Synthesis method and application of acetylated sodium hyaluronate

Abstract

The invention discloses a synthesis method of acetylated sodium hyaluronate. The method comprises one-step esterification and two-step esterification. Wherein in the one-step esterification step, a certain mass of sodium hyaluronate is added into a certain mass of acetic acid, and heat preservation and stirring are performed for a certain time at a certain temperature; after controlling a certain temperature, dropwise adding a certain amount of acetic anhydride, and keeping the temperature for a certain time at a certain temperature to obtain a reaction solution A; then, adding a certain mass of absolute ethyl alcohol into the reaction liquid A to obtain an acetylated hyaluronic acid solid-liquid mixture; and filtering to obtain a white solid, and drying at a certain temperature to obtain the partially esterified acetylated hyaluronic acid. According to the method, the esterification substitution degree is improved through a fractional step method, meanwhile, the use of absolute ethyl alcohol is reduced, the condition of ester group hydrolysis under post-treatment high pH is reduced, and the use of concentrated sulfuric acid or acetyl chloride is reduced, so that the reaction is safe during quenching, and the acetylation degree of acetylated sodium hyaluronate is improved.

Description

Technical Field

[0001] The invention relates to the technical field of sodium hyaluronate synthesis, and in particular to a synthesis method and application of acetylated sodium hyaluronate. Background Art

[0002] Acetylated sodium hyaluronate (AcHA) is obtained by acetylation of the natural moisturizing factor sodium hyaluronate (HA). Due to the introduction of a large number of acetyl groups, the lipophilicity of acetylated hyaluronate is greatly improved, so it is more efficient in moisturizing, repairing the skin barrier and increasing skin elasticity than traditional sodium hyaluronate. It can play a biologically active role in double moisturizing, repairing the keratin barrier, and improving skin elasticity, thereby improving dry and rough skin conditions, making the skin soft and elastic, and then promoting the proliferation of epidermal cells, deeply repairing damaged epidermal cells, enhancing the barrier function of the epidermal stratum corneum, and improving the skin's natural resistance.

[0003] Among them, from the structure of AcHA, there are four hydroxyl hydrogens on each disaccharide unit that can be replaced by acetyl groups, so the degree of substitution for a disaccharide structure ranges from 0 to 4, and the degree of substitution will affect the hydrophilicity and lipophilicity of HA. The purpose of acetylation modification is to improve the lipophilicity while maintaining the hydrophilicity of HA, so the degree of substitution that achieves a balance between the hydrophilicity and lipophilicity of HA is the most suitable.

[0004] Among the preparation methods of acetylated sodium hyaluronate in the prior art, one is to use acetic acid / acetic anhydride as a solvent and to prepare it by catalysis of concentrated sulfuric acid. Using concentrated sulfuric acid as a catalyst is highly dangerous. Another is to use hyaluronate and acetyl chloride to react in N, N-dimethylformamide (DMF), and the product can be separated and purified and then salted with alkali to obtain the acetylated sodium hyaluronate product. This method does not use concentrated sulfuric acid as a catalyst, but acetyl chloride participates in the reaction. Acetyl chloride is highly corrosive and is easy to wear out equipment during process production. And when the pH needs to be adjusted during post-process treatment, the ester group is easily hydrolyzed in an alkaline environment, resulting in a decrease in the degree of acetyl substitution, and peroxide decolorization also brings great risks. Summary of the invention

[0005] The present application provides a synthesis method and application of acetylated sodium hyaluronate, which increases the degree of esterification substitution by a step-by-step method, reduces the use of anhydrous ethanol and the hydrolysis of ester groups under high pH in post-treatment, and reduces the use of concentrated sulfuric acid or acetyl chloride, making the reaction safe during quenching; at the same time, the acetylated sodium hyaluronate provided by the present application has a high degree of acetylation, and can be more efficient in moisturizing than traditional sodium hyaluronate in application, and has better effects in repairing the skin barrier and increasing skin elasticity.

[0006] On the one hand, the present application provides a method for synthesizing acetylated sodium hyaluronate, characterized in that it includes one-step esterification and two-step esterification; the one-step esterification includes the following steps: S1, adding a certain mass of sodium hyaluronate to a certain mass of acetic acid, keeping warm and stirring at a certain temperature for a certain time; and after controlling the temperature to a certain level, dripping a certain amount of acetic anhydride, keeping warm at a certain temperature for a certain time, to obtain a reaction solution A; S2, adding a certain mass of anhydrous ethanol to the reaction solution A to obtain an acetylated hyaluronic acid solid-liquid mixture; and filtering to obtain a white solid, drying at a certain temperature, to obtain a part The partially esterified acetylated hyaluronic acid; the two-step esterification comprises the following steps: S3, adding the partially esterified acetylated hyaluronic acid to a certain mass of a mixed solution of DMF / acetic acid / acetic anhydride, keeping the mixture at a certain temperature for a certain time to obtain a B reaction solution; S4, adjusting the pH of the B reaction solution to a suitable range with a certain proportion of sodium acetate / sodium citrate / sodium oxalate, and then adding the mixture to a mixed solution of anhydrous ethanol / 95% ethanol / isopropanol in proportion to obtain a solid-liquid mixture of acetylated sodium hyaluronate; and filtering to obtain a white solid, which is dried at a certain temperature to obtain acetylated sodium hyaluronate.

[0007] By adopting the above technical scheme, the present application uses acetic acid in the first step to free the hyaluronic acid in sodium hyaluronate under mild conditions to obtain hyaluronic acid with a certain solubility under the conditions of acetic acid and acetic anhydride, and then the mixture is kept warm for esterification. After the reaction is completed, 1-5 times of anhydrous ethanol is used for crystallization to obtain partially esterified acetylated hyaluronic acid. In addition, in the second step, the partially esterified acetylated hyaluronic acid is added to a mixed solvent of DMF and acetic acid / acetic anhydride, and the esterification reaction is further carried out. After the reaction is completed, sodium acetate is used to adjust the pH to about 7, and then 1-5 times of anhydrous ethanol is added for crystallization to obtain acetylated sodium hyaluronate. The step-by-step method reduces the use of anhydrous ethanol and the hydrolysis of ester groups under high pH in the post-treatment while increasing the degree of esterification substitution.

[0008] Preferably, in step S1, the mass fraction ratio of sodium hyaluronate to acetic acid is 1-2:2-10; the mass fraction ratio of sodium hyaluronate to acetic anhydride is 1-2:1-5.

[0009] Preferably, in step S1, sodium hyaluronate is added to acetic acid, and the mixture is kept warm at 10-60°C with stirring for 2-8 hours; after the mixture is cooled to 0-10°C, acetic anhydride is added dropwise, and the mixture is kept warm at 60-80°C for 4-24 hours to obtain reaction solution A.

[0010] Preferably, in the S3 reaction step, in the DMF / acetic acid / acetic anhydride mixed solution, the ratio of DMF:acetic acid:acetic anhydride is 20:1:0.5.

[0011] Preferably, in the S3 reaction step, the acetylated hyaluronic acid is added to a 5-20 times DMF / acetic acid / acetic anhydride mixed solution and kept at 60-80° C. for 24-48 hours.

[0012] Preferably, in the S4 reaction step, the pH of the reaction solution is adjusted to 5.5-7.5 using 5-20% sodium acetate / sodium citrate / sodium oxalate.

[0013] Preferably, in the reaction step S4, the acetylated sodium hyaluronate solid-liquid mixture is filtered to obtain a white solid; and the solid is dried at 60-100° C. to obtain acetylated sodium hyaluronate.

[0014] On the other hand, the present application provides an application of a method for synthesizing acetylated sodium hyaluronate, wherein the acetylated sodium hyaluronate is mainly used in facial masks and essence products.

[0015] Preferably, the acetylated sodium hyaluronate is compounded with an oxygen-containing salt oligomer material through polyvinyl alcohol and sodium alginate, and loaded on a facial mask.

[0016] Preferably, the oxygen-containing salt oligomer material includes one or more of calcium phosphate oligomers and calcium carbonate oligomers.

[0017] One or more technical solutions provided in this application have at least the following technical effects or advantages:

[0018] 1. The present application adopts a two-step method, which can reduce the use of concentrated sulfuric acid or acetyl chloride and is safe during reaction quenching.

[0019] 2. The two-step method of the present application avoids the use of strong alkaline reagents during post-treatment, and sodium acetate is used to adjust the pH to neutral, thereby avoiding the hydrolysis of the ester group and retaining the degree of substitution of the acetyl group to the maximum extent.

[0020] 3. The acetylated sodium hyaluronate provided in the present application has a higher degree of acetylation, so it is suitable for the application of acetylated sodium hyaluronate in facial masks and essence products.

[0021] 4. The present application provides an application of acetylated sodium hyaluronate with a high degree of acetylation on a facial mask to improve the loading effect of acetylated sodium hyaluronate on the facial mask, thereby making it have a higher moisturizing effect than traditional sodium hyaluronate, as well as the ability to repair the skin barrier and increase skin elasticity. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0023] Figure 1 is the infrared spectrum of acetylated sodium hyaluronate in Example 1;

[0024] Figure 2 is the infrared spectrum of acetylated sodium hyaluronate in Example 2;

[0025] Figure 3 The infrared spectrum of acetylated sodium hyaluronate in Example 3

[0026] Figure 4 This is the infrared spectrum of acetylated sodium hyaluronate in Comparative Example 2. DETAILED DESCRIPTION

[0027] The present application provides a method for synthesizing and applying acetylated sodium hyaluronate, which increases the degree of esterification substitution by a step-by-step method, reduces the use of anhydrous ethanol and the hydrolysis of ester groups under high pH in post-treatment, and reduces the use of concentrated sulfuric acid or acetyl chloride, making the reaction safe during quenching. At the same time, the acetylated sodium hyaluronate provided by the present application has a higher degree of acetylation, and can be more efficient in moisturizing, repairing the skin barrier and increasing skin elasticity than traditional sodium hyaluronate in application, and the technical means of the present application can improve the loading capacity of acetylated sodium hyaluronate on facial masks.

[0028] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0029] It should be noted that the terms "first", "second", etc. in the specification and claims of the present application and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present application described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions, for example, a process, method, system, product, or server that includes a series of steps or units is not necessarily limited to those steps or units that are clearly listed, but may include other steps or modules that are not clearly listed or inherent to these processes, methods, products, or devices.

[0030] raw material:

[0031] Sodium Hyaluronate CAS: 9067-32-7 Molecular Weight: 799.638 Purity: 99.5%

[0032] Acetic acid CAS: 367-64-6 Molecular weight: 170.130 Purity: 99.5%

[0033] Acetic anhydride CAS: 108-24-7 Molecular weight: 102.089 Purity: 99.5%

[0034] DMF CAS: 1000612-40-7 Molecular weight: 142.109 Purity: N / A

[0035] Sodium acetate CAS: 6131-90-4 Molecular weight: 136.080 Purity: 99.5%

[0036] Sodium citrate CAS: 68-04-2 Molecular weight: 258.069 Purity: 99.5%

[0037] Sodium Oxalate CAS: 62-76-0 Molecular Weight: 133.999 Purity: 95.0%

[0038] Example

[0039] Example 1

[0040] S1. Add 1 wt% sodium hyaluronate to 2 wt% acetic acid, keep warm at 10°C and stir for 2 hours; cool to 0°C, add 1 wt% acetic anhydride dropwise, and keep warm at 60°C for 4 hours to obtain reaction solution A;

[0041] S2, adding 1 wt% of anhydrous ethanol to the reaction solution A to obtain a solid-liquid mixture of acetylated hyaluronic acid; filtering to obtain a white solid, and drying at 40° C. to obtain dried acetylated hyaluronic acid;

[0042] S3, adding 1 wt % acetylated hyaluronic acid to a 5-fold DMF / acetic acid / acetic anhydride mixed solution (wherein the ratio of DMF:acetic acid:acetic anhydride is 20:1:0.5), and keeping the mixture at 60° C. for 24 hours to obtain a reaction solution B;

[0043] S4. Adjust the pH of reaction solution B to 5.5 with 5% sodium acetate, and then add 2 times anhydrous ethanol to obtain a solid-liquid mixture of acetylated sodium hyaluronate; filter to obtain a white solid, and dry at 60° C. to obtain acetylated sodium hyaluronate.

[0044] Example 2-3

[0045] The difference between Example 2-3 and Example 1 is that in step S1, the mass fraction ratios of sodium hyaluronate, acetic acid and acetic anhydride are different, and the data are sorted into the following table. The data are sorted into the following table.

[0046] Table 1. Composition of raw materials in Examples 1-3

[0047] Sodium hyaluronate / concentration Acetic acid / concentration Acetic anhydride / concentration Example 1 1wt% 2wt% 1wt% Example 2 1wt% 8wt% 1wt% Example 3 1wt% 8wt% 5wt%

[0048] Comparative Example

[0049] Comparative Example 1

[0050] The difference between Comparative Example 1 and Example 1 is that, in the synthesis process of the acetylated sodium hyaluronate product, acetic acid / acetic anhydride is used as a solvent, and then concentrated sulfuric acid is used as a catalytic step to obtain the product.

[0051] Comparative Example 2

[0052] The difference between Comparative Example 2 and Example 2 is that hyaluronate and acetyl chloride are reacted in N,N-dimethylformamide (DMF), and the product is separated and purified and then salted with alkali to prepare acetylated sodium hyaluronate.

[0053] Performance testing

[0054] In order to further study the effects of various components and preparation parameters on acetylated sodium hyaluronate, the present application further carried out the following examples for verification.

[0055] 1. Acetylation substitution degree detection: This application uses liquid chromatography-mass spectrometry (LC-MS) to detect the acetylation site, and the following acetylation substitution degree is obtained by calculation.

[0056] 2. Viscosity test of acetylated sodium hyaluronate: This application is determined according to the general rules in the "Pharmacopoeia of the People's Republic of China" in the YY / T1571-2017 standard, and an Ubbelohde capillary viscometer is used. The temperature field of the automatic viscometer is set to 25.00°C and stabilized, then 12-15 ml of 0.2 mol / L sodium chloride is added, and then the sodium hyaluronate solution samples in the examples and comparative examples are added, and the specific formula in the software is started to calculate the viscosity.

[0057] 3. Yield calculation: The yield in this application is based on the amount of target product (acetylated sodium hyaluronate) produced / theoretical amount of target product produced × 100% = amount of raw materials used to produce the target product / amount of raw materials fed × 100%, and is calculated to obtain the following table.

[0058] Table 2, Performance test table of Examples 1-3 and Comparative Examples 1-2

[0059] Test batch <![CDATA[Degree of acetylation / ω DS > Intrinsic viscosity dl / g Yield % Example 1 2.6 0.78 90 Example 2 2.8 0.81 89 Example 3 2.8 0.90 92 Comparative Example 1 2.7 0.72 84 Comparative Example 2 2.1 0.55 88

[0060] According to the data analysis of Example 1 and Comparative Example 1, the two-step method of the present application is compared with the method of using acetic acid / acetic anhydride as solvent and concentrated sulfuric acid as one-step catalysis in Comparative Example 1. The difference in the acetylation substitution degree between the two is not large, so the difference in the value of the intrinsic viscosity is not large, but the yield is not as good as that of Example 1. This is because the use of concentrated sulfuric acid or acetyl chloride is reduced, which can avoid reaction quenching and reduce the yield of acetylated sodium hyaluronate during the operation.

[0061] In addition, the analysis between Example 1 and Comparative Example 2 shows that the two-step method of the present application avoids the use of strong alkaline reagents during post-treatment, can avoid the hydrolysis of the ester group, and retains the degree of substitution of the acetyl group to the maximum extent. Therefore, the degree of substitution of Example 1 is greater than that of Comparative Example 2, and the value of its intrinsic viscosity is also greater than that of Comparative Example 2. At the same time, in the comparison of the yields of the two, the two-step method can make the reaction more complete, so the yield can be improved.

[0062] In addition, refer to Figures 1 to 4 , the present application performs infrared spectroscopy analysis on Examples 1-3 and Comparative Example 2. Among them, Figure 1-3 is the infrared spectrum of acetylated sodium hyaluronate in Example 1-3; Figure 4It is the infrared spectrum of acetylated sodium hyaluronate in Comparative Example 2. It can be seen from the infrared spectrum of sodium hyaluronate that there is a strong absorption near 3400 wavenumbers, which is the hydroxyl absorption peak; the acetylated sodium hyaluronate obtained in Examples 1-3 has only weak or almost no absorption at this wavenumber, which indicates that there is almost no hydroxyl group; while Comparative Example 2 still has absorption at this wave peak, and its acetylation substitution is slightly lower than that in Example 1. In addition, the infrared spectra of the acetylated sodium hyaluronate in Example 1 and Comparative Example 2 have a strong absorption peak near 1740 wavenumbers, which is the carbonyl absorption peak of the acetyl group. Through the analysis between Example 1 and Comparative Example 2, it can be obtained that the synthesis method of Example 1 of the present application can improve the acetylation degree of acetylated sodium hyaluronate.

[0063] In addition, according to the analysis between Example 1 and Example 3, it can be obtained through the performance test data analysis that Example 3 is the optimal example, wherein the acetylation substitution degree of Example 3 is greater than that of Example 1-2, and at the same time, its intrinsic viscosity and yield are also greater than those of Example 1-2.

[0064] Embodiment 4-6

[0065] The difference between Example 4-6 and Example 3 is that in step S1, during the preparation of reaction solution A, the temperature and time of adding sodium hyaluronate to acetic acid are different; and the temperature and time of the reaction after adding acetic anhydride are different, and the data are organized into the following table.

[0066] Table 3. Reaction conditions in Examples 3-6

[0067]

[0068] Performance testing

[0069] In order to further study the effects of various components and preparation parameters on acetylated sodium hyaluronate, the present application further carried out the same example verification as above.

[0070] Table 4. Performance test table of Examples 3-6

[0071] Test batch <![CDATA[Degree of acetylation / ω DS > Intrinsic viscosity dl / g Yield % Example 3 2.8 0.90 92 Example 4 2.7 0.85 90 Example 5 2.9 0.91 93 Example 6 2.7 0.90 91

[0072] According to the data analysis of Examples 3-6, the reaction temperature and reaction time of S1 in the one-step esterification reaction process will affect the acetylation substitution degree and yield of acetylated sodium hyaluronate. The present application has obtained through experiments that Example 5 is the optimal embodiment, wherein the reaction conditions in step S1 are to react sodium hyaluronate and acetic acid at a temperature of 60°C for 2 hours, and after cooling it to 0°C, acetic anhydride is added dropwise, and then kept at 60°C for 12 hours.

[0073] Embodiment 7-8

[0074] The difference between Example 7-8 and Example 5 is that in the two-step esterification process of S3, the ratio of acetylated hyaluronic acid to the mixed solution (DMF / acetic acid / acetic anhydride) is different.

[0075] Examples 9-10

[0076] The difference between Examples 9-10 and Example 5 is that in the two-step esterification process of S3, the reaction temperature and reaction time of the acetylated hyaluronic acid and the mixed solution (DMF / acetic acid / acetic anhydride) are different.

[0077] Table 5. Table of reactants and reaction conditions in Examples 5 and 7-10

[0078]

[0079] Performance testing

[0080] In order to further study the effects of various components and preparation parameters on acetylated sodium hyaluronate, the present application further carried out the same example verification as above.

[0081] Table 6, Performance test table of Examples 5 and 7-10

[0082] Test batch <![CDATA[Degree of acetylation / ω DS > Intrinsic viscosity dl / g Yield % Example 5 2.9 0.91 93 Example 7 2.9 0.92 94 Example 8 2.8 0.91 93 Example 9 2.7 0.90 92 Example 10 2.7 0.89 93

[0083] According to the data analysis of Example 5 and Examples 7-10, when the ratio of acetylated hyaluronic acid to the mixed solution (DMF / acetic acid / acetic anhydride) is 1:10, it has a higher degree of acetylation substitution and yield. And the mixed solution satisfies the ratio of DMF: acetic acid: acetic anhydride of 20:1:0.5. In addition, by analyzing Implementation 9-10 and Example 5, during the two-step esterification reaction, as the reaction temperature and reaction time advance, by-products will be produced, which will reduce the degree of acetylation and the yield will also decrease accordingly.

[0084] In summary, among embodiments 1-10, embodiment 7 is the best embodiment.

[0085] The present application also provides an application of acetylated sodium hyaluronate. The acetylated sodium hyaluronate in the present application is suitable for use in facial masks and essence products. Since the acetylated sodium hyaluronate in the present application has a higher degree of acetylation, it can be used more efficiently than traditional sodium hyaluronate in terms of moisturizing, repairing the skin barrier and increasing skin elasticity.

[0086] And due to its high degree of acetylation, it can be compounded with inorganic oxygen-containing salt oligomer materials. The inorganic oxygen-containing salt oligomer materials in the present application include one or more of calcium phosphate oligomers and calcium carbonate oligomers. Specifically, the present application compounds calcium phosphate oligomers with acetylated sodium hyaluronate through polyvinyl alcohol and sodium alginate to form an organic-inorganic hybrid material with a continuous structure and high mechanical properties.

[0087] Due to the small size of oligomers (about 1nm) and high specific surface area, the contact area between inorganic units and organic matrices can be increased; and due to the high degree of acetylation on acetylated sodium hyaluronate, the defects of the organic-inorganic composite interface are reduced, which can improve the loading effect of the essence on the mask. More acetylated sodium hyaluronate per unit area of ​​the mask can help to exert biologically active functions such as moisturizing effect, repairing keratin barrier, and improving skin elasticity; thereby improving dry and rough skin, making the skin soft and elastic, and then promoting epidermal cell proliferation, deeply repairing damaged epidermal cells, enhancing the barrier function of the epidermal stratum corneum, and improving the skin's natural resistance.

[0088] It should be noted that the above-mentioned sequence of the embodiments of the present application is only for description and does not represent the advantages and disadvantages of the embodiments. And the above-mentioned specific embodiments of this specification are described. Other embodiments are within the scope of the attached claims. In some cases, the actions or steps recorded in the claims can be performed in an order different from that in the embodiments and still achieve the desired results. In addition, the processes depicted in the drawings do not necessarily require the specific order or continuous order shown to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0089] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.

[0090] This specification and drawings are merely exemplary illustrations of the present application and are deemed to cover any and all modifications, variations, combinations or equivalents within the scope of the present application. Obviously, a person skilled in the art may make various modifications and variations to the present application without departing from the scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the present application and its equivalents, the present application intends to include these modifications and variations.

Claims

1. A method for synthesizing acetylated sodium hyaluronate, characterized in that: Including one-step esterification and two-step esterification; The one-step esterification comprises the following steps: S1. Add a certain mass of sodium hyaluronate to a certain mass of acetic acid, keep warm and stir at a certain temperature for a certain time; and after controlling the temperature to a certain value, dropwise add a certain amount of acetic anhydride, keep warm at a certain temperature for a certain time, to obtain a reaction solution A; S2, adding a certain amount of anhydrous ethanol to the reaction solution A to obtain a solid-liquid mixture of acetylated hyaluronic acid; filtering to obtain a white solid, and drying at a certain temperature to obtain partially esterified acetylated hyaluronic acid; The two-step esterification comprises the following steps: S3, adding the partially esterified acetylated hyaluronic acid to a certain mass of a mixed solution of DMF / acetic acid / acetic anhydride, keeping the mixture at a certain temperature for a certain time, and obtaining a reaction solution B; S4. After adjusting the pH of reaction solution B to an appropriate range with a certain proportion of sodium acetate / sodium citrate / sodium oxalate, add it to a mixed solution of anhydrous ethanol / 95% ethanol / isopropanol in proportion to obtain a solid-liquid mixture of acetylated sodium hyaluronate; and obtain a white solid by filtering, and dry it at a certain temperature to obtain acetylated sodium hyaluronate.

2. The method for synthesizing acetylated sodium hyaluronate according to claim 1, characterized in that: In step S1, the mass fraction ratio of sodium hyaluronate to acetic acid is 1-2:2-10; the mass fraction ratio of sodium hyaluronate to acetic anhydride is 1-2:1-5.

3. The method for synthesizing acetylated sodium hyaluronate according to claim 2, characterized in that: In step S1, sodium hyaluronate is added to acetic acid, and the mixture is kept warm at 10-60°C with stirring for 2-8 hours. After the mixture is cooled to 0-10°C, acetic anhydride is added dropwise, and the mixture is kept warm at 60-80°C for another 4-24 hours to obtain reaction solution A.

4. The method for synthesizing acetylated sodium hyaluronate according to claim 1, characterized in that: In the S3 reaction step, in the DMF / acetic acid / acetic anhydride mixed solution, the ratio of DMF:acetic acid:acetic anhydride is 20:1:0.

5.

5. The method for synthesizing acetylated sodium hyaluronate according to claim 4, characterized in that: In the S3 reaction step, the acetylated hyaluronic acid is added to a 5-20 times DMF / acetic acid / acetic anhydride mixed solution and kept at 60-80° C. for 24-48 hours.

6. The method for synthesizing acetylated sodium hyaluronate according to claim 1, characterized in that: In the S4 reaction step, the pH of the reaction solution is adjusted to 5.5-7.5 using 5-20% sodium acetate / sodium citrate / sodium oxalate.

7. The method for synthesizing acetylated sodium hyaluronate according to claim 6, characterized in that: In the S4 reaction step, the solid-liquid mixture of acetylated sodium hyaluronate is filtered to obtain a white solid; and the solid is dried at 60-100° C. to obtain acetylated sodium hyaluronate.

8. A use of acetylated sodium hyaluronate as claimed in claims 1 to 7, characterized in that: Application of acetylated sodium hyaluronate in facial masks and essence products.

9. The use of acetylated sodium hyaluronate as claimed in claim 8, characterized in that: The acetylated sodium hyaluronate is compounded with the oxygen-containing salt oligomer material through polyvinyl alcohol and sodium alginate, and loaded on the facial mask.

10. The use of acetylated sodium hyaluronate as claimed in claim 9, characterized in that: The oxygen-containing salt oligomer material includes one or more of calcium phosphate oligomers and calcium carbonate oligomers.

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