Preparation process of multi-target whitening compound based on molecular self-assembly and application of multi-target whitening compound in cosmetics

Abstract

The invention belongs to the technical field of cosmetics, and particularly relates to a preparation process of a multi-target whitening compound based on molecular self-assembly and application of the multi-target whitening compound in cosmetics. According to the invention, ergothioneine, pterostilbene, hexylresorcinol and SDL chromene are integrated in a deep eutectic solvent system through a molecular self-assembly technology, so that the extreme environment stability breakthrough is realized, the skin care requirements of whitening, aging resistance and oxidation resistance are met, multiple effects are integrated, and the skin care process is simplified.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, and in particular relates to a preparation process of a multi-target whitening complex based on molecular self-assembly and its application in cosmetics. Background Art

[0002] As people's living standards improve, their demand for skin health and beauty continues to grow. Whitening, anti-aging, antioxidants, and skin repair have become popular research areas in the skincare field. In their pursuit of beauty, consumers desire products that can simultaneously address multiple skin concerns, simplifying their skincare routine and improving their effectiveness.

[0003] Deep eutectic solvents, a novel green solvent, have recently gained increasing attention in the skincare field. These low-melting-point mixtures, formed by interactions between two or more substances through hydrogen bonding and van der Waals forces, offer advantages such as low melting point, wide availability, strong dissolving power, low toxicity, good thermal stability, and biodegradability. Their unique physicochemical properties, such as low melting point, high solubility, and good biocompatibility, offer new insights and avenues for the development of skincare products. However, the current application of deep eutectic solvents in skincare products still faces several challenges. For one thing, existing applications of deep eutectic solvents focus on achieving a single benefit, such as whitening or anti-aging. However, skin problems are often complex and diverse, and a single ingredient cannot meet the diverse needs of the skin, lacking the synergistic benefits of multiple benefits. For example, a single whitening ingredient may not be able to simultaneously address skin aging and oxidative damage, whereas skin health requires a comprehensive consideration of multiple factors. Furthermore, some deep eutectic solvents exhibit poor stability at low temperatures or during long-term storage, prone to phase separation or crystallization, causing the solvent to revert from liquid to solid. This not only affects the appearance and user experience of the product, but may also lead to the inactivation of active ingredients, reduce the efficacy of the product, and severely limit its widespread application in skin care products.

[0004] Among the many skincare ingredients, ergothioneine, hexylresorcinol, and pterostilbene all possess unique skincare benefits. Ergothioneine is a powerful antioxidant that effectively scavenges free radicals, repairs DNA damage, and slows skin aging. It plays a crucial antioxidant role within human cells, protecting the skin from free radical damage caused by factors like ultraviolet rays and environmental pollution, thereby maintaining normal skin cell metabolism and function. Pterostilbene possesses antioxidant, anti-inflammatory, and anti-ultraviolet properties, reducing oxidative stress damage to the skin and slowing skin aging. It can inhibit inflammatory responses, alleviating symptoms like redness, swelling, and pain, while also resisting UV damage to the skin and preventing photoaging. Hexylresorcinol significantly whitens and reduces melanin production by inhibiting tyrosinase activity. Tyrosinase is a key enzyme in melanin synthesis, and inhibiting its activity can reduce melanin production at the source, thereby achieving the goal of whitening. For example, Chinese patent publication number CN118477012 A discloses an anti-wrinkle and firming composition containing collagen and its application in cosmetics. The composition includes bosacein, pterostilbene, soluble collagen, ergothioneine, palmitoyl tripeptide-5 and an appropriate amount of solvent component.

[0005] However, preparing deep eutectic solvents from ergothioneine, pterostilbene, and hexylresorcinol presents challenges. This is due to the difficulty in forming deep eutectic solutions from these three components, as well as the tendency of these solutions to revert to a solid state or precipitate solids, resulting in poor stability, which limits their application in skincare products. Therefore, developing a highly stable deep eutectic solvent that can fully exploit the synergistic effects is crucial for meeting market demand for highly effective whitening, anti-aging, and skin repair products. Summary of the Invention

[0006] The present invention provides a multi-target whitening complex based on molecular self-assembly and its preparation process, which solves the problems of poor stability and single efficacy of deep eutectic solvents in the prior art through the following innovative designs: 1. Ternary active component synergistic system: (1) The present invention utilizes three effective ingredients, namely ergothioneine (antioxidant / anti-aging), pterostilbene (anti-inflammatory / anti-ultraviolet), and hexylresorcinol (whitening), to achieve synergistic enhancement of the three pathways of antioxidant, anti-inflammatory, and whitening by regulating the molar ratio of 1:1 to 1:5.

[0007] (2) Since it is difficult for the three components to form a deep eutectic solution, the deep eutectic solution has poor stability after formation and is easy to return to a solid state or solid precipitation. Therefore, the present invention reduces the surface tension of the deep eutectic solvent by adding SDL (a complex of sucrose dilaurate and sucrose laurate, provided by Procter & Gamble's raw material supplier), inhibits the aggregation of active ingredients, and enhances low-temperature stability and transdermal absorption efficiency. It should be noted that the present invention tried nearly 20 types of surfactants, including sodium lauryl sulfate, sodium lauryl ether sulfate, sodium alkyl alcohol polyether sulfate, octylphenoxyethanol, octyl / decyl glucoside, sodium lauryl sulfate, diethyl succinamide, sodium cocoyl glutamate, cocamide, sodium cocoyl lactylate, polyvinyl alcohol, polysorbate-20, polysorbate-80, lauramidopropyl betaine, PEG-40 hydrogenated castor oil, fatty alcohol polyether, olefin-20, and lauryl glucoside. The best effect could only adjust the stability of the complex to -5°C~-10°C for 48 hours without solid precipitation, and could not achieve the effect of the complex of the present invention remaining liquid and without precipitation for more than 336 hours under a -20°C environment.

[0008] 2. Solvent system optimization: The present invention utilizes propylene glycol-glycerol-water (volume ratio 0.5-1.5:1-3:3-5) to form a flexible network through multiple hydrogen bonds, and combines it with a gradient heating process to promote orderly molecular self-assembly, thereby improving stability in extreme environments (-20°C).

[0009] 3. Gradient temperature control process: The present invention utilizes stage-controlled temperature heating (50-80°C gradient) combined with a static activation step (30-40°C) for step-by-step regulation to form a "rigid skeleton-flexible buffer" composite structure, effectively inhibiting phase separation and improving the stability of the composite.

[0010] 4. Application scalability: The complex of the present invention can be added to skin care products such as creams, essences, and masks (0.5% to 5% w / w), meeting skin care needs in multiple scenarios and having commercial value.

[0011] Compared with the prior art, the technical effects of the present invention are: (1) The multi-target whitening complex based on molecular self-assembly of the present invention achieves a breakthrough in extreme environmental stability, including low temperature tolerance and long-term storage stability.

[0012] (2) The breakthrough in the stability of the composite of the present invention in extreme environments is inseparable from process innovation, including the influence of unique gradient heating temperature control and static activation temperature, and is also inseparable from the selection of solvent system.

[0013] (3) The present invention integrates ergothioneine, pterostilbene, hexylresorcinol and SDL chromatin into a deep eutectic solvent system for the first time through molecular self-assembly technology, which simultaneously meets the skin care needs of whitening, anti-aging and anti-oxidation, combines multiple effects into one, and simplifies the skin care process. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 : Appearance of the composite of Example 1 (left), the composite of Comparative Example 1 (middle), and the composite of Group E (right) after being stored at -20°C for 336 h.

[0015] Figure 2 : DPPH free radical scavenging rate, tyrosinase inhibition rate. DETAILED DESCRIPTION

[0016] In order to make the purpose and technical solution of the present invention more clear, the present invention is further described below in conjunction with the embodiments, but the scope of protection of the present invention is not limited to these embodiments, and the embodiments are only used to illustrate the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the scope of protection of the present invention.

[0017] Example 1 formula: Ergothioneine 0.5 mmol, pterostilbene 1.0 mmol (molar ratio 1:2), hexylresorcinol 0.3 g (accounting for 0.1% of the total mass of the solvent), SDL selenite 0.5 g (accounting for 0.5% of the total mass of the solvent), the solvent is a mixture of propylene glycol, glycerol, and water in a volume ratio of 0.5:1:3 (total amount 100 g).

[0018] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent, add hexylresorcinol, and let stand at 30°C for 1 hour; (2) Add SDL and stir continuously at 200 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 50°C, stirring for 1 hour; temperature 60°C, stirring for 1 hour; temperature 40°C, stirring for 1 hour; temperature 70°C, stirring for 1 hour; (4) Cool to 25°C and filter to obtain the product.

[0019] Example 2 formula: Ergothioneine 0.2 mmol, pterostilbene 1.0 mmol (molar ratio 1:5), hexylresorcinol 0.1 g (0.3%), SDL chromatin 0.5 g (2.0%), the solvent is a mixture of propylene glycol, glycerol, and water in a ratio of 1:2:4.

[0020] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent, add hexylresorcinol, and let stand at 35°C for 2 hours; (2) Add SDL and continue stirring at 350 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 55°C, stirring for 2 h; temperature 65°C, stirring for 2 h; temperature 45°C, stirring for 2 h; temperature 75°C, stirring for 2 h; (4) Cool to 25°C and filter to obtain the product.

[0021] Example 3 formula: Ergothioneine 0.3 mmol, pterostilbene 0.3 mmol (molar ratio 1:1), hexylresorcinol 0.5 g (0.5%), SDL chromatin 5 g (5%), the solvent is a mixture of propylene glycol, glycerol and water in a ratio of 1.5:3:5.

[0022] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a mixed solvent, add hexylresorcinol, and let stand at 40°C for 3 hours; (2) Add SDL and continue stirring at 500 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 60°C, stirring for 3 h; temperature 70°C, stirring for 3 h; temperature 50°C, stirring for 3 h; temperature 80°C, stirring for 3 h; (4) Cool to 25°C and filter to obtain the product.

[0023] Example 4 Essence Formula: 2.5% of the complex of Example 1, 6% of propylene glycol, 1.0% of trehalose, 0.5% of carbomer, 1.0% of sodium hyaluronate, 0.2% of triethanolamine, 0.02% of sodium methylparaben, and the balance of purified water. Prepare according to conventional methods.

[0024] Example 5 Cream Formula: 5.0% of the complex of Example 1, sodium hyaluronate, glycerin, polydimethylsiloxane, trehalose, cetearyl alcohol, white petrolatum, carbomer, phenoxyethanol, triethanolamine, sodium methylparaben, and purified water are prepared according to conventional methods.

[0025] Example 6 Facial Mask Formula: 0.1% of the complex of Example 1, 0.5%-2% of sodium hyaluronate, 0.05%-0.35% of trehalose, 0.02%-0.35% of glycerol, 0.02% of sodium methylparaben, purified water, and non-woven fabric.

[0026] Comparative Example 1 formula: 0.5 mmol of ergothioneine, 1.0 mmol of pterostilbene (molar ratio 1:2), 0.3 g of hexylresorcinol (0.3% of the total mass of the solvent), and the solvent is a mixture of propylene glycol, glycerol, and water in a volume ratio of 1:2:4 (total amount 100 g).

[0027] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent, add hexylresorcinol, and let stand at 35°C for 2 hours; (2) The solution in step (1) was heated in a gradient manner: temperature 55°C, stirring for 2 h; temperature 65°C, stirring for 2 h; temperature 45°C, stirring for 2 h; temperature 75°C, stirring for 2 h; (4) Cool to 25°C and filter to obtain the product.

[0028] Comparative Example 2 formula: Ergothioneine 0.5 mmol, pterostilbene 1.0 mmol (molar ratio 1:2), hexylresorcinol 0.3 g (accounting for 0.3% of the total mass of the solvent), SDL selenite 1.5 g (accounting for 1.5% of the total mass of the solvent), the solvent is a mixture of ethanol, glycerol and water in a volume ratio of 1:2:4 (total amount 100 g).

[0029] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent, add hexylresorcinol, and let stand at 35°C for 2 hours; (2) Add SDL and continue stirring at 350 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 55°C, stirring for 2 h; temperature 65°C, stirring for 2 h; temperature 45°C, stirring for 2 h; temperature 75°C, stirring for 2 h; (4) Cool to 25°C and filter to obtain the product.

[0030] Comparative Example 3 formula: Ergothioneine 0.5 mmol, pterostilbene 1.0 mmol (molar ratio 1:2), hexylresorcinol 0.3 g (accounting for 0.3% of the total mass of the solvent), SDL chromatin 1.5 g (accounting for 1.5% of the total mass of the solvent), the solvent is a mixture of propylene glycol, glycerol, and water in a volume ratio of 1:2:4 (total amount 100 g).

[0031] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent, add hexylresorcinol, and let stand at 25°C for 2 hours; (2) Add SDL and continue stirring at 350 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 55°C, stirring for 2 h; temperature 65°C, stirring for 2 h; temperature 45°C, stirring for 2 h; temperature 75°C, stirring for 2 h; (4) Cool to 25°C and filter to obtain the product.

[0032] Comparative Example 4 formula: Ergothioneine 0.5 mmol, pterostilbene 1.0 mmol (molar ratio 1:2), hexylresorcinol 0.3 g (accounting for 0.3% of the total mass of the solvent), SDL chromatin 1.5 g (accounting for 1.5% of the total mass of the solvent), the solvent is a mixture of propylene glycol, glycerol, and water in a volume ratio of 1:2:4 (total amount 100 g).

[0033] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent and add hexylresorcinol; (2) Add SDL and continue stirring at 350 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 55°C, stirring for 2 h; temperature 65°C, stirring for 2 h; temperature 45°C, stirring for 2 h; temperature 75°C, stirring for 2 h; (4) Cool to 25°C and filter to obtain the product.

[0034] Comparative Example 5 formula: Ergothioneine 0.5 mmol, pterostilbene 1.0 mmol (molar ratio 1:2), hexylresorcinol 0.3 g (accounting for 0.3% of the total mass of the solvent), SDL chromatin 1.5 g (accounting for 1.5% of the total mass of the solvent), the solvent is a mixture of propylene glycol, glycerol, and water in a volume ratio of 1:2:4 (total amount 100 g).

[0035] Preparation method: (1) Dissolve ergothioneine and pterostilbene in a solvent, add hexylresorcinol, and let stand at 10°C for 2 hours; (2) Add SDL and continue stirring at 350 rpm for 30 min; (3) The solution in step (2) was heated in a gradient manner: temperature 55°C, stirring for 2 h; temperature 65°C, stirring for 2 h; temperature 45°C, stirring for 2 h; temperature 75°C, stirring for 2 h; (4) Cool to 25°C and filter to obtain the product.

[0036] Stability of Examples and Comparative Examples The composites of Examples 1 to 3 and Comparative Examples 1 to 5 were stored at 30° C. Samples were taken at 6 h, 12 h, 24 h, 48 h, 168 h, and 336 h to observe whether solids were precipitated and their fluidity.

[0037] Table 1 Stability of the composites of Examples 1-3 and Comparative Examples 1-5 at 30°C The composites of Examples 1 to 3 and Comparative Examples 1 to 5 were stored in an environment at 10° C. Samples were taken at 6 h, 12 h, 24 h, 48 h, 168 h, and 336 h to observe whether solids were precipitated and the fluidity.

[0038] Table 2 Stability of the composites of Examples 1-3 and Comparative Examples 1-5 at 10°C The composites of Examples 1 to 3 and Comparative Examples 1 to 5 were stored at -10°C, and samples were taken at 6h, 12h, 24h, 48h, 168h, and 336h to observe whether solids were precipitated and the fluidity.

[0039] Table 3 Stability of the composites of Examples 1 to 3 and Comparative Examples 1 to 5 at -10°C The composites of Examples 1 to 3 and Comparative Examples 1 to 5 were stored at -20°C, and samples were taken at 6h, 12h, 24h, 48h, 168h, and 336h to observe whether solids were precipitated and the fluidity.

[0040] Table 4 Stability of the composites of Examples 1 to 3 and Comparative Examples 1 to 5 at -20°C Tables 1 to 4 show the environmental stability at 30°C, 10°C, -10°C, and -25°C, respectively. Examples 1 to 3 all remained transparent liquids during the test, with no solid precipitation, and were able to maintain good fluidity, indicating that the complex of the present invention has excellent stability. First, SDL can reduce the interfacial tension of the deep eutectic system through surface activity, inhibit component aggregation and phase separation, and enhance low-temperature stability to prevent the destruction of the hydrogen bond network at extreme temperatures. Secondly, the propylene glycol-glycerol-water system forms a stable deep eutectic network through multiple hydrogen bonds (which can be compared with Comparative Example 2, which crystallizes at low temperatures and has a poor mobile phase). Finally, the 30-40°C pre-standing design can optimize molecular pre-arrangement and improve low-temperature stability.

[0041] Effect of gradient temperature control steps on the stability of the complex To demonstrate the effect of the gradient temperature control step on the stability of the complex, the R&D data was organized into a clearer single-factor comparative experiment. Based on the formulation and preparation method of the complex in Example 2, the control variables were the parameters of the gradient temperature increase step as follows: A: 50°C, stir for 8 hours.

[0042] B: 60℃, stir for 8h.

[0043] C: 70℃, stir for 8h.

[0044] D: Temperature 55°C, stirring for 2 hours; temperature 65°C, stirring for 2 hours; temperature 75°C, stirring for 2 hours.

[0045] E: Temperature 45°C, stirring for 2 hours; temperature 55°C, stirring for 2 hours; temperature 65°C, stirring for 2 hours; temperature 75°C, stirring for 2 hours.

[0046] F: Temperature 45℃, stirring for 4h; temperature 75℃, stirring for 4h.

[0047] The prepared A~F composites were stored at 30°C, 10°C, -10°C, and -25°C. Samples were taken at 6h, 12h, 24h, 48h, 168h, and 336h to observe whether solid precipitation and fluidity were observed. Only partial data are shown here.

[0048] Table 5 Stability of complexes A~F at -20℃ Table 5 demonstrates that a single temperature or simple gradient (e.g., D-F) cannot achieve multi-level molecular self-assembly. The stability advantage of Example 2 lies in the flexible framework formed by gradient temperature control, which inhibits low-temperature phase separation. In particular, cooling at 45°C ± 5°C induces flexible folding of the molecular chains, forming a structure resistant to low-temperature deformation. This provides elastic space for the molecular structure and resists low-temperature shrinkage and deformation. Furthermore, the stability of the complexes in groups A-F at 30°C, 10°C, and -10°C is far inferior to that of the complexes in Examples 1-3. Since the experimental data at -20°C are the most representative, only a subset of the data is presented here.

[0049] DPPH free radical scavenging rate DPPH (1,1-diphenyl-2-trinitrophenylhydrazine) is a stable free radical commonly used to evaluate the free radical scavenging ability of antioxidants. Prepare a 0.1 mM DPPH ethanol solution. Dilute the sample solution to 2 mg / mL with ethanol and mix with an equal volume of the DPPH solution. Incubate the mixture at room temperature in the dark for 30 minutes. Measure absorbance at 517 nm using a UV-visible spectrophotometer. Use vitamin E as a positive control.

[0050] Tyrosinase inhibition rate Examples 1 to 3, Comparative Example 1, and nicotinamide (positive control) were used as test products, and measurements and calculations were performed according to the method in CN110721134A.

[0051] Table 6 DPPH free radical scavenging rate and tyrosinase inhibition rate Table 6 Figure 2 The results show that the DPPH free radical scavenging rates of Examples 1 to 3 are significantly better than those of the positive control group, indicating that the synergistic antioxidant effect of ergothioneine, pterostilbene, and hexylresorcinol is significantly improved. The clearance rate of Comparative Example 1 is 85.36%, which is higher than vitamin E, but significantly lower than that of the embodiment (the difference is about 8%), proving that SDL Sedanlin enables the active ingredient to act more efficiently on free radical scavenging by enhancing permeability. Ergothioneine scavenges free radicals to protect melanocyte DNA, pterostilbene inhibits oxidative stress inflammation, and hexylresorcinol blocks melanin synthesis, forming an ergothioneine-pterostilbene-hexylresorcinol ternary system, which achieves the best balance between anti-oxidation and whitening through the "defense-blocking" dual pathway.

Claims

1. A multi-target whitening complex based on molecular self-assembly, characterized in that: The composition ratio of the complex components is as follows: the molar ratio of ergothioneine to pterostilbene is 1:1-1:5, hexylresorcinol accounts for 0.1%-0.5% of the total mass of the solvent, and SDL chromophore accounts for 0.5%-5% of the total mass of the solvent. The complex is formed by gradient heating self-assembly.

2. The composite according to claim 1, characterized in that The solvent is a combination of propylene glycol, glycerin and water.

3. The composite according to claim 1, characterized in that The molar ratio of ergothioneine to pterostilbene is 1:2, hexylresorcinol accounts for 0.3% of the total mass of the solvent, and SDL chromophore accounts for 1.5% of the total mass of the solvent.

4. The composite according to claim 1, characterized in that The solvent is propylene glycol, glycerin and water in a volume ratio of 0.5-1.5:1-3:3-5.

5. The composite according to claim 1, characterized in that The preparation method of the composite is as follows: a. Dissolve ergothioneine and pterostilbene in solvent, add hexylresorcinol, and let stand at 30-40℃ for 1-3 hours. b. Add SDL color light forest and continue stirring, c. Heat gradually at 40-80℃ and maintain stirring for 4-12 hours. d. After cooling, filter and remove impurities to obtain the product.

6. The composite according to claim 1 or 5, characterized in that The gradient heating in step c is as follows: temperature 50-60°C, stirring for 1-3 hours; temperature 60-70°C, stirring for 1-3 hours; temperature 40-50°C, stirring for 1-3 hours; temperature 70-80°C, stirring for 1-3 hours.

7. The composite according to claim 5, characterized in that The stirring rate in step b is 200-500 rpm.

8. The composite according to claim 1, characterized in that The complex remains liquid at -20°C without precipitation.

9. Use of the complex according to claim 1 in preparing a skin care product, characterized in that: The skin care products include facial cream, essence, facial mask, lotion and toner.

10. The use according to claim 9, characterized in that The addition amount of the compound is 0.5% to 5%.

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