glycol, add concentrated sulfuric acid, raise the temperature to 70-80°C, and react for 2-4 hours to obtain polyethylene glycol oxalate; A2, 1-formaldehyde piperazine was added to anhydrous ethanol, stirred and ultrasonicated until clear, then 8-12wt% sodium hydroxide aqueous solution was added dropwise, 3-acetylpyridine was added after stirring for 5-10min, 25-28wt% ammonia water was added after stirring at room temperature for 4-6h, and stirring was continued for 4-6h, then heated to reflux at 70-80°C for 9-11h, cooled to room temperature, evaporated at 60-80°C until viscous, washed with 0-5°C anhydrous ethanol and deionized water for 3-5 times respectively, dried and recrystallized with anhydrous ethanol, and dried to obtain a terpyridine compound; A3. Add the terpyridine compound and dicyclohexylcarbodiimide obtained in step A2 to the polyethylene glycol oxalate obtained in step A1, heat to 60-80° C. and stir for 2-3 h to obtain a recyclable catalyst.

3. The method for preparing acetylated sodium hyaluronate according to claim 2, characterized in that: The number average molecular weight of the polyethylene glycol is 400-600.

4. The method for preparing acetylated sodium hyaluronate according to claim 2, characterized in that: The mass ratio of the polyethylene glycol to oxalic acid is 1:(0.12-0.2).

5. The method for preparing acetylated sodium hyaluronate according to claim 2, characterized in that: The mass ratio of the polyethylene glycol oxalate to the terpyridine compound in step A3 is 1:(0.6-1).

6. The method for preparing acetylated sodium hyaluronate according to claim 1, characterized in that: The mass ratio of the sodium hyaluronate to acetyl chloride is 1:(1.6-3).

7. The method for preparing acetylated sodium hyaluronate according to claim 1, characterized in that: The mass ratio of the sodium hyaluronate to the recyclable catalyst is 1:(0.01-0.05).

8. The method for preparing acetylated sodium hyaluronate according to claim 1, characterized in that: The average molecular weight of the sodium hyaluronate is 800KDa-2000KDa.

9. The method for preparing acetylated sodium hyaluronate according to claim 1, characterized in that: The decolorizing agent is an aqueous solution of hydrogen peroxide.

10. The method for preparing acetylated sodium hyaluronate according to claim 1, characterized in that: The decolorization temperature in step S2 is 40-50°C, and the spray drying temperature is 70-90°C.