External repairing anti-wrinkle composition and preparation method thereof

Abstract

The invention discloses an external repairing anti-wrinkle composition. The external repairing anti-wrinkle composition comprises a first active component, a second active component, a third active component and a carrier, wherein the first active component comprises a corn germ extract and retinol; the second active component comprises a ligusticum wallichii extract, a pseudo-ginseng extract, a dogwood extract and a herba artemisiae scopariae extract; the third active component comprises a palmitoyl pentapeptide-4 and hyaluronic acid conjugate; the carrier is an oil phase, a water phase and / or an excipient. According to the invention, all the active ingredients are scientifically proportioned to realize synergistic interaction, and the skin care product can be prepared into essence, skin moistening oil, facial mask and other skin care products for external use, is safe and free of side effects, can slow down the deepening and diffusion of wrinkles to a certain extent, and helps the skin to recover elasticity and compactness.

Description

Technical Field

[0001] The present invention relates to the technical field of repairing and anti-wrinkle compositions, and more specifically, to an externally-used repairing and anti-wrinkle composition and a preparation method thereof. Background Art

[0002] As we age, our skin inevitably undergoes an aging process, and environmental factors, such as ultraviolet radiation, dry climate, and environmental pollution, further exacerbate skin damage and accelerate the pace of aging. In order to enhance the skin's own defense and repair capabilities, consumers tend to use skin care products for daily maintenance. As an important type of skin care product, topical repair and anti-wrinkle compositions are designed to effectively slow down the deepening and spread of wrinkles and promote the recovery of skin elasticity and the improvement of firmness through prevention and improvement mechanisms. These compositions can be flexibly prepared into a variety of forms, such as anti-wrinkle masks, creams, essences, and moisturizing oils, to meet the personalized needs of different consumers. In addition, in order to improve the repair and anti-wrinkle effects, these compositions often work in synergy with other cosmetic methods such as laser treatment and microneedle therapy to form a comprehensive skin care solution.

[0003] However, the current facial cream products on the market generally have insufficient active ingredient content, resulting in a high reliance on ingredient concentration for anti-wrinkle effects and ineffective results. Although some products incorporate a variety of plant extracts in an attempt to utilize the antioxidant properties of natural ingredients, these ingredients may cause adverse skin reactions such as redness, swelling, and itching for sensitive skin, limiting their widespread use.

[0004] In view of this, it is particularly important to develop an external anti-wrinkle repair composition that is safe, highly effective and has low side effects. The composition needs to precisely control the proportion of active ingredients to ensure that while improving the anti-wrinkle effect, it reduces unnecessary irritation to the skin, thereby providing consumers with a more ideal and reliable skin care option. Summary of the invention

[0005] The present invention provides an external repair and anti-wrinkle composition and a preparation method thereof, which can achieve synergistic efficacies by scientifically proportioning various active ingredients, can be prepared into skin care products such as essence, moisturizing oil, and facial mask for external use, is safe and has no side effects, can slow down the deepening and spread of wrinkles to a certain extent, and help the skin restore elasticity and firmness.

[0006] In order to achieve these purposes and other advantages according to the present invention, there is provided an external anti-wrinkle repair composition, comprising a first active ingredient, a second active ingredient, a third active ingredient and a carrier: The first active ingredient includes corn germ extract and retinol; The second active ingredient includes chuanxiong extract, notoginseng extract, cornus officinalis extract, and capillaris extract; The third active ingredient includes a conjugate of palmitoyl pentapeptide-4 and hyaluronic acid; The carrier is an oil phase, an aqueous phase and / or an excipient.

[0007] Preferably, corn germ oil is obtained by extracting corn germ using n-hexane, extract is obtained by molecular distillation, and corn germ extract is obtained by vacuum distillation; Dissolve corn germ extract and retinol in sweet almond oil respectively, dissolve maltodextrin and glycerol in water, add ethanol as a co-solvent, slowly add the oil phase into the water phase, the mass ratio of the oil phase to the water phase is 1:2, homogenize and emulsify, stir to form an emulsion, spray dry, the inlet air temperature is 50°C, and the outlet air temperature is 30°C, so as to obtain the first active ingredient, wherein the mass ratio of corn germ extract, retinol, maltodextrin and glycerol is 2:0.5:10:10.

[0008] Preferably, the mass ratio of Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract and Artemisia capillaris extract is 50:40-50:20-30:10-20; The extract of Chuanxiong is prepared by the following method: washing, drying and crushing the rhizome of Chuanxiong, adding the powder of Chuanxiong to 75% ethanol at a weight volume ratio of g / mL of 1:5-8, reflux extraction at 60-80°C for 2-3 h, filtering, collecting the filtrate, and distilling under reduced pressure to obtain the extract of Chuanxiong; The Panax notoginseng extract is prepared by the following method: washing, drying, and crushing the roots of Panax notoginseng, mixing them with an entrainer, and subjecting them to supercritical extraction. The supercritical extraction conditions are a pressure of 20-30 MPa and a temperature of 40-60° C. After the extraction, the carbon dioxide is converted into a gaseous state by reducing the pressure, collecting the extract, adsorbing and eluting it with a macroporous resin, rotary evaporating it, and distilling it under reduced pressure to obtain the Panax notoginseng extract; The cornus extract is prepared by the following method: washing, drying and crushing cornus fruit, adding cornus powder to 75% ethanol at a weight volume ratio of g / mL of 1:5-8, soaking for 12-24 hours, filtering, vacuum distillation, separation by polyamide column chromatography, rotary evaporation, and vacuum distillation to obtain the cornus extract; The Artemisia capillaris extract is prepared by the following method: wash, dry and crush the Artemisia capillaris, add the Artemisia capillaris powder to 75% ethanol at a weight-to-volume ratio of g / mL of 1:5-8, reflux extract at 50-70°C for 1-2 h, filter, collect the filtrate, and distill under reduced pressure to obtain the Artemisia capillaris extract.

[0009] Preferably, a phosphate buffer solution containing 1 mol / L palmitoyl pentapeptide-4 and a phosphate buffer solution containing 2 mol / L hyaluronic acid are prepared. Prepare 0.2% glutaraldehyde phosphate buffer, slowly add palmitoyl pentapeptide-4 phosphate buffer, slowly add hyaluronic acid phosphate buffer, and react for 3 h; The reaction solution was placed in a dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed with a large amount of deionized water at 4°C for 24 hours. During this period, the dialysis external fluid was replaced every 4-6 hours. The dialyzed solution was freeze-dried to obtain a conjugate of palmitoyl pentapeptide-4 and hyaluronic acid.

[0010] Preferably, the amount of each component in parts by weight, the preparation method comprises: Dissolving the first active ingredient with sweet almond oil, stirring until completely dissolved, to obtain a mixed solution I with a concentration of 25-30%; Mix glycerol and butanediol in a mass ratio of 1-2:1, stir, add the second active ingredient, stir until completely dissolved, and obtain a mixed solution II with a concentration of 20-25%; Add 100 parts of water into a stirring pot, slowly add 0.1-0.5 parts of carbomer, and continue stirring for 15-20 minutes until the carbomer is fully swollen to form a uniform colloidal solution, slowly pour 3-4 parts of mixed solution II into the stirring pot, stir for 10-15 minutes until it is evenly dispersed, then slowly pour 0.8-1 parts of mixed solution I into the stirring pot, stir for 5-10 minutes, add 0.08-0.1 parts of triethanolamine dropwise into the pot, adjust the pH to 5.5-6.5, add 0.05-0.08 parts of the third active ingredient, stir for 5-10 minutes until it is completely dissolved, add 0.3-0.5 parts of phenoxyethanol, stir for 5 minutes, and obtain.

[0011] Preferably, the amount of each component is calculated by weight, and the preparation method comprises: Dissolving the first active ingredient with sweet almond oil, stirring until completely dissolved, to obtain a mixed solution III with a concentration of 25-30%; Dissolving the third active ingredient in ethanol and stirring until completely dissolved to obtain a mixed solution IV with a concentration of 50-60%; Add 100 parts of sweet almond oil into a stirring pot, slowly pour 0.8-1 parts of mixed solution III into the stirring pot, stir for 5-10 minutes until uniformly dispersed, slowly add 1-2 parts of the second active ingredient, stir for 10-15 minutes until fully blended, slowly pour 0.1-0.15 parts of mixed solution IV into the stirring pot, stir for 5-10 minutes, drop 0.1 parts of lavender essential oil, stir for 5 minutes, add 3 parts of beeswax and 5 parts of lanolin, heat the stirring pot in a water bath, slowly raise the temperature to 60-65°C, continue stirring until the beeswax and lanolin are completely melted, and obtain the product.

[0012] The application of the external repairing and anti-wrinkle composition in the preparation of cosmetics.

[0013] Preferably, the external repairing and anti-wrinkle composition is used in the preparation of repairing and anti-wrinkle cosmetics.

[0014] The present invention has at least the following beneficial effects: First, the repair and anti-wrinkle composition prepared by the present invention can achieve synergistic effects by scientifically proportioning the active ingredients, and can be prepared into skin care products such as essence, moisturizing oil, facial mask, etc. for external use. It is safe and has no side effects. It can slow down the deepening and spread of wrinkles to a certain extent, help the skin restore elasticity and firmness, improve the anti-wrinkle effect, and reduce unnecessary stimulation to the skin, thereby providing consumers with a more ideal and reliable skin care option.

[0015] Second, the first active ingredient added in the present invention includes corn germ extract and retinol. The tocopherol in the corn germ extract can stabilize retinol, prevent retinol from being oxidized, avoid the isomerization reaction of retinol, give full play to the anti-wrinkle effect of retinol, promote cell renewal, and reduce wrinkles.

[0016] Third, the second active ingredient added by the present invention includes Chinese medicine extracts. The ferulic acid in the Chuanxiong extract can remove free radicals in the skin. It also contains some ingredients that can promote collagen synthesis, replenishing the collagen lost by the skin due to aging and other reasons from the source, and reducing the formation of wrinkles. The ginsenosides in the Panax notoginseng extract can promote the metabolism of skin cells, stimulate the activity of fibroblasts, and synthesize collagen. The flavonoids in the Cornus extract can protect collagen and elastic fibers from damage, increase the elasticity and firmness of the skin, and reduce the formation of wrinkles. The flavonoids and chlorogenic acid in the Artemisia capillaris extract can remove free radicals and reduce the damage to collagen and elastic fibers, and make the skin tighter by promoting skin cells to produce more collagen.

[0017] Fourth, the third active ingredient added by the present invention includes palmitoyl pentapeptide-4 and hyaluronic acid, which are chemically connected to form a conjugate to jointly promote the anti-wrinkle effect. Palmitoyl pentapeptide-4 can simulate the signal molecules in the skin, stimulate fibroblasts to produce collagen and elastic fibers, and hyaluronic acid can fill between the newly generated collagen fibers to maintain the fullness of the skin, make the skin more firm, and reduce the generation of wrinkles. At the same time, the moisturizing effect of hyaluronic acid can provide a good environment for skin cells, which is conducive to palmitoyl pentapeptide-4 to better play its function of stimulating cell activity and promote the synthesis of extracellular matrix components.

[0018] Other advantages, objectives and features of the present invention will be embodied in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below with reference to examples so that those skilled in the art can implement the invention with reference to the description.

[0020] It should be understood that the terms such as “having”, “including” and “comprising” used herein do not exclude the existence or addition of one or more other elements or combinations thereof.

[0021] It should be noted that the experimental methods described in the following embodiments are conventional methods unless otherwise specified, and the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0022] <Example 1> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Preparing the first active ingredient: Place 500 g corn germ in a conical flask, slowly add 1500 mL of n-hexane to completely immerse the corn germ, oscillate at a frequency of 150 times / min for 4 h, take the mixed solution, let it stand for 30 min to separate the layers, collect the n-hexane extract at the lower layer, perform molecular distillation at 180°C, connect a vacuum pump, and a feed rate of 2 mL / min. Light components (volatile impurities such as n-hexane) are evaporated, collect the remaining corn germ oil extract, perform reduced pressure distillation at 120°C, connect a vacuum pump, and remove the residual volatile components. Collect the corn germ extract, weigh about 20 g, and seal it for later use.

[0023] 20 g corn germ extract and 5 g retinol were slowly added to 15 mL sweet almond oil, respectively, placed on a magnetic stirrer, and stirred at 300 r / min for 30 min until completely dissolved to obtain an oil phase; 10 g maltodextrin and 10 mL glycerol were added to 30 mL water, and then 5 mL ethanol was added and stirred for 20 min until completely dissolved to obtain an aqueous phase; the oil phase was slowly added dropwise to the aqueous phase, and the emulsifier was turned on at the same time, and the speed was set to 8000 r / min to form a stable emulsion; the emulsion was transferred to the feed tank of the spray dryer, and the inlet air temperature was set to 50°C, the outlet air temperature was set to 30°C, and the feed rate was 10 mL / min, and spray drying was performed, and the dried powder was collected to obtain the first active ingredient, weighing about 40-45 g, and sealed for storage for later use.

[0024] (2) Preparation of the second active ingredient: The rhizome of Chuanxiong was washed, dried and crushed. 100 g of Chuanxiong powder was added to 600 mL of 75% ethanol at a weight-to-volume ratio of g / mL of 1:6. The mixture was placed on a reflux condenser and refluxed at 70 °C for 2 h. The color of the solution gradually deepened and became brown. The solution was filtered and the filtrate was collected. The filtrate was transferred to a rotary evaporator and distilled under reduced pressure. A vacuum pump was connected to obtain a brown-black viscous Chuanxiong extract, which weighed about 20 g and was sealed for later use.

[0025] The roots of Panax notoginseng were washed, dried and crushed. 100 g of Panax notoginseng powder was put into a supercritical extraction kettle. Anhydrous ethanol (30% by weight of the powder) was added as an entrainer and mixed for supercritical extraction. The supercritical extraction conditions were a pressure of 25 MPa and a temperature of 50°C. The carbon dioxide cylinder was opened with a flow rate of 15 L / h and the extraction was performed for 2 h. After the extraction, the carbon dioxide was converted into a gas by decompression. The extract was collected and adsorbed on an AB-8 macroporous resin. It was first rinsed with 3 times the column volume of deionized water and then eluted with 70% ethanol at a flow rate of 2 mL / min. The eluate was collected and distilled under reduced pressure. A vacuum pump was connected to obtain a light yellow Panax notoginseng extract, which was weighed about 20 g and sealed for later use.

[0026] Wash, dry and crush the cornus officinalis fruit. Add 60 g of cornus officinalis powder into 400 mL of 75% ethanol at a weight-to-volume ratio of 1:7. Soak for 18 h, filter, and distill under reduced pressure. Load the column onto a polyamide column. Rinse with 4 times the column volume of deionized water, and elute with 30% ethanol at a flow rate of 1.5 mL / min. Collect the eluate, rotary evaporate, and distill under reduced pressure to obtain a dark red cornus officinalis extract, weigh about 10 g, and seal it for later use.

[0027] Wash, dry and crush the Artemisia capillaris. Add 40 g of Artemisia capillaris powder to 250 mL of 75% ethanol at a weight-to-volume ratio of 1:6. Install a reflux condenser and reflux extract at 60°C for 1.5 h. The solution turns from yellow-green to dark green. Filter and collect the filtrate. Transfer the filtrate to a rotary evaporator, distill under reduced pressure, and connect a vacuum pump to obtain a dark green Artemisia capillaris extract, weighing about 8 g. Seal and store for later use.

[0028] Take Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract and Artemisia capillaris extract in a mass ratio of 5:5:3:2, physically mix them, and obtain the second active ingredient.

[0029] (3) Preparation of the third active ingredient: Prepare 0.1 M phosphate buffer (PBS), dissolve 1 mmol of palmitoyl pentapeptide-4 in 10 mL of phosphate buffer to prepare a phosphate buffer with a concentration of 1 mol / L of palmitoyl pentapeptide-4, dissolve 2 mmol of hyaluronic acid with a molecular weight of 1-1.5 million Da in 10 mL of phosphate buffer to prepare a phosphate buffer with a concentration of 2 mol / L of hyaluronic acid; Prepare 0.2% glutaraldehyde phosphate buffer, take 2 mL and slowly drop it into the phosphate buffer of palmitoyl pentapeptide-4 to mix evenly, slowly drop it into the phosphate buffer of hyaluronic acid to complete the dropping process within 30 min, and react for 3 h; In order to remove unreacted glutaraldehyde and other impurities, the reaction solution was placed in a dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed with a large amount of deionized water at 4°C for 24 h. During this period, the dialysis external fluid was replaced every 6 h. The dialyzed solution was freeze-dried to obtain a white palmitoyl pentapeptide-4 and hyaluronic acid conjugate, i.e., the third active ingredient, weighing approximately 355 g and sealed for storage.

[0030] (4) Preparation of composition: The first active ingredient is dissolved in sweet almond oil and stirred until completely dissolved to obtain a mixed solution I with a concentration of 30%; glycerol and butylene glycol are mixed in a mass ratio of 2:1, stirred, and the second active ingredient is added and stirred until completely dissolved to obtain a mixed solution II with a concentration of 25%; Add 1000 g of water to a stirring pot, slowly add 3.5 g of carbomer, and continue stirring for 20 min until the carbomer is fully swollen to form a uniform colloidal solution, slowly pour 40 g of mixed solution II into the stirring pot, stir for 15 min until it is evenly dispersed, then slowly pour 10 g of mixed solution I into the stirring pot, stir for 10 min, add 1 g of triethanolamine dropwise to the pot, adjust the pH to 5.5-6.5, add 0.8 g of the third active ingredient, stir for 10 min until it is completely dissolved, add 5 g of phenoxyethanol, and stir for 5 min to obtain.

[0031] <Example 2> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Prepare the first active ingredient using the same method as in Example 1.

[0032] (2) Preparing the second active ingredient: The preparation method of the raw materials is the same as that of Example 1. Take the Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract, and Artemisia capillaris extract in a mass ratio of 5:4:2:1, and physically mix them to obtain the second active ingredient.

[0033] (3) Prepare the third active ingredient using the same method as in Example 1.

[0034] (4) Preparation of composition: Dissolve the first active ingredient in sweet almond oil and stir until completely dissolved to obtain a mixed solution I with a concentration of 25%; mix glycerol and butylene glycol in a mass ratio of 1:1, stir, add the second active ingredient, stir until completely dissolved, and obtain a mixed solution II with a concentration of 20%; Add 1000 g of water to a stirring pot, slowly add 2 g of carbomer, and continue stirring for 15 min until the carbomer is fully swollen to form a uniform colloidal solution, slowly pour 30 g of mixed solution II into the stirring pot, stir for 10 min until it is evenly dispersed, then slowly pour 8 g of mixed solution I into the stirring pot, stir for 5 min, add 0.8 g of triethanolamine dropwise into the pot, adjust the pH to 5.5-6.5, add 0.5 g of the third active ingredient, stir for 5 min until it is completely dissolved, add 3 g of phenoxyethanol, and stir for 5 min to obtain.

[0035] <Example 3> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Prepare the first active ingredient using the same method as in Example 1.

[0036] (2) Preparing the second active ingredient: The preparation method of the raw materials is the same as that of Example 1. Take the Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract, and Artemisia capillaris extract in a mass ratio of 5:5:3:2, and physically mix them to obtain the second active ingredient.

[0037] (3) Prepare the third active ingredient using the same method as in Example 1.

[0038] (4) Preparation of composition: The first active ingredient is dissolved in sweet almond oil and stirred until completely dissolved to obtain a mixed solution III with a concentration of 30%; the third active ingredient is dissolved in ethanol and stirred until completely dissolved to obtain a mixed solution IV with a concentration of 60%; Add 1000 g of sweet almond oil into a stirring pot, slowly pour 10 g of mixed solution III into the stirring pot, stir for 10 min until evenly dispersed, slowly add 20 g of the second active ingredient, stir for 15 min until fully blended, slowly pour 1.5 g of mixed solution IV into the stirring pot, stir for 10 min, drop 1 g of lavender essential oil, stir for 5 min, add 30 g of beeswax and 50 g of lanolin, heat the stirring pot in a water bath, slowly raise the temperature to 60-65°C, and continue stirring until the beeswax and lanolin are completely melted.

[0039] <Example 4> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Prepare the first active ingredient using the same method as in Example 1.

[0040] (2) Preparing the second active ingredient: The preparation method of the raw materials is the same as that of Example 1. Take the Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract, and Artemisia capillaris extract in a mass ratio of 5:4:2:1, and physically mix them to obtain the second active ingredient.

[0041] (3) Prepare the third active ingredient using the same method as in Example 1.

[0042] (4) Preparation of composition: The first active ingredient is dissolved in sweet almond oil and stirred until completely dissolved to obtain a mixed solution III with a concentration of 25%; the third active ingredient is dissolved in ethanol and stirred until completely dissolved to obtain a mixed solution IV with a concentration of 50%; Add 1000 g of sweet almond oil into a stirring pot, slowly pour 8 g of mixed solution III into the stirring pot, stir for 5 min until evenly dispersed, slowly add 10 g of the second active ingredient, stir for 10 min until fully blended, slowly pour 1 g of mixed solution IV into the stirring pot, stir for 5 min, drop 1 g of lavender essential oil, stir for 5 min, add 30 g of beeswax and 50 g of lanolin, heat the stirring pot in a water bath, slowly raise the temperature to 60-65°C, and continue stirring until the beeswax and lanolin are completely melted.

[0043] <Comparative Example 1> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Prepare corn germ extract using the same method as in Example 1.

[0044] (2) Preparation of Chinese herbal medicine extracts: The preparation method of the raw materials is the same as that of Example 1. The mass ratio of Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract and Artemisia capillaris extract is 5:5:3:2, and the mixture is physically mixed to obtain a Chinese herbal medicine extract.

[0045] (3) Prepare the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid using the same method as in Example 1.

[0046] (4) Preparation of composition: Mix a Chinese herbal medicine extract and a corn germ extract in a mass ratio of 5:1 to obtain a powder, mix glycerol and butanediol in a mass ratio of 2:1, stir, add the powder, stir until completely dissolved, and obtain a mixed solution with a concentration of 25%; Add 1000 g of water to a stirring pot, slowly add 3.5 g of carbomer, and continue stirring for 20 min until the carbomer is fully swollen to form a uniform colloidal solution. Slowly pour 40 g of the mixed solution into the stirring pot and stir for 15 min until it is evenly dispersed. Add 0.5 g of retinol and slowly pour it into the stirring pot and stir for 10 min. Add 1 g of triethanolamine dropwise to the pot and adjust the pH to 5.5-6.5. Add 0.8 g of palmitoyl pentapeptide-4 and hyaluronic acid conjugate and stir for 10 min until it is completely dissolved. Add 5 g of phenoxyethanol and stir for 5 min.

[0047] <Comparative Example 2> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Prepare corn germ extract retinol complex using the same method as in Example 1.

[0048] (2) Preparation of Chinese herbal medicine extracts: The preparation method of the raw materials is the same as that of Example 1. The mass ratio of Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract and Artemisia capillaris extract is 5:5:3:2, and the mixture is physically mixed to obtain a Chinese herbal medicine extract.

[0049] (3) Preparation of composition: Dissolve the corn germ extract retinol complex with sweet almond oil, stir until completely dissolved, and obtain a mixed solution I with a concentration of 30%; mix glycerol and butylene glycol in a mass ratio of 2:1, stir, add the traditional Chinese medicine extract, stir until completely dissolved, and obtain a mixed solution II with a concentration of 25%; Add 1000 g of water to a stirring pot, slowly add 3.5 g of carbomer, and continue stirring for 20 min until the carbomer is fully swollen to form a uniform colloidal solution. Slowly pour 40 g of mixed solution II into the stirring pot and stir for 15 min until it is evenly dispersed. Then slowly pour 10 g of mixed solution I into the stirring pot and stir for 10 min. Add 1 g of triethanolamine dropwise to the pot, adjust the pH to 5.5-6.5, add 0.4 g of palmitoyl pentapeptide-4 and 0.4 g of hyaluronic acid, stir for 10 min until it is completely dissolved, add 5 g of phenoxyethanol, and stir for 5 min.

[0050] <Comparative Example 3> A method for preparing an external repairing and anti-wrinkle composition, the preparation method comprising: (1) Prepare corn germ extract retinol complex using the same method as in Example 1.

[0051] (2) Prepare the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid using the same method as in Example 1.

[0052] (3) Preparation of composition: Dissolve the corn germ extract retinol complex in sweet almond oil and stir until completely dissolved to obtain a mixed solution with a concentration of 30%; Add 1000 g of water to a stirring pot, slowly add 3.5 g of carbomer, and continue stirring for 20 min until the carbomer is fully swollen to form a uniform colloidal solution. Slowly pour 10 g of the mixed solution into the stirring pot and stir for 10 min. Add 1 g of triethanolamine dropwise to the pot, adjust the pH to 5.5-6.5, add 0.8 g of palmitoyl pentapeptide-4 and hyaluronic acid conjugate, stir for 10 min until completely dissolved, add 5 g of phenoxyethanol, and stir for 5 min.

[0053] <Cell proliferation assay> The human skin fibroblast cell line HSF was cultured in DMEM high-glucose medium containing 10% fetal bovine serum and 1% penicillin-streptomycin in a 37°C, 5% CO2 incubator and passaged every 2-3 days.

[0054] Human skin fibroblasts HSF in the logarithmic growth phase were inoculated in a 96-well plate at a density of 5×10³ / well, and 6 replicates were set for each group. After the cells adhered to the wall (about 24 h), the following treatments were performed: an equal volume of medium without drugs was added to the blank control group, and the final concentration of 50 μg / mL was diluted with medium in Example 1-4 and Comparative Example 1-3. After 48 h of culture, subsequent detection was performed. The MTT method was used to detect cell proliferation. 20 μL of MTT solution (5 mg / mL) was added to each well, and the culture was continued for 4 h. The supernatant was removed, 150 μL of DMSO was added to each well, and the crystals were fully dissolved by shaking for 10 min. The absorbance (OD value) of each well was measured at a wavelength of 570 nm using an enzyme marker. The OD value reflects the cell proliferation activity, and the cell proliferation rate (%) was calculated. The test results are shown in Table 1.

[0055] Table 1 Group Average OD value Cell proliferation rate (%) Blank control 0.45 - Example 1 0.63 40 Example 2 0.56 24.4 Example 3 0.68 48.9 Example 4 0.59 31.1 Comparative Example 1 0.50 11.1 Comparative Example 2 0.48 6.7 Comparative Example 3 0.46 2.2 Human skin fibroblasts are key cells for synthesizing collagen and elastic fibers. The increase in their proliferation activity means that more extracellular matrix components can be produced, which helps to fill skin depressions and repair damaged tissues, thereby reducing wrinkle formation. As can be seen from Table 1, Examples 1-4 can all promote cell proliferation, thanks to the various active ingredients therein, by promoting the proliferation of human skin fibroblasts, providing support for skin repair at the cellular level. Specifically, the first active ingredient comprises corn germ extract and retinol, and the tocopherol in the corn germ extract can stabilize retinol. In the second active ingredient, Chuanxiong, Panax notoginseng, Cornus officinalis, and Artemisia capillaris extracts are mixed in a specific ratio, containing a variety of active ingredients, such as ferulic acid, ginsenosides, flavonoids, chlorogenic acid, etc., which synergistically resist wrinkles from multiple aspects such as scavenging free radicals and enhancing skin metabolism. The third active ingredient is a palmitoyl pentapeptide-4 and hyaluronic acid conjugate, and the coupling structure synergizes in the skin, and hyaluronic acid can be filled between the newly generated collagen fibers to maintain the fullness of the skin.

[0056] <Safety Evaluation Test> 40 volunteers aged between 18 and 60 years old, with no history of skin allergies (especially allergies to cosmetic ingredients), and who had not used glucocorticoids, immunosuppressants, and other drugs that may affect skin reactions in the past month were selected and randomly divided into 4 groups, with 10 people in each group, and safety tests were performed on the products prepared in Examples 1 to 4. A spot tester coated with 0.02-0.03 mL of the sample was applied to the test site (both sides of the back spine, one side was the test area, and the other side was the blank control area), and gently fixed with medical tape to ensure that the spot tester fits tightly to the skin without bubbles or wrinkles. After application, the test site was observed at three time points: 24 h, 48 h and 72 h, and the skin reaction grading standard was: Grade 0: no reaction; Grade 1: mild erythema, possibly accompanied by mild itching; Grade 2: moderate erythema, infiltration, occasional papules, obvious itching; Grade 3: severe erythema, infiltration, papules, small blisters, severe itching; Grade 4: large blisters, erosion, ulcers, accompanied by pain. The experimental results show that after using Examples 1-4 of the present invention, the subjects in each group did not experience skin irritation reactions such as erythema, itching, papules, and pain within 72 h, indicating that the present invention is non-irritating to human skin and has good safety.

[0057] <Repair and Anti-wrinkle Effect Test> 70 volunteers aged between 45 and 60 with obvious facial wrinkles (crow's feet, frown lines, nasolabial folds, etc.) were selected and randomly divided into 7 groups, 10 people in each group, and divided into a test group and a blank control group. The products prepared in Examples 1-4 and Comparative Examples 1-2 and commercially available ordinary moisturizing lotions (not containing the above-mentioned special active ingredients) were tested for repair and anti-wrinkle effects. All volunteers were required to stop using any skin care products with anti-wrinkle effects for 1 week before the start of the experiment, and only use mild cleansing products and ordinary moisturizing lotions for blank controls for basic cleansing and moisturizing to restore the skin condition to the natural baseline level. After cleansing every morning and evening, each group of volunteers took an appropriate amount of the product and evenly applied it to the face, gently massaged until completely absorbed, and the amount used was controlled to 1 mL each time to ensure that the product could cover the entire face, and the product was used continuously for 8 weeks.

[0058] MPA580 multifunctional skin tester was used to measure the wrinkle depth, wrinkle area, skin moisture content, skin elasticity and other indicators of each volunteer's face at the 0th, 4th and 8th weeks of using the product. The wrinkle depth and wrinkle area were measured using the optical three-dimensional imaging technology of the skin tester; the skin moisture content was measured using the capacitance method; the skin elasticity was measured by measuring the mechanical changes of the skin during stretching and retraction, expressed as the R2 value. The higher the R2 value, the better the skin elasticity. The test results are shown in Table 2-3.

[0059] Table 2 Group Initial wrinkle depth (μm) Wrinkle depth after 4 weeks (μm) Wrinkle depth after 8 weeks (μm) Initial wrinkle area (mm²) Wrinkle area after 4 weeks (mm²) Wrinkle area after 8 weeks (mm²) Example 1 150±20 130±15 110±10 30±5 26±4 22±3 Example 2 145±18 128±16 105±12 28±4 25±3 21±4 Example 3 155±22 132±18 112±14 32±6 27±5 23±6 Example 4 148±13 126±17 108±13 30±5 26±4 22±3 Comparative Example 1 152±19 138±12 122±15 31±5 28±6 25±1 Comparative Example 2 146±21 135±16 120±14 29±4 27±3 24±3 Blank control 153±25 148±19 142±18 32±6 30±5 28±4 Table 3 Group Initial skin moisture content (%) Skin moisture content after 4 weeks (%) Skin moisture content after 8 weeks (%) Initial skin elasticity (R2) Skin elasticity after 4 weeks (R2) Skin elasticity after 8 weeks (R2) Example 1 40±3 45±4 50±5 0.50±0.05 0.55±0.04 0.62±0.03 Example 2 38±4 43±3 48±2 0.52±0.03 0.57±0.05 0.60±0.04 Example 3 41±3 46±4 51±5 0.48±0.04 0.53±0.03 0.60±0.05 Example 4 39±3 44±2 49±4 0.51±0.05 0.56±0.04 0.61±0.03 Comparative Example 1 41±3 43±3 46±3 0.5±0.04 0.53±0.03 0.58±0.04 Comparative Example 2 38±6 42±3 45±2 0.51±0.03 0.54±0.04 0.57±0.03 Blank control 39±4 40±3 42±4 0.48±0.04 0.49±0.03 0.51±0.03 It can be seen from Table 2-3 that Examples 1-4 are superior to the blank control group in terms of wrinkle improvement, skin moisturizing and elasticity enhancement.

[0060] The effect of Example 1 is better than that of Comparative Example 1. This is probably because an organic solvent is used to extract the oil part in corn germ, and a corn germ extract mainly composed of γ-tocopherol is obtained by molecular distillation. When the corn germ extract reacts with retinol, the phenolic hydroxyl group of the corn germ extract can provide hydrogen atoms, thereby interrupting the chain oxidation reaction of free radicals, and can preferentially react with free radicals to protect retinol from the attack of free radicals, thereby improving the stability of retinol to a certain extent, stabilizing the structure of retinol, preventing retinol from being oxidized, avoiding the isomerization reaction of retinol, and giving full play to the anti-wrinkle effect of retinol, promoting cell renewal, and reducing wrinkles.

[0061] The effect of Example 1 is better than that of Comparative Example 2, probably because palmitoyl pentapeptide-4 and hyaluronic acid form a conjugate through chemical connection to jointly promote the anti-wrinkle effect, palmitoyl pentapeptide-4 can simulate the signal molecules in the skin, stimulate fibroblasts to produce collagen and elastic fibers, and hyaluronic acid can fill between the newly generated collagen fibers to maintain the fullness of the skin, make the skin more firm, and reduce the generation of wrinkles. At the same time, the moisturizing effect of hyaluronic acid can provide a good environment for skin cells, which is conducive to palmitoyl pentapeptide-4 to better play its function of stimulating cell activity and promote the synthesis of extracellular matrix components.

[0062] <Skin irritation test> Thirty healthy adult white rabbits were selected, half male and half female, with a body weight between 2.0-2.5 kg. Before the test, the animals were adaptively raised in the laboratory for 3 days, and the temperature and relative humidity in the breeding environment were maintained at (22±2)℃ and (50±5)%, and they were allowed to eat freely. The 30 rabbits were randomly divided into 3 groups, 10 in each group, and divided into a test group and a blank control group. The products prepared in Example 1 and Comparative Example 3 and physiological saline were subjected to skin irritation tests. Hair was removed on both sides of the spine on the back of the rabbit, and the depilatory area was about 3 cm×3 cm. The amount used was controlled at 1 mL each time to ensure that the product could cover the entire depilatory area. It was gently fixed with medical tape and applied once a day for 7 consecutive days.

[0063] The skin reactions of the rabbits were observed at 0.5 h, 2 h, 24 h, 48 h and 72 h after application, including erythema, edema, itching, desquamation, etc. The skin reaction scoring level: 0 means no visible local reaction, no erythema, no edema; 1 means faintly visible erythema, desquamation and slight edema; 2 means moderate erythema, desquamation, moderate edema; 3 means severe erythema, desquamation, severe edema; 4 means purple-red erythema accompanied by eschar formation and skin damage. The average score = the sum of the local irritation scores of all observed animals on the same day ÷ the number of observed animals.

[0064] The test results showed that the rabbit skin in the blank control group showed no obvious irritation reactions such as erythema and edema at any time point, and the scores were all 0, indicating that the test operation and environment did not cause additional irritation to the rabbit skin.

[0065] In Example 1 group, 2 hours after applying the product, some rabbits developed slight erythema, with an average score of 0.2±0.1; 24 hours later, the erythema gradually subsided, and only a very small number of rabbits showed very slight desquamation, with an average score maintained at 0.1±0.05; by 72 hours, the skin had basically returned to normal, with no obvious adverse reactions, and the overall skin irritation score was low.

[0066] In the comparative example 3 group, 0.5 h after applying the product, more rabbits developed mild erythema, some accompanied by slight edema, with an average score of 1.2±0.3; 2 h later, erythema and edema worsened, and some rabbits showed itching symptoms, with an average score of 2.0±0.4; during the period of 4-24 h, although erythema and edema were alleviated, there were still obvious traces, with an average score of 1.5±0.3; after 48-72 h, a small amount of desquamation and slight erythema residues were still visible, with an average score of 0.8±0.2.

[0067] The skin irritation of Example 1 is lower than that of Comparative Example 3, which is probably because the addition of Chinese herbal extracts can not only serve as anti-wrinkle active ingredients, but also effectively reduce the adverse effects of irritating ingredients (possibly from retinol, etc.) on the skin, making the composition safer and suitable for use in skin care products. The volatile oils in Chuanxiong extract and Artemisia capillaris extract can soothe and calm the skin, have certain anti-inflammatory properties, can inhibit the release of inflammatory mediators, and achieve the effect of soothing the skin. The polysaccharides in Panax notoginseng extract and Cornus officinalis extract can soothe the skin, form a protective film on the skin surface, reduce the loss of skin moisture, and keep the skin moist. The organic acids in Cornus officinalis extract can adjust the pH value of the skin, maintaining it in a weakly acidic environment, which is conducive to the stability of the skin barrier function.

[0068] The number of devices and processing scales described here are used to simplify the description of the present invention. Applications, modifications and variations of the present invention will be obvious to those skilled in the art.

[0069] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes, and they can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and the examples shown and described herein.

Claims

1. An external anti-wrinkle repairing composition, characterized in that: Comprising a first active ingredient, a second active ingredient, a third active ingredient and a carrier: The first active ingredient includes corn germ extract and retinol; The second active ingredient includes chuanxiong extract, notoginseng extract, cornus officinalis extract, and capillaris extract; The third active ingredient includes a conjugate of palmitoyl pentapeptide-4 and hyaluronic acid; The carrier is an oil phase, an aqueous phase and / or an excipient.

2. The external anti-wrinkle repairing composition according to claim 1, characterized in that: Extracting corn germ with n-hexane to obtain corn germ oil, using molecular distillation to obtain an extract, and performing vacuum distillation to obtain a corn germ extract; Dissolve corn germ extract and retinol in sweet almond oil respectively, dissolve maltodextrin and glycerol in water, add ethanol as a co-solvent, slowly add the oil phase into the water phase, the mass ratio of the oil phase to the water phase is 1:2, homogenize and emulsify, stir to form an emulsion, spray dry, the inlet air temperature is 50°C, and the outlet air temperature is 30°C, so as to obtain the first active ingredient, wherein the mass ratio of corn germ extract, retinol, maltodextrin and glycerol is 2:0.5:10:

10.

3. The external anti-wrinkle repairing composition according to claim 1, characterized in that: The mass ratio of Chuanxiong extract, Panax notoginseng extract, Cornus officinalis extract and Artemisia capillaris extract is 50:40-50:20-30:10-20; The extract of Chuanxiong is prepared by the following method: washing, drying and crushing the rhizome of Chuanxiong, adding the powder of Chuanxiong to 75% ethanol at a weight volume ratio of g / mL of 1:5-8, reflux extraction at 60-80°C for 2-3 h, filtering, collecting the filtrate, and distilling under reduced pressure to obtain the extract of Chuanxiong; The Panax notoginseng extract is prepared by the following method: washing, drying, and crushing the roots of Panax notoginseng, mixing them with an entrainer, and subjecting them to supercritical extraction. The supercritical extraction conditions are a pressure of 20-30 MPa and a temperature of 40-60° C. After the extraction, the carbon dioxide is converted into a gaseous state by reducing the pressure, collecting the extract, adsorbing and eluting it with a macroporous resin, rotary evaporating it, and distilling it under reduced pressure to obtain the Panax notoginseng extract; The cornus extract is prepared by the following method: washing, drying and crushing cornus fruit, adding cornus powder to 75% ethanol at a weight volume ratio of g / mL of 1:5-8, soaking for 12-24 hours, filtering, vacuum distillation, separation by polyamide column chromatography, rotary evaporation, and vacuum distillation to obtain the cornus extract; The Artemisia capillaris extract is prepared by the following method: wash, dry and crush the Artemisia capillaris, add the Artemisia capillaris powder to 75% ethanol at a weight-to-volume ratio of g / mL of 1:5-8, reflux extract at 50-70°C for 1-2 h, filter, collect the filtrate, and distill under reduced pressure to obtain the Artemisia capillaris extract.

4. The external anti-wrinkle repairing composition according to claim 1, characterized in that: Prepare a phosphate buffer solution of 1 mol / L palmitoyl pentapeptide-4 and a phosphate buffer solution of 2 mol / L hyaluronic acid. Prepare 0.2% glutaraldehyde phosphate buffer, slowly add palmitoyl pentapeptide-4 phosphate buffer, slowly add hyaluronic acid phosphate buffer, and react for 3 h; The reaction solution was placed in a dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed with a large amount of deionized water at 4°C for 24 h. During this period, the dialysis external fluid was replaced every 4-6 h. The dialyzed solution was freeze-dried to obtain a conjugate of palmitoyl pentapeptide-4 and hyaluronic acid.

5. A method for preparing the external anti-wrinkle repairing composition according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: Dissolving the first active ingredient with sweet almond oil, stirring until completely dissolved, to obtain a mixed solution I with a concentration of 25-30%; Mix glycerol and butanediol in a mass ratio of 1-2:1, stir, add the second active ingredient, stir until completely dissolved, and obtain a mixed solution II with a concentration of 20-25%; Add 100 parts of water into a stirring pot, slowly add 0.1-0.5 parts of carbomer, and continue stirring for 15-20 minutes until the carbomer is fully swollen to form a uniform colloidal solution, slowly pour 3-4 parts of mixed solution II into the stirring pot, stir for 10-15 minutes, until it is evenly dispersed, then slowly pour 0.8-1 parts of mixed solution I into the stirring pot, stir for 5-10 minutes, add 0.08-0.1 parts of triethanolamine dropwise into the pot, adjust the pH to 5.5-6.5, add 0.05-0.08 parts of the third active ingredient, stir for 5-10 minutes, until it is completely dissolved, add 0.3-0.5 parts of phenoxyethanol, stir for 5 minutes, and obtain.

6. A method for preparing the external anti-wrinkle repairing composition according to any one of claims 1 to 4, characterized in that: The amount of each component is calculated by weight, and the preparation method comprises: Dissolving the first active ingredient with sweet almond oil, stirring until completely dissolved, to obtain a mixed solution III with a concentration of 25-30%; Dissolving the third active ingredient in ethanol and stirring until completely dissolved to obtain a mixed solution IV with a concentration of 50-60%; Add 100 parts of sweet almond oil into a stirring pot, slowly pour 0.8-1 parts of mixed solution III into the stirring pot, stir for 5-10 minutes until uniformly dispersed, slowly add 1-2 parts of the second active ingredient, stir for 10-15 minutes until fully blended, slowly pour 0.1-0.15 parts of mixed solution IV into the stirring pot, stir for 5-10 minutes, drop 0.1 parts of lavender essential oil, stir for 5 minutes, add 3 parts of beeswax and 5 parts of lanolin, heat the stirring pot in a water bath, slowly raise the temperature to 60-65°C, continue stirring until the beeswax and lanolin are completely melted, and obtain the product.

7. Use of the external repairing and anti-wrinkle composition according to any one of claims 1 to 4 in the preparation of cosmetics.

8. The use according to claim 7, characterized in that: The application of the external repairing and anti-wrinkle composition in the preparation of repairing and anti-wrinkle cosmetics.