PH-responsive supramolecular salicylic acid nanogel as well as preparation method and application thereof

Abstract

The invention discloses a pH-responsive supramolecular salicylic acid nanogel and a preparation method and application thereof, and the pH-responsive supramolecular salicylic acid nanogel comprises the following preparation raw materials by mass: 3-30% of salicylic acid; 0.6 to 1.5 percent of orthoester; 30 to 50% of poloxamer; 0.5 to 5.0 percent of polyhydric alcohol; 0.5-1% of a surfactant; and the balance solvent. Through supramolecular design, salicylic acid molecules and a precursor containing a pH sensitive group (orthoester) are integrally constructed into a nanogel network through non-covalent self-assembly, so that the contradiction between solubility and irritation of high-concentration salicylic acid is fundamentally solved; the prepared pH-responsive supramolecular salicylic acid nanogel can realize the synergistic effects of stable loading of high-concentration salicylic acid, targeted response release of an inflammatory site and low skin irritation, and the preparation process is simple, convenient and environment-friendly, is suitable for industrial production, and has a wide application prospect in the field of functional skin care products.

Description

Technical Field

[0001] This invention belongs to the field of functional skincare technology, specifically relating to a pH-responsive supramolecular salicylic acid nanogel, its preparation method, and its application. Background Technology

[0002] Salicylic acid (SA), a classic β-hydroxy acid, has been widely used in the treatment of skin diseases such as acne due to its excellent keratolytic, anti-inflammatory, and mild antibacterial activities. Its mechanism of action lies in its ability to penetrate the lipid-rich pilosebaceous unit, loosening the adhesion between keratinocytes and promoting the expulsion of comedones. However, SA faces several inherent challenges in actual formulation and application, which seriously restrict its efficacy and safety: (1) poor solubility, SA has extremely low solubility in water (about 0.2 g / L, 20°C), which greatly limits its formulation concentration, stability and bioavailability in aqueous carriers (such as gels and emulsions); (2) irritation risk, in order to achieve an effective therapeutic concentration, traditional formulations often require a high dose (usually >2%), which can easily lead to damage to the skin barrier function and cause adverse reactions such as stinging, erythema, dryness and desquamation; (3) insufficient targeted delivery efficiency, SA has limited transdermal absorption capacity and it is difficult to accumulate in the deep part of acne lesions (especially deep in the hair follicle and inflammatory microenvironment) to achieve an effective therapeutic concentration, resulting in limited efficacy.

[0003] To overcome the aforementioned shortcomings, research on drug delivery systems (DSS) has provided important insights. Among them, nanogels, as an emerging nanocarrier, exhibit unique advantages. Nanogels are three-dimensional network structures with nanoscale dimensions (typically 20-500 nm) formed by chemical cross-linking or physical interactions of hydrophilic or amphiphilic polymers. They combine the high water content, good biocompatibility, and high loading capacity of traditional hydrogels with the large specific surface area, enhanced skin / hair follicle penetration potential, and improved stability of nanoparticles. Through molecular design, nanogels can be further endowed with responsiveness to external stimuli (such as pH, temperature, enzymes, and redox states), thereby achieving intelligent and controlled drug release. Among various stimulus-response strategies, pH responsiveness is of great application value due to its close correlation with various pathophysiological environments. For example, acne is often accompanied by excessive keratinization of the hair follicle duct, sebum accumulation, and proliferation of Propionibacterium acnes, resulting in a weakly acidic local microenvironment (pH approximately 5.0-6.0), which differs from the pH of normal skin (approximately 4.5-6.0, but more neutral or varying with inflammation). Designing pH-responsive nanogels that remain stable under physiological or storage conditions and rapidly release drugs at specific acidic targets can achieve lesion-specific drug delivery, improve the therapeutic index, and reduce systemic and local side effects.

[0004] Currently, most reported pH-responsive nanogels rely on permanently cross-linked networks constructed through covalent bonds (such as amide and ester bonds). Although such structures are structurally stable, their dynamic regulation, bioreversibility, and adaptability to complex physiological environments are often insufficient. Summary of the Invention

[0005] To address the shortcomings of the prior art, the present invention aims to provide a pH-responsive supramolecular salicylic acid nanogel, which can achieve a synergistic effect of high drug loading, targeted release at inflammatory sites, and low skin irritation.

[0006] This invention is achieved through the following technical solution:

[0007] A pH-responsive supramolecular salicylic acid nanogel comprises, by mass percentage, the following raw materials: 3-30% salicylic acid; 0.6-1.5% orthoester; 30-50% poloxamer; 0.5-5.0% polyol; 0.5-1% surfactant; and the balance being solvent.

[0008] This invention utilizes pH-responsive supramolecular solvent technology to form a three-tiered sustained-release system: a reservoir-barrier-target. Salicylic acid and orthoester form supramolecular aggregates, which, combined with the synergistic solubilizing effects of polyols and surfactants, and the construction of a poloxamer gel network, create a system that integrates supramolecular aggregates and a target. Salicylic acid and orthoester form supramolecular aggregates through non-covalent self-assembly. This supramolecular structure significantly improves the solubility of salicylic acid, achieving high drug loading and self-loading. The acetal bonds of the orthoester are stable in the normal pH environment of the skin, preventing premature release of salicylic acid and reducing irritation. However, in the weakly acidic environment of inflamed areas, the acetal bonds rapidly hydrolyze, releasing salicylic acid for targeted, on-demand release. The mixed solvent system formed by polyols and surfactants further enhances the stability of the supramolecular aggregates and creates a gentle moisturizing barrier on the skin surface, reducing direct contact between salicylic acid and normal skin, further minimizing irritation.

[0009] As a preferred embodiment of the present invention, the structural formula of the orthoester is shown below:

[0010]

[0011] In this context, R represents methyl or amino.

[0012] In a preferred embodiment of the present invention, the poloxamer is at least one of poloxamer 407 or poloxamer 188.

[0013] In a preferred embodiment of the present invention, the polyol is at least one of propylene glycol, glycerin, polyethylene glycol-8, polysorbate 20, or polysorbate 80.

[0014] In a preferred embodiment of the present invention, the surfactant is at least one of lauryl ether-4, PEG-40 hydrogenated castor oil, or decyl glucoside.

[0015] In a preferred embodiment of the present invention, the solvent is ultrapure water, PBS buffer, or physiological saline.

[0016] This invention also provides a method for preparing the above-mentioned pH-responsive supramolecular salicylic acid nanogel, comprising the following steps:

[0017] (1) Mix salicylic acid with orthoester to form supramolecular aggregates; then add polyol and surfactant, and continue stirring to obtain drug-loaded solution;

[0018] (2) Dissolve poloxamer in water to obtain a poloxamer solution;

[0019] (3) The drug-loaded solution was mixed with poloxamer solution to obtain pH-responsive supramolecular salicylic acid nanogel.

[0020] In a preferred embodiment of the present invention, the mixing temperature in step (1) is 85-95°C.

[0021] In a preferred embodiment of the present invention, in step (1), the average particle size of the supramolecular aggregates is 240-260 nm. The nanoscale size and surface properties of the present invention can promote penetration and retention in hair follicles, and enhance lesion accumulation.

[0022] The present invention also provides the application of the above-mentioned pH-responsive supramolecular salicylic acid nanogel in the preparation of functional skin care products, wherein the functional skin care products are anti-acne skin care products.

[0023] Compared with the prior art, the present invention has the following advantages:

[0024] This invention utilizes supramolecular design to integrate salicylic acid molecules with a precursor containing pH-sensitive groups (orthoester esters) through non-covalent self-assembly to construct a nanogel network. This fundamentally solves the contradiction between the solubility and irritation of high-concentration salicylic acid. The resulting pH-responsive supramolecular salicylic acid nanogel achieves a synergistic effect of stable loading of high-concentration salicylic acid, targeted release at inflamed sites, and low skin irritation. Furthermore, the preparation process is simple and environmentally friendly, suitable for industrial production, and has broad application prospects in the field of functional skincare products. Attached Figure Description

[0025] Figure 1 bicyclic orthoester 1 H spectrum;

[0026] Figure 2DSC results for salicylic acid alone and the nanogel prepared in Example 1;

[0027] Figure 3 Optical photographs of salicylic acid alone and the nanogels prepared in Examples 1-3, and the corresponding DLS results;

[0028] Figure 4 TEM results for salicylic acid alone and the supramolecular aggregates prepared in Example 1;

[0029] Figure 5 The results show the solubility of salicylic acid in water and its orthoesters.

[0030] Figure 6 For standard curves;

[0031] Figure 7 The drug release results are for the nanogels prepared in Example 1 and Comparative Example 1;

[0032] Figure 8 The results of acute skin irritation of the pH-responsive supramolecular salicylic acid nanogels prepared in Examples 1-3;

[0033] Figure 9 The results show the long-term skin irritation of the pH-responsive supramolecular salicylic acid nanogels prepared in Examples 1-3. Detailed Implementation

[0034] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. The described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] Synthesis of bicyclic orthoesters:

[0036] Diglycerides (21.3 g, 0.128 mol) were weighed and added to a 500 mL three-necked flask. Then, triethyl orthoacetate (62.38 g, 0.384 mol) and PTSA catalyst (10.3 mg, 0.054 μmol) were weighed. 50 mL of anhydrous DCM was added to the flask, and the mixture was stirred and reacted overnight under nitrogen protection. The reaction was terminated by adding triethylamine. Dichloromethane was removed by rotary evaporation. The product was extracted three times with ethyl acetate solution and once with saturated NaCO3. The organic phase was dried over anhydrous magnesium sulfate for 6 h. The product was then filtered, and the organic solvent was removed by rotary evaporation to obtain a colorless oily product with a yield of 78.2%.

[0037] Approximately 8 mg of the bicyclic orthoester was weighed and dissolved thoroughly in 600 μL of deuterated DMSO. The structure of the orthoester was determined by measuring its 1H NMR spectrum using a 400 MHz nuclear magnetic resonance spectrometer. The structure of the bicyclic orthoester was determined by the ratio of the areas of the characteristic proton peaks in the 1H NMR spectrum.

[0038] The results are as follows Figure 1 As shown, the integral area ratio of proton peak e(-CH-) to a(-CH3) is 1:3.12, which is consistent with the theoretical value of 1:3. In addition, all other proton hydrogens can be assigned, proving that the bicyclic orthoester ester was successfully prepared.

[0039] Preparation of diamino orthoesters:

[0040] Weigh appropriate amounts of diglycerol, trimethyl orthoformate, and catalyst (p-toluenesulfonic acid-hydrate) in a molar ratio of 1:6:0.01, and stir overnight at 25°C under nitrogen protection. Subsequently, a small amount of triethylamine is added to terminate the catalysis, and the mixture is extracted twice with a saturated sodium carbonate solution. After evaporation to dryness, the mixture is filtered under vacuum to obtain 4,4'-dimethyleneoxy-di-(2-methoxy-1,3-dioxopentane) (monomer one). Using the above-synthesized product as a starting material, appropriate amounts of monomer one, N-(dihydroxyethyl)trifluoroacetamide, and the catalyst p-toluenesulfonic acid pyridinium salt are weighed, and the mixture is reacted at 130°C for 6-8 hours. After the reaction, the mixture is cooled to room temperature, and a small amount of triethylamine is added to terminate the catalysis, followed by dissolution with an appropriate amount of ethyl acetate. The solution is extracted three times with saturated sodium bicarbonate and sodium chloride solutions, and then evaporated to dryness. The product obtained after evaporation is then dissolved again in an appropriate amount of tetrahydrofuran (THF), and a certain volume of aqueous sodium hydroxide solution is added. The mixture is stirred vigorously overnight at room temperature. Finally, tetrahydrofuran was removed by rotary evaporation, and a certain volume of dichloromethane was added to extract the aqueous phase. The product obtained after drying was the diamino orthoester monomer.

[0041] Example 1: (9% salicylic acid)

[0042] (1) 1g of salicylic acid and 0.17g of bicyclic orthoester were stirred and mixed at 90°C to form supramolecular aggregates; then 0.2g of polyethylene glycol-8, 0.5ml of propylene glycol and 0.45ml of lauryl ether-4 were added and stirred and mixed for 1h to obtain a drug-loaded solution.

[0043] (2) Dissolve 4.25g of poloxamer 407 in water to obtain a poloxamer solution;

[0044] (3) The drug-loaded solution was mixed with poloxamer solution to obtain pH-responsive supramolecular salicylic acid nanogel.

[0045] Example 2: (14% salicylic acid)

[0046] (1) 1.5g of salicylic acid and 0.34g of bicyclic orthoester were stirred and mixed at 90°C to form supramolecular aggregates; then 0.2g of polyethylene glycol-8, 0.5ml of propylene glycol and 0.45ml of lauryl ether-4 were added and stirred and mixed for 1h to obtain a drug-loaded solution.

[0047] (2) Dissolve 4.25g of poloxamer 407 in water to obtain a poloxamer solution;

[0048] (3) The drug-loaded solution was mixed with poloxamer solution to obtain pH-responsive supramolecular salicylic acid nanogel.

[0049] Example 3: (18% salicylic acid)

[0050] (1) 2g of salicylic acid and 0.4g of bicyclic orthoester were stirred and mixed at 90°C to form supramolecular aggregates; then 0.2g of polyethylene glycol-8, 0.5ml of propylene glycol and 0.45ml of lauryl ether-4 were added and stirred and mixed for 1h to obtain a drug-loaded solution.

[0051] (2) Dissolve 4.25g of poloxamer 407 in water to obtain a poloxamer solution;

[0052] (3) The drug-loaded solution was mixed with poloxamer solution to obtain pH-responsive supramolecular salicylic acid nanogel.

[0053] Example 4: (30% salicylic acid)

[0054] (1) Mix 3g of salicylic acid and 0.5g of diamino orthocyanin at 90°C to form supramolecular aggregates; then add 0.2g of polyethylene glycol-8, 0.5ml of glycerol and 0.45ml of PEG-40 hydrogenated castor oil, and continue to stir and mix for 1h to obtain a drug-loaded solution;

[0055] (2) Dissolve 4.25g of poloxamer 188 in water to obtain a poloxamer solution;

[0056] (3) The drug-loaded solution was mixed with poloxamer solution to obtain pH-responsive supramolecular salicylic acid nanogel.

[0057] Comparative Example 1:

[0058] (1) Mix 1g of salicylic acid with 0.2g of polyethylene glycol-8, 0.5ml of propylene glycol and 0.45ml of lauryl ether-4 for 1h to obtain a drug-loaded solution;

[0059] (2) Dissolve 4.25g of poloxamer 407 in water to obtain a poloxamer solution;

[0060] (3) Mix the drug-loaded solution with poloxamer solution to obtain salicylic acid nanogel.

[0061] Test Example 1: DSC Test

[0062] First, weigh an empty crucible as a blank. Then, weigh each empty crucible before placing the sample inside. Next, weigh 5-10 mg of the sample (salicylic acid and the nanogel prepared in Example 1) into the empty crucible and record the total weight of the sample and crucible. Finally, perform the analysis using a differential scanning calorimeter. The specific test results are as follows: Figure 2 .

[0063] The results showed that in DSC analysis of salicylic acid alone, the salicylic acid decomposed upon melting, exhibiting two peaks. In the mixture of salicylic acid and orthoester, the hollow alkyl chains of the orthoester encapsulated the SA molecule through hydrophobic interactions and hydrogen bonds. Since salicylic acid completely dissolved upon heating and was subsequently physically captured and immobilized by the formed poloxamer gel network, transforming it from a crystalline to an amorphous or non-crystalline state, the phase transition energy required for melting was eliminated, thus completely eliminating its sharp melting peak in DSC.

[0064] Test Example 2: DLS Test

[0065] A certain amount of salicylic acid and the nanogels formed in Examples 1-3 were added to pure water for ultrasonic dissolution and dilution. The particle size was then determined using a particle size analyzer and DLS measurement. Specific test results are shown below. Figure 3 .

[0066] The results showed that the average particle size of salicylic acid was around 447 nm. This is likely due to the low solubility of salicylic acid in water; simply dispersing it in water easily leads to the formation of nanoscale crystals or aggregates. After gelation, the particle size decreased, indicating that the gel formulation, through orthoester inclusion, surfactant dispersion, and gel matrix fixation, transformed salicylic acid from micron-sized large particles into a nanoscale dispersed state, thereby reducing the hydrodynamic diameter measured by DLS. This treatment can significantly improve the solubility and stability of salicylic acid. Furthermore, with increasing salicylic acid content, the particle size of the formed nanogel gradually increased. The average particle size of this nanogel was around 250 nm.

[0067] Test Example 3: TEM

[0068] A certain amount of salicylic acid, the supramolecular aggregate formed by the salicylic acid and orthoester prepared in Example 1, was dissolved in pure water by ultrasonication, diluted, and then dropped onto a copper mesh. The particle morphology and size were observed under a transmission electron microscope. Specific test results are shown below. Figure 4 .

[0069] The results showed that salicylic acid alone exhibited an uneven and irregular sheet-like structure under TEM, and the supramolecular aggregates formed were spherical particles.

[0070] Test Example 4: Stability Test

[0071] A portion of the nanogels prepared in Examples 1-3 was dissolved and diluted with 10 mL of methanol, and the absorbance was measured by ultraviolet spectrophotometry. The nanogels were then placed at high temperature (40℃), room temperature (25℃), and low temperature (-4℃) for 1, 2, and 3 weeks, respectively, and the absorbance of the gels after different periods at different temperatures was measured again. Finally, the absorbance of the gels immediately after preparation and those placed for different times was compared, and the percentage change was calculated to determine their stability. If the percentage change in absorbance is ≤5%, the gel is considered stable. Specific test results are shown in Tables 1-3.

[0072] Table 1. Stability test results at high temperature

[0073] Table 2. Stability test results at room temperature

[0074]

[0075] Table 3. Stability test results at low temperature

[0076]

[0077] The results in Table 1-3 show that the supramolecular nanogels become unstable after two weeks at high temperatures, while they remain stable at room temperature and low temperatures.

[0078] Test Example 5: Solubility Test

[0079] Take 1 mL of water and bicyclic orthoester, add 1 mg of salicylic acid to the water, and add 10 mg of salicylic acid to the bicyclic orthoester. Stir at 800 rpm and observe every 1 hour. If it dissolves, continue to add more gradually to obtain the maximum saturation solubility.

[0080] Specific test results are as follows: Figure 5 The results showed that the solubility of salicylic acid in water was about 3 mg / mL, while the maximum solubility in bicyclic orthoesters was 140 mg / mL, which significantly improved the solubility of salicylic acid.

[0081] Test Example 6: pH Response and Sustained Release Effect

[0082] Standard curve establishment: First, weigh 10 mg of salicylic acid reference standard and place it in a 10 mL volumetric flask. Dilute to the mark with pure water to prepare a 1 mg / mL stock solution. Then, accurately measure 200 μL, 300 μL, 400 μL, 500 μL, and 600 μL of the stock solution, respectively, and add them to 10 mL volumetric flasks. Dilute to the mark with pure water to prepare solutions of 20 μg / mL, 30 μg / mL, 40 μg / mL, 50 μg / mL, and 60 μg / mL. Finally, measure the absorbance at 296 nm. Plot a standard curve with concentration on the x-axis and absorbance on the y-axis (see [link to standard curve]). Figure 6 ).

[0083] Drug Release: First, the dialysis bags were pretreated by soaking them in boiling water. Then, a piece of nanogel (approximately 0.5 g) prepared in Example 4 and Comparative Example 1 was placed in a dialysis bag, and the two ends of the dialysis bag were tied tightly with thread. The bag was then placed in a 15 mL centrifuge tube, and 10 mL of PBS solution with pH=5.8 / 7.4 was added. Three replicates were prepared and placed in beakers. The bags were then placed in a shaker for release. A specific volume (2 mL) of sample solution was precisely aspirated from the release medium at 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 hours. After each sampling, an equal volume of fresh release medium at the same temperature was immediately added to the container to maintain a constant total volume. The absorbance of the sample solution was measured at a selected wavelength using a UV spectrophotometer. If the concentration was too high, it could be appropriately diluted with the appropriate medium. Based on the measured concentration, dilution factor, and total volume of release medium, the total amount of salicylic acid (M_t) released from the dialysis bag from time 0 to that time point was calculated. Finally, calculate the cumulative release percentage.

[0084] The results are as follows Figure 7 As shown: The nanogel prepared in Example 4 exhibited the highest salicylic acid release rate, reaching approximately 95%, under acidic conditions (PBS 5.8). However, under neutral conditions (PBS 7.4), the salicylic acid release rate significantly decreased, indicating that salicylic acid exhibits pH-responsive release under acidic conditions. In contrast, Comparative Example 1, compared to Example 1 under acidic PBS, showed a lower drug release rate of only about 60%, demonstrating the targeting advantage of orthoester esters.

[0085] Test Example 7: Acute Skin Irritation Test

[0086] Eight guinea pigs were used, and the hair on both sides of the spine on their backs was removed using a hair removal machine, covering an area of ​​approximately 3×3 cm. The pH-responsive supramolecular salicylic acid nanogel prepared in Examples 1-3 was applied to the intact skin on the left side of the guinea pig after hair removal. The application time was 24 hours, after which the gel was removed with warm water. At 0, 24, and 48 hours after gel removal, the local skin reaction was observed and compared with the symmetrical intact skin on the right side of the guinea pig. The degree of irritation was judged according to the scoring criteria in Table 4-6.

[0087] Table 4. Skin Irritation Response Scoring Criteria Stimulus response Score erythema No erythema 0 Mild erythema (barely visible) 1 Moderate erythema (visible) 2 Severe erythema 3 From purplish-red erythema to mild crusting 4 edema No edema 0 Mild edema (barely visible) 1 Moderate edema (obvious swelling) 2 Severe edema (skin bulges 1mm, with clear contours) 3 Severe edema (skin bulges more than 1 mm and enlarges) 4 Highest total score 8

[0088] Table 5. Evaluation Criteria for Skin Irritation Intensity Score evaluate 0-0.49 Non-irritating 0.5-2.99 Mild irritation 3.0-5.99 Severe irritation 6.0-8.0 Strong irritant

[0089] Table 6 Specific Scores Example 1 Example 2 Example 3 Before 0 0 0 0h 0 0 0 24h 0 0 0 48h 0 0 0 Overall score 0 0 0

[0090] The results are shown in Table 6 and Figure 8 As shown, the pH-responsive supramolecular salicylic acid nanogel prepared in this invention does not cause skin irritation in a short period of time.

[0091] Test Example 8: Long-term skin irritation test

[0092] Eight guinea pigs were used, and the hair on symmetrical areas on both sides of the spine on their backs was removed using a hair removal machine, covering an area of ​​approximately 3×3 cm. The pH-responsive supramolecular salicylic acid nanogel prepared in Examples 1-3 was applied to the intact skin on the left side of the guinea pig after hair removal. The gel was applied once daily for 14 consecutive days. The local skin reaction was observed at 0, 24, and 48 hours after the last gel removal, comparing the skin to the symmetrical intact skin on the right side of the guinea pig. Specific experimental results are as follows: Figure 9 As shown.

[0093] The results show that the pH-responsive supramolecular salicylic acid nanogel prepared in this invention does not cause skin irritation over a long period of time.

Claims

1. A pH-responsive supramolecular salicylic acid nanogel, characterized in that, The preparation materials, by mass percentage, include the following: salicylic acid 3-30%; orthoester 0.6-1.5%; poloxamer 30-50%; polyol 0.5-5.0%; surfactant 0.5-1%; and solvent balance.

2. The pH-responsive supramolecular salicylic acid nanogel according to claim 1, characterized in that, The structural formula of the orthoester is shown below: In this context, R represents methyl or amino.

3. The pH-responsive supramolecular salicylic acid nanogel according to claim 1, characterized in that, The poloxamer is at least one of poloxamer 407 or poloxamer 188.

4. The pH-responsive supramolecular salicylic acid nanogel according to claim 1, characterized in that, The polyol is at least one of propylene glycol, glycerin, polyethylene glycol-8, polysorbate 20, or polysorbate 80.

5. The pH-responsive supramolecular salicylic acid nanogel according to claim 1, characterized in that, The surfactant is at least one of lauryl ether-4, PEG-40 hydrogenated castor oil, or decyl glucoside.

6. The pH-responsive supramolecular salicylic acid nanogel according to claim 1, characterized in that, The solvent is ultrapure water, PBS buffer, or physiological saline.

7. The method for preparing pH-responsive supramolecular salicylic acid nanogel according to any one of claims 1-6, characterized in that, Includes the following steps: (1) Mix salicylic acid with orthoester to form a supramolecular aggregate solution; then add polyol and surfactant, and continue stirring to obtain a drug-loaded solution; (2) Dissolve poloxamer in water to obtain a poloxamer solution; (3) The drug-loaded solution was mixed with poloxamer solution to obtain pH-responsive supramolecular salicylic acid nanogel.

8. The method for preparing pH-responsive supramolecular salicylic acid nanogel according to claim 7, characterized in that, In step (1), the mixing temperature is 85-95℃.

9. The method for preparing pH-responsive supramolecular salicylic acid nanogel according to claim 7, characterized in that, In step (1), the average particle size of the supramolecular aggregate is 200-250 nm.

10. The application of the pH-responsive supramolecular salicylic acid nanogel according to any one of claims 1-6 in the preparation of functional skin care products, characterized in that, The functional skincare product in question is an anti-acne skincare product.

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