A macromolecular active agent having a natural active ingredient, and a method of preparing and using the same

Abstract

The application discloses a macromolecular active preparation with natural active ingredients and a preparation method and application thereof, and belongs to the technical field of biomedical materials, and aims at the defects of the existing anti-acne preparations, such as single active ingredient, limited efficacy and strong irritation, wherein salicylic acid is heated to melt in a nitrogen environment, curcumin is added to dissolve, and polyethylene glycol is added to heat polymerization to obtain poly(salicylic acid-curcumin)-polyethylene glycol polymer, the polymer is dissolved in deionized water, dialysis is carried out for 2-3 days by using a dialysis bag with a molecular weight cut-off of 500-3500 Da, and the macromolecular active preparation with curcumin and salicylic acid as natural active ingredients is prepared through freeze-drying.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a macromolecular active preparation with natural active ingredients, its preparation method, and its application. Background Technology

[0002] Acne is a common skin problem worldwide, affecting a large population, especially teenagers and young adults. Treatment strategies for acne primarily focus on antibacterial, anti-inflammatory, oil-controlling, and keratinocyte-stimulating metabolism. Developing active formulations with multiple mechanisms and high bioactivity is key to effective clinical control of acne. Salicylic acid, a classic lipid-soluble β-hydroxy acid, has excellent exfoliating and pore-unclogging properties and is widely used in anti-acne products. Salicylic acid can dissolve sebum and keratin plugs in pores, preventing blockage, and can inhibit the expression of inflammatory factors, exhibiting certain anti-inflammatory and antibacterial effects. Curcumin, a natural polyphenolic compound extracted from turmeric, possesses various bioactivities, including antioxidant, anti-inflammatory, antibacterial, and immunomodulatory effects. Currently, most acne treatments on the market rely on single active ingredients, resulting in limited efficacy, high irritation, and significant side effects, making it difficult to achieve a gentle, effective, and comprehensive treatment outcome. Existing anti-acne preparations based on a single active ingredient cannot simultaneously achieve multiple effects such as antibacterial, anti-inflammatory, and regulation of keratin metabolism. Some preparations also have the problems of strong skin irritation and obvious side effects, failing to achieve a gentle, efficient, and comprehensive skin treatment effect. Summary of the Invention

[0003] The technical problem to be solved by this invention is that existing anti-acne preparations are mostly based on a single active ingredient, which has the defects of limited efficacy, strong skin irritation and significant side effects, making it difficult to achieve a gentle, efficient and comprehensive skin treatment effect. At the same time, there is currently no relevant technology to effectively integrate salicylic acid and curcumin to develop a macromolecular active preparation and apply it to the field of acne treatment.

[0004] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides a method for preparing a macromolecular active preparation containing natural active ingredients, comprising the following steps: Salicylic acid was heated to a molten state under a protective atmosphere, curcumin was added to dissolve it, and then polyethylene glycol was added to carry out a thermal polymerization reaction to obtain a poly(salicylic acid-curcumin)-polyethylene glycol polymer. The poly(salicylic acid-curcumin)-polyethylene glycol polymer was dissolved in deionized water and purified by dialyzing to obtain a macromolecular active preparation with natural active ingredients.

[0005] As a further improvement of the present invention, the salicylic acid is heated in a nitrogen environment at a temperature of 160-200°C for a heating time of 10-50 minutes.

[0006] As a further improvement to the present invention, after adding curcumin and polyethylene glycol, the temperature of the reaction system is 100-150℃ and the reaction time is 5-24 hours.

[0007] As a further improvement to the present invention, the poly(salicylic acid-curcumin)-polyethylene glycol polymer is dissolved in deionized water and purified by dialysis, specifically including: After the thermal polymerization reaction is complete, dialyze the polymer for 2-3 days using a dialysis bag with a molecular weight cutoff of 500-3500 Da. Then freeze-dry the dialyzed poly(salicylic acid-curcumin)-polyethylene glycol polymer and store it in a refrigerator.

[0008] As a further improvement of the present invention, the reaction system is kept under a vacuum of 0.08-0.1 MPa and stirred at a stirring speed of 150-250 r / min.

[0009] As a further improvement to the present invention, the poly(salicylic acid-curcumin)-polyethylene glycol polymer is dissolved in deionized water and purified by dialysis, specifically including: After the thermal polymerization reaction is complete, dialyze the polymer for 2-3 days using a dialysis bag with a molecular weight cutoff of 500-3500 Da. Then freeze-dry the dialyzed poly(salicylic acid-curcumin)-polyethylene glycol polymer and store it in a refrigerator.

[0010] As a further improvement of the present invention, the refrigerator temperature is set to a refrigeration range of 2-8°C, and the poly(salicylic acid-curcumin)-polyethylene glycol polymer is placed in a vacuum bag, sealed, and stored.

[0011] As a further improvement of the present invention, the molar ratio of salicylic acid, curcumin and polyethylene glycol is 1:(0.3–0.8):(0.8–1.5).

[0012] Secondly, this invention provides a macromolecular active preparation containing natural active ingredients, obtained by the aforementioned preparation method, and the structural formula of the macromolecular active preparation containing natural active ingredients is as follows:

[0013] The value of n ranges from 2 to 200.

[0014] As a further improvement of the present invention, the macromolecular active formulation further comprises, by weight percentage, 0.001–10% (w / w) of preservative and / or 0.1–10% (w / w) of moisturizing agent; the preservative is selected from one or more of phenoxyethanol, ethylhexylglycerin, potassium sorbate, gluconolactone and sodium benzoate complex, and octanediol; the moisturizing agent is selected from one or more of butylene glycol, pentanediol, and hexanediol.

[0015] Thirdly, the present invention provides an application of a macromolecular active preparation containing natural active ingredients, characterized in that it is used in the preparation of topical products for anti-acne, anti-inflammatory, and skin barrier repair; the topical products include masks, sprays, gels, and lotions.

[0016] Fourthly, the present invention provides a medical or cosmetic facial mask, characterized in that it contains the aforementioned macromolecular active agent; the active agent is impregnated in a nonwoven fabric matrix at a content of 0.1–10 mg / cm².

[0017] Fifthly, the present invention provides a spray, characterized in that the spray contains 0.1–10% (w / v) of the aforementioned macromolecular active agent.

[0018] In a sixth aspect, the present invention provides a gel formulation prepared by mixing the aforementioned macromolecular active formulation with one or more matrices selected from carbomer, sodium hyaluronate, and glycerin.

[0019] In a seventh aspect, the present invention provides an emulsion formulation containing the aforementioned macromolecular active agent, wherein the emulsion is a water-in-oil or oil-in-water emulsion system, and the mass concentration of the macromolecular active agent in the emulsion is 0.1–10%.

[0020] Compared with the prior art, the present invention has the following beneficial effects: This application utilizes a thermal polymerization reaction to couple salicylic acid, curcumin, and polyethylene glycol to form a PSGC polymer. The entire process requires no organic solvents, features mild reaction conditions, is simple to operate, and is environmentally friendly. The product purification efficiency is high, with good reproducibility, making it suitable for large-scale preparation. This polymerization method effectively improves the solubility and physicochemical stability of salicylic acid and curcumin, solving the problem of poor solubility when used alone. It also reduces the skin irritation of traditional small-molecule formulations, improving safety and skin tolerance. The resulting PSGC polymer combines the exfoliating, antibacterial, and anti-inflammatory effects of salicylic acid with the antioxidant and immunomodulatory effects of curcumin. The synergistic effect of the two active ingredients achieves multiple effects including anti-acne, anti-inflammation, and skin barrier repair, making it suitable for a wide range of applications. Furthermore, this macromolecular active formulation exhibits good biocompatibility and can be adapted to various topical formulations such as masks, sprays, gels, and lotions, providing a new direction for product development in the medical and cosmetic fields. Attached Figure Description

[0021] Figure 1 This is the structural formula of the monomer and polymer in the macromolecular active preparation containing natural active ingredients synthesized in this invention; Figure 2The Fourier transform infrared (FTIR) spectrum of the PSGC polymer prepared in this invention is shown below. Figure 3 The ¹H NMR spectrum of the PSGC polymer prepared in this invention is shown below. Figure 4 This is a comparative test chart showing the solubility of salicylic acid, curcumin, and PSGC polymer prepared in this invention; Figure 5 This is a schematic diagram illustrating the therapeutic effect of the PSGC polymer prepared in this invention on a mouse acne model. Detailed Implementation

[0022] The technical solutions of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The components of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely represents selected embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application. It should be noted that similar reference numerals and letters in the following drawings indicate similar items; therefore, once an item is defined in one drawing, it does not need to be further defined and explained in subsequent drawings. Furthermore, in the description of this application, the terms "first," "second," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0023] To better understand the present invention, the present invention will be described in detail below with reference to specific embodiments, but the content of the present invention is not limited to the following embodiments.

[0024] Studies have shown that curcumin has potential applications in treating skin inflammation and microbial infections. Developing a multifunctional active formulation based on a combination of salicylic acid and curcumin, which achieves multiple effects such as antibacterial, anti-inflammatory, and exfoliating properties while also considering skin tolerance and user comfort, has significant clinical value and promising industrial application prospects.

[0025] This invention provides a method for preparing a macromolecular active preparation containing natural active ingredients, comprising the following steps: Poly(salicylic acid-curcumin)-polyethylene glycol (PSGC) polymers were synthesized by thermal polymerization of salicylic acid (SA), curcumin, and polyethylene glycol (PEG) in different molar ratios. The PSGC polymers were dissolved in deionized water and purified by dialysis to obtain a macromolecular active formulation with natural active ingredients.

[0026] The hydrothermal reaction of salicylic acid (SA) in a nitrogen environment is carried out at a temperature of 160-200℃ for a reaction time of 10-50 minutes. After the addition of curcumin and PEG, the reaction system temperature is 100-150℃, and the reaction time is 5-24 hours. The heating temperature can be selected within the range of 160℃, 180℃, or 200℃, and the heating time can be adjusted according to the temperature, such as heating for 30 minutes at 160℃ and heating for 10 minutes at 200℃. A constant-temperature oil bath with a temperature and time control system is used for heating to precisely control the reaction conditions. The nitrogen gas introduction rate is 0.5L / min, continuously introduced until the end of the heating stage to ensure that the reaction is carried out in an oxygen-free environment. The temperature range of 160-200℃ ensures that salicylic acid is completely melted while avoiding excessive temperature that could lead to salicylic acid decomposition. The heating time of 10-50 minutes provides sufficient time for the salicylic acid to melt, laying a uniform matrix foundation for the subsequent dissolution and polymerization of curcumin. Precise temperature and time parameters ensure that salicylic acid melts fully and does not decompose, improving the consistency and stability of the polymerization reaction and ensuring uniform performance of each batch of products.

[0027] Furthermore, the post-processing method for obtaining the PSGC polymer is as follows: After the reaction is complete, dialyze the polymer using a dialysis bag with a molecular weight cutoff of 500-3500 Da for 2-3 days. The dialyzed PSGC polymer is then freeze-dried and stored in a refrigerator. The polymerization temperature can be selected within the range of 120℃ or 140℃, and the reaction time can be adjusted accordingly to 20 hours or 12 hours. The reaction system needs to be maintained under a vacuum of 0.08-0.1 MPa, while using a stirring speed of 150-250 r / min to ensure uniform reaction. Temperature control is achieved through the constant temperature module of the oil bath, and time control is achieved through the timer function of the equipment. A temperature range of 100-150℃ promotes the formation of ester bonds between the three components, facilitating the smooth progress of the polymerization reaction. A reaction time of 5-24 hours ensures complete polymerization, and the vacuum environment allows for timely removal of small molecule byproducts generated during the reaction, preventing them from affecting the polymer structure. A PSGC polymer with uniform molecular weight distribution was obtained, which fully preserved the bioactivity of salicylic acid and curcumin, achieving a synergistic effect between the two components and enhancing the anti-inflammatory and anti-acne effects of the formulation.

[0028] Furthermore, the refrigerator temperature is set within the 2-8°C refrigeration range. The formulation must be sealed in an aluminum foil vacuum bag before storage to prevent moisture absorption and oxidation. The aluminum foil vacuum bag is 0.1mm thick, providing good oxygen barrier and moisture protection. In practical applications, polyethylene vacuum bags, etc., can also be selected; this application does not limit this option. The low-temperature environment of 2-8°C reduces the mobility of polymer molecules, slowing down their degradation rate. The sealed packaging isolates the formulation from external air and moisture, preventing moisture absorption and oxidation. This extends the shelf life of the macromolecular active formulation; after 6 months of storage, the physicochemical properties and biological activity of the formulation show no significant changes, facilitating subsequent formulation development and market application.

[0029] The macromolecular active formulations prepared by the above method have important applications in the preparation of anti-acne, anti-inflammatory, and skin barrier repair masks, sprays, and gels. The macromolecular active formulations further include 0.001–10% (w / w) of preservatives and / or 0.1–10% (w / w) of moisturizing agents.

[0030] Specifically, pharmaceutical-grade salicylic acid with a purity ≥99.5% can be used. A nitrogen atmosphere is achieved by continuously introducing nitrogen into the constant-temperature oil bath reactor to isolate oxygen and prevent salicylic acid oxidation and decomposition. A constant-temperature oil bath with a temperature control accuracy of ±1℃ is used for precise temperature control. Cosmetic-grade curcumin with a purity ≥95% is used, and after addition, it is stirred with a magnetic stirrer at 200 r / min to ensure complete dissolution. PEG4000 polyethylene glycol is used, as this type of polyethylene glycol has excellent hydrophilicity and flexible segment properties, which can improve the water solubility and skin affinity of the final polymer. In practical applications, PEG6000 and other types can also be selected, but this application does not limit this. The thermal polymerization reaction is carried out in a vacuum reactor at 0.08-0.1 MPa to remove small molecule byproducts generated during the reaction. The dialysis bags are made of cellulose material, and the molecular weight cutoff can be selected as 1000 Da, 2000 Da, or 3500 Da. The bags are replaced daily during dialysis. The water is deionized to ensure effective removal of impurities; a vacuum freeze dryer at -40℃ is used for 24 hours to avoid damage to the active ingredients.

[0031] The working principle of this invention is as follows: Salicylic acid is heated to a molten state under nitrogen atmosphere to provide a uniform reaction matrix for curcumin and polyethylene glycol; thermal polymerization promotes the formation of ester bonds between the three components, and covalent coupling forms a PSGC polymer; dialysis removes unreacted small molecule raw materials to improve polymer purity; freeze drying converts the polymer aqueous solution into a solid powder, which is convenient for subsequent storage and formulation development.

[0032] The preparation method does not introduce organic solvents throughout the process, making it green, environmentally friendly, and easy to operate, suitable for large-scale production. The obtained PSGC polymer has significantly improved solubility and physicochemical stability, reduces skin irritation when salicylic acid and curcumin are used alone, and has multiple effects such as anti-inflammatory, antibacterial and skin barrier repair.

[0033] This invention relates to a PSGC macromolecular active formulation based on curcumin, salicylic acid, and polyethylene glycol. The PSGC achieves efficient coupling and stabilization of the natural active ingredients through a thermal polymerization reaction, resulting in an active formulation with both good physicochemical stability and skin compatibility. Simultaneously, PSGC can form a stable presence on the skin surface and achieve sustained release, thereby improving the overall utilization efficiency of curcumin and salicylic acid and reducing the irritation risks associated with direct application of traditional small molecules. Therefore, PSGC can be used to prepare medical or cosmetic topical formulations with anti-acne, anti-inflammatory, soothing, and skin barrier repair effects, and has significant potential for widespread application.

[0034] The PSGC polymer synthesized in this invention has good physicochemical stability, biocompatibility and potential anti-inflammatory activity. It can be widely used as a multifunctional active material in medical or cosmetic scenarios such as anti-acne, wound repair, anti-oxidation or other skin barrier function enhancement, and has good application prospects.

[0035] For example, a medical or cosmetic face mask may be provided containing the aforementioned macromolecular active agent, wherein the active agent is impregnated in a nonwoven fabric matrix at a concentration of 0.1–10 mg / cm².

[0036] For example, a spray is provided containing 0.1–10% (w / v) of a macromolecular active formulation.

[0037] Furthermore, a gel formulation is provided, which is prepared by mixing a macromolecular active agent with one or more matrices selected from carbomer, sodium hyaluronate, and glycerin.

[0038] Furthermore, an emulsion formulation is provided, wherein the emulsion contains the aforementioned macromolecular active agent, the emulsion being a water-in-oil (O / W) or oil-in-water (W / O) emulsion system, and the mass concentration of the macromolecular active agent in the emulsion is 0.1–10% (w / v). In practical applications, the active formulation may contain preservatives or non-preservative substances with preservative properties. The preservative is selected from one or more of phenoxyethanol, ethylhexylglycerin, potassium sorbate, a compound of gluconolactone and sodium benzoate, and octanediol, and its addition amount is preferably one ten-thousandth to one percent of the total weight of the active formulation.

[0039] More preferably, the non-preservative component with antibacterial synergistic effect is selected from one or more of butanediol, pentanediol, and hexanediol, and the amount added is preferably one-thousandth to ten percent of the total weight of the active preparation.

[0040] Furthermore, the present invention also provides a facial mask sheet, which includes a base material and an active preparation impregnated in the base material. The facial mask sheet has a wet-application type structure, and the active preparation is impregnated into the base material to form the final product.

[0041] The matrix material is used to carry and sustain the release of the active agent. Its type is not particularly limited, and those skilled in the art can select it according to specific needs. Materials used include, but are not limited to, paper, non-woven fabric, rayon, and silk. The amount of the active agent impregnated in the matrix material is also not particularly limited, but is preferably saturated, meaning the matrix material is completely impregnated.

[0042] Furthermore, the present invention also provides a facial mask sheet kit, which includes a packaging container and the aforementioned facial mask sheet or base material. The base material may be placed in the packaging container in a form pre-impregnated with the active preparation, or the active preparation may be placed directly in the packaging container, with at least a portion or all of the base material immersed in the active preparation.

[0043] The packaging container is not limited to a specific shape or material, but conventional packaging materials such as aluminum foil, polyethylene film, and polypropylene film are preferred. It is also preferred to have a sealed packaging structure to prevent the active ingredients from volatilizing, contaminating, or degrading.

[0044] The facial mask sheet and kit provided by this invention are suitable for medical or cosmetic purposes. They can be further supplemented with commonly used medical or cosmetic auxiliary ingredients according to usage needs to enhance their efficacy.

[0045] The present invention also provides the use of the active preparation in the preparation of a face mask or face mask kit for medical or cosmetic purposes.

[0046] Furthermore, the present invention also provides a spray, comprising a spray liquid and a container for achieving spray release. The spray liquid is preferably the active preparation provided by the present invention, or a solution or dispersion containing the active preparation. This spray is suitable for uniformly applying active ingredients to the skin surface in an atomized form, thereby achieving medical or cosmetic effects such as soothing, repairing, moisturizing, anti-inflammatory, and anti-acne treatment.

[0047] In the spray solution, the active preparation can be in a dissolved or dispersed state, or it can be encapsulated in the form of nanomicelles, liposomes, microemulsions, etc. Water is preferably used as the main solvent, and moisturizing or dissolving agents such as glycerol, butylene glycol, propylene glycol, and octyl glycol can be added as needed to enhance the performance.

[0048] Depending on the actual functional requirements, active ingredients with good skin care effects, such as sodium hyaluronate, ceramide, tocopherol, tea polyphenols, and centella asiatica extract, can be further added to the spray to enhance the overall skin care effect.

[0049] The spray container is not limited to a specific type and may include, but is not limited to, manually operated pump spray bottles, vacuum pump bottles, aerosol cans (using nitrogen or compressed air as propellants), or other containers capable of atomization and release. A sealed packaging structure is preferred to ensure the hygiene, stability, and long-term shelf life of the spray solution.

[0050] The spray of this invention is suitable for daily care, postoperative sedation, inflammation management, and skin barrier repair in medical or beauty settings, and can be matched with different packaging specifications according to different usage needs.

[0051] Furthermore, the present invention also provides the use of the active formulation in the preparation of a spray for medical or cosmetic purposes.

[0052] Furthermore, the present invention also provides a gel formulation comprising an active ingredient and a gel matrix. This gel formulation is suitable for stably encapsulating active ingredients and applying them to the skin surface in a semi-solid form to achieve medical or cosmetic effects such as anti-inflammatory, soothing, anti-acne, moisturizing, and repairing properties.

[0053] The active preparation used in the gel formulation is preferably the active preparation provided by the present invention, which may be a water-soluble, lipid-soluble or composite preparation encapsulated in the form of microcapsules, nanoparticles, liposomes, etc., and may further contain other functional ingredients with synergistic effects.

[0054] The gel matrix is ​​used to construct the physical structure of the gel and plays a role in regulating the release rate of active ingredients, prolonging residence time, and enhancing skin adhesion. Its specific type is not limited. Preferably, the gel matrix is ​​selected from one or more of the following: sodium hyaluronate, carbomer, xanthan gum, trehalose, hydroxyethyl cellulose, polyvinyl alcohol, etc. Depending on performance requirements, humectants such as glycerin, propylene glycol, and butylene glycol, as well as appropriate pH adjusters and preservatives, may be further added to the gel to achieve the desired gel strength, skin feel, stability, and transdermal properties.

[0055] The gel formulation of this invention can be used alone as a topical dosage form, or as a component in other dosage forms (such as face masks, dressings, sprays, etc.). The gel can be filled into various forms of packaging containers such as tubes, pump bottles, and gel capsules as needed, preferably with a sealed structure to ensure the storage stability and safety of the product.

[0056] The gel formulation of this invention is suitable for medical or cosmetic applications, and is especially suitable for daily care or post-operative repair of sensitive skin, acne-prone skin, and inflamed skin.

[0057] Furthermore, the present invention also provides the use of the active preparation in the preparation of gel formulations for medical or cosmetic purposes.

[0058] Furthermore, the present invention also provides an emulsion formulation comprising an active ingredient and an emulsifying matrix. This emulsion formulation is suitable for stably encapsulating active ingredients and uniformly applying them to the skin surface in a fluid or semi-fluid form to achieve medical or cosmetic effects such as anti-inflammatory, soothing, moisturizing, barrier repair, anti-acne, and anti-aging properties.

[0059] The active ingredient used in the emulsion formulation is preferably the active ingredient provided by the present invention, which can be in a dissolved or dispersed state, or can be encapsulated in the form of nanomicelles, liposomes, microemulsions, microcapsules or nanoparticles to improve the stability, skin affinity and transdermal delivery capability of the active ingredient.

[0060] The emulsifying matrix is ​​used to construct the emulsion structure and improve the skin feel, and its specific type is not limited. Preferably, the emulsion is a water-in-oil (O / W) or oil-in-water (W / O) emulsion system, wherein the oil phase component can be selected from squalane, petrolatum, vegetable oil, fatty alcohol, fatty acid ester, silicone oil, or a combination thereof; the emulsifier can be selected from one or more of polysorbate, PEG emulsifiers, lecithin, cetearyl alcohol, and their derivatives.

[0061] Depending on the specific functional requirements, the emulsion formulation may further include moisturizers such as sodium hyaluronate, glycerin, butylene glycol, propylene glycol, and octyl glycol, as well as functional ingredients with good skincare effects such as ceramides, tocopherols, tea polyphenols, and centella asiatica extract, to enhance the overall skincare effect. The emulsion system may also contain appropriate amounts of thickeners, preservatives, and pH adjusters to improve emulsion stability, safety, and long-term shelf life.

[0062] The emulsion formulation of this invention is suitable for daily care, post-operative repair, inflammation management, and skin barrier repair in medical or cosmetic settings, and can be matched with different packaging specifications according to different usage needs. The emulsion can be filled into pump bottles, vacuum pump bottles, tubes, or other sealed packaging containers, preferably with a sealed structure to prevent the volatilization, contamination, or degradation of active ingredients.

[0063] Furthermore, the present invention also provides the use of the active agent in the preparation of emulsion formulations for medical or cosmetic purposes.

[0064] Example 1 Synthesis method of active formulation PSGC: SA was placed in an oil bath and heated to 160°C under nitrogen protection for 20 minutes until completely melted. Curcumin was then added and stirred continuously until dissolved to form a homogeneous mixture. Polyethylene glycol was then added and stirred continuously until homogeneous. The resulting mixture was placed at 140°C under vacuum for 12 hours to promote polymerization.

[0065] After the reaction, the product was dissolved in deionized water and transferred to a dialysis bag with a molecular weight cutoff of 1000 Da. Dialysis was performed in deionized water for 2–3 days, with the dialysis solution changed periodically to remove unreacted small molecules. After dialysis, the sample was freeze-dried to obtain the target product—poly(salicylic acid-curcumin)-polyethylene glycol-polymer, abbreviated as PSGC. The molar ratio of the three substances was SA:curcumin:PEG = 1:0.5:1.

[0066] The obtained PSGC is a yellow paste-like solid with good water dispersibility and stability. It can be used to further prepare various topical formulations for medical or cosmetic purposes, such as sprays, gels, and facial mask sheets.

[0067] Figure 1 This is a schematic diagram of the synthesis mechanism of the active preparation PSGC synthesized in this invention, where A is the molecular structure of salicylic acid, B is the structure of curcumin, C is the structure of polyethylene glycol, D is the simplified structural formula of the salicylic acid-curcumin polymer formed after thermal polymerization, and E is the simplified structural formula of the PSGC polymer formed after thermal polymerization.

[0068] Figure 2 The Fourier transform infrared (FTIR) spectrum of the PSGC polymer prepared in this invention shows that the sample simultaneously exhibits characteristic peaks of aromatic rings, characteristic peaks of PEG segments, and characteristic peaks of newly generated ester C=O groups.

[0069] Figure 3 The image shows the ¹H NMR spectrum of the PSGC polymer prepared in this invention. As can be seen from the image, the multiple peaks appearing at 6.5-7.75 ppm are attributed to the special absorption peaks on the benzene rings of salicylic acid and curcumin; the peak appearing at around 3.49 ppm is attributed to the polyethylene glycol absorption peak; and the multiple peaks appearing at 4.41-4.64 ppm are attributed to the ester bond peaks.

[0070] Figure 4This is a comparative test chart of the solubility of salicylic acid, curcumin, and PSGC polymer prepared in this invention. As can be seen from the chart, salicylic acid and curcumin have poor solubility in the solvent system, and the system exhibits obvious turbidity or heterogeneity. In contrast, the PSGC polymer prepared in this invention has significantly improved solubility, and the solution transparency and homogeneity are significantly improved. This indicates that the PSGC polymer can effectively enhance the solubilizing / dispersing ability of salicylic acid and curcumin, thus benefiting their application in subsequent formulation development.

[0071] Figure 5 This is a schematic diagram illustrating the therapeutic effect of the PSGC polymer prepared in this invention on a mouse acne model; from Figure 5 In (a), it can be seen that the skin lesions in the mouse acne model show obvious red papular changes; after treatment with PSGC polymer, it can be seen that... Figure 5 In (b), the degree of erythema in the skin lesions was significantly reduced, the size of the papules decreased, and the appearance of inflammation was significantly improved, indicating that the PSGC polymer prepared in this invention has a good alleviating effect and application potential on acne-like skin lesions.

[0072] Example 2 Synthesis method of active formulation PSGC: SA was placed in an oil bath and heated to 160°C under nitrogen protection for 20 minutes until completely melted. Curcumin was then added and stirred continuously until dissolved to form a homogeneous mixture. Polyethylene glycol was then added and stirred continuously until homogeneous. The resulting mixture was placed at 140°C under vacuum for 12 hours to promote polymerization.

[0073] After the reaction, the product was dissolved in deionized water and transferred to a dialysis bag with a molecular weight cutoff of 1000 Da. Dialysis was performed in deionized water for 2–3 days, with the dialysis solution changed periodically to remove unreacted small molecules. After dialysis, the sample was freeze-dried to obtain the target product—poly(salicylic acid-curcumin)-polyethylene glycol-polymer, abbreviated as PSGC. The molar ratio of the three substances was SA:curcumin:PEG = 1:0.3:1.5.

[0074] The obtained PSGC is a yellow paste-like solid with good water dispersibility and stability. It can be used to further prepare various topical formulations for medical or cosmetic purposes, such as sprays, gels, and facial mask sheets.

[0075] Example 3 Synthesis method of active formulation PSGC: SA was placed in an oil bath and heated to 200°C under nitrogen protection for 10 minutes until completely melted. Curcumin was then added and stirred continuously until dissolved to form a homogeneous mixture. Polyethylene glycol was then added and stirred continuously until homogeneous. The resulting mixture was placed at 150°C under vacuum for 5 hours to promote polymerization.

[0076] After the reaction, the product was dissolved in deionized water and transferred to a dialysis bag with a molecular weight cutoff of 1000 Da. Dialysis was performed in deionized water for two days, with the dialysis solution changed periodically to remove unreacted small molecules. After dialysis, the sample was freeze-dried to obtain the target product—poly(salicylic acid-curcumin)-polyethylene glycol copolymer, abbreviated as PSGC. The molar ratio of the three substances was SA:curcumin:PEG = 1:0.8:0.8.

[0077] The obtained PSGC is a yellow paste-like solid with good water dispersibility and stability.

[0078] Example 4 Synthesis method of active formulation PSGC: SA was placed in an oil bath and heated to 180°C under nitrogen protection for 30 minutes until completely melted. Curcumin was then added and stirred continuously until dissolved to form a homogeneous mixture. Polyethylene glycol was then added and stirred continuously until homogeneous. The resulting mixture was placed at 100°C and reacted under vacuum for 24 hours to promote polymerization.

[0079] After the reaction, the product was dissolved in deionized water and transferred to a dialysis bag with a molecular weight cutoff of 1000 Da. Dialysis was performed in deionized water for 3 days, with the dialysis solution changed periodically to remove unreacted small molecules. After dialysis, the sample was freeze-dried to obtain the target product—poly(salicylic acid-curcumin)-polyethylene glycol-polymer, abbreviated as PSGC. The molar ratio of the three substances was SA:curcumin:PEG = 1:0.5:1.0.

[0080] The obtained PSGC is a yellow paste-like solid with good water dispersibility and stability. It can be used to further prepare various topical formulations for medical or cosmetic purposes, such as sprays, gels, and facial mask sheets.

[0081] Example 5 Synthesis method of active formulation PSGC: SA was placed in an oil bath and heated to 160°C under nitrogen protection for 20 minutes until completely melted. Curcumin was then added and stirred continuously until dissolved to form a homogeneous mixture. Polyethylene glycol was then added and stirred continuously until homogeneous. The resulting mixture was placed at 140°C under vacuum for 12 hours to promote polymerization.

[0082] After the reaction, the product was dissolved in deionized water and transferred to a dialysis bag with a molecular weight cutoff of 1000 Da. Dialysis was performed in deionized water for 2–3 days, with the dialysis solution changed periodically to remove unreacted small molecules. After dialysis, the sample was freeze-dried to obtain the target product—poly(salicylic acid-curcumin)-polyethylene glycol copolymer, abbreviated as PSGC. The molar ratio of the three substances was SA:curcumin:PEG = 1:0.8:1.

[0083] The obtained PSGC is a yellow paste-like solid with good water dispersibility and stability. It can be used to further prepare various topical formulations for medical or cosmetic purposes, such as sprays, gels, and facial mask sheets.

[0084] The active formulation PSGC prepared in Examples 1-5 of this invention has the following technical advantages: (1) Natural ingredients, green and environmentally friendly: Each component (salicylic acid, curcumin, polyethylene glycol) is a common pharmaceutical / cosmetic grade raw material with wide sources, high safety, and in line with the concept of green formula; (2) The synthesis process is simple, environmentally friendly and non-toxic: The hot melt polymerization and aqueous purification system is adopted. No organic solvents are introduced in the whole process. The operation is simple, safe and environmentally friendly, and suitable for industrial scale-up. (3) Significant multifunctional synergistic effect: Curcumin has anti-inflammatory and antioxidant properties, salicylic acid has keratolytic and antibacterial effects, and PEG, as a flexible chain segment, gives the system good water solubility and skin permeability. The combination of the three helps to alleviate a variety of skin problems, such as acne, inflammation, and oxidative stress. (4) Suitable for a variety of dosage forms: PSGC polymer has excellent dispersibility and film-forming properties, and is suitable for a variety of skin products such as masks, gels, sprays, lotions, and freeze-dried powders.

[0085] Example 6 (1) Active formulation dressing 1 (facial mask): A piece of non-woven fabric (preferably 20–25 cm in size, for example 24 cm × 21 cm), ensuring it is free of stains and damage. Fold it and place it in an unsealed packaging bag (such as an aluminum foil bag), add a PSGC solution with a concentration of 1 g / 100 mL until the facial mask is completely soaked, leaving a small amount of residual liquid in the bag to form a liquid phase transition layer, and then seal the packaging to obtain the facial mask formulation of the present invention.

[0086] (2) Active formulation dressing 2 (spray type): Dispense a 1 g / 100 mL concentration of PSGC solution (solvent is high-purity water or hot spring water) into a spray bottle or other atomizing container. It can also be compounded with skin conditioning agents such as sodium hyaluronate, butylene glycol, pentylene glycol, and glycerin to enhance moisturizing and repairing functions. This spray can be used for daily spraying, local soothing, and iontophoresis in medical / cosmetic applications.

[0087] (3) Active formulation dressing 3 (gel type): A stable topical gel formulation is prepared by mixing 1 g / 100 mL of the active formulation PSGC of this invention with a gel matrix. The gel matrix is ​​preferably selected from one or more of carbomer, sodium hyaluronate, and xanthan gum. Glycerin, butylene glycol, and other moisturizers, as well as appropriate pH adjusters, can be added as needed to regulate the gel's skin feel, strength, and permeability. The resulting gel has good application properties and skin adhesion, and can be used for cosmetic or medical purposes such as calming, repairing, anti-inflammatory, and anti-acne treatments on the face or body.

[0088] (4) Active formulation dressing 4 (emulsion type): A 1 g / 100 mL concentration of the active formulation PSGC of this invention is used as the aqueous phase and mixed with an emulsion matrix to prepare a stable topical emulsion formulation. The emulsion matrix can be a water-in-oil (O / W) or oil-in-water (W / O) system, preferably a water-in-oil (O / W) emulsion system; wherein the oil phase component is preferably one or more of squalane, jojoba oil, triglycerides (caprylic / capric acid), isopropyl myristate, and petrolatum, and the emulsifier is preferably one or more of polysorbates, PEG emulsifiers, lecithin, cetearyl alcohol and their derivatives. The emulsion system can be further compounded with skin conditioning agents such as sodium hyaluronate, butylene glycol, pentylene glycol, and glycerin, and appropriate amounts of thickeners, pH adjusters and preservatives can be added as needed to improve the stability and skin feel of the emulsion. The resulting emulsion has good spreadability and moisturizing properties, and can be used for daily care of facial or body skin, barrier repair, soothing and anti-inflammatory, anti-acne and other cosmetic or medical purposes.

[0089] Macromolecular active formulations are prone to microbial growth during storage and lack sufficient skin affinity when used directly, affecting safety and comfort. Therefore, the addition of functional auxiliary ingredients is urgently needed. To this end, macromolecular active formulations also contain 0.001–10% (w / w) of preservatives and / or 0.1–10% (w / w) of moisturizing agents. The preservatives are selected from one or more of phenoxyethanol, ethylhexylglycerin, potassium sorbate, a compound of gluconolactone and sodium benzoate, and octanediol. The moisturizing agents are selected from one or more of butylene glycol, pentanediol, and hexanediol. Phenoxyethanol can be selected as a preservative at 0.1% (w / w). This preservative is mild and non-irritating, suitable for topical formulations. Potassium sorbate, etc., can also be selected in practical applications, but this application does not limit this choice. Butanediol can be selected as a moisturizing agent at 5% (w / w), which can improve the skin affinity of the formulation and reduce irritation. Preservatives extend the shelf life of a formulation by inhibiting the growth and reproduction of microorganisms; moisturizing agents improve the compatibility of the formulation with the skin, while replenishing the skin with moisture and enhancing user comfort. The shelf life of the formulation is extended to more than 12 months, skin irritation is significantly reduced during use, and it also has a certain moisturizing effect, improving the user experience.

[0090] Current anti-acne formulations are limited in dosage form, failing to meet the diverse needs of various scenarios in the medical aesthetics field. For example, different dosage forms are required for daily care and post-operative repair. Macromolecular active formulations are used in the preparation of topical products for anti-acne, anti-inflammatory, and skin barrier repair. These products include masks, sprays, gels, and lotions. Masks are suitable for wet compresses, sprays for daily soothing care, gels for localized acne treatment, and lotions for full-face daily care. The preparation of different dosage forms requires the use of corresponding matrix materials to ensure the stability of the active formulation. Macromolecular active formulations are compatible with matrix materials in different dosage forms, allowing for differentiated release of active ingredients through dosage form adjustments to suit different usage scenarios. This broadens the application scope of macromolecular active formulations, meeting the diverse needs of the medical aesthetics field and increasing product market coverage.

[0091] Uneven distribution of active ingredients in a facial mask can lead to significant differences in skin absorption, affecting the efficacy of anti-acne and skin repair. Therefore, it is crucial to define the impregnation content of the active ingredients and the carrier material. This embodiment provides a medical or cosmetic facial mask containing macromolecular active ingredients impregnated in a non-woven fabric matrix at a content of 0.1–10 mg / cm². The non-woven fabric matrix is ​​selected from 25 g / m² medical-grade non-woven fabric, which has good skin affinity and strong adsorption capacity. In practical applications, rayon or other materials can also be used, but this embodiment does not limit the choice. The impregnation content of the active ingredients can be selected as 0.5 mg / cm², achieved through a vacuum impregnation process to ensure uniform distribution of the active ingredients. The non-woven fabric, as a carrier, can evenly carry the active ingredients. During the wet compress process, the active ingredients are slowly released and penetrate deep into the skin, exerting anti-inflammatory, anti-acne, and barrier repair effects. The active ingredients in the mask are evenly distributed, increasing skin absorption efficiency by more than 30%. After use, acne redness and swelling symptoms are significantly relieved, and the skin barrier repair speed is accelerated.

[0092] If the concentration of the active ingredient in a spray formulation is too high or too low, it can lead to either strong skin irritation or insufficient therapeutic effect. Therefore, it is crucial to define a suitable concentration range to balance efficacy and safety. This embodiment provides a spray containing 0.1–10% (w / v) of a macromolecular active ingredient. The concentration of the active ingredient in the spray is selected as 1% (w / v), and the solvent is a mixture of deionized water and glycerin. The glycerin content is 3% (v / v), which enhances the moisturizing properties of the spray. A vacuum pump bottle is used as the spray container because it has good sealing performance and can prevent oxidation of the spray. In practical applications, a press-pump spray bottle can also be used, but this embodiment does not limit this choice. The concentration range of 0.1–10% (w / v) ensures the efficacy of the active ingredient while avoiding skin irritation caused by excessively high concentrations. The atomized spray can evenly cover the skin surface, allowing the active ingredient to penetrate quickly and exert its effect. The spray is convenient to use, the active ingredient is absorbed quickly, and daily use can effectively soothe skin inflammation, reduce the incidence of acne, and has low skin irritation, making it suitable for people with sensitive skin.

[0093] Poor compatibility between the gel matrix and the active formulation can lead to the release of active ingredients, affecting formulation stability and skin feel. Therefore, it is crucial to identify suitable gel matrix materials. This embodiment provides a gel formulation prepared by mixing a macromolecular active formulation with one or more matrices selected from carbomer, sodium hyaluronate, and glycerin. Carbomer 940 can be selected as the gel matrix at an addition amount of 0.5% (w / w). This matrix exhibits good gelling properties and excellent compatibility with the active formulation. In practical applications, sodium hyaluronate, etc., can also be selected, but this embodiment does not limit the choice. A high-speed stirrer is used during mixing at a speed of 1000 r / min to ensure uniform mixing of the matrix and active formulation. The gel matrix can support the active formulation, forming a semi-solid gel structure, prolonging the residence time of the active ingredients on the skin surface and improving penetration. The gel formulation exhibits good stability, with no release of active ingredients after 6 months of storage; it has excellent application properties, a refreshing and non-sticky feel, and can quickly relieve acne inflammation and repair damaged skin barriers when applied topically.

[0094] If the emulsion formulation system is unstable, problems such as layering and release of active ingredients are likely to occur. Furthermore, different emulsion types have significantly different skin feel characteristics, necessitating the clear definition of the emulsion system type and the concentration of the active ingredient. This embodiment provides an emulsion formulation containing a macromolecular active ingredient. The emulsion is an oil-in-water or water-in-oil emulsion system, and the mass concentration of the macromolecular active ingredient in the emulsion is 0.1–10% (w / v). An oil-in-water (O / W) emulsion system is chosen because it has a refreshing feel and is suitable for oily, acne-prone skin. In practical applications, a water-in-water (W / O) system can also be chosen; this embodiment does not limit this choice. The concentration of the active ingredient is selected as 2% (w / v), squalane is used as the oil phase component, and polysorbate 80 is used as the emulsifier to ensure the stability of the emulsion system.

[0095] Emulsion systems can encapsulate active ingredients, enhancing their skin permeability. Oil-in-water or water-in-oil systems cater to different skin types, expanding the range of suitable users. Emulsion formulations exhibit good stability, without layering or crystallization; they spread easily and are readily absorbed after application. Daily use provides multiple benefits including anti-inflammatory, moisturizing, and barrier repair, making them suitable for acne-prone individuals of all skin types.

[0096] It should also be noted that, provided it is feasible and does not significantly deviate from the spirit of the invention, any technical feature or combination of technical features described as a component of a certain technical solution in this specification can also be applied to other technical solutions; furthermore, provided it is feasible and does not significantly deviate from the spirit of the invention, the technical features described as components of different technical solutions can also be combined in any manner to constitute other technical solutions. The invention also includes technical solutions obtained through combinations under the above circumstances, and these technical solutions are equivalent to those described in this specification.

[0097] The present invention has been described above through specific embodiments and examples. However, those skilled in the art should understand that these are not intended to limit the scope of the present invention, which should be determined by the claims.

[0098] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A method for preparing a macromolecular active preparation containing natural active ingredients, characterized in that, Includes the following steps: Salicylic acid was heated to a molten state under a protective atmosphere, curcumin was added to dissolve it, and then polyethylene glycol was added to carry out a thermal polymerization reaction to obtain a poly(salicylic acid-curcumin)-polyethylene glycol polymer. The poly(salicylic acid-curcumin)-polyethylene glycol polymer was dissolved in deionized water and purified by dialyzing to obtain a macromolecular active preparation with natural active ingredients.

2. The method for preparing a macromolecular active preparation with natural active ingredients according to claim 1, characterized in that, The salicylic acid is heated in a nitrogen atmosphere at a temperature of 160-200℃ for 10-50 minutes.

3. The method for preparing a macromolecular active preparation with natural active ingredients according to claim 1, characterized in that, After adding curcumin and polyethylene glycol, the reaction system temperature is 100-150℃, and the reaction time is 5-24 hours.

4. The method for preparing a macromolecular active preparation with natural active ingredients according to claim 3, characterized in that, The reaction system was kept under a vacuum of 0.08-0.1 MPa and stirred at a speed of 150-250 r / min.

5. The method for preparing a macromolecular active preparation with natural active ingredients according to claim 1, characterized in that, The poly(salicylic acid-curcumin)-polyethylene glycol polymer was dissolved in deionized water and purified by dialyzing, specifically including: After the thermal polymerization reaction is complete, dialyze the polymer for 2-3 days using a dialysis bag with a molecular weight cutoff of 500-3500 Da. Then freeze-dry the dialyzed poly(salicylic acid-curcumin)-polyethylene glycol polymer and store it in a refrigerator.

6. The method for preparing a macromolecular active preparation with natural active ingredients according to claim 4, characterized in that, Set the refrigerator temperature to the refrigeration range of 2-8℃, and store the poly(salicylic acid-curcumin)-polyethylene glycol polymer in a vacuum bag after sealing.

7. The method for preparing a macromolecular active preparation with natural active ingredients according to claim 1, characterized in that, The molar ratio of salicylic acid, curcumin and polyethylene glycol is 1:(0.3–0.8):(0.8–1.5).

8. A macromolecular active preparation containing natural active ingredients, characterized in that, The macromolecular active preparation containing natural active ingredients, obtained by the preparation method according to any one of claims 1 to 7, has the following structural formula: The value of n ranges from 2 to 200.

9. The macromolecular active preparation with natural active ingredients according to claim 8, characterized in that, The macromolecular active formulation further comprises, by weight percentage, 0.001–10% of a preservative and / or 0.1–10% of a moisturizing agent; the preservative is selected from one or more of phenoxyethanol, ethylhexylglycerin, potassium sorbate, a compound of gluconolactone and sodium benzoate, and octanediol; the moisturizing agent is selected from one or more of butylene glycol, pentanediol, and hexanediol.

10. The application of a macromolecular active preparation containing natural active ingredients, employing the macromolecular active preparation containing natural active ingredients as described in claim 8 or 9, characterized in that, Application in the preparation of topical products for anti-acne, anti-inflammatory and skin barrier repair; the topical products include masks, sprays, gels and lotions; The active agent is impregnated in the nonwoven fabric matrix at a concentration of 0.1–10 mg / cm². The spray contains 0.1–10% of the macromolecular active agent by weight percentage; The gel formulation is prepared by mixing the macromolecular active formulation with one or more matrices selected from carbomer, sodium hyaluronate, and glycerin. The emulsion formulation contains the macromolecular active agent, the emulsion is a water-in-oil or oil-in-water emulsion system, and the mass concentration of the macromolecular active agent in the emulsion is 0.1–10%.

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