Resveratrol-loaded antioxidant composite hydrogel and preparation method thereof

Abstract

The present invention provides a resveratrol-loaded antioxidant composite hydrogel and a preparation method thereof, belonging to the technical field of bionanomaterials. The present invention provides resveratrol self-assembled nanoparticles, comprising resveratrol, dopamine nonanoate, and vitamin C ethyl ether. The nanoparticles have the characteristics of uniform and controllable particle size and simple synthesis method. By coating the resveratrol self-assembled nanoparticles by an electrostatic spraying method, a resveratrol-loaded antioxidant composite hydrogel can be obtained. The antioxidant composite hydrogel can achieve controlled release of resveratrol and can achieve a synergistically enhanced free radical scavenging effect of resveratrol, dopamine nonanoate, and vitamin C ethyl ether, and has broad application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of biological nanomaterials and relates to a resveratrol-loaded antioxidant composite hydrogel and a preparation method thereof. Background Art

[0002] Resveratrol, also known as resveratrol, is a natural diphenylethylene compound found in plants such as grapes, peanuts, and Japanese knotweed. It has antibacterial, anti-aging, cardiovascular protection, antioxidant, anti-inflammatory, bactericidal and moisturizing effects. It is suitable for removing skin acne, herpes, wrinkles, etc. and can be used in moisturizing, night creams, and moisturizing cosmetics. However, resveratrol is a fat-soluble substance and is basically insoluble in water. Its low bioavailability and low solubility limit its use.

[0003] Nanomicelles are one of the newest areas of cosmetic application, gaining increasing popularity and commercialization. Their high surface area enables efficient delivery of bioactive ingredients to the skin. Hydrophilic micellar nanoparticles play a key role in effective cosmetic formulations, including makeup removers, facial cleansers, anti-aging lotions, sunscreens, and other water-based cosmetics.

[0004] Vitamin C, also known as ascorbic acid, is a water-soluble vitamin with antioxidant and whitening properties. Its whitening mechanism lies in its ability to directly inhibit tyrosinase activity, reducing melanin synthesis, and its reducing properties, which reduces dopamine quinone to dopamine and prevents dopamine from being oxidized to dopamine quinone. Due to its water-soluble nature, vitamin C cannot penetrate the intact stratum corneum barrier to exert its effect. Vitamin C ethyl ether, on the other hand, is not only chemically very stable but also a hydrophilic and lipophilic substance, which greatly expands its scope of application, especially in daily chemical applications. 3-O-ethyl ascorbic acid ether (vitamin C ethyl ether) easily penetrates the stratum corneum and enters the dermis. Once in the body, it is easily decomposed by biological enzymes in the body, thereby exerting the biological effects of vitamin C.

[0005] Nonanoic acid dopamine (NND) is a derivative of dopamine. Its structure is dopamine bonded to a molecule of nonanoic acid through an amide bond. The introduction of the nonanoic acid group makes nonanoic acid dopamine less likely to undergo self-polymerization, thereby improving the stability of dopamine and enhancing its hydrophobicity. There are also related reports that the structure of nonanoic acid dopamine is similar to that of catecholamine compounds and has anti-inflammatory effects similar to catecholamines.

[0006] Nanogel particles are three-dimensional networks formed by cross-linking polymer chains. In different solvents, the gel particles swell to varying degrees depending on the solvent quality and cross-link density, reaching sizes ranging from tens to hundreds of nanometers. When the size reaches the micrometer level, they are generally referred to as microgels. In recent years, the application of micro-nanogels in drug delivery, tissue engineering, and biopharmaceutical implants has garnered increasing attention.

[0007] The molecular structure of sodium alginate is composed of β-D-mannuronic acid (M) and α-L-guluronic acid (G) linked by a (1→4) bond. Aqueous solutions of sodium alginate have a high viscosity and have been used as a thickener, stabilizer, and emulsifier in foods. It was included in the United States Pharmacopoeia as early as 1938.

[0008] Electrostatic spraying (electrospray) is a simple technology that can prepare almost all polymer materials into particles with diameters ranging from nanometers to micrometers. Its working principle is that under a high-voltage electrostatic field, the target substance (electrospray liquid) rapidly generates a large amount of charge. The huge Coulomb repulsion between the charges gradually splits the electrospray liquid into small droplets. After the small droplets solidify, particles with controllable particle size can be obtained. By adjusting the parameters of the electrostatic spray, monodisperse microspheres of different particle sizes can be obtained. The biggest advantage of this preparation method is that it can produce high-quality, highly monodisperse microspheres with a controllable particle size range, and it only contains an aqueous phase. It is a simple and environmentally friendly preparation method.

[0009] Chinese patent CN117398361A provides resveratrol-loaded exosome-liposome hybrid nanoparticles, their preparation method, and applications. The raw materials include lipids, resveratrol, and exosomes. The exosomes are derived from dental pulp stem cells. These nanoparticles can be used to prepare antioxidants, anti-inflammatory drugs, or immunomodulatory drugs. However, this technology utilizes cellular exosomes, which poses a potential biogenic risk, and does not address the self-assembly process of dopamine pelargonate and vitamin C ethyl ether with resveratrol.

[0010] Chinese patent CN117297090A provides a method for preparing a resveratrol-loaded ovalbumin fibril / chitosan composite hydrogel and its application. This technology prepares a method for loading a composite hydrogel with bioactive molecules through the self-assembly characteristics of amyloid fibrils. The process is simple to operate, and no additional organic cross-linking reagents are added during the preparation process. It is safe and has no toxic side effects. The prepared hydrogel has the advantages of good stability, high loading rate, and good biocompatibility, and can be applied to the fields of food, medicine, health products, and cosmetics. However, the gel material provided by this technology is large in size (hundreds of microns in size and in sheet form), and resveratrol is loaded on the outside of the gel, and the release rate is very fast.

[0011] Shui Yu et al., in the article "Controlled Fabrication of Polydopamine Nanocapsules via Polymerization-Induced Self-Assembly" (Chem. Mater. 2022, 34, 19, 8705-8710), provide a method for synthesizing a hollow poly (nonanoic acid dopamine)-dopamine micelle system, in which micelles are formed by self-assembly of the hydrophobic tail of nonanoic acid dopamine, and then converted into a shell structure of a nanocapsule by ripening. However, this technology does not involve the preparation of resveratrol self-assembled nanoparticles.

[0012] In summary, the existing technologies cannot provide a nanomaterial that overcomes the following problems:

[0013] (1) Resveratrol is easily oxidized, has poor water solubility, and low bioavailability. Chemical modification of resveratrol poses biosafety risks.

[0014] (2) Conventional encapsulation technology is difficult to control the release behavior of resveratrol and it is difficult to provide a material with a high release rate and slow release.

[0015] (3) Conventional encapsulation technology is cumbersome and requires a large amount of organic solvents, and the encapsulation affects the antioxidant properties of resveratrol. Summary of the Invention

[0016] In view of this, in order to solve the problem that the existing technology is difficult to provide a resveratrol nanomaterial with more stable controlled release, higher release rate and better antioxidant effect, the purpose of the present invention is to provide a resveratrol-loaded antioxidant composite hydrogel and a preparation method thereof.

[0017] To achieve the above object of the invention, in one aspect, the present invention provides a resveratrol self-assembled nanoparticle comprising resveratrol, dopamine nonanoate and vitamin C ethyl ether.

[0018] Preferably, the resveratrol self-assembled nanoparticles are self-assembled from resveratrol, dopamine pelargonate and vitamin C ethyl ether.

[0019] More preferably, the driving force for the self-assembly includes hydrogen bonding and hydrophobic forces.

[0020] Preferably, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.0001-5:0.0001-5.

[0021] More preferably, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.001-2:0.001-2.

[0022] More preferably, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.14-0.185:0.02-0.1.

[0023] Further preferably, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine and the resveratrol is 1:0.14-0.185:0.08.

[0024] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.145:0.08.

[0025] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.15:0.08.

[0026] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.155:0.08.

[0027] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.16:0.08.

[0028] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.165:0.08.

[0029] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.17:0.08.

[0030] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.18:0.08.

[0031] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.185:0.08.

[0032] Further preferably, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine and the resveratrol is 1:0.175:0.02-0.1.

[0033] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.175:0.02.

[0034] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.175:0.04.

[0035] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.175:0.06.

[0036] As an embodiment of the present invention, in the resveratrol self-assembled nanoparticles, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine, and the resveratrol is 1:0.175:0.1.

[0037] Most preferably, and as an embodiment of the present invention, the mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine and the resveratrol is 1:0.175:0.08.

[0038] Preferably, the average hydrated particle size of the resveratrol self-assembled nanoparticles is 200-700 nm.

[0039] More preferably, the average hydrated particle size of the resveratrol self-assembled nanoparticles is 223.83-633.8 nm.

[0040] More preferably, the average hydrated particle size of the resveratrol self-assembled nanoparticles is 223.83-445.93 nm.

[0041] In another aspect, the present invention provides a method for preparing the above-mentioned resveratrol self-assembled nanoparticles, comprising the following steps:

[0042] S1. Mixing vitamin C ethyl ether, dopamine nonanoate, and resveratrol with a solvent to obtain liquid A, liquid B, and liquid C, respectively;

[0043] S2. Mixing the liquid A, liquid B, and liquid C obtained in step S1, ultrasonically dispersing, rotary evaporating, adding water, and ultrasonically dispersing again to obtain resveratrol self-assembled nanoparticles dispersed in water.

[0044] Preferably, in step S1, the solvent is selected from at least one of water, alcohol, ester, dimethyl sulfoxide, tetrahydrofuran, and N,N-dimethylformamide.

[0045] More preferably, in step S1, the solvent is selected from at least one of alcohol, ester, dimethyl sulfoxide, tetrahydrofuran, and N,N-dimethylformamide.

[0046] More preferably, in step S1, the solvent is selected from at least one of methanol, ethanol, ethyl acetate, and dimethyl sulfoxide.

[0047] Further preferably, and as a specific embodiment of the present invention, the solvent is methanol.

[0048] Preferably, in step S1, the concentration of solution A is 0.01-5 mg / mL.

[0049] More preferably, in step S1, the concentration of solution A is 0.1-2 mg / mL.

[0050] More preferably, in step S1, the concentration of solution A is 1 mg / mL.

[0051] Preferably, in step S1, the concentration of solution B is 0.01-5 mg / mL.

[0052] More preferably, in step S1, the concentration of solution B is 0.1-2 mg / mL.

[0053] More preferably, in step S1, the concentration of solution B is 1 mg / mL.

[0054] Preferably, in step S1, the concentration of solution C is 0.01-5 mg / mL.

[0055] More preferably, in step S1, the concentration of solution C is 0.1-2 mg / mL.

[0056] More preferably, in step S1, the concentration of solution C is 1 mg / mL.

[0057] Preferably, in step S2, the volume ratio of the mixture of liquid A, liquid B and liquid C is 1:0.01-1:0.01-1.

[0058] More preferably, in step S2, the volume ratio of the mixture of liquid A, liquid B and liquid C is 1:0.1-0.5:0.01-0.5.

[0059] More preferably, in step S2, the volume ratio of the mixture of liquid A, liquid B and liquid C is 1:0.14-0.185:0.01-0.1.

[0060] Further preferably, in step S2, the volume ratio of the mixture of liquid A, liquid B and liquid C is 1:0.14-0.185:0.02-0.1.

[0061] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.14:0.08.

[0062] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.145:0.08.

[0063] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.15:0.08.

[0064] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.155:0.08.

[0065] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.16:0.08.

[0066] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.17:0.08.

[0067] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.175:0.08.

[0068] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.18:0.08.

[0069] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.185:0.08.

[0070] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.175:0.02.

[0071] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.175:0.04.

[0072] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.175:0.06.

[0073] As an embodiment of the present invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.175:0.1.

[0074] Most preferably, and as an embodiment of the invention, in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.175:0.08.

[0075] Preferably, in step S2, the mixing is uniform mixing.

[0076] Preferably, in step S2, the ultrasonic dispersion time is 5-15 minutes.

[0077] More preferably, and as an example of the present invention, in step S2, the ultrasonic dispersion time is 10 minutes.

[0078] Preferably, in step S2, the rotary evaporation is specifically a rotary evaporation to remove the solvent described in step S1.

[0079] Preferably, the volume ratio of the amount of water added in step S2 to the amount of liquid A in step S1 is 2-8:1.

[0080] More preferably, and as an example of the present invention, the volume ratio of the amount of water added in step S2 to the volume ratio of the liquid A in step S1 is 5:1.

[0081] Preferably, in step S2, before the secondary ultrasonic dispersion, the mixture is heated to 30-50°C for 15-30 minutes.

[0082] More preferably, and as an example of the present invention, in step S2, before the secondary ultrasonic dispersion, the mixture is heated to 40°C for 20 minutes.

[0083] Preferably, in step S2, the duration of the secondary ultrasound is 5-15 minutes.

[0084] More preferably, and as an example of the present invention, in step S2, the time of the secondary ultrasound is 10 minutes.

[0085] In another aspect, the present invention provides a resveratrol-loaded antioxidant composite hydrogel, wherein the active ingredient comprises the above-mentioned resveratrol self-assembled nanoparticles and / or the resveratrol self-assembled nanoparticles prepared by the above-mentioned preparation method.

[0086] In another aspect, the present invention provides a method for preparing the above-mentioned antioxidant composite hydrogel, comprising the following steps:

[0087] T1. Mixing sodium alginate with water to obtain a sodium alginate aqueous solution;

[0088] T2, mixing the resveratrol self-assembled nanoparticles dispersed in water with the sodium alginate aqueous solution obtained in step T1, and stirring to obtain a gel precursor solution;

[0089] T3. Electrostatically spray the gel precursor solution obtained in step T2 and collect it using a receiving liquid to obtain an antioxidant composite hydrogel.

[0090] Preferably, in step T1, the concentration of the sodium alginate aqueous solution is 2-6 g / 100 mL.

[0091] As an embodiment of the present invention, in step T1, the concentration of the sodium alginate aqueous solution is 2 g / 100 mL.

[0092] More preferably, in step T1, the concentration of the sodium alginate aqueous solution is 4-6 g / 100 mL.

[0093] As an embodiment of the present invention, in step T1, the concentration of the sodium alginate aqueous solution is 6 g / 100 mL.

[0094] More preferably, and as an embodiment of the present invention, in step T1, the concentration of the sodium alginate aqueous solution is 4 g / 100 mL.

[0095] Preferably, in step T2, the concentration of the resveratrol self-assembled nanoparticles dispersed in water is 0.1-1 mg / mL.

[0096] More preferably, in step T2, the concentration of the resveratrol self-assembled nanoparticles dispersed in water is 0.1-0.5 mg / mL.

[0097] More preferably, and as an embodiment of the present invention, in step T2, the concentration of the resveratrol self-assembled nanoparticles dispersed in water is 0.251 mg / mL.

[0098] Preferably, the volume ratio of the resveratrol self-assembled nanoparticles dispersed in water in step T2 to the sodium alginate aqueous solution in step T1 is 1:0.1-10.

[0099] More preferably, and as an example of the present invention, the volume ratio of the resveratrol self-assembled nanoparticles dispersed in water in step T2 to the sodium alginate aqueous solution in step T1 is 1:1.

[0100] Preferably, the stirring is stirring at room temperature.

[0101] Preferably, the stirring time is 10-100 min.

[0102] More preferably, the stirring time is 30 min.

[0103] Preferably, in step T3, the conditions for the electrostatic spraying include a flow rate of 8-12 mL / h.

[0104] As an embodiment of the present invention, in step T3, the conditions of the electrostatic spraying include a flow rate of 10 mL / h.

[0105] As an embodiment of the present invention, in step T3, the conditions of the electrostatic spraying include a flow rate of 8 mL / h.

[0106] As an embodiment of the present invention, in step T3, the conditions of the electrostatic spraying include a flow rate of 12 mL / h.

[0107] More preferably, in step T3, the conditions of the electrostatic spraying include a flow rate of 12 mL / h or a flow rate of 8 mL / h.

[0108] More preferably, in step T3, the conditions for the electrostatic spraying include a flow rate of 8 mL / h.

[0109] Preferably, in step T3, the electrostatic spraying conditions include a voltage of 15-25 kV.

[0110] As an embodiment of the present invention, in step T3, the electrostatic spraying condition includes a voltage of 25 kV.

[0111] More preferably, in step T3, the electrostatic spraying conditions include a voltage of 15-20 kV.

[0112] As an embodiment of the present invention, in step T3, the electrostatic spraying condition includes a voltage of 20 kV.

[0113] More preferably, and as an embodiment of the present invention, in step T3, the conditions for the electrostatic spraying include a voltage of 15 kV.

[0114] Preferably, in step T3, the receiving liquid is selected from one of water, alcohol aqueous solution, surfactant aqueous solution, and surfactant alcohol aqueous solution.

[0115] More preferably, in step T3, the receiving liquid is selected from one of water, an alcohol aqueous solution, and an aqueous surfactant solution.

[0116] Wherein, the surfactant is a water-soluble surfactant, including but not limited to PEG, PAA, PEI, PVP and the like.

[0117] More preferably, the surfactant is PEG.

[0118] More preferably, the surfactant is PEG400.

[0119] More preferably, the alcohol in the alcohol aqueous solution is selected from methanol, ethanol, propanol, ethylene glycol, propylene glycol, and glycerol.

[0120] More preferably, the alcohol aqueous solution is an alcohol aqueous solution with a mass ratio of 1%-15%.

[0121] More preferably, the alcohol aqueous solution is an alcohol aqueous solution with a mass ratio of 5%.

[0122] More preferably, the surfactant aqueous solution is an alcohol aqueous solution with a mass ratio of 1-15%.

[0123] More preferably, the surfactant aqueous solution is a 5% by mass alcohol aqueous solution.

[0124] As an embodiment of the present invention, in step T3, the receiving liquid is water.

[0125] As an embodiment of the present invention, in step T3, the receiving liquid is an ethanol aqueous solution with a mass ratio of 5%.

[0126] As an embodiment of the present invention, in step T3, the receiving liquid is a 5% by mass glycerol aqueous solution.

[0127] As an embodiment of the present invention, in step T3, the receiving solution is a 5% by mass PEG400 aqueous solution.

[0128] In another aspect, the present invention provides a drug, the active ingredients of which include the above-mentioned resveratrol self-assembled nanoparticles and / or the resveratrol self-assembled nanoparticles prepared by the above-mentioned preparation method and / or the above-mentioned antioxidant composite hydrogel and / or the antioxidant composite hydrogel prepared by the above-mentioned preparation method.

[0129] In another aspect, the present invention provides a cosmetic, the active ingredients of which include the above-mentioned resveratrol self-assembled nanoparticles and / or the resveratrol self-assembled nanoparticles prepared by the above-mentioned preparation method and / or the above-mentioned antioxidant composite hydrogel and / or the antioxidant composite hydrogel prepared by the above-mentioned preparation method.

[0130] In another aspect, the present invention provides the use of the above-mentioned resveratrol self-assembled nanoparticles and preparation methods thereof, antioxidant composite hydrogel and preparation methods thereof in the production of antioxidant products.

[0131] Preferably, the antioxidant products include medicines and cosmetics.

[0132] Compared with the prior art, the present invention has the following beneficial effects:

[0133] (1) Resveratrol self-assembled nanoparticles were successfully synthesized by utilizing the intermolecular hydrogen bonding and hydrophobic forces of amphiphilic vitamin C ethyl ether, nonanoic acid dopamine (NND) and resveratrol molecules.

[0134] (2) An antioxidant composite hydrogel was prepared using the above-mentioned nanoparticles. The antioxidant composite hydrogel was prepared by an electrostatic spraying method and has the characteristics of small particle size, large specific surface area, simple preparation, and large-scale preparation. It broadens the application range of resveratrol-loaded nanoparticles in drug delivery or cosmetics.

[0135] (3) The prepared resveratrol self-assembled nanoparticles and antioxidant composite hydrogel have the effect of controlled release of resveratrol, and the resveratrol release rate is high.

[0136] (4) DPPH test showed that the prepared resveratrol self-assembled nanoparticles had synergistically enhanced free radical scavenging ability.

[0137] (5) The preparation process of the self-assembled nanoparticles and antioxidant composite hydrogel provided by the present invention is simple, easy to implement, green and environmentally friendly, and suitable for large-scale promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0138] Figure 1 This is the H NMR spectrum of dopamine nonanoate.

[0139] Figure 2 This is a graph of the critical micelle concentration of the nanoparticles prepared in Comparative Example 1.

[0140] Figure 3 This is a standard curve diagram for determining resveratrol concentration using UV-visible absorption spectroscopy.

[0141] Figure 4 It is a line graph showing the encapsulation efficiency and drug loading of the self-assembled nanoparticles prepared in Example 1 and Examples 3.1-3.4 as a function of the dosage of resveratrol; wherein, a dosage of 20 μg corresponds to Example 3.1, a dosage of 40 μg corresponds to Example 3.2, a dosage of 60 μg corresponds to Example 3.3, a dosage of 80 μg corresponds to Example 1, and a dosage of 100 μg corresponds to Example 3.4.

[0142] Figure 5 Graphs showing the resveratrol drug release curves of the resveratrol self-assembled nanoparticles prepared in Example 1 and the antioxidant composite hydrogels prepared in Example 4 and Example 8.3.

[0143] Figure 6 3. It is a graph showing the DPPH clearance test results of the resveratrol self-assembled nanoparticles prepared in Example 1, the antioxidant composite hydrogel prepared in Example 8.3, and the nanoparticles without resveratrol prepared in Comparative Example 1. DETAILED DESCRIPTION

[0144] The following non-limiting examples are provided to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way. The following is merely an illustrative description of the scope of the present invention, and those skilled in the art may make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0145] The present invention will be further described below by way of specific examples. The various chemical reagents used in the examples of the present invention were obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all by weight. Unless otherwise specified, it is understood that the experiments were conducted at room temperature.

[0146] In the present invention, the instrument used for preparing resveratrol nanogel by electrostatic spraying is a professional electrospinning device, manufactured by Foshan Qingzi Precision Measurement and Control Technology Co., Ltd., and the model is E02-001.

[0147] In the following examples, the sources of some raw materials are shown in Table 1:

[0148] Table 1

[0149]

[0150] The preparation method of the raw material nonanoic acid dopamine used in each embodiment of the present invention is based on the method described in Angewandte Chemie 2015, 127, 4840-4845. The specific steps are as follows:

[0151] 1mmol of nonanoic acid, 1mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and 1mmol of 1-hydroxybenzotriazole (HOBt) were added to 5mL of anhydrous DMF, stirred in an ice-salt bath at 0℃, and then stirred at room temperature for 30min. Then 1mmol of dopamine hydrochloride and 3mmol of triethylamine were added, stirred at room temperature for 14h, then extracted twice with 30mL of ethyl acetate, and finally purified by flash chromatography column (developing solvent ratio of dichloromethane: methanol = 50:2) to obtain nonanoic acid dopamine (NND). The nonanoic acid dopamine obtained by dissolving in deuterated DMSO was detected by nuclear magnetic resonance hydrogen spectrum, and the detection results are as follows: Figure 1 As shown, it can be seen that each peak is completely assigned, and dopamine nonanoate is successfully synthesized with a purity of 98.52%.

[0152] Example 1

[0153] Preparation of resveratrol self-assembled nanoparticles.

[0154] S1. Dissolve vitamin C ethyl ether, dopamine nonanoate, and resveratrol in methanol respectively to prepare the following:

[0155] Solution A: 1 mg / mL ascorbyl ethyl ether methanol solution;

[0156] Solution B: 1 mg / mL dopamine nonanoate solution in methanol;

[0157] Solution C: 1 mg / mL resveratrol solution in methanol.

[0158] S2. Mix 1 mL of Solution A, 0.175 mL of Solution B, and 0.08 mL of Solution C, and disperse them ultrasonically for 10 minutes. Remove the methanol solvent by rotary evaporation. Add 5 mL of water, heat at 40°C for 20 minutes, and ultrasonicate for 10 minutes to obtain water-dispersed resveratrol self-assembled nanoparticles.

[0159] Examples 2.1-2.9

[0160] Compared with Example 1, the amounts of Solution B in Step S2 were changed to the amounts shown in Table 2 below, respectively, and the other conditions remained the same.

[0161] Table 2

[0162]

[0163] Examples 3.1-3.4

[0164] Compared with Example 1, the amounts of Solution C in Step S2 were changed to the amounts shown in Table 3 below, respectively, and the other conditions remained the same.

[0165] Table 3

[0166] Group Liquid C dosage / mL Example 3.1 0.02 Example 3.2 0.04 Example 3.3 0.06 Example 3.4 0.1

[0167] The mass fractions of resveratrol, dopamine nonanoate, and vitamin C ethyl ether in the nanoparticles prepared by the methods described in Example 1, Examples 2.1-2.9, and Examples 3.1-3.4 are shown in Table 4 below:

[0168] Table 4

[0169]

[0170]

[0171] Example 4

[0172] Preparation of resveratrol-loaded antioxidant composite hydrogel.

[0173] T1. Sodium alginate is mixed with water to prepare a sodium alginate aqueous solution with a sodium alginate concentration of 4 g / 100 mL.

[0174] T2. Take 5 mL of the sodium alginate aqueous solution prepared in step T1 and mix it with the water-dispersed resveratrol self-assembled nanoparticles prepared in Example 1 (nanoparticle aqueous solution, volume 5 mL, concentration 0.251 mg / mL). Stir at room temperature for 30 minutes to prepare a gel precursor solution.

[0175] T3. Electrostatically spray the gel precursor solution prepared in step T2. The electrostatic spray conditions are 40°C, 20% relative humidity, 8 mL / h flow rate, and 15 kV voltage. Deionized water is used as a receiving solution for collection to obtain an antioxidant composite hydrogel.

[0176] Separately, the antioxidant composite hydrogel obtained in step T3 was centrifuged at 7000 rpm for 20 minutes, and the supernatant was collected and freeze-dried for 24 hours to obtain a lyophilized antioxidant composite hydrogel. This lyophilized antioxidant composite hydrogel was reconstituted in water to obtain an antioxidant composite hydrogel. The reconstituted antioxidant composite hydrogel showed no significant differences in properties, structure, or performance compared to the antioxidant composite hydrogel obtained in step T3.

[0177] Example 5.1

[0178] Compared with Example 4, in step T1, a sodium alginate aqueous solution with a sodium alginate concentration of 2 g / 100 mL was prepared, and other conditions were the same.

[0179] Example 5.2

[0180] Compared with Example 4, in step T1, a sodium alginate aqueous solution with a sodium alginate concentration of 6 g / 100 mL was prepared, and other conditions were the same.

[0181] Example 6.1

[0182] Compared with Example 4, the flow rate in step T3 was changed to 12 mL / h, and the other conditions were the same.

[0183] Example 6.2

[0184] Compared with Example 4, the flow rate in step T3 was changed to 10 mL / h, and the other conditions were the same.

[0185] Example 7.1

[0186] Compared with Example 4, the voltage in step T3 is changed to 20 kV, and the other conditions are the same.

[0187] Example 7.2

[0188] Compared with Example 4, the voltage in step T3 is changed to 25 kV, and the other conditions are the same.

[0189] Example 8.1

[0190] Compared with Example 4, in step T3, 5% by weight ethanol aqueous solution was used as the receiving solution, and the other conditions were the same.

[0191] Example 8.2

[0192] Compared with Example 4, in step T3, a 5% by mass glycerol aqueous solution was used as the receiving liquid, and the other conditions were the same.

[0193] Example 8.3

[0194] Compared with Example 4, in step T3, a 5% by mass PEG400 aqueous solution was used as the receiving solution, and the other conditions were the same.

[0195] Comparative Example 1

[0196] Preparation of nanoparticles assembled from vitamin C ethyl ether and dopamine nonanoate.

[0197] S1. Dissolve vitamin C ethyl ether and dopamine nonanoate in methanol respectively to prepare:

[0198] Solution A: 1 mg / mL ascorbyl ethyl ether methanol solution;

[0199] Solution B: 1 mg / mL dopamine nonanoate solution in methanol;

[0200] S2. Mix 1 mL of Solution A and 0.175 mL of Solution B, and disperse them ultrasonically for 10 minutes. Remove the methanol solvent by rotary evaporation. Add 5 mL of water, heat at 40°C for 20 minutes, and ultrasonicate for 10 minutes to obtain water-dispersed resveratrol-free nanoparticles.

[0201] Effect evaluation

[0202] 1. Evaluation of the hydrated particle size of resveratrol self-assembled nanoparticles

[0203] The hydrated particle size (average particle size ± standard deviation) of the nanoparticles was measured using dynamic light scattering (DLS). The results are shown in Table 5:

[0204] Table 5

[0205] Group Average hydrated particle size / nm Standard deviation / nm Example 2.1 354.10 25.14 Example 2.2 342.26 17.78 Example 2.3 296.70 12.60 Example 2.4 438.96 8.02 Example 2.5 445.93 30.72 Example 2.6 316.63 30.06 Example 2.7 286.90 7.86 Example 1 223.83 7.28 Example 2.8 606.30 17.16 Example 2.9 633.80 21.09 Example 3.1 228.87 13.40 Example 3.2 227.62 9.14 Example 3.3 230.44 15.75 Example 3.4 225.52 18.80

[0206] It can be seen that the average particle size of the resveratrol self-assembled nanoparticles obtained in Example 1 is the smallest.

[0207] 2. Evaluation of the critical micelle concentration (CMC) of nanoparticles assembled from vitamin C ethyl ether and dopamine nonanoate

[0208] The resveratrol-free nanoparticle solution prepared in Comparative Example 1 was used as the stock solution. This stock solution was serially diluted to prepare 10 mL of each of eight different nanoparticle solutions with nanoparticle concentrations ranging from 0.047 to 18.8 μg / mL. Each of these eight solutions was placed into eight headspace vials containing 0.12 μg of pyrene and then heated at 50°C for 90 minutes.

[0209] Measure the fluorescence intensity of 8 solutions: excitation wavelength 335nm, emission wavelength 350-450nm, excitation slit width 5nm, emission slit width 5nm. Use the fluorescence intensity as the ordinate and the negative logarithm of the nanoparticle concentration in the solution to the base 10 as the abscissa to fit two straight lines, such as Figure 2 shown. Figure 2 The concentration obtained by calculating the negative logarithm of the concentration corresponding to the intersection of the two straight lines is the critical micelle concentration.

[0210] Calculations show that the critical micelle concentration of the nanoparticles formed by vitamin C ethyl ether and dopamine pelargonate is 0.2 μg / mL. This shows that the nanoparticles have good micelle-forming ability and a certain degree of dilution resistance. Since the amount of resveratrol added to the resveratrol self-assembled nanoparticles is very low relative to vitamin C and dopamine pelargonate, the addition of resveratrol has little effect on the critical micelle concentration. Therefore, the resveratrol self-assembled nanoparticles prepared in Example 1 have similar micelle-forming ability and dilution resistance compared to the nanoparticles without resveratrol prepared in Comparative Example 1.

[0211] 3. Encapsulation efficiency and drug loading test of antioxidant composite hydrogel

[0212] Accurately weigh pure resveratrol, dissolve it in methanol, and dilute to volume to obtain a resveratrol standard solution stock solution. Use methanol to perform gradient dilution of the stock solution, and use a UV-visible spectrophotometer to measure a series of absorbances at 325nm to draw a resveratrol standard curve as shown below: Figure 3 .

[0213] Weigh the freeze-dried resveratrol self-assembled nanoparticles (mass M (g)) and fully redissolve them in an appropriate amount of deionized water to a total volume of V (mL). Divide the redissolved solution into two equal volumes. Take 1 mL of one aliquot and dilute it with 4 mL of anhydrous methanol. Determine the absorbance at 325 nm by UV spectrophotometry, and record the absorbance (A1). Centrifuge the other aliquot at 7000 rpm for 20 minutes. Take 1 mL of the supernatant and dilute it with 4 mL of anhydrous methanol. Determine the absorbance (A2) at 325 nm by UV spectrophotometry.

[0214] Substitute the absorbance A2 into Figure 3The resveratrol concentration C1 (g / mL) was calculated from the resveratrol standard curve shown. The formulas for calculating the encapsulation efficiency and drug loading of resveratrol self-assembled nanoparticles are as follows:

[0215] Encapsulation efficiency = (A2 ÷ A1) × 100%

[0216]

[0217] The above method was used to test the drug loading and encapsulation efficiency of the resveratrol self-assembled nanoparticles prepared in Example 1 and Examples 3.1-3.4. The results were as follows: Figure 4 As shown in the figure, as the resveratrol dosage increases, the drug loading gradually increases, while the encapsulation efficiency gradually decreases. When the resveratrol dosage reaches 100 μg, the encapsulation efficiency decreases the most. This phenomenon occurs because the resveratrol content is too high, exceeding the nanoparticle loading limit. Considering the effects of drug loading and encapsulation efficiency, Example 1 is the best example.

[0218] Similarly, the above method was used to test the encapsulation efficiency and drug loading of the antioxidant composite hydrogel prepared in each example. The test results are shown in Table 6:

[0219] Table 6

[0220] Group Encapsulation efficiency / % Drug loading / % Example 4 94.44 0.001 Example 5.1 84.43 0.014 Example 5.2 88.79 0.019 Example 6.1 92.45 0.018 Example 6.2 88.81 0.011 Example 7.1 93.06 0.016 Example 7.2 92.52 0.017 Example 8.1 92.35 0.037 Example 8.2 87.31 0.022 Example 8.3 94.33 0.009

[0221] 4. Evaluation of the release behavior of resveratrol from antioxidant composite hydrogels

[0222] The resveratrol self-assembled nanoparticles dispersed in water prepared in Example 1 (the nanoparticles have a resveratrol concentration of 0.2 mg / mL and a volume of 5 mL), and the antioxidant composite hydrogels prepared in Example 4 and Example 8.3 (the antioxidant composite hydrogels have a resveratrol concentration of 0.2 mg / mL and a volume of 5 mL) were placed in a dialysis bag with a molecular weight cutoff of 3500 Da, tied at both ends, and incubated for 72 hours in a PBS buffer solution containing 0.5% Tween 80 at pH 7.4. 1 mL of the solution was taken at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours, and supplemented with 1 mL of the corresponding medium (PBS buffer solution containing 0.5% Tween 80 at pH 7.4). The taken-out solution was diluted with 4 mL of methanol and analyzed using an ultraviolet spectrophotometer. The absorbance was recorded and brought into the standard curve to calculate the cumulative drug release amount and the drug release behavior curve. The specific results are shown in FIG. Figure 5 shown.

[0223] Depend on Figure 5It can be seen that the nanoparticles prepared in Example 1 have a burst release phenomenon in the solution. This is because the resveratrol self-assembled nanoparticles are composed of vitamin C ethyl ether, dopamine nonanoate, and resveratrol. The three of them self-assemble mainly through hydrogen bonds and hydrophobic forces. These self-assembly driving forces are relatively weak, and the stability in the medium is relatively low, so they are released quickly in the medium. The antioxidant composite hydrogel prepared in Example 4 solves the burst release phenomenon. This is because the gel is coated with sodium alginate on the outside during preparation. Sodium alginate presents a network hydrogel skeleton structure, which requires resveratrol to pass through the cross-linked structure before it can be released into the medium, thereby slowing the release rate of resveratrol and eliminating the burst release effect. Compared with Example 4, the total amount of resveratrol released by the antioxidant composite hydrogel prepared in Example 8.3 is higher. This is because the addition of PEG400 during the coating process intersperses the sodium alginate hydrogel network to a certain extent, making the hydrogel network structure, which should be dense, become relatively loose. Therefore, the nanogel prepared in Example 8.3 not only improves the total drug release but also solves the problem of resveratrol burst release to a certain extent.

[0224] 5. Evaluation of the antioxidant properties of nanomaterials

[0225] The DPPH method was used to evaluate the antioxidant properties of nanomaterials. The specific test steps are as follows:

[0226] Weigh 0.0019g of DPPH powder and add 70% ethanol solution to 100mL to prepare 0.05mmol / L DPPH solution, which is ready for use. Use 70% ethanol to prepare 1mg / mL of resveratrol, add 2.5, 5, 7.5, 10 and 100μL of resveratrol solution to the test tube respectively, add 4mL of DPPH solution and mix, use 70% ethanol to make up to a total volume of 5mL, mix the solution evenly, react in the dark for 30min, and measure the absorbance A1, A2, A3, A4, and A5 at 520nm respectively. Add 4mL of 70% ethanol solution to 1ml of resveratrol solution as the blank control group and measure the absorbance A0 at 520nm. Add 4mL of DPPH solution to 1mL of 70% ethanol solution as the positive control and measure the absorbance A at 520nm. The free radical scavenging rate is calculated according to the following formula:

[0227] Clearance rate = (1-(A i -A0) / A)×100%

[0228] Where i is 1, 2, 3, 4, or 5. The resveratrol clearance curve can be obtained by plotting the resveratrol concentration as the abscissa and the DPPH clearance rate as the ordinate.

[0229] The above method was used to test the DPPH clearance curves of resveratrol at different concentrations, resveratrol self-assembled nanoparticles prepared in Example 1, antioxidant composite hydrogel prepared in Example 8.3, and nanoparticles without resveratrol prepared in Comparative Example 1. The results are as follows: Figure 6 As shown. The concentration of resveratrol is the concentration of this product. The concentration of resveratrol self-assembled nanoparticles prepared in Example 1, the concentration of antioxidant composite hydrogel prepared in Example 8.3, and the concentration of nanoparticles without resveratrol prepared in Comparative Example 1 are all based on the concentration of vitamin C ethyl ether contained therein. The measurement and calculation method of vitamin C ethyl ether concentration is: Figure 3 The resveratrol concentration was calculated using the standard curve shown, and then converted using the mass ratio of vitamin C ethyl ether, dopamine nonanoate, and resveratrol of 1:0.175:0.08.

[0230] Depend on Figure 6 It can be seen that within a certain range (when the concentration of vitamin C ethyl ether is less than 4 μg / mL), the addition of resveratrol (relative to 0.32 μg / mL resveratrol) significantly improves the DPPH scavenging ability of the resveratrol self-assembled nanoparticles prepared in Example 1, that is, vitamin C ethyl ether, dopamine nonanoate and resveratrol have a certain synergistic effect. When the concentration of vitamin C ethyl ether is high, the resveratrol self-assembled nanoparticles prepared in Example 1 play a leading role in the DPPH clearance rate of vitamin C ethyl ether, and vitamin C ethyl ether, dopamine nonanoate and resveratrol have a combined effect. Among them, the antioxidant composite hydrogel prepared in Example 8.3 has a lower clearance rate than the antioxidant composite hydrogel prepared in Example 4. The reason is that sodium alginate as a shell limits the contact of vitamin C ethyl ether, dopamine nonanoate and resveratrol with DPPH to a certain extent, and the three cannot fully react with DPPH, thereby resulting in a lower clearance rate. Therefore, it can be seen that vitamin C ethyl ether, dopamine nonanoate and resveratrol can not only form nanoparticles through self-assembly, but also have the effect of synergistically or jointly enhancing antioxidant effects.

[0231] Furthermore, the DPPH scavenging rate was detected for the following substances at a concentration of 2.5 μg / mL, wherein the concentrations of the resveratrol self-assembled nanoparticles prepared in Example 1, the antioxidant composite hydrogel prepared in Example 8.3, and the self-assembled nanoparticles without resveratrol prepared in Comparative Example 1 were all calculated based on the total mass concentration of the self-assembled nanoparticles or nanogels, and dopamine nonanoate, vitamin C, and vitamin C ethyl ether were all calculated based on their own mass concentrations.

[0232] The test results are shown in Table 7 below:

[0233] Table 7

[0234] Group DPPH clearance rate / % Example 1 45.58 Example 8.3 38.20 Comparative Example 1 35.99 Dopamine nonanoate 30.47 Vitamin C 31.86 Vitamin C ethyl ether 32.06

[0235] As can be seen from Table 7, the DPPH scavenging ability of dopamine nonanoate and vitamin C ethyl ether is comparable to that of vitamin C. The resveratrol self-assembled nanoparticles prepared in Example 1 are significantly higher than those in Comparative Example 1. This is because the resveratrol in the resveratrol self-assembled nanoparticles prepared in Example 1 (the resveratrol concentration in the resveratrol nanoparticles in Example 1 is 0.2 μg / mL, and the DPPH scavenging rate at this concentration is only 0.48%) plays a certain synergistic role.

[0236] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A resveratrol self-assembled nanoparticle, characterized in that: Made with resveratrol, dopamine pelargonate, and vitamin C ethyl ether; The mass ratio of the vitamin C ethyl ether, the nonanoic acid dopamine and the resveratrol is 1:0.14-0.185:0.02-0.1, and the average hydrated particle size of the resveratrol self-assembled nanoparticles is 223.83-633.8 nm.

2. The method for preparing resveratrol self-assembled nanoparticles according to claim 1, characterized in that: The following steps are involved: S1. Mixing vitamin C ethyl ether, dopamine nonanoate, and resveratrol with a solvent to obtain liquid A, liquid B, and liquid C, respectively; S2. Mixing the solution A, solution B, and solution C obtained in step S1, performing ultrasonic dispersion, rotary evaporation, adding water, and performing ultrasonic dispersion again to obtain resveratrol self-assembled nanoparticles dispersed in water.

3. The preparation method according to claim 2, characterized in that In step S1, the concentration of liquid A is 0.01-5 mg / mL, the concentration of liquid B is 0.01-5 mg / mL, and the concentration of liquid C is 0.01-5 mg / mL; in step S2, the volume ratio of the mixture of liquid A, liquid B, and liquid C is 1:0.01-1:0.01-1.

4. A resveratrol-loaded antioxidant composite hydrogel, characterized in that: The active ingredient comprises the resveratrol self-assembled nanoparticles according to claim 1 or the resveratrol self-assembled nanoparticles prepared by the preparation method according to any one of claims 2 to 3; The preparation method of the antioxidant composite hydrogel comprises the following steps: T1. Mixing sodium alginate with water to obtain a sodium alginate aqueous solution; T2, mixing the resveratrol self-assembled nanoparticles dispersed in water with the sodium alginate aqueous solution obtained in step T1, and stirring to obtain a gel precursor solution; T3, electrostatically spraying the gel precursor solution obtained in step T2, and collecting it with a receiving liquid to obtain an antioxidant composite hydrogel; In step T1, the concentration of the sodium alginate aqueous solution is 2-6 g / 100 mL; in step T2, the concentration of the resveratrol self-assembled nanoparticles dispersed in water is 0.1-1 mg / mL.

5. The method for preparing the antioxidant composite hydrogel according to claim 4, characterized in that: The following steps are involved: T1. Mixing sodium alginate with water to obtain a sodium alginate aqueous solution; T2, mixing the resveratrol self-assembled nanoparticles dispersed in water with the sodium alginate aqueous solution obtained in step T1, and stirring to obtain a gel precursor solution; T3, electrostatically spraying the gel precursor solution obtained in step T2, and collecting it with a receiving liquid to obtain an antioxidant composite hydrogel; In step T1, the concentration of the sodium alginate aqueous solution is 2-6 g / 100 mL; in step T2, the concentration of the resveratrol self-assembled nanoparticles dispersed in water is 0.1-1 mg / mL.

6. The preparation method according to claim 5, characterized in that In step T3, the conditions of the electrostatic spray include a flow rate of 8-12 mL / h and a voltage of 15-25 kV, and the receiving liquid is selected from one of water, an alcohol aqueous solution, a surfactant aqueous solution, and a surfactant alcohol aqueous solution.

7. A drug, characterized in that The active ingredient is the resveratrol self-assembled nanoparticles according to claim 1, or the resveratrol self-assembled nanoparticles prepared by the preparation method according to any one of claims 2-3, or the antioxidant composite hydrogel according to claim 4, or the antioxidant composite hydrogel prepared by the preparation method according to any one of claims 5-6.

8. A cosmetic, characterized in that: The active ingredient is the resveratrol self-assembled nanoparticles according to claim 1, or the resveratrol self-assembled nanoparticles prepared by the preparation method according to any one of claims 2-3, or the antioxidant composite hydrogel according to claim 4, or the antioxidant composite hydrogel prepared by the preparation method according to any one of claims 5-6.

9. Use of the resveratrol self-assembled nanoparticles according to claim 1, the preparation method according to any one of claims 2-3, the antioxidant composite hydrogel according to claim 4, or the preparation method according to any one of claims 5-6 in the production of antioxidant drugs or cosmetics.

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