A preparation method of acetylated sodium hyaluronate

Abstract

The present invention relates to the field of organic chemical synthesis and provides a method for preparing acetylated sodium hyaluronate, comprising the following steps: first, reacting sodium hyaluronate with acetyl chloride under the catalytic action of a recyclable catalyst; after completion of the reaction, adding the reaction solution to water to precipitate the precipitate; filtering and washing the precipitate to obtain acetylated hyaluronic acid; adding an alkaline solution to adjust the pH of the solution to neutral; filtering the solution, and spray drying the solution to obtain acetylated sodium hyaluronate. The prepared acetylated sodium hyaluronate has the advantages of a simple preparation method, a recyclable catalyst, a high degree of substitution, a high yield, and high safety.

Description

Technical Field

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

[0002] Acetylated sodium hyaluronate is a derivative of sodium hyaluronate produced through an acetylation reaction. Acetylated sodium hyaluronate has some hydrogen atoms on its hydroxyl groups replaced with acetyl groups, enhancing its lipophilicity while retaining its hydrophilicity. In cosmetics, acetylated sodium hyaluronate exhibits excellent moisturizing properties and can repair the skin barrier, improve skin elasticity, and maintain skin smoothness. In the pharmaceutical field, acetylated sodium hyaluronate can be used to prepare drug carriers and injectables. It also has cellular immune activation, bone formation promotion, and drug targeting properties. Therefore, as demand for acetylated sodium hyaluronate increases, its preparation methods are also gaining increasing attention.

[0003] Patent CN113121721B provides a method for preparing acetylated sodium hyaluronate, comprising the following steps: catalyzing a reaction of hyaluronate and acetic anhydride in toluene with a catalyst under inert gas protection, adding a water absorbent during the reaction, and post-treating the reaction solution, separating, purifying, and drying to obtain the product. This invention effectively avoids excessive or insufficient substitution, thereby obtaining a product with an acetyl substitution degree of 2.7-3.2. The method utilizes mild reaction materials and conditions, and simplifies the separation and purification steps. However, toluene is acutely toxic and may pose a health risk to experimenters.

[0004] Patent CN113150184B provides a method for preparing acetylated sodium hyaluronate. The key points of this method are to dissolve sodium hyaluronate in a formamide solvent, then add acetic anhydride along with cyclohexylamine to carry out the acetylation reaction. After the reaction is completed, a 5% sodium bicarbonate solution is added. Finally, the acetylated sodium hyaluronate is washed with water until neutral, and the precipitate is collected and dried to obtain the product. This method avoids the use of organic reagents in the water washing step, protecting the environment while reducing costs and making it suitable for industrial production. However, the water washing method makes it difficult to remove cyclohexylamine, which may remain in the acetylated sodium hyaluronate and affect its safety.

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

[0006] In view of 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, recoverable catalyst, high yield and high degree of substitution.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] The present invention provides a method for preparing 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 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. and the reaction is carried out 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 the filtrate and 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;

[0010] S2. Dissolve the acetylated hyaluronic acid obtained in step S1 with a sodium hydroxide aqueous solution until there is no precipitation, then adjust the pH to alkaline, add a decolorizing agent for decolorization, adjust the pH to neutral after decolorization, filter, and spray-dry the filtrate to obtain acetylated sodium hyaluronate.

[0011] The applicant disclosed a method for preparing acetylated sodium hyaluronate in patent CN110724171A: hyaluronate and acetyl chloride react in an organic solvent under protective gas, the product is separated and purified, and then salted with an alkali to obtain the product. This method does not require corrosive catalysts such as concentrated sulfuric acid or difficult-to-purify pyridine catalysts, resulting in a mild reaction, simple steps, and simple separation and purification steps. However, the lack of a pyridine catalyst in this preparation process results in low catalytic efficiency and a low product yield. To address these shortcomings, the applicant has developed a new method for preparing acetylated sodium hyaluronate after extensive research and experimentation. The method involves first reacting sodium hyaluronate with acetyl chloride in the presence of a recyclable catalyst. After the reaction, the reaction solution is added to water to precipitate the precipitate, which is then filtered and washed to obtain acetylated hyaluronic acid. Alkaline solution is added to adjust the solution pH to neutral, and the solution is filtered and spray-dried to obtain acetylated sodium hyaluronate. The resulting acetylated sodium hyaluronate has the advantages of a simple preparation method, a recyclable catalyst, a high degree of substitution, a high yield, and high safety.

[0012] In some embodiments, the method for preparing the recyclable catalyst comprises the following steps:

[0013] 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;

[0014] A2, 1-formaldehyde piperazine is added to anhydrous ethanol, stirred ultrasonically until clarified, then 8-12wt% sodium hydroxide aqueous solution is added dropwise, 3-acetylpyridine is added after stirring for 5-10min, 25-28wt% ammonia water is added after stirring at room temperature for 4-6h, and stirring is continued for 4-6h, then 70-80 ℃ of heating reflux 9-11h, standing and cooling to room temperature, 60-80 ℃ of rotary evaporation until viscous, with 0-5 ℃ anhydrous ethanol and deionized water each washing 3-5 times, dried and recrystallized from anhydrous ethanol, and dried to obtain a terpyridine compound;

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

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

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

[0018] In the present application, polyethylene glycol oxalate is prepared by reacting polyethylene glycol with oxalic acid, and then reacting the polyethylene glycol oxalate with a terpyridine compound containing a secondary amine group and a tertiary amine group to obtain a catalyst containing a polyethylene glycol segment, a pyridine group, and a tertiary amine group. The catalyst is water-soluble and can be separated in the step of separating acetylated hyaluronic acid with water in step S1, thereby improving the safety of acetylated sodium hyaluronate.

[0019] During the synthesis of the recyclable catalyst, the nitrogen atom in the tertiary amine 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 and accelerating the reaction rate. This is beneficial to improving the production efficiency of the recyclable catalyst and thus reducing the catalyst dosage and reaction temperature, thereby reducing the production cost of the recyclable catalyst.

[0020] During the preparation of acetylated sodium hyaluronate, two tertiary amine groups and three pyridine groups simultaneously play a catalytic role, which can accelerate the reaction rate, reduce the generation of side reactions, and help improve the degree of substitution and yield of acetylated sodium 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 polyethylene glycol to oxalic acid is 1:(0.12-0.2).

[0023] The present application increases the degree of substitution and yield of acetylated sodium hyaluronate by limiting the molecular weight of polyethylene glycol and the ratio of polyethylene glycol to oxalic acid. This may be because the molecular weight and hydroxyl content of the recyclable catalyst affect the reaction rate of sodium hyaluronate and acetyl chloride, thereby affecting the degree of substitution and yield of acetylated sodium 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] The present application improves the yield and degree of substitution of acetylated sodium hyaluronate by limiting the ratio of polyethylene glycol oxalate to the terpyridine compound. This may be because at this ratio, only a small amount of terpyridine compound is grafted onto the recyclable catalyst segment, thereby improving the water solubility of the recyclable catalyst and facilitating the improvement of the dispersibility of the recyclable catalyst. Moreover, each terpyridine compound is only connected to one polyethylene glycol oxalate segment, which can expose the tertiary amino group and pyridine group on the recyclable catalyst, thereby improving the catalytic rate and thereby improving the yield and degree of substitution of acetylated sodium hyaluronate.

[0026] In some embodiments, the mass ratio of 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] The present application limits the ratio of sodium hyaluronate to acetyl chloride and the ratio of sodium hyaluronate to the recyclable catalyst, so that the hydroxyl groups carried on the recyclable catalyst are less likely to rob the acetyl groups in the system, thereby facilitating the improvement of the yield and degree of substitution of acetylated sodium hyaluronate.

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

[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 decolorization temperature in step S2 is 40-50°C, and the spray drying temperature is 70-90°C.

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

[0034] 1. The present invention has developed a method for preparing acetylated sodium hyaluronate. The method comprises reacting sodium hyaluronate with acetyl chloride under the catalytic action of a recyclable catalyst. After the reaction, the reaction solution is added to water to precipitate the precipitate, which is then filtered and washed to obtain acetylated hyaluronic acid. The solution is then adjusted to a neutral pH by adding an alkaline solution, filtered, and spray-dried to obtain acetylated sodium hyaluronate. The resulting acetylated sodium hyaluronate has the advantages of a simple preparation method, a recyclable catalyst, a high degree of substitution, a high yield, and high safety.

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

[0036] 3. The two tertiary amine groups and three pyridine groups contained in the recyclable catalyst prepared by the present invention 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 help improve the degree of substitution and yield of acetylated sodium hyaluronate. DETAILED DESCRIPTION

[0037] The present invention will be described below in conjunction with specific embodiments. It should be noted that the following examples are illustrative of the present invention and are intended only to illustrate the present invention and are not intended to limit the present invention. Other combinations and various modifications within the scope of the present invention may be made without departing from the spirit or scope of the present invention.

[0038] In the following examples, the compounds and related reagents used can be purchased from the market, wherein the number average molecular weight of polyethylene glycol-1 is 400, and the number average molecular weight of polyethylene glycol-2 is 1000, both of which are purchased from Jinan Xinke Chemical Co., Ltd.; the average molecular weight of sodium hyaluronate is 800 KDa; and the 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] The preparation method of the recyclable catalyst-1 comprises 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 to 75°C, and react for 3 h to obtain polyethylene glycol oxalate;

[0042] A2, 10g 1-formaldehyde piperazine is added in absolute ethanol, stirring is ultrasonic to clarification, then in 3min, 25g10wt% aqueous sodium hydroxide solution is dripped, 20g 3-acetylpyridine is added after stirring 7min, and the ammoniacal liquor of 70g26wt% is added after stirring at room temperature for 5h and continues to stir for 5h, then 75 ℃ of reflux 10h, leave standstill and cool to room temperature, 70 ℃ of rotary evaporations are to viscosity, with 3 ℃ absolute ethanol and deionized water respectively washing 4 times, dry back and use absolute ethanol recrystallization, obtain terpyridine compound after the drying;

[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 to 70° C. and stir for 2.5 h to obtain recyclable catalyst-1.

[0044] Preparation Example 2

[0045] The preparation method of recyclable catalyst-2 is the same as that of Preparation Example 1, except that an equal amount of polyethylene glycol-1 is replaced by polyethylene glycol-2.

[0046] Preparation Example 3

[0047] The preparation method of recyclable catalyst-3 is the same as that of Preparation Example 1, except that the amount of oxalic acid added is 2.5 g.

[0048] Preparation Example 4

[0049] The preparation method of recyclable catalyst-4 is the same as that of Preparation Example 1, except that the amount of terpyridine compound added is 12 g.

[0050] Example 1

[0051] A method for preparing acetylated sodium hyaluronate comprises 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, add the solution dropwise to the suspension, add 0.3 g of recyclable catalyst-1, react at 70° C. for 8 h, then cool 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 is precipitated, filter to obtain a filtrate and a precipitate, wash the precipitate, and dry 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 a sodium hydroxide aqueous solution with a pH of 12 until no precipitation occurs, then adjust the pH to 12, add 30 g of a hydrogen peroxide aqueous solution and decolorize at 45° C. After decolorization, adjust the pH to 7, filter, and spray-dry the filtrate at 80° C. to obtain sodium acetylated hyaluronate.

[0054] Example 2

[0055] A method for preparing acetylated sodium hyaluronate comprises 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, add the solution dropwise to the suspension, add 0.1 g of recyclable catalyst-1, react at 60° C. for 9 h, then cool 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 is precipitated, filter to obtain a filtrate and a precipitate, wash the precipitate, and dry to obtain acetylated hyaluronic acid, and dry the filtrate to obtain a recyclable catalyst;

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

[0058] Example 3

[0059] A method for preparing acetylated sodium hyaluronate comprises 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, add the solution dropwise to the suspension, add 0.5 g of recyclable catalyst-1, react at 80° C. for 7 h, then cool 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, filter to obtain a filtrate and a precipitate, wash the precipitate, and dry to obtain acetylated hyaluronic acid, and dry the filtrate to obtain a recyclable catalyst;

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

[0062] Example 4

[0063] A method for preparing acetylated sodium hyaluronate, the specific implementation method is the same as Example 1, except that the amount of acetyl chloride added is 13g.

[0064] Example 5

[0065] A method for preparing acetylated sodium hyaluronate, the specific implementation method is the same as Example 1, except that the added amount of recyclable catalyst-1 is 0.7g.

[0066] Example 6

[0067] A method for preparing acetylated sodium hyaluronate, the specific implementation method is the same as Example 1, except that an equal amount of recyclable catalyst-1 is replaced by recyclable catalyst-2.

[0068] Example 7

[0069] A method for preparing acetylated sodium hyaluronate, the specific implementation method is the same as that of Example 1, except that an equal amount of recyclable catalyst-1 is replaced by recyclable catalyst-3.

[0070] Example 8

[0071] A method for preparing acetylated sodium hyaluronate, the specific implementation method is the same as Example 1, except that an equal amount of recyclable catalyst-1 is replaced by recyclable catalyst-4.

[0072] Comparative Example 1

[0073] A method for preparing acetylated sodium hyaluronate, the specific implementation method is the same as that of Example 1, except that an equal amount of the recyclable catalyst-1 is replaced by 4-dimethylaminopyridine.

[0074] Performance Testing

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

[0076] (1) Degree of substitution: The degree of acetyl substitution of each sample was determined using the hydroxylamine colorimetric method.

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

[0078] μ=401.3*m2 / m1*(401.3﹢(43﹣1)*DS);

[0079] m1 is the mass of sodium hyaluronate fed, m2 is the mass of the acetylated sodium hyaluronate obtained, and DS is the degree of acetyl substitution.

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

[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] As can be seen from the data in Table 1, the acetylated sodium hyaluronate prepared in Examples 1-3 has a high yield and degree of substitution. A comparison of Examples 4 and 5 with Example 1 shows that after changing the ratio of sodium hyaluronate to acetyl chloride or sodium hyaluronate to the recyclable catalyst, the hydroxyl groups carried on the recyclable catalyst are more likely to rob the acetyl groups in the system, thereby reducing the yield and degree of substitution of the acetylated sodium hyaluronate. A comparison of Examples 6 and 7 with Example 1 shows that after changing the number average molecular weight of polyethylene glycol or the ratio of polyethylene glycol to oxalic acid, the yield of the acetylated sodium hyaluronate is improved. The molecular weight and hydroxyl content of the alcohol affect the reaction rate of sodium hyaluronate and acetyl chloride, thereby reducing the degree of substitution and yield of acetylated sodium hyaluronate. A comparison between Example 8 and Example 1 shows that after changing the ratio of polyethylene glycol oxalate to the terpyridine compound, the water solubility of the recyclable catalyst decreases, resulting in a decrease in the reaction rate of sodium hyaluronate and acetyl chloride, and thus a decrease in the degree of substitution and yield of acetylated sodium hyaluronate. A comparison between Comparative Example 1 and Example 1 shows that the degree of substitution and yield of acetylated sodium hyaluronate prepared directly using a conventional catalyst are reduced.

[0084] The above embodiments are only for illustrating the technical concept and features of the present invention. Its purpose is to enable people familiar with this technology to understand the content of the present invention and implement it. It cannot be used to limit the scope of protection of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be covered by the scope of protection 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. and the reaction is carried out 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 the filtrate and 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. Dissolving the acetylated hyaluronic acid obtained in step S1 with an aqueous sodium hydroxide solution until no precipitation occurs, then adjusting the pH to alkaline, adding a decolorizing agent for decolorization, adjusting the pH to neutral after decolorization, filtering, and spray-drying the filtrate to obtain sodium acetylated hyaluronate; 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 is added to anhydrous ethanol, stirred ultrasonically until clarified, then 8-12wt% sodium hydroxide aqueous solution is added dropwise, 3-acetylpyridine is added after stirring for 5-10min, 25-28wt% ammonia water is added after stirring at room temperature for 4-6h, and stirring is continued for 4-6h, then 70-80 ℃ of heating reflux 9-11h, standing and cooling to room temperature, 60-80 ℃ of rotary evaporation until viscous, with 0-5 ℃ anhydrous ethanol and deionized water each washing 3-5 times, dried and recrystallized from 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, raise the temperature to 60-80° C. and stir for 2-3 hours to obtain a recyclable catalyst.

2. The method for preparing acetylated sodium hyaluronate according to claim 1, wherein The number average molecular weight of the polyethylene glycol is 400-600.

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

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

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

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

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

8. The method for preparing acetylated sodium hyaluronate according to claim 1, wherein The decolorizing agent is an aqueous solution of hydrogen peroxide.

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