Hyaluronic acid esters, their preparation methods and applications

Abstract

The present application relates to the field of cosmetics, food, medicine and health care products, and particularly relates to hyaluronic acid ester with emulsification function and a preparation method and application thereof. The present application controls the substitution degree to be between 0.05 and 2.8 by connecting fatty acids with a carbon chain length of 4-22 to the main chain of hyaluronic acid in an esterification manner. The obtained hyaluronic acid ester has good hydrophilic and lipophilic properties, can realize the emulsification effect of oil-in-water or water-in-oil, and has the original functions (such as moisturizing, thickening, etc.) of hyaluronic acid while exerting the emulsification function. The hyaluronic acid ester provided by the present application provides a new idea for the development of new cosmetics, and has a wide and practical use in the field of cosmetics.

Description

Technical Field

[0001] This invention relates to the fields of cosmetics, food, medicine and health products, and specifically to hyaluronic acid esters with emulsifying function, their preparation methods and applications. Background Technology

[0002] Hyaluronic acid, also known as hyaluronic acid, is a water-soluble natural polymer widely used in cosmetics. However, there are few reports on esterifying it to unlock its full potential. A more common approach is to acetylate hyaluronic acid or its salts, which further enhances the moisturizing effects of hyaluronic acid.

[0003] Hyaluronic acid, as a natural hydrophilic polymer, has significant potential for modification. However, in current technologies, hyaluronic acid and its salts, as well as acetylated hyaluronic acid and its salts, are typically only used in the cosmetics field for thickening and moisturizing, limiting their applications.

[0004] In view of this, the present invention is hereby proposed. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a hyaluronic acid ester with emulsifying function, its preparation method, and its applications, as detailed below:

[0006] In a first aspect, the present invention provides a hyaluronic acid ester, which is prepared by esterification reaction of hyaluronic acid and / or hyaluronic acid salt with fatty acids, wherein the hydroxyl groups on the hyaluronic acid and / or hyaluronic acid salt undergo a condensation reaction with the fatty acids, the degree of substitution of the fatty acids is 0.05-2.8, and the carbon chain length of the fatty acids is 4-22.

[0007] This invention involves esterifying fatty acids with carbon chain lengths of 4-22 onto the backbone of hyaluronic acid, controlling the degree of substitution between 0.05 and 2.8. The resulting hyaluronic acid ester exhibits excellent hydrophilic and lipophilic properties, enabling water-in-oil or oil-in-water emulsions while retaining the original functionalities of hyaluronic acid (such as moisturizing and thickening). The hyaluronic acid ester provided by this invention offers new insights for the development of novel cosmetics and has broad and practical applications in the cosmetic field.

[0008] In this invention, the fatty acid can be saturated or unsaturated, and can be straight-chain or branched. This invention does not particularly limit the specific source of the fatty acid; fatty acids prepared by conventional methods in the art, or fatty acids obtained through conventional commercial channels in the art, are all acceptable.

[0009] Preferably, the carbon chain length of the fatty acid of the present invention is 8-20, and more preferably, the carbon chain length of the fatty acid is 8-18.

[0010] Preferably, the fatty acids described in this invention do not contain benzene ring structures. The resulting hyaluronic acid esters exhibit higher biocompatibility and are suitable for widespread application in the cosmetics industry.

[0011] In a more specific preferred embodiment of the present invention, the fatty acid is selected from at least one of palmitic acid, isopalmitic acid, lauric acid, isooctanoic acid, stearic acid, isostearic acid, oleic acid, icosanoic acid, and butyric acid.

[0012] In this invention, the relative molecular mass of the hyaluronic acid and / or hyaluronic acid salt is preferably 1,000-2,000,000.

[0013] More preferably, the relative molecular mass of the hyaluronic acid and / or hyaluronic acid salt is 1000, 2000, 5000, 7000, 10000, 20000, 50000, 70000, 100000, 200000, 500000, 700000, 1000000, 2000000, or a value within the range formed by any two of the above values.

[0014] In a more specific preferred embodiment of the present invention, the hyaluronic acid salt may be selected from sodium hyaluronate or potassium hyaluronate.

[0015] The degree of substitution in the esterification reaction of the present invention is 0.05-2.8. Preferably, the degree of substitution in the esterification reaction is 0.05, 0.07, 0.1, 0.2, 0.5, 0.7, 1, 1.5, 2, 2.5, 2.8, or a value within the range formed by any two of the above values. More preferably, the degree of substitution of the fatty acid is 0.1-2.8; more preferably, the degree of substitution is 0.2-2.8. Hyaluronic acid esters within the above preferred degree of substitution range all have relatively good emulsifying ability.

[0016] Secondly, the present invention provides a method for preparing the hyaluronic acid ester, comprising the following steps:

[0017] S1. Disperse hyaluronic acid and / or hyaluronic acid salts in dimethylformamide to obtain a solution or dispersion of hyaluronic acid and / or hyaluronic acid salts;

[0018] S2. Add fatty acids to the solution or dispersion of the hyaluronic acid and / or hyaluronic acid salt, and esterify for 3-10 hours to obtain the hyaluronic acid salt.

[0019] The hyaluronic acid ester described in this invention is prepared by reacting hyaluronic acid and / or hyaluronic acid salts with fatty acids through an esterification reaction.

[0020] Preferably, the hyaluronic acid ester of the present invention is prepared by esterification reaction of hyaluronic acid and / or hyaluronic acid salt with fatty acid acyl chloride, which is more efficient.

[0021] The dispersion concentration of hyaluronic acid and / or hyaluronic acid salt in step S1 is preferably 0.05-1 g / mL, more preferably 0.15-0.60 g / mL, and even more preferably 0.15-0.30 g / mL.

[0022] Preferably, the temperature of the esterification reaction in step S2 is ≤100℃.

[0023] More preferably, after the esterification reaction in step S2 is completed, the process further includes the steps of adding ethanol for precipitation and vacuum filtration and drying.

[0024] Thirdly, the present invention provides the application of the hyaluronic acid ester, or the hyaluronic acid ester prepared by the preparation method, as an emulsifier.

[0025] The hyaluronic acid ester provided by this invention is a modified product of hyaluronic acid. It not only possesses excellent thickening and moisturizing properties but can also be used as an emulsifier in the production of cosmetic products. The hyaluronic acid ester provided by this invention offers new ideas for the development of novel cosmetics and has wide and practical applications in the cosmetic field.

[0026] Beneficial effects:

[0027] This invention provides a hyaluronic acid ester with emulsifying function, its preparation method, and its application. The hyaluronic acid ester is prepared by esterification of hyaluronic acid and / or hyaluronic acid salts with fatty acids, wherein the hydroxyl groups on the hyaluronic acid and / or hyaluronic acid salts condense with the carboxyl groups of the fatty acids, with a degree of substitution of 0.05-2.8; the carbon chain length of the fatty acids is 4-22. This invention controls the degree of substitution between 0.05-2.8 by esterifying fatty acids with a carbon chain length of 4-22 onto the main chain of hyaluronic acid. The obtained hyaluronic acid ester exhibits excellent hydrophilic and lipophilic properties, achieving oil-in-water or water-in-oil emulsification effects, while retaining the original efficacy of hyaluronic acid (such as moisturizing and thickening) while performing its emulsifying function. The hyaluronic acid ester provided by this invention offers new ideas for the development of novel cosmetics and has wide and practical applications in the cosmetic field. Detailed Implementation

[0028] This invention provides a hyaluronic acid ester, which is prepared by esterification reaction of hyaluronic acid and / or hyaluronic acid salt with fatty acids, wherein the hydroxyl groups on the hyaluronic acid and / or hyaluronic acid salt undergo a condensation reaction with the fatty acids, the degree of substitution of the fatty acids is 0.05-2.8, and the carbon chain length of the fatty acids is 4-22.

[0029] The hyaluronic acid ester described in this invention is prepared using sodium hyaluronate as an example:

[0030] Sodium hyaluronate has the molecular formula (C 14 H 21 NO 11 Na) n The repeating unit has a molecular weight of 388, and its general structural formula is shown below:

[0031]

[0032] The molecular formula of hyaluronic acid ester (sodium salt) prepared from sodium hyaluronate is [(C 14 H 21-m NO 11 Na) n R m ] k , where R is an acyl group with a C4-22 straight or branched structure, m = 1-4, n = 1-100; for example, when m = 4 and n = 1, the degree of substitution is 4; when m = 1 and n = 100, the degree of substitution is 0.01.

[0033] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention. Unless otherwise specified, the experimental methods used in the embodiments are all conventional methods; the materials and reagents used are all commercially available.

[0034] Example 1

[0035] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0036] 10 g of sodium hyaluronate (molecular weight less than 5000) was dispersed and dissolved in dimethylformamide (30 mL), 3.5 g of palmitoyl chloride was added, and the mixture was reacted at 40 °C for 3 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 0.5).

[0037] Example 2

[0038] This embodiment provides a hyaluronic acid ester and its preparation method, specifically: 10 g of sodium hyaluronate (molecular weight less than 5000) is dispersed and dissolved in dimethylformamide (25 mL), 1.4 g of isopalmitoyl chloride is added, the reaction is carried out at 30 °C for 4 hours, 100-150 mL of anhydrous ethanol is added to precipitate, and the mixture is dried at 60 °C after vacuum filtration to obtain the hyaluronic acid ester (degree of substitution is about 0.2).

[0039] Example 3

[0040] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0041] 10 g of sodium hyaluronate (molecular weight less than 5000) was dispersed and dissolved in dimethylformamide (30 mL), 5.6 g of isostearyl chloride was added, and the mixture was reacted at 40 °C for 3 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 0.8).

[0042] Example 4

[0043] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0044] 10 g of sodium hyaluronate (molecular weight 5000-10000) was dispersed and dissolved in dimethylformamide (45 mL), 0.56 g of lauroyl chloride was added, and the mixture was reacted at 60 °C for 4 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 0.1).

[0045] Example 5

[0046] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0047] 10 g of sodium hyaluronate (molecular weight 100,000-200,000) was dispersed and dissolved in dimethylformamide (45 mL), and 4.2 g of isooctanoyl chloride (MW163) was added. The mixture was reacted at 90 °C for 8 hours, and 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 1).

[0048] Example 6

[0049] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0050] 10 g of sodium hyaluronate (molecular weight 200,000-400,000) was dispersed and dissolved in dimethylformamide (45 mL), 11.7 g of stearoyl chloride was added, and the mixture was reacted at 90 °C for 10 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 1.5).

[0051] Example 7

[0052] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0053] 10 g of sodium hyaluronate (molecular weight 5000-10000) was dispersed and dissolved in dimethylformamide (45 mL), 15.5 g of oleoyl chloride was added, and the mixture was reacted at 50 °C for 4 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 2).

[0054] Example 8

[0055] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0056] 10 g of sodium hyaluronate (molecular weight less than 5000) was dispersed and dissolved in dimethylformamide (30 mL), 23.1 g of docosanoyl chloride was added, and the mixture was reacted at 30 °C for 3 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 2.5).

[0057] Example 9

[0058] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0059] 10 g of sodium hyaluronate (molecular weight greater than 1,000,000) was dispersed and dissolved in dimethylformamide (45 mL), 7.7 g of butyryl chloride was added, and the mixture was reacted at 90 °C for 9 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 2.8).

[0060] Example 10

[0061] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0062] 10 g of sodium hyaluronate (molecular weight less than 5000) was dispersed and dissolved in dimethylformamide (40 mL), 14 g of stearoyl chloride was added, and the mixture was reacted at 50 °C for 6 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 1.8).

[0063] Example 11

[0064] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0065] 10 g of sodium hyaluronate (molecular weight greater than 1,000,000) was dispersed and dissolved in dimethylformamide (50 mL), 0.28 g of lauroyl chloride was added, and the mixture was reacted at 90 °C for 8 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 0.05).

[0066] Example 12

[0067] This embodiment provides a hyaluronic acid ester and its preparation method, specifically:

[0068] 10 g of sodium hyaluronate (molecular weight 200,000-400,000) was dispersed and dissolved in dimethylformamide (40 mL), 2.3 g of oleoyl chloride was added, and the mixture was reacted at 90 °C for 5 hours. 100-150 mL of anhydrous ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 0.3).

[0069] Comparative Example 1

[0070] This comparative example provides another hyaluronic acid ester and its preparation method, specifically:

[0071] 10 g of sodium hyaluronate (molecular weight less than 5000) was dispersed and dissolved in dimethylformamide (30 mL), 28 g of palmitoyl chloride was added, the reaction was carried out at 40 °C for 3 hours, 100-150 mL of ethanol was added to precipitate, the mixture was filtered under vacuum and dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 4).

[0072] Comparative Example 2

[0073] This comparative example provides another hyaluronic acid ester and its preparation method, specifically:

[0074] 10 g of sodium hyaluronate (molecular weight 5000-10000) was dispersed and dissolved in dimethylformamide (30 mL), 0.07 g of palmitoyl chloride was added, and the mixture was reacted at 40 °C for 3 hours. 100-150 mL of ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 0.01).

[0075] Comparative Example 3

[0076] This comparative example provides another hyaluronic acid ester and its preparation method, specifically:

[0077] 10 g of sodium hyaluronate (molecular weight less than 5000) was dispersed and dissolved in dimethylformamide (30 mL), 27.3 g of palmitoyl chloride was added, and the mixture was reacted at 40 °C for 3 hours. 100-150 mL of ethanol was added to precipitate the hyaluronic acid ester. After vacuum filtration, the ester was dried at 60 °C to obtain hyaluronic acid ester (degree of substitution approximately 3.5).

[0078] Experimental Example 1

[0079] This experiment used the hyaluronic acid ester products provided in Examples 1-12, the products provided in Comparative Examples 1-3, and commercially available sodium hyaluronate (Shandong Freda) and commercially available acetylated sodium hyaluronate (Bloomage Biotech) as experimental reagents to evaluate the emulsifying properties of each group of experimental reagents, as detailed below:

[0080] The emulsifying properties of the above samples were evaluated using standard oil-in-water and water-in-oil formulations. The test formulation consisted of 28 parts caprylic / capric triglyceride, 2 parts emulsifier (the hyaluronic acid ester obtained in the above examples), and 70 parts deionized water. The oil-in-water emulsifying properties were evaluated for hyaluronic acid esters with a degree of substitution ≤1.5, while the water-in-oil emulsifying properties were evaluated for hyaluronic acid esters with a degree of substitution >1.5. The specific procedures are as follows: For the oil-in-water system: Hyaluronic acid esters are added to water and heated to 75°C with stirring until dissolved or completely dispersed. Simultaneously, the oil phase (caprylic / capric triglycerides) is also heated to 75°C. Then, the oil phase is added to the water with stirring, and the mixture is kept at 75°C. Homogenizing is then performed at 3000 rpm for 2 minutes, followed by stirring at 200 rpm and cooling to room temperature. The mixture is allowed to stand for 15 minutes before observing its condition. For the water-in-oil system: Hyaluronic acid esters are added to caprylic / capric triglycerides and heated to 75°C with stirring until dissolved or completely dispersed to form the oil phase. Simultaneously, the aqueous phase is also heated to 75°C. Then, the aqueous phase is slowly added to the oil phase with stirring at 500 rpm, while maintaining the temperature at 75°C. After the aqueous phase is added, stirring is started at 1000 rpm, and stirring is continued for 5 minutes. The mixture is then cooled to room temperature with stirring at 500 rpm and allowed to stand for 15 minutes before observing its condition. The results are summarized in Table 1 below.

[0081] Table 1. Results of the investigation of hyaluronic acid emulsification properties obtained in each example.

[0082]

[0083]

[0084] The embodiments described above are merely illustrative of several implementations of the present invention, designed to facilitate a detailed understanding of the technical solutions of the present invention. However, they should not be construed as limiting the scope of patent protection. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. Hyaluronic acid ester, characterized in that, The hyaluronic acid ester is prepared by esterification reaction of hyaluronic acid and / or hyaluronic acid salt with fatty acid, wherein the hydroxyl group of hyaluronic acid and / or hyaluronic acid salt is condensed with fatty acid, the degree of substitution is 0.8-2.8 based on the maximum degree of substitution of repeatable monomer of hyaluronic acid and / or salt, which is 4; the carbon chain length of the fatty acid is 4-22; The relative molecular mass of the hyaluronic acid and / or hyaluronic acid salt is 1000-1000000; The fatty acid does not contain benzene ring structure; The preparation method of the hyaluronic acid ester comprises the following steps: S1, dispersing hyaluronic acid and / or hyaluronic acid salt in dimethylformamide to obtain hyaluronic acid and / or hyaluronic acid salt dispersion liquid; S2, adding fatty acid into the hyaluronic acid and / or hyaluronic acid salt dispersion liquid, and esterifying for 3-10 hours to obtain the hyaluronic acid ester; After the esterification reaction in step S2, the method further comprises the steps of adding ethanol for precipitation and drying by suction filtration.

2. Hyaluronate according to claim 1, characterized in that, The carbon chain length of the fatty acid is 8-20.

3. The hyaluronate ester according to claim 1 or 2, characterized in that, The fatty acid is linear or branched fatty acid with carbon chain length of 4-12.

4. The hyaluronate of claim 1, wherein The dispersion concentration of the hyaluronic acid and / or hyaluronic acid salt in step S1 is 0.05-1 g / mL.

5. The hyaluronate of claim 4, wherein The dispersion concentration of the hyaluronic acid and / or hyaluronic acid salt in step S1 is 0.15-0.60 g / mL.

6. The hyaluronate of claim 1, wherein The temperature of the esterification reaction in step S2 is ≤100℃.

7. Use of the hyaluronic acid ester in any one of claims 1-6 as emulsifier.

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