Nano-micelle composite hydrogel containing green tea essential oil and preparation method and application thereof

Abstract

The present invention discloses a nano-micelle composite hydrogel containing green tea essential oil, and a preparation method and application thereof. The nano-micelle composite hydrogel containing green tea essential oil provided by the present invention comprises a hydrogel matrix and an amphiphilic copolymer micelle, wherein the amphiphilic copolymer micelle comprises an amphiphilic brush-type PBMA-DSEA-PNIPAm copolymer and green tea essential oil entrapped therein. The nano-micelle composite hydrogel containing green tea essential oil provided by the present invention has a good anti-aging effect, and the hydrophobic green tea essential oil is encapsulated by the specific core-shell structure of the amphiphilic micelle to improve the interaction between the hydrophobic green tea essential oil and the hydrophilic hydrogel, increase the loading rate and stability of the green tea essential oil in the polymer hydrogel, and enhance the effect of the green tea essential oil, and the copolymer nano-micelles with dual responsiveness to temperature / light stimulation are used to encapsulate the green tea essential oil, and the controlled release of the green tea essential oil can be achieved by controlling the temperature / light.

Description

Technical Field

[0001] The present invention belongs to the field of hydrogel preparation, and particularly relates to a nano-micelle composite hydrogel containing green tea essential oil, and a preparation method and application thereof. Technical Background

[0002] A hydrogel is a three-dimensional network system crosslinked by hydrophilic polymers. Due to the existence of a crosslinked network, a hydrogel can swell and retain a large amount of water, has a strong water absorption capacity (the water content can be as high as 99%), and the water absorption amount is closely related to the degree of crosslinking. As one of the most popular biomaterials in recent years, a hydrogel has various excellent chemical and structural properties, and is widely used in fields such as drug controlled release, artificial organs, material separation, and tissue engineering. There are various classification methods for hydrogels: (1) According to the material source, they can be divided into natural hydrogels (such as hyaluronic acid, collagen, sodium alginate, etc.) and synthetic hydrogels (such as polyacrylamide, polyethylene glycol, etc.); (2) According to the crosslinking method, they can be divided into physically crosslinked hydrogels and chemically crosslinked hydrogels. The former is crosslinked by electrostatic interaction, hydrogen bond interaction, etc., and can turn back into a solution state when the external conditions change, which is reversible; the latter constructs a three-dimensional network by chemical bonds, and the structure is stable and permanent; (3) According to the environmental response situation, they can be divided into traditional hydrogels and intelligent hydrogels. The latter can exhibit different swelling behaviors according to external environmental stimuli (such as temperature, pH, enzyme, magnetic field, etc.); the former does not have this ability.

[0003] Due to the hydrophobicity of green tea essential oil, this will minimize the interaction between them and the hydrophilic phase of the hydrogel, resulting in very little green tea essential oil loaded in the polymer hydrogel. Green tea essential oil is extracted by steam distillation to extract the essence of beneficial components in green tea, and is composed of small and volatile hydrophobic molecules. In green tea essential oil, there is a substance called tea polyphenols, which has the functions of antioxidant and anti-aging, and can effectively resist the stimulation and damage caused by free radicals to the skin, reduce the precipitation of melanin, prevent the generation of wrinkles and fine lines, enable the skin to restore its original vitality and elasticity, and effectively improve skin problems such as dryness, dullness, and roughness; it also has the functions of antibacterial and anti-inflammatory, can avoid the growth of acne and acne, and can improve the allergic symptoms caused by allergic skin. However, in existing research, the utilization effect of green tea essential oil is relatively poor, and it is difficult to exert its effect; for example, existing research has studied the preparation of liposome micelles to encapsulate hydrophobic drugs, but its stability is poor and often requires freeze-drying storage.

[0004] Hydrogels are commonly used carriers for drugs. In existing studies, the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAm)-based thermoresponsive micelles can be adjusted, making them intelligent materials applicable to many fields, such as the delivery of hydrophobic drugs and biosensing. When PNIPAm forms a block copolymer with another hydrophobic monomer, when the external temperature is lower than the LCST, the PNIPAm chain segments are hydrophilic, and the amphiphilic copolymer can self-assemble into thermoresponsive core-shell micelles. The hydrophobic inner shell can be used to encapsulate hydrophobic substances, and the PNIPAm chain segments serve as the outer shell to stabilize the micelle structure. If a hydrophobic drug is loaded into the inner core region, when the external temperature is higher than the LCST, the hydrophobicity of PNIPAm increases, causing the micelles to shrink and triggering the release of drug molecules. Therefore, hydrophobic essential oils can be encapsulated by amphiphilic micelles and then compounded into a hydrogel matrix to load hydrophobic essential oils and prepare a hydrogel by mixing with a hydrophilic matrix, improving the loading rate of the hydrogel for hydrophobic drugs. For example, in existing studies, poly(N-isopropylacrylamide)-b-(butyl methacrylate) block copolymer (PIPAAm-PBMA) was used to prepare temperature-sensitive polymer micelles loaded with the hydrophobic drug doxorubicin for cancer treatment. However, for the polymer micelles combined with doxorubicin, due to the change in the PIPAAm structure, the drug release and interaction with cells increased, resulting in higher cytotoxicity of the micelles above the LCST temperature, thus limiting the application of this drug. Moreover, due to the differences in the properties of different drugs, the encapsulation stability of different copolymer micelles for different hydrophobic drugs is different, and there are also problems with poor encapsulation stability of drugs in existing studies.

[0005] For a long time, the efficacy and applications of green tea essential oil have been widely studied, but there are few reports on applying green tea essential oil to hydrogel patches. In order to improve the utilization rate of green tea essential oil and solve the problems of water-oil incompatibility, low loading rate, and easy loss in the hydrogel caused by directly filling green tea essential oil into the hydrogel matrix, it is urgent to research and develop more hydrogel products that can encapsulate green tea essential oil. Summary of the Invention

[0006] The present invention aims to solve the defects and deficiencies such as the loading of hydrophobic green tea essential oil by hydrogels, and provides a nano-micelle composite hydrogel containing green tea essential oil with good anti-aging effect, high loading rate, and temperature / light stimulus dual responsiveness, as well as its preparation method and application.

[0007] The purpose of the present invention is to provide an amphiphilic brush-type PBMA-DSEA-PNIPAm copolymer.

[0008] Another purpose of the present invention is to provide an amphiphilic copolymer micelle containing plant essential oil.

[0009] Another object of the present invention is to provide a nano - micelle composite hydrogel containing plant essential oil.

[0010] Another object of the present invention is to provide a preparation method of the nano - micelle composite hydrogel containing plant essential oil.

[0011] Another object of the present invention is to provide an application of the nano - micelle composite hydrogel containing plant essential oil.

[0012] The above objects of the present invention are achieved by the following technical solutions:

[0013] The present invention provides an amphiphilic brush - type PBMA - DSEA - PNIPAm copolymer, which is prepared by atom transfer radical polymerization of poly(tert - butyl methacrylate) (PBMA), 2,2 - dithiobis(ethanol acrylate) (DSEA) and poly(N - isopropylacrylamide) (PNIPAm).

[0014] The present invention uses a block copolymer as a raw material and a high - molecular - weight disulfide bond as the main skeleton to synthesize an amphiphilic brush - type copolymer micelle, and prepares a copolymer with a specific brush - type structure arranged alternately on the disulfide bond skeleton. The polymer chains at the hydrophobic end and the hydrophilic end in the brush - type copolymer can self - assemble into a polymer micelle with a stable cavity structure in a medium. The formed cavity has a specific hydrophilic outer shell and hydrophobic inner core structure, so that the polymer micelle can encapsulate hydrophobic substances and be dispersed in a hydrophilic matrix.

[0015] A brush - type polymer is a macromolecule with a special structure composed of a linear chain as the backbone and multiple side chains. The backbone chain of the brush - type polymer is in an extended state, which causes steric hindrance between the side chains, resulting in different physical properties (such as maintaining the shape unchanged, hindering curling, and promoting the formation of a larger spatial structure). Brush - type polymers have potential application values from the field of nanotechnology (such as photonic crystals, nanotubes, and nanowires) to the field of biomedical applications (such as drug delivery, etc.).

[0016] Further, the mass ratio of the poly(tert - butyl methacrylate) (PBMA), 2,2 - dithiobis(ethanol acrylate) (DSEA) and poly(N - isopropylacrylamide) (PNIPAm) is (1 - 5):1:(5 - 9).

[0017] The present invention provides an amphiphilic copolymer micelle containing plant essential oil, which includes an amphiphilic brush - type PBMA - DSEA - PNIPAm copolymer and a hydrophobic substance encapsulated therein.

[0018] Preferably, the hydrophobic substance is a plant essential oil.

[0019] More preferably, the plant essential oil is green tea essential oil.

[0020] The amphiphilic copolymer micelles provided by the present invention not only improve the encapsulation rate of plant essential oils, but also greatly enhance the utilization efficiency of plant essential oils, giving full play to the role of the hydrophobic substances encapsulated inside, such as plant essential oils. They have good anti-aging effects and good safety, and the quality inspection meets the requirements of national quality standards.

[0021] The present invention provides a nano-micelle composite hydrogel containing plant essential oils, which includes a hydrogel matrix and the above-mentioned amphiphilic copolymer micelles. The present invention encapsulates plant essential oils through the cavity structure of the brush copolymer, solving the problems of incompatibility between water and oil, low loading rate of plant essential oils, and easy loss in the hydrogel caused by directly filling plant essential oils into the hydrogel matrix, thereby improving the utilization degree and effect of plant essential oils. The encapsulation stability thereof cannot be achieved by carriers formed by other small molecules and ordinary amphiphilic copolymers.

[0022] The nano-micelle composite hydrogel containing plant essential oils provided by the present invention can not only improve the loading rate of the hydrogel for hydrophobic plant essential oils, but also has the characteristics of temperature / light dual responsiveness. By linking a PNIPAm polymer chain with thermosensitive characteristics on the copolymer molecular chain, the amphiphilic copolymer micelles have the characteristics of temperature-responsive control, so that the copolymer micelles can achieve temperature-controlled release of plant essential oils. When in a room temperature environment, where the external temperature is lower than the lower critical solution temperature (LCST), the PNIPAm molecular chain is in a stable state, and the PBMA-DSEA-PNIPAm micelles stably store the plant essential oils in the hydrogel. When the hydrogel acts on the skin, where the external temperature is higher than the LCST, due to the unique thermosensitive characteristics of PNIPAm, the micelle molecular chain shrinks, the micelle structure deforms, and the plant essential oils are triggered to be released, realizing the temperature-controlled release characteristics of plant essential oils.

[0023] At the same time, the unique disulfide bond backbone structure in the hydrogel has the characteristics of ultraviolet light responsiveness, enabling the copolymer micelles to achieve ultraviolet light-controlled release of green tea essential oils. When the hydrogel is irradiated with ultraviolet light, the disulfide bonds formed by DSEA in the micelles are broken, the main chain of the copolymer degrades, and the micelles disintegrate, thereby releasing the green tea essential oils with anti-photoaging effects to protect the skin from ultraviolet light damage. Therefore, the hydrogel patch of the present invention can achieve controlled release of green tea essential oils through the characteristics of temperature / light dual responsiveness.

[0024] Preferably, the mass ratio of the hydrogel matrix to the amphiphilic copolymer micelles is 5-10:1.

[0025] More preferably, the mass of the hydrogel matrix to the amphiphilic copolymer micelles is 5:1.

[0026] Preferably, the hydrogel matrix is sodium hyaluronate.

[0027] The present invention also provides a method for preparing the above-mentioned nanomicelle composite hydrogel. First, an amphiphilic brush-shaped PBMA-DSEA-PNIPAm copolymer is prepared, then green tea essential oil is encapsulated, and after dialysis and drying, a nanomicelle powder loaded with green tea essential oil is obtained; then the nanomicelle powder loaded with green tea essential oil is reacted with the hydrogel matrix to obtain a nanomicelle composite hydrogel containing green tea essential oil.

[0028] Preferably, the dosage ratio of the amphiphilic brush-shaped PBMA-DSEA-PNIPAm copolymer to green tea essential oil is: 200 - 400 mg: 1 mL.

[0029] More preferably, the dosage ratio of the amphiphilic brush-shaped PBMA-DSEA-PNIPAm copolymer to green tea essential oil is: 200 mg: 1 mL.

[0030] As the most preferred embodiment, the present invention provides a specific method for preparing a nanomicelle composite hydrogel containing green tea essential oil, including the following steps:

[0031] (1) Synthesis of hydroxyl-terminated poly(N-isopropylacrylamide) (PNIPAm-OH) and poly(tert-butyl methacrylate) (PBMA-OH)

[0032] PNIPAm-OH and PBMA-OH are synthesized by free radical polymerization. First, (50 mmol) N-isopropylacrylamide is dissolved in (17 mL) tetrahydrofuran (THF), purged with N 2 for 10 min, (4 mmol) 2-mercaptoethanol (8% of the monomer amount) is added until completely dissolved, and after about 20 min, 2,2'-azobisisobutyronitrile (AIBN) (5% of the monomer mass) is added. Under N 2 atmosphere, the mixture is magnetically stirred and heated to 60 °C for 24 h. After the reaction, the solution is concentrated to 10 - 15 mL and precipitated with 100 mL of ether.

[0033] PBMA-OH is synthesized using tert-butyl methacrylate as the monomer raw material by the same synthesis method as PNIPAm-OH, and the precipitating agent used is a mixture of methanol and water (v:v = 1:1). The synthesized product is filtered, washed once more with ether, and vacuum dried for 24 h.

[0034] (2) Synthesis of vinyl-terminated poly(N-isopropylacrylamide) (PNIPAm-AA) and poly(tert-butyl methacrylate) (PBMA-AA)

[0035] Dissolve the PNIPAm-OH or PBMA-OH synthesized in step (1) and triethylamine (8% of the molar amount of the monomer) in THF. Then, add ice to the water bath to cool the temperature to 0 °C, and slowly drip the THF solution (10 - 15 mL) containing acryloyl chloride (8% of the molar amount of the monomer) into it using a constant pressure funnel. The dripping is completed in about 2 h. Keep the temperature at 0 °C and stir for 2 h to fully mix. Finally, heat to 30 °C and react for 24 h.

[0036] The precipitation methods of PNIPAm-AA and PBMA-AA are the same as those of PNIPAm-OH and PBMA-OH.

[0037] (3) Synthesis of 2,2'-dithiodiethanol diacrylate monomer (DSEA)

[0038] Put β-mercaptoethanol (1.56 g, 1 mmol) and sodium iodide (3 mg, 0.01 mmol) into a three-necked flask, add ethyl acetate (6 mL) as the solvent, and slowly drip 30% hydrogen peroxide (0.22 mL, 1 mmol) under magnetic stirring. After the dripping is completed, continue to stir at 30 °C for 30 min. After the stirring is completed, add saturated aqueous sodium thiosulfate solution (30 mL), then extract the aqueous phase with ethyl acetate (30 mL), and combine the organic phases. The extract is washed with saturated brine (30 mL), then dried with anhydrous sodium sulfate. Finally, rotary evaporate to remove the solvent to obtain the product 2,2'-dithiodiethanol.

[0039] Put 2,2'-dithiodiethanol (15.4 g, 50 mmol) and triethylamine (100 mL, 400 mmol) into a flask, add anhydrous tetrahydrofuran (300 mL), place the flask in an ice-water bath for 15 min, and then slowly drip acryloyl chloride (36.2 g, 200 mmol) under magnetic stirring. After the dripping is completed, remove the ice-water bath and stir at 30 °C for 24 h. After the reaction is completed, rotary evaporate to remove tetrahydrofuran, then add chloroform (300 mL) to dissolve, wash with potassium carbonate solution (0.1 mol L -1 ) and then wash with deionized water, and add anhydrous sodium sulfate for drying. Finally, rotary evaporate to remove the solvent to obtain DSEA.

[0040] (4) Synthesis of PBMA-DSEA-PNIPAm copolymer

[0041] Completely dissolve (10 - 50 mg) PBMA-AA, (90 - 50 mg) PNIPAm-AA, and (10 mg) DSEA in (10 mL) THF, fill with N 2 Add AIBN (5% of the mass of the monomer) after about 10 min. React at 60 °C for 24 h, precipitate and purify the product once with ether, and dry it in vacuum at room temperature.

[0042] (5) Preparation of PBMA-DSEA-PNIPAm copolymer micelles and loading of green tea essential oil

[0043] The micelles were prepared by dialysis. First, (200 mg) of PBMA-DSEA-PNIPAm copolymer and (1 mL) of essential oil were dissolved in (100 mL) of THF, and then placed in a dialysis bag and dialyzed against distilled water at room temperature for 24 h in a 1000 mL beaker. After dialysis, the dialysate was lyophilized to obtain the nano-micelle powder loaded with green tea essential oil.

[0044] (6) Preparation of nano-micelle composite hyaluronic acid hydrogel

[0045] (0.5 g) of HA was dissolved in (20 mL) of deionized water to form an HA aqueous solution, and then the micelle powder loaded with green tea essential oil was added. The weight ratio of HA to micelles was (5:1). Then, (3 g) of adipic dihydrazide (ADH) (6 times the weight of HA) was added with vigorous stirring and stirring was continued. After adjusting the pH value of the mixed solution to 3.5 - 4.75 by adding 1 mol / L HCl, (0.4 g) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) was added with vigorous stirring, and the reaction solution was allowed to gel overnight at room temperature. The pH value was adjusted to 7 with NaOH. Then it was placed in a dialysis bag and dialyzed against distilled water at room temperature for 24 h in a 1000 mL beaker to obtain the product.

[0046] The present invention provides the application of the nano-micelle composite hydrogel containing plant essential oil in anti-aging or in the preparation of anti-aging products.

[0047] The present invention also provides a hydrogel product containing green tea essential oil.

[0048] Preferably, the product is a green tea essential oil hydrogel patch; the tea essential oil hydrogel patch provided by the present invention has good skin adaptability, and has a significant anti-wrinkle effect and comprehensive skin improvement effect when used.

[0049] Preferably, the green tea essential oil hydrogel patch includes a non-woven fabric backing layer, a CPP embossed film, and a gel layer between the non-woven fabric backing layer and the CPP embossed film; the gel layer includes a hydrogel matrix and amphiphilic copolymer micelles; the amphiphilic copolymer micelles include green tea essential oil.

[0050] Preferably, the preparation method of the green tea essential oil hydrogel patch is: coating the hydrogel loaded with green tea essential oil on the non-woven fabric to form a gel layer; pasting a CPP embossed film on the other side of the gel layer and cutting to obtain the product.

[0051] The present invention has the following beneficial effects:

[0052] The present invention provides a nano - micelle composite hydrogel containing green tea essential oil, its preparation method and application. In the present invention, the unique cavity structure formed by the amphiphilic copolymer in the medium is used to encapsulate the green tea essential oil, and an amphiphilic brush - type copolymer micelle with temperature / light dual - responsiveness is prepared. Then it is compounded into the hyaluronic acid hydrogel. The prepared nano - micelle composite hydrogel containing green tea essential oil has good anti - aging effects and improves the effect of green tea essential oil. By using the hydrophobic inner shell and hydrophilic outer shell of the amphiphilic micelles to encapsulate hydrophobic drugs, the interaction between the hydrophobic substance and the hydrophilic hydrogel is improved, and the loading rate and stability of the hydrophobic substance in the polymer hydrogel are increased. Moreover, through the control of temperature / light, the controlled release of green tea essential oil can be achieved.

[0053] The present invention uses nano - micelles to encapsulate green tea essential oil, forming a specific hydrophilic outer shell and hydrophobic inner core structure, so that the polymer micelles can encapsulate hydrophobic plant essential oils and can be well - dispersed in the hydrophilic matrix, improving the encapsulation stability of the micelles and the loading rate of hydrophobic plant essential oils. The prepared hydrogel patch can well solve the problems of incompatibility between water and oil caused by directly filling green tea essential oil into the hydrogel matrix, low loading rate of green tea essential oil, and easy loss of green tea essential oil in the hydrogel, thus greatly improving the utilization rate of green tea essential oil.

[0054] The nano - micelle composite hydrogel containing green tea essential oil provided by the present invention has the characteristics of temperature / light dual - responsiveness and can achieve the controlled release of green tea essential oil. At room temperature, when the external temperature is lower than the LCST, the molecular chains of PNIPAm are in a stable state, and the PBMA - DSEA - PNIPAm micelles enable the green tea essential oil to be stably stored in the hydrogel. When the hydrogel patch acts on the skin, the external temperature is higher than the LCST. Due to the unique thermosensitive property of PNIPAm, the molecular chains of the micelles contract, the micelle structure deforms, and the green tea essential oil is triggered to be released, realizing the temperature - controlled release characteristic of green tea essential oil. Or when irradiated by ultraviolet light, the disulfide bonds formed by DSEA in the micelles break, the main chain of the copolymer degrades, resulting in the disassembly of the micelles, and thus the green tea essential oil with anti - photo - aging effects can be released to protect the skin from the damage of ultraviolet light. Detailed Embodiments

[0055] The following further illustrates the present invention with specific embodiments. However, the described embodiments are intended to explain the present invention and should not be construed as limiting the present invention. For the specific technologies or conditions not specified in the embodiments, they shall be carried out according to the technologies or conditions described in the literature in the field or according to the product specifications.

[0056] The sources of the existing research records involved in the following embodiments:

[0057] Chung J E, Yokoyama M, Yamato M, et al. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate) [J]. Journal of Controlled Release, 1999, 62(1-2): 115-127.

[0058] Lee R S, Chen W H, Huang Y T. Synthesis and characterization of dual-stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid) [J]. Polymer, 2010, 51(25): 5942-5951.

[0059] Example 1 Preparation of PBMA-DSEA-PNIPAm copolymer nanomicelles

[0060] 1. Synthesis of hydroxyl-terminated poly(N-isopropylacrylamide) (PNIPAm-OH) and poly(tert-butyl methacrylate) (PBMA-OH)

[0061] PNIPAm-OH and PBMA-OH were synthesized by radical polymerization. First, (50 mmol) N-isopropylacrylamide was dissolved in (17 mL) tetrahydrofuran (THF), and N2 was purged for 10 min. Then, (4 mmol) 2-mercaptoethanol (8% of the molar amount of the monomer) was added until completely dissolved. After about 20 min, 2,2'-azobisisobutyronitrile (AIBN) (5% of the mass of the monomer) was added. Under a N2 atmosphere, the mixture was heated to 60 °C with magnetic stirring and reacted for 24 h. After the reaction, the solution was concentrated to 10-15 mL and precipitated with 100 mL of diethyl ether. 2 10 min, add (4 mmol) 2-mercaptoethanol (8% of the molar amount of the monomer) until completely dissolved. After about 20 min, add 2,2'-azobisisobutyronitrile (AIBN) (5% of the mass of the monomer). Under a N2 2 atmosphere, magnetically stir and heat to 60 °C and react for 24 h. After the reaction, concentrate the solution to 10-15 mL and precipitate with 100 mL of diethyl ether.

[0062] PBMA-OH was synthesized using tert-butyl methacrylate as the monomer raw material by the same synthesis method as PNIPAm-OH, and the precipitant was a mixture of methanol and water (v:v = 1:1). The product was filtered, washed once more with diethyl ether, and dried in vacuo for 24 h.

[0063] 2. Synthesis of Poly(N-isopropylacrylamide) (PNIPAm-AA) and Poly(tert-butyl methacrylate) (PBMA-AA) with Vinyl Groups at Both Ends

[0064] Dissolve the PNIPAm-OH (PBMA-OH) synthesized in step (1) and triethylamine (8% of the molar amount of the monomer) in THF. Then, add ice to the water bath to cool the temperature to 0 °C, and slowly drip the THF solution (10 - 15 mL) containing acryloyl chloride (8% of the molar amount of the monomer) into it using a constant-pressure funnel. The dripping is completed in about 2 h. Keep the temperature at 0 °C and stir for 2 h to mix them thoroughly. Finally, heat to 30 °C and react for 24 h.

[0065] The precipitation methods of PNIPAm-AA and PBMA-AA are the same as those of PNIPAm-OH and PBMA-OH.

[0066] 3. Synthesis of 2,2'-Dithiodiethanol Diacrylate Monomer (DSEA)

[0067] Put β-mercaptoethanol (1.56 g, 1 mmol) and sodium iodide (3 mg, 0.01 mmol) into a three-necked flask, add ethyl acetate (6 mL) as the solvent, and slowly drip 30% hydrogen peroxide (0.22 mL, 1 mmol) under magnetic stirring. After the dripping is completed, continue to stir at 30 °C for 30 min. After stirring, add saturated aqueous sodium thiosulfate solution (30 mL), then extract the aqueous phase with ethyl acetate (30 mL), and combine the organic phases. The extraction solution is washed with saturated brine (30 mL), then dried with anhydrous sodium sulfate. Finally, remove the solvent by rotary evaporation to obtain the product 2,2'-dithiodiethanol.

[0068] Put 2,2'-dithiodiethanol (15.4 g, 50 mmol) and triethylamine (100 mL, 400 mmol) into a flask, add anhydrous tetrahydrofuran (300 mL), place the flask in an ice-water bath for 15 min, and then slowly drip acryloyl chloride (36.2 g, 200 mmol) under magnetic stirring. After the dripping is completed, remove the ice-water bath and stir at 30 °C for 24 h. After the reaction is completed, remove tetrahydrofuran by rotary evaporation, then add chloroform (300 mL) to dissolve it, wash it with potassium carbonate solution (0.1 mol L -1 ) and then wash it with deionized water, and add anhydrous sodium sulfate to dry. Finally, remove the solvent by rotary evaporation to obtain DSEA.

[0069] 4. Synthesis of PBMA-DSEA-PNIPAm Copolymer

[0070] PBMA-AA (10 mg, 20 mg, 30 mg, 40 mg, 50 mg), PNIPAm-AA (90 mg, 80 mg, 70 mg, 60 mg, 50 mg) and DSEA (10 mg) with different mass ratios were completely dissolved in (10 mL) THF respectively to obtain mixed solutions of PBMA-AA and PNIPAm-AA with different mass ratios (1:9, 2:8, 3:7, 4:6, 5:5), and N 2 AIBN (5% of the monomer mass) was added after about 10 min. The reaction was carried out at 60 °C for 24 h. The product was precipitated and purified with ether once and dried in vacuum at room temperature.

[0071] 5. Preparation of PBMA-DSEA-PNIPAm copolymer micelles

[0072] The micelles were prepared by dialysis method. Weigh (30 mg) of PBMA-DSEA-PNIPAm copolymers with different mass ratios and dissolve them in (10 mL) THF, then place them in a dialysis bag and put it into a 1000 mL beaker and dialyze with distilled water at room temperature for 24 h. Change the water every 1 h for the first 3 h. After dialysis, collect the dialysis solution into a volumetric flask to obtain PBMA-DSEA-PNIPAm copolymer micelles.

[0073] Example 2 Performance determination of PBMA-DSEA-PNIPAm copolymer micelles

[0074] 1. Determination of critical micelle concentration (CMC)

[0075] The CMC of PBMA-DSEA-PNIPAm copolymer micelles was determined according to the surface tension. First, prepare a series of PBMA-DSEA-PNIPAm copolymer micelle solutions with different concentrations, and the concentration range is from 1×10 -1 g / L -1 to 5×10 -5 g / L -1 , then use a surface tensiometer to measure the surface tension of each solution respectively and conduct statistical analysis.

[0076] The CMC determination results are shown in Table 1. From the results in Table 1, it can be seen that the CMC values of a series of micelle samples prepared in the present invention range from 2.12 to 8.07 mg / L -1 , which is lower than that of the block copolymer PBMA-b-PNIPAm (20 mg / L) reported in the literature by Chung J E et al. -1) has a much lower CMC value, indicating that the micelles prepared by the present invention can exhibit good thermodynamic stability at low concentrations. Moreover, as the proportion of the hydrophobic substance part PBMA increases, its CMC value also decreases correspondingly, indicating that the more hydrophobic part there is, the easier it is for micelles to form. Therefore, the polymer micelle particles of the present invention can adjust their CMC values by changing the ratio of the hydrophilic and hydrophobic parts.

[0077] Table 1 Measurement results of critical micelle concentration (CMC)

[0078] Sample PBMA:DSEA:PNIPAm <![CDATA[CMC (mg L -1 )]]> PBMA-DSEA-PNIPAm-1 1:1:9 8.07 PBMA-DSEA-PNIPAm-2 2:1:8 6.82 PBMA-DSEA-PNIPAm-3 3:1:7 5.43 PBMA-DSEA-PNIPAm-4 4:1:6 3.65 PBMA-DSEA-PNIPAm-5 5:1:5 2.12

[0079] 2. Measurement of lower critical solution temperature (LCST)

[0080] As recorded in existing studies by Lee R S et al., half of the change in transmittance is defined as the lower critical solution temperature or cloud point. Usually, the LCST value of PNIPAm comonomer is 32 °C. When hydrophilic or hydrophobic segments are attached to PNIPAm, its LCST value will change. The transmittance of the micelle solutions (250 mg / L -1 ) with different mass ratios prepared in Example 1 was measured using a UV-visible spectrophotometer at a measurement wavelength λ = 500 nm and a temperature range of 15 - 55 °C. Different micelle solution samples were placed in quartz cuvettes, and the transmittance T% was measured using a UV-visible spectrophotometer, and then the LCST of the samples was obtained.

[0081] The LCST measurement results of the present invention are shown in Table 2. It can be seen that the polymer micelles prepared by the present invention all have temperature sensitivity. The LCST values of a series of samples prepared are in the range of 29.75 - 31.51 °C, and their phase transition temperatures are all above room temperature. Moreover, as the proportion of the hydrophobic substance part PBMA increases, its LCST value also decreases correspondingly. The reason is that the hydrophobic part PBMA changes the balance between the hydrophilic and hydrophobic parts in PNIPAm, promoting the phase transition of PNIPAm at low temperatures. It can be known from Table 2 that the hydrophobic PBMA has little effect on the LCST value, indicating that after PNIPAm is attached to the hydrophobic part PBMA, as the temperature rises, the PNIPAm part shrinks, and the hydrophobic part of PBMA promotes the contraction of the chain segments, so the LCST value is lower than 32 °C. The intermolecular forces between hydrophobic chains promote the formation of micelles with a core-shell structure in the polymer chains, and the LCST of the polymer can be changed by adjusting the mass ratio of the hydrophilic segment PNIPAm and the hydrophobic segment PBMA, which can be more flexibly applied to scenarios with different requirements.

[0082] Table 2 Measurement results of lower critical solution temperature (LCST)

[0083]

[0084]

[0085] 3. Zeta Potential Measurement

[0086] Measure the Zeta potential of the micelles with different mass ratios prepared in Example 1 to prove the stability of the micelle particles in the aqueous environment. Configure each micelle sample into an aqueous solution with a concentration of 250 mg / L -1 and measure the micelle solution on a laser particle size Zeta potential analyzer at 25°C.

[0087] The Zeta potential measurement results are shown in Table 3. Generally, the colloidal stability depends on the interaction among van der Waals force, electrostatic interaction, and steric hindrance. For the series of polymer micelle solutions prepared by the present invention measured at 25°C in Table 3, their potential values are all negative, ranging from -31.67 to -28.83 mV, indicating that they all have good stability, and show a trend of first increasing and then decreasing with the appropriate increase in the proportion of the hydrophobic part of the substance PBMA. Through the measurement of the Zeta potential, it is shown that linking an appropriate proportion of the hydrophobic part in PNIPAm is beneficial to the stability of the micelle particles and is suitable for application as a hydrophobic drug carrier.

[0088] Table 3 Results of Zeta Potential Measurement

[0089] Sample PBMA:DSEA:PNIPAm ζ (mV) PBMA-DSEA-PNIPAm-1 1:1:9 -29.78 PBMA-DSEA-PNIPAm-2 2:1:8 -30.25 PBMA-DSEA-PNIPAm-3 3:1:7 -31.67 PBMA-DSEA-PNIPAm-4 4:1:6 -29.94 PBMA-DSEA-PNIPAm-5 5:1:5 -28.83

[0090] 4. Particle Size Measurement

[0091] The particle size and particle size distribution of the micelles are measured with a laser particle size analyzer, a He-Ne laser (wavelength 660 nm). Configure each micelle sample into an aqueous solution with a concentration of 250 mg / L -1 and measure the particle sizes of the micelles with different mass ratios prepared in Example 1.

[0092] The measured results of different micelle particle sizes are shown in Table 4. The particle size of the micelles is related to the ratio between the hydrophilic chain and the hydrophobic chain. It can be seen from Table 4 that the particle size of the micelles decreases with the increase of the hydrophobic part. Because more hydrophobic parts promote the contraction and aggregation of the chain segments. At the same time, it is proved that the polymer micelles prepared by the present invention can form a stable core-shell structure in the aqueous environment, can encapsulate hydrophobic drugs and make them stably compounded in the hydrogel matrix. And the particle sizes of the series of polymer micelles prepared by the present invention are all below 200 nm, meeting the requirements in biomedicine.

[0093] Table 4 Different Micelle Particle Sizes

[0094] Sample PBMA:DSEA:PNIPAm Particle size (nm) PBMA-DSEA-PNIPAm-1 1:1:9 197 PBMA-DSEA-PNIPAm-2 2:1:8 188 PBMA-DSEA-PNIPAm-3 3:1:7 174 PBMA-DSEA-PNIPAm-4 4:1:6 165 PBMA-DSEA-PNIPAm-5 5:1:5 152

[0095] 5. Measurement of Encapsulation Efficiency of Green Tea Essential Oil

[0096] First, weigh (20 mg) of the PBMA-DSEA-PNIPAm copolymer and (0.1 mL) of essential oil and dissolve them in (10 mL) of THF. Then, place the solution in a dialysis bag and put it into a 1000 mL beaker. Dialyze it with distilled water at room temperature for 24 h. After dialysis, freeze-dry the dialysis solution to obtain the nano-micelle powder loaded with green tea essential oil. Dissolve the nano-micelle powder loaded with green tea essential oil in a THF solution and measure the drug encapsulation efficiency with a UV spectrophotometer.

[0097] The measurement results of the green tea essential oil encapsulation efficiency are shown in Table 5. The encapsulation efficiency of the polymer nano-micelles for the drug is related to the ratio between the hydrophilic chain and the hydrophobic chain. As can be seen from Table 5, the loading amount of green tea essential oil decreases with the increase of the hydrophobic part. Because the increase of the hydrophobic part promotes the contraction and aggregation of the chain segments, resulting in a smaller cavity of the prepared nano-micelles. Moreover, the encapsulation efficiency of a series of polymer micelles prepared in the present invention is greater than 67%, indicating its good drug encapsulation performance.

[0098] Table 5 Encapsulation efficiency of green tea essential oil

[0099] Sample PBMA:DSEA:PNIPAm Entrapment efficiency (%) PBMA-DSEA-PNIPAm-1 1:1:9 74.3 PBMA-DSEA-PNIPAm-2 2:1:8 73.5 PBMA-DSEA-PNIPAm-3 3:1:7 72.7 PBMA-DSEA-PNIPAm-4 4:1:6 70.6 PBMA-DSEA-PNIPAm-5 5:1:5 67.9

[0100] In summary, the PBMA-DSEA-PNIPAm copolymer micelles prepared in the present invention use the block copolymer as the raw material and the high-polymerized disulfide bond as the main skeleton to synthesize amphiphilic brush copolymer micelles. A specific brush-type structure copolymer arranged alternately on the disulfide bond skeleton is prepared. Through the self-assembly of the polymer chains at the hydrophobic end and the hydrophilic end in the copolymer in the medium, a polymer micelle with a stable cavity structure can be formed. The formed cavity has a specific hydrophilic outer shell and hydrophobic inner core structure, so that the polymer micelle can encapsulate hydrophobic drugs and be dispersed in a hydrophilic matrix. The amphiphilic copolymer prepared in the present invention has a brush-type structure and has the unique properties of brush polymers, making the micelles have better static and dynamic stability. The cavity structure formed by the micelles can achieve a drug encapsulation efficiency of 74.2%, and the particle size is less than 200 nm, having good prospects for biomedical applications. Through the above test results of a series of copolymer micelles prepared in the present invention, we will select the micelles with a mass ratio of PBMA-AA / PNIPAm-AA of 3:7 for the next hydrogel composite.

[0101] Example 3 Preparation of green tea essential oil hydrogel patch

[0102] 1. Preparation of PBMA-DSEA-PNIPAm copolymer-encapsulated green tea essential oil nano-micelles

[0103] It was prepared by dialysis. Based on the mass ratio of PBMA-AA / PNIPAm-AA being 3:7, (200 mg) of the PBMA-DSEA-PNIPAm copolymer and (1 mL) of green tea essential oil were weighed and dissolved in (100 mL) of THF. Then it was placed in a dialysis bag and put into a 1000 mL beaker and dialyzed with distilled water at room temperature for 24 h. After dialysis, the dialysate was freeze-dried to obtain the nano-micelle powder loaded with green tea essential oil.

[0104] 2. Preparation of nano-micelle composite hyaluronic acid hydrogel

[0105] Dissolve (0.5 g) of hyaluronic acid (HA) in (20 mL) of deionized water to form an HA aqueous solution. Then add the micelle powder loaded with green tea essential oil, and the weight ratio of HA to the micelle powder is 5:1. Then add (3 g) of adipic dihydrazide (ADH) (6 times the weight of HA) and continue stirring under sufficient stirring. After adding 1 mol / L HCl to adjust the pH value of the mixed solution to 3.5 - 4.75, add (0.4 g) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) under sufficient stirring, and let the reaction solution gel overnight at room temperature. Adjust the pH value to 7 with NaOH. Then place it in a dialysis bag and put it into a 1000 mL beaker and dialyze with distilled water at room temperature for 24 h to obtain the nano-micelle composite hydrogel containing green tea essential oil.

[0106] 3. Preparation of green tea essential oil hydrogel patch

[0107] Coat the hydrogel loaded with green tea essential oil on the non-woven fabric to form a gel layer; stick the CPP embossed film on the other side of the gel layer and cut to obtain the hydrogel patch.

[0108] Example 4 Safety detection of green tea essential oil hydrogel patch

[0109] Use the green tea essential oil hydrogel patch prepared in Example 3 to conduct microbial detection and hygienic chemistry detection respectively, and the test standards are carried out in accordance with the "Technical Specifications for Cosmetics Safety" (2015 Edition).

[0110] The detection results are shown in Table 6 and Table 7, indicating that the green tea essential oil hydrogel patch prepared by the present invention is lower than the limit values in the results of microbial and hygienic chemistry detections, and the quality detection results meet the requirements of national quality standards.

[0111] Table 6 Microbial detection results

[0112] Test item Test result Limit value Total number of colonies (CFU / g) ＜10 ≤1000 Total number of molds and yeasts (CFU / g) ＜10 ≤100 Thermotolerant coliforms / g Not detected Shall not be detected Staphylococcus aureus / g Not detected Shall not be detected Pseudomonas aeruginosa / g Not detected Shall not be detected

[0113] Table 7 Hygienic chemistry detection results

[0114] Test item Unit Test result Test method Detected concentration Limit value Mercury mg / kg Not detected Hydride generation atomic fluorescence spectrometry Not detected ≤1 Arsenic mg / kg Not detected Hydride generation atomic fluorescence spectrometry Not detected ≤2 Lead mg / kg Not detected Flame atomic absorption spectrometry Not detected ≤10 Cadmium mg / kg Not detected Flame atomic absorption spectrometry Not detected ≤5 Dioxane mg / kg Not detected Gas chromatography - mass spectrometry Not detected ≤30

[0115] Preparation of Green Tea Essential Oil Hydrogel Patch of Comparative Example 1

[0116] 1. Preparation of Green Tea Essential Oil Composite Hyaluronic Acid Hydrogel

[0117] Dissolve (0.5 g) HA in (20 mL) deionized water to form an HA aqueous solution, and then add (0.1 mL) green tea essential oil. Then add (3 g) adipic dihydrazide (ADH) (6× the weight of HA) with sufficient stirring and continue stirring. After adjusting the pH value of the mixed solution to 3.5 - 4.75 by adding 1 mol / L HCl, add (0.4 g) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) with sufficient stirring, let the reaction solution gel overnight at room temperature, and adjust the pH value to 7 with NaOH. Then place it in a dialysis bag and dialyze it in a 1000 mL beaker with distilled water at room temperature for 24 h.

[0118] 2. Preparation of Green Tea Essential Oil Hydrogel Patch

[0119] Coat the hydrogel loaded with green tea essential oil on the non-woven fabric to form a gel layer; stick a CPP embossed film on the other side of the gel layer and cut to obtain.

[0120] 3. Measurement of Encapsulation Efficiency of Green Tea Essential Oil

[0121] Measure the encapsulation efficiency of the green tea essential oil composite hyaluronic acid hydrogels prepared in Example 3 and Comparative Example 1. The measurement method is the same as that in Example 2. The results are shown in Table 8. From the results in Table 8, it can be seen that compared with directly loading green tea essential oil into the hydrogel, the encapsulation efficiency of green tea essential oil by the polymer micelles prepared in Example 3 of the present invention and then compounding with the hydrogel is increased by nearly 1.5 times, indicating that the green tea hydrogel patch of the present invention has good drug loading capacity and greatly improves the utilization rate of green tea essential oil.

[0122] Table 8 Encapsulation Efficiencies of Example 3 and Comparative Example 1

[0123] Group Entrapment efficiency (%) Example 3 72.7 Comparative Example 1 47.5

[0124] Preparation of Hyaluronic Acid Hydrogel Patch of Comparative Example 2

[0125] 1. Preparation of PBMA-b-PNIPAm Micelles

[0126] Prepare PBMA-b-PNIPAm micelles according to the method described in the existing research by Chung J E et al. PNIPAm-OH is prepared by free radical polymerization using ME as a chain transfer agent. Dissolve NIPAm (3 M), 2-mercaptoethanol (ME) and benzoyl peroxide (BPO) (5×10 3M) was dissolved in THF (100 mL). In the freeze-thaw cycle, each solution was repeatedly degassed under reduced pressure and sealed in an ampoule. Polymerization was carried out at 70 °C and stopped by freezing after 7 h. After most of the THF had evaporated, the polymer was precipitated three times in excess diethyl ether and dried in vacuo. The dried polymer was dissolved in cold water and dialyzed against water for 3 days at 4 °C using a dialysis membrane. After dialysis, freeze-drying was performed to obtain PNIPAm-OH powder. Poly(butyl methacrylate)-COOH (PBMA-COOH) was prepared by radical polymerization using 3-mercaptopropionic acid (MPA) as a chain transfer agent. 0.01 N CH 3 NaO was dissolved in a mixed solution of methanol and dioxane, and the terminal carboxyl concentration was determined by non-aqueous potentiometric titration. PBMA-COOH (5.7×10 -5 mol) was reacted with SOC1 2 (2.7×10 -3 mol) at 60 °C for 24 h. The freeze-dried product, triethylamine (2.9×10 -4 mol), and pyridine (2.9×10 -4 mol) were dissolved in THF (5 mL). Under a N 2 atmosphere, the solution was dropped into a large excess of PIPAAm-OH solution (PIPAAm-OH = 1.1×10 -4 mol / THF 5 ml). After reacting at room temperature for 24 h, the product was precipitated twice in a large excess of diethyl ether and then precipitated again in warm water (30 °C) to obtain pure PNIPAm-PBMA block copolymer. The PNIPAm-PBMA block copolymer solution (15 mg) was added to N-ethylacetamide (3 ml), placed in a dialysis bag, and dialyzed against water at 20 °C for 24 h. After dialysis, the dialysate was freeze-dried to obtain PBMA-b-PNIPAm micelle powder.

[0127] 2. Preparation of hyaluronic acid hydrogel

[0128] (0.5 g) of HA was dissolved in (20 mL) of deionized water to form an HA aqueous solution. Then, PBMA-b-PNIPAm micelle powder was added, and the weight ratio of HA to micelle powder was 5:1. Then, (3 g) of adipic dihydrazide (ADH) (6× the weight of HA) was added with continuous stirring. After adjusting the pH value of the mixed solution to 3.5 - 4.75 by adding 1 mol / L HCl, (0.4 g) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) was added with sufficient stirring, and the reaction solution was allowed to gel overnight at room temperature. The pH value was adjusted to 7 with NaOH. Then, it was placed in a dialysis bag and dialyzed against distilled water at room temperature for 24 h in a 1000 mL beaker.

[0129] 3. Preparation of hyaluronic acid hydrogel patch

[0130] Coat the hyaluronic acid hydrogel on the non-woven fabric to form a gel layer; stick the CPP embossed film on the other side of the gel layer and cut to obtain.

[0131] Example 5 Skin Anti-aging Efficacy Test

[0132] Randomly select 50 female volunteers aged 35 - 55 years old. Use the green tea essential oil hydrogel patch prepared in Example 3 as the sample group and the hyaluronic acid hydrogel patch of Comparative Example 2 as the control group for testing (the dosage and usage concentration of each group are the same). Randomly divide them into 2 groups, with 25 people in each group. Before the test, all volunteers sign a consent form. All volunteers have skin aging phenomena such as rough, loose facial skin, or deepening wrinkles. After the volunteers wash their faces, they are placed in an environment with constant temperature and humidity (indoor temperature 22 - 25 °C, humidity 40 - 60%) and balanced for 40 minutes. Then, the facial skin condition of the volunteers is evaluated by a contour curve instrument and taking pictures to obtain the initial value. Then, the green tea essential oil hydrogel patch sample and the hyaluronic acid hydrogel patch control in the examples of the present invention are respectively used on the 2 groups of volunteers. The volunteers use the test hydrogel patch sample on their faces once a day. After continuous use for 2 months, the facial skin condition after using the test hydrogel patch sample is evaluated again by a contour curve instrument and taking pictures to obtain the final value.

[0133] Use statistical methods to analyze the initial value and final value data of the facial skin wrinkles of the volunteers, and judge the change of the facial skin wrinkles of the volunteers after using the test hydrogel patch sample and the improvement effect of comprehensive skin improvement including skin flexibility and skin color (p >= 0.05 means no significant difference, p < 0.05 means significant difference).

[0134] The test results are shown in Table 9, indicating that compared with the control group of the hyaluronic acid hydrogel patch only compounded with PBMA-b-PNIPAm micelles, the green tea essential oil hydrogel patch provided by the present invention has good skin adaptability, and significant anti-wrinkle effects and comprehensive skin improvement effects are obtained after use, indicating that the green tea essential oil hydrogel patch of the present invention has good anti-aging effects on the skin.

[0135] Table 9 Anti-aging Effect

[0136] Test item Example 3 Comparative Example 2 Area of deep wrinkles (>200μm) Significant Not significant Density of main wrinkles Significant Not significant Average density of main wrinkles Significant Not significant Roughness Significant Not significant Comprehensive skin improvement effect Significant Not significant

[0137] (Note: The difference in facial skin before and after the test is indicated by "not significant" or "significant")

[0138] At the same time, the present invention also tested the hydrogel of Comparative Example 2 loaded with plant essential oil. However, due to the problem of its PBMA-b-PNIPAm micelle structure, its CMC value is relatively high, which is not conducive to loading plant essential oil, and its stability and loading rate are both poor, and the effect of the present invention cannot be achieved.

[0139] The present invention provides a preparation idea and method for a green tea essential oil hydrogel patch. There are many methods and ways to specifically implement this technical solution. The above are only feasible implementation manners of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and retouches can be made, and these improvements and retouches should also be regarded as the protection scope of the present invention. Each component not clearly defined in this embodiment can be implemented by using the prior art.

Claims

1. An amphiphilic copolymer micelle containing plant essential oil, characterized in that: It includes an amphiphilic brush-type PBMA-DSEA-PNIPAm copolymer and green tea essential oil encapsulated therein; The amphiphilic brush-type PBMA-DSEA-PNIPAm copolymer is prepared from poly(tert-butyl methacrylate), 2,2-dithiodiethanol diacrylate and poly(N-isopropylacrylamide) by atom transfer radical polymerization, wherein the mass ratio of poly(tert-butyl methacrylate), 2,2-dithiodiethanol diacrylate and poly(N-isopropylacrylamide) is (1-5):1:(5-9); The preparation method of the amphiphilic copolymer micelle containing plant essential oil is as follows: firstly prepare an amphiphilic brush-type PBMA-DSEA-PNIPAm copolymer, respectively dissolve poly(tert-butyl methacrylate), 2,2-dithiodiethanol diacrylate and poly(N-isopropylacrylamide) completely in tetrahydrofuran, add azobisisobutyronitrile after filling with N2 for 10 minutes, react at 60°C for 24 hours, purify the product once by ether precipitation, and obtain the product by vacuum drying at room temperature; then dissolve the PBMA-DSEA-PNIPAm copolymer and green tea essential oil in tetrahydrofuran, then place them in a dialysis bag, dialyze with distilled water at room temperature for 24 hours, and after the dialysis is completed, freeze-dry the dialyzate to obtain nano micelles loaded with green tea essential oil; the dosage ratio of the PBMA-DSEA-PNIPAm to the green tea essential oil is: 200-400 mg:1 mL; The brush-type structure of the amphiphilic brush-type PBMA-DSEA-PNIPAm copolymer is as follows: a high-poly disulfide bond is used as a linear backbone chain, and a hydrophobic end polymer chain and a hydrophilic end polymer chain are alternately arranged on the disulfide bond skeleton, wherein the hydrophobic end polymer chain is a poly(tert-butyl methacrylate) polymer chain, and the hydrophilic end polymer chain is a poly(N-isopropylacrylamide) polymer chain.

2. A nano-micelle composite hydrogel containing plant essential oil, characterized in that: The invention comprises a hydrogel matrix and the amphiphilic copolymer micelles according to claim 1.

3. The nano-micelle composite hydrogel according to claim 2, characterized in that: The mass ratio of the hydrogel matrix to the amphiphilic copolymer micelles is 5-10:

1.

4. The nano-micelle composite hydrogel according to claim 2 or 3, characterized in that: The hydrogel matrix is ​​sodium hyaluronate.

5. The method for preparing the nano-micelle composite hydrogel according to claim 2 or 3, characterized in that: The nano-micelle powder loaded with plant essential oil is reacted with a hydrogel matrix to obtain a nano-micelle composite hydrogel containing the plant essential oil.

6. Use of the nano-micelle composite hydrogel according to claim 2 or 3 in anti-aging or in the preparation of anti-aging products.

7. A hydrogel product containing green tea essential oil, characterized in that: A nano-micelle composite hydrogel comprising any one of claims 2 to 4.

Images