Cationized hyaluronic acid or salt thereof, and preparation method therefor and use thereof

Abstract

The present application relates to the field of the synthesis of raw materials for daily-use products, and provides cationized hyaluronic acid or a salt thereof, and a preparation method therefor and the use thereof. The cationized hyaluronic acid or a salt thereof provided by the present application has a structural formula represented by formula (I); and in the structure of the aforementioned cationized hyaluronic acid or a salt thereof, at least one hydroxyl group and at least one carboxyl group are simultaneously cationized. The cationized hyaluronic acid not only maintains the high moisture-retention property of hyaluronic acid itself, but also achieves a specific adsorption property to hair provided by the cationic side chains, thus providing the product with a good hydrophilicity and affinity. When used in hair care products and cosmetics, it can be directly adsorbed onto the hair surface to maintain a moisturized and smooth condition, is not prone to running off, and exhibits good moisturizing effects.

Description

A cationized hyaluronic acid or its salt thereof, its preparation method and application

[0001] This application claims priority to Chinese Patent Application No. 202510359499.3, filed on March 25, 2025, entitled “A cationic hyaluronic acid or a salt thereof and its preparation method and application”, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This application relates to the field of raw material synthesis for daily necessities, and in particular to a cationic hyaluronic acid or its salt, its preparation method, and its application. Background Technology

[0003] Hyaluronic acid (HA) is a water-soluble linear polysaccharide composed of alternating β-D(1→3)glucuronic acid and β-D(1→4)N-acetyl-β-D-glucosamine units. It is a widely distributed polysaccharide in the human body and a biodegradable and biocompatible carbohydrate polymer. Hyaluronic acid has excellent moisturizing properties, capable of carrying more than 500 times its own weight in water. It is currently recognized as the best natural moisturizing factor and is widely used in cosmetics and other fields.

[0004] However, hyaluronic acid (HA) is a polyanionic polysaccharide. When applied to the negatively charged keratin surface of hair, its adsorption is hindered due to charge repulsion, thus preventing natural hyaluronic acid from achieving its ideal moisturizing effect. By modifying hyaluronic acid chemically to make it positively charged, the mutual attraction between positive and negative charges allows the modified hyaluronic acid to be effectively adsorbed onto the hair surface, thereby achieving a good moisturizing effect.

[0005] Currently, cationic hyaluronic acid is mainly prepared by modifying only the hydroxyl or carboxyl sites of hyaluronic acid. For example, patent CN202111674528.3 describes a method that only substitutes the carboxyl site, reducing the negative charge on the carboxyl group of the hyaluronic acid itself and decreasing aggregation caused by the attraction of positive and negative charges after cationization. However, its degree of cationization is relatively low. Existing technologies modifying the hydroxyl site of hyaluronic acid include patents WO 2023 / 285663A1, CN200680044541.8, CN202211446277.8, CN202211628673.2, and CN202010446769.1. However, cationic hyaluronic acid with substitution at both the hydroxyl and carboxyl sites is rarely reported. Given that current cationic hyaluronic acid primarily modifies the hydroxyl site, its adsorption and moisturizing properties still need improvement. Summary of the Invention

[0006] The purpose of this application is to address the shortcomings of the prior art by providing a cationic hyaluronic acid or its salt with dual substitution of hydroxyl and carboxyl sites, as well as its preparation method and application.

[0007] To achieve the above objectives, the technical solution adopted in this application is as follows:

[0008] On the one hand, a cationic hyaluronic acid or its salt is provided, characterized in that the structural formula of the cationic hyaluronic acid or its salt is shown in the following formula (I);

[0009] In equation (I), A1 is independently H or

[0010] A2 can be independently a metal ion, H, or

[0011] n represents a positive integer representing the degree of aggregation;

[0012] m is 1 to 5;

[0013] In the structure of the above-mentioned cationic hyaluronic acid or its salt, at least one hydroxyl group and at least one carboxyl group are simultaneously cationic.

[0014] Furthermore, R1, R2, and R3 in A1 and A2 are each independently an alkyl group; preferably, R1, R2, and R3 are each independently an alkyl group having 1 to 12 carbon atoms; more preferably;

[0015] R1 is -CH3, -CH2CH3, or

[0016] R2 is -CH3, -CH2CH3, or

[0017] R3 is -CH3, -CH2CH3, or

[0018] X represents a halogen atom; preferably, X is chlorine, bromine or iodine.

[0019] Further, the degree of polymerization n = 10 to 2500, for example, can be 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 11 The values ​​are 00, 1150, 1200, 1250, 1300, 1350, 1400, 1450, 1500, 1550, 1600, 1650, 1700, 1750, 1800, 1850, 1900, 1950, 2000, 2100, 2150, 2200, 2250, 2300, 2350, 2400, 2450, 2500, or any range between them, preferably 20 to 1500.

[0020] Further, the total degree of cationization of the cationic hyaluronic acid or its salt is 0.1 to 4.5, for example, it can be 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, 1.08, The values ​​are 1.09, 1.1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, or any range thereof, preferably 1.0 to 3.3.

[0021] Furthermore, the total cationization degree of the cationic hyaluronic acid or its salt includes the etherification cationization degree and the esterification cationization degree; wherein,

[0022] The degree of etherification is 0.09 to 4.1, for example, it can be any range from 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, or 0.98 to 3.0;

[0023] The degree of esterification cationicity is 0.01 to 0.4, for example, it can be 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 or any range thereof, preferably 0.02 to 0.3.

[0024] On the other hand, a method for preparing the above-mentioned cationic hyaluronic acid or its salt is provided, comprising the following steps:

[0025] (1) Dissolve hyaluronic acid or its salt in an alkaline aqueous solution, alkalize it, add a cationizing reagent to carry out an etherification reaction, and obtain solution I;

[0026] (2) Directly add acid to adjust the pH of reaction solution I to 3-5, or first add acid to adjust the pH of reaction solution I to 6-7 and then add acidic buffer reagent to 3-5 to obtain solution II;

[0027] (3) Add a cationic reagent to solution II to carry out an esterification reaction to obtain solution III;

[0028] (4) Purify solution III to obtain cationic hyaluronic acid or its salt solid pure product.

[0029] Further, in step (1), the alkali in the alkaline aqueous solution is an inorganic alkali or an organic alkali. The inorganic alkali or organic alkali is a conventional inorganic alkali or organic alkali in the art and is not particularly limited. Preferably, the alkali is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium alkoxide, and potassium alkoxide.

[0030] Further, in step (1), the concentration of the alkaline aqueous solution is 0.2 to 1.5 mol / L, for example, it can be 0.2 mol / L, 0.3 mol / L, 0.4 mol / L, 0.5 mol / L, 0.6 mol / L, 0.7 mol / L, 0.8 mol / L, 0.9 mol / L, 1.0 mol / L, 1.1 mol / L, 1.2 mol / L, 1.3 mol / L, 1.4 mol / L, 1.5 mol / L or any range thereof, preferably 0.2 to 0.8 mol / L.

[0031] Further, in step (1), the molar ratio of the hyaluronic acid or its salt to the cationizing agent is 1:(4-15), for example, it can be 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15 or any range therefrom, preferably 1:(6-10).

[0032] Further, in step (1), the reaction temperature is 20℃~60℃, for example, it can be 20℃, 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃ or any range therebetween, preferably 20℃~30℃.

[0033] Further, in step (1), the reaction time is 4-20h, for example, it can be any range between 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 8.5h, 9h, 9.5h, 10h, 20h, or 6-6.5h, preferably 6-6.5h.

[0034] Furthermore, the cationizing agent in step (1) can be selected from any of the structural formulas shown in formula (II);

[0035] In formula (II), R1, R2, and R3 are each independently an alkyl group; X represents a halogen atom, preferably, R1, R2, and R3 are each independently an alkyl group having 1 to 12 carbon atoms; more preferably;

[0036] R1 is -CH3, -CH2CH3, or

[0037] R2 is -CH3, -CH2CH3, or

[0038] R3 is -CH3, -CH2CH3, or

[0039] X is chlorine, bromine, or iodine; m = 1 to 5.

[0040] Or it can be selected from any of the structural formulas (III) below;

[0041] In formula (III), R1, R2, and R3 are each independently an alkyl group; X represents a halogen atom. Preferably, R1, R2, and R3 are each independently an alkyl group having 1 to 12 carbon atoms; more preferably;

[0042] R1 is -CH3, -CH2CH3, or

[0043] R2 is -CH3, -CH2CH3, or

[0044] R3 is -CH3, CH2CH3, or

[0045] X is chlorine, bromine, or iodine; m = 1 to 5.

[0046] Optionally, the cationizing agent may be glycidyltrimethylammonium chloride, glycidyltriethylammonium chloride, glycidyltripropylammonium chloride, 2,3-epoxypropyltrimethylammonium chloride, 3-chloro-2-hydroxypropyltriethylammonium chloride, 3-chloro-2-hydroxypropyltripropylammonium chloride, 3-chloro-2-hydroxypropyldimethyloctylammonium chloride, or other cationizing agents with structures satisfying the above formulas (II) and (III).

[0047] Further, in step (2), adjusting the pH of reaction solution I means adjusting it by using at least one of an acid, a salt, or other pH adjusters conventional in the art. The acid can be an inorganic acid or an organic acid, such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, citric acid, lactic acid, tartaric acid, etc.; the salt can be potassium citrate, sodium citrate, sodium carbonate, sodium bicarbonate, etc.

[0048] Further, in step (2), the concentration of HA in solution II is 0.5% to 10% (w / v), for example, it can be 0.5% (w / v), 1% (w / v), 1.5% (w / v), 2% (w / v), 3% (w / v), 4% (w / v), 5% (w / v), 6% (w / v), 7% (w / v), 8% (w / v), 9% (w / v), 10% (w / v) or any range thereto.

[0049] Further, in step (2), the acid or acidic buffer reagent is selected from at least one of hydrochloric acid, acetic acid, and 2-(N-morpholino)ethanesulfonic acid (MES), preferably MES.

[0050] Further, in step (2), the amount of acid or acidic buffer added is 1%-10% of the mass of solution II, for example, it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or any range between them, preferably 2%-5%.

[0051] Further, in step (3), the molar ratio of the hyaluronic acid salt to the cationizing agent is 1:(1 to 10), for example, it can be 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10 or any range thereof, preferably 1:(1 to 5).

[0052] Optionally, the halogen atom can be chlorine, bromine, iodine, etc.

[0053] Furthermore, the cationizing agent in step (3) can be selected from any of the structural formulas shown in formula (II);

[0054] In formula (II), R1, R2, and R3 are each independently an alkyl group; X represents a halogen atom, preferably, R1, R2, and R3 are each independently an alkyl group having 1 to 12 carbon atoms; more preferably;

[0055] R1 is -CH3, -CH2CH3, or

[0056] R2 is -CH3, -CH2CH3, or

[0057] R3 is -CH3, -CH2CH3, or

[0058] X is chlorine, bromine, or iodine; m = 1 to 5.

[0059] Optionally, the cationizing agent may be 2,3-epoxypropyltrimethylammonium chloride or other cationizing agents with a structural formula satisfying formula (II) above.

[0060] Further, in step (4), the reaction temperature is 40℃~80℃, for example, it can be 40℃, 45℃, 50℃, 55℃, 60℃, 65℃, 70℃, 75℃, 80℃ or any range therebetween;

[0061] Further, in step (4), the reaction time is 4 to 24 hours, for example, it can be 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours, 9 hours, 9.5 hours, 10 hours, 20 hours, 24 hours or any range therebetween.

[0062] Furthermore, in step (4), the purification is selected from any one of alcohol precipitation, dialysis, and nanofiltration. Alcohol precipitation, dialysis, and nanofiltration are all conventional techniques in the field, and their specific process conditions can be adjusted according to actual conditions. For example, when using alcohol precipitation for purification, the volume ratio of solution III to ethanol is 1:(1~10), and during washing, the volume fraction of ethanol in the ethanol-water solution is 70%~85%.

[0063] A third aspect of this application provides a composition comprising the cationic hyaluronic acid or a salt thereof as described in any one of the preceding claims.

[0064] A fourth aspect of this application provides the use of cationic hyaluronic acid or its salt prepared by any of the above-described methods in the preparation of cosmetic or medical device products.

[0065] Preferably, the application is to improve the hair adhesion of cosmetic or medical device products.

[0066] Preferably, the application is a skin care product or medical device product with cleansing and moisturizing effects.

[0067] Compared with the prior art, the beneficial effects of this application include, but are not limited to:

[0068] This application prepares cationic hyaluronic acid or its salts by a method of etherification followed by esterification, with a degree of substitution greater than 1.0. This cationic hyaluronic acid or its salts retain the high moisturizing properties of hyaluronic acid itself while increasing the unique hair-adsorption properties of the cationic side chains, endowing the product with good hydrophilicity and affinity. When applied in hair improvement products and cosmetics, it can be directly adsorbed onto the hair surface, keeping it moisturized and smooth, and is not easily lost, thus achieving a good moisturizing effect. In the preparation of cationic hyaluronic acid, the etherification reaction is carried out using a high-concentration homogeneous method under alkaline conditions, resulting in a small reaction volume and high reaction efficiency. The esterification reaction is carried out using a catalytic esterification method in a weakly acidic buffer solution, without the use of organic solvents, simplifying post-processing and being environmentally friendly. The overall reaction process is simple, has a high yield, and uses readily available raw materials, making it suitable for industrial production. Attached Figure Description

[0069] Figure 1 is an infrared spectrum of the cationic hyaluronic acid product in Example 20 of this application;

[0070] Figure 2 is the 1H NMR spectrum of the cationic hyaluronic acid product in Example 20 of this application;

[0071] Figure 3 is the infrared spectrum of the cationic hyaluronic acid product in Example 7 of this application. Detailed Implementation

[0072] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following description is merely an exemplary illustration of the scope of protection of the present invention, and those skilled in the art can make various changes and modifications to the invention based on the disclosed content, which should also fall within the scope of protection of the present invention.

[0073] In this application, the "degree of cationization" of hyaluronic acid or its salts refers to the number of hydroxyl and carboxyl groups substituted per molecule of the disaccharide that forms the building blocks of hyaluronic acid or its salts; the "degree of etherification" refers to the number of hydroxyl groups substituted, and the "degree of esterification" refers to the number of carboxyl groups substituted. Furthermore, the term "salt of hyaluronic acid" is not particularly limited, but preferably refers to pharmaceutically permissible salts, such as sodium salts, potassium salts, calcium salts, zinc salts, magnesium salts, and ammonium salts. Correspondingly, when A2 in the structure of the cationized hyaluronic acid or its salts is a metal ion, the metal ion is the corresponding sodium, potassium, calcium, zinc, magnesium, or ammonium ion.

[0074] In the following specific embodiments, hyaluronic acid or its salts are expressed in terms of molecular weight. It is understood that the molecular weight = molecular weight of hyaluronic acid monomer * degree of polymerization n, that is, the molecular weight and the degree of polymerization n can be converted to each other.

[0075] In the specific embodiments described below, the total degree of substitution was determined by proton nuclear magnetic resonance spectroscopy, and the calculation method is as follows:

[0076] Using the absorption peak of acetylamino group in HA at 1.9-2.2 ppm as a reference, HA has 3 hydrogen atoms with absorption peaks at this location, and the integral area is set to 3. The characteristic peak of the grafted cationic hyaluronic acid is the absorption peak of the quaternary ammonium group at around 3.28 ppm. One 2,3-epoxypropyltrimethylammonium chloride has 11 hydrogen atoms with absorption peaks at this location. Therefore, the area ratio of the grafted 2,3-epoxypropyltrimethylammonium chloride to the characteristic peak of HA is 11:3, and the degree of substitution is the integral value of the absorption peak at 3.28 ppm / 11.

[0077] In the following specific embodiments, the degree of esterification substitution was determined by ion chromatography, as follows:

[0078] First, 2,3-dihydroxypropyl-trimethylammonium chloride (DTA) in the graft is released through a hydrolysis reaction. The content of grafted GTA is indirectly detected by detecting the DTA content, and then the degree of substitution is calculated.

[0079] The standard curve for DTA is y = ax + b, where a and b are coefficients. The correlation coefficient r of the linear equation... 2 The value must be greater than 0.999, and the linear range is 5-100 mg / L.

[0080] Substituting the peak area S of DTA in the test solution into y = ax + b, we can obtain the concentration C of DTA in the test solution, in mg / L.

[0081] The formula for calculating the DTA content in a sample is as follows:

[0082] Z—DTA content in the sample, in mg / g;

[0083] C—DTA detection concentration calculated from the standard curve, in mg / L;

[0084] V—Sample pretreatment volume, in L;

[0085] f—dilution factor;

[0086] m — Sample weight, in grams.

[0087] The formula for calculating the degree of substitution is as follows:

[0088] DS—Degree of Substitution, in percentage (%);

[0089] Z—DTA content in the sample, in mg / g;

[0090] h0% — Loss on drying of the sample;

[0091] 170—Relative molecular mass of DTA, in g / mol;

[0092] X—Total degree of substitution, in units of 1;

[0093] 379+151.6*X—Relative molecular mass of a single HA disaccharide molecule after GTA substitution, in g / mol;

[0094] The relative molecular mass of 401-HA disaccharide molecule, in g / mol.

[0095] In the following specific embodiments, the molecular weight of cationic hyaluronic acid or its salts was determined using a DAWN multi-angle laser light scattering system coupled with high performance liquid chromatography; the specific chromatographic conditions are as follows:

[0096] Chromatographic column: TSKgel GMPWXL liquid chromatography column, 7.8mm x 300mm, 13μm;

[0097] Column temperature: 35℃;

[0098] Mobile phase: 0.20 mol / L sodium chloride solution (containing 0.2% ProClin 200);

[0099] Flow rate: 0.6 mL / min.

[0100] The present invention will be further described below with reference to specific embodiments. To facilitate understanding of the present invention by those skilled in the art, the present invention uses glycidyl trimethylammonium chloride as an example to prepare cationic hyaluronic acid or its salt in the following embodiments. This does not constitute a limitation of the present application. It is understood that by modifying any cationic reagent that satisfies the structural formula shown in formula (II) above, cationic hyaluronic acid or its salt with hydroxyl and carboxyl substitutions can be successfully prepared, thereby achieving the effects of the present application. The reaction formula for cationic hyaluronic acid or its salt is as follows:

[0101] Example 1: Product 1#

[0102] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.2g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA (2,3-epoxypropyltrimethylammonium chloride) was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the hyaluronic acid. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, cationic hyaluronic acid (i.e., product 1#) was obtained, weighing 5.01g, with a degree of cationization of 1.55.

[0103] Example 2: Product 2#

[0104] 5g of HA with a molecular weight of 226kDa was weighed and dissolved in 25ml of water. 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. 12.5g of NaCl was added to dissolve the precipitate, and then 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #2 was obtained with a weight of 4.88g and a degree of cationization of 1.75.

[0105] Example 3: Product 3#

[0106] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.8g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #3 was obtained with a weight of 4.53g and a degree of cationization of 1.62.

[0107] Example 4: Product 4#

[0108] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 1g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #4 was obtained with a weight of 4.38g and a degree of cationization of 1.30.

[0109] Example 5: Product 5#

[0110] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 1.89g of GTA was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #5 was obtained with a weight of 4.99g and a degree of cationization of 0.22.

[0111] Example 6: Product 6#

[0112] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 7.55g of GTA was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #6 was obtained with a weight of 4.97g and a degree of cationization of 1.02.

[0113] Example 7: Product 7#

[0114] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. 12.5g of NaCl was added to dissolve the precipitate, followed by 750ml of 95% ethanol. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 7# was obtained with a weight of 4.64g and a degree of cationization of 1.98. As shown in Figure 3, in product 7#, at 1750cm⁻¹… -1 The absence of characteristic peaks for esterification structures nearby indicates that substitution only occurs at the hydroxyl position.

[0115] Example 8: Product 8#

[0116] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 18.95g of GTA was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #8 was obtained with a weight of 4.84g and a degree of cationization of 2.22.

[0117] Example 9: Product 9#

[0118] 5g of HA with a molecular weight of 226kDa was weighed and dissolved in 25ml of water. 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 28.43g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. 12.5g of NaCl was added to dissolve the precipitate, and then 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product #9 was obtained with a weight of 0.66g and a degree of cationization of 3.00.

[0119] Example 10: Product 10#

[0120] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 18.95g of GTA was added, and the mixture was reacted at 40℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 10# was obtained with a weight of 2.27g and a degree of cationization of 1.99.

[0121] Example 11: Product 11#

[0122] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 18.95g of GTA was added, and the mixture was reacted at 60℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 11# was obtained with a weight of 1.99g and a degree of cationization of 1.34.

[0123] Example 12: Product 12#

[0124] 5g of HA with a molecular weight of 9kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. The reaction solution was dialyzed for 72 hours, and after lyophilization, product 12# was obtained with a weight of 2.85g and a degree of cationization of 1.44.

[0125] Example 13: Product 13#

[0126] 5g of HA with a molecular weight of 40kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. The reaction solution was dialyzed for 72 hours, and after lyophilization, product 13# was obtained with a weight of 3.12g and a degree of cationization of 1.70.

[0127] Example 14: Product 14#

[0128] 5g of HA with a molecular weight of 960kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 11.37g of GTA was added, and the mixture was reacted at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, 12.5g of NaCl was added to dissolve the precipitate, and 750ml of 95% ethanol was added to precipitate the precipitate. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 14# was obtained with a weight of 5.02g and a degree of cationization of 1.23.

[0129] Example 15: Product 15#

[0130] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to approximately 4 with hydrochloric acid. Then, 5.67g of GTA was added, and the temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was completed, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 15# was obtained with a weight of 4.68g and a total cationization degree of 1.99.

[0131] Example 16: Product 16#

[0132] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to approximately 4 with acetic acid. Then, 5.67g of GTA was added, and the temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was completed, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 16# was obtained with a weight of 4.49g and a total cationization degree of 2.00.

[0133] Example 17: Product 17#

[0134] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the mixture was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. Then, the pH was adjusted to 4±0.2 with acetate-sodium acetate buffer solution. 5.67g of GTA was added, and the temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was completed, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The product was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, the weight of product 17# was 4.69g, and the total cationization degree was 2.02.

[0135] Example 18: Product 18#

[0136] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water. 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was complete, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. 9.76g of MES was added to adjust the pH to 4±0.2, and 5.67g of GTA was added. The temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was complete, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 18# weighed 4.97g, with a total cationization degree of 2.23.

[0137] Example 19: Product 19#

[0138] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water. 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was complete, 225ml of purified water was added, and the pH was adjusted to 6.5±0.5 with hydrochloric acid. 9.76g of MES was added to adjust the pH to 4±0.2, and 1.89g of GTA was added. The temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was complete, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 19# was obtained with a weight of 4.99g and a total cationization degree of 2.20.

[0139] Example 20: Product 20#

[0140] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction, 225ml of purified water was added to adjust the pH to 6.5±0.5, 9.76g of MES was added to adjust the pH to 4±0.2, and 9.44g of GTA was added. The temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was complete, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The solution was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 20# was obtained with a weight of 4.90g and a total cationization degree of 2.16. The infrared spectrum and 1H NMR spectrum of product 20# are shown in Figure 1 and Figure 2, respectively. In the infrared spectrum of Figure 1, product 20# is at 1750cm⁻¹. -1 The presence of absorption peaks on both sides indicates the presence of ester bonds in the product. The degree of substitution of the esterified portion was measured to be approximately 0.18 by ion chromatography. The NMR in Figure 2 shows a distinct characteristic peak of the cationizing reagent at 3.0-3.3 ppm, and the total degree of substitution was measured to be 2.16. Therefore, the product is composed of both hydroxyl and carboxyl substitutions.

[0141] Example 21: Product 21#

[0142] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water. 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was complete, 225ml of purified water was added to adjust the pH to 6.5±0.5. 9.76g of MES was added to adjust the pH to 4±0.2. 18.89g of GTA was added, and the temperature was raised to 60℃, and the reaction was carried out for 15 hours. After the reaction was complete, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The precipitate was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 21# was obtained with a weight of 4.55g and a total cationization degree of 2.03.

[0143] Example 22: Product 22#

[0144] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added to adjust the pH to 6.5±0.5, 9.76g of MES was added to adjust the pH to 4±0.2, and 5.67g of GTA was added. The temperature was raised to 40℃, and the reaction was carried out for 15 hours. After the reaction was completed, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The product was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, the weight of product 21# was 4.95g, and the total cationization degree was 2.08.

[0145] Example 23: Product 23#

[0146] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added to adjust the pH to 6.5±0.5, 9.76g of MES was added to adjust the pH to 4±0.2, and 5.67g of GTA was added. The temperature was raised to 50℃, and the reaction was carried out for 15 hours. After the reaction was completed, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The product was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, the product 22# weighed 4.88g and had a total cationization degree of 2.15.

[0147] Example 24: Product 24#

[0148] 5g of HA with a molecular weight of 226kDa was dissolved in 25ml of water, 0.4g of NaOH was added, and the solution was alkalized for 1 hour. Then, 15.2g of GTA was added, and the reaction was carried out at 25℃ for 20 hours. After the reaction was completed, 225ml of purified water was added to adjust the pH to 6.5±0.5, 9.76g of MES was added to adjust the pH to 4±0.2, 5.67g of GTA was added, and the temperature was raised to 80℃ for 15 hours. After the reaction was completed, 12.5g of NaCl was added, followed by 750ml of 95% ethanol for precipitation. The product was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 23# was obtained with a weight of 3.47g and a total cationization degree of 2.11.

[0149] The specific process conditions for preparing cationic hyaluronic acid products 1# to 23# in Examples 1-23 above are shown in Table 1 below, and the degree of cationization of the products is shown in Table 2.

[0150] Table 1

[0151] Table 2

[0152] The results show that, as can be seen from Examples 1-4, the alkali concentration in the etherification stage has a certain impact on the reaction efficiency. When the alkali concentration is too low, the catalytic concentration required for a full reaction cannot be reached, resulting in low reaction efficiency. When the alkali concentration is too high, the product will decompose, reducing the reaction efficiency.

[0153] As can be seen from Examples 2 and 5-9, the degree of cationization gradually increases with the increase of the molar ratio of HA to cationizing reagent during the etherification stage. When the molar ratio reaches 1:10, the degree of cationization can reach 2.22. However, if the substitution is too high, it will reduce the substitution in the subsequent esterification stage. Therefore, the degree of substitution in the etherification stage should not be too high.

[0154] As can be seen from Examples 8 and 10-11, the degree of cationization of the product decreases with increasing etherification reaction temperature. Excessive temperature is detrimental to reaction efficiency. Furthermore, as the temperature increases, the color of the reaction solution changes from yellow to reddish-brown, and the final product color also darkens, which is not conducive to obtaining a product with stable properties.

[0155] As can be seen from Examples 2 and 12-14, cationic hyaluronic acid or its salts with a degree of cationization of 0.1-4.3 can be obtained when the molecular weight of HA is in the range of 9kDa-960kDa.

[0156] Comparative Example 1

[0157] 5g of HA with a molecular weight of 226kDa was dissolved in 200ml of water, and 9.76g of MES was added to dissolve it. 5.67g of GTA was dissolved in 50ml of water and added to the HA solution. The mixture was heated to 60℃ and reacted for 15h. After the reaction was complete, 12.5g of NaCl was added, followed by 750ml of 95% ethanol to precipitate the product. The product was washed three times with 250ml of 85% ethanol and dehydrated twice with 250ml of 95% ethanol. After filtration and vacuum drying, product 23# was obtained with a weight of 4.97g and a degree of cationization of 0.25.

[0158] Experimental Example 1: Adsorption Test of Damaged Hair

[0159] Experimental principle: The absorbance of different cationic hyaluronic acid and HA solutions before and after hair adsorption was measured by ultraviolet spectrophotometer to observe the adsorption capacity of cationic hyaluronic acid and HA on hair.

[0160] Experimental methods:

[0161] (1) Preparation of sample solution: Products 7#, 18#, Comparative Example 1 and HA were prepared into 0.1% aqueous solutions as mother liquors. The mother liquors were diluted to 0.008% sample solution as test solutions.

[0162] (2) Preparation of damaged hair: Human black hair was soaked in a 1% aqueous solution of lauryl ether ammonium sulfate for 1 minute. Then, the human black hair was washed with water and dried with a towel, then the moisture was removed with paper towels and dried with a dryer (washing treatment). Then, bleaching treatment was carried out in the following order: First, a bleaching solution was prepared by mixing 5% hydrogen peroxide aqueous solution and 2.5% ammonia aqueous solution at a volume ratio of 1:1. The human black hair was soaked in the bleaching solution at 30°C for 20 minutes (bleaching treatment). After soaking, it was washed. The soaking-washing steps were repeated 10 times to make damaged hair.

[0163] (3) Damaged hair adsorption test: Accurately weigh 1.00g of dry and clean damaged hair into a small plastic bottle; preheat 0.008% test solution in a 37℃ water bath; transfer 10ml of test solution to soak the hair and incubate in a 37℃ water bath for 10min; take 1ml of the test solution after it has been adsorbed by the hair and add it to a glass test tube for determination by carbazole colorimetric method; take another 1ml of the test solution that has not been adsorbed by the hair and add it to a glass test tube for determination by carbazole colorimetric method.

[0164] Test method:

[0165] Take 1 ml of the test solution, and slowly add 5.0 ml of 0.025 mol / L borax-sulfuric acid solution cooled to below 4℃ while shaking. Shake well. Heat in a boiling water bath for 10 min, then cool in an ice water bath. Accurately add 0.20 ml of carbazole reagent, shake well, and heat in a boiling water bath for 15 min. A purple-red color will appear.

[0166] The adsorption rate is calculated as follows: Adsorption rate = (average absorbance before adsorption - average absorbance after adsorption) / average absorbance before adsorption × 100%.

[0167] The adsorption enhancement rate was calculated by comparing the adsorption rates of cationic hyaluronic acid and hyaluronic acid (HA). The formula is: Adsorption enhancement rate = (Adsorption rate of cationic hyaluronic acid - Adsorption rate of HA) / Adsorption rate of HA × 100%.

[0168] The test results are shown in Table 3 below.

[0169] Table 3

[0170] Adsorption effect of damaged hair on each sample: Product 18# > Product 24# > Product 15# > Product 7# > Comparative Example 1 > HA. This indicates that both cationic hyaluronic acid and HA have adsorption capacity for damaged hair. The adsorption effect of cationized HA is better than that of uncationized HA. Furthermore, by comparing the adsorption enhancement rate of Product 18#, Product 7#, and Comparative Example 1 with hyaluronic acid, it can be found that the cationic hyaluronic acid of this application has a synergistic effect on adsorption compared with the cationic hyaluronic acid of simple esterification or simple etherification, indicating that the cationic hyaluronic acid of this application is more conducive to retention on hair.

[0171] Therefore, the cationic hyaluronic acid of this application is suitable for addition to shampoo and conditioner products to promote the repair of damaged hair.

[0172] It should be noted that the above embodiments only exemplify the preparation of cationic hyaluronic acid or its salts when the cationic reagent is GTA. Other cationic reagents with structural formulas that satisfy formulas (II) and (III) above can be used with the method of this application to achieve substitution of the hydroxyl and carboxyl positions of hyaluronic acid or its salts, resulting in cationic hyaluronic acid with a total cationic degree of 0.1–4.5. This solves the technical problem of this application, namely, retaining the high moisturizing properties of hyaluronic acid itself while increasing the hair-adsorption properties unique to cationic side chains, giving the product good hydrophilicity and affinity. When applied in hair improvement products and cosmetics, it can be directly adsorbed onto the hair surface to keep it moisturized and smooth, and is not easily lost, thus achieving a good moisturizing effect. Since the above cationic reagents involve many types of raw materials, this application will not list them all. Those skilled in the art, based on a clear understanding of the technical concept of this application, can infer that the resins with the above structures can achieve the above-mentioned effects.

[0173] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A cationic hyaluronic acid or a salt thereof, characterized in that, The structural formula of the cationic hyaluronic acid or its salt is shown in formula (I) below: In equation (I), A1 is independently H or A2 can be independently a metal ion, H, or n represents a positive integer representing the degree of aggregation; m is 1 to 5; In the structure of the above-mentioned cationic hyaluronic acid or its salt, at least one hydroxyl group and at least one carboxyl group are simultaneously cationic.

2. The cationic hyaluronic acid or its salt according to claim 1, characterized in that, R1, R2, and R3 in A1 and A2 are each independently an alkyl group; preferably, R1, R2, and R3 are each independently an alkyl group having 1 to 12 carbon atoms; more preferably; R1 is -CH3, -CH2CH3, or R2 is -CH3, -CH2CH3, or R3 is -CH3, -CH2CH3, or X represents a halogen atom; preferably, X is chlorine, bromine or iodine.

3. The cationic hyaluronic acid or its salt according to claim 1, characterized in that, The degree of polymerization n is 10 to 2500, preferably 20 to 1500.

4. The cationic hyaluronic acid or its salt according to claim 1, characterized in that, The total degree of cationization of the cationic hyaluronic acid or its salt is 0.1 to 4.5, preferably 1.0 to 3.

3.

5. The cationic hyaluronic acid or its salt according to claim 4, characterized in that, The total degree of cationization includes etherification cationization and esterification cationization; wherein... The degree of etherification is 0.09–4.1, preferably 0.98–3.0; The degree of esterification cationicity is 0.01 to 0.4, preferably 0.02 to 0.

3.

6. The method for preparing cationic hyaluronic acid or its salt according to any one of claims 1-5, characterized in that, Includes the following steps: (1) Hyaluronic acid or its salt is dissolved in an alkaline aqueous solution, and after alkalization, a cationizing reagent is added to carry out an etherification reaction to obtain solution I; preferably, the base in the alkaline aqueous solution is an inorganic base or an organic base, and the inorganic base or organic base is a conventional inorganic base or organic base in the art, without any special limitation; more preferably, the base is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium alkoxide, and potassium alkoxide; the concentration of the alkaline aqueous solution is 0.2 to 1.5 mol / L; (2) Directly add acid to adjust the pH of reaction solution I to 3-5, or first add acid to adjust the pH of reaction solution I to 6-7 and then add acid buffer to 3-5 to obtain solution II; preferably, the acid or acid buffer is selected from at least one of hydrochloric acid, acetic acid, acetic acid-sodium acetate, and MES, and more preferably MES; (3) Add a cationic reagent to solution II to carry out an esterification reaction to obtain solution III; (4) Purify solution III to obtain cationic hyaluronic acid or its salt solid pure product.

7. The preparation method according to claim 6, characterized in that, In step (1), the molar ratio of hyaluronic acid or its salt to the cationizing agent is 1:(4-15), preferably 1:(6-10).

8. The preparation method according to claim 6, characterized in that, In step (3), the molar ratio of hyaluronic acid or its salt to the cationizing agent is 1:(1-10).

9. A composition, characterized in that, It comprises cationic hyaluronic acid or its salt as described in any one of claims 1-5, or cationic hyaluronic acid or its salt prepared by the preparation method described in any one of claims 6-8.

10. Use of the cationic hyaluronic acid or its salt as described in any one of claims 1-5, or the cationic hyaluronic acid or its salt prepared by any one of claims 6-8, or the composition as described in claim 9 in the preparation of cosmetic or medical device products, preferably in the preparation of cosmetic or medical device products that improve hair absorption.

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