A thermosensitive, sustained-release, high-efficiency transdermal delivery gel mask, its preparation method and application

Abstract

This invention discloses a thermosensitive, sustained-release, highly efficient transdermal delivery gel mask, its preparation method, and its application, relating to the fields of hydrogels and cosmetics technology. The preparation method of this gel mask includes the following steps: (1) reacting Pluronic F127 with acryloyl chloride to obtain PF127-DA; reacting hyaluronic acid with glycidyl methacrylate to obtain HA-GMA; (2) mixing the PF127-DA and HA-GMA obtained in step (1) with a photoinitiator, thickener, active ingredient, preservative, and pre-dissolved water, and after complete dissolution, pouring the mixture into a mold, and placing it under ultraviolet light for photocrosslinking to obtain the gel mask. The gel mask of this invention can reduce irritation to human skin, increase skin affinity, provide long-lasting hydration, optimize the user experience, and achieve sustained-release and penetration-enhancing effects through thermosensitive in-situ release, showing promising application prospects.

Description

Technical Field

[0001] This invention relates to the fields of hydrogels and cosmetics, and in particular to a thermosensitive, sustained-release, highly efficient transdermal delivery gel mask, its preparation method, and its application. Background Technology

[0002] Compared to traditional masks made from silk, bio-cellulose, non-woven fabrics, and cotton, hydrogel masks have stronger adsorption capacity, higher liquid carrying capacity, and a more comfortable fit to the skin. Hydrogels are semi-solid structures with a three-dimensional network structure composed of hydrophilic macromolecular chains. They have strong swelling capacity but are insoluble in water. Hydrogels possess good biocompatibility, a soft texture, and a certain degree of elasticity, reducing irritation to epidermal cells and tissues and increasing comfort, making them an ideal raw material for human skin care. To enable the essence ingredients in gel masks to be released more fully and act on the human skin, more and more research is introducing thermosensitive materials into hydrogels, such as monomers N-isopropylacrylamide and acrylic acid. However, these reagents have certain biotoxicity. To avoid potential toxicity, Pluronic F127 (PF127), with a molecular weight of approximately 12600 Da and approved by the US Food and Drug Administration (FDA), can be used as a thermosensitive material introduced into the gel system. PF127, containing PEO-PPO-PEO (polyethylene oxide-polypropylene oxide-polyethylene oxide), is composed of three hydrophilic-hydrophobic-hydrophilic blocks arranged in a spaced manner. It can achieve the effect of slow release and enhanced penetration of essence at skin temperature by forming micelles with a self-hydrophobic effect close to human body temperature.

[0003] However, when PF127 is used alone at a certain concentration close to human body temperature, the gel formed by physical action is relatively weak and cannot meet the requirements for use as a mask substrate.

[0004] Therefore, developing a bio-friendly, strength-controllable, and temperature-sensitive gel material for hydrogel masks is of great significance. It can reduce skin irritation, increase skin affinity, provide long-lasting hydration, optimize the user experience, and achieve a slow-release and penetration-enhancing effect through temperature-sensitive in-situ release. Summary of the Invention

[0005] To overcome the technical shortcomings of existing thermosensitive hydrogel masks, the primary objective of this invention is to provide a method for preparing a thermosensitive, sustained-release, highly efficient transdermal delivery gel mask. This invention modifies acrylate double bonds by grafting Pluronic F127 and hyaluronic acid, and introduces a photoinitiator to induce chemical cross-linking between the materials under 365nm ultraviolet light, forming a stable and strong hydrogel. The introduction of PF127 imparts thermosensitive properties to the hydrogel, while the introduction of hyaluronic acid allows for controllable adjustment of gel strength and provides moisturizing and skin-care effects. By optimizing the feed ratio and increasing the number of feed cycles, the grafting rate of PF127-DA is significantly improved, resulting in higher gel strength after ultraviolet cross-linking of PF127-DA with a higher grafting rate.

[0006] Another objective of this invention is to provide a thermosensitive, slow-release, highly efficient transdermal delivery gel mask. In the presence of a photoinitiator, this invention pre-dissolves natural polymer thickeners, ingredients with whitening, moisturizing, soothing, and anti-aging effects, preservatives, and other substances into a precursor solution. These are then compounded with PF127-DA and HA-GMA in a specific ratio. Under ultraviolet light, the materials undergo photopolymerization, loading the functional components into the gel and endowing the gel mask with certain strength, elasticity, and skincare effects such as whitening and moisturizing.

[0007] Another object of the present invention is to provide an application of the above-mentioned thermosensitive sustained-release high-efficiency transdermal delivery gel mask. The hydrophobic group (PPO) of Pluronic F127 has a low LCST (low critical phase transition temperature), and therefore has the ability to self-assemble into micelles at a certain temperature, exhibiting temperature sensitivity. However, the molecular weight of polymers, including Pluronic, is not always constant. Therefore, the rate of thermosensitive release of gels obtained by photocrosslinking with PF127-DA as a substrate is not always the same, and varies to some extent.

[0008] The above-mentioned objective of the present invention is achieved through the following technical solution:

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

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

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

[0012] Preferably, PF127-DA in step (1) is PF127 modified with terminal acrylate double bonds.

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

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

[0015] Further, the reaction of Pluronic F127 with acryloyl chloride involves dissolving Pluronic F127 in dichloromethane, adding triethylamine and stirring until homogeneous, then adding acryloyl chloride and reacting under stirring to obtain a reaction solution; removing the dichloromethane from the reaction solution by rotary evaporation; adding the reaction solution to n-hexane while stirring, recrystallizing to precipitate a white solid product, filtering, dissolving the filtered solid product in dichloromethane, recrystallizing again, and repeating the same recrystallization operation to obtain PF127-DA after purification.

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

[0017] Furthermore, in step (1), the mass-to-volume ratio of Pluronic F127 to dichloromethane used to dissolve Pluronic F127 is 1 g: (1-5) mL, the mass-to-volume ratio of Pluronic F127 to triethylamine is (20-40) g: 1 mL, and the mass-to-volume ratio of 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-to-volume ratio of Pluronic F127 to dichloromethane is 1 g: 2 mL.

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

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

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

[0023] Preferably, the acryloyl chloride is fed three times. Repeated feeding can improve the grafting rate of PF127-DA.

[0024] Preferably, the volume of acryloyl chloride in the second and third feedings is halved.

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

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

[0027] Further, in step (1), the reaction of hyaluronic acid with glycidyl methacrylate is as follows: hyaluronic acid is fully dissolved in water, glycidyl methacrylate is added dropwise to the hyaluronic acid aqueous solution, stirred evenly, the pH is adjusted to acidic, and then heated to obtain a reaction solution; ethanol is taken, and the reaction solution is added to the ethanol while stirring, and after standing and separating into layers, it is filtered. The solid product obtained after filtration is then dissolved in water, and the same ethanol recrystallization operation is repeated to complete the purification 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 140 W.

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

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

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

[0033] Preferably, the mass-to-volume ratio of 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 1–12 mol / L.

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

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

[0037] Preferably, the heating reaction is carried out at a temperature of 60°C for 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 10-20 wt%, the amount of HA-GMA is 0.2-2 wt%, the amount of photoinitiator is 0.05-0.5 wt%, the amount of thickener is 0.5-3 wt%, the amount of active ingredient is 10-20 wt%, and the amount of preservative is 0.01-0.2 wt%.

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

[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 active 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-methylphenylacetone (Irgacure 2959).

[0044] Preferably, the thickener includes one or more of the following: carrageenan, long bean gum, cellulose gum, xanthan gum, guar gum, trehalose, gelatin, gum arabic, and agar. The thickener is primarily a water-soluble natural polymer.

[0045] Preferably, the active ingredients include one or more of the following: whitening ingredients, moisturizing ingredients, soothing and calming 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 vera extract, proanthocyanidins, niacinamide, resveratrol, and vitamin A; the moisturizing 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 vera extract, vitamin B5, allantoin, palmitoyl inositol, purslane extract, Centella asiatica extract, and chamomile extract; and 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 365nm, the light intensity is 50-196W, and the photocrosslinking time is 1-10min.

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

[0050] In a second aspect, a thermosensitive, sustained-release, high-efficiency transdermal delivery gel mask is provided, which is prepared by the method described in the first aspect.

[0051] Thirdly, the application of the thermosensitive, sustained-release, high-efficiency transdermal delivery gel mask as described in the second aspect in cosmetics is provided.

[0052] While PF127 alone, at a certain concentration and near human body temperature, exhibits relatively weak mechanical strength in the resulting gel due to physical processes, making it unsuitable for use as a mask substrate. This invention modifies PF127 by attaching acrylate double bonds to both ends, generating acrylated PF127 (PF127-DA). Further, ultraviolet light-induced free radical polymerization induces chemical crosslinking, resulting in a hydrogel with higher mechanical strength. Furthermore, hyaluronic acid, a commonly used "natural moisturizing factor" in cosmetics and a natural high-molecular-weight polysaccharide, can moisturize the stratum corneum, providing long-lasting hydration for human skin. By modifying the hydroxyl groups on the side chains of hyaluronic acid to methacrylate hyaluronic acid (HA-GMA), the introduced acrylate double bonds allow HA-GMA and PF127-DA to form a double-layered photocrosslinking network. The introduction of HA-GMA endows the gel with long-lasting moisturizing and skin-care functions. The addition of HA-GMA reduces the gel's strength. To ensure long-lasting hydration while maintaining high gel strength, the grafting rate of PF127-DA was significantly increased through optimization of the synthesis process, ultimately resulting in a thermosensitive, slow-release hydrogel mask containing a dual cross-linked network system. PF127-DA and HA-GMA constitute the base material of the hydrogel mask. Based on this, products with different skincare functions can be obtained by introducing other commonly used functional substances and essence ingredients in cosmetics.

[0053] The beneficial effects of this invention are as follows:

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

[0055] (2) By increasing the number of feedings and optimizing the reaction conditions, the grafting rate of PF127-DA is increased to over 90%.

[0056] (3) The hydrogel mask of the present invention has good skin affinity and is easy to peel off 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, which is conducive to achieving long-lasting moisturizing effect.

[0059] (6) The hydrogel of the present invention has strong tensile properties and a maximum tensile breaking strength of up to 250 kPa. The above data is sufficient to meet the basic mechanical strength requirements of the gel mask when it is attached to the skin in daily life. Attached Figure Description

[0060] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the following description of the embodiments will be briefly introduced. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

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

[0062] Figure 2 These are stretch data diagrams of the face masks prepared in Embodiment 1 and Comparative Examples 1-3 of the present invention;

[0063] Figure 3 This is the proton NMR spectrum of PF127-DA in Example 1 of this invention;

[0064] Figure 4 This is the proton NMR spectrum of PF127-DA in Comparative Example 1 of this invention;

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

[0066] Figure 6 This is a macroscopic view of the thermosensitive sustained-release high-efficiency transdermal delivery gel mask prepared in Example 1 of this invention;

[0067] Figure 7 This is an electron micrograph of the thermosensitive sustained-release high-efficiency transdermal delivery gel mask prepared in Example 1 of the present invention. Detailed Implementation

[0068] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort 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 "comprising" and "including" indicate the presence of the described features, integrals, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

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

[0071] It should also be further understood that the term "and / or" as used in this specification and the appended claims refers to any combination of one or more of the associated listed items and all possible combinations, and includes such combinations.

[0072] To better understand the technical content of the present invention, the technical solution of the present invention will be further introduced and explained below with reference to specific embodiments.

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

[0074] Example 1

[0075] A method for preparing a thermosensitive, sustained-release, highly efficient transdermal delivery gel mask includes the following steps:

[0076] (1) Pluronic F127 (400g) was dissolved in dichloromethane (800mL) at low temperature (3℃). Triethylamine (15mL) was added and stirred until well mixed. Acryloyl chloride (15mL) was then added and reacted for 12h under stirring to obtain a reaction solution. To improve the grafting rate of the product, the reaction was repeated twice every 12h. The amount of acryloyl chloride added in the second and third reactions was 7.5mL. More than half (by volume) of dichloromethane in the reaction solution was removed by rotary evaporation. An excess of n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. After recrystallization, a white solid product was precipitated and filtered. The solid product obtained after filtration was dissolved in dichloromethane and recrystallized again. The same recrystallization operation was repeated 3 times to obtain PF127-DA after purification. The obtained PF127-DA solid powder was dried under vacuum at room temperature (25℃). A high grafting rate PF127 (PF127-DA) material with acrylate double bonds attached to both ends was prepared.

[0077] Hyaluronic acid (9.3 g) was dissolved in deionized water (900 mL) and stirred for 6 hours until completely dissolved. Glycidyl methacrylate (11.6 mL) was added dropwise to the hyaluronic acid aqueous solution, and after stirring until homogeneous, the pH was adjusted to 5 with hydrochloric acid (1 mol / L). The mixture was heated at 60 °C for 12 hours to obtain a reaction solution. Excess ethanol was added to the reaction solution while stirring, and the mixture was allowed to stand for separation and then filtered. The solid product obtained after filtration 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 °C. A hydroxyl group modified hyaluronic acid (HA-GMA) material with methacrylate on the side chain was prepared.

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

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

[0080] Comparative Example 1

[0081] A method for preparing a high-grafting-rate PF127 hydrogel mask includes the following steps:

[0082] (1) Pluronic F127 (400g) was dissolved in dichloromethane (800mL) at low temperature (3℃). Triethylamine (15mL) was added and stirred until well mixed. Acryloyl chloride (15mL) was then added and reacted for 12h under stirring to obtain a reaction solution. To improve the grafting rate of the product, the reaction was repeated twice every 12h. The amount of acryloyl chloride added in the second and third reactions was 7.5mL. More than half (by volume) of dichloromethane in the reaction solution was removed by rotary evaporation. An excess of n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. After recrystallization, a white solid product was precipitated and filtered. The solid product obtained after filtration was dissolved in dichloromethane and recrystallized again. The same recrystallization operation was repeated 3 times to obtain PF127-DA after purification. The obtained PF127-DA solid powder was dried under vacuum at room temperature (25℃). A high grafting rate PF127 (PF127-DA) material with acrylate double bonds attached to both ends was prepared.

[0083] (2) Add PF127-DA (0.6g) and Irgacure 2959 (0.012g) to a 10mL centrifuge tube. To further enhance the elasticity of the gel and provide a superior user experience, carrageenan (0.08g) and carob gum (0.02g) were added to the centrifuge tube as thickeners. Glycerin (0.4g), dipotassium glycyrrhizate (0.02g), nicotinamide (0.08g), collagen (0.2g), and betaine (0.02g) were added to the centrifuge tube as active ingredients. Chlorphenesin (0.002g) was added to the centrifuge tube as a preservative. Finally, deionized water (2.566mL) was added to dissolve the gel completely, and the bubbles were eliminated by sonication. After complete dissolution, the precursor solution of the hydrogel was poured into the mold, and the mold was placed under ultraviolet light at 365nm and 100W intensity for 5 minutes to obtain the hydrogel, thus preparing the high grafting rate PF127 hydrogel mask of Comparative Example 1.

[0084] (3) Soak the prepared high grafting rate PF127 hydrogel mask in deionized water for 10 minutes, and then rinse it with deionized water 3 times.

[0085] Comparative Example 2

[0086] A method for preparing a low-grafting-rate PF127 / hyaluronic acid hydrogel mask includes the following steps:

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

[0088] Hyaluronic acid (9.3 g) was dissolved in deionized water (900 mL) and stirred for 6 hours until completely dissolved. Glycidyl methacrylate (11.6 mL) was added dropwise to the hyaluronic acid aqueous solution, and after stirring until homogeneous, the pH was adjusted to 5 with hydrochloric acid (1 mol / L). The mixture was heated at 60 °C for 12 hours to obtain a reaction solution. Excess ethanol was added to the reaction solution while stirring, and after standing and separating into layers, the mixture was filtered. The solid product obtained after filtration was dissolved in water, and the same ethanol recrystallization operation was repeated 3 times to obtain HA-GMA after purification. The purified sample was dried in a vacuum drying oven at 40 °C. A hydroxyl-modified hyaluronic acid (HA-GMA) material with methacrylate on the side chain was prepared.

[0089] (2) PF127-DA (0.6g), HA-GMA (0.02g), and Irgacure 2959 (0.012g) were added to a 10mL centrifuge tube. To further enhance the elasticity of the gel and provide a superior user experience, carrageenan (0.08g) and carob gum (0.02g) were added as thickeners to the centrifuge tube. Glycerin (0.4g), dipotassium glycyrrhizate (0.02g), nicotinamide (0.08g), collagen (0.2g), and betaine (0.02g) were added as active ingredients to the centrifuge tube. Chlorphenesin (0.002g) was added as a preservative to the centrifuge tube. Finally, deionized water (2.546mL) was added and stirred to dissolve the gel. The mixture was then sonicated to remove air bubbles. After complete dissolution, the hydrogel precursor solution was poured into a mold. The mold was then placed under 365nm ultraviolet light with an intensity of 100W for photocrosslinking for 5min. A low grafting rate PF127 / hyaluronic acid hydrogel mask was prepared.

[0090] (4) Soak the prepared low grafting rate PF127 / hyaluronic acid hydrogel mask in deionized water for 10 minutes, and rinse it 3 times with deionized water.

[0091] Comparative Example 3

[0092] A method for preparing a low-grafting-rate PF127 hydrogel mask includes the following steps:

[0093] (1) Pluronic F127 (400g) was dissolved in dichloromethane (800mL) at low temperature (3℃). Triethylamine (15mL) was added and stirred until homogeneous. Acryloyl chloride (15mL) was then added and reacted for 12h under stirring to obtain a reaction solution. More than half (by volume) of the dichloromethane in the reaction solution was removed by rotary evaporation. An excess of n-hexane was prepared, and the reaction solution was added to the excess n-hexane while stirring. After recrystallization, a white solid product was precipitated 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 to obtain PF127-DA after purification. The obtained PF127-DA solid powder was dried under vacuum at room temperature (25℃). A low-grafting-rate PF127 (PF127-DA) material with acrylate double bonds attached to both ends to form acrylated PF127 was prepared.

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

[0095] (3) Soak the prepared low grafting rate PF127 hydrogel mask in deionized water for 10 minutes, and rinse it 3 times with deionized water.

[0096] Performance Testing – Temperature-Sensitive Release Effect Test

[0097] To study the thermosensitive release effect of the gel mask, the hydrogel sample (thermosensitive sustained-release high-efficiency transdermal delivery gel mask) obtained in Example 1 was immersed in deionized water and stored at 4°C for 24 hours, during which the hydrogel completely swelled in the water. Afterwards, the sample was removed 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 shrinkage. The shrinkage was calculated according to the following formula:

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

[0099] When determining the weight of a hydrogel, the weight of the sample should be measured after removing as much surface moisture as possible, as water droplets on the surface may introduce errors. Figure 1 This is a shrinkage rate graph of the thermosensitive sustained-release high-efficiency transdermal delivery gel mask prepared in Example 1 of this invention. Figure 1 As shown, the hydrogel sample containing 20 wt% PF127-DA exhibited a release rate of nearly 30% within 15 minutes. While patent KR101462390B1 also uses PF127-DA to prepare hydrogels, the sample containing 25 wt% PF127-DA in that patent only reached 30% release after 30 minutes. In contrast, the thermosensitive sustained-release high-efficiency transdermal delivery gel mask prepared in this invention exhibits a faster thermosensitive release effect.

[0100] Performance testing – Mechanical performance testing

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

[0102] Figure 2 These are stretch data diagrams of the face masks prepared in Embodiment 1 and Comparative Examples 1-3 of the present invention. Figure 2 As shown, the high-grafting-rate PF127 / hyaluronic acid hydrogel mask of Example 1 has a maximum tensile strength of 250 kPa and a maximum tensile strain of approximately 90%. The high-grafting-rate PF127 hydrogel mask of Comparative Example 1 has a maximum tensile strength of approximately 320 kPa and a maximum tensile strain of approximately 110%. The low-grafting-rate PF127 / hyaluronic acid hydrogel mask of Comparative Example 2 has a maximum tensile strength of approximately 17 kPa and a maximum tensile strain of approximately 150%. The low-grafting-rate PF127 hydrogel mask of Comparative Example 3 has a maximum tensile strength of approximately 30 kPa and a maximum tensile strain of approximately 240%.

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

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

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

[0106] 2) The presence of PF127 with a high grafting rate enables the gel mask to provide high mechanical strength while retaining the hyaluronic acid crosslinking network. Simultaneously, the gel prepared by this method achieves excellent temperature-sensitive release.

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

[0108] 4) Figure 7 This is an electron micrograph of the thermosensitive sustained-release high-efficiency transdermal delivery gel mask prepared in Example 1 of the present invention. Figure 7 The SEM image of the gel shows that it contains a dense micro-network of pores, which enables it to load and release the mask's functional solution.

[0109] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the technical scope disclosed in the present invention, and these modifications or substitutions should all be covered within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A method for preparing a thermosensitive, sustained-release, high-efficiency transdermal delivery gel mask, characterized in that, Includes the following steps: (1) Pluronic F127 was reacted with acryloyl chloride to obtain PF127-DA; hyaluronic acid was reacted with glycidyl methacrylate to obtain HA-GMA; (2) The PF127-DA and HA-GMA obtained in step (1) are mixed with photoinitiator, thickener, active ingredient, preservative and water pre-dissolved and poured into the mold after complete dissolution. The mold is placed under ultraviolet light for photocrosslinking to obtain hydrogel, thus obtaining the temperature-sensitive sustained-release high-efficiency transdermal delivery gel mask. In step (1), the reaction of Pluronic F127 with acryloyl chloride is as follows: Pluronic F127 is dissolved in dichloromethane, triethylamine is added and stirred until homogeneous, then acryloyl chloride is added and reacted under stirring to obtain a reaction solution; dichloromethane in the reaction solution is removed by rotary evaporation; the reaction solution is added to n-hexane while stirring, and after recrystallization, a white solid product is precipitated and filtered. The solid product obtained after filtration is dissolved in dichloromethane and recrystallized again. The same recrystallization operation is repeated to complete the purification and obtain PF127-DA. In step (1), acryloyl chloride is added 1 to 3 times; each time it is added, the reaction time between Pluronic F127 and acryloyl chloride is 12 to 24 hours. In step (1), the reaction of hyaluronic acid with glycidyl methacrylate is as follows: hyaluronic acid is fully dissolved in water, glycidyl methacrylate is added dropwise to the hyaluronic acid aqueous solution, stirred evenly, the pH is adjusted to acidic, and then heated to obtain a reaction solution; ethanol is taken, and the reaction solution is added to the ethanol while stirring, allowed to stand for layering, and then filtered. The solid product obtained after filtration is then dissolved in water, and the same ethanol recrystallization operation is repeated to complete the purification and obtain HA-GMA; the molecular weight range of the hyaluronic acid is 70-140W. In step (1), the mass-to-volume ratio of Pluronic F127 to dichloromethane used to dissolve Pluronic F127 is 1 g: (1-5) mL, the mass-to-volume ratio of Pluronic F127 to triethylamine is (20-40) g: 1 mL, and the mass-to-volume ratio of Pluronic F127 to acryloyl chloride is (20-40) g: 1 mL. In step (2), the amount of PF127-DA is 10-20 wt%, the amount of HA-GMA is 0.2-2 wt%, the amount of photoinitiator is 0.05-0.5 wt%, the amount of thickener is 0.5-3 wt%, the amount of active ingredient is 10-20 wt%, and the amount of preservative is 0.01-0.2 wt%. In step (2), the wavelength of the ultraviolet light is 365nm, the light intensity is 50-196W, and the photocrosslinking time is 1-10min.

2. The method for preparing the thermosensitive sustained-release high-efficiency transdermal delivery gel mask as described in claim 1, characterized in that, The mass-to-volume ratio of the hyaluronic acid to glycidyl methacrylate is 1 g: (1-5) mL.

3. A temperature-sensitive, sustained-release, high-efficiency transdermal delivery gel mask, characterized in that, The thermosensitive sustained-release high-efficiency transdermal delivery gel mask is prepared by the method described in any one of claims 1-2.

4. The application of the thermosensitive, sustained-release, high-efficiency transdermal delivery gel mask as described in claim 3 in cosmetics.

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