CN110790960A - Hyaluronic acid quaternary ammonium salt crosslinked powder and preparation method and application thereof - Google Patents
Hyaluronic acid quaternary ammonium salt crosslinked powder and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to the technical field of hyaluronic acid, in particular to hyaluronic acid quaternary ammonium salt cross-linked powder and a preparation method and application thereof: dissolving a hyaluronic acid compound in purified water, adding quaternary ammonium salt, adding EDC and NHS, stirring until the hyaluronic acid compound is dissolved, reacting at normal temperature, maintaining the pH value of the solution acidic during the reaction until the pH value of the solution does not rise any more, adding a certain amount of sodium hydroxide and a crosslinking agent, stirring and heating; diluting with purified water after the crosslinking reaction is finished, precipitating with an organic solvent, dehydrating, adjusting the pH value to be neutral, and drying in vacuum to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The method has relatively simple production process, is environment-friendly and is suitable for industrial production. The hyaluronic acid quaternary ammonium salt cross-linked powder has good moisture absorption performance, has a care effect on human skin and hair, and is smooth in skin feel and not sticky after being prepared into a solution. The product has good application prospect in the field of daily chemicals.
Description
Technical Field
The invention relates to the technical field of hyaluronic acid, and particularly relates to hyaluronic acid quaternary ammonium salt cross-linked powder as well as a preparation method and application thereof.
Background
Hyaluronic acid is an acidic mucopolysaccharide and is widely found in tissues such as skin, ligaments, eyes and joint fluid of the human body. Hyaluronic acid has effects of keeping moisture, removing wrinkle, softening skin, promoting proliferation and differentiation of epidermal cell, scavenging oxygen free radical, and preventing and repairing skin injury. Hyaluronic acid is the best natural moisturizing component of high-grade cosmetics, has good compatibility, can be added into almost any cosmetic, and can be widely used in cosmetics such as cream, lotion, astringent, essence, facial cleanser, bath lotion, shampoo, mousse, lipstick and the like.
The hyaluronic acid quaternary ammonium salt greatly enhances the adhesion of hyaluronic acid to human hair and skin due to the charge effect, and improves the effect efficiency of hyaluronic acid to human tissues. After the hyaluronic acid quaternary ammonium salt is crosslinked, the space structure of the chain-shaped hyaluronic acid is changed into a stable reticular space structure, the water locking capacity of the chain-shaped hyaluronic acid is greatly improved, and the crosslinked hyaluronic acid quaternary ammonium salt is smooth and not sticky in skin feel.
Patent publication No. CN107739417A discloses a method for preparing cationized hyaluronic acid, which couples hyaluronic acid with a cationic reagent, namely glycidyltrimethylammonium chloride, and the reaction occurs under alkaline conditions, which easily results in degradation of hyaluronic acid and results in low hydrogel viscosity.
Patent publication No. CN 103923328A discloses a high-quality cross-linked sodium hyaluronate gel and a preparation method thereof, which comprises the steps of dissolving sodium hyaluronate in a solution mixed by sodium hydroxide and acetone, cross-linking with BDDE, drying to obtain cross-linked powder, washing the cross-linked powder by DMSO, washing by ethanol, drying in vacuum, swelling the powder, and purifying to obtain the sodium hyaluronate gel. The preparation process of the patent needs a large amount of organic reagents, so that the environmental pollution is easily caused, and the organic reagents are easily remained in the product.
Patent publication No. CN 108484794A discloses a hyaluronic acid quaternary ammonium group derivative and a preparation and purification method thereof, which comprises the steps of adding hyaluronic acid into ethanol, adding 2, 3-glycidyl trimethyl ammonium chloride and initiator cerium ammonium sulfate, performing nitrogen protection, standing after the reaction is finished, adding isopropanol, washing and precipitating, dissolving with purified water, washing and precipitating with ethanol, repeating twice, performing suction filtration and drying. The preparation process needs anaerobic operation, has harsh industrial production conditions, needs repeated precipitation, dissolution and purification, and is easy to cause product loss.
Disclosure of Invention
The invention aims to provide hyaluronic acid quaternary ammonium salt cross-linked powder which has excellent water solubility, can be prepared into solutions or gels with different viscosities according to requirements, and has smooth skin feel and no stickiness.
The invention also aims to provide a preparation method of the powder, which has relatively simple production process, is environment-friendly and is suitable for industrial production.
The invention also provides the application of the powder.
In order to achieve the purpose, the invention adopts the following technical scheme:
a hyaluronic acid quaternary ammonium salt crosslinked powder, wherein the general formula of the crosslinked material is as follows:
in the formula, R is quaternary ammonium salt or hydroxyl, and Y is a cross-linking agent or a hydrogen atom.
Further, the quaternary ammonium salt has a general formula:
in the formula，R1、R2、R3Each represents an alkyl group having 1 to 3 carbon atoms, R4Represents an alkyl group or other organic functional group, and X represents a halogen atom.
Preferably, the number of carbon atoms in the quaternary ammonium salt should be less than 10.
Preferably, the 0.2% aqueous solution is colorless transparent viscous solution with smooth skin feeling, and has light transmittance of 90% or more, viscosity of 500 mPa & s or more, and pH value of 6.00-8.00.
The preparation method of the hyaluronic acid quaternary ammonium salt crosslinked powder comprises the following steps:
(1) dissolving a hyaluronic acid compound in a certain volume of purified water, adding a certain amount of quaternary ammonium salt after hyaluronic acid is fully dissolved, adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, stirring until the hyaluronic acid is dissolved, adjusting the pH value of the solution by using 1mol/L hydrochloric acid during the reaction, keeping the pH value at 4.50-6.00, and finishing the reaction when the pH value does not rise any more;
(2) adding sodium hydroxide into the reaction liquid prepared in the step (1), adding a cross-linking agent, and heating at a certain temperature
Stirring and reacting for 4 hours, after the reaction is finished, adding purified water with the volume 3 times that of the reaction solution for dilution, precipitating by using an organic solvent with the volume 2.5 times that of the reaction solution, dehydrating, adjusting the pH value to 6.5-7.5, and performing suction filtration to obtain wet powder;
(3) and drying the obtained wet powder to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder.
Preferably, the hyaluronic acid compound of step (1) is dissolved in water at a concentration of 0.05-0.14g/ml
The hyaluronic acid is hyaluronic acid or hyaluronate; the molecular weight of the hyaluronic acid compound is
1×106Da-3×106At Da, the mass ratio of the solid crosslinking agent to the hyaluronic acid compound is 1: 30-40 parts of; the volume mass ratio of the liquid cross-linking agent to the hyaluronic acid compound is 4.2-6.35 μ l: 1g of the total weight of the composition. When the molecular weight of the hyaluronic acid compound is 5 x 105-9 x 105Da, the mass ratio of the solid cross-linking agent to the hyaluronic acid is 1: 10-20.
Preferably, the water in the step (1) and the water in the step (2) are both purified water; the step (1) mentioned above
The mass ratio of the hyaluronic acid compound to the 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) is
1: 0.3, the mass ratio of the hyaluronic acid compound to the N-hydroxysuccinimide (NHS) is 1: 0.2, through
The mass ratio of the bright acid compound quaternary ammonium salt is 1: 0.4; adding the cross-linking agent, stirring and heating to
20-50 ℃, preferably 30-40 ℃; the mass ratio of the hyaluronic acid compound to the sodium hydroxide in the step (2) is
1: 0.08; and (3) drying, namely drying the obtained wet powder in a vacuum drying oven at the temperature of 30-40 ℃.
Preferably, in step (2), an organic reagent is added in an amount of 2.5 times the volume of the reaction solution after the reaction is completed
The organic reagent added for precipitation is one or more of ethanol, methanol, acetone and diethyl ether; step (2)
The selected cross-linking agent is sodium trimetaphosphate, divinyl sulfone, 1, 4-butanediol diglycidyl ether, diglycidyl
Ethers, 1, 3-diglycidyl ether glycerol, neopentyl glycol diglycidyl ether, 4' -biphenol diglycidyl ether
And butadiene diepoxide.
Preferably, the pH is adjusted to 4.50-6.00 by adding hydrochloric acid in the step (1); adding quaternary ammonium salt while maintaining pH at 4.50-6.00.
The application of the hyaluronic acid quaternary ammonium salt crosslinked powder is applied to the field of daily chemicals.
Advantageous effects
The hyaluronic acid quaternary ammonium salt cross-linked powder prepared by the invention has excellent water solubility, can be prepared into solutions or gels with different viscosities according to requirements, and has smooth skin feel and no stickiness. The cross-linked hyaluronic acid quaternary ammonium salt has good adhesion to human hair and skin, and improves the effect efficiency of hyaluronic acid on human tissues. After the hyaluronic acid quaternary ammonium salt is crosslinked, the space structure of the chain-shaped hyaluronic acid is changed into a stable reticular space structure, the water locking capacity of the chain-shaped hyaluronic acid is greatly improved, and the sticky skin feeling of the hyaluronic acid quaternary ammonium salt is improved. The preparation process is simple, environment-friendly and suitable for industrial production, and the product has good application prospect in the field of daily chemicals.
Drawings
FIG. 1 is a skin moisture content test chart;
FIG. 2 is a skin feel evaluation test chart;
fig. 3 is a hair combing test chart.
Detailed Description
For a better understanding of the present invention, reference will now be made to the following examples and comparative examples,
however, the present invention is not limited to the following specific examples.
Example 1
Accurately weighing 150ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 3 × 10)6Da), pass through
After hyaluronic acid is fully dissolved, 8g of trimethyl ammonium acethydrazide chloride is added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g of N-hydroxysuccinimide (NHS) are added and stirred until the hyaluronic acid is dissolved, 1mol/L of hydrochloric acid is used for maintaining the pH value of the solution at 4.50 during the reaction, the reaction is ended when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 0.5g of sodium trimetaphosphate serving as a crosslinking agent are added, the temperature is increased to 40 ℃, the stirring is carried out, and the reaction is ended after 4 hours. Adding 450ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a viscous solution having colorless transparency, smooth skin feel, and dynamic viscosity of 960 mPas.
Example 2
Accurately weighing 400ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid was sufficiently dissolved, 8g of trimethylammonium chloride acethydrazide was added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) were further added and stirred until dissolved,
during the reaction, 1mol/L hydrochloric acid is used to maintain the pH value of the solution at 6.00, the reaction is finished when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 0.66g of cross-linking agent sodium trimetaphosphate are added, the temperature is raised to 30 ℃, the stirring is carried out, and the reaction is finished after 4 hours. Diluting the reaction solution with 1.2L of purified water, adding ethanol 2.5 times the volume of the reaction solution, precipitating, standing, pouring out the supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.9 with hydrochloric acid,
and (4) performing suction filtration, and drying the wet powder in a vacuum drying oven at 40 ℃ overnight to obtain hyaluronic acid quaternary ammonium salt crosslinked powder.
The 0.2% water solution of the above powder is colorless and transparent, and has smooth skin feeling and dynamic viscosity of 723 mPas
A thick solution.
Example 3
Accurately weighing 150ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 9 × 10)5Da) to be
After hyaluronic acid is fully dissolved, 8g of trimethyl ammonium acethydrazide chloride is added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) are added and stirred until the hyaluronic acid is dissolved, 1mol/L of hydrochloric acid is used for maintaining the pH value of the solution at 4.75 during the reaction, the reaction is ended when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 1g of sodium trimetaphosphate serving as a crosslinking agent are added, the temperature is increased to 40 ℃, the stirring is carried out, and the reaction is ended after 4 hours. Adding 450ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a viscous solution which was colorless and transparent, had smooth skin feel and had a kinematic viscosity of 866 mPas.
Example 4
Accurately weighing 400ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 5 × 10)5Da) to be
After hyaluronic acid is fully dissolved, 8g of trimethyl ammonium acethydrazide chloride is added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) are added and stirred until the hyaluronic acid is dissolved, 1mol/L of hydrochloric acid is used for maintaining the pH value of the solution at 4.75 during the reaction, the reaction is ended when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 2g of sodium trimetaphosphate serving as a crosslinking agent are added, the temperature is increased to 40 ℃, the stirring is carried out, and the reaction is ended after 4 hours. Adding 1.2L of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 7.1 with hydrochloric acid, performing suction filtration, and drying the wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a viscous solution having colorless transparency, smooth skin feel, and dynamic viscosity of 628 mPas.
Example 5
20g of potassium hyaluronate (molecular weight 3X 10) is selected for the experiment6Da), the rest steps are the same as example 1.
The 0.2% aqueous solution of the above powder is colorless and transparent, and has smooth skin feeling and dynamic viscosity of 931 mPas
A thick solution.
Example 6
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da），
After hyaluronic acid was sufficiently dissolved, 8g of trimethylammonium chloride acethydrazide was added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) were added and stirred until dissolved, the pH of the solution was maintained at 4.75 with 1mol/L hydrochloric acid during the reaction, the reaction was terminated when the reaction pH did not rise any more, 10ml of 4mol/L sodium hydroxide solution and 84. mu.l of 1, 4-butanediol diglycidyl ether were added and stirred at 30 ℃ for 4 hours, and the reaction was terminated. Adding 600ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.9 with hydrochloric acid, performing suction filtration, and drying wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was colorless and transparent, and had smooth skin feel and dynamic viscosity of 582 mPas.
Example 7
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid was sufficiently dissolved, 8g of trimethylammonium chloride acethydrazide was added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) were further added and stirred until dissolved, the pH of the solution was maintained at 4.75 with 1mol/L hydrochloric acid during the reaction, the reaction was terminated when the reaction pH did not rise, 10ml of 4mol/L sodium hydroxide solution and 127. mu.l of 1, 4-butanediol diglycidyl ether were added and stirred at 30 ℃ for 4 hours, and the reaction was terminated. Adding 600ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out the supernatant, dehydrating twice with ethanol, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying the wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a viscous solution which was colorless and transparent, had smooth skin feel and had a kinematic viscosity of 864 mPas.
Example 8
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid was sufficiently dissolved, 8g of trimethylammonium chloride acethydrazide was added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) were further added and stirred until dissolved, the pH of the solution was maintained at 4.75 with 1mol/L hydrochloric acid during the reaction, the reaction was terminated when the reaction pH did not rise, 10ml of 4mol/L sodium hydroxide solution and 84. mu.l of divinylsulfone were added and stirred at 30 ℃ for 4 hours, and the reaction was terminated. Adding 600ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying the wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a viscous solution having colorless transparency, smooth skin feel, and dynamic viscosity of 815 mPas.
Example 9
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid was sufficiently dissolved, 8g of trimethylammonium chloride acethydrazide was added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) were added and stirred until dissolved, the pH of the solution was maintained at 4.75 with 1mol/L hydrochloric acid during the reaction, the reaction was terminated when the reaction pH did not rise any more, 10ml of 4mol/L sodium hydroxide solution was added, stirring 84 mu l of 1, 3-diglycidyl ether glycerol at 30 ℃, finishing the reaction after 4 hours, adding 600ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out the supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying the wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a viscous solution which was colorless and transparent, had smooth skin feel, and had a dynamic viscosity of 736mPa · s.
Comparative example 1
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 7 × 10)5Da) to be
After hyaluronic acid is fully dissolved, 8g of trimethylammonium chloride acethydrazide is added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) are added and stirred until the hyaluronic acid is dissolved, 1mol/L of hydrochloric acid is used for maintaining the pH value of the solution at 4.75 during the reaction, the reaction is ended when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 0.5g of cross-linking agent sodium trimetaphosphate are added, the temperature is increased to 40 ℃, the stirring is carried out, and the reaction is ended after 4 hours. Diluting the reaction solution with 600ml of purified water, adding ethanol with 2.5 times of the volume of the reaction solution to precipitate, standing for a period of time, removing the supernatant, dehydrating with ethanol twice, adjusting the pH value of the precipitation solution to 6.8 with hydrochloric acid, and filtering. Vacuum drying at 30 deg.C overnight to obtain hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was colorless and transparent, and had a dynamic viscosity of 230 mPas.
Comparative example 2
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid is fully dissolved, 8g of trimethylammonium chloride acethydrazide is added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) are added and stirred until the hyaluronic acid is dissolved, 1mol/L of hydrochloric acid is used for maintaining the pH value of the solution at 4.75 during the reaction, the reaction is ended when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 0.66g of cross-linking agent sodium trimetaphosphate are added, the temperature is increased to 60 ℃, and the stirring is carried out, and the reaction is ended after 4 hours. Adding 600ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was a relatively viscous solution which was colorless and transparent, smooth in skin feel, and had a dynamic viscosity of 436 mPas.
Comparative example 3
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid is fully dissolved, 8g of trimethyl ammonium acethydrazide chloride is added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) are added and stirred until the hyaluronic acid is dissolved, 1mol/L of hydrochloric acid is used for maintaining the pH value of the solution at 4.75 during the reaction, the reaction is ended when the reaction pH value does not rise any more, 10ml of 4mol/L sodium hydroxide solution and 1g of sodium trimetaphosphate serving as a crosslinking agent are added, the temperature is increased to 40 ℃, the stirring is carried out, and the reaction is ended after 4 hours. Adding 600ml of purified water to dilute the reaction solution, adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying wet powder in a vacuum drying oven at 30 ℃ overnight to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder. The 0.2% aqueous solution obtained from the above powder was milky white and had a dynamic viscosity of 159 mPas.
Comparative example 4
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid is fully dissolved, 10ml of 4mol/L sodium hydroxide solution and 0.5g of cross-linking agent sodium trimetaphosphate are added,
the temperature is increased to 40 ℃ and the mixture is stirred, and the reaction is finished after 4 hours. 600ml of purified water was added to dilute the reaction solution, and then
Precipitating with 2.5 times of ethanol, standing, removing supernatant, dehydrating with ethanol twice, and regulating with hydrochloric acid
Precipitating to pH 6.8, vacuum filtering, drying wet powder in vacuum drying oven at 30 deg.C overnight to obtain hyaluronic acid
Acid crosslinking the powder. The 0.2% aqueous solution obtained from the above powder is milky white, smooth in skin feel, and has dynamic viscosity of
748 mPas in viscous solution.
Comparative example 5
Accurately weighing 200ml of purified water, adding 20g of sodium hyaluronate (molecular weight of 1 × 10)6Da) to be
After hyaluronic acid was sufficiently dissolved, 8g of trimethylammonium chloride acethydrazide was added, 6g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 4g N-hydroxysuccinimide (NHS) were stirred until dissolved, and the reaction was terminated when the pH of the solution was maintained at 4.75 with 1mol/L hydrochloric acid during the reaction and when the pH of the reaction did not rise any more. Adding ethanol with the volume 2.5 times of that of the reaction solution for precipitation, standing, pouring out supernatant, dehydrating with ethanol twice, adjusting the pH of the precipitation solution to 6.8 with hydrochloric acid, performing suction filtration, and drying wet powder in a vacuum drying oven at 30 ℃ overnight to obtain hyaluronic acid quaternary ammonium salt powder. The 0.2% aqueous solution obtained from the above powder was colorless and transparent, had smooth skin feel and had a kinematic viscosity of 120 mPas.
Effect study of hyaluronic acid Quaternary ammonium salt crosslinked powder
Skin moisture test
20 subjects aged 25-35 were recruited and two 3X 3cm markers were marked on the left and right forearms of the subjects
The test area of (1) was coated with each of comparative example 4 having a concentration of 0.2% and example 1 having a concentration of 0.2%, by the amount of
2 + -0.1 mg/CM2, gently massaging until the sample is absorbed, and using a skin moisture tester Corneometer CM 825
And (5) carrying out a test, and drawing a graph according to the average growth rate of the tested population.
The experimental results are as follows: product without quaternization of hyaluronic acid (comparative example 4) and product with hyaluronic acid
The product of example 1 provides longer retention of skin than the product of example 1, indicating that the product has a longer duration of action on the skin.
Skin feel evaluation test
20 subjects aged 25-35 years were recruited and each subject was smeared on the back of the left hand at a concentration of 0.2%
Example 1 and comparative example 5 at a concentration of 0.2%, the sample on the back of the left hand was gently rubbed between the index finger and middle finger of the right hand
And (4) carrying out somatosensory test, and dividing the somatosensory effect into three categories, namely no feeling, stickiness, greasiness and smoothness.
The experimental results are as follows: the product not crosslinked with hyaluronic acid (comparative example 5) was crosslinked with hyaluronic acid
The combined product (example 1) had a smoother skin feel and no slimy feel as compared to the product of example 1.
Hair combing test
Subjects were recruited 20 years of age 25-35 years and first washed with a basal shampoo to eliminate individual hair variation. Washing and drying, dividing the hair into two parts, firstly testing the combing work of the hair without any sample, then coating 0.2% concentration of example 1 on one side, coating 0.2% concentration of comparative example 4 on the other side, rubbing for 20 minutes, washing, drying, testing by using a hair combing property tester TA, and drawing according to the average value of the number of tested people.
The experimental results are as follows: the unmodified hyaluronic acid, the product without quaternization of hyaluronic acid (comparative example 4) compared to the product with quaternization of hyaluronic acid (example 1), the product of example 1 was adsorbed on human hair, making the hair smoother and reducing the resistance to combing.
TABLE 1
Claims (10)
1. A hyaluronic acid quaternary ammonium salt crosslinked powder, characterized in that the general formula of the crosslinked product is:
in the formula, R is quaternary ammonium salt or hydroxyl, and Y is a cross-linking agent or a hydrogen atom.
2. The crosslinked powder of hyaluronic acid quaternary ammonium salt according to claim 1, characterized in that said quaternary ammonium salt has the general formula:
in the formula, R1、R2、R3Each represents an alkyl group having 1 to 3 carbon atoms, R4Represents an alkyl group or other organic functional group, and X represents a halogen atom.
3. The crosslinked powder of hyaluronic acid quaternary ammonium salt according to claim 2, characterized in that the number of carbon atoms in the quaternary ammonium salt is less than 10.
4. The cross-linked powder of hyaluronic acid quaternary ammonium salt according to any one of claims 1-3, wherein the 0.2% aqueous solution is colorless and transparent, and smooth and sticky to skin, and has a light transmittance of 90% or more, a viscosity of 500 mPa-s or more, and a pH value of 6.00-8.00.
5. The method for preparing the hyaluronic acid quaternary ammonium salt crosslinked powder of any one of claims 1-4, characterized by comprising the following steps:
(1) dissolving a hyaluronic acid compound in a certain volume of purified water, adding a certain amount of quaternary ammonium salt after hyaluronic acid is fully dissolved, adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, stirring until the hyaluronic acid is dissolved, adjusting the pH value of the solution by using 1mol/L hydrochloric acid during the reaction, keeping the pH value at 4.50-6.00, and finishing the reaction when the pH value does not rise any more;
(2) adding sodium hydroxide into the reaction liquid prepared in the step (1), adding a cross-linking agent, and heating at a certain temperature
Stirring and reacting for 4 hours, after the reaction is finished, adding purified water with the volume 3 times that of the reaction solution for dilution, precipitating by using an organic solvent with the volume 2.5 times that of the reaction solution, dehydrating, adjusting the pH value to 6.5-7.5, and performing suction filtration to obtain wet powder;
(3) and drying the obtained wet powder to obtain the hyaluronic acid quaternary ammonium salt crosslinked powder.
6. The method of claim 5, wherein the hyaluronic acid compound of step (1)
The concentration of the substance dissolved in water is 0.05g/ml-0.14 g/ml; the hyaluronic acid compound is hyaluronic acid or hyaluronic acid
A salt of a hyaluronic acid; the molecular weight of the hyaluronic acid compound is 1 × 106Da-3×106At Da, the solid cross-linking agent is permeated
Mass ratio of the bright acid compound 1: 30-40 parts of; volume-to-mass ratio of liquid crosslinking agent to hyaluronic acid compound
4.2. mu.l-6.35. mu.l: 1g of a compound; the molecular weight of the hyaluronic acid compound is 5 x 105-9×105At Da, solid crosslinking
The mass ratio of the agent to the hyaluronic acid is 1: 10-20.
7. The method according to claim 5, wherein the steps (1) and (2) are carried out in the same manner as described above
The water of (a) is purified water; the mass ratio of the hyaluronic acid compound in the step (1) to 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) is 1: 0.3, the mass ratio of the hyaluronic acid to the N-hydroxysuccinimide (NHS) is 1: 0.2, the mass ratio of the hyaluronic acid compound to the quaternary ammonium salt is 1: 0.4; adding a cross-linking agent, stirring, heating to 20-50 ℃, preferably 30-40 ℃; the mass ratio of the hyaluronic acid compound in the step (2) to the sodium hydroxide is 1: 0.08; and (3) drying, namely drying the obtained wet powder in a vacuum drying oven at the temperature of 30-40 ℃.
8. The preparation method according to claim 5, characterized in that, in the step (2), after the reaction is finished, an organic reagent with the volume 2.5 times that of the reaction liquid is added for precipitation, and the added organic reagent is one or more of ethanol, methanol, acetone and diethyl ether; the crosslinking agent selected in the step (2) is one or more of sodium trimetaphosphate, divinyl sulfone, 1, 4-butanediol diglycidyl ether, 1, 3-diglycidyl ether glycerol, neopentyl glycol diglycidyl ether, 4' -biphenol diglycidyl ether and butadiene dioxide.
9. The method according to claim 5, wherein the pH is adjusted to 4.50 to 6.00 by adding hydrochloric acid in the step (1).
10. The use of the crosslinked powder of hyaluronic acid quaternary ammonium salt according to any of claims 1 to 4, wherein the crosslinked powder of hyaluronic acid quaternary ammonium salt is used in the field of daily chemicals.
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| CN112724278A (en) * | 2020-12-24 | 2021-04-30 | 华熙生物科技股份有限公司 | Hyaluronic acid graft copolymer and preparation method and application thereof |
| CN112773734A (en) * | 2020-12-28 | 2021-05-11 | 杭州欧菲健康科技有限公司 | Hyaluronic acid skin-changing essence and preparation method thereof |
| CN116410346A (en) * | 2021-12-31 | 2023-07-11 | 华熙生物科技股份有限公司 | Reductive hyaluronic acid ester and preparation method thereof |
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