External bioactive biomimetic membrane skin care preparation for relieving allergy and itching and preparation method thereof

Abstract

The invention relates to the technical field of cosmetics, and discloses an external-use allergy-relieving itching-relieving bioactive biomimetic membrane skin care preparation and a preparation method thereof.The preparation is prepared from, by weight, red ginseng extract rich in rare ginsenoside, colloidal oat powder, cetostearyl alcohol and distearyl dimethyl ammonium chloride; the preparation method comprises the following steps: firstly, carrying out ultrasonic activation treatment on the red ginseng extract, then carrying out high-temperature emulsification on the oil phase and the water phase, and finally, carrying out programmed control cooling on the obtained emulsion. According to the method, all the components are subjected to in-situ self-assembly on the skin surface to form the layered liquid crystal biomimetic membrane; the biomimetic membrane structure simulates skin cuticle lipid, and can effectively reduce percutaneous moisture loss and repair a skin barrier; meanwhile, as a carrier, rare ginsenoside is promoted to permeate into the skin, so that instant and long-acting allergy-relieving and itching-relieving effects are realized.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a topical soothing and itch-relieving bioactive biomimetic film skin care preparation and its preparation method. Background Technology

[0002] Sensitive skin is a common sub-healthy skin condition characterized by impaired skin barrier function, reduced tolerance to external stimuli, and a tendency to experience discomfort such as redness, dryness, tightness, and itching. Therefore, skincare product development targeting this issue typically focuses on repairing the skin barrier and soothing inflammatory responses.

[0003] Currently, existing soothing and anti-itch skincare products on the market typically employ a technical approach that involves adding active ingredients with anti-inflammatory or soothing effects to the formula, combined with occlusive agents or emollients to create a physical protective film, aiming to alleviate discomfort and reduce external irritation. However, most existing formulations are conventional emulsion systems, and the protective film they form on the skin surface differs significantly in structure from the natural lipid layer of the stratum corneum.

[0004] This structural mismatch results in insufficient affinity and poor adhesion between the protective film and the skin, making it prone to detachment due to friction or washing, thus limiting the durability of its barrier protection effect. Furthermore, the delivery efficiency of active ingredients is also a bottleneck in these conventional systems. Active ingredients are typically encapsulated in droplets or dispersed in a continuous phase, lacking effective penetration-enhancing mechanisms. Most active substances struggle to penetrate the stratum corneum barrier to reach their target sites, leading to low bioavailability and impacting actual efficacy. Therefore, developing a topical formulation that can form a durable protective film highly biomimetic to the skin structure while simultaneously improving the penetration efficiency of active ingredients is a pressing technical challenge in this field. Summary of the Invention

[0005] The technical problem solved by this invention is that existing products for relieving skin sensitivity and itching generally suffer from low penetration efficiency of active ingredients, insufficient affinity with the skin, and poor water resistance and durability of the protective film formed, resulting in limited skin barrier repair effects and short duration of action.

[0006] To address the above problems, the present invention provides the following technical solution: In a first aspect, the present invention provides a topical, soothing, and itch-relieving bioactive biomimetic film skin care preparation, which is made from the following raw materials in parts by weight: 0.8 to 1.5 parts of red ginseng extract enriched with rare ginsenosides; 1.5 to 2.5 parts of colloidal oat flour; 2.5 to 3.5 parts of cetearyl alcohol; 1.5 to 2.5 parts of distearate dimethyl ammonium chloride; and the balance being water and cosmetically acceptable excipients.

[0007] By employing the above technical solution, the formulation of the present invention can form an ordered layered liquid crystal biomimetic film structure in situ on the skin surface. The formation mechanism is as follows: In this invention, the red ginseng extract enriched with rare ginsenosides plays a structural role in the preparation process due to the amphiphilic properties of its molecules, which possess a rigid steroidal ring backbone and flexible glycosyl groups. Cetearyl alcohol and distearate dimethyl ammonium chloride provide the hydrophobic long chains and hydrophilic groups required to form the layered structure. In specific preparation methods, especially during programmed cooling, rare ginsenoside molecules intervene between cetearyl alcohol and distearate dimethyl ammonium chloride molecules, guiding these amphiphilic molecules to arrange themselves in an orderly manner through intermolecular interactions such as hydrogen bonds and van der Waals forces, thereby self-assembling to form a dense and regularly arranged layered liquid crystal structure. β-glucan from colloidal oat flour interweaves or adheres to this layered structure, further enhancing the system's stability and moisturizing properties.

[0008] The beneficial effects of this structure: Physical barrier function: The formed lamellar liquid crystal structure morphologically mimics the lipid bilayer structure of the stratum corneum of human skin. This dense, ordered arrangement increases the path length for water molecule penetration, thereby reducing transepidermal water loss (TEWL) and providing immediate physical occlusion. Simultaneously, this structure possesses strong cohesion and adhesion to the skin, improving the water resistance of the formulation and allowing the protective film and active ingredients to remain on the skin surface for an extended period, thus prolonging the duration of action.

[0009] Bioactive Delivery: This biomimetic membrane structure serves as a reservoir for active ingredients. Its structural similarity to the lipids in the stratum corneum of the skin enhances their affinity, facilitating the delivery of enriched rare ginsenosides and other active ingredients into the skin and their accumulation at sites of action such as the active epidermis. The enriched rare ginsenosides themselves possess anti-inflammatory and soothing activities.

[0010] Therefore, this invention constructs a biomimetic membrane system that combines physical barrier repair and bioactive delivery through the synergistic effect of specific components, achieving both immediate and long-lasting soothing and antipruritic effects.

[0011] Preferably, the red ginseng extract enriched with rare ginsenosides is prepared by a method comprising the following steps: (a) Processing: Steam the red ginseng at 115-120℃ with saturated steam for 3.0-3.5 hours; (b) Extraction: The processed red ginseng was extracted with an ethanol solution; (c) Chromatographic enrichment: The extract is loaded onto a macroporous adsorption resin column, eluted sequentially with water and 40-45% v / v ethanol solution and the eluent is discarded, then eluted again with 75-80% v / v ethanol solution and the eluent is collected. (d) Post-processing: The collected eluent is concentrated and dried to obtain the extract.

[0012] By employing the above-described technical solution, the high-temperature and high-pressure processing can promote the transformation of the original saponins in red ginseng into rarer ginseng saponins with higher bioactivity. Subsequent chromatographic steps using gradient elution with ethanol solutions of specific concentrations effectively remove water-soluble impurities and selectively enrich the target rare ginseng saponin components. This ensures that the extract, as the core of the structural organization and the core active ingredient, possesses high purity and high activity, which is the foundation for achieving the technical effects of this invention.

[0013] Preferably, the raw materials are in the following proportions by weight: 1.0 part of red ginseng extract enriched with rare ginsenosides, 2.0 part of colloidal oat flour, 3.0 part of cetearyl alcohol, and 2.0 part of distearate dimethyl ammonium chloride.

[0014] By adopting the above technical solution, this formulation enables the components to work synergistically, which is conducive to forming a biomimetic membrane with complete structure and stable performance, thereby achieving a good comprehensive effect of barrier repair and active delivery.

[0015] Preferably, the raw material further comprises one or more selected from ascorbyl glucoside, hydroxyphenylpropionamide benzoic acid, polyols, oils, and silicone oils.

[0016] By employing the above technical solutions, other functional ingredients can be compounded in the biomimetic membrane system of this invention. For example, ascorbate glucoside can slowly release vitamin C under the action of α-glucosidase present on the skin surface, providing a long-lasting antioxidant effect; hydroxyphenylpropionamide benzoic acid is a biomimetic molecule of oat alkaloids, which can provide rapid anti-irritation and antipruritic effects. The addition of these ingredients further enhances the comprehensive skin care efficacy of the formulation without disrupting the formation of the main biomimetic membrane structure.

[0017] Secondly, the present invention provides a method for preparing a topical soothing and antipruritic bioactive biomimetic membrane skin care preparation, which adopts the following technical solution: A method for preparing a topical, soothing, and antipruritic bioactive biomimetic membrane skincare formulation includes the following steps: (A) Saponin molecule activation: Red ginseng extract enriched with rare ginsenosides was mixed with polyol and subjected to ultrasonic treatment to obtain an activation solution; (B) Emulsification: The oil phase containing cetearyl alcohol and distearate dimethyl ammonium chloride is homogenized and emulsified with the aqueous phase containing the activated liquid obtained in step (A) and colloidal oat flour at high temperature; (C) Programmed cooling: The emulsion obtained in step (B) is cooled at a controlled rate of 0.5 to 1.0 °C / min to form a layered liquid crystal structure.

[0018] By employing the above technical solution, the preparation method of the present invention, through a specific combination of process steps, achieves the control of the molecular arrangement of components, which is the basis for forming the aforementioned ordered biomimetic membrane structure. Its working principle is as follows: Step (A) Saponin molecule activation: This step is a pretreatment process. Saponin molecules in red ginseng extract enriched with rare ginsenosides readily form aggregates of varying sizes in the solid state or at high concentrations through intermolecular forces. The acoustic energy provided by ultrasonic treatment can overcome intermolecular constraints, dispersing these aggregates and allowing saponin molecules to exist in the polyol medium as single molecules or small, uniform aggregates. This provides conditions for the subsequent uniform integration of saponin molecules into lipid molecules.

[0019] Step (B) Emulsification: Homogenization was performed at high temperature to ensure that solid lipids such as cetearyl alcohol were completely melted and that all amphiphilic molecules in the system had sufficient molecular mobility. High-speed shearing dispersed the oil phase into uniform microdroplets, forming the initial emulsion system required for subsequent ordered structural transformation.

[0020] Step (C) Programmed Cooling: This step is crucial for the formation of an ordered layered liquid crystal structure. Unlike conventional rapid cooling, slow and controlled cooling is a quasi-thermodynamic equilibrium process. This process allows amphiphilic molecules in the system sufficient time to rearrange before losing their high mobility, achieving a lower-energy ordered state. During this process, activated rare ginsenoside molecules play a structural organizing role, guiding molecules such as cetearyl alcohol and distearate dimethyl ammonium chloride to undergo ordered self-assembly, ultimately forming a more thermodynamically stable layered liquid crystal structure. If rapid cooling is used, the molecules solidify in a disordered state due to a rapid decrease in mobility, making it impossible to form an effective biomimetic film structure.

[0021] In summary, the method of the present invention achieves the construction of the product's microstructure through a combination of saponin molecule activation and programmed cooling, thereby ensuring the functionality of the final formulation.

[0022] Preferably, the ultrasonic treatment in step (A) is performed in a water bath at 45-50°C, and the ultrasonic frequency is 20-30 kHz.

[0023] By adopting the above technical solution, the process parameter range provides energy for the dispersion of saponin molecules, while avoiding the degradation of active ingredients that may be caused by excessive temperature or excessive ultrasonic power, thus ensuring the structural integrity and biological activity of saponin molecules.

[0024] Preferably, the high temperature in step (B) is 75-85°C, and the shearing speed for homogenization emulsification is 3000-5000 rpm.

[0025] By employing the above technical solution, this temperature range ensures that all oil phase components in the formulation are completely melted, which is beneficial for forming a homogeneous liquid mixture. This rotation speed range can shear the oil phase into fine droplets, increasing the contact area between the oil and water phases and providing a basis for subsequent ordered molecular arrangement.

[0026] Preferably, after step (C), the method further includes adding the heat-sensitive active ingredient when the system temperature drops below 45°C.

[0027] By adopting the above technical solution, the heat-labile active ingredients are added at a low temperature stage, which helps to prevent them from decomposing or becoming inactive during high-temperature emulsification, thereby ensuring the effectiveness of these ingredients in the final product.

[0028] Preferably, prior to step (B), the step of preparing the aqueous phase includes: dispersing colloidal oat flour in water at a temperature of 75–85°C and stirring at a constant temperature for at least 20 minutes.

[0029] By employing the above technical solution, this step promotes the swelling of colloidal oat flour and the hydration of its macromolecules, such as β-glucan, forming a uniform and stable aqueous matrix. This not only helps improve the skin feel and moisturizing properties of the final product but also contributes to enhancing the stability of the subsequent emulsification system.

[0030] Preferably, the polyol in step (A) is 1,2-pentanediol.

[0031] By adopting the above technical solution, 1,2-pentanediol can serve as a solvent and dispersant for rare ginsenosides, which aids in the activation process. It is also a humectant and preservative synergist.

[0032] In summary, the present invention has at least one of the following beneficial technical effects: 1. This invention utilizes a specific combination of raw materials and preparation method, particularly a programmed cooling step, to induce the orderly self-assembly of components such as red ginseng extract rich in rare ginsenosides, cetearyl alcohol, and distearate dimethyl ammonium chloride, forming a layered liquid crystal biomimetic film on the skin surface that mimics the lipid bilayer of the stratum corneum. This biomimetic film has a dense structure, effectively reducing transepidermal water loss and providing immediate and long-lasting physical barrier repair. Furthermore, its excellent adhesion and water resistance prolong the duration of action of the formulation on the skin.

[0033] 2. In the preparation method of this invention, the red ginseng extract enriched with rare ginsenosides undergoes ultrasonic activation treatment, ensuring that the active ingredients exist in the form of more easily permeable single molecules or small aggregates. Simultaneously, the resulting biomimetic membrane structure has high affinity with the stratum corneum of the skin, serving as a reservoir and permeation-enhancing carrier for the active ingredients, delivering rare ginsenosides to the active epidermal layer more efficiently, thereby more fully exerting their anti-inflammatory, soothing, and antipruritic biological effects.

[0034] 3. This invention utilizes a high-temperature, high-pressure processing technique to convert low-bioavailability proto-ginsenosides in red ginseng into rarer ginsenosides with higher bioactivity; further, selective enrichment is achieved through macroporous resin chromatography. Compared to using ordinary red ginseng extract, this invention ensures the high activity and purity of the core active ingredients from the source, providing a solid material basis for the final soothing and antipruritic effect of the formulation. Detailed Implementation

[0035] The main raw materials and reagents used in the following examples and comparative examples have the following sources and specifications. Reagents not specifically mentioned are all commercially available analytical grade or higher grade products.

[0036] The red ginseng extract enriched with rare ginsenosides is not a commercially available product. It is prepared through specific processing, extraction, and macroporous resin chromatography processes. For details of the preparation method, please refer to the preparation examples.

[0037] Colloidal oat flour is obtained by processing oat caryopsis. Its main active ingredient is a linear polysaccharide (β-glucan) composed of D-glucan units linked by β-(1→4) and β-(1→3) glycosidic bonds. The particle size distribution D90 used in this invention is in the range of 40–60 μm.

[0038] Cetearyl alcohol is a solid fatty alcohol mixture of cetyl alcohol (CAS No.: 36653-82-4) and stearyl alcohol (CAS No.: 112-92-5), with the ratio of the two in the specifications being approximately 30 / 70.

[0039] Preparation Example 1: This preparation example provides a method for preparing a red ginseng extract enriched with rare ginsenosides, including the following steps: 1. Raw material processing: Take 500g of 5-year-old red ginseng from Jilin, place it in a sealed pressure container, pass saturated steam through it, steam at 120℃ for 3.0 hours, take it out, and dry it at 60℃ with forced air until constant weight.

[0040] 2. Extraction: Grind the processed red ginseng to 50 mesh, add 4.0L of 80% (v / v) ethanol solution, and reflux at 70℃ twice, 2.0 hours each time. Combine the two extracts and filter.

[0041] 3. Concentration: The extract filtrate was concentrated under reduced pressure at 60℃ and -0.07MPa to recover ethanol and obtain a thick extract.

[0042] 4. Chromatographic enrichment: Pack 1 kg of pretreated D101 macroporous adsorption resin into a column. Dissolve and dilute the viscous extract from step 3 with deionized water to a saponin concentration of approximately 12 mg / mL, and load the sample onto the resin column. First, elute with 4 column volumes of deionized water, then elute with 5 column volumes of 40% (v / v) ethanol solution, discarding both eluent portions. Finally, elute with 6 column volumes of 80% (v / v) ethanol solution, collecting this eluent portion.

[0043] 5. Post-processing: The collected 80% ethanol eluent was concentrated to dryness under reduced pressure at 60°C, then vacuum dried at 65°C for 5 hours, and pulverized through a 100-mesh sieve to obtain product P1.

[0044] Preparation Example 2: This preparation example provides a method for preparing a red ginseng extract enriched with rare ginsenosides. This method uses different processing parameters than Preparation Example 1 and includes the following steps: 1. Raw material processing: Take 500g of 5-year-old red ginseng from Jilin, place it in a sealed pressure container, pass saturated steam through it, steam at 115℃ for 3.5 hours, take it out, and dry it at 60℃ with forced air until constant weight.

[0045] 2. Extraction: The procedure is the same as step 2 in Preparation Example 1.

[0046] 3. Concentration: The procedure is the same as step 3 in Preparation Example 1.

[0047] 4. Chromatographic enrichment: The procedure is the same as step 4 in Preparation Example 1.

[0048] 5. Post-processing: The operation is the same as step 5 of preparation example 1, which yields product P2.

[0049] Preparation Example 3: This preparation example provides a method for preparing red ginseng extract enriched with rare ginsenosides. This method uses chromatographic enrichment process parameters different from those in Preparation Example 1, and includes the following steps: 1. Raw material preparation: The operation is the same as step 1 in Preparation Example 1.

[0050] 2. Extraction: The procedure is the same as step 2 in Preparation Example 1.

[0051] 3. Concentration: The procedure is the same as step 3 in Preparation Example 1.

[0052] 4. Chromatographic enrichment: Pack 1 kg of pretreated D101 macroporous adsorption resin into a column. Dissolve and dilute the viscous extract from step 3 with deionized water to a saponin concentration of approximately 12 mg / mL, and load the sample onto the resin column. First, elute with 4 column volumes of deionized water, then elute with 5 column volumes of 45% (v / v) ethanol solution, discarding both eluent portions. Finally, elute with 6 column volumes of 75% (v / v) ethanol solution, collecting this eluent portion.

[0053] 5. Post-processing: The operation is the same as step 5 of preparation example 1, which yields product P3.

[0054] Example 1: This embodiment provides a method for preparing a topical, soothing, and antipruritic bioactive biomimetic membrane skin care formulation, using preferred intermediate parameters. Based on 100 parts by weight, the formulation consists of the following components: 1.0 part of red ginseng extract enriched with rare ginsenosides (product P1), 2.0 parts of colloidal oat flour, 3.0 parts of cetearyl alcohol, 2.0 parts of distearate dimethyl ammonium chloride, 1.0 part of ascorbate glucoside, 5.0 parts of glycerin, 3.0 parts of butylene glycol, 2.0 parts of 1,2-pentanediol, 4.0 parts of isopropyl palmitate, 1.0 part of polydimethylsiloxane, 2.0 parts of petrolatum, 0.1 part of hydroxyphenylpropionamide benzoic acid, 0.1 part of disodium EDTA, 0.4 parts of benzyl alcohol, a small amount of triethanolamine (used to adjust the pH to the target range, and not included in the 100 parts of the main formulation), and 73.4 parts of deionized water.

[0055] Its preparation method includes the following steps: 1. Aqueous phase preparation: Add glycerol, butylene glycol, and all deionized water to an emulsifying vessel, start stirring (800 rpm), and heat to 80°C. At this temperature, slowly sprinkle in colloidal oat flour and stir at a constant temperature for 20 minutes.

[0056] 2. Saponin molecule activation and pre-complexation: In a beaker, 1,2-pentanediol was mixed with a small amount of water, and product P1 was added. The mixture was then subjected to low-frequency ultrasonic treatment at 30 kHz for 10 minutes in a 50°C water bath. This activated solution was then added to the aqueous phase from step 1 and mixed thoroughly.

[0057] 3. Oil phase preparation: In another container, add cetearyl alcohol, isopropyl palmitate, distearate dimethyl ammonium chloride, polydimethylsiloxane, and petrolatum, heat to 80°C, and stir until completely melted and homogeneous.

[0058] 4. Emulsification: Turn on the high-speed shear homogenization function of the emulsification pot (4000 rpm), add the oil phase from step 3 to the aqueous phase from step 2 at a uniform speed, and continue homogenization for 8 minutes.

[0059] 5. Control the cooling: Turn off the homogenizer and switch to slow frame-type wall-scraping agitator (45 rpm) to program the cooling at a rate of 1.0℃ / minute.

[0060] 6. Post-addition: When the system temperature drops below 45℃, add ascorbate glucoside, hydroxyphenylpropionamide benzoic acid, benzyl alcohol and disodium EDTA, and stir for 15 minutes.

[0061] 7. pH adjustment: Adjust the pH of the system to 5.8 with triethanolamine, continue stirring slowly for 10 minutes, and then discharge the material to obtain product S1.

[0062] Example 2: This embodiment provides a method for preparing a topical, soothing, and antipruritic bioactive biomimetic membrane skincare formulation, using the lower limit of the content of core components. Based on 100 parts by weight, the formulation is made from the following components: 0.8 parts of red ginseng extract enriched with rare ginsenosides (product P2), 1.5 parts of colloidal oat flour, 2.5 parts of cetearyl alcohol, 2.0 parts of distearate dimethyl ammonium chloride, 0.8 parts of ascorbate glucoside, 5.0 parts of glycerin, 3.0 parts of butylene glycol, 2.0 parts of 1,2-pentanediol, 4.0 parts of isopropyl palmitate, 1.0 part of polydimethylsiloxane, 2.0 parts of petrolatum, 0.1 parts of hydroxyphenylpropionamide benzoic acid, 0.1 parts of disodium EDTA, 0.4 parts of benzyl alcohol, an appropriate amount of triethanolamine, and 74.8 parts of deionized water.

[0063] The preparation method is the same as in Example 1. This yields product S2.

[0064] Example 3: This embodiment provides a method for preparing a topical, soothing, and antipruritic bioactive biomimetic membrane skincare formulation, using the upper limit of the content of core components. Based on 100 parts by weight, the formulation is made from the following components: 1.5 parts of red ginseng extract enriched with rare ginsenosides (product P3), 2.5 parts of colloidal oat flour, 3.5 parts of cetearyl alcohol, 2.0 parts of distearate dimethyl ammonium chloride, 1.5 parts of ascorbate glucoside, 5.0 parts of glycerin, 3.0 parts of butylene glycol, 2.0 parts of 1,2-pentanediol, 4.0 parts of isopropyl palmitate, 1.0 part of polydimethylsiloxane, 2.0 parts of petrolatum, 0.1 parts of hydroxyphenylpropionamide benzoic acid, 0.1 parts of disodium EDTA, 0.4 parts of benzyl alcohol, an appropriate amount of triethanolamine, and 71.4 parts of deionized water.

[0065] The preparation method is the same as in Example 1. This yields product S3.

[0066] Example 4: This embodiment provides a method for preparing a topical, soothing, and itch-relieving bioactive biomimetic membrane skincare formulation. This method utilizes endpoint values ​​for key process parameters. The components used and their amounts are the same as in Example 1.

[0067] The difference in its preparation method lies in the following: In step 2, the ultrasonic treatment conditions for saponin molecule activation and pre-complexation are: ultrasonic treatment at 20 kHz for 12 minutes under a 45°C water bath; in step 5, the cooling rate is controlled at 0.5°C / minute. The remaining steps are the same as in Example 1. This yields product S4.

[0068] Comparative Example 1: This comparative example uses a conventional soothing product formulation and preparation process. Its formulation includes commercially available common red ginseng extract and a conventional emulsifier (a compound of glyceryl stearate and PEG-100 stearate), but does not contain distearate dimethyl ammonium chloride or the red ginseng extract enriched with rare ginsenosides prepared according to this invention. The preparation method is a conventional homogenization emulsification and rapid cooling process, excluding saponin molecule activation and controlled cooling steps. Product DS1 was obtained.

[0069] Comparative Example 2: Compared with Example 1, the difference is that an equal amount of commercially available common red ginseng extract was used instead of product P1 obtained in Preparation Example 1. All other components, amounts, and preparation methods were the same as in Example 1. Product DS2 was obtained.

[0070] Comparative Example 3: Compared to Example 1, the difference lies in the preparation method: this comparative example uses a conventional emulsification process, i.e., the saponin molecule activation and pre-complexation in step 2 are omitted, and rapid natural cooling is used instead of programmed cooling in step 5. All other components and amounts are the same as in Example 1. Product DS3 was obtained.

[0071] Comparative Example 4: Compared to Example 1, the difference lies in the construction method of the emulsion system: this comparative example does not use distearate dimethylammonium chloride, but instead uses an equal amount of a commercially available olive-derived liquid crystal emulsifier (a complex of cetearyl oleate and sorbitan oleate), and uses commercially available common red ginseng extract instead of product P1. The preparation process follows the conventional method recommended by the supplier of the commercially available liquid crystal emulsifier. Product DS4 was obtained.

[0072] Test Example 1: The experimental steps are as follows: 1. Coat the test samples (S1, DS1, DS3) onto the Strat-M® synthetic skin membrane and dry them at 32°C to form a film.

[0073] 2. Rinse the formed skin membrane with PBS buffer at pH 7.4 at a flow rate of 1.0 mL / min for 10 minutes.

[0074] 3. Collect the rinsing fluid separately and extract the residue on the membrane after rinsing.

[0075] 4. The content of marker (hydroxyphenylpropionamide benzoic acid) in the rinsing solution and membrane residue was determined by HPLC.

[0076] 5. Calculate the marker retention rate based on the initial coating amount and the content in the membrane residue. Calculation formula: Marker retention rate (%) = (Mass of marker in membrane residue / Total mass of marker initially coated) × 100.

[0077] The experimental results are shown in Table 1.

[0078] Table 1. Retention rate of biomarkers in in vitro water resistance tests for different samples: Test data showed that the biomarker retention rate of S1 formulation after rinsing was 92.8%, DS3 was 61.2%, and DS1 was 36.3%.

[0079] Comparing S1 and DS3, both have the same composition, but S1's specific preparation process (saponin molecule activation and programmed cooling) promotes the ordered arrangement of molecules, forming a dense, layered liquid crystal film. In contrast, DS3's conventional rapid cooling process results in a disordered, mixed film. S1's structure gives it stronger cohesion and substrate adhesion, thus exhibiting a higher marker retention rate after rinsing.

[0080] Comparative Example 1 (DS1) is a conventional O / W emulsion, which forms a loosely structured oil phase deposit that is easily washed away by water, resulting in the lowest marker retention rate.

[0081] Comprehensive analysis shows that, from a water resistance perspective, the test results demonstrate that the combination of specific components and specific processes is a necessary condition for constructing highly stable biomimetic membranes. The structured membrane formed by S1 exhibits superior physical adhesion properties compared to membranes prepared by conventional processes and conventional emulsion systems.

[0082] Test Example 2: The experimental steps are as follows: 1. Add saturated potassium acetate solution to the permeation cup and seal the cup opening with Strat-M® synthetic skin membrane.

[0083] 2. The apparatus was divided into two groups: a blank control group and a sample group in which equal amounts of S1, DS1, DS2 and DS3 samples were applied.

[0084] 3. Apply a sample of 2.0 mg / cm² to the membrane of each sample group.

[0085] 4. After weighing the initial total weight (m0) of each device, place it in a desiccator at 25°C.

[0086] 5. Weigh again after 24 hours (m) 24 The water vapor transmission rate (WVTR) is calculated based on the mass loss over 24 hours. The formula is: WVTR = (m0 - m...) 24 ) / (A×24), where m0 is the initial mass, m 24 The mass is the mass after 24 hours, and A is the effective area of ​​the permeation cup opening (approximately 1.018 × 10⁻⁶). -3 m 2 ).

[0087] The experimental results are shown in Table 2.

[0088] Table 2. Water vapor transmission rate (WVTR) of different samples over 24 hours: This test evaluated the water vapor permeation barrier capability of membranes formed by different formulations using the cup method.

[0089] The WVTR of Example 1 (S1) was 2.6 g·m -2 ·h -1 The lowest value among all groups indicates that the formed membrane has strong water-blocking ability. This effect is attributed to the layered liquid crystal biomimetic membrane formed by the scheme. In this structure, polar lipid molecules are arranged in an orderly manner under the action of rare ginsenosides, forming a dense layered structure, which increases the diffusion path of water molecules, thereby reducing the permeation rate.

[0090] Comparative Example 1 (DS1), as a conventional emulsion, had a WVTR of 9.1 g·m³. -2 ·h -1 The physical shielding layer it forms has a loose structure and limited efficiency in blocking water molecules.

[0091] Comparison of S1 and DS3 (WVTR is 5.3 g·m) -2 ·h -1 The results confirm the necessity of the specific process. DS3 uses the same components as S1 but employs a conventional process, resulting in a higher WVTR. This indicates that the lack of saponin molecule activation and programmed cooling steps prevents the formation of an ordered layered liquid crystal structure, leading to decreased film density and weakened water-blocking ability.

[0092] Comparison of S1 and DS2 (WVTR is 7.2 g·m) -2 ·h -1 The results confirm the necessity of specific raw materials. DS2, using the specific process of this invention but employing ordinary red ginseng extract, exhibits a higher WVTR. This indicates that ordinary red ginseng extract cannot act as a structural organizer to guide polar lipids to form an effective barrier structure, while the extract enriched with rare ginsenosides prepared in this invention is key to forming this structure.

[0093] In summary, the WVTR test data validates the technical concept of this invention. By combining a specifically prepared red ginseng extract with a specific preparation process, an ordered and low-permeability biomimetic membrane can be constructed on the substrate surface, achieving effective skin barrier function.

[0094] Test Example 3: The experimental steps are as follows: 1. Install a dialysis membrane with a molecular weight cutoff of 1 kDa onto a Franz diffusion cell and pre-equilibrate it in a phosphate-citrate buffer at pH 5.5.

[0095] 2. The experiment was divided into two groups: Group A received the medium as pH 5.5 buffer; Group B received the medium as the same buffer containing 50 U / mL α-glucosidase.

[0096] 3. Place the diffusion cell in a 32°C water bath and apply 100 mg of sample S1 onto the dialysis membrane.

[0097] 4. Take samples from the receiving cell at 0, 1, 2, 4, 8, and 12 hours, and replenish with an equal volume of fresh medium.

[0098] 5. The concentration of L-ascorbic acid (L-AA) in the sample was determined by HPLC.

[0099] 6. Calculate the cumulative release rate of L-AA based on the measured concentration. The formula is: Cumulative release rate (%) = [(V0 × C] / (V0 × C)] n +Σ(V i ×C i )) / m]×100, where V0 is the volume of the receiving cell, V i For the sampling volume, C n Let C be the concentration of the nth sample. i Let m be the concentration of the i-th sample, and m be the total theoretical mass of L-AA contained in ascorbate glucoside in the initial sample.

[0100] The experimental results are shown in Table 3.

[0101] Table 3. Cumulative release rate of L-ascorbic acid (L-AA) under different conditions: This test aims to verify whether the release of ascorbate glucoside (AA2G) in formulation S1 is regulated by α-glucosidase.

[0102] Data showed that in group A, which did not contain α-glucosidase, the cumulative release rate of L-ascorbic acid (L-AA) was less than 0.6% within 12 hours. In group B, which contained α-glucosidase, the release of L-AA increased over time, with a cumulative release rate of approximately 53.7% after 12 hours.

[0103] The results from Group A indicate that AA2G is stable in the formulation matrix and exhibits a low rate of spontaneous hydrolysis in the weakly acidic environment simulating skin. The release curves in Group B conform to the kinetics of an enzyme-catalyzed reaction. The difference in release behavior between Group A and Group B demonstrates that the release of the active ingredient from the formulation depends on an enzyme-catalyzed reaction.

[0104] This mechanism demonstrates that the biomimetic membrane structure immobilizes AA2G. When applied to the skin, α-glucosidase in the stratum corneum hydrolyzes AA2G in situ to generate active L-AA, thereby achieving controlled release.

[0105] Test Example 4: The experimental steps are as follows: 1. Prepare isolated pig skin and determine its initial TEWL value (TEWL). 正常值 ).

[0106] 2. Treat pigskin with 5% SDS solution to establish a TEWL value of 35-45 g·m³. -2 ·h -1 A barrier damage model of the extent was established, and the TEWL value after damage was recorded. 损伤值 ).

[0107] 3. Injured skin was divided into groups: a normal control group, an injured control group, and sample groups S1, DS1, DS2, DS3, and DS4. A 2 mg / cm³ solution was applied to the skin surface of each sample group. 2 The corresponding sample.

[0108] 4. The TEWL value of each group of skin was measured at 2, 4, 8, 12 and 24 hours after the sample was applied.

[0109] 5. According to the formula: TEWL recovery rate (%) = (TEWL 损伤值 -TEWL 处理后值 ) / (TEWL 损伤值 -TEWL 正常值 )×100, calculate the TEWL recovery rate.

[0110] The experimental results are shown in Table 4.

[0111] Table 4. Changes in TEWL values ​​of damaged skin after different sample treatments (mean ± standard deviation, g·m) -2 ·h -1 ): This test assesses the repair effect of each formulation on chemically damaged skin barriers by monitoring changes in TEWL values.

[0112] The TEWL value of the treatment group in Example 1 (S1) decreased rapidly within 2 hours and recovered to near-normal skin levels after 24 hours. This indicates that the biomimetic membrane formed by S1 can provide immediate physical closure and promote biological repair by delivering active ingredients.

[0113] The comparative results analyzed the source of the mechanism of action of S1. Comparative Example 1 (DS1), as a conventional emulsion, showed a slow decrease in its TEWL value, indicating that its emulsion structure could not provide effective barrier repair. Comparing S1 and DS2 (using conventional red ginseng extract), DS2 showed a weaker repair effect, confirming that the extract enriched with rare ginsenosides is the key ingredient for achieving the repair effect. Comparing S1 and DS3 (using conventional processes), DS3 also showed a weaker repair effect than S1, indicating that the specific preparation process of this invention is necessary for forming an effective barrier repair film. Comparative Example 4 (DS4), using a commercially available liquid crystal emulsifier, also showed a weaker repair effect than S1, indicating that the biomimetic film formed by the synergistic effect of specific components in this invention is superior in structure and function to the system formed by a general liquid crystal emulsifier.

[0114] Comprehensive data indicate that the barrier repair performance of S1 is the result of the synergistic effect of its specific components and specific preparation process. The membrane structure constructed by this combination can simultaneously achieve physical closure and bioactive delivery.

[0115] Test Example 5: The experimental steps are as follows: 1. Prepare detached pigskin with a thickness of 700±100μm and mount it on a Franz diffusion cell with the cuticle facing the supply chamber.

[0116] 2. Add PBS buffer (pH 7.4) containing 2% Tween-80 to the receiving chamber.

[0117] 3. After equilibrating the diffusion cell at 32°C, apply 10 mg / cm² of the test sample (S1, DS1, DS2, DS3) to the skin surface.

[0118] 4. The experiment lasted for 24 hours. After the experiment, the skin surface residue, stratum corneum (by tape peeling method), epidermis and dermis (by thermal separation method), and receiving pool liquid were collected respectively.

[0119] 5. Extraction was performed on each collected sample, and the content of compound K was quantitatively analyzed by HPLC-MS / MS. The results were expressed in μg / cm³. 2 express.

[0120] The experimental results are shown in Table 5.

[0121] Table 5. Distribution of compound K in different skin layers of different samples after 24 hours (mean ± standard deviation, μg / cm³) 2 ): This test evaluates the transdermal delivery efficiency of each formulation by quantitatively analyzing the distribution of compound K in different layers of the skin.

[0122] Example 1 (S1) showed the highest retention of compound K (3.49 μg / cm³) in the active epidermis and dermis. 2 The permeation in the receiving fluid is low (0.21 μg / cm³). 2 This data indicates that S1 can deliver the active ingredient to the effective site of action in the skin and concentrate it there, while controlling the amount that enters the systemic circulation. The delivery efficiency of S1 is related to its lamellar liquid crystal structure. The similarity of this structure to stratum corneum lipids promotes affinity, and the amphiphilic component fluidizes the stratum corneum lipids, reducing permeability resistance. Simultaneously, this formulation system maintains a high concentration of the active ingredient on the skin surface, increasing the concentration gradient for penetration.

[0123] The results of the comparative examples confirmed the above analysis. Comparative Example 1 (DS1), as a conventional emulsion, showed very low permeability in all layers. Comparative Example 2 (DS2), using the process of this invention and conventional red ginseng extract, had a lower permeability than S1, indicating that the raw material enriched with rare ginsenosides is the basis for achieving efficient delivery. Comparative Example 3 (DS3), using the raw material of this invention and conventional process, had a high retention in the stratum corneum, but the permeability in the epidermis and dermis was much lower than S1, indicating that the membrane structure formed by the conventional process hinders the transfer of active ingredients to the deeper layers of the skin.

[0124] Comprehensive data indicate that the delivery efficiency of S1 is the result of the synergistic effect of its specific components and specific preparation process. The biomimetic membrane structure constructed by this combination promotes the effective penetration and enrichment of active ingredients in the skin.

[0125] Test Example 6: The experimental steps are as follows: 1. Place the formulation samples (S1, DS1, DS2, DS3) in dialysis bags with a molecular weight cutoff of 3.5 kDa and dialyze in deionized water at 4°C for 48 hours, changing the water 6 times during this period. Collect the samples and freeze-dry them into powder. Before use, dissolve the freeze-dried powder in serum-free DMEM medium to prepare a stock solution containing an equivalent concentration of red ginseng extract, and filter to sterilize.

[0126] 2. RAW 264.7 macrophages were cultured at a concentration of 1×10⁻⁶ cells / mL. 5 The cells were seeded at a density of cells / mL in 96-well plates.

[0127] 3. The working concentration of each sample stock solution that has no significant toxicity to cells was screened using the MTT assay.

[0128] 4. The experimental groups included: blank control group (culture medium only), model group (1 μg / mL LPS), positive control group (10 μM dexamethasone + 1 μg / mL LPS), and each sample group (sample stock solution of a screened safe concentration + 1 μg / mL LPS).

[0129] 5. Each sample group was pretreated with the corresponding stock solution for 1 hour. Then, except for the blank control group, all other groups were treated with LPS to induce inflammation.

[0130] 6. After culturing at 37℃ and 5% CO2 for 24 hours, the cell culture supernatant was taken, reacted with Griess reagent, and the absorbance was measured at 540nm using an ELISA reader.

[0131] 7. Calculate the NO concentration based on the sodium nitrite standard curve, and use the formula: NO inhibition rate (%) = [(OD200%) - NO200%] 模型组 -OD 样品组 ) / (OD 模型组 -OD 空白对照组 )]×100, calculate the NO inhibition rate.

[0132] The experimental results are shown in Table 6.

[0133] Table 6. Inhibitory effects of each sample on LPS-induced NO production in RAW 264.7 cells: This test evaluated the ability of different formulations to inhibit the production of the inflammatory mediator NO at the cellular level.

[0134] The extract of Example 1 (S1) exhibited a NO inhibition rate of 82.7%, demonstrating the highest anti-inflammatory activity among all groups. This activity is mainly attributed to the enrichment of rare ginsenosides (such as compound K), which can inhibit iNOS expression and thus reduce NO production. Furthermore, the formulation structure of this invention may exist in specific aggregate forms after pretreatment, which helps the active ingredients to function better in cell experiments.

[0135] The results of the comparative examples analyzed the source of S1 activity. Comparative Example 1 (DS1) used conventional red ginseng extract, and its NO inhibition rate was only 16.9%, indicating that the concentration of active ingredients in the conventional extract was insufficient. Comparative Example 2 (DS2) used the process of this invention and conventional extract, and its NO inhibition rate was 38.2%, higher than DS1, indicating that the formulation matrix can enhance activity, but the overall activity is still not high due to the limited efficacy of the raw materials, which proves that raw materials enriched with rare ginsenosides are fundamental. Comparative Example 3 (DS3) used the raw materials of this invention and conventional process, and its NO inhibition rate was 54.5%, lower than S1, indicating that even if effective active raw materials are used, their biological activity cannot be fully expressed without the specific preparation process of this invention.

[0136] Comparing the data from each group, the high anti-inflammatory activity of S1 is the result of the combined effect of specific raw materials (extracts enriched with rare ginsenosides) and specific preparation processes.

[0137] In summary, the results of Test Examples 1-6 systematically verified the beneficial effects of the present invention from multiple dimensions, including physicochemical properties, bioactivity, active ingredient delivery efficiency, and final efficacy. The data clearly demonstrate that by combining a specifically prepared red ginseng extract enriched with rare ginsenosides with a specific saponin molecule activation and programmed cooling process, a formulation that forms a biomimetic film in situ on the skin surface can be prepared. This biomimetic film not only possesses excellent adhesion stability (Test Example 1) and physical barrier function (Test Examples 2, 4), but also serves as a highly efficient transdermal delivery system (Test Example 5), effectively enriching highly bioactive components (Test Example 6) at the site of action, and achieving controlled release of active ingredients through an enzymatic response mechanism (Test Example 3), ultimately achieving a superior and long-lasting skin barrier repair effect. These effects are unattainable by existing conventional formulations or comparative examples that only meet some of the technical features of the present invention.

[0138] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A topical, soothing, and antipruritic bioactive biomimetic film skincare preparation, characterized in that, Made from the following ingredients in parts by weight: Red ginseng extract enriched with rare ginsenosides: 0.8–1.5 parts; Colloidal oat flour: 1.5–2.5 parts; Cetearyl alcohol: 2.5–3.5 parts; Distearate dimethyl ammonium chloride: 1.5–2.5 parts; And the remainder of water and cosmetic excipients acceptable to the cosmetics industry.

2. The topical soothing and antipruritic bioactive biomimetic film skincare preparation according to claim 1, characterized in that, The red ginseng extract enriched with rare ginsenosides was prepared by a method comprising the following steps: (a) Processing: Steam the red ginseng at 115-120℃ with saturated steam for 3.0-3.5 hours; (b) Extraction: The processed red ginseng was extracted with an ethanol solution; (c) Chromatographic enrichment: The extract is loaded onto a macroporous adsorption resin column, eluted sequentially with water and 40-45% v / v ethanol solution and the eluent is discarded, then eluted again with 75-80% v / v ethanol solution and the eluent is collected. (d) Post-processing: The collected eluent is concentrated and dried to obtain the extract.

3. The topical soothing and antipruritic bioactive biomimetic film skincare preparation according to claim 1, characterized in that, The raw materials are in the following weight parts: 1.0 part of red ginseng extract enriched with rare ginsenosides, 2.0 parts of colloidal oat flour, 3.0 parts of cetearyl alcohol, and 2.0 parts of distearate dimethyl ammonium chloride.

4. The topical soothing and antipruritic bioactive biomimetic film skincare preparation according to claim 1, characterized in that, The raw materials also include one or more selected from ascorbyl glucoside, hydroxyphenylpropionamide benzoic acid, polyols, oils, and silicone oils.

5. A method for preparing a topical soothing and antipruritic bioactive biomimetic film skin care formulation according to any one of claims 1-4, characterized in that, Includes the following steps: (A) Saponin molecule activation: Red ginseng extract enriched with rare ginsenosides was mixed with polyol and subjected to ultrasonic treatment to obtain an activation solution; (B) Emulsification: The oil phase containing cetearyl alcohol and distearate dimethyl ammonium chloride is homogenized and emulsified with the aqueous phase containing the activated liquid obtained in step (A) and colloidal oat flour at high temperature; (C) Programmed cooling: The emulsion obtained in step (B) is cooled at a controlled rate of 0.5 to 1.0 °C / min to form a layered liquid crystal structure.

6. The preparation method according to claim 5, characterized in that, The ultrasonic treatment described in step (A) is carried out in a water bath at 45-50°C and the ultrasonic frequency is 20-30kHz.

7. The preparation method according to claim 5, characterized in that, The high temperature mentioned in step (B) is 75-85°C, and the shearing speed for homogenization emulsification is 3000-5000 rpm.

8. The preparation method according to claim 5, characterized in that, Following step (C), the process also includes adding the heat-sensitive active ingredient when the system temperature drops below 45°C.

9. The preparation method according to claim 5, characterized in that, Before step (B), the steps for preparing the aqueous phase include: dispersing colloidal oat flour in water at a temperature of 75–85°C and stirring at a constant temperature for at least 20 minutes.

10. The preparation method according to claim 5, characterized in that, The polyol mentioned in step (A) is 1,2-pentanediol.

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