Self-assembled complex of centella asiatica active and its preparation method and application

Abstract

The application discloses a centella asiatica active self-assembled compound, a preparation method thereof and application thereof in cosmetics, and belongs to the technical field of cosmetics. The centella asiatica active self-assembled compound is formed by supramolecular self-assembly of a centella asiatica triterpene active ingredient and curcumin and / or tetrahydrocurcumin, wherein the centella asiatica triterpene active ingredient is selected from one or more of centella asiatica acid, hydroxyl centella asiatica acid, asiaticoside and hydroxyl asiaticoside, and the curcumin compound is curcumin and / or tetrahydrocurcumin. The application has the effects of soothing, anti-inflammation, redness fading, promoting collagen synthesis, antioxidation and / or repairing skin barrier, and effectively solves the technical problems of poor solubility, insufficient stability and low transdermal absorption rate of the centella asiatica active ingredient, and has a significant industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic technology, specifically relating to a self-assembled complex of Centella asiatica active ingredients, its preparation method, and its application. Background Technology

[0002] Centella asiatica ( Centella asiatica As a highly regarded source of plant-based active ingredients in dermatology, the core pharmacological effects of asiatic acid are primarily attributed to the synergistic effects of triterpenoid compounds. These active ingredients are mainly divided into two categories: aglycones (including asiatic acid and hydroxyasiatic acid) and glycosides (including asiaticoside and hydroxyasiaticoside). In terms of efficacy, glycosides (asiaticoside and hydroxyasiaticoside) mainly play a role in "repair and regeneration." Asiaticoside can significantly promote fibroblast proliferation and activate the SMAD signaling pathway, thereby inducing the biosynthesis of type I and type III collagen, which is crucial for repairing photoaging damage and reducing fine lines. Hydroxyasiaticoside exhibits stronger anti-inflammatory activity, inhibiting the release of inflammatory mediators and accelerating wound healing. In contrast, aglycones (asiatic acid and hydroxyasiatic acid) have smaller molecular weights and focus more on "defense and regulation." Centella asiatica acid possesses broad-spectrum antibacterial properties, capable of disrupting bacterial cell walls and inhibiting Propionibacterium acnes. Simultaneously, all four components exhibit significant antioxidant activity, scavenging free radicals and inhibiting lipid peroxidation, thereby protecting the integrity of cell membrane structures. These four molecules, through different signaling pathways, collectively construct a three-dimensional skincare network from epidermal anti-inflammatory to dermal remodeling. However, Centella asiatica extract faces several limitations in practical applications due to its physicochemical properties. Firstly, the difference in solubility limits its formulation. Glycosides, containing hydrophilic sugar chains, are readily soluble in water and alcohol; while aglycones (centella asiatica acid, hydroxycentella asiatica acid) are lipid-soluble and poorly soluble in water. This "polarity split" makes it difficult to simultaneously add high concentrations of the full-spectrum extract without using large amounts of solubilizers when developing water-based serums or toners, often sacrificing the product's texture or causing turbidity. The most critical application challenge lies in its permeability. Asiaticoside and hydroxyasiaticoside have large molecular weights (usually greater than 900 Da) and are highly hydrophilic, making it difficult for them to penetrate the stratum corneum barrier, which is mainly composed of lipids, resulting in low bioavailability. Although asiatic acid has a smaller molecular weight and some transdermal ability, overall, the active ingredients of Centella asiatica tend to remain on the skin surface.

[0003] Supramolecular chemistry mainly discusses how multiple molecules are associated by means of non-covalent bonds and other weak interaction forces, and is a science focusing on intermolecular interactions. In this field, supramolecular self-assembly refers to the spontaneous combination of molecules into well-defined and stable aggregates under thermodynamic equilibrium conditions through weak forces such as hydrogen bonds, van der Waals forces, pi-pi stacking, halogen bonds, cation-pi and CH-pi interactions, ionic bonds and solvation effects. These assemblies often exhibit rich morphologies such as micelles, liposomes, vesicles, nanotubes or helical ribbons, and have become one of the core hotspots in the research of contemporary drug delivery systems. SUMMARY

[0004] The present application aims to solve the problems of formulation limitations, insufficient storage stability and low transdermal absorption rate caused by poor solubility of active ingredients of Centella asiatica in cosmetic applications in the prior art, and provides a Centella asiatica active substance self-assembly complex. The stable nanoscale complex is formed by supramolecular self-assembly technology of Centella asiatica triterpenoid active ingredients and curcumin and / or tetrahydrocurcumin compounds, thereby synergistically solving the three application problems of solubility, stability and permeability.

[0005] Another object of the present application is to provide a preparation method of the above-mentioned Centella asiatica active substance self-assembly complex.

[0006] Still another object of the present application is to provide the application of the above-mentioned Centella asiatica active substance self-assembly complex in cosmetics.

[0007] To achieve the above-mentioned objects, the present application adopts the following technical solutions: A Centella asiatica active substance self-assembly complex is a nanoscale aggregate formed by non-covalent bond interaction self-assembly of Centella asiatica triterpenoid active ingredients and curcumin compounds. The Centella asiatica triterpenoid active ingredients are selected from one or more of Asiatic Acid (CAS No. 464-92-6), Madecassic Acid (CAS No. 18449-41-7), Asiaticoside (CAS No. 16830-15-2) and Madecassoside (CAS No. 34540-22-2). The curcumin compound is curcumin (CAS No. 458-37-7) and / or tetrahydrocurcumin (CAS No. 36062-04-1).

[0008] In the self-assembly system, the curcumin compound acts as a molecular bridging agent to form stable nanoscale aggregates with the asiaticoside active ingredient through hydrogen bonds, van der Waals forces, π-π stacking and hydrophobic interactions and other non-covalent bond forces.

[0009] Preferably, the molar ratio of the asiaticoside active ingredient to the curcumin compound is 1:(0.99-1.01), more preferably 1:1.

[0010] Preferably, the non-covalent bond interaction includes one or more of hydrogen bonds, van der Waals forces, π-π stacking and hydrophobic interactions.

[0011] Preferably, in the asiaticoside active self-assembly complex, the asiaticoside active is asiatic acid, and the curcumin compound is curcumin; or the asiaticoside active ingredient is hydroxyl asiatic acid, and the curcumin compound is curcumin; or the asiaticoside active ingredient is asiaticoside, and the curcumin compound is curcumin; or the asiaticoside active ingredient is hydroxyl asiaticoside, and the curcumin compound is curcumin; or the asiaticoside active ingredient is asiatic acid, and the curcumin compound is tetrahydrocurcumin; or the asiaticoside active ingredient is hydroxyl asiatic acid, and the curcumin compound is tetrahydrocurcumin; or the asiaticoside active ingredient is asiaticoside, and the curcumin compound is tetrahydrocurcumin; or the asiaticoside active ingredient is hydroxyl asiaticoside, and the curcumin compound is tetrahydrocurcumin.

[0012] In another aspect, the present application also provides a method for preparing the asiaticoside active self-assembly complex, which comprises the following steps: S1, dissolving the asiaticoside active ingredient in a first aqueous ethanol solution as phase A; S2, dissolving the curcumin compound in a second aqueous ethanol solution as phase B; S3, mixing the A phase and the B phase, and performing a supramolecular self-assembly reaction under ultrasonic conditions, and collecting the mixed solution; S4, drying the mixed solution after removing the solvent to obtain the asiaticoside active self-assembly complex.

[0013] Preferably, the volume concentration of the first aqueous ethanol solution is 40%-60%, more preferably 50%; and the volume concentration of the second aqueous ethanol solution is 90%-100%, more preferably 95%.

[0014] Preferably, the concentration of the asiatic acid in the A phase is 4.0-4.2 mmol / L, more preferably 4.1 mmol / L; the concentration of the curcuminoids in the B phase is 4.0-4.2 mmol / L, more preferably 4.1 mmol / L.

[0015] Preferably, in step S3, the flow rate of the A phase and the B phase into the ultrasonic microfluidic device is independently 5 mL / min-15 mL / min, preferably 10 mL / min; the ultrasonic frequency is 2-20 kHz, preferably 6 kHz; the temperature is 25-45 ℃, preferably 35 ℃.

[0016] Preferably, in step S4, the solvent removal method is evaporation under reduced pressure, the temperature is 30-40 ℃, more preferably 35 ℃; the drying method is freeze-drying, the freeze-drying temperature is -70 ℃ to -90 ℃, preferably -80 ℃, and the time is 20 h-30 h, preferably 24 h.

[0017] In another aspect, the present application also provides the use of the asiatic acid active self-assembly complex in the preparation of cosmetics for soothing, anti-inflammatory, redness reduction, collagen synthesis promotion, antioxidant and / or skin barrier repair.

[0018] Preferably, the addition amount of the asiatic acid active self-assembly complex in the cosmetics is 0.01%-5% by mass, more preferably 0.05%-1%.

[0019] Preferably, the dosage form of the cosmetics includes but is not limited to one of a cream, an essence, a lotion, a toner, a mask or a gel. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 Molecular dynamics simulation of asiatic acid and curcumin.

[0021] Figure 2 Molecular dynamics simulation of hydroxyasiatic acid and curcumin.

[0022] Figure 3 Molecular dynamics simulation of asiaticoside and curcumin.

[0023] Figure 4 Molecular dynamics simulation of hydroxyasiaticoside and curcumin.

[0024] Figure 5 Molecular dynamics simulation of asiatic acid and tetrahydrocurcumin.

[0025] Figure 6 Molecular dynamics simulation of hydroxyasiatic acid and tetrahydrocurcumin.

[0026] Figure 7 Molecular dynamics simulations of asiaticoside and tetrahydrocurcumin are shown.

[0027] Figure 8 Molecular dynamics simulations of hydroxyasiaticoside and tetrahydrocurcumin are shown. Detailed Implementation

[0028] To facilitate understanding of the present invention, a more complete description will be given below with reference to specific embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the present invention.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0030] Unless otherwise specified, the experimental methods used in the following examples and comparative examples are conventional methods; the materials and reagents used are commercially available or can be obtained by existing known methods unless otherwise specified.

[0031] Example 1 1) Dissolve 0.2g of asiatic acid in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of curcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0032] Example 2 1) Dissolve 0.208 g of asiatic acid in 100 mL of 50% (v / v) ethanol to form phase A; 2) Dissolve 0.152 g of curcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0033] Example 3 1) Dissolve 0.392g of asiaticoside in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of curcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0034] Example 4 1) Dissolve 0.4g of asiaticoside in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of curcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0035] Example 5 1) Dissolve 0.2g of asiatic acid in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of tetrahydrocurcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0036] Example 6 1) Dissolve 0.208 g of asiatic acid in 100 mL of 50% (v / v) ethanol to form phase A; 2) Dissolve 0.152 g of tetrahydrocurcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0037] Example 7 1) Dissolve 0.392g of asiaticoside in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of tetrahydrocurcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0038] Example 8 1) Dissolve 0.4g of asiaticoside in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of tetrahydrocurcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Phase A and Phase B were introduced into an ultrasonic microfluidic device at a flow rate of 10 mL / min. The ultrasonic frequency was set to 6 kHz and the temperature was set to 35 °C. The mixture was collected, and after removing ethanol under reduced pressure at 35 °C, it was freeze-dried at -80 °C for 24 h to obtain the composite powder.

[0039] Comparative Example 1 Mix 0.2g of asiatic acid and 0.152g of curcumin to obtain a complex powder.

[0040] Comparative Example 2 Mix 0.208g of hydroxyasiatic acid and 0.152g of curcumin to obtain a complex powder.

[0041] Comparative Example 3 Mix 0.392g of asiaticoside and 0.152g of tetrahydrocurcumin to obtain a complex powder.

[0042] Comparative Example 4 Mix 0.4g of asiaticoside and 0.152g of tetrahydrocurcumin to obtain a complex powder.

[0043] Comparative Example 5 1) Dissolve 0.2g of asiatic acid in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of curcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Mix phase A and phase B, stir at 50℃ and 200 rpm for 1 h, remove ethanol under reduced pressure at 35℃, freeze dry at -80℃ for 24 h to obtain composite powder.

[0044] Comparative Example 6 1) Dissolve 0.208 g of asiatic acid in 100 mL of 50% (v / v) ethanol to form phase A; 2) Dissolve 0.152 g of curcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Mix phase A and phase B, stir at 50℃ and 200 rpm for 1 h, remove ethanol under reduced pressure at 35℃, freeze dry at -80℃ for 24 h to obtain composite powder.

[0045] Comparative Example 7 1) Dissolve 0.392g of asiaticoside in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of tetrahydrocurcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Mix phase A and phase B, stir at 50℃ and 200 rpm for 1 h, remove ethanol under reduced pressure at 35℃, freeze dry at -80℃ for 24 h to obtain composite powder.

[0046] Comparative Example 8 1) Dissolve 0.4g of asiaticoside in 100mL of 50% (v / v) ethanol as phase A; 2) Dissolve 0.152 g of tetrahydrocurcumin in 100 mL of 95% (v / v) ethanol as phase B; 3) Mix phase A and phase B, stir at 50℃ and 200 rpm for 1 h, remove ethanol under reduced pressure at 35℃, freeze dry at -80℃ for 24 h to obtain composite powder.

[0047] Experimental Example 1: Molecular dynamics simulation of Centella asiatica components with curcumin and tetrahydrocurcumin Molecular dynamics simulations were used to analyze the pairwise interactions between four active components of Centella asiatica (asiaticoside, hydroxyasiaticoside, asiaticoside, and hydroxyasiaticoside) and curcuminoids (curcumin and tetrahydrocurcumin). Topology files for all small molecules were generated using an ATB server, employing GROMOS 54A7 force field parameters. Each combination system was placed in a 5.0 nm cubic box, filled with solvent using an SPC / E water model, and an appropriate amount of Na was added. + / Cl -Ions neutralize the system charge. Energy minimization was achieved using the steepest descent method, followed by sequential 100 ps NVT ensemble equilibration and 100 ps NPT ensemble equilibration, maintained at 300 K (V-rescale thermostat) and 1 bar (Berendsen pressure regulator). A final 100 ns simulation was performed with an integration step of 1 fs and a cutoff radius of 1.2 nm. Long-range electrostatic interactions were handled using the PME method, and the bond lengths of all hydrogen bonds were constrained using the LINCS algorithm. The binding stability and interaction modes of each combination were evaluated by calculating the solvent accessible surface area (SASA) and the centroid distance between molecules.

[0048] To assess the stability and binding tightness of the complex, this study calculated three key structural parameters: root mean square deviation (RMSD), solvent accessible surface area (SASA), and minimum interatomic distance (Distance). RMSD reflects the degree of deviation of the molecular structure from its initial conformation; when RMSD tends to plateau over time, it indicates that the system has reached equilibrium. SASA measures the surface area of ​​the molecule exposed to the solvent; the lower the SASA value, the tighter the molecular surface is bound. Generally, a stable SASA at a low level (below 15 nm²) without significant fluctuations indicates the formation of a stable aggregate. Distance represents the distance between the nearest pair of atoms between two molecules; when this distance is stable below 0.3 nm, it indicates a sustained close contact between the two molecules.

[0049] The experimental results are shown in Figures 1-8 .

[0050] The results show that, through comprehensive analysis of the above three parameters, it can be determined that stable bonds have been formed between eight pairs of molecules: asiatic acid and curcumin, hydroxyasiatic acid and curcumin, asiaticoside and curcumin, hydroxyasiaticoside and curcumin, asiatic acid and tetrahydrocurcumin, hydroxyasiatic acid and tetrahydrocurcumin, asiaticoside and tetrahydrocurcumin, and hydroxyasiaticoside and tetrahydrocurcumin.

[0051] Experimental Example 2: Stability Study 0.2 g of each sample from Examples 1-8 and Comparative Examples 1-8 was dissolved in 19.8 g of 40% (v / v) butanediol aqueous solution to obtain sample solutions of Examples 1-8 and Comparative Examples 1-8. The stability of these solutions was investigated at room temperature (25℃±2℃) and at low temperature (4℃±2℃) when sealed and protected from light for 7 days, 14 days, and 28 days.

[0052] The test results for Experiment Example 2 are shown in Table 1.

[0053] Table 1. Stability test results

[0054] As shown in Table 1, the sample solutions from Examples 1-8 remained clear liquids with no visible precipitate after 28 days under both room temperature and low temperature conditions. Comparative Examples 1-6, after 28 days under both room temperature and low temperature conditions, appeared cloudy with precipitate; Comparative Examples 7 and 8, after 28 days under low temperature conditions, became cloudy. This indicates that the samples prepared using the process described in Examples 1-8 exhibited better stability.

[0055] Experimental Example 3: Osmosis Experiment 0.2 g of each sample from Examples 1-8 and Comparative Examples 1-8 was dissolved in 19.8 g of 40% (v / v) butanediol aqueous solution to obtain sample solutions of Examples 1-8 and Comparative Examples 1-8. 0.1 g of each solution was then used for permeability testing.

[0056] This experimental example uses a Franz vertical dual-chamber permeation diffusion cell for permeation experiments, with an effective permeation area of ​​1.77 cm². 2 The receiving chamber volume was 12 mL, and a PBS buffer solution containing 30% (v / v) ethanol was prepared as the receiving solution. Excised pigskin was cut to a suitable size and placed with the stratum corneum facing upwards between the diffusion chamber and the two halves of the receiving chamber in a Franz vertical diffusion cell, secured with clamps. The receiving chamber was filled with the receiving solution, ensuring the liquid surface was just in contact with the skin, guaranteeing no air bubbles between the receiving solution and the pigskin. A magnetic stirrer was added to the receiving chamber. 0.1 g of each sample was accurately weighed and placed in the diffusion chamber. The receiving chamber was then heated in a constant temperature water bath at 32 ± 0.5 °C. The magnetic stirrer was turned on and stirred at 300 rpm. 1 mL of the receiving solution was collected at 2, 6, 8, 10, and 24 hours. After each sampling, 1 mL of blank receiving solution at the same temperature was immediately added. The concentration of the analyte in the receiving solution at different time points was determined using the HLPC-DAD method. The data were processed according to the following formula to calculate the cumulative permeation (μg).

[0057] Formula for calculating cumulative permeability Q: .

[0058] Q: Cumulative permeation volume; V: Volume of receiving liquid in the receiving chamber; V0: Volume of each sample taken; Ci: Concentration of the analyte in the receiving liquid from the first to the last sample; Cn: Concentration of the analyte measured at the nth sampling point.

[0059] The liquid chromatography detection conditions for asiaticoside, hydroxyasiaticoside, asiatic acid, and hydroxyasiatic acid were as follows: Agilent 1260 high performance liquid chromatograph, ZORBAX Eclipse XDB-C18 column (4.6×250mm, 5μm), mobile phase consisting of 0.1% (v / v) phosphoric acid aqueous solution (A) and acetonitrile (B) with gradient elution as shown in Table 2; flow rate set at 1.0 mL / min; column temperature at room temperature; detection wavelength at 207 nm; and injection volume at 10 μL.

[0060] Table 2 Gradient elution conditions

[0061] The results of the permeability test are shown in Table 3, and the values ​​are the mean values.

[0062] Table 3. Permeability Test Results

[0063] As shown in Table 3, the permeability of asiatic acid, hydroxyasiatic acid, asiaticoside, and hydroxyasiaticoside in the sample solutions of Application Examples 1-8 was better than that of Comparative Examples 1-8 at the corresponding time points. This indicates that the preparation process used in Application Examples 1-8 improved the permeability of asiatic acid, hydroxyasiatic acid, asiaticoside, and hydroxyasiaticoside, and that the complex has better permeability.

[0064] Application Experiment Example 1: Capsaicin Sensory Stimulation Test Application Example 9 provides a face cream containing the compound powder of Example 7. The formulation, by weight percentage, is shown in Table 4, with values ​​representing the mean.

[0065] Table 4 Face Cream Formula

[0066] Preparation method: Mix all components and stir to homogenize to obtain face cream.

[0067] The difference between Comparative Example 9 and Application Example 9 is that Comparative Example 9 replaces the composite powder of Example 7 with an equal amount of the composite powder of Comparative Example 7, while the other components, amounts, and preparation methods are the same as in Application Example 9.

[0068] The difference between the blank group and application example 9 is that the blank group replaces the compound powder of example 7 with an equal amount of water, while the other components, dosages and preparation methods are the same as in application example 9.

[0069] Capsaicin is the active ingredient in chili peppers. Upon contact with the human body, capsaicin activates the TRPV1 sensory receptor, producing burning and stinging sensations, and also dilates blood vessels, leading to increased skin erythema and inflammation. Based on this principle, a capsaicin receptor stimulation model was established, and the soothing and redness-reducing effects of topical samples were evaluated.

[0070] Thirty-two subjects, aged 25–50 years, were selected. One 1cm × 1cm test site was chosen on each upper arm. A 1cm × 1cm filter paper was soaked in a 10% capsaicin solution and then applied to the test site for 30 minutes. After 30 minutes, the filter paper was removed. Cream from Application Example 9 was applied to one test site on the left arm, and Cream from Comparative Example 9 was applied to one test site on the right arm. Pain and burning sensations were observed within 30 minutes, and scores were assigned based on the perceived sensations. Each indicator was assessed on a scale of 0 (no relief) to 3 (significant relief) according to its severity.

[0071] The test results of Application Experiment Example 1 are shown in Table 5, and the values ​​are the mean values.

[0072] Table 5. Results of Capsaicin Sensory Stimulation Test

[0073] As shown in Table 5, Application Example 9, which incorporates the compound powder prepared in Example 7, can better alleviate pain and burning sensation compared to Application Comparative Example 9.

[0074] Application Test Example 2: Fading Redness Test Thirty-two subjects, aged 25–50 years, were selected. Two 1cm × 1cm test sites were chosen on each of their left and right upper arms. 1cm × 1cm filter paper was soaked in a 10% capsaicin solution and then applied to the test sites for 30 minutes. After 30 minutes, the filter paper was removed. On the left hand, one test site was treated with the cream from Application Example 9, and the other test site was treated with the blank group. On the right hand, one test site was treated with the cream from Application Example 9, and the other test site was treated with the blank group. After 30 minutes of sample application, the samples were wiped off. The a-value of each test site was measured using a skin colorimeter probe and compared with the blank group. The reduction rate of the a-value was calculated to evaluate the redness-reducing efficacy of the samples.

[0075] The calculation method is as follows: Reduction rate (%) = (a 空白组 -a 受试组 ) / a 空白组 ×100%.

[0076] The test results of application experiment example 2 are shown in Table 6, and the values ​​are the mean.

[0077] Table 6 Results of the redness fading test

[0078] As shown in Table 6, Application Example 9, which incorporated the complex powder prepared in Example 7, exhibited a better redness-reducing effect compared to Application Comparative Example 9. This may be because the active ingredients can penetrate more quickly and exert their soothing effect earlier.

[0079] Application Trial Example 3: Soothing and Repair Test The soothing efficacy of the face creams in the above application example 9, application comparison example 9, and the blank group was evaluated.

[0080] Thirty volunteers, aged 25-50 years, with an equal number of men and women, were selected and divided into three groups, using the face cream from Application Example 9, Comparative Example 9, and a control group, respectively. The test site was the face. After cleansing morning and evening, participants applied an appropriate amount of product evenly to the face and massaged until absorbed. The product was used twice daily, once in the morning and once in the evening. Follow-up was conducted at 14 and 28 days after product use. Evaluation indicators included skin erythema and desquamation at the test site, with each indicator rated from 0 (ineffective) to 5 (significant improvement) based on its severity. Additionally, the repairing and soothing efficacy of the product was evaluated by comparing skin hydration and transepidermal water loss (TEWL) before and after product use, at 14 and 28 days post-use.

[0081] The test results are shown in Table 7, and the values ​​are the mean.

[0082] Table 7. Results of the Soothing and Repair Test

[0083] As shown in Table 7, the application of Example 9 has better repair and soothing effects.

[0084] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A self-assembled complex of Centella asiatica active ingredients, characterized in that, The Centella asiatica active ingredient self-assembled complex is a nanoscale aggregate formed by the self-assembly of Centella asiatica triterpenoid active ingredients and curcumin-like compounds through non-covalent interactions. The active triterpenoids of Centella asiatica are selected from one or more of asiatic acid, hydroxyasiatic acid, asiaticoside, and hydroxyasiaticoside. The curcumin compounds are curcumin and / or tetrahydrocurcumin.

2. The self-assembled complex of Centella asiatica active ingredients according to claim 1, characterized in that, The molar ratio of the active triterpenoid component of Centella asiatica to the curcuminoid compound is 1:(0.99-1.01).

3. The self-assembled complex of Centella asiatica active ingredients according to claim 2, characterized in that, The molar ratio of the active triterpenoid component of Centella asiatica to the curcuminoid compound is 1:

1.

4. The self-assembled complex of Centella asiatica active ingredients according to claim 1, characterized in that, The non-covalent interactions include one or more of hydrogen bonds, van der Waals forces, π-π stacking, and hydrophobic interactions.

5. A method for preparing a self-assembled complex of Centella asiatica active ingredients as described in any one of claims 1 to 4, characterized in that, Includes the following steps: S1. Dissolve the active triterpenoid components of Centella asiatica in a first ethanol aqueous solution to form phase A; S2. Dissolve curcumin-like compounds in a second ethanol aqueous solution to form phase B; S3. Mix the A phase and the B phase, carry out a supramolecular self-assembly reaction under ultrasonic conditions, and collect the mixture; S4. After removing the solvent from the mixture, it is dried to obtain the Centella Asiatica active ingredient self-assembled complex.

6. The method according to claim 5, characterized in that, The volume concentration of the first ethanol aqueous solution is 40%~60%; the volume concentration of the second ethanol aqueous solution is 90%~100%.

7. The method according to claim 5, characterized in that, The concentration of Centella asiatica active ingredients in phase A is 4.0-4.2 mmol / L; the concentration of curcuminoids in phase B is 4.0-4.2 mmol / L.

8. The method according to claim 5, characterized in that, In step S3, the flow rates of phase A and phase B entering the ultrasonic microfluidic device are each independently 5 mL / min to 15 mL / min; the ultrasonic frequency is 2-20 kHz; and the temperature is 25-45 ℃.

9. The use of the Centella Asiatica active ingredient self-assembled complex as described in any one of claims 1 to 5 in the preparation of cosmetics for soothing, anti-inflammatory, redness-reducing, collagen-promoting, antioxidant, and / or skin barrier-repairing purposes.

10. The application according to claim 9, characterized in that, The amount of the Centella Asiatica active ingredient self-assembled complex added to the cosmetic is 0.01%-5% by mass.

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