A nano-carrier-based active ingredient sustained-release mask and a preparation method thereof

Abstract

The application discloses a kind of active ingredient sustained-release mask based on nano-carrier and preparation method thereof, it is related to mask technical field, the method first utilizes anhydrous betaine, 1,3-propanediol, water and arginine to construct deep eutectic solvent (NADES) core layer phase, and high-efficiency dissolution of poorly soluble active ingredient;Subsequently, lipid film is prepared with phospholipid, cholesterol and stearic acid, and NADES core layer is wrapped in lipid bilayer by hydration and homogenization process, and nano-lipid carrier with "core-shell interface interlocking structure" is formed;Finally, it is dispersed in cosmetic base and infiltrated base cloth to obtain mask;The application utilizes the interface ion pair effect of arginine and stearic acid, significantly enhances the structural stability and encapsulation efficiency of carrier, effectively solves the problems such as active ingredient easy to leak, easy to crystallize and oxidation discoloration, and the prepared mask has high permeability, long-acting sustained-release and auxiliary preservative and moisturizing effect, and the process is green and environmentally friendly, suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of facial mask technology, specifically to a sustained-release facial mask based on a nanocarrier and its preparation method. Background Technology

[0002] As living standards improve, consumers' demand for functional facial mask products is increasing, especially for products with high efficacy such as whitening, anti-aging, and anti-oxidation. To achieve these effects, formulators usually need to add specific highly active ingredients to the mask essence, such as glycyrrhizin, ferulic acid, resveratrol, and retinol.

[0003] However, in practical applications, the above-mentioned active ingredients generally face the triple challenges of being "poorly soluble, unstable, and difficult to penetrate": First, poor solubility. Many highly effective active ingredients are fat-soluble or poorly soluble substances, which are extremely difficult to dissolve in water-based mask bases. Often, a large amount of organic solvents (such as ethanol) or surfactants are needed for solubilization. This not only reduces the gentleness of the product, but also easily leads to the precipitation or recrystallization of the ingredients (such as the "re-sanding" phenomenon of resveratrol), which seriously affects the skin feel and shelf life.

[0004] Second, it has low stability. Ingredients such as ferulic acid and retinol are extremely sensitive to light, heat, and oxygen. They are very prone to oxidation, discoloration, or degradation and inactivation during production and storage, which greatly reduces the efficacy of the product.

[0005] Third, the transdermal absorption rate is low. The stratum corneum of the skin acts as a natural barrier, limiting the penetration of topical macromolecules or polar molecules, causing most active ingredients to remain on the skin surface and unable to reach deeper targets to exert their effects.

[0006] To address these issues, nanocarrier technologies (such as liposomes, nanoemulsions, and solid lipid nanoparticles) have been widely adopted in the cosmetics field. Among them, liposomes are considered one of the most ideal transdermal delivery carriers due to their excellent biocompatibility and biomembrane-like structure. However, traditional liposomes still have significant limitations when encapsulating poorly soluble drugs: for lipophilic drugs, they can only be embedded within the limited space of the lipid bilayer, resulting in extremely low drug loading and easy "extrusion"; for drugs with poor water solubility, the internal aqueous phase cannot dissolve them at all, making effective encapsulation impossible.

[0007] In recent years, natural deep eutectic solvent (NADES) has attracted attention as a novel green solvent due to its astonishing supersolubilizing ability (more than 100 times) for poorly soluble natural products. Theoretically, encapsulating NADES as an "internal aqueous phase" within liposomes to construct a "NADES-liposome" composite carrier can perfectly combine the high solubility of NADES with the transdermal protective effect of liposomes.

[0008] However, existing attempts often face serious interfacial stability problems: NADES has extremely high polarity, viscosity, and osmotic pressure, resulting in a huge difference in interfacial tension between it and the hydrophobic lipid bilayer. During preparation or storage, the NADES core layer is highly susceptible to leakage through the lipid shell, leading to the disintegration of the carrier structure and the loss of active ingredients. In addition, the structure of ordinary liposomes is relatively loose and cannot withstand the osmotic pressure shock generated by the high concentration of solute inside NADES.

[0009] Therefore, how to construct a nanocarrier delivery system with a stable structure and tight interface that can both leverage the super-solubilizing advantages of NADES and effectively prevent leakage of contents, and apply it to the development of high-performance facial mask products, is a problem that urgently needs to be solved in the field of cosmetic technology. Summary of the Invention

[0010] To address the shortcomings of existing technologies, the present invention aims to provide a sustained-release facial mask based on a nanocarrier and its preparation method. The present invention constructs a stable nanodelivery system with "core-shell interface interlocking," utilizing a deep eutectic solvent to break the lattice energy of poorly soluble components, achieving significant solubilization; the unique interface molecular rivet structure significantly solves the problem of drug leakage; the system has both auxiliary antiseptic and deep moisturizing effects, providing a green and safe solution for the efficient transdermal delivery of poorly soluble active ingredients.

[0011] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Preparation of deep eutectic solvent core phase: Anhydrous betaine (as hydrogen bond acceptor), 1,3-propanediol (as hydrogen bond donor), water and arginine were mixed to construct a deep eutectic solvent system matrix; then the active ingredient was added and dissolved to obtain the deep eutectic solvent core phase.

[0012] Arginine, as a basic amino acid, plays a dual key role in the deep eutectic solvent system of this invention: on the one hand, it participates in the construction of the supramolecular network of the deep eutectic solvent as a hydrogen bond donor / acceptor, and its unique guanidinium structure can significantly enhance the solvent's solubility and stability for specific poorly soluble active ingredients (especially those containing phenolic hydroxyl or carboxyl groups); on the other hand, arginine carries a positive charge, which enables it to migrate to the oil-water interface, providing the necessary structural basis for subsequent electrostatic interactions with acidic components in the lipid layer, and serving as a key anchor point for the formation of a stable core-shell interlocking structure.

[0013] (2) Preparation of lipid films: lipid films are prepared using lipid components containing phospholipids, cholesterol and stearic acid.

[0014] Stearic acid, a long-chain saturated fatty acid, is introduced into lipid films primarily as a "skeleton enhancer" and "interfacial reactant." Firstly, the long carbon chain of stearic acid can embed into the hydrophobic tail region of the phospholipid bilayer, increasing the film's density and rigidity and preventing fusion or breakage of the carrier during storage. More importantly, the carboxyl terminus of stearic acid is exposed at the inner aqueous phase interface during hydration, undergoing an in-situ ion-pair reaction with arginine in the deep eutectic solvent core layer. This specific interaction tightly connects the core and shell, significantly reducing the leakage rate of active ingredients and endowing the nanocarrier with resistance to external environmental changes (such as pH fluctuations and dilution).

[0015] (3) Hydration and homogenization: The deep eutectic solvent core layer obtained in step (1) is hydrated relative to the lipid film obtained in step (2) to obtain a crude emulsion; then the crude emulsion is homogenized to obtain a nano lipid carrier dispersion.

[0016] In this process, the deep eutectic solvent core phase is encapsulated within the lipid bilayer, forming a nanocarrier with a "core-shell" structure.

[0017] (4) Mask forming: Prepare mask essence using the nano-lipid carrier dispersion obtained in step (3) and combine it with the mask base fabric to obtain the active ingredient sustained-release mask based on nano-carrier.

[0018] As a preferred embodiment of the present invention, in step (1), the molar ratio of anhydrous betaine, arginine, 1,3-propanediol, and water is 1:0.2~0.5:1.5~2.5:0.4~0.6. The deep eutectic solvent formed under this ratio has suitable viscosity and polarity, which is beneficial for the solubilization of the active ingredients. If necessary, citric acid or lactic acid can be used to adjust the pH of the core phase of the deep eutectic solvent to 7.5~9.0. This weakly alkaline environment helps maintain the dissociation state of arginine and the stability of certain specific active ingredients.

[0019] Furthermore, in step (1), the active ingredient is preferably selected from glycyrrhizin, ferulic acid, resveratrol, curcumin, astaxanthin, or retinol. These active ingredients typically suffer from poor water solubility, easy oxidation and inactivation, or poor skin permeability. The deep eutectic solvent nanocarrier system of the present invention can significantly improve their solubility, stability, and transdermal absorption.

[0020] Further, in step (1), the specific process of mixing is as follows: anhydrous betaine, arginine, 1,3-propanediol and water are stirred at 50~70℃ for 30~60min.

[0021] The heating conditions of 50~70℃ are chosen to disrupt the original crystal lattice structure of the raw material molecules, promote the formation of hydrogen bond networks, and thus obtain a uniform, transparent, and clear blank deep eutectic solvent matrix.

[0022] The active ingredient is then added, and stirring continues until dissolved. The amount of the active ingredient added is 1-5% of the mass of the blank deep eutectic solvent matrix.

[0023] As a preferred embodiment of the present invention, in step (2), the phospholipid is preferably hydrogenated soybean lecithin (HSPC) or dipalmitoylphosphatidylcholine (DPPC). These two types of phospholipids have high phase transition temperatures, which can impart better rigidity and stability to the nanocarrier.

[0024] The specific process for preparing the lipid film involves dissolving phospholipids, cholesterol, and stearic acid in an organic solvent, removing the organic solvent by rotary evaporation under reduced pressure at a water bath temperature of 40-60°C, thereby forming a uniform thin film of lipids on the container wall, and then vacuum drying overnight to completely remove any residual organic solvent. The organic solvent can be one or a mixture of anhydrous ethanol, methanol, and chloroform.

[0025] Furthermore, in step (2), in order to ensure the balance between the fluidity and stability of the membrane structure, the preferred mass ratio of phospholipids, cholesterol and stearic acid is 55~65:12~18:4~8; the ratio of the total mass of lipid components to the volume of organic solvent is 1 g:20~100mL.

[0026] As a key process parameter of the present invention, in step (3), the specific operation of hydration is as follows: the deep eutectic solvent core phase is preheated to 55~65°C and added to a container containing a lipid film.

[0027] Preheating is to ensure that the core phase temperature is higher than the phase transition temperature of the lipid, so that the lipid film is in a liquid crystal state, which facilitates hydration and stripping.

[0028] Under constant temperature water bath conditions of 55~65℃, the lipid film is rotated and hydrated for 30~60 min at a speed of 100~200 r / min. Shear force is used to completely detach and disperse the lipid film, which then self-assembles to form multivesicular liposomes (crude emulsion).

[0029] To obtain suitable encapsulation efficiency and drug loading, the total mass ratio of lipid components to the deep eutectic solvent core phase is controlled at 1:20~50.

[0030] Further, in step (3), the homogenization process specifically involves: homogenizing the crude emulsion at a temperature of 55-65°C using a high-pressure homogenizer. The homogenization pressure is 600-900 bar, and the number of cycles is 3-6.

[0031] High-pressure homogenization can further reduce particle size and decrease particle size distribution width.

[0032] After processing, the average particle size of the obtained nanolipid carrier dispersion is 100~200nm, and the polydispersity index (PDI) is less than 0.25.

[0033] In step (4), the preparation method of the mask essence is as follows: the nanolipid carrier dispersion and the cosmetic matrix are mixed evenly at a mass ratio of 10~20:80~90. The cosmetic matrix usually contains water, moisturizers (such as glycerin, butylene glycol, etc.), thickeners (such as carbomer, xanthan gum, etc.) and other conventional skin care excipients.

[0034] The process of combining the essence with the mask base fabric is as follows: the essence is soaked into the mask base fabric at a mass ratio of 8~12:1 to obtain the finished mask.

[0035] The present invention also provides a nanocarrier-based sustained-release facial mask for active ingredients prepared by the above preparation method.

[0036] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention proposes a green and efficient process for preparing nanocarriers based on deep eutectic solvents (NADES). First, this invention utilizes a NADES system constructed from anhydrous betaine, 1,3-propanediol, and water as a solvent, eliminating the use of toxic organic solvents commonly used in traditional extraction or drug loading processes, thus exhibiting high biosafety and environmental friendliness. This system not only efficiently dissolves poorly soluble active ingredients (such as glycyrrhizin and resveratrol), enabling the one-pot preparation of high-concentration core-layer phases, but also avoids complex subsequent impurity removal steps. Second, the process route of this invention cleverly achieves simultaneous nanoscale encapsulation and interfacial assembly of active ingredients during the two-phase mixing process by controlling the hydration temperature and homogenization pressure. The resulting nanolipid carriers have a narrow particle size distribution, good uniformity, and high process reproducibility, greatly reducing production costs and energy consumption, making them suitable for large-scale industrial production.

[0037] 2. This invention constructs a stable nano-delivery system with a "core-shell interface interlocking structure" and endows the mask with unexpected comprehensive effects through the special properties of the deep eutectic solvent: (1) This invention utilizes the in-situ ion pair reaction of arginine and stearic acid at the oil-water interface to generate a strong electrostatic attraction effect, which anchors the hydrophilic deep eutectic solvent core layer and the hydrophobic lipid shell layer tightly like "molecular rivets", significantly enhancing the compactness and interfacial modulus of the lipid bilayer, thereby effectively blocking the channel for the migration of encapsulated active ingredients to the outside and solving the problem of easy leakage of traditional lipid carriers. (2) Using the NADES core layer to replace the traditional aqueous core layer, its special supramolecular hydrogen bond network structure can break the lattice energy of insoluble active ingredients (such as ferulic acid, glycyrrhizin, etc.), making its solubility significantly higher than that of the traditional aqueous system. This extremely high concentration of "liquid drug library" is encapsulated in the nanocarrier, which makes the effective drug loading of a single mask a qualitative leap. (3) The NADES system has extremely high osmotic pressure and a dense hydrogen bond network, which can effectively inhibit the metabolic activity of microorganisms. Even when the mask essence is diluted, this nanocarrier system still exhibits significant auxiliary antibacterial effects, allowing the product to significantly reduce or even eliminate the need for traditional chemical preservatives in certain formulations, thereby significantly reducing the risk of product allergies. At the same time, the NADES component itself is a highly effective natural moisturizing factor, and its water-locking ability is superior to hyaluronic acid, giving the mask product an excellent deep nourishing and long-lasting moisturizing experience. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. Of course, the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention.

[0039] Unless otherwise specified, all chemical reagents and materials in this invention are purchased from the market or synthesized from raw materials purchased from the market.

[0040] A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, arginine, 1,3-propanediol and water are stirred at 50~70℃ for 30~60min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient (selected from one or more of glycyrrhizin, ferulic acid, resveratrol, curcumin, astaxanthin or retinol) is added and stirred until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase is adjusted to 7.5~9.0 using citric acid or lactic acid. The molar ratio of anhydrous betaine, arginine, 1,3-propanediol and water is 1:0.2~0.5:1.5~2.5:0.4~0.6. The amount of the active ingredient added is 1~5% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 55-65 parts of phospholipids (hydrogenated soybean lecithin or dipalmitoylphosphatidylcholine), 12-18 parts of cholesterol and 4-8 parts of stearic acid in an organic solvent (one or more of anhydrous ethanol, methanol and chloroform). The ratio of the total mass of lipid components to the volume of organic solvent is 1g: 20-100mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 40-60℃. A lipid film is formed on the container wall. The film is then vacuum dried overnight to remove residual solvent. (3) Preheat the deep eutectic solvent core phase to 55~65℃ and add it to a container containing a lipid film; the total mass ratio of lipid components to the mass ratio of deep eutectic solvent core phase is 1:20~50; under constant temperature water bath conditions of 55~65℃, rotate and hydrate at a speed of 100~200r / min for 30~60min to completely detach and disperse the lipid film to obtain a crude emulsion; under the condition of keeping the crude emulsion at 55~65℃, perform circulating homogenization through a high pressure homogenizer; the homogenization pressure is 600~900bar, and the number of cycles is 3~6 times to obtain a nano lipid carrier dispersion; (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 10~20:80~90 to prepare the mask essence; soak the mask base cloth with the essence at a mass ratio of 8~12:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0041] The preparation method of cosmetic base includes the following steps: Weigh the raw materials according to the following formula: 40g glycerin, 40g butylene glycol, 10g betaine, 50g 0.5wt% sodium hyaluronate solution, 1.5g carbomer, 1g allantoin, 2g panthenol, 4g p-hydroxyacetophenone, 4g 1,2-hexanediol, 0.5g disodium EDTA, and add deionized water to a final volume of 1000g. Add deionized water to the main reactor, then add disodium EDTA, allantoin, and panthenol, and stir until completely dissolved. Mix glycerin, butylene glycol, p-hydroxyacetophenone, and 1,2-hexanediol evenly, then add to the main reactor and stir evenly. Disperse carbomer in an appropriate amount of deionized water until fully swollen, then add to the main reactor and stir evenly. Adjust the pH of the system to 6.0-7.0 using a 10wt% arginine aqueous solution. At this point, the viscosity of the system increases, forming a transparent gel-like liquid. Add sodium hyaluronate solution and betaine, stir at low speed until evenly mixed, and defoamed to obtain the cosmetic matrix.

[0042] The present invention will be further described below through specific embodiments.

[0043] Example 1

[0044] A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, arginine, 1,3-propanediol and water were stirred at 60°C for 45 min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient glycyrrhizin was added and stirring was continued until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase was adjusted to 9.0 using citric acid. The molar ratio of anhydrous betaine, arginine, 1,3-propanediol and water was 1:0.3:2.0:0.5. The amount of the active ingredient added was 3% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 600g dipalmitoylphosphatidylcholine, 150g cholesterol and 60g stearic acid in anhydrous ethanol. The ratio of the total mass of lipid components to the volume of organic solvent is 1g:60mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 50℃. A lipid film is formed on the container wall and vacuum dried overnight to remove residual solvent. Prepare the lipid film. (3) The deep eutectic solvent core phase was preheated to 60°C and added to a container containing a lipid film. The total mass ratio of the lipid components to the deep eutectic solvent core phase was 1:35. Under constant temperature water bath conditions of 60°C, the lipid film was rotated and hydrated for 45 minutes at a speed of 150 r / min to completely detach and disperse the lipid film, thus obtaining a crude emulsion. The crude emulsion was then subjected to cyclic homogenization by a high-pressure homogenizer under the condition of heat preservation at 60°C. The homogenization pressure was 700 bar and the number of cycles was 5 to obtain a nano lipid carrier dispersion. (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 15:85 to prepare the mask essence; soak the mask base fabric (all-cotton spunlace nonwoven fabric) with the essence at a mass ratio of 10:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0045] Example 2

[0046] A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, arginine, 1,3-propanediol and water were stirred at 60°C for 45 min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient ferulic acid was added and stirring was continued until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase was adjusted to 9.0 using citric acid. The molar ratio of anhydrous betaine, arginine, 1,3-propanediol and water was 1:0.3:2.0:0.5. The amount of the active ingredient added was 3% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 600g dipalmitoylphosphatidylcholine, 150g cholesterol and 60g stearic acid in anhydrous ethanol. The ratio of the total mass of lipid components to the volume of organic solvent is 1g:60mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 50℃. A lipid film is formed on the container wall and vacuum dried overnight to remove residual solvent. Prepare the lipid film. (3) The deep eutectic solvent core phase was preheated to 60°C and added to a container containing a lipid film. The total mass ratio of the lipid components to the deep eutectic solvent core phase was 1:35. Under constant temperature water bath conditions of 60°C, the lipid film was rotated and hydrated for 45 minutes at a speed of 150 r / min to completely detach and disperse the lipid film, thus obtaining a crude emulsion. The crude emulsion was then subjected to cyclic homogenization by a high-pressure homogenizer under the condition of heat preservation at 60°C. The homogenization pressure was 700 bar and the number of cycles was 5 to obtain a nano lipid carrier dispersion. (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 15:85 to prepare the mask essence; soak the mask base fabric (all-cotton spunlace nonwoven fabric) with the essence at a mass ratio of 10:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0047] Example 3

[0048] A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, arginine, 1,3-propanediol and water were stirred at 60°C for 45 min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient resveratrol was added and stirring was continued until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase was adjusted to 9.0 using citric acid. The molar ratio of anhydrous betaine, arginine, 1,3-propanediol and water was 1:0.3:2.0:0.5. The amount of the active ingredient added was 3% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 600g dipalmitoylphosphatidylcholine, 150g cholesterol and 60g stearic acid in anhydrous ethanol. The ratio of the total mass of lipid components to the volume of organic solvent is 1g:60mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 50℃. A lipid film is formed on the container wall and vacuum dried overnight to remove residual solvent. Prepare the lipid film. (3) The deep eutectic solvent core phase was preheated to 60°C and added to a container containing a lipid film. The total mass ratio of the lipid components to the deep eutectic solvent core phase was 1:35. Under constant temperature water bath conditions of 60°C, the lipid film was rotated and hydrated for 45 minutes at a speed of 150 r / min to completely detach and disperse the lipid film, thus obtaining a crude emulsion. The crude emulsion was then subjected to cyclic homogenization by a high-pressure homogenizer under the condition of heat preservation at 60°C. The homogenization pressure was 700 bar and the number of cycles was 5 to obtain a nano lipid carrier dispersion. (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 15:85 to prepare the mask essence; soak the mask base fabric (all-cotton spunlace nonwoven fabric) with the essence at a mass ratio of 10:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0049] Comparative Example 1 A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, 1,3-propanediol and water were stirred at 60°C for 45 min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient glycyrrhizin was added and stirring was continued until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase was adjusted to 9.0. The molar ratio of anhydrous betaine, 1,3-propanediol and water was 1:2.0:0.5. The amount of the active ingredient added was 3% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 600g dipalmitoylphosphatidylcholine, 150g cholesterol and 60g stearic acid in anhydrous ethanol. The ratio of the total mass of lipid components to the volume of organic solvent is 1g:60mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 50℃. A lipid film is formed on the container wall and vacuum dried overnight to remove residual solvent. Prepare the lipid film. (3) The deep eutectic solvent core phase was preheated to 60°C and added to a container containing a lipid film. The total mass ratio of the lipid components to the deep eutectic solvent core phase was 1:35. Under constant temperature water bath conditions of 60°C, the lipid film was rotated and hydrated for 45 minutes at a speed of 150 r / min to completely detach and disperse the lipid film, thus obtaining a crude emulsion. The crude emulsion was then subjected to cyclic homogenization by a high-pressure homogenizer under the condition of heat preservation at 60°C. The homogenization pressure was 700 bar and the number of cycles was 5 to obtain a nano lipid carrier dispersion. (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 15:85 to prepare the mask essence; soak the mask base fabric (all-cotton spunlace nonwoven fabric) with the essence at a mass ratio of 10:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0050] Comparative Example 2 A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, arginine, 1,3-propanediol and water were stirred at 60°C for 45 min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient glycyrrhizin was added and stirring was continued until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase was adjusted to 9.0 using citric acid. The molar ratio of anhydrous betaine, arginine, 1,3-propanediol and water was 1:0.3:2.0:0.5. The amount of the active ingredient added was 3% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 600g dipalmitoylphosphatidylcholine and 150g cholesterol in anhydrous ethanol. The ratio of the total mass of lipid components to the volume of organic solvent is 1g:60mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 50℃. A lipid film is formed on the container wall and vacuum dried overnight to remove residual solvent. Prepare the lipid film. (3) The deep eutectic solvent core phase was preheated to 60°C and added to a container containing a lipid film. The total mass ratio of the lipid components to the deep eutectic solvent core phase was 1:35. Under constant temperature water bath conditions of 60°C, the lipid film was rotated and hydrated for 45 minutes at a speed of 150 r / min to completely detach and disperse the lipid film, thus obtaining a crude emulsion. The crude emulsion was then subjected to cyclic homogenization by a high-pressure homogenizer under the condition of heat preservation at 60°C. The homogenization pressure was 700 bar and the number of cycles was 5 to obtain a nano lipid carrier dispersion. (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 15:85 to prepare the mask essence; soak the mask base fabric (all-cotton spunlace nonwoven fabric) with the essence at a mass ratio of 10:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0051] Comparative Example 3 A method for preparing an active ingredient sustained-release facial mask based on a nanocarrier includes the following steps: (1) Anhydrous betaine, 1,3-propanediol and water were stirred at 60°C for 45 min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient glycyrrhizin was added and stirring was continued until dissolved to obtain a deep eutectic solvent core phase. The pH of the deep eutectic solvent core phase was adjusted to 9.0 using citric acid. The molar ratio of anhydrous betaine, 1,3-propanediol and water was 1:2.0:0.5. The amount of the active ingredient added was 3% of the mass of the blank deep eutectic solvent matrix. (2) Dissolve 600g dipalmitoylphosphatidylcholine and 150g cholesterol in anhydrous ethanol. The ratio of the total mass of lipid components to the volume of organic solvent is 1g:60mL. Remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 50℃. A lipid film is formed on the container wall and vacuum dried overnight to remove residual solvent. Prepare the lipid film. (3) The deep eutectic solvent core phase was preheated to 60°C and added to a container containing a lipid film. The total mass ratio of the lipid components to the deep eutectic solvent core phase was 1:35. Under constant temperature water bath conditions of 60°C, the lipid film was rotated and hydrated for 45 minutes at a speed of 150 r / min to completely detach and disperse the lipid film, thus obtaining a crude emulsion. The crude emulsion was then subjected to cyclic homogenization by a high-pressure homogenizer under the condition of heat preservation at 60°C. The homogenization pressure was 700 bar and the number of cycles was 5 to obtain a nano lipid carrier dispersion. (4) Mix the nano-lipid carrier dispersion with the cosmetic matrix at a mass ratio of 15:85 to prepare the mask essence; soak the mask base fabric (all-cotton spunlace nonwoven fabric) with the essence at a mass ratio of 10:1 to obtain the active ingredient sustained-release mask based on the nano-carrier.

[0052] Experiment 1: Determination of Physicochemical Properties and Encapsulation Efficiency of Nanocarriers Experimental methods: 1. Particle size and PDI: The average particle size and polydispersity index (PDI) of each group of samples were determined by dynamic light scattering (DLS).

[0053] 2. Zeta potential: a measure of surface potential.

[0054] 3. Encapsulation efficiency (EE%): Free drug was separated by ultrafiltration centrifugation, and the content of glycyrrhizin encapsulated in the carrier was determined by HPLC.

[0055] Formula: EE% = (Total drug amount - Free drug amount) / Total drug amount × 100%.

[0056] Table 1 Physicochemical properties and encapsulation efficiency of nanocarriers Experimental results show that the nanocarrier prepared in Example 1 has the smallest particle size and the narrowest distribution, with an encapsulation efficiency as high as 92.4%.

[0057] Compared to Comparative Example 3, the encapsulation efficiency of Example 1 was improved by nearly 40%, indicating that the binding of NADES to liposomes requires a specific interfacial medium. Example 1 showed a significant advantage compared to Comparative Examples 1 and 2. This demonstrates that arginine and stearic acid form a tight "ion-pair" anchoring structure at the interface: the positive charge of arginine and the negative charge of stearic acid attract each other, compressing the lipid bilayer and making it more compact. This allows for more effective encapsulation of the deep eutectic solvent core layer, preventing drug loss during preparation.

[0058] Experiment 2: Storage Stability and Drug Leakage Rate Test Experimental methods: Each group of nanocarrier dispersions was stored in a constant temperature incubator at 40℃ (accelerated aging conditions). Samples were taken on days 0, 7, 14, and 28 to determine the proportion of drug leaked into the medium (leakage rate).

[0059] Table 2 Drug leakage rate under accelerated storage at 40℃ In the accelerated test at 40°C, Example 1 showed remarkable stability, with a cumulative leakage rate of only 8.2% over 28 days.

[0060] In comparison, Comparative Examples 1, 2, and 3, lacking the "interface interlocking" mechanism, all exhibited severe drug leakage. It is particularly noteworthy that although Comparative Example 1 (containing stearic acid) and Comparative Example 2 (containing arginine) each had a unilateral enhancing effect on the shell or core layer, respectively, their leakage rates remained high. Only when both were present simultaneously (Example 1) did the leakage rate drop dramatically. This fully demonstrates that the "core-shell interface interlocking structure" acts like a "molecular rivet," effectively preventing the hydrophilic NADES core layer from migrating outward through the hydrophobic lipid layer, thereby achieving long-term stable encapsulation of the poorly soluble active ingredient.

[0061] Experiment 3: In vitro transdermal absorption experiment Experimental methods: A Franz diffusion cell was used, with excised pig skin as a barrier. The essence of each mask was added to the supply chamber, and the receiving chamber contained PBS buffer. Drug retention in each skin layer was measured after 24 hours (representing the site of action).

[0062] Table 3. Cumulative drug retention at different skin layers over 24 hours (μg / cm³) 2 ) Example 1 showed a drug retention rate as high as 42.6 μg / cm³ in the deep layers of the skin (active epidermis + dermis). 2 This is 3.5 times that of Comparative Example 3, and approximately twice that of Comparative Examples 1 and 2. This indicates that the nanocarrier of the present invention not only has a high drug loading capacity, but also possesses excellent deformability and skin affinity. The ion pairing of arginine and stearic acid moderately regulates the "flexibility-rigidity balance" of the membrane, making the nanocarrier both sufficiently stable to resist friction and sufficiently flexible to be squeezed through the gaps in the stratum corneum (squeezing effect). At the same time, the superosmotic pressure characteristics of the NADES core layer may further drive the penetration of active ingredients into the deeper layers of the skin, achieving the effect of "deep nourishment".

[0063] Experiment 4: Applicability Verification of Different Active Ingredients To verify the applicability of the preparation method of the present invention to different types of poorly soluble active ingredients, the key performance indicators of the nanocarriers prepared in Example 2 (containing ferulic acid) and Example 3 (containing resveratrol) were measured.

[0064] Table 4 Key performance parameters and special effects evaluation of Examples 2 and 3 The experimental results (Table 4) show that the preparation process of the present invention has good universality.

[0065] For ferulic acid (Example 2): Ferulic acid is usually easily oxidized and discolored in aqueous solution, and its carbomer gel structure is easily destroyed. In this invention, it is encapsulated in a deep eutectic solvent core layer, and its chemical stability is significantly improved by utilizing the strong hydrogen bonding network of NADES and the dual protection of the lipid shell. The color does not change significantly after 28 days of storage.

[0066] For resveratrol (Example 3): This component is extremely prone to recrystallization in traditional cosmetic systems. This invention utilizes a deep eutectic solvent to disrupt its lattice energy, achieving high-concentration liquid encapsulation with an encapsulation rate as high as 91.2%, and completely inhibiting crystallization during long-term storage, thus solving the problem of "returning sand" in the product.

[0067] In summary, the "core-shell interface interlocking" nanocarrier of this invention can provide excellent solubilization and stabilization protection for both easily oxidized and easily crystallized components.

[0068] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a sustained-release facial mask based on a nanocarrier, characterized in that, Includes the following steps: (1) Preparation of deep eutectic solvent core phase: Anhydrous betaine, 1,3-propanediol, water and arginine are mixed to dissolve the active ingredients and obtain deep eutectic solvent core phase; (2) Preparation of lipid films: lipid films are prepared using lipid components containing phospholipids, cholesterol and stearic acid; (3) Hydration and homogenization: The lipid film is hydrated using a deep eutectic solvent core layer to obtain a crude emulsion. The crude emulsion is then homogenized to obtain a nano lipid carrier dispersion. (4) Mask forming: Prepare mask essence using nano lipid carrier dispersion and combine it with mask base fabric to obtain the active ingredient sustained-release mask based on nano carrier.

2. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of anhydrous betaine, arginine, 1,3-propanediol and water is 1:0.2~0.5:1.5~2.5:0.4~0.6; the pH value of the deep eutectic solvent core phase is 7.5~9.

0.

3. The preparation method according to claim 1, characterized in that, In step (1), the active ingredient is selected from one or more of glycyrrhizin, ferulic acid, resveratrol, curcumin, astaxanthin or retinol.

4. The preparation method according to claim 1, characterized in that, In step (1), the mixing process is as follows: anhydrous betaine, arginine, 1,3-propanediol and water are stirred at 50~70℃ for 30~60min to form a transparent and clear blank deep eutectic solvent matrix. Then, the active ingredient is added and stirring is continued until dissolved. The amount of the active ingredient added is 1~5% of the mass of the blank deep eutectic solvent matrix.

5. The preparation method according to claim 1, characterized in that, In step (2), the phospholipid is hydrogenated soybean lecithin or dipalmitoylphosphatidylcholine; the process of preparing the lipid film is as follows: phospholipid, cholesterol and stearic acid are dissolved in an organic solvent, and the organic solvent is removed by rotary evaporation under reduced pressure under water bath conditions of 40~60℃, forming a lipid film on the container wall, and then vacuum dried overnight to remove residual solvent; the organic solvent is one or more of anhydrous ethanol, methanol and chloroform.

6. The preparation method according to claim 1, characterized in that, In step (2), the mass ratio of phospholipids, cholesterol and stearic acid is 55~65:12~18:4~8.

7. The preparation method according to claim 1, characterized in that, In step (3), the specific operation of hydration is as follows: the deep eutectic solvent core phase is preheated to 55~65℃ and added to a container containing a lipid film; under constant temperature water bath conditions of 55~65℃, the lipid film is rotated and hydrated for 30~60min at a speed of 100~200r / min to completely detach and disperse the lipid film, and a crude emulsion is obtained; the total mass ratio of lipid components to the mass ratio of deep eutectic solvent core phase is 1:20~50.

8. The preparation method according to claim 1, characterized in that, In step (3), the homogenization process specifically involves: homogenizing the crude emulsion in a high-pressure homogenizer at a temperature of 55-65°C; the homogenization pressure is 600-900 bar, and the number of cycles is 3-6.

9. The preparation method according to claim 1, characterized in that, In step (4), the preparation method of the mask essence is as follows: the nano lipid carrier dispersion and the cosmetic matrix are mixed evenly at a mass ratio of 10~20:80~90; the cosmetic matrix contains water, moisturizer and thickener; the process of combining with the mask base cloth is as follows: the essence is soaked in the mask base cloth at a mass ratio of 8~12:

1.

10. A sustained-release facial mask based on a nanocarrier, prepared by the method according to any one of claims 1 to 9.

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