Cationic hyaluronic acid or salt thereof as well as preparation method and application thereof

Abstract

The invention provides cationized hyaluronic acid or salt thereof as well as a preparation method and application thereof, and relates to the field of synthesis of raw materials of daily necessities. According to the cationized hyaluronic acid or the salt thereof provided by the invention, the structural formula of the cationized hyaluronic acid or the salt thereof is shown as a formula (I); # imgabs0 # is cationized at the positions of at least one hydroxyl group and at least one carboxyl group at the same time in the structure of the cationized hyaluronic acid or the salt thereof; the cationic hyaluronic acid not only maintains the high moisture retention of hyaluronic acid, but also increases the specific hair adsorbability of a cationic side chain, endows the product with good hydrophilicity and affinity, can be directly adsorbed on the hair surface to keep the hair in a moist and smooth state when being applied to hair improvement products and cosmetics, and is not easy to lose; the moisturizing effect is good.

Description

Technical Field

[0001] The present application relates to the field of synthesis of daily necessities raw materials, and particularly to a cationized hyaluronic acid or its salt, a preparation method thereof, and an application thereof. Background Art

[0002] 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 polysaccharide widely present in the human body and is a biodegradable and biocompatible carbohydrate polymer. Hyaluronic acid has good moisturizing properties. It can carry more than 500 times its own weight of water and is currently recognized as the best natural moisturizing factor, being widely used in fields such as cosmetics.

[0003] However, HA is a polyanionic polysaccharide. When used on the keratin surface of negatively charged hair, due to charge repulsion, it hinders its adsorption on the hair surface. Therefore, natural hyaluronic acid cannot achieve an ideal moisturizing effect. By modifying hyaluronic acid and making it positively charged through chemical modification, the modified hyaluronic acid can be well adsorbed on the hair surface by the attraction between positive and negative charges, thus achieving a good moisturizing effect.

[0004] Currently, the prepared cationized hyaluronic acid is mainly modified only at the hydroxyl sites or carboxyl sites of hyaluronic acid. For example, in patent CN202111674528.3, this scheme only substitutes at the carboxyl sites, which can reduce the negative charges carried by the carboxyl groups of hyaluronic acid itself and reduce the aggregation caused by the attraction between positive and negative charges after cationization, but its degree of cationization is relatively low. In the prior art, the modification of the hydroxyl sites of hyaluronic acid is as described in patents WO 2023 / 285663Al, CN200680044541.8, CN202211446277.8, CN202211628673.2, and CN202010446769.1, etc. There are few reports on cationized hyaluronic acid with substitutions at both hydroxyl sites and carboxyl sites. Given that most of the current cationized hyaluronic acids are modified at the hydroxyl sites of hyaluronic acid, their adsorption properties, moisturizing properties, etc. still need to be enhanced. Summary of the Invention

[0005] The purpose of the present application is to provide a cationized hyaluronic acid or its salt with double substitutions at hydroxyl sites and carboxyl sites, a preparation method thereof, and an application thereof in view of the deficiencies of the prior art.

[0006] To achieve the above purpose, the technical solutions adopted in the present application are as follows:

[0007] On the one hand, a cationized hyaluronic acid or its salt is provided, which is characterized in that the structural formula of the cationized hyaluronic acid or its salt is as shown in the following formula (I);

[0008]

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

[0010] A2 is independently a metal ion, H or

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

[0012] m is 1 to 5;

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

[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] Furthermore, the degree of polymerization n = 10 to 2500, for example, it 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, 1100, 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 therebetween, preferably 20 to 1500.

[0020] Furthermore, the total degree of cationization of the cationized hyaluronic acid or its salt is 0.1 to 4.5, and can be, for example, 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, 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 therebetween, preferably 1.0 to 3.3.

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

[0022] The etherification degree of cationization is 0.09 to 4.1, and can be, for example, 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 any range therebetween, preferably 0.98 to 3.0;

[0023] The esterification degree of cationization is 0.01 to 0.4, and can be, for example, 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 therebetween, preferably 0.02 to 0.3.

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

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

[0026] (2) Adjust the pH of Reaction Solution I directly to 3 - 5 with an acid, or first adjust the pH of Reaction Solution I to 6 - 7 with an acid and then add an acidic buffer reagent to 3 - 5 to obtain Solution II. ；

[0027] (3) Add a cationization reagent to Solution II for an esterification reaction to obtain Solution III.

[0028] (4) Purify Solution III to obtain a solid pure product of cationized hyaluronic acid or its salt.

[0029] Furthermore, in step (1), 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 special limitation; preferably, the base is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium alkoxide, and potassium alkoxide.

[0030] Furthermore, in step (1), the concentration of the alkaline aqueous solution is 0.2 - 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 therebetween, and preferably 0.2 - 0.8 mol / L.

[0031] Furthermore, in step (1), the molar ratio of the hyaluronic acid or its salt to the cationization reagent 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 therebetween, and preferably 1:(6 - 10).

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

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

[0034] Furthermore, the cationization reagent in step (1) can be selected from any one of the following structural formulas (II);

[0035]

[0036] 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;

[0037] R1 is -CH3, -CH2CH3 or

[0038] R2 is -CH3, -CH2CH3 or

[0039] R3 is -CH3, -CH2CH3 or

[0040] X is chlorine, bromine or iodine; m = 1 to 5.

[0041] Or it is any one selected from the structural formulas as follows: formula (III);

[0042]

[0043] 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;

[0044] R1 is -CH3, -CH2CH3 or

[0045] R2 is -CH3, -CH2CH3 or

[0046] R3 is -CH3, CH2CH3 or

[0047] X is chlorine, bromine or iodine; m = 1 to 5.

[0048] Optionally, the cationizing agent may be glycidyltrimethylammonium chloride, glycidyltriethylammonium chloride, glycidyltripropylammonium chloride, 2,3-epoxypropyl-trimethylammonium chloride, 3-chloro-2-hydroxypropyltriethylammonium chloride, 3-chloro-2-hydroxypropyltripropylammonium chloride, 3-chloro-2-hydroxypropyldimethyloctylammonium chloride, etc., or other cationizing agents whose structural formulas satisfy the above formula (II) and formula (III).

[0049] Further, in step (2), adjusting the pH of the reaction solution I means adjusting it using at least one of an acid and a salt or other conventional pH adjusters 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.

[0050] Further, in step (2), the concentration of HA in the solution II is 0.5% - 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 therebetween.

[0051] 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.

[0052] Further, in step (2), the addition amount of the acid or acidic buffer reagent is 1% - 10% of the mass of the solution II, for example, it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or any range therebetween, preferably 2% - 5%.

[0053] Further, in step (3), the molar ratio of the hyaluronate to the cationizing reagent is 1:(1 - 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 therebetween, preferably 1:(1 - 5).

[0054] Optionally, the halogen atom can be chlorine, bromine, iodine, etc.

[0055] Further, the cationizing reagent in step (3) can be selected from any one of the following structural formulas (II);

[0056]

[0057] 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 with 1 - 12 carbon atoms; more preferably;

[0058] R1 is -CH3, -CH2CH3 or

[0059] R2 is -CH3, -CH2CH3 or

[0060] R3 is -CH3, -CH2CH3 or

[0061] X is chlorine, bromine or iodine; m = 1 - 5.

[0062] Optionally, the cationizing agent may be 2,3-epoxypropyl-trimethylammonium chloride or other cationizing agents whose structural formula satisfies the above formula (II).

[0063] Further, in step (4), the reaction temperature is 40°C to 80°C, for example, it can be 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C or any range therebetween;

[0064] Further, in step (4), the reaction time is 4 - 24 h, for example, it can be 4 h, 4.5 h, 5 h, 5.5 h, 6 h, 6.5 h, 7 h, 7.5 h, 8 h, 8.5 h, 9 h, 9.5 h, 10 h, 20 h, 24 h or any range therebetween.

[0065] Further, 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 art, and their specific process conditions can be adjusted according to the actual situation. For example, when using alcohol precipitation for purification, the volume ratio of solution III to ethanol is 1:(1 - 10), and when washing, the volume fraction of ethanol in the ethanol-aqueous solution is 70% - 85%.

[0066] In the third aspect of the present application, a composition is provided, which contains the cationized hyaluronic acid or its salt described in any one of the above.

[0067] In the fourth aspect of the present application, the application of the cationized hyaluronic acid or its salt described in any one of the above, or the cationized hyaluronic acid or its salt prepared by the preparation method of the cationized hyaluronic acid or its salt described in any one of the above in the preparation of cosmetic or medical device products is provided.

[0068] Preferably, the application is to improve the hair adsorption of cosmetic or medical device products.

[0069] Preferably, the application is skin care products or medical device products with cleaning and moisturizing effects.

[0070] Compared with the prior art, the beneficial effects of the present application include but are not limited to:

[0071] In this application, a method of etherification followed by esterification is used to prepare cationized hyaluronic acid or its salt, with a degree of substitution greater than 1.0. This cationized hyaluronic acid or its salt not only retains the high moisture retention of hyaluronic acid itself but also increases the unique adsorption to hair of the cationic side chain, endowing the product with good hydrophilicity and affinity. When applied in hair improvement products and cosmetics, it can directly adsorb on the hair surface to keep it moisturized, smooth, and not easily lost, thus achieving a good moisturizing effect. During the preparation of cationic hyaluronic acid, the etherification reaction is prepared by a high-concentration homogeneous method under alkaline conditions, with a small reaction volume and high reaction efficiency; the esterification reaction uses a method of catalytic esterification in a weak acidic buffer solution without using organic solvents, with simple post-treatment and environmental friendliness; the overall reaction process is simple, with a high yield and easily available raw materials, being suitable for industrial production. Description of the Drawings

[0072] Figure 1 is the infrared spectrum of the cationized hyaluronic acid product in Example 20 of this application;

[0073] Figure 2 is the proton nuclear magnetic resonance spectrum of the cationized hyaluronic acid product in Example 20 of this application;

[0074] Figure 3 is the infrared spectrum of the cationized hyaluronic acid product in Example 7 of this application. Detailed Embodiments

[0075] The following non-limiting examples can enable those of ordinary skill in the art to more comprehensively understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary illustration of the scope claimed by the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and it should also fall within the scope claimed by the present invention.

[0076] In this application, the so-called "cationization degree" of hyaluronic acid or its salt refers to the number of substitutions (substitution number) of hydroxyl groups and carboxyl groups per molecule of disaccharide, which is a constituent unit of hyaluronic acid or its salt; the so-called "etherification cationization degree" refers to the number of substitutions of hydroxyl groups, and the so-called "esterification cationization degree" refers to the number of substitutions of carboxyl groups. In addition, as the "salt of hyaluronic acid", there is no particular limitation, and preferably it is a pharmaceutically acceptable salt. For example, sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt, ammonium salt, etc. can be cited. Correspondingly, when A2 in the structure of cationized hyaluronic acid or its salt is a metal ion, the metal ion is the corresponding sodium, potassium, calcium, zinc, magnesium, ammonium, etc.

[0077] In the following specific examples, hyaluronic acid or its salt is represented by molecular weight. It can be understood that its 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 mutually converted.

[0078] In the following specific examples, the total degree of substitution was determined by nuclear magnetic resonance hydrogen spectroscopy, and the calculation method was as follows:

[0079] Based on the absorption peak of the acetylamino group of HA at 1.9 - 2.2 ppm, there are 3 hydrogens with absorption peaks of HA at this position, and the set value of the integral area is 3. The characteristic peak of the grafted cationic hyaluronic acid is the absorption peak of the quaternary ammonium group at about 3.28 ppm. There are 11 hydrogens with absorption peaks of a 2,3-epoxypropyltrimethylammonium chloride at this position. Therefore, when one 2,3-epoxypropyltrimethylammonium chloride is grafted, the area ratio 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.

[0080] In the following specific examples, the degree of esterification substitution was determined by ion chromatography, and the method was as follows:

[0081] First, 2,3-dihydroxypropyltrimethylammonium chloride (DTA) in the grafted product was released through a hydrolysis reaction, and the content of grafted GTA was indirectly detected by detecting the DTA content, and then the degree of substitution was calculated.

[0082] The standard curve of DTA is y = ax + b, where a and b are coefficients. The correlation coefficient r of the linear equation 2 should be greater than 0.999, and the linear range is 5 - 100 mg / L.

[0083] Substitute the peak area S of DTA in the test solution as the y value into y = ax + b, and the concentration C of DTA in the test solution can be obtained, unit: mg / L.

[0084] The calculation formula for the DTA content in the sample is as follows:

[0085]

[0086] Z—the DTA content in the sample, unit mg / g;

[0087] C—the detected concentration of DTA calculated from the standard curve, unit mg / L;

[0088] V—the volume of sample pretreatment, unit L;

[0089] f—the dilution factor;

[0090] m—the sample weighing amount, unit g.

[0091] The calculation formula for the degree of substitution is as follows:

[0092]

[0093] DS—the degree of substitution (Degree of Substitution), unit %;

[0094] Z—the DTA content in the sample, unit: mg / g;

[0095] h0%—the drying loss of the sample to be measured;

[0096] 170—the relative molecular mass of DTA, unit: g / mol;

[0097] X—the total degree of substitution, unit: 1;

[0098] 379 + 151.6*X—the relative molecular mass of a single HA disaccharide molecule after GTA substitution, unit: g / mol;

[0099] 401—the relative molecular mass of HA disaccharide molecule, unit: g / mol.

[0100] In the following specific embodiments, the molecular weight of cationized hyaluronic acid or its salt is measured by a DAWN multi-angle laser light scattering instrument - high performance liquid chromatography combined system; the specific chromatographic conditions are as follows:

[0101] Chromatographic column: TSKgel GMPWXL liquid chromatography column, 7.8mm x 300mm, 13μm;

[0102] Column temperature: 35°C;

[0103] Mobile phase: 0.20mol / L sodium chloride solution (containing 0.2% ProClin 200);

[0104] Flow rate: 0.6mL / min.

[0105] The present invention will be further described below by way of specific embodiments. For the convenience of those skilled in the art to understand the content of the present invention, in the following embodiments of the present invention, the cationizing reagent glycidyl trimethyl ammonium chloride is used as an example to prepare cationized hyaluronic or its salt, which does not constitute a limitation to this application. It can be understood that by changing any cationizing reagent that satisfies the structural formula shown in the above formula (II), cationized hyaluronic acid or its salt substituted at the hydroxyl group and carboxyl group can be successfully prepared, so as to achieve the effect of this application. The reaction formula of cationized hyaluronic or its salt is as follows:

[0106]

[0107] Example 1: Product 1#

[0108] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.2 g of NaOH, alkalize for 1 h, add 11.37 g of GTA (2,3-epoxypropyl-trimethylammonium chloride), and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and obtain cationic hyaluronic acid (i.e., Product 1#) after vacuum drying, with a weight of 5.01 g and a cationization degree of 1.55.

[0109] Example 2: Product 2#

[0110] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 11.37 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and the weight of Product 2# obtained after vacuum drying is 4.88 g, and the cationization degree is 1.75.

[0111] Example 3: Product 3#

[0112] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.8 g of NaOH, alkalize for 1 h, add 11.37 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and the weight of Product 3# obtained after vacuum drying is 4.53 g, and the cationization degree is 1.62.

[0113] Example 4: Product 4#

[0114] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 1 g of NaOH, alkalize for 1 h, add 11.37 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and the weight of Product 4# obtained after vacuum drying is 4.38 g, and the cationization degree is 1.30.

[0115] Example 5: Product 5#

[0116] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH and alkalize for 1 h. Then add 1.89 g of GTA and react at 25 °C for 20 h. After the reaction, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Next, add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and vacuum dry. The weight of Product 5# obtained is 4.99 g, and the degree of cationization is 0.22.

[0117] Example 6: Product 6#

[0118] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH and alkalize for 1 h. Then add 7.55 g of GTA and react at 25 °C for 20 h. After the reaction, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Next, add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and vacuum dry. The weight of Product 6# obtained is 4.97 g, and the degree of cationization is 1.02.

[0119] Example 7: Product 7#

[0120] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH and alkalize for 1 h. Then add 15.2 g of GTA and react at 25 °C for 20 h. After the reaction, add 225 ml of purified water. Adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then add 12.5 g of NaCl to dissolve. Next, add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and vacuum dry. The weight of Product 7# obtained is 4.64 g, and the degree of cationization is 1.98. It can be seen that in the obtained Product 7#, no characteristic peak of the esterification structure appears near 1750 cm Figure 3 which indicates that substitution occurs only at the hydroxyl position. -1

[0121] Example 8: Product 8#

[0122] ​Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 18.95 g of GTA, and react at 25 °C for 20 h. After the reaction, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, add 12.5 g of NaCl to dissolve, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 8# is 4.84 g, and the cationic degree is 2.22.

[0123] Example 9: Product 9#

[0124] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 28.43 g of GTA, and react at 25 °C for 20 h. After the reaction, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, add 12.5 g of NaCl to dissolve, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 9# is 0.66 g, and the cationic degree is 3.00.

[0125] Example 10: Product 10#

[0126] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 18.95 g of GTA, and react at 40 °C for 20 h. After the reaction, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, add 12.5 g of NaCl to dissolve, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 10# is 2.27 g, and the cationic degree is 1.99.

[0127] Example 11: Product 11#

[0128] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 18.95 g of GTA, and react at 60 °C for 20 h. After the reaction, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, add 12.5 g of NaCl to dissolve, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 11# is 1.99 g, and the cationic degree is 1.34.

[0129] Example 12: Product 12#

[0130] Weigh 5 g of HA with a molecular weight of 9 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 11.37 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then dialyze the reaction solution for 72 h. After freeze-drying, the weight of product 12# is 2.85 g, and the degree of cationization is 1.44.

[0131] Example 13: Product 13#

[0132] Weigh 5 g of HA with a molecular weight of 40 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 11.37 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then dialyze the reaction solution for 72 h. After freeze-drying, the weight of product 13# is 3.12 g, and the degree of cationization is 1.70.

[0133] Example 14: Product 14#

[0134] Weigh 5 g of HA with a molecular weight of 960 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 11.37 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then dissolve 12.5 g of NaCl, add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 14# is 5.02 g, and the degree of cationization is 1.23.

[0135] Example 15: Product 15#

[0136] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to about 4 with hydrochloric acid, add 5.67 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 15# is 4.68 g, and the total degree of cationization is 1.99.

[0137] Example 16: Product 16#

[0138] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to about 4 with acetic acid, add 5.67 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 16# is 4.49 g, and the total cationization degree is 2.00.

[0139] Example 17: Product 17#

[0140] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, then adjust to pH 4 ± 0.2 with acetic acid-sodium acetate buffer solution, add 5.67 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 17# is 4.69 g, and the total cationization degree is 2.02.

[0141] Example 18: Product 18#

[0142] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 5.67 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 18# is 4.97 g, and the total cationization degree is 2.23.

[0143] Example 19: Product 19#

[0144] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5 with hydrochloric acid, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 1.89 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 19# is 4.99 g, and the total cationization degree is 2.20.

[0145] Example 20: Product 20#

[0146] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 9.44 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 20# is 4.90 g, and the total cationization degree is 2.16. The infrared spectrum and proton nuclear magnetic resonance spectrum of product 20# are shown respectively as Figure 1 、 Figure 2 shown. Figure 1 In the infrared spectrum, product 20# has an absorption peak at about 1750 cm -1 −1, indicating the presence of an ester bond in the product. The degree of substitution of the esterified part measured by ion chromatography is about 0.18. Figure 2 There is an obvious characteristic peak of the cationization reagent at 3.0 - 3.3 ppm in the nuclear magnetic resonance, and the total degree of substitution is measured to be 2.16. Therefore, the product is composed of both hydroxyl substitution and carboxyl substitution.

[0147] Example 21: Product 21#

[0148] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 18.89 g of GTA, raise the temperature to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 21# is 4.55 g, and the total cationization degree is 2.03.

[0149] Example 22: Product 22#

[0150] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 5.67 g of GTA, raise the temperature to 40 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 21# is 4.95 g, and the total cationization degree is 2.08.

[0151] Example 23: Product 23#

[0152] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction is completed, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 5.67 g of GTA, raise the temperature to 50 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of product 22# is 4.88 g, and the total cationization degree is 2.15.

[0153] Example 24: Product 24#

[0154] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 25 ml of water. Add 0.4 g of NaOH, alkalize for 1 h, add 15.2 g of GTA, and react at 25 °C for 20 h. After the reaction, add 225 ml of purified water, adjust the pH to 6.5 ± 0.5, add 9.76 g of MES to adjust the solution pH to 4 ± 0.2, add 5.67 g of GTA, heat up to 80 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of the product of No. 23 is 3.47 g, and the total cationization degree is 2.11.

[0155] In the process of preparing the cationized hyaluronic acid products No. 1# to No. 23# in the above Examples 1 - 23, the process conditions are specifically shown in Table 1 below, and the cationization degrees of the products are shown in Table 2.

[0156] Table 1

[0157]

[0158]

[0159] Table 2

[0160]

[0161] The results show that it can be seen from Examples 1 - 4 that the alkali concentration in the etherification stage has a certain influence on the reaction efficiency. When the alkali concentration is too low, the catalytic concentration for sufficient reaction cannot be achieved, and the reaction efficiency is low. When the alkali concentration is too high, the product will decompose and the reaction efficiency will decrease.

[0162] It can be seen from Examples 2, 5 - 9 that with the increase of the molar ratio of HA to the cationization reagent in the etherification stage, the cationization degree gradually increases. When the molar ratio reaches 1:10, the cationization degree can reach 2.22. However, when the substitution degree is too high, the substitution in the subsequent esterification stage will be reduced. Therefore, the substitution degree in the etherification stage should not be too high.

[0163] It can be seen from Examples 8, 10 - 11 that with the increase of the etherification reaction temperature, the cationization degree of the product decreases. Too high a temperature is not conducive to the reaction efficiency. Moreover, with the increase of temperature, the color of the reaction solution changes from yellow to red - brown, and the color of the final product also becomes darker, which is not conducive to obtaining a product with stable properties.

[0164] It can be seen from Examples 2 and 12 - 14 that when the molecular weight of HA is in the range of 9 kDa - 960 kDa, cationized hyaluronic acid or its salt with a cationization degree of 0.1 - 4.3 can be obtained.

[0165] Comparative Example 1

[0166] Weigh 5 g of HA with a molecular weight of 226 kDa and dissolve it in 200 ml of water. Add 9.76 g of MES and dissolve it. Dissolve 5.67 g of GTA in 50 ml of water, add it to the HA solution, heat up to 60 °C, and react for 15 h. After the reaction is completed, add 12.5 g of NaCl, then add 750 ml of 95% ethanol for precipitation, wash three times with 250 ml of 85% ethanol, dehydrate twice with 250 ml of 95% ethanol, filter by suction, and after vacuum drying, the weight of the product 23# is 4.97 g, and the degree of cationization is 0.25.

[0167] Experimental Example 1: Adsorption Test on Damaged Hair

[0168] Experimental Principle: Measure the absorbance of different cationized hyaluronic acids and HA solutions before and after adsorption on hair by an ultraviolet spectrophotometer to observe the adsorption ability of cationized hyaluronic acid and HA on hair.

[0169] Experimental Method:

[0170] (1) Preparation of sample solution: Use products 7#, 18#, Comparative Example 1, and HA to prepare 0.1% aqueous solutions as stock solutions respectively, and dilute the stock solutions to 0.008% sample solutions as test solutions.

[0171] (2) Preparation of damaged hair: Immerse human black hair in a 1% aqueous solution of ammonium lauryl polyether sulfate for 1 min. Then wash the human black hair with water, dry it with a towel, remove the moisture with a paper towel, and dry it with a dryer (cleaning treatment). Then carry out the bleaching treatment in the following order: First, mix 5% hydrogen peroxide aqueous solution and 2.5% ammonia aqueous solution in a volume ratio of 1:1 to prepare a bleaching solution, and immerse the human black hair in this bleaching solution at 30 °C for 20 min (bleaching treatment). After immersion, wash it, and repeat the immersion-washing step 10 times to make damaged hair.

[0172] (3) Adsorption test on damaged hair: Accurately weigh 1.00 g of dry and clean damaged hair into a plastic vial; preheat the 0.008% test solution in a 37 °C water bath; transfer 10 ml of the test solution, soak the hair, and keep it in a 37 °C water bath for 10 min; pipette 1 ml of the test solution adsorbed by the hair and add it to a glass test tube, and measure it by the carbazole colorimetric method; take another 1 ml of the test solution not adsorbed by the hair and add it to a glass test tube, and measure it by the carbazole colorimetric method.

[0173] Test Method:

[0174] 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°C dropwise while shaking, and shake well. After heating in a boiling water bath for 10 min, cool in an ice water bath, accurately add 0.20 ml of carbazole reagent, shake well, place in a boiling water bath and heat for 15 min to develop a purplish red color.

[0175] The calculation formula for the adsorption rate is: Adsorption rate = (Average absorbance before adsorption - Average absorbance after adsorption) / Average absorbance before adsorption × 100%.

[0176] Calculate the adsorption improvement rate based on the comparison of the adsorption rates of cationized hyaluronic acid and hyaluronic acid HA. The calculation formula is: Adsorption improvement rate = (Adsorption rate of cationized hyaluronic acid - Adsorption rate of HA) / Adsorption rate of HA × 100%.

[0177] The test results are shown in Table 3 below.

[0178] Table 3

[0179]

[0180] The adsorption effects of damaged hair on various samples are: Product 18# > Product 24# > Product 15# > Product 7# > Comparative Example 1 > HA. That is, it shows that both the cationized hyaluronic acid product and HA have the ability to adsorb on damaged hair. The adsorption effect of the cationized HA sample is better than that of the non-cationized HA. And by comparing the adsorption improvement rates of Product 18#, Product 7# and Comparative Example 1 compared with hyaluronic acid, it can be found that the cationized hyaluronic acid with the structure of this application has a synergistic effect in the adsorption effect compared with the simply esterified or simply etherified cationic hyaluronic acid, indicating that the cationized hyaluronic acid of this application is more conducive to retention on hair.

[0181] Therefore, the cationized hyaluronic acid of this application is suitable for being added to hair washing and hair care products and can promote the repair of damaged hair quality.

[0182] It should be noted that the above-mentioned embodiments only exemplarily give the cationized hyaluronic acid or its salt prepared when the cationic reagent is GTA. By selecting other cationic reagents that can satisfy the formulas (II) and (III) in the above text and using the method of the present application, the substitution of the hydroxyl group and carboxyl group of hyaluronic acid or its salt can be achieved, and cationized hyaluronic acid with a total cationization degree of 0.1 to 4.5 can be obtained, thereby solving the technical problem of the present application, that is, the high moisture retention of hyaluronic acid itself can be retained, and the adsorption property of the cationic side chain to hair can be increased, endowing the product with good hydrophilicity and affinity. When applied to hair improvement products and cosmetics, it can directly adsorb on the hair surface to keep it moist and smooth, and is not easy to lose, thus achieving a good moisturizing effect. Since there are many types of raw materials involved in the above-mentioned cationic reagents, they will not be listed one by one in the present application. Those skilled in the art can infer that the resins with the above structures can all achieve the above functions and thus achieve the above effects on the basis of clarifying the technical concept of the present application.

[0183] The above description of the embodiments is to enable those of ordinary skill in the art to understand and use the invention. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative efforts. Therefore, the present invention is not limited to the above embodiments, and all improvements and modifications made by those skilled in the art without departing from the scope of the present invention according to the disclosure of the present 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 the following formula (I): In formula (I), A1 is independently H or A2 is independently a metal ion, H or n represents a positive integer representing the degree of polymerization; m is 1 to 5; In the structure of the above-mentioned cationized hyaluronic acid or its salt, at least one hydroxyl group and at least one carboxyl group are simultaneously cationized.

2. The cationized hyaluronic acid or a salt thereof 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 with a carbon number of 1 to 12; 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 cationized hyaluronic acid or a salt thereof according to claim 1, characterized in that The degree of polymerization n=10-2500, preferably 20-1500.

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

3.

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

3.

6. The method for preparing a cationized hyaluronic acid or a salt thereof according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) dissolving hyaluronic acid or its salt in an alkaline aqueous solution, adding a cationizing agent after alkalization to carry out an etherification reaction to obtain a solution I; preferably, the alkali in the alkaline aqueous solution is an inorganic alkali or an organic alkali, and the inorganic alkali or organic alkali is a conventional inorganic alkali or organic alkali in the art and is not particularly limited; more preferably, the alkali is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium alcoholate, and potassium alcoholate; the concentration of the alkaline aqueous solution is 0.2 to 1.5 mol / L; (2) directly adding acid to adjust the pH of the reaction solution I to 3-5, or first adding acid to adjust the pH of the reaction solution I to 6-7 and then adding an acidic buffer to 3-5, to obtain solution II; preferably, the acid or acidic buffer is selected from at least one of hydrochloric acid, acetic acid, acetic acid-sodium acetate, and MES, and more preferably MES; (3) adding a cationizing agent to solution II for esterification reaction to obtain solution III; (4) Purifying solution III to obtain a pure solid product of cationized hyaluronic acid or its salt.

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

9. A composition, characterized in that The invention comprises the cationized hyaluronic acid or its salt according to any one of claims 1 to 5, or the cationized hyaluronic acid or its salt prepared by the preparation method according to any one of claims 6 to 8.

10. Use of the cationized hyaluronic acid or its salt according to any one of claims 1 to 5, or the cationized hyaluronic acid or its salt prepared by the preparation method according to any one of claims 6 to 8, or the composition according to claim 9 in the preparation of cosmetics or medical devices, preferably in the preparation of cosmetics or medical devices that improve hair adsorption.

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