PH / GSH dual-responsive polymer precursor as well as preparation method and application thereof

Abstract

The invention relates to a pH / GSH dual-responsive polymer precursor and a preparation method and application thereof. The pH / GSH dual-responsive polymer precursor is prepared from a pH response unit and a GSH response unit, and the pH / GSH dual-responsive polymer precursor based on a polyethylene glycol unit, a diisopropylamino unit and a disulfide bond connecting unit can form compact nano-micelles in an aqueous solution, so that perfume is effectively protected, and the problem of poor stability of the perfume is fundamentally solved. When in use, due to the precise dual-response switch performance, the nano-micelle is depolymerized and the disulfide bond is broken only under the conditions that the pH is lower than the critical pH and GSH exists, so that the precise control on the release of the perfume is realized. In addition, the polymer precursor has excellent universality, and can meet the requirement for accurate release of alcohol and phenol perfumes under different environmental conditions. By utilizing the antibacterial property of the perfume, the precursor perfume can be applied to the fields of medical instruments, wound dressing and the like.

Description

Technical Field

[0001] This invention relates to the field of polymer latent fragrance technology, and in particular to a pH / GSH dual-responsive polymer latent fragrance, its preparation method, and its application. Background Technology

[0002] Fragrances are functional aromatic compounds that produce pleasant scents in the air, making them popular with people. The most abundant components of fragrances are terpenes and aromatic and aliphatic derivatives, including carbohydrates, alcohols, ethers, aldehydes, and ketones. These are the sources of the aromatic and biological properties of aromatic and medicinal plants. Research has confirmed that fragrances possess broad-spectrum antibacterial, antifungal, antioxidant, and anti-inflammatory effects. Their active ingredients exert antibacterial effects through mechanisms such as disrupting microbial cell membranes, inhibiting biofilm formation, and interfering with metabolic enzyme activity. Currently, fragrances are widely used in natural food preservation, medical antibacterial dressings, and the development of daily chemical products. Their anti-biofilm properties offer new insights into addressing antibiotic resistance.

[0003] Late fragrance compounds originate from the concept of "prodrugs" in drug delivery, but differ in molecular release, control conditions, and application targets. Late fragrance compounds are a class of precursor compounds that can control fragrance release by breaking covalent or hydrogen bonds under everyday environmental conditions such as light, pH changes, and hydrolysis. Late fragrance compounds consist of three key components: a non-volatile matrix, environmentally responsive chemical bonds, and the target fragrance. The non-volatile matrix fixes the fragrance through intermolecular forces, and surface modification enhances system stability. Environmentally responsive chemical bonds (such as acid-sensitive and photosensitizing bonds) act as smart switches, breaking under specific conditions to achieve release. The fragrance molecule is bonded to the matrix through functional groups, ensuring storage stability and precise fragrance release in a predetermined environment. This modular design gives latent fragrance compounds intelligent controlled-release properties, making them widely used in the fields of sustained-release fragrances and functional materials.

[0004] Bacterial infections cause significant changes in their surrounding environment, including increased levels of bacterial secreted enzymes and a decrease in the pH of the microenvironment due to acidic metabolites. During rapid bacterial growth, an acidic environment (pH 5.5-6.5) is created, and glutathione (GSH), a widely present compound in bacterial infections, plays a crucial role in bacterial survival and function. In bacterial infections, GSH not only acts as an antioxidant, helping to scavenge reactive oxygen species and protect bacteria from oxidative stress, but also participates in various biological processes, including the regulation of gene expression and biofilm formation.

[0005] To date, there are no commercially viable pH / GSH dual-responsive polymeric latent fragrance nanomicelles for the fragrance and flavor industry to address the trade-off between fragrance stability and controlled release. Furthermore, there are no existing examples of using latent fragrance technology to target bacterial microenvironment responses for antibacterial effects. Therefore, there is an urgent need in this field to develop a polymeric latent fragrance preparation technology and products capable of achieving precise fragrance release and effective antibacterial properties.

[0006] Chinese patent CN119591806A discloses a pH-responsive polymer nanomicelle, its preparation method, and its applications. Based on polyethylene glycol and diisopropylamine units, the pH-responsive polymer nanomicelle forms tightly packed nanomicelles during storage to protect fragrances, fundamentally solving the problem of poor fragrance stability. During use, due to its precise on / off performance, the tightly packed nanomicelles depolymerize below the critical pH, achieving controlled fragrance release. It also exhibits excellent versatility, meeting the requirements for precise release of different fragrances under varying environmental conditions, and is suitable for a variety of fragrance products, including hydrophilic daily cosmetics, cleaning products, and indoor air fresheners. Summary of the Invention

[0007] The purpose of this invention is to provide a pH / GSH dual-responsive polymeric pheromone, its preparation method, and its applications. The pH / GSH dual-responsive polymeric pheromone is prepared from pH-responsive units and GSH-responsive units. Based on polyethylene glycol units, diisopropylamino units, and disulfide bond linkage units, the pH / GSH dual-responsive polymeric pheromone exhibits excellent on / off performance, precise controlled-release performance, high stability, and excellent versatility, making it suitable for applications in medical devices and wound dressings.

[0008] The objective of this invention can be achieved through the following technical solutions: A pH / GSH dual-responsive polymeric latent fragrance compound, the structural formula of which is shown in Formula I'-8: In formula I'-8, R is selected from any one or more alkyl or substituted aryl groups. The range of x is 50 to 80, and the range of y is 4 to 8.

[0009] Furthermore, R is selected from... , or .

[0010] This invention also provides a method for preparing a pH / GSH dual-responsive polymeric latent fragrance, the specific steps of which are as follows: S1. In solvent F, the compound shown in formula I'-1 is reacted with the substitution reagent A under nitrogen protection and stirred under reflux to obtain the compound shown in formula I'-2. S2. In solvent F, the compound shown in formula I'-3 was reacted with the substitution reagent B under nitrogen protection and stirred under reflux to obtain the compound shown in formula I'-4. S3. In solvent F, the compound shown in formula I'-5 is reacted with the substitution reagent B under nitrogen protection and stirred under reflux for a period of time to obtain the compound shown in formula I'-6. S4. Under nitrogen protection, the compound shown in Formula I'-2 obtained in step S1, the compound shown in Formula I'-4 obtained in step S2, the compound shown in Formula I'-6 obtained in step S3, and solvent F are mixed, and catalysts C and D are added. After polymerization, a pH / GSH dual-responsive polymer shown in Formula I'-7 is obtained. S5. Under nitrogen protection, the pH / GSH dual-responsive polymer, fragrance intermediate, and solvent F obtained in step S4 as shown in Formula I'-7 are mixed, catalyst E is added, and the reaction is stirred to obtain the pH / GSH dual-responsive polymer latent fragrance body as shown in Formula I'-8. The structural formulas of equations I'-1 to I'-8 are shown below: , In the formula, R is selected from any one or more alkyl or substituted aryl groups. The range of x is 50 to 80, and the range of y is 4 to 8.

[0011] Further, in step S1, the molar ratio of the compound as shown in Formula I'-1 to the substituted reagent A is 1:(1~5), preferably 1:4.

[0012] Further, in step S1, the substitution reagent A is selected from... N 1-Bromosuccinimide (NBS), acrylate (AE), 2-methyl-2-bromopropionyl bromide, carbon tetrabromide (CBr4), or trimethylphenyltribromium tribromide.

[0013] Further, in step S2, the molar ratio of the compound shown in formula I'-3 to the substituted reagent B is 1:(1~5), preferably 1:1.

[0014] Further, in step S3, the molar ratio of the compound shown in formula I'-5 to the substituted reagent B is 1:(1~5), preferably 1:1.

[0015] Further, in steps S2 and S3, the substituted reagent B is selected from any one or more of acetyl chloride, benzoyl chloride, methacryloyl chloride, chloroacetyl chloride, or trichloroacetyl chloride.

[0016] Furthermore, in steps S1-S3, the stirring time is 6-12 hours, and the stirring temperature is room temperature.

[0017] Further, in step S4, the following compounds are used: the compound shown in Formula I'-2; the compound shown in Formula I'-4; the compound shown in Formula I'-6; and the solvent F = 1g: 0.5~1.5g: 0.2~0.5g: 5~15mL.

[0018] Further, in step S4, the molar ratio of the compound shown in Formula I'-2, catalyst C and catalyst D is 1:(1~3):(1~3), preferably 1:1:1.

[0019] Furthermore, in step S4, the polymerization reaction time is 36~60h.

[0020] Further, in step S4, the catalyst C is selected from triethylenediamine (TEDA) and pentamethyldiethylenetriamine (PMDETA). N - Dimethylcyclohexylamine (DMCHA), dimethylethanolamine (DMEA) or N - Any one or more of benzyl dimethylamine (BDMA).

[0021] Further, in step S4, the catalyst D is selected from any one or more of aluminum chloride, boron trifluoride, tin tetrachloride, cuprous bromide, or zinc chloride.

[0022] Further, in step S5, the compound as shown in Formula I'-7: fragrance intermediate: solvent F = 1g: 3~5g: 100~200mL.

[0023] Further, in step S5, the molar ratio of the compound shown in formula I'-7 to catalyst E is 1:(1~3), preferably 1:1.

[0024] Furthermore, in step S5, the flavor intermediate is selected from any one of geraniol, cinnamyl alcohol, or thymol.

[0025] Further, in step S5, the catalyst E is selected from... N Any one or more of 4-methylimidazole, 4-dimethylaminopyridine, or 4-pyrrolidinylpyridine.

[0026] Furthermore, in step S5, the stirring time is 6 to 12 hours, and the stirring temperature is room temperature.

[0027] Further, in steps S1-S5, the solvent F is selected from dichloromethane, petroleum ether, ethyl acetate, etc. N,N Any one or more of dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, or acetonitrile.

[0028] This invention also provides a method for preparing pH / GSH dual-responsive polymer nanomicelles, the specific steps of which are as follows: S1. Dissolve the above-mentioned pH / GSH dual-responsive polymer latent fragrance in solvent G to obtain a mixture; S2. The mixture prepared in step S2 is mixed with solvent H, and after stirring, pH / GSH dual-responsive polymer nanomicelles are obtained.

[0029] Further, in step S1, the mass ratio of the pH / GSH dual-responsive polymer latent fragrance to solvent G is 1:(10~100).

[0030] Further, in step S2, the mass ratio of the mixture and solvent H prepared in step S2 is 1:(100~1000).

[0031] Furthermore, in step S2, the stirring temperature is room temperature, and the stirring time is 6 to 24 hours.

[0032] Further, in steps S1 and S2, the solvent G and solvent H are selected from deionized water, dichloromethane, petroleum ether, ethyl acetate, etc. N,N Any one or more of dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, or acetonitrile.

[0033] As a preferred technical solution, solvent G and solvent H are two different solvents used in practice.

[0034] In addition, the present invention also provides the application of a pH / GSH dual-responsive polymer latent fragrance in the preparation of bacterial microenvironment controlled-release fragrance.

[0035] Furthermore, the bacterial microenvironment controlled-release fragrance is suitable for use in medical devices and wound dressings to achieve antibacterial purposes.

[0036] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The pH / GSH dual-responsive polymer latent fragrance provided by the present invention has ultra-sensitive switching performance and can be used for stable storage and precise controlled release of alcohol and phenolic fragrances. The present invention not only improves the stability and selectivity of amphiphilic block polymer latent fragrances, but also improves their high sensitivity and precise controlled release performance as nanomicelles.

[0037] 2. The method for preparing pH / GSH dual-responsive polymeric fragrance nanomicelles provided by the present invention prepares compact nano-sized micelles by solvent evaporation, which can both release alcohols and phenolic fragrances by breaking covalent bonds and provide a basis for encapsulating active substances.

[0038] 3. The pH / GSH dual-responsive polymer latent fragrance provided by this invention is applicable to the application of various alcohol or phenolic fragrances, and is also applicable to the fields of medical devices and wound dressings.

[0039] 4. A pH / GSH dual-responsive polymeric fragrance compound based on polyethylene glycol units, diisopropylamino units, and disulfide bond linkage units forms tight nanomicelles in aqueous solution, effectively protecting the fragrance and fundamentally solving the problem of poor fragrance stability. During use, due to its precise dual-response switching performance, the nanomicelles depolymerize and the disulfide bonds break only under conditions below the critical pH and in the presence of GSH, achieving precise control over fragrance release. Furthermore, this polymeric fragrance compound exhibits excellent versatility, meeting the needs for precise release of alcohol and phenolic fragrances under various environmental conditions. Utilizing its antibacterial properties, this fragrance compound can be applied in fields such as medical devices and wound dressings.

[0040] 5. This invention improves the stability and selectivity of amphiphilic block polymers, and also enhances their high sensitivity and precise controlled-release performance as nano-fragrance molecules. The polyethylene glycol unit improves the polymer's hydrophilicity and stability; the diisopropylamine unit enables the polymer to switch on and off under specific pH conditions, meeting its structural requirements for pH switching; the disulfide bond linking unit is covalently linked to a specific fragrance to meet the GSH response requirement, further improving its stability. In the bacterial microenvironment (pH and GSH), protonation causes the micelle core to change from hydrophobic to hydrophilic, leading to micelle depolymerization and exposing the disulfide bond linking units of the antibacterial fragrance molecule. Under the action of glutathione, the disulfide bonds break, releasing the antibacterial fragrance molecule, thereby achieving controlled-release sterilization and possessing enormous potential for medical applications.

[0041] 6. This invention, based on the physical coating technology of Chinese patent CN119591806A, makes a fundamental improvement: upgrading the loading method of fragrance from physical coating to covalent chemical bonding via disulfide bonds. This key change brings significant beneficial effects. First, the chemical bond energy is much higher than the physical force, significantly enhancing the thermal stability of fragrance molecules during processing and storage, effectively preventing non-target leakage. Second, the disulfide bond, as a "smart switch," has its cleavage strictly dependent on specific reducing stimuli (such as specific biological environments), thus achieving precise and controllable release behavior and avoiding problems such as initial burst release and incomplete sustained release caused by diffusion-driven release in traditional physical coating technologies. Therefore, this invention overcomes the shortcomings of the physical coating system in the comparative patent, which suffers from high environmental sensitivity and insufficient reliability of controlled release, achieving significant improvements in the targeting, stability, and efficiency of release. Attached Figure Description

[0042] Figure 1 This is a schematic diagram of the technical route of pH / GSH dual-responsive polymer latent fragrance nanomicelles in this invention. In Formula I, the red spheres represent R fragrance substances, the blue squares represent compounds as shown in Formula I'-4, the green short lines represent compounds as shown in Formula I'-6, and the blue and yellow wavy curves represent compounds as shown in Formula I'-2 (the blue end represents the hydrophilic end, and the yellow end represents the hydrophobic end).

[0043] Figure 2 The image shows the 1H NMR spectrum of the polymeric latent fragrance compound PEG-PND-SSC (the compound shown in Formula I'-8-2).

[0044] Figure 3 Gel chromatogram of the polymeric latent fragrance compound PEG-PND-SSC (the compound shown in Formula I'-8-2).

[0045] Figure 4 The particle size and particle size distribution of PEG-PND-SSC nanomicelles (the compound shown in Formula I'-8-2) in aqueous solution are shown.

[0046] Figure 5 Thermogravimetric analysis (TGA) plot of polymeric aroma nanomicelles PEG-PND-SSC (the compound shown in Formula I'-8-2).

[0047] Figure 6 The release curves of cinnamyl alcohol from the polymer PEG-PND-SSC (the compound shown in Formula I'-8-2) in different pH and GSH buffer solutions (pH=7.4, pH=7.4 and 5Mm GSH, pH=6, pH=6 and 5mM GSH).

[0048] Figure 7The diagram shows the antibacterial activity of the polymeric volatile organic compound PEG-PND-SSG (the compound shown in Formula I'-8-1) against Escherichia coli and Staphylococcus aureus. Detailed Implementation

[0049] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments.

[0050] The room temperature mentioned in this embodiment of the invention is 25~28℃.

[0051] The reagents and materials used in the embodiments of this invention are as follows: Dichloromethane, triethylamine, tetrahydrofuran, polyethylene glycol monomethyl ether (Me-PEG-OH), methacryloyl chloride (MACl), etc. were purchased from Shanghai Titan Technology Co., Ltd.; cinnamyl alcohol, geraniol, thymol, etc. were purchased from Shanghai Myriel Technology Co., Ltd.

[0052] All reagents and raw materials used in this invention are commercially available or can be prepared according to literature methods. Unless otherwise stated, percentages and parts are by weight.

[0053] The following detailed description of some embodiments of the present invention is provided in conjunction with the accompanying drawings. Unless otherwise specified, the following embodiments and features can be combined with each other.

[0054] Example 1 This embodiment provides a pH / GSH dual-responsive polymeric latent fragrance compound PEG-PND-SSG, the structural formula of which is shown in Formula I'-8-1: In the formula, x is 50~80 and y is 4~8.

[0055] Furthermore, this embodiment also provides a method for preparing PEG-PND-SSG (the compound shown in Formula I'-8-1), the specific steps of which are as follows: (1) Synthesis of I'-2 5 g of polyethylene glycol monomethyl ether, 228 mg of 2-methyl-2-bromopropionyl bromide and 253 mg of triethylamine were added to a three-necked flask containing 20 mL of dichloromethane. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the mixture was filtered. The resulting white filter cake was dried under vacuum for 3 hours to obtain a pure white solid as shown in Formula I'-2. Yield: 80%.

[0056] The proton NMR spectrum of I'-2: 1 H NMR (400 MHz, Chloroform-d) delta 4.34 (d, J = 5.1Hz, 2H), 3.67 (d, J = 1.6 Hz, 486H), 3.40 (d, J = 1.4 Hz, 3H), 1.97 (d, J =1.4 Hz, 7H), 1.66–0.96 (m, 121H), 0.93–0.78 (m, 30H). (2) Synthesis of I'-4 5 g of diisopropylaminoethanol, 3.6 g of methacryloyl chloride and 3.5 g of triethylamine were added to a three-necked flask containing 20 mL of tetrahydrofuran. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the product was purified by silica gel column chromatography to obtain a colorless oil as shown in Formula I'-4, with a yield of 47%.

[0057] The proton NMR spectrum of I'-4: 1 H NMR (400 MHz, Chloroform- d ) δ 6.14 (s, 1H), 5.59 (q, J = 1.6 Hz, 1H), 4.12 (td, J = 7.1, 1.6 Hz, 2H), 3.06 (td, J = 6.6, 1.6 Hz, 2H), 2.73 (td, J = 7.1, 1.5 Hz, 2H), 1.98 (s, 3H), 1.06 (dd, J = 6.7, 1.6 Hz, 12H). The carbon NMR spectrum of I'-4: 13 C NMR (101 MHz, Chloroform- d ) δ 136.51, 125.29,77.38, 65.53, 49.41, 20.79, 18.42. High-resolution mass spectrometry of I'-4: HRMS (TOF-ES+): m / z: calcd for C 12 H 24 NO2: 214.1811[M+H] + Found: 214.1807. (3) Synthesis of I'6 3 g of 2-hydroxyethyl disulfide, 4.06 g of methacryloyl chloride and 5 g of triethylamine were added to a three-necked flask containing 100 mL of tetrahydrofuran. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the product was purified by silica gel column chromatography to obtain a colorless oil as shown in Formula I'-6, with a yield of 54%.

[0058] The proton NMR spectrum of I'-6: 1 H NMR (400 MHz, CDCl3, ppm): δ 6.14 (t, J = 1.0Hz, 1H), 5.60 (t, J = 1.6 Hz, 1H), 4.43 (t, J = 6.7 Hz, 2H), 3.89 (t, J = 5.9Hz, 2H), 2.98 (t, J = 6.7 Hz, 2H), 2.89 (t, J = 5.9 Hz, 2H), 1.95 (t, J = 1.2Hz, 3H). I'-6 carbon NMR spectrum: 13 C NMR (100 MHz, CDCl3, ppm): δ 167.30, 135.94,126.19, 62.65, 60.20, 41.55, 36.95, 18.28. High-resolution mass spectrometry of I'-6: HRMS (TOF-ESI+): m / z: calcd for C8H 14 NaO3S2: 245.0282[M+Na] + Found: 245.0286. (4) Synthesis of I'-7 1 g of the pure white solid as shown in Formula I'-2, 1.7 g of the colorless oil as shown in Formula I'-4, and 0.28 g of the colorless oil as shown in Formula I'-6 were added to a solution containing 8 mL of... N,N Dimethylformamide was placed in a Shrek tube, and then 35 mg of pentamethyldiethylenetriamine and 29 mg of cuprous bromide were added. The mixture was refluxed and stirred for 48 hours under nitrogen protection. After the reaction was completed, the mixture was freeze-dried for 12 hours to obtain a white flocculent solid as shown in Formula I'-7, with a yield of 31.7%.

[0059] (5) Synthesis of I'-8-1 1 g of a pure white solid as shown in Formula I'-7, 1.7 g of geraniol intermediate, and 0.28 g of 4-dimethylaminopyridine were added to a solution containing 8 mL of... N,N The reaction of dimethylformamide in a Shrek tube was carried out under nitrogen protection and stirred at room temperature for 12 hours. After the reaction was completed, the mixture was freeze-dried for 12 hours to obtain a white flocculent solid as shown in Formula I'-8-1, with a yield of 54.4%.

[0060] Example 2 This embodiment provides a pH / GSH dual-responsive polymeric latent fragrance compound PEG-PND-SSC, the structural formula of which is shown in Formula I'-8-2: In the formula, x is 50~80 and y is 4~8.

[0061] Furthermore, this embodiment also provides a method for preparing PEG-PND-SSC (the compound shown in Formula I'-8-2), the specific steps of which are as follows: (1) Synthesis of I'-2 5 g of polyethylene glycol monomethyl ether, 228 mg of 2-methyl-2-bromopropionyl bromide and 253 mg of triethylamine were added to a three-necked flask containing 20 mL of dichloromethane. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the mixture was filtered. The resulting white filter cake was dried under vacuum for 3 hours to obtain a pure white solid as shown in Formula I'-2. Yield: 80%.

[0062] The proton NMR spectrum of I'-2: 1 H NMR (400 MHz, Chloroform-d) delta 4.34 (d, J = 5.1Hz, 2H), 3.67 (d, J = 1.6 Hz, 486H), 3.40 (d, J = 1.4 Hz, 3H), 1.97 (d, J =1.4 Hz, 7H), 1.66–0.96 (m, 121H), 0.93–0.78 (m, 30H). (2) Synthesis of I'-4 5 g of diisopropylaminoethanol, 3.6 g of methacryloyl chloride and 3.5 g of triethylamine were added to a three-necked flask containing 20 mL of tetrahydrofuran. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the product was purified by silica gel column chromatography to obtain a colorless oil as shown in Formula I'-4, with a yield of 47%.

[0063] The proton NMR spectrum of I'-4: 1 H NMR (400 MHz, Chloroform- d ) δ 6.14 (s, 1H), 5.59 (q, J = 1.6 Hz, 1H), 4.12 (td, J = 7.1, 1.6 Hz, 2H), 3.06 (td, J = 6.6, 1.6 Hz, 2H), 2.73 (td, J = 7.1, 1.5 Hz, 2H), 1.98 (s, 3H), 1.06 (dd, J = 6.7, 1.6 Hz, 12H). The carbon NMR spectrum of I'-4: 13 C NMR (101 MHz, Chloroform- d ) δ 136.51, 125.29,77.38, 65.53, 49.41, 20.79, 18.42. High-resolution mass spectrometry of I'-4: HRMS (TOF-ES+): m / z: calcd for C 12 H 24 NO2: 214.1811[M+H] + Found: 214.1807. (3) Synthesis of I'6 3 g of 2-hydroxyethyl disulfide, 4.06 g of methacryloyl chloride and 5 g of triethylamine were added to a three-necked flask containing 100 mL of tetrahydrofuran. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the product was purified by silica gel column chromatography to obtain a colorless oil as shown in Formula I'-6, with a yield of 54%.

[0064] The proton NMR spectrum of I'-6: 1H NMR (400 MHz, CDCl3, ppm): δ 6.14 (t, J = 1.0Hz, 1H), 5.60 (t, J = 1.6 Hz, 1H), 4.43 (t, J = 6.7 Hz, 2H), 3.89 (t, J = 5.9Hz, 2H), 2.98 (t, J = 6.7 Hz, 2H), 2.89 (t, J = 5.9 Hz, 2H), 1.95 (t, J = 1.2Hz, 3H). I'-6 carbon NMR spectrum: 13 C NMR (100 MHz, CDCl3, ppm): δ 167.30, 135.94,126.19, 62.65, 60.20, 41.55, 36.95, 18.28. High-resolution mass spectrometry of I'-6: HRMS (TOF-ESI+): m / z: calcd for C8H 14 NaO3S2: 245.0282[M+Na] + Found: 245.0286. (4) Synthesis of I'-7 1 g of the pure white solid as shown in Formula I'-2, 1.7 g of the colorless oil as shown in Formula I'-4, and 0.28 g of the colorless oil as shown in Formula I'-6 were added to a solution containing 8 mL of... N,N Dimethylformamide was placed in a Shrek tube, and then 35 mg of pentamethyldiethylenetriamine and 29 mg of cuprous bromide were added. The mixture was refluxed and stirred for 48 hours under nitrogen protection. After the reaction was completed, the mixture was freeze-dried for 12 hours to obtain a white flocculent solid as shown in Formula I'-7, with a yield of 31.7%.

[0065] (1) Synthesis of I'-8-2 1 g of a pure white solid as shown in Formula I'-7, 1.7 g of cinnamyl alcohol intermediate, and 0.28 g of 4-dimethylaminopyridine were added to a solution containing 8 mL of... N,N After the reaction of dimethylformamide in a Shrek tube was stirred at room temperature under nitrogen protection for 12 hours, the mixture was freeze-dried for 12 hours to obtain a white flocculent solid as shown in Formula I'-8-2, with a yield of 54.4%.

[0066] Example 3 This embodiment provides a pH / GSH dual-responsive polymeric latent fragrance compound PEG-PND-SST, the structural formula of which is shown in Formula I'-8-3: In the formula, x is 50~80 and y is 4~8.

[0067] Furthermore, this embodiment also provides a method for preparing PEG-PND-SST (the compound shown in Formula I'-8-3), the specific steps of which are as follows: (1) Synthesis of I'-2 5 g of polyethylene glycol monomethyl ether, 228 mg of 2-methyl-2-bromopropionyl bromide and 253 mg of triethylamine were added to a three-necked flask containing 20 mL of dichloromethane. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the mixture was filtered. The resulting white filter cake was dried under vacuum for 3 hours to obtain a pure white solid as shown in Formula I'-2. Yield: 80%.

[0068] The proton NMR spectrum of I'-2: 1 H NMR (400 MHz, Chloroform-d) delta 4.34 (d, J = 5.1Hz, 2H), 3.67 (d, J = 1.6 Hz, 486H), 3.40 (d, J = 1.4 Hz, 3H), 1.97 (d, J =1.4 Hz, 7H), 1.66–0.96 (m, 121H), 0.93–0.78 (m, 30H). (2) Synthesis of I'-4 5 g of diisopropylaminoethanol, 3.6 g of methacryloyl chloride and 3.5 g of triethylamine were added to a three-necked flask containing 20 mL of tetrahydrofuran. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the product was purified by silica gel column chromatography to obtain a colorless oil as shown in Formula I'-4, with a yield of 47%.

[0069] The proton NMR spectrum of I'-4: 1 H NMR (400 MHz, Chloroform- d ) δ 6.14 (s, 1H), 5.59 (q, J = 1.6 Hz, 1H), 4.12 (td, J= 7.1, 1.6 Hz, 2H), 3.06 (td, J = 6.6, 1.6 Hz, 2H), 2.73 (td, J = 7.1, 1.5 Hz, 2H), 1.98 (s, 3H), 1.06 (dd, J = 6.7, 1.6 Hz, 12H). The carbon NMR spectrum of I'-4: 13 C NMR (101 MHz, Chloroform- d ) δ 136.51, 125.29,77.38, 65.53, 49.41, 20.79, 18.42. High-resolution mass spectrometry of I'-4: HRMS (TOF-ES+): m / z: calcd for C 12 H 24 NO2: 214.1811[M+H] + Found: 214.1807. (3) Synthesis of I'6 3 g of 2-hydroxyethyl disulfide, 4.06 g of methacryloyl chloride and 5 g of triethylamine were added to a three-necked flask containing 100 mL of tetrahydrofuran. The mixture was stirred at room temperature for 12 hours under nitrogen protection. After the reaction was completed, the product was purified by silica gel column chromatography to obtain a colorless oil as shown in Formula I'-6, with a yield of 54%.

[0070] The proton NMR spectrum of I'-6: 1 H NMR (400 MHz, CDCl3, ppm): δ 6.14 (t, J = 1.0Hz, 1H), 5.60 (t, J = 1.6 Hz, 1H), 4.43 (t, J = 6.7 Hz, 2H), 3.89 (t, J = 5.9Hz, 2H), 2.98 (t, J = 6.7 Hz, 2H), 2.89 (t, J = 5.9 Hz, 2H), 1.95 (t, J = 1.2Hz, 3H). I'-6 carbon NMR spectrum: 13 C NMR (100 MHz, CDCl3, ppm): δ 167.30, 135.94,126.19, 62.65, 60.20, 41.55, 36.95, 18.28. High-resolution mass spectrometry of I'-6: HRMS (TOF-ESI+): m / z: calcd for C8H 14 NaO3S2: 245.0282[M+Na] + Found: 245.0286. (4) Synthesis of I'-7 1 g of the pure white solid as shown in Formula I'-2, 1.7 g of the colorless oil as shown in Formula I'-4, and 0.28 g of the colorless oil as shown in Formula I'-6 were added to a solution containing 8 mL of... N,N Dimethylformamide was placed in a Shrek tube, and then 35 mg of pentamethyldiethylenetriamine and 29 mg of cuprous bromide were added. The mixture was refluxed and stirred for 48 hours under nitrogen protection. After the reaction was completed, the mixture was freeze-dried for 12 hours to obtain a white flocculent solid as shown in Formula I'-7, with a yield of 31.7%.

[0071] (1) Synthesis of I'-8-3 1 g of a pure white solid as shown in Formula I'-7, 1.7 g of thymol intermediate, and 0.28 g of 4-dimethylaminopyridine were added to a solution containing 8 mL of... N,N After the reaction of dimethylformamide in a Shrek tube was stirred at room temperature under nitrogen protection for 12 hours, the mixture was freeze-dried for 12 hours to obtain a white flocculent solid as shown in Formula I'-8-3, with a yield of 54.4%.

[0072] Performance testing: Nanomicelles were prepared by a nanoprecipitation method, the specific method of which is as follows: 10 mg of the compound shown in Formula I'-8 was dispersed in 1 mL of tetrahydrofuran, and then 10 mL of ultrapure water was added dropwise while stirring. After the addition was complete, the mixture was stirred for 2 h to obtain a nanomicelle solution.

[0073] Figure 2 and Figure 3 The figures show the 1H NMR spectrum and gel permeation chromatogram of PEG-PND-SSC (the compound shown in Formula I'-8-2) prepared in Example 2. The figures demonstrate the successful preparation of PEG-PND-SSC, with a molecular weight of 17402 and a PDI of 1.5.

[0074] Figure 4This is a particle size and particle size distribution diagram of the PEG-PND-SSC (compound shown in Formula I'-8-2) nanomicelles prepared in Example 2. The diagram shows that PEG-PND-SSC forms nanomicelles of 50.9 ± 0.49 nm in aqueous solution, indicating that the polymeric fragrance has a certain degree of stability in aqueous solution.

[0075] Figure 5 The figures show the thermogravimetric TGA (TGA) graphs of PEG-PND-SSC (the compound shown in Formula I'-8-2), PEG-PND-SSOH (the compound shown in Formula I'-7), and cinnamyl alcohol prepared in Example 2. As can be seen from the graphs, the polymeric latent fragrance enhances the thermal stability of cinnamyl alcohol while also exhibiting stable loading performance, indicating that the polymeric latent fragrance possesses excellent versatility and fragrance loading capacity.

[0076] Figure 6 This is a cinnamyl alcohol release curve of PEG-PND-SSC (the compound shown in Formula I'-8-2) prepared in Example 2 in different pH and GSH buffer solutions (pH=7.4, pH=6, and 5mM GSH). As can be seen from the figure, below the critical pH and in the presence of GSH, the protonation behavior of the polymer nanomicelles leads to micelle depolymerization and disulfide bond breakage, resulting in rapid cinnamyl alcohol release, with a release rate as high as 65% after 6 hours. However, under neutral conditions without GSH, the cinnamyl alcohol release rate in the micelle state is extremely low. This indicates that the micelles formed by the polymer latent fragrance components have excellent fragrance release performance.

[0077] Figure 7 The figures show the plate colony counts of PEG-PND-SSG (the compound shown in Formula I'-8-1) and geraniol prepared in Example 1 against *Escherichia coli* and *Staphylococcus aureus*. As can be seen from the figures, the antibacterial properties of PEG-PND-SSG are significantly better than those of geraniol. This indicates that, at the same equivalence, the polymeric aromatic compound possesses excellent antibacterial properties.

[0078] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A pH / GSH dual-responsive polymeric latent fragrance, characterized in that, The structural formula of the pH / GSH dual-responsive polymer latent fragrance is shown in Formula I'-8: In formula I'-8, R is selected from any one or more alkyl or substituted aryl groups. The range of x is 50 to 80, and the range of y is 4 to 8.

2. The pH / GSH dual-responsive polymeric latent fragrance compound according to claim 1, characterized in that, The R is selected from , or .

3. A method for preparing a pH / GSH dual-responsive polymeric latent fragrance as described in claim 1 or claim 2, characterized in that, The specific steps are as follows: S1. In solvent F, the compound shown in formula I'-1 is reacted with the substitution reagent A under nitrogen protection and stirred under reflux to obtain the compound shown in formula I'-2. S2. In solvent F, the compound shown in formula I'-3 was reacted with the substitution reagent B under nitrogen protection and stirred under reflux to obtain the compound shown in formula I'-4. S3. In solvent F, the compound shown in formula I'-5 is reacted with the substitution reagent B under nitrogen protection and stirred under reflux for a period of time to obtain the compound shown in formula I'-6. S4. Under nitrogen protection, the compound shown in Formula I'-2 obtained in step S1, the compound shown in Formula I'-4 obtained in step S2, the compound shown in Formula I'-6 obtained in step S3, and solvent F are mixed, and catalysts C and D are added. After polymerization, a pH / GSH dual-responsive polymer shown in Formula I'-7 is obtained. S5. Under nitrogen protection, the pH / GSH dual-responsive polymer, fragrance intermediate, and solvent F obtained in step S4 as shown in Formula I'-7 are mixed, catalyst E is added, and the reaction is stirred to obtain the pH / GSH dual-responsive polymer latent fragrance body as shown in Formula I'-8. The structural formulas of equations I'-1 to I'-8 are shown below: ， In the formula, R is selected from any one or more alkyl or substituted aryl groups. The range of x is 50 to 80, and the range of y is 4 to 8.

4. The method for preparing the pH / GSH dual-responsive polymeric latent fragrance according to claim 3, characterized in that, In step S1, the molar ratio of the compound shown in Formula I'-1 to the substitution reagent A is 1:(1~5). In step S2, the molar ratio of the compound shown in formula I'-3 to the substitution reagent B is 1:(1~5). In step S3, the molar ratio of the compound shown in formula I'-5 to the substitution reagent B is 1:(1~5). In step S4, the following compounds are used: Compound 1'-2; Compound 1'-4; Compound 1'-6; Solvent F = 1g: 0.5~1.5g: 0.2~0.5g: 5~15mL. In step S4, the molar ratio of the compound shown in Formula I'-2, catalyst C, and catalyst D is 1:(1~3):(1~3). In step S5, the compound as shown in formula I'-7: fragrance intermediate: solvent F = 1g: 3~5g: 100~200mL, In step S5, the molar ratio of the compound shown in Formula I'-7 to catalyst E is 1:(1~3).

5. The method for preparing the pH / GSH dual-responsive polymeric latent fragrance according to claim 3, characterized in that, In step S1, the substitution reagent A is selected from... N 1-Brominated succinimide (NBS), acrylate (AE), 2-methyl-2-bromopropionyl bromide, carbon tetrabromide (CBr4), or trimethylphenyltribromium tribromide; In steps S2 and S3, the substitution reagent B is selected from any one or more of acetyl chloride, benzoyl chloride, methacryloyl chloride, chloroacetyl chloride, or trichloroacetyl chloride; In step S4, the catalyst C is selected from triethylenediamine (TEDA) and pentamethyldiethylenetriamine (PMDETA). N - Dimethylcyclohexylamine (DMCHA), dimethylethanolamine (DMEA) or N Any one or more of benzyl dimethylamine (BDMA); In step S4, the catalyst D is selected from any one or more of aluminum chloride, boron trifluoride, tin tetrachloride, cuprous bromide, or zinc chloride; In step S5, the flavor intermediate is selected from any one of geraniol, cinnamyl alcohol, or thymol; In step S5, the catalyst E is selected from... N 4-methylimidazolium, 4-dimethylaminopyridine, or 4-pyrrolidinylpyridine; In steps S1-S5, the solvent F is selected from dichloromethane, petroleum ether, ethyl acetate, etc. N,N Any one or more of dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, or acetonitrile.

6. A method for preparing pH / GSH dual-responsive polymer nanomicelles, characterized in that, The specific steps are as follows: S1. Dissolve the pH / GSH dual-responsive polymer latent fragrance as described in claim 1 or claim 2 in solvent G to obtain a mixture; S2. The mixture prepared in step S2 is mixed with solvent H, and after stirring, pH / GSH dual-responsive polymer nanomicelles are obtained.

7. The method for preparing pH / GSH dual-responsive polymer nanomicelles according to claim 6, characterized in that, In step S1, the mass ratio of the pH / GSH dual-responsive polymer latent fragrance to solvent G is 1:(10~100).

8. The method for preparing pH / GSH dual-responsive polymer nanomicelles according to claim 6, characterized in that, In step S2, the mass ratio of the mixture and solvent H prepared in step S2 is 1:(100~1000).

9. The method for preparing pH / GSH dual-responsive polymer nanomicelles according to claim 6, characterized in that, In steps S1 and S2, the solvent G and solvent H are selected from deionized water, dichloromethane, petroleum ether, ethyl acetate, etc. N,N Any one or more of dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, or acetonitrile.

10. The use of a pH / GSH dual-responsive polymeric latent fragrance as described in claim 1 or claim 2 in the preparation of a bacterial microenvironment controlled-release fragrance.

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