Temperature-sensitive slow-release efficient transdermal transmission gel mask as well as preparation method and application thereof

Abstract

The invention discloses a temperature-sensitive slow-release efficient transdermal transmission gel mask as well as a preparation method and application thereof, and relates to the technical field of hydrogel and cosmetics. The preparation method of the gel mask comprises the following steps: (1) carrying out a reaction on Pluronic F127 and acryloyl chloride to obtain PF127-DA; the preparation method comprises the following steps: reacting hyaluronic acid with glycidyl methacrylate to obtain HA-GMA; and (2) pre-dissolving and blending the PF127-DA and the HA-GMA obtained in the step (1) with a photoinitiator, a thickening agent, a functional component, a preservative and water, pouring the mixture into a mold after the mixture is completely dissolved, and carrying out photo-crosslinking under ultraviolet light to obtain the gel mask. The gel mask provided by the invention can reduce irritation to human skin, increase skin affinity, moisturize for a long time, optimize use feeling and achieve slow-release and permeation-promoting effects by means of in-situ release of thermosensitivity, and has a good application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogel and cosmetics, and in particular to a temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask and a preparation method and application thereof. Background Art

[0002] Compared with the traditional masks on the market based on silk, biofiber, non-woven fabrics, cotton cloth, etc., hydrogel masks have stronger adsorption, higher liquid carrying capacity, and more docile contact with the skin. Hydrogel is a three-dimensional network structure semisolid composed of hydrophilic macromolecular chains, with strong swelling ability, but insoluble in water. Hydrogel has good biocompatibility, soft texture and certain elasticity, can reduce stimulation to epidermal cells and tissues, increase comfort, and can be used as an ideal raw material for human skin care. In order to make the essence ingredients in the gel mask more fully released and act on human skin, more and more studies have introduced thermosensitive materials into hydrogels, such as monomer N-isopropylacrylamide, monomer acrylic acid and other materials. However, these reagents have certain biological toxicity. In order to avoid the potential toxicity, Pluronic F127 (PF127) with a molecular weight of about 12600Da, which has been approved by the US Food and Drug Administration (FDA), can be used as a thermosensitive material and introduced into the gel system. PF127 containing PEO-PPO-PEO (polyethylene oxide-polypropylene oxide-polyethylene oxide) is composed of three blocks of hydrophilic-hydrophobic-hydrophilic arranged at intervals. It can achieve the effect of sustained release and promoted penetration of essence substances at skin temperature by virtue of the self-hydrophobic effect of forming micelles close to human body temperature.

[0003] However, when PF127 alone is at a certain concentration close to human body temperature, the gel formed due to physical effects is weak and cannot be used as a mask base material.

[0004] Therefore, it is of great significance to develop a biofriendly, strength-controllable and temperature-sensitive gel material as a hydrogel mask, which can reduce irritation to human skin, increase skin affinity, moisturize for a long time, optimize the feel of use, and achieve the effect of sustained release and penetration promotion by relying on the in situ release of temperature sensitivity. Summary of the invention

[0005] In order to overcome the technical defects of the existing thermosensitive hydrogel mask, the primary purpose of the present invention is to provide a method for preparing a thermosensitive sustained-release high-efficiency transdermal transmission gel mask. The present invention forms a stable and tough hydrogel by modifying the double bonds of Pluronic F127 and hyaluronic acid by grafting acrylates, and introducing a photoinitiator to chemically crosslink the materials under a wavelength of 365nm ultraviolet light. The introduction of PF127 material gives the hydrogel the function of thermosensitivity, and the introduction of hyaluronic acid is to make the gel strength controllable and provide a moisturizing and skin care effect. By optimizing the feed ratio and increasing the number of feeds, the grafting rate of PF127-DA is greatly improved, and the gel strength of PF127-DA with a high grafting rate is higher after ultraviolet crosslinking.

[0006] Another object of the present invention is to provide a thermosensitive sustained-release high-efficiency transdermal transmission gel mask. In the presence of a photoinitiator, the present invention pre-dissolves a natural polymer thickener, ingredients with whitening, moisturizing, soothing, anti-aging effects, preservatives and other substances into a precursor solution, and then compound them with PF127-DA and HA-GMA in a certain proportion, and then initiates photopolymerization of the material under ultraviolet conditions, loads the functional ingredients into the gel, and gives the gel mask a certain strength, elasticity, and skin care effects such as whitening and moisturizing.

[0007] Another object of the present invention is to provide the application of the above-mentioned temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask. The hydrophobic group (PPO) of Pluronic F127 has a low LCST (low critical phase transition temperature), so it has the ability to self-assemble to form micelles at a certain temperature and has temperature sensitivity. However, the molecular weight of high molecular polymers including Pluronic is not always constant. Therefore, the rate of temperature-sensitive release of the gel obtained by photocrosslinking with PF127-DA as the substrate in response to temperature is not always the same, and there is a certain difference.

[0008] The above-mentioned object of the present invention is achieved by the following technical solutions:

[0009] In a first aspect, a method for preparing a thermosensitive sustained-release high-efficiency transdermal transmission gel mask is provided, comprising the following steps:

[0010] (1) reacting Pluronic F127 with acryloyl chloride to obtain PF127-DA; reacting hyaluronic acid with glycidyl methacrylate to obtain HA-GMA;

[0011] (2) PF127-DA and HA-GMA obtained in step (1) are mixed with a photoinitiator, a thickener, an effective ingredient, a preservative, and water, and poured into a mold after complete dissolution. The mold is placed under ultraviolet light for photocrosslinking to obtain a hydrogel, thereby obtaining the thermosensitive sustained-release high-efficiency transdermal transmission gel mask.

[0012] Preferably, the PF127-DA in step (1) is PF127 modified with an acrylate double bond at the terminal end.

[0013] Preferably, the HA-GMA in step (2) is HA with a side chain modified with an acrylate double bond.

[0014] Preferably, the water used in the present invention is deionized water.

[0015] Furthermore, the step of reacting Pluronic F127 with acryloyl chloride is as follows: dissolving Pluronic F127 in dichloromethane, adding triethylamine and stirring, then adding acryloyl chloride, reacting under stirring to obtain a reaction solution; removing dichloromethane from the reaction solution by rotary evaporation; adding the reaction solution into n-hexane while stirring, recrystallizing to precipitate a white solid product and filtering it with suction, dissolving the solid product obtained after filtering in dichloromethane, recrystallizing it again, repeating the same recrystallization operation, and purifying to obtain PF127-DA.

[0016] Preferably, the obtained PF127-DA solid powder or granules are vacuum dried.

[0017] Furthermore, in step (1), the mass volume ratio of the Pluronic F127 to the dichloromethane used to dissolve the Pluronic F127 is 1 g: (1-5) mL, the mass volume ratio of the Pluronic F127 to triethylamine is (20-40) g: 1 mL, and the mass volume ratio of the Pluronic F127 to acryloyl chloride is (20-40) g: 1 mL.

[0018] Preferably, the dissolution temperature of Pluronic F127 in dichloromethane is 0-5°C.

[0019] Preferably, the mass volume ratio of Pluronic F127 to dichloromethane is 1 g:2 mL.

[0020] Preferably, the mass volume ratio of Pluronic F127 to triethylamine is 80 g:3 mL.

[0021] Preferably, the mass volume ratio of Pluronic F127 to acryloyl chloride is 80 g:3 mL.

[0022] Furthermore, in step (1), the number of times of feeding acryloyl chloride is 1 to 3 times; and the reaction time of Pluronic F127 and acryloyl chloride is 12 to 24 hours for each feeding.

[0023] Preferably, the feeding times of acryloyl chloride is 3 times. Among them, repeated feeding can improve the grafting rate of PF127-DA.

[0024] Preferably, the volume of acryloyl chloride added for the second and third times is halved.

[0025] Preferably, the recrystallization operation is repeated 1 to 3 times.

[0026] Preferably, the recrystallization operation is repeated 3 times.

[0027] Furthermore, in step (1), the step of reacting the hyaluronic acid with glycidyl methacrylate is as follows: fully dissolving the hyaluronic acid in water, adding glycidyl methacrylate dropwise into the hyaluronic acid aqueous solution, stirring evenly, adjusting the pH to be acidic and then heating the reaction to obtain a reaction solution; taking ethanol, adding the reaction solution to ethanol while stirring, standing and stratifying, and then filtering, the solid product obtained after filtering is dissolved in water, and the same ethanol recrystallization operation is repeated to purify and obtain HA-GMA.

[0028] Preferably, the obtained HA-GMA is vacuum dried at a temperature of 30-50°C.

[0029] Preferably, the molecular weight of the hyaluronic acid is in the range of 70 to 140W.

[0030] Preferably, in the hyaluronic acid aqueous solution, the mass volume ratio of hyaluronic acid to water is 1 g: (50-200) mL.

[0031] Preferably, in the hyaluronic acid aqueous solution, the mass volume ratio of hyaluronic acid to water is 9.3g:900mL.

[0032] Furthermore, the mass volume ratio of the hyaluronic acid to glycidyl methacrylate is 1 g: (1-5) mL.

[0033] Preferably, the mass volume ratio of the hyaluronic acid to glycidyl methacrylate is 9.3 g:11.6 mL.

[0034] Preferably, the reagent used to adjust the pH is hydrochloric acid with a concentration of 1 to 12 mol / L.

[0035] Preferably, adjusting the pH to be acidic means adjusting the pH to 4-6.

[0036] Preferably, the heating reaction is carried out at a temperature of 40 to 70° C. and for a time of 12 to 24 hours.

[0037] Preferably, the heating reaction temperature is 60° C. and the time is 12 hours.

[0038] Preferably, the ethanol recrystallization operation is repeated 1 to 3 times.

[0039] Preferably, the ethanol recrystallization operation is repeated 3 times.

[0040] Furthermore, in step (2), the amount of PF127-DA is 10-20wt%, the amount of HA-GMA is 0.2-2wt%, the amount of photoinitiator is 0.05-0.5wt%, the amount of thickener is 0.5-3wt%, the amount of functional ingredient is 10-20wt%, and the amount of preservative is 0.01-0.2wt%.

[0041] Preferably, in step (2), the amount of PF127-DA is 14-16wt%, the amount of HA-GMA is 0.2-0.6wt%, the amount of photoinitiator is 0.2-0.5wt%, the amount of thickener is 2-3wt%, the amount of functional ingredient is 15-18wt%, and the amount of preservative is 0.04-0.1wt%.

[0042] Preferably, in step (2), the amount of PF127-DA is 15wt%, the amount of HA-GMA is 0.5wt%, the amount of photoinitiator is 0.3wt%, the amount of thickener is 2.5wt%, the amount of functional ingredient is 18wt%, and the amount of preservative is 0.05wt%.

[0043] Preferably, in step (2), the photoinitiator is 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959).

[0044] Preferably, the thickener includes one or more of Zoubo carrageenan (carrageenan), locust bean gum, cellulose gum, xanthan gum, guar gum, trehalose, gelatin, gum arabic, and agar. Wherein, the thickener is mainly a water-soluble natural polymer material.

[0045] Preferably, the functional ingredients include one or more of whitening ingredients, moisturizing ingredients, soothing ingredients, and anti-aging ingredients.

[0046] Preferably, the whitening ingredients include one or more of Centella asiatica, vitamin C, arbutin, kojic acid, azelaic acid, fruit acid, salicylic acid, glutathione, aloe extract, proanthocyanidins, niacinamide, resveratrol, and vitamin A; the moisturizing and hydrating ingredients include one or more of hyaluronic acid, sodium hyaluronate, hydroxyethyl urea, betaine, lecithin, glycerin, polyols (propylene glycol, glycerol, butylene glycol), amino acids, xylitol, ethylhexylglycerin, caprylyl glycol, ceramide, squalane, panthenol, and betaine; the soothing and calming ingredients include one or more of dipotassium glycyrrhizate, aloe extract, vitamin B5, allantoin, palmitoyl inositol, purslane extract, Centella asiatica extract, and chamomile extract; the anti-aging ingredients include one or more of collagen, vitamin E, proanthocyanidins, tea polyphenols, evening primrose, sunflower seed extract, ginseng extract, and hops extract.

[0047] Preferably, the preservative includes one or more of phenoxyethanol, p-hydroxyacetophenone, and chlorphenesin.

[0048] Furthermore, in step (2), the wavelength of the ultraviolet light is 365 nm, the light intensity is 50 to 196 W, and the photocrosslinking time is 1 to 10 min.

[0049] Preferably, the wavelength of the ultraviolet light is 365 nm, the light intensity is 100 W, and the photocrosslinking time is 5 min.

[0050] In the second aspect, a temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask is provided, which is prepared by the preparation method of the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask described in the first aspect.

[0051] In a third aspect, there is provided application of the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask as described in the second aspect in cosmetics.

[0052] Among them, when the single PF127 is close to human body temperature at a certain concentration, the mechanical strength of the gel formed by physical action is weak and cannot meet the use as a mask substrate. The present invention generates acrylated PF127 (PF127-DA) by modifying PF127 and connecting acrylate double bonds at both ends, and further initiates free radical polymerization by ultraviolet cross-linking to produce chemical cross-linking, thereby generating a hydrogel with higher mechanical strength. In addition, hyaluronic acid, as a "natural moisturizing factor" commonly used in cosmetics and a natural high molecular polysaccharide, can moisturize the stratum corneum and provide a long-term moisturizing effect for human skin. By modifying the hydroxyl group on the side chain of the hyaluronic acid molecule to methacrylate hyaluronic acid (HA-GMA), the introduced acrylate double bonds make HA-GMA and PF127-DA jointly form a double-layer light cross-linking network, and the introduction of HA-GMA gives the gel the function of lasting moisturizing and skin care. The addition of HA-GMA will reduce the strength of the gel. In order to ensure a long-lasting moisturizing effect while still maintaining a high gel strength, the grafting rate of PF127-DA was greatly improved through the optimization of the synthesis process, and finally a thermosensitive sustained-release hydrogel mask containing a double cross-linked network system was obtained. PF127-DA and HA-GMA constitute the base material of the hydrogel mask. On this basis, products with different skin care functions can be obtained by introducing functional substances and essence ingredients commonly used in other cosmetics.

[0053] The beneficial effects of the present invention are:

[0054] (1) The temperature-sensitive material PF127 used in the present invention has been approved by the FDA and has higher biosafety.

[0055] (2) The present invention increases the grafting rate of PF127-DA to more than 90% by increasing the number of feeding times and optimizing the reaction conditions.

[0056] (3) The hydrogel mask of the present invention has good skin affinity and is easy to remove from the skin surface.

[0057] (4) The thermosensitive hydrogel mask of the present invention can respond to changes in skin temperature and promote the release and absorption of essence ingredients.

[0058] (5) The present invention achieves controllable gel strength by introducing methacrylate-modified hyaluronic acid, and is conducive to achieving a long-lasting moisturizing effect.

[0059] (6) The hydrogel of the present invention has strong tensile properties, and the maximum tensile breaking strength can reach 250 kPa. The above data are sufficient to meet the basic mechanical strength requirements of the gel mask attached to the skin in daily human life. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying any creative work.

[0061] Figure 1 This is a graph showing the shrinkage rate of the thermosensitive sustained-release high-efficiency transdermal transmission gel mask prepared in Example 1 of the present invention;

[0062] Figure 2 It is a tensile data diagram of the facial masks prepared in Example 1 and Comparative Examples 1-3 of the present invention;

[0063] Figure 3 is the hydrogen nuclear magnetic resonance spectrum of PF127-DA in Example 1 of the present invention;

[0064] Figure 4 is the hydrogen nuclear magnetic resonance spectrum of PF127-DA in Comparative Example 1 of the present invention;

[0065] Figure 5 is the hydrogen nuclear magnetic resonance spectrum of HA-GMA in Example 1 of the present invention;

[0066] Figure 6 This is a macroscopic picture of the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask prepared in Example 1 of the present invention;

[0067] Figure 7 This is an electron microscope scanning image of the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0068] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0069] It should be understood that when used in this specification and the appended claims, the terms "include" and "comprises" indicate the presence of described features, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or combinations thereof.

[0070] It should also be understood that the terms used in this specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. As used in the specification of the present invention and the appended claims, unless the context clearly indicates otherwise, the singular forms "a", "an" and "the" are intended to include plural forms.

[0071] It should be further understood that the term "and / or" used in the present description and the appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0072] In order to more fully understand the technical content of the present invention, the technical solution of the present invention is further introduced and illustrated in conjunction with specific embodiments below.

[0073] The molecular weight of the hyaluronic acid used in the following examples ranges from 70 to 140 W.

[0074] Example 1

[0075] The preparation method of a thermosensitive sustained-release high-efficiency transdermal transmission gel mask comprises the following steps:

[0076] (1) Pluronic F127 (400 g) was dissolved in dichloromethane (800 mL) at low temperature (3°C). Triethylamine (15 mL) was added and stirred to mix well. Acryloyl chloride (15 mL) was then added and reacted for 12 h under stirring to obtain a reaction solution. In order to increase the grafting rate of the product, the feed was repeated twice every 12 h. The second and third acryloyl chloride feeds were 7.5 mL. More than half (volume) of the dichloromethane in the reaction solution was removed by rotary evaporation. Excess n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. The white solid product was recrystallized and filtered. The solid product obtained after filtration was dissolved in dichloromethane and recrystallized again. The same recrystallization operation was repeated 3 times. PF127-DA was purified. The obtained PF127-DA solid powder was placed in a vacuum dryer at room temperature (25°C). A PF127 (PF127-DA) material with a high grafting rate and acrylic acid esterification is prepared by connecting acrylic acid double bonds at both ends.

[0077] Dissolve hyaluronic acid (9.3g) in deionized water (900mL) and stir for 6h to fully dissolve. Glycidyl methacrylate (11.6mL) was added dropwise to the hyaluronic acid aqueous solution. After stirring evenly, hydrochloric acid (1mol / L) was used to adjust the pH to 5, and the reaction was heated at 60℃ for 12h to obtain a reaction solution. Take excess ethanol, add the reaction solution to ethanol while stirring, let it stand and filter after stratification. The solid product obtained after filtration was dissolved in water again, and the same ethanol recrystallization operation was repeated 3 times. HA-GMA was obtained after purification. The purified sample was dried in a vacuum drying oven at 40℃. The hydroxyl group on the side chain was modified into methacrylate hyaluronic acid (HA-GMA) material.

[0078] (2) PF127-DA (0.6 g), HA-GMA (0.02 g), and Irgacure 2959 (0.012 g) were added to a 10 mL centrifuge tube. To further enhance the elasticity of the gel and provide an excellent feel, carrageenan (0.08 g) and locust bean gum (0.02 g) were added as thickeners to the centrifuge tube. Glycerol (0.4 g), dipotassium glycyrrhizinate (0.02 g), niacinamide (0.08 g), collagen (0.2 g), and betaine (0.02 g) were added as active ingredients to the centrifuge tube. Chlorphenesin (0.002 g) was added as a preservative to the centrifuge tube. Finally, deionized water (2.546 mL) was added to fully dissolve the gel, and air bubbles were eliminated by ultrasound. After complete dissolution, the hydrogel precursor solution was poured into the mold, and the mold was placed under ultraviolet light at 365 nm and an illumination intensity of 100 W for photocrosslinking for 5 min. The thermosensitive sustained-release high-efficiency transdermal transmission gel mask of Example 1 was prepared. The thermosensitive sustained-release high-efficiency transdermal transmission gel mask of Example 1 is a high-grafting rate PF127 / hyaluronic acid hydrogel mask.

[0079] (3) Soak the prepared thermosensitive sustained-release high-efficiency transdermal transmission gel mask in deionized water for 10 minutes, and replace the deionized water for washing three times.

[0080] Comparative Example 1

[0081] The preparation method of the high grafting rate PF127 hydrogel mask comprises the following steps:

[0082] (1) Pluronic F127 (400 g) was dissolved in dichloromethane (800 mL) at low temperature (3°C). Triethylamine (15 mL) was added and stirred to mix well. Acryloyl chloride (15 mL) was then added and reacted for 12 h under stirring to obtain a reaction solution. In order to increase the grafting rate of the product, the feed was repeated twice every 12 h. The second and third acryloyl chloride feeds were 7.5 mL. More than half (volume) of the dichloromethane in the reaction solution was removed by rotary evaporation. Excess n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. The white solid product was recrystallized and filtered. The solid product obtained after filtration was dissolved in dichloromethane and recrystallized again. The same recrystallization operation was repeated 3 times. PF127-DA was purified. The obtained PF127-DA solid powder was placed in a vacuum dryer at room temperature (25°C). A PF127 (PF127-DA) material with a high grafting rate and acrylic acid esterification is prepared by connecting acrylic acid double bonds at both ends.

[0083] (2) PF127-DA (0.6 g) and Irgacure 2959 (0.012 g) were added to a 10 mL centrifuge tube. In order to further enhance the elasticity of the gel and provide an excellent feel during use, carrageenan (0.08 g) and locust bean gum (0.02 g) were selected as thickeners and added to the centrifuge tube. Glycerol (0.4 g), dipotassium glycyrrhizinate (0.02 g), niacinamide (0.08 g), collagen (0.2 g), and betaine (0.02 g) were selected as active ingredients and added to the centrifuge tube. Chlorphenesin (0.002 g) was selected as a preservative and added to the centrifuge tube. Finally, deionized water (2.566 mL) was added to fully dissolve the gel, and bubbles were eliminated by ultrasound. After complete dissolution, the precursor solution of the hydrogel is poured into the mold, and the mold is placed under ultraviolet light with a light intensity of 100 W at 365 nm for photocrosslinking for 5 minutes to obtain the hydrogel, thereby preparing the high grafting rate PF127 hydrogel mask of Comparative Example 1.

[0084] (3) The prepared high grafting rate PF127 hydrogel mask was soaked in deionized water for 10 min and then washed with changed deionized water three times.

[0085] Comparative Example 2

[0086] The preparation method of the low grafting rate PF127 / hyaluronic acid hydrogel mask comprises the following steps:

[0087] (1) Pluronic F127 (400 g) was dissolved in dichloromethane (800 mL) at low temperature (3°C). Triethylamine (15 mL) was added and stirred, and then acryloyl chloride (15 mL) was added and reacted for 12 h under stirring to obtain a reaction solution. More than half (volume) of the dichloromethane in the reaction solution was removed by rotary evaporation. Excess n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. The white solid product was recrystallized and filtered. The solid product obtained after filtration was dissolved in dichloromethane and recrystallized again. The same recrystallization operation was repeated 3 times. PF127-DA was purified. The obtained PF127-DA solid powder was placed in vacuum drying at room temperature (25°C). A PF127 (PF127-DA) material with a low grafting rate and acrylate double bonds at both ends was prepared.

[0088] Hyaluronic acid (9.3g) was dissolved in deionized water (900mL) and stirred for 6h to fully dissolve. Glycidyl methacrylate (11.6mL) was added dropwise to the hyaluronic acid aqueous solution. After stirring evenly, hydrochloric acid (1mol / L) was used to adjust the pH to 5, and the reaction was heated at 60℃ for 12h to obtain a reaction solution. Take excess ethanol, add the reaction solution to ethanol while stirring, let it stand for stratification and filter. After the solid product was obtained after filtration, it was dissolved in water and the same ethanol recrystallization operation was repeated 3 times. After purification, HA-GMA was obtained. The purified sample was dried in a vacuum drying oven at 40℃. The hydroxyl group on the side chain was modified into methacrylate hyaluronic acid (HA-GMA) material.

[0089] (2) PF127-DA (0.6 g), HA-GMA (0.02 g), and Irgacure 2959 (0.012 g) were added to a 10 mL centrifuge tube. To further enhance the elasticity of the gel and provide an excellent feel, carrageenan (0.08 g) and locust bean gum (0.02 g) were added to the centrifuge tube as thickeners. Glycerol (0.4 g), dipotassium glycyrrhizinate (0.02 g), niacinamide (0.08 g), collagen (0.2 g), and betaine (0.02 g) were added to the centrifuge tube as active ingredients. Chlorphenesin (0.002 g) was added to the centrifuge tube as a preservative. Finally, deionized water (2.546 mL) was added and stirred to dissolve. The bubbles were eliminated by ultrasound. After complete dissolution, the hydrogel precursor solution was poured into the mold, and the mold was placed under ultraviolet light at 365 nm and an illumination intensity of 100 W for photocrosslinking for 5 min. A low grafting rate PF127 / hyaluronic acid hydrogel mask was prepared.

[0090] (4) The prepared low grafting rate PF127 / hyaluronic acid hydrogel mask was soaked in deionized water for 10 min, and the deionized water was replaced and washed three times.

[0091] Comparative Example 3

[0092] The preparation method of the low grafting rate PF127 hydrogel mask comprises the following steps:

[0093] (1) Pluronic F127 (400 g) was dissolved in dichloromethane (800 mL) at low temperature (3°C). Triethylamine (15 mL) was added and stirred, and then acryloyl chloride (15 mL) was added and reacted for 12 h under stirring to obtain a reaction solution. More than half (volume) of the dichloromethane in the reaction solution was removed by rotary evaporation. Excess n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. The white solid product was recrystallized and filtered. The solid product obtained after filtration was dissolved in a small amount of dichloromethane and recrystallized again. The same recrystallization operation was repeated 3 times, and PF127-DA was purified. The obtained PF127-DA solid powder was placed in a vacuum dryer at room temperature (25°C). A PF127 (PF127-DA) material with a low grafting rate and acrylate double bonds at both ends was prepared.

[0094] (2) PF127-DA (0.6 g) and Irgacure 2959 (0.012 g) were added to a 10 mL centrifuge tube. To further enhance the elasticity of the gel and provide an excellent feel, carrageenan (0.08 g) and locust bean gum (0.02 g) were added to the centrifuge tube as thickeners. Glycerol (0.4 g), dipotassium glycyrrhizinate (0.02 g), niacinamide (0.08 g), collagen (0.2 g), and betaine (0.02 g) were added to the centrifuge tube as active ingredients. Chlorphenesin (0.002 g) was added to the centrifuge tube as a preservative. Finally, deionized water (2.566 mL) was added and stirred to dissolve. The bubbles were eliminated by ultrasound. After complete dissolution, the precursor solution of the hydrogel was poured into the mold, and the mold was placed under ultraviolet light at 365 nm and a light intensity of 100 W for photocrosslinking for 5 min. A low grafting rate PF127 hydrogel mask was prepared.

[0095] (3) Soak the prepared low grafting rate PF127 hydrogel mask in deionized water for 10 min, and replace the deionized water for washing three times.

[0096] Performance test - Thermosensitive release effect test

[0097] In order to study the effect of thermosensitive release of the gel mask, the hydrogel sample (thermosensitive sustained-release high-efficiency transdermal transmission gel mask) obtained in Example 1 was soaked in deionized water and stored at 4°C for 24 hours. The hydrogel was completely swollen in water. After that, the sample was taken out and applied to the skin, and the hydrogel was weighed at regular time intervals (5 minutes, 10 minutes and 15 minutes) to determine the degree of contraction of the hydrogel. Calculation was performed according to the following formula:

[0098] Shrinkage rate (%) = [weight of the initial sample (g) - weight of the sample after different time intervals (g)] / weight of the initial sample × 100;

[0099] When measuring the weight of the hydrogel, since water droplets on the surface may cause errors, the weight of the sample is measured after removing as much surface water as possible. Figure 1 1 is a graph showing the shrinkage rate of the thermosensitive sustained-release high-efficiency transdermal transmission gel mask prepared in Example 1 of the present invention. Figure 1 As shown, the hydrogel sample containing 20wt% PF127-DA showed a release rate of nearly 30% within 15 minutes, while patent KR101462390B1 also used PF127-DA to prepare hydrogel, but the hydrogel sample containing 25wt% PF127-DA in the patent only reached 30% in 30 minutes. In contrast, the thermosensitive sustained-release high-efficiency transdermal transmission gel mask prepared by the present invention showed a faster thermosensitive release effect.

[0100] Performance test - mechanical performance test

[0101] Comparison of mechanical properties of Example 1 and Comparative Examples 1-3:

[0102] Figure 2 1 is a tensile data diagram of the facial mask prepared in Example 1 and Comparative Examples 1-3 of the present invention. Figure 2 As shown, the maximum breaking strength of the high grafting rate PF127 / hyaluronic acid hydrogel mask of Example 1 can reach 250kPa, and the maximum tensile strain is about 90%. The maximum breaking strength of the high grafting rate PF127 hydrogel mask of Comparative Example 1 can reach about 320kPa, and the maximum tensile strain is about 110%. The maximum breaking strength of the low grafting rate PF127 / hyaluronic acid hydrogel mask of Comparative Example 2 is about 17kPa, and the maximum tensile strain is about 150%. The maximum breaking strength of the low grafting rate PF127 hydrogel mask of Comparative Example 3 is about 30kPa, and the maximum tensile strain is about 240%.

[0103] Comparison of Example 2 with Example 3 shows that the introduction of hyaluronic acid reduces the mechanical properties of the hydrogel to a certain extent, while the introduction of high grafting rate PF127-DA (Example 1 and Comparative Example 1) greatly improves the overall mechanical strength of the hydrogel, but the toughness decreases. Figure 3 is the hydrogen nuclear magnetic resonance spectrum of PF127-DA in Example 1 of the present invention; Figure 4 is the hydrogen nuclear magnetic resonance spectrum of PF127-DA in Comparative Example 1 of the present invention; Figure 5 is the hydrogen nuclear magnetic resonance spectrum of HA-GMA in Example 1 of the present invention. Figure 3-Figure 5It can be seen that the PF127 (PF127-DA) material (Example 1) containing a high grafting rate not only maintains the existence of the hyaluronic acid cross-linked network, providing the hydrogel with long-lasting moisturizing properties, but also provides a higher mechanical strength.

[0104] In general, the thermosensitive sustained-release high-efficiency transdermal transmission gel mask of Example 1 has the following characteristics:

[0105] 1) The maximum tensile strength is 250kPa, and the maximum tensile strain is 90%, which can meet the strength requirements of daily gel masks.

[0106] 2) The presence of high grafting rate modified PF127 enables the gel mask to provide higher mechanical strength on the basis of maintaining the hyaluronic acid cross-linked network. At the same time, the gel prepared by this method achieves an excellent thermosensitive release effect.

[0107] 3) Figure 6 This is a macroscopic image of the thermosensitive sustained-release high-efficiency transdermal transmission gel mask prepared in Example 1 of the present invention. Figure 6 The macroscopic image shown indicates that the gel mask has good skin affinity and adhesion on human skin.

[0108] 4) Figure 7 This is an electron microscope scanning image of the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask prepared in Example 1 of the present invention. Figure 7 The SEM image of the gel shown indicates that the gel contains a dense microscopic network of pores and has a structure for loading and releasing the mask efficacy solution.

[0109] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed by the present invention, and these modifications or replacements should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims.

Claims

1. A method for preparing a thermosensitive sustained-release high-efficiency transdermal transmission gel mask, characterized in that: The following steps are involved: (1) reacting Pluronic F127 with acryloyl chloride to obtain PF127-DA; reacting hyaluronic acid with glycidyl methacrylate to obtain HA-GMA; (2) PF127-DA and HA-GMA obtained in step (1) are mixed with a photoinitiator, a thickener, an effective ingredient, a preservative, and water, and poured into a mold after complete dissolution. The mold is placed under ultraviolet light for photocrosslinking to obtain a hydrogel, thereby obtaining the thermosensitive sustained-release high-efficiency transdermal transmission gel mask.

2. The method for preparing the thermosensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 1, characterized in that: In step (1), the step of reacting Pluronic F127 with acryloyl chloride comprises dissolving Pluronic F127 in dichloromethane, adding triethylamine and stirring to mix, then adding acryloyl chloride, reacting under stirring to obtain a reaction solution; removing dichloromethane from the reaction solution by rotary evaporation; adding the reaction solution to n-hexane while stirring, recrystallizing to precipitate a white solid product and filtering it by suction, dissolving the solid product obtained after filtration in dichloromethane, recrystallizing it again, repeating the same recrystallization operation, and purifying to obtain PF127-DA.

3. The method for preparing the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 2, characterized in that: In step (1), the mass volume ratio of the Pluronic F127 to the dichloromethane used to dissolve the Pluronic F127 is 1 g: (1-5) mL, the mass volume ratio of the Pluronic F127 to triethylamine is (20-40) g: 1 mL, and the mass volume ratio of the Pluronic F127 to acryloyl chloride is (20-40) g: 1 mL.

4. The method for preparing the thermosensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 2, characterized in that: In step (1), the number of times of feeding acryloyl chloride is 1 to 3 times; each time of feeding, the reaction time of Pluronic F127 and acryloyl chloride is 12 to 24 hours.

5. The method for preparing the thermosensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 1, characterized in that: In step (1), the step of reacting hyaluronic acid with glycidyl methacrylate is as follows: fully dissolving hyaluronic acid in water, adding glycidyl methacrylate dropwise into the hyaluronic acid aqueous solution, stirring evenly, adjusting the pH to be acidic and then heating to react to obtain a reaction solution; taking ethanol, adding the reaction solution to ethanol while stirring, standing and stratifying, and then filtering, the solid product obtained after filtering is dissolved in water, and the same ethanol recrystallization operation is repeated to purify and obtain HA-GMA.

6. The method for preparing the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 5, characterized in that: The mass volume ratio of the hyaluronic acid to glycidyl methacrylate is 1g: (1-5)mL.

7. The method for preparing the thermosensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 1, characterized in that: In step (2), the amount of PF127-DA is 10-20wt%, the amount of HA-GMA is 0.2-2wt%, the amount of photoinitiator is 0.05-0.5wt%, the amount of thickener is 0.5-3wt%, the amount of functional ingredient is 10-20wt%, and the amount of preservative is 0.01-0.2wt%.

8. The method for preparing the thermosensitive sustained-release high-efficiency transdermal transmission gel mask according to claim 1, characterized in that: In step (2), the wavelength of the ultraviolet light is 365 nm, the light intensity is 50 to 196 W, and the photocrosslinking time is 1 to 10 min.

9. A thermosensitive sustained-release high-efficiency transdermal transmission gel mask, characterized in that: The mask is prepared by the method for preparing the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask described in any one of claims 1 to 8.

10. Use of the temperature-sensitive sustained-release high-efficiency transdermal transmission gel mask as claimed in claim 9 in cosmetics.

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