CN113214511A - Preparation method of colored cross-linked sodium hyaluronate gel and gel particles - Google Patents
Preparation method of colored cross-linked sodium hyaluronate gel and gel particles Download PDFInfo
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Abstract
The invention discloses a preparation method of a colored cross-linked sodium hyaluronate gel, which comprises the following steps: dissolving a dye in an acidic or alkaline solution, and uniformly stirring to obtain a first solution; adding a cross-linking agent into the first solution, and uniformly stirring to obtain a second solution; and adding sodium hyaluronate into the second solution, uniformly mixing, keeping constant temperature, and performing crosslinking reaction within a given time to obtain the colored crosslinked sodium hyaluronate gel. The invention also relates to application of the colored cross-linked hyaluronic acid gel. The invention discloses a preparation method of a colored cross-linked sodium hyaluronate gel and particles thereof, the colored cross-linked sodium hyaluronate gel prepared by the method is firm and uniform in coloring, the colored gel particles are not decolored in a solution, and the gel and the particles thereof also have the effects of moisturizing and resisting wrinkles.
Description
Technical Field
The application relates to the field of cosmetic raw materials, and more particularly relates to a preparation method of a colored cross-linked sodium hyaluronate gel and gel particles.
Background
Hyaluronic Acid (HA), also known as hyaluronic acid, is a long-chain polymeric mucopolysaccharide composed of alternating arrangements of D-glucuronic acid and N-acetylglucosamine. Hyaluronic acid is an endogenous substance in a human body, has good biocompatibility and safety, and also has good hydrophilicity, viscoelasticity and lubricity.
Both cross-linked and non-cross-linked hyaluronic acids have been widely used. The non-crosslinked hyaluronic acid is mainly used for skin moisturizing, and the addition amount is small, otherwise, the hyaluronic acid is sticky and can be drawn into mud, and the skin feeling is affected. The cross-linked sodium hyaluronate has rheological property which is not possessed by non-cross-linked hyaluronic acid, still retains good biocompatibility of hyaluronic acid, and is commonly used in the fields of medical and aesthetic plastic surgery, ophthalmic surgery, joint cavity injection and cosmetics. In view of the colorless property and the property of being not easily dyed, the application range of the cross-linked sodium hyaluronate gel in the field of cosmetics is limited, the cross-linked sodium hyaluronate gel is not applied to color cosmetics at present, and no report for preparing colored cross-linked sodium hyaluronate gel is provided.
Disclosure of Invention
The present application is proposed to solve the above-mentioned technical problems. The invention provides a preparation method of a colored cross-linked sodium hyaluronate gel and gel particles, the colored cross-linked sodium hyaluronate gel prepared by the method is firm and uniform in coloring, the colored gel particles are not decolored in a solution, and the gel and the particles thereof also have the effects of moisturizing and resisting wrinkles.
In order to achieve the purpose, the invention adopts the following technical scheme.
1. A preparation method of colored cross-linked sodium hyaluronate gel comprises the following steps:
dissolving a dye in an acidic or alkaline solution, and uniformly stirring to obtain a first solution;
adding a cross-linking agent into the first solution, and uniformly stirring to obtain a second solution;
and adding sodium hyaluronate into the second solution, uniformly mixing, keeping the constant temperature, and performing crosslinking reaction within a given time to obtain the colored crosslinked sodium hyaluronate gel.
2. The preparation method of the colored cross-linked sodium hyaluronate gel according to item 1, wherein the dye is natural dye or synthetic dye, and after the dye is dissolved in an acidic solution, the pH of the formed first solution is 2-5.
3. The preparation method of the colored cross-linked sodium hyaluronate gel according to item 1, characterized in that the dye is natural dye or synthetic dye, and after the dye is dissolved in alkaline solution, the pH of the formed first solution is 9-13.
4. The method for preparing a colored cross-linked sodium hyaluronate gel according to any one of claims 1 to 3, wherein said cross-linking agent is one or more selected from diglycidyl ether, divinyl sulfone, 1,2,7, 8-diepoxyoctane, 1, 3-diepoxybutane and sodium trimetaphosphate.
5. The method for preparing a colored crosslinked sodium hyaluronate gel according to any one of claims 1 to 4, wherein the molecular weight of the sodium hyaluronate is 50 to 350 ten thousand Da, preferably 80 to 250 ten thousand Da.
6. The method for preparing a colored crosslinked sodium hyaluronate gel according to any one of items 1 to 5, wherein the ratio of the addition amounts of the dye, the crosslinking agent and the sodium hyaluronate is (0.05 to 6): 0.1 to 15):100, preferably (0.1 to 3): 0.5 to 9): 100.
7. The method for preparing a colored cross-linked sodium hyaluronate gel according to any one of items 1 to 6, wherein sodium hyaluronate is added to the second solution, and the mixture is uniformly mixed, kept at a temperature of 20 to 50 ℃, preferably 25 to 40 ℃, and subjected to a cross-linking reaction within a given time of 2 to 72 hours, preferably 6 to 36 hours.
8. The method for preparing the colored crosslinked sodium hyaluronate gel according to any one of claims 1 to 7, wherein the content of sodium hyaluronate in the colored crosslinked sodium hyaluronate gel is 50-600 mg/g.
9. The method for preparing a colored crosslinked sodium hyaluronate gel according to any one of claims 1 to 8, wherein the colored crosslinked sodium hyaluronate gel is purified.
10. The method for preparing a colored crosslinked sodium hyaluronate gel according to item 9, wherein the colored crosslinked sodium hyaluronate gel is purified by one selected from phosphate buffered saline, physiological saline or water to obtain the purified colored crosslinked sodium hyaluronate gel.
11. The method for preparing a colored crosslinked sodium hyaluronate gel according to item 9 or 10, wherein the purified colored crosslinked sodium hyaluronate gel contains 8 to 50mg/g of sodium hyaluronate.
12. A preparation method of colored cross-linked sodium hyaluronate gel particles comprises the following steps:
dissolving a dye in an acidic or alkaline solution, and uniformly stirring to obtain a first solution;
adding a cross-linking agent into the first solution, and uniformly stirring to obtain a second solution;
adding sodium hyaluronate into the second solution, uniformly mixing, keeping constant temperature, and performing crosslinking reaction within a given time to obtain the colored crosslinked sodium hyaluronate gel;
and purifying and granulating the colored cross-linked sodium hyaluronate gel to obtain the colored cross-linked sodium hyaluronate gel particles.
13. The preparation method of the colored crosslinked sodium hyaluronate gel particle according to claim 12, wherein the dye is natural dye or synthetic dye, and after the dye is dissolved in an acidic solution, the pH of the formed first solution is 2-5.
14. The preparation method of the colored crosslinked sodium hyaluronate gel particle according to claim 12, wherein the dye is natural dye or synthetic dye, and after the dye is dissolved in an alkaline solution, the pH of the formed first solution is 9-13.
15. The method of preparing colored cross-linked sodium hyaluronate gel particles according to any one of claims 12 to 14, wherein said cross-linking agent is one or more selected from diglycidyl ether, divinyl sulfone, 1,2,7, 8-diepoxyoctane, 1, 3-diepoxybutane and sodium trimetaphosphate.
16. The method for preparing the colored crosslinked sodium hyaluronate gel particles according to any one of claims 12 to 15, wherein the molecular weight of the sodium hyaluronate is 50 to 350 ten thousand Da, preferably 80 to 250 ten thousand Da.
17. The method for preparing a colored crosslinked sodium hyaluronate gel particle according to any one of items 12 to 16, wherein the ratio of the addition amount of the dye, the crosslinking agent and the sodium hyaluronate is (0.05 to 6): 0.1 to 15):100, preferably (0.1 to 3): 0.5 to 9): 100.
18. The preparation method of the colored cross-linked sodium hyaluronate gel particles according to any one of claims 12 to 17, wherein sodium hyaluronate is added to the second solution, and the mixture is uniformly mixed, kept at a temperature of 20-50 ℃, preferably 25-40 ℃, and subjected to a cross-linking reaction within a given time of 2-72 hours, preferably 6-36 hours.
19. The preparation method of the colored cross-linked sodium hyaluronate gel particles according to any one of claims 12 to 18, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 50-600 mg/g.
20. The method for preparing the colored crosslinked sodium hyaluronate gel particles according to any one of claims 12 to 19, wherein the colored crosslinked sodium hyaluronate gel is purified by one selected from phosphate buffered saline, physiological saline or water.
21. The method for preparing the colored cross-linked sodium hyaluronate gel particle according to item 20, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel particle is 8-50 mg/g.
22. Use of a colored cross-linked sodium hyaluronate gel prepared according to the method of any one of claims 1 to 11 in the cosmetic field.
23. Use of the colored cross-linked sodium hyaluronate gel particles prepared according to the preparation method of any one of items 12 to 21 in the field of cosmetics.
According to the preparation method of the colored cross-linked sodium hyaluronate gel, the dye is added into a reaction system before cross-linking reaction, and the dye is wrapped in the sodium hyaluronate molecules while the sodium hyaluronate molecules form a three-dimensional structure along with the progress of the cross-linking reaction, so that the gel is firmly and uniformly colored, and colored gel particles are not decolored in a solution.
Detailed Description
The present invention will be described in detail below.
The invention provides a preparation method of a colored cross-linked sodium hyaluronate gel, which comprises the following steps:
the method comprises the following steps: dissolving a dye in an acidic or alkaline solution, and uniformly stirring to obtain a first solution;
step two: adding a cross-linking agent into the first solution, and uniformly stirring to obtain a second solution;
step three: and adding sodium hyaluronate into the second solution, uniformly mixing, keeping the constant temperature, and performing crosslinking reaction within a given time to obtain the colored crosslinked sodium hyaluronate gel.
In step one of the present invention, the dye is a natural dye or a synthetic dye.
The natural dyes include blue, green, red, yellow, violet, black and white.
The synthetic dye is a chemical synthetic dye prepared by a series of chemical treatment processing.
In the present invention, dyes include red, yellow and toluidine blue.
The acidic solution can be acetic acid, citric acid, lactic acid and the like with weak acidity, and the alkaline solution can be sodium hydroxide solution, potassium hydroxide solution, quaternary ammonium base solution and the like.
The first solution formed after dissolution of the dye in an acidic solution has a pH of 2 to 5, preferably 3 to 4, for example the pH may be 2, 3, 4 or 5.
The first solution formed after dissolution of the dye in the alkaline solution has a pH of 9 to 13, preferably 10 to 11, for example the pH may be 9, 10, 11, 12 or 13.
In step two of the present invention, the crosslinking agent is selected from one or more of diglycidyl ether, divinyl sulfone, 1,2,7, 8-diepoxyoctane, 1, 3-diepoxybutane and sodium trimetaphosphate.
In step three of the present invention, the molecular weight of the sodium hyaluronate is 50 to 350 ten thousand Da, preferably 80 to 250 ten thousand Da.
In the invention, the ratio of the addition amount of the dye, the cross-linking agent and the sodium hyaluronate is (0.05-6): 0.1-15): 100, preferably (0.1-3): 0.5-9): 100.
In the third step of the invention, sodium hyaluronate is added into the second solution, and the mixture is uniformly mixed, the temperature is kept between 20 and 50 ℃, preferably between 25 and 40 ℃, and the crosslinking reaction is carried out within a given time between 2 and 72 hours, preferably between 6 and 36 hours.
In the invention, the content of the sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 50-600 mg/g.
The invention also comprises a step four of purifying the colored cross-linked sodium hyaluronate gel.
In the fourth step of the invention, one of phosphate buffer solution, normal saline or water is adopted to purify the color cross-linked sodium hyaluronate gel, so as to obtain the purified color cross-linked sodium hyaluronate gel.
The pH value of the phosphate buffer solution is 5.8-8.4, and the mass of the buffer solution for purification is 1-4 times of that of the color cross-linked sodium hyaluronate gel.
In the invention, the content of the sodium hyaluronate in the purified colored cross-linked sodium hyaluronate gel is 8-50 mg/g.
The invention also relates to a preparation method of the colored cross-linked sodium hyaluronate gel particles, which comprises the following steps:
the method comprises the following steps: dissolving a dye in an acidic or alkaline solution, and uniformly stirring to obtain a first solution;
step two: adding a cross-linking agent into the first solution, and uniformly stirring to obtain a second solution;
step three: adding sodium hyaluronate into the second solution, uniformly mixing, keeping constant temperature, and performing crosslinking reaction within a given time to obtain the colored crosslinked sodium hyaluronate gel;
step four: and purifying and granulating the colored cross-linked sodium hyaluronate gel to obtain the colored cross-linked sodium hyaluronate gel particles.
In step one of the present invention, the dye is a natural dye or a synthetic dye.
The natural dyes include blue, green, red, yellow, violet, black and white.
The synthetic dye is a chemical synthetic dye prepared by a series of chemical treatment processing.
The dyes in the invention include red dye, yellow dye, toluidine blue dye and the like.
The acidic solution can be acetic acid, citric acid, lactic acid and the like with weak acidity, and the alkaline solution can be sodium hydroxide solution, potassium hydroxide solution, quaternary ammonium base solution and the like.
The first solution formed after dissolution of the dye in an acidic solution has a pH of 2 to 5, preferably 3 to 4.
The first solution formed after the dye is dissolved or alkaline solution has a pH of 9 to 13, preferably 10 to 11.
In step two of the present invention, the crosslinking agent is one or more of diglycidyl ether, divinyl sulfone, 1,2,7, 8-diepoxyoctane, 1, 3-diepoxybutane and sodium trimetaphosphate.
In step three of the present invention, the molecular weight of the sodium hyaluronate is 50 to 350 ten thousand Da, preferably 80 to 250 ten thousand Da.
In the invention, the ratio of the addition amount of the dye, the cross-linking agent and the sodium hyaluronate is (0.05-6): 0.1-15): 100, preferably (0.1-3): 0.5-9): 100.
In the third step of the invention, sodium hyaluronate is added into the second solution, and the mixture is uniformly mixed, the temperature is kept between 20 and 50 ℃, preferably between 25 and 40 ℃, and the crosslinking reaction is carried out within a given time between 2 and 72 hours, preferably between 6 and 36 hours.
In the third step of the invention, the content of the sodium hyaluronate in the color cross-linked sodium hyaluronate gel is 50-600 mg/g.
In the fourth step of the invention, one of phosphate buffer solution, normal saline or water is adopted to purify the color cross-linked sodium hyaluronate gel, and the color cross-linked sodium hyaluronate gel particles are obtained by granulation.
The pH value of the phosphate buffer solution is 5.8-8.4, and the mass of the buffer solution for purification is 1-4 times of that of the color cross-linked sodium hyaluronate gel.
The content of the sodium hyaluronate in the colored cross-linked sodium hyaluronate gel particles is 8-50 mg/g.
The sodium hyaluronate in the invention is pure product and is produced by Huaxi biotechnology limited company.
The invention also relates to an application of the colored cross-linked sodium hyaluronate gel or the colored cross-linked sodium hyaluronate gel particles in the field of cosmetics. The color cross-linked sodium hyaluronate gel or the color cross-linked sodium hyaluronate gel particles can be applied to facial cleanser, lipstick, foundation liquid, massage cream and other color cosmetics, and have the effects of moisturizing, wrinkle resistance, stability and no decolorization.
The following examples of the present invention are merely illustrative of specific embodiments for carrying out the present invention and are not to be construed as limiting the invention. Other changes, modifications, substitutions, combinations, and simplifications which may be made without departing from the spirit and principles of the invention are intended to be equivalents thereof and to fall within the scope of the invention.
Examples
The experimental methods used in the following examples are all conventional methods, unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1
Dissolving 0.001g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 9, then adding 0.002g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 50 ten thousand Da (daltons) into the second solution, and uniformly mixing; then controlling the reaction temperature to be 20 ℃ and the reaction time to be 72h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into pieces, and purifying the pieces by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 8 mg/g.
Example 2
Dissolving 0.12g of dye yellow in 10g of acetic acid solution, uniformly mixing to obtain a first solution with the pH value of 2, then adding 0.3g of 1,2,7, 8-diepoxyoctane into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 350 kilodaltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 20 ℃ and the reaction time to be 40h to obtain the colored cross-linked sodium hyaluronate gel;
cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 10 mg/g.
Example 3
Dissolving 0.08g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with a pH value of 13, adding 0.008g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, adding 2g of sodium hyaluronate with a molecular weight of about 60 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 50 ℃ and the reaction time to be 2h to obtain the colored cross-linked sodium hyaluronate gel;
cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 10 mg/g.
Example 4
Dissolving 0.01g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 10, then adding 0.01g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 80 kilodaltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 30 ℃ and the reaction time to be 24h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 50 mg/g.
Example 5
Dissolving 0.002g of toluidine blue in 10g of acetic acid solution, uniformly mixing to obtain a first solution with the pH value of 4, then adding 0.06g of 1, 3-diepoxybutane into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 150 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 35 ℃ and the reaction time to be 36h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 48 mg/g.
Example 6
Dissolving 0.06g of dye yellow in 8g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 11, then adding 0.18g of sodium trimetaphosphate into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 250 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 40 ℃ and the reaction time to be 6h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 45 mg/g.
Example 7
Dissolving 0.05g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 11, then adding 0.06g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 200 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 25 ℃ and the reaction time to be 30h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 42 mg/g.
Example 8
Dissolving 0.01g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 9.5, then adding 0.04g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 150 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 40 ℃ and the reaction time to be 4h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into pieces, and purifying the pieces by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 25 mg/g.
Example 9
Dissolving 0.01g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 10.5, then adding 0.003g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 150 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 30 ℃ and the reaction time to be 24h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into pieces, and purifying the pieces by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 23 mg/g.
Example 10
Dissolving 0.01g of toluidine blue in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 12, then adding 0.04g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 150 ten thousand daltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 50 ℃ and the reaction time to be 6h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 20 mg/g.
Example 11
The cross-linked sodium hyaluronate gel before purification is prepared according to the method of example 4, and then the colored cross-linked sodium hyaluronate gel is cut into pieces, purified by Phosphate Buffered Saline (PBS), and granulated by a 60-mesh stainless steel screen mesh to obtain colored cross-linked sodium hyaluronate gel particles, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel particles is 50 mg/g.
Comparative example 1
A cross-linked sodium hyaluronate gel was prepared as in example 4 except that no dye was added to the first solution.
Comparative example 2
Dissolving 0.001g of dye red in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 11, then adding 0.008g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 60 kilodaltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 60 ℃ and the reaction time to be 1h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 5 mg/g.
Comparative example 3
Dissolving 0.13g of dye yellow in 10g of sodium hydroxide solution, uniformly mixing to obtain a first solution with the pH value of 8, then adding 0.001g of 1, 4-butanediol diglycidyl ether into the first solution, uniformly mixing to obtain a second solution, then adding 2g of sodium hyaluronate with the molecular weight of about 40 kilodaltons into the second solution, and uniformly mixing; then controlling the reaction temperature to be 60 ℃ and the reaction time to be 75h to obtain the colored cross-linked sodium hyaluronate gel;
and cutting the colored cross-linked sodium hyaluronate gel into blocks, and purifying by Phosphate Buffered Saline (PBS) to obtain the purified colored cross-linked sodium hyaluronate gel, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 4 mg/g.
Application example 1
The colored cross-linked sodium hyaluronate gel prepared in example 4 was applied to lipstick.
Weighing 25.0g of beeswax, 4.0g of vitamin E, 10.0g of lanolin, 30.0g of castor oil, 10.0g of shea butter, 10.0g of polydimethylsiloxane, 10.0g of isopropyl palmitate, 5g of red cross-linked sodium hyaluronate gel and 0.2g of methylparaben. The raw materials are heated and melted, and are mixed and stirred uniformly. After the temperature is reduced to 55 ℃, 0.5g of essence is added. Cooling and forming to obtain the lipstick test article. The lipstick has the effects of high moistening degree, firm coloring, uniform color, no peeling, and good safety.
Table 1 shows the parameters of each example and comparative example
Effect test
1. Modulus of elasticity test
The colored crosslinked sodium hyaluronate gels of examples 1 to 10 and comparative examples 1 to 3 were measured for elastic modulus using a Haake RS6000 (seimer feishell science, china) instrument under the conditions: a rotor: p20 TiL; gap value: 1.00 mm; temperature: 25 ℃; measurement mode: oscillating frequency scan CD; stress: 1 percent; frequency range: 0.01 to 1 Hz. The modulus of elasticity (G') at 0.1Hz was recorded. The results are shown in Table 2.
2. In vitro degradation
An appropriate amount of the colored cross-linked sodium hyaluronate gel (containing about 8mg of HA) of examples 1-11 and comparative examples 1-4 is put into a penicillin bottle, 4mL of self-made HA enzyme (the enzyme activity is 600IU/mL) is added, and the mixture is vortexed and mixed uniformly. Shaking in a water bath at 42 deg.C, sampling 50 μ L every 10min and diluting appropriately, measuring absorbance at 232nm until absorbance no longer changes, considering degradation is complete, and recording the time taken for complete degradation. The results of the in vitro degradation experiments are shown in table 2 below.
3. Decolorization test
And (3) respectively dispersing a proper amount of the colored sodium hyaluronate gel prepared in the examples 1-10 and the comparative examples 1-3 into purified water, stirring for 15min, standing, and comparing the color of the supernatant after the gel particles are settled to the bottom of the beaker. The degree of discoloration was 0 to 10 points from light to heavy, and was scored by a panel of 30 panelists, and the results are shown in Table 2.
4. Stability test
And (3) dispersing a proper amount of the colored sodium hyaluronate gel prepared in the examples 1-10 and the comparative examples 1-3 into purified water, uniformly mixing, respectively storing in a refrigerator at 4 ℃ for one week and at 40 ℃ for 24 hours, stirring for 15min, standing until the gel particles are settled to the bottom of a beaker, and comparing the color of the supernatant. The color of the supernatant was 0-10 points from light to dark, and the results were shown in Table 2, with the evaluation performed by a panel of 30 persons.
Table 2 shows the comparison of the properties of the colored crosslinked sodium hyaluronate gels prepared in the examples and comparative examples
And (3) knotting: the results of the elastic modulus test and the in vitro degradation experiment show that the colored cross-linked sodium hyaluronate gel prepared in examples 1 to 10 has higher elastic modulus, complete degradation time, high-temperature stability, low-temperature stability, difficult decolorization and the like compared with the colored cross-linked sodium hyaluronate gel prepared in comparative examples 2 to 3, and the addition of the dye can not influence the reaction process of the cross-linking reaction as seen in comparative example 1, and the prepared colored cross-linked sodium hyaluronate gel still has the effects of moisturizing and anti-wrinkle of the conventional cross-linked sodium hyaluronate gel.
The method can prepare the color cross-linked sodium hyaluronate gel with excellent enzymolysis resistance, the color gel particles are not decolored in the solution, and a decoloration test and a stability test show that the color gel is firmly and uniformly colored and is an ideal cosmetic raw material.
Claims (10)
1. The preparation method of the colored cross-linked sodium hyaluronate gel is characterized by comprising the following steps:
dissolving a dye in an acidic or alkaline solution, and uniformly stirring to obtain a first solution;
adding a cross-linking agent into the first solution, and uniformly stirring to obtain a second solution;
and adding sodium hyaluronate into the second solution, uniformly mixing, keeping the constant temperature, and performing crosslinking reaction within a given time to obtain the colored crosslinked sodium hyaluronate gel.
2. The method for preparing the colored cross-linked sodium hyaluronate gel according to claim 1, wherein the dye is natural dye or synthetic dye, and after the dye is dissolved in an acidic solution, the pH of the formed first solution is 2-5.
3. The method for preparing the colored cross-linked sodium hyaluronate gel according to claim 1, wherein the dye is natural dye or synthetic dye, and after the dye is dissolved in an alkaline solution, the pH of the formed first solution is 9-13.
4. The method for preparing the colored cross-linked sodium hyaluronate gel according to any one of claims 1 to 3, wherein the cross-linking agent is one or more selected from diglycidyl ether, divinyl sulfone, 1,2,7, 8-diepoxyoctane, 1, 3-diepoxybutane and sodium trimetaphosphate.
5. The method for preparing the colored cross-linked sodium hyaluronate gel according to any one of claims 1 to 4, wherein the molecular weight of the sodium hyaluronate is 50 to 350 ten thousand Da, preferably 80 to 250 ten thousand Da.
6. The method for preparing the colored cross-linked sodium hyaluronate gel according to any one of claims 1 to 5, wherein the ratio of the addition amount of the dye, the cross-linking agent and the sodium hyaluronate is (0.05-6): 0.1-15): 100, preferably (0.1-3): 0.5-9): 100.
7. The method for preparing the colored cross-linked sodium hyaluronate gel according to any one of claims 1 to 6, wherein the sodium hyaluronate is added to the second solution, and the mixture is uniformly mixed, kept at the temperature of 20-50 ℃, preferably 25-40 ℃, and subjected to cross-linking reaction within a given time of 2-72 hours, preferably 6-36 hours.
8. The method for preparing the colored cross-linked sodium hyaluronate gel according to any one of claims 1 to 7, wherein the content of sodium hyaluronate in the colored cross-linked sodium hyaluronate gel is 50-600 mg/g.
9. The method for preparing the colored crosslinked sodium hyaluronate gel according to any one of claims 1 to 8, wherein the colored crosslinked sodium hyaluronate gel is purified.
10. The method for preparing a colored cross-linked sodium hyaluronate gel according to claim 9, wherein the colored cross-linked sodium hyaluronate gel is purified by one selected from phosphate buffered saline, physiological saline or water to obtain a purified colored cross-linked sodium hyaluronate gel.
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