External repair and anti-wrinkle composition and its preparation method

Abstract

The present invention discloses an externally applied repair and anti-wrinkle composition, which comprises a first active ingredient, a second active ingredient, a third active ingredient and a carrier: the first active ingredient comprises corn germ extract and retinol; the second active ingredient comprises chuanxiong extract, panax notoginseng extract, cornel extract and artemisia capillaris extract; the third active ingredient comprises a palmitoyl pentapeptide-4 and hyaluronic acid conjugate; and the carrier is an oil phase, an aqueous phase and / or an excipient. The present invention can achieve synergistic effects by scientifically proportioning each active ingredient, and can be prepared into skin care products such as essence, skin care oil, facial mask, etc. for external use, which is safe and has no side effects, and can, to a certain extent, slow down the deepening and spreading of wrinkles and help the skin restore elasticity and firmness.

Description

Technical Field

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

[0002] With the natural growth of age, the skin inevitably undergoes the aging process, and environmental factors such as ultraviolet radiation, dry climate, and environmental pollution further exacerbate skin damage and accelerate the aging pace. 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, external repair and anti-wrinkle compositions aim to effectively slow down the deepening and spread of wrinkles and promote the restoration of skin elasticity and the improvement of firmness through preventive and improvement mechanisms. These compositions can be flexibly prepared into various forms such as anti-wrinkle masks, creams, serums, and body lotions to meet the personalized needs of different consumers. In addition, to improve the repair and anti-wrinkle effects, these compositions are often used in combination with other beauty treatments such as laser therapy and microneedle therapy to form a comprehensive skin care plan.

[0003] However, in the currently commercially available cream products, there is generally a problem of insufficient active ingredient content, resulting in a high dependence of the anti-wrinkle effect on the ingredient concentration and insignificant results. Although some products incorporate a variety of plant extracts, aiming to utilize the antioxidant properties of natural ingredients, for sensitive skin, such ingredients may cause adverse skin reactions such as redness and itching, limiting their wide application.

[0004] In view of this, it is particularly important to develop an external repair and anti-wrinkle composition with safety, high efficiency, and low side effects. The composition needs to precisely regulate the proportion of active ingredients to ensure that while enhancing the anti-wrinkle efficacy, 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 effects by scientifically proportioning various active ingredients, can be prepared into skin care products such as serums, body lotions, and masks for external use, are safe without side effects, and can, to a certain extent, slow down the deepening and spread of wrinkles and help the skin restore elasticity and firmness.

[0006] To achieve these and other advantages in accordance with the present invention, there is provided an external repair and anti-wrinkle composition, comprising a first active ingredient, a second active ingredient, a third active ingredient, and a carrier:

[0007] The first active ingredient includes corn germ extract and retinol;

[0008] The second active ingredient includes ligusticum wallichii extract, panax notoginseng extract, cornel fruit extract, and artemisia capillaris extract;

[0009] The third active ingredient includes a palmitoyl pentapeptide-4 and hyaluronic acid conjugate;

[0010] The carrier is an oil phase, an aqueous phase, and / or an excipient.

[0011] Preferably, corn germ oil is obtained by extracting corn germ with n-hexane, and the extract is obtained by molecular distillation and then by vacuum distillation to obtain corn germ extract;

[0012] The corn germ extract and retinol are separately dissolved in sweet almond oil, maltodextrin and glycerol are dissolved in water, ethanol is added as a co-solvent, the oil phase is slowly added to the water phase, the mass ratio of the oil phase to the water phase is 1:2, homogenized and emulsified, stirred to form an emulsion, and spray-dried. The inlet air temperature is 50 °C and the outlet air temperature is 30 °C to obtain the first active ingredient, wherein the mass ratio of the corn germ extract, retinol, maltodextrin, and glycerol is 2:0.5:10:10.

[0013] Preferably, the mass ratio of the ligusticum wallichii extract, panax notoginseng extract, cornel fruit extract, and artemisia capillaris extract is 50:40 - 50:20 - 30:10 - 20;

[0014] The ligusticum wallichii extract is prepared by the following method: washing, drying, and pulverizing the ligusticum wallichii rhizome, adding the ligusticum wallichii powder to 75% ethanol at a weight-to-volume ratio of g / mL of 1:5 - 8, refluxing and extracting at 60 - 80 °C for 2 - 3 h, filtering, collecting the filtrate, and performing vacuum distillation to obtain the ligusticum wallichii extract;

[0015] The panax notoginseng extract is prepared by the following method: washing, drying, and pulverizing the panax notoginseng root, mixing it with an entrainer for supercritical extraction, with the supercritical extraction conditions being a pressure of 20 - 30 MPa and a temperature of 40 - 60 °C. After the extraction, carbon dioxide is turned into a gaseous state by reducing the pressure, the extract is collected, adsorbed and eluted by macroporous resin, and rotary evaporated and vacuum distilled to obtain the panax notoginseng extract;

[0016] The cornel fruit extract is prepared by the following method: washing, drying, and pulverizing the cornel fruit, adding the cornel fruit powder to 75% ethanol at a weight-to-volume ratio of g / mL of 1:5 - 8, soaking for 12 - 24 h, filtering, performing vacuum distillation, separating by polyamide column chromatography, rotary evaporating, and vacuum distilling to obtain the cornel fruit extract;

[0017] The artemisia capillaris extract is prepared by the following method: washing, drying, and pulverizing the artemisia capillaris, adding the artemisia capillaris powder to 75% ethanol at a weight-to-volume ratio of g / mL of 1:5 - 8, refluxing and extracting at 50 - 70 °C for 1 - 2 h, filtering, collecting the filtrate, and performing vacuum distillation to obtain the artemisia capillaris extract.

[0018] Preferably, prepare a phosphate buffer solution of palmitoyl pentapeptide-4 with a concentration of 1 mol / L and a phosphate buffer solution of hyaluronic acid with a concentration of 2 mol / L.

[0019] Prepare a phosphate buffer solution of glutaraldehyde with a concentration of 0.2%, slowly add it to the phosphate buffer solution of palmitoyl pentapeptide-4, and slowly add it to the phosphate buffer solution of hyaluronic acid, and react for 3 h.

[0020] Load the reaction solution into a dialysis bag with a molecular weight cut-off of 3500 Da, dialyze it with a large amount of deionized water at 4°C for 24 h, change the external dialysis solution every 4 - 6 h during this period, and the dialyzed solution is freeze-dried to obtain the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid.

[0021] Preferably, it includes the dosage of each component in parts by weight, and the preparation method includes:

[0022] Dissolve the first active ingredient with sweet almond oil and stir until completely dissolved to obtain a mixed solution I with a concentration of 25 - 30%.

[0023] Mix glycerol and butanediol with a mass ratio of 1 - 2:1, stir, add the second active ingredient, and stir until completely dissolved to obtain a mixed solution II with a concentration of 20 - 25%.

[0024] Add 100 parts of water to a stirring pot, slowly add 0.1 - 0.5 parts of carbomer, continuously stir for 15 - 20 min until the carbomer is fully swollen to form a uniform colloidal solution, slowly pour 3 - 4 parts of the mixed solution II into the stirring pot, stir for 10 - 15 min until uniformly dispersed, then slowly pour 0.8 - 1 part of the mixed solution I into the stirring pot, stir for 5 - 10 min, dropwise add 0.08 - 0.1 part of triethanolamine to adjust the pH to 5.5 - 6.5, add 0.05 - 0.08 part of the third active ingredient, stir for 5 - 10 min until completely dissolved, and add 0.3 - 0.5 part of phenoxyethanol and stir for 5 min to obtain the product.

[0025] Preferably, it includes the dosage of each component in parts by weight, and the preparation method includes:

[0026] Dissolve the first active ingredient with sweet almond oil and stir until completely dissolved to obtain a mixed solution III with a concentration of 25 - 30%.

[0027] Dissolve the third active ingredient with ethanol and stir until completely dissolved to obtain a mixed solution IV with a concentration of 50 - 60%.

[0028] Add 100 parts of sweet almond oil to a stirring pot, slowly pour 0.8 - 1 part of mixed solution III into the stirring pot, stir for 5 - 10 min until evenly dispersed, slowly add 1 - 2 parts of the second active ingredient, stir for 10 - 15 min until fully blended, slowly pour 0.1 - 0.15 part of mixed solution IV into the stirring pot, stir for 5 - 10 min, add 0.1 part of lavender essential oil dropwise, stir for 5 min, 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, and keep stirring until the beeswax and lanolin are completely melted to obtain the product.

[0029] Use of the external repair and anti-wrinkle composition in the preparation of cosmetics.

[0030] Preferably, use of the external repair and anti-wrinkle composition in the preparation of repair and anti-wrinkle cosmetics.

[0031] The present invention has at least the following beneficial effects:

[0032] First, the repair and anti-wrinkle composition prepared by the present invention can achieve synergistic effects by scientifically proportioning each active ingredient, can be prepared into skin care products such as essence, skin care oil, mask, etc. for external use, is safe and has no side effects, can slow down the deepening and spreading of wrinkles to a certain extent, help the skin restore elasticity and firmness, improve the anti-wrinkle efficacy while reducing unnecessary irritation to the skin, and provide a more ideal and reliable skin care choice for consumers.

[0033] Second, the first active ingredient added in the present invention includes corn germ extract and retinol. 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.

[0034] Third, the second active ingredient added in the present invention includes traditional Chinese medicine extracts. Ferulic acid in the ligusticum wallichii extract can scavenge free radicals in the skin, and also contains some ingredients that can promote collagen synthesis, supplement collagen lost by the skin due to aging and other reasons from the source, and reduce the generation of wrinkles. Ginsenosides in the panax notoginseng extract can promote the metabolism of skin cells, stimulate the activity of fibroblasts, and synthesize collagen. Flavonoids in the cornel fruit extract can protect collagen and elastic fibers from damage, increase the elasticity and firmness of the skin, and reduce the formation of wrinkles. Flavonoids and chlorogenic acid in the artemisia capillaris extract can scavenge free radicals and reduce the damage to collagen and elastic fibers, and make the skin more firm by promoting skin cells to produce more collagen.

[0035] Fourth, the third active ingredient added in the present invention includes a conjugate formed by chemically linking palmitoyl pentapeptide-4 and hyaluronic acid, which jointly promotes the anti-wrinkle effect. Palmitoyl pentapeptide-4 can mimic signal molecules in the skin, stimulate fibroblasts to produce collagen and elastic fibers, and hyaluronic acid can be filled 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 beneficial for palmitoyl pentapeptide-4 to better play its function of stimulating cell activity and promoting the synthesis of extracellular matrix components.

[0036] Other advantages, objectives, and features of the present invention will be partially reflected by the following description, and partially will also be understood by those skilled in the art through the research and practice of the present invention. Detailed implementation mode

[0037] The following further detailed description of the present invention is made in conjunction with examples, so that those skilled in the art can implement it according to the description in the specification.

[0038] It should be understood that terms such as "having", "comprising", and "including" used herein do not exclude the presence or addition of one or more other elements or their combinations.

[0039] It should be noted that the experimental methods described in the following implementation examples are all conventional methods unless otherwise specified, and the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0040] <Example 1>

[0041] A preparation method of an external repair and anti-wrinkle composition, the preparation method includes:

[0042] (1) Prepare the first active ingredient:

[0043] Place 500 g of 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 layers, collect the lower n-hexane extraction solution, perform molecular distillation at a temperature of 180 °C, connect to a vacuum pump, and the feed rate is 2 mL / min. The light components (volatile impurities such as n-hexane) are distilled out, collect the remaining corn germ oil extract, perform vacuum distillation at a temperature of 120 °C, connect to a vacuum pump, and the remaining volatile components are removed. Collect the corn germ extract, weigh about 20 g, and seal it for storage for later use.

[0044] Slowly add 20 g of corn germ extract and 5 g of retinol into 15 mL of sweet almond oil respectively, place it on a magnetic stirrer, and stir at a speed of 300 r / min for 30 min until completely dissolved to obtain the oil phase; add 10 g of maltodextrin and 10 mL of glycerol into 30 mL of water, then add 5 mL of ethanol, and stir for 20 min until completely dissolved to obtain the aqueous phase; slowly drip the oil phase into the aqueous phase, and at the same time turn on the emulsifier, set the rotation speed to 8000 r / min to form a stable emulsion; transfer the emulsion to the feed tank of the spray dryer, set the inlet air temperature to 50 °C, the outlet air temperature to 30 °C, and the feeding rate to 10 mL / min, and carry out spray drying. Collect the dried powder to obtain the first active ingredient, weigh about 40 - 45 g, and store it sealed for later use.

[0045] (2)Prepare the second active ingredient:

[0046] Wash, dry, and crush the rhizome of Ligusticum chuanxiong. Add 100 g of Ligusticum chuanxiong powder to 600 mL of 75% ethanol according to the weight - volume ratio of g / mL of 1:6. Install a reflux condenser and reflux - extract at 70 °C for 2 h. The color of the solution gradually deepens and becomes brownish - black. Filter and collect the filtrate. Transfer the filtrate to a rotary evaporator, carry out vacuum distillation, connect to a vacuum pump to obtain a brown - black viscous Ligusticum chuanxiong extract, weigh about 20 g, and store it sealed for later use.

[0047] Wash, dry, and crush the root of Panax notoginseng. Put 100 g of Panax notoginseng powder into a supercritical extraction kettle, add anhydrous ethanol accounting for 30% of the powder mass as an entrainer and mix for supercritical extraction. The supercritical extraction conditions are a pressure of 25 MPa and a temperature of 50 °C. Open the carbon dioxide cylinder, with a flow rate of 15 L / h, and extract for 2 h. After extraction, make carbon dioxide become gaseous by reducing the pressure, collect the extract, adsorb it on AB - 8 macroporous resin, first wash it with 3 times the column volume of deionized water, and then elute it with 70% ethanol at a flow rate of 2 mL / min. Collect the eluate, carry out vacuum distillation, connect to a vacuum pump to obtain a light - yellow Panax notoginseng extract, weigh about 20 g, and store it sealed for later use.

[0048] Wash, dry, and crush the fruit of Cornus officinalis. Add 60 g of Cornus officinalis powder to 400 mL of 75% ethanol according to the weight - volume ratio of g / mL of 1:7, soak for 18 h, filter, carry out vacuum distillation, load it onto a polyamide column, wash it with 4 times the column volume of deionized water, and then elute it with 30% ethanol at a flow rate of 1.5 mL / min. Collect the eluate, carry out rotary evaporation and vacuum distillation to obtain a dark - red Cornus officinalis extract, weigh about 10 g, and store it sealed for later use.

[0049] Wash the Artemisia capillaris, dry it, and pulverize it. Add 40 g of Artemisia capillaris powder to 250 mL of 75% ethanol according to the weight-to-volume ratio of g / mL of 1:6. Install a reflux condenser and reflux extract at 60 °C for 1.5 h. The solution changes from yellow-green to dark green. Filter and collect the filtrate. Transfer the filtrate to a rotary evaporator, perform vacuum distillation, connect to a vacuum pump, and obtain a dark green Artemisia capillaris extract. Weigh it, about 8 g, and store it sealed for later use.

[0050] Take the Ligusticum wallichii 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.

[0051] (3)Prepare the third active ingredient:

[0052] Prepare 0.1 M phosphate buffer (PBS). Take 1 mmol of palmitoyl pentapeptide-4 and dissolve it in 10 mL of phosphate buffer to prepare a phosphate buffer solution of palmitoyl pentapeptide-4 with a concentration of 1 mol / L. Take 2 mmol of hyaluronic acid with a molecular weight of 1 million - 1.5 million Da and dissolve it in 10 mL of phosphate buffer to prepare a phosphate buffer solution of hyaluronic acid with a concentration of 2 mol / L;

[0053] Prepare a 0.2% glutaraldehyde phosphate buffer. Take 2 mL and slowly drip it into the palmitoyl pentapeptide-4 phosphate buffer to mix it evenly. Then slowly drip it into the hyaluronic acid phosphate buffer, and complete the dripping process within 30 min. React for 3 h;

[0054] To remove unreacted glutaraldehyde and other impurities, load the reaction solution into a dialysis bag with a molecular weight cut-off of 3500 Da and dialyze it with a large amount of deionized water at 4 °C for 24 h. Replace the outer dialysis solution every 6 h during this period. The dialyzed solution is freeze-dried to obtain a white palmitoyl pentapeptide-4 and hyaluronic acid conjugate, which is the third active ingredient. Weigh it, about 355 g, and store it sealed for later use.

[0055] (4)Prepare the composition:

[0056] Dissolve the first active ingredient in sweet almond oil and stir until completely dissolved to obtain a 30% mixed solution I; Mix glycerol and butanediol in a mass ratio of 2:1, stir, add the second active ingredient, and stir until completely dissolved to obtain a 25% mixed solution II;

[0057] Add 1000 g of water to a stirring pot, slowly add 3.5 g of carbomer, and continuously stir 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 uniformly dispersed. Then slowly pour 10 g of mixed solution I into the stirring pot and stir for 10 min. Dropwise add 1 g of triethanolamine into the pot, adjust the pH to 5.5 - 6.5, add 0.8 g of the third active ingredient, and stir for 10 min until it is completely dissolved. Add 5 g of phenoxyethanol and stir for 5 min to obtain the product.

[0058] <Example 2>

[0059] A preparation method of an externally applied repair and anti-wrinkle composition, the preparation method comprising:

[0060] (1) Prepare the first active ingredient, with the method the same as in Example 1.

[0061] (2) Prepare the second active ingredient. The preparation method of the raw materials is the same as in Example 1. Take the extracts of Ligusticum chuanxiong, Panax notoginseng, Cornus officinalis, and Artemisia capillaris in a mass ratio of 5:4:2:1, and physically mix them to obtain the second active ingredient.

[0062] (3) Prepare the third active ingredient, with the method the same as in Example 1.

[0063] (4) Prepare the composition:

[0064] Dissolve the first active ingredient with sweet almond oil and stir until it is completely dissolved to obtain a 25% mixed solution I; mix glycerol and butanediol in a mass ratio of 1:1, stir, add the second active ingredient, and stir until it is completely dissolved to obtain a 20% mixed solution II;

[0065] Add 1000 g of water to a stirring pot, slowly add 2 g of carbomer, and continuously stir 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 and stir for 10 min until it is uniformly dispersed. Then slowly pour 8 g of mixed solution I into the stirring pot and stir for 5 min. Dropwise add 0.8 g of triethanolamine into the pot, adjust the pH to 5.5 - 6.5, add 0.5 g of the third active ingredient, and stir for 5 min until it is completely dissolved. Add 3 g of phenoxyethanol and stir for 5 min to obtain the product.

[0066] <Example 3>

[0067] A preparation method of an externally applied repair and anti-wrinkle composition, the preparation method comprising:

[0068] (1) Prepare the first active ingredient, with the method the same as in Example 1.

[0069] (2) Prepare the second active ingredient. The preparation method of the raw materials is the same as that in Example 1. Take the extracts of Ligusticum chuanxiong, Panax notoginseng, Cornus officinalis, and Artemisia capillaris with a mass ratio of 5:5:3:2, and physically mix them to obtain the second active ingredient.

[0070] (3) Prepare the third active ingredient. The method is the same as that in Example 1.

[0071] (4) Prepare the composition:

[0072] Dissolve the first active ingredient with sweet almond oil and stir until completely dissolved to obtain a mixed solution III with a concentration of 30%; dissolve the third active ingredient with ethanol and stir until completely dissolved to obtain a mixed solution IV with a concentration of 60%;

[0073] Add 1000 g of sweet almond oil to the stirring pot, slowly pour 10 g of the 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 integrated, slowly pour 1.5 g of the mixed solution IV into the stirring pot, stir for 10 min, add 1 g of lavender essential oil dropwise, 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 continuously stir until the beeswax and lanolin are completely melted to obtain the product.

[0074] <Example 4>

[0075] A preparation method of an externally applied repair and anti-wrinkle composition, the preparation method comprising:

[0076] (1) Prepare the first active ingredient. The method is the same as that in Example 1.

[0077] (2) Prepare the second active ingredient. The preparation method of the raw materials is the same as that in Example 1. Take the extracts of Ligusticum chuanxiong, Panax notoginseng, Cornus officinalis, and Artemisia capillaris with a mass ratio of 5:4:2:1, and physically mix them to obtain the second active ingredient.

[0078] (3) Prepare the third active ingredient. The method is the same as that in Example 1.

[0079] (4) Prepare the composition:

[0080] Dissolve the first active ingredient with sweet almond oil and stir until completely dissolved to obtain a mixed solution III with a concentration of 25%; dissolve the third active ingredient with ethanol and stir until completely dissolved to obtain a mixed solution IV with a concentration of 50%;

[0081] Add 1000 g of sweet almond oil to 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 integrated, slowly pour 1 g of mixed solution IV into the stirring pot, stir for 5 min, add 1 g of lavender essential oil dropwise, 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 to obtain the product.

[0082] <Comparative Example 1>

[0083] A preparation method of an externally applied repair and anti-wrinkle composition, the preparation method includes;

[0084] (1) Prepare corn germ extract, the method is the same as in Example 1.

[0085] (2) Prepare traditional Chinese medicine extract, the preparation method of the raw materials is the same as in Example 1, take the ligusticum wallichii extract, notoginseng extract, cornel extract, and artemisia capillaris extract in a mass ratio of 5:5:3:2, and physically mix to obtain the traditional Chinese medicine extract.

[0086] (3) Prepare the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid, the method is the same as in Example 1.

[0087] (4) Prepare the composition:

[0088] Mix the traditional Chinese medicine extract and corn germ extract with a mass ratio of 5:1 to obtain a powder, mix glycerol and butanediol with a mass ratio of 2:1, stir, add the powder, and stir until completely dissolved to obtain a mixed solution with a concentration of 25%.

[0089] Add 1000 g of water to a stirring pot, slowly add 3.5 g of carbomer, continuously stir 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, stir for 15 min until evenly dispersed, add 0.5 g of retinol, slowly pour it into the stirring pot, stir for 10 min, gradually add 1 g of triethanolamine dropwise to the pot to adjust the pH to 5.5 - 6.5, add 0.8 g of the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid, stir for 10 min until completely dissolved, add 5 g of phenoxyethanol, and stir for 5 min to obtain the product.

[0090] <Comparative Example 2>

[0091] A preparation method of an externally applied repair and anti-wrinkle composition, the preparation method includes;

[0092] (1) Prepare the corn germ extract-retinol complex, the method is the same as in Example 1.

[0093] (2) Prepare a traditional Chinese medicine extract. The preparation method of the raw materials is the same as that in Example 1. Take the ligusticum wallichii extract, panax notoginseng extract, cornel extract, and artemisia capillaris extract in a mass ratio of 5:5:3:2, and physically mix them to obtain the traditional Chinese medicine extract.

[0094] (3) Prepare the composition:

[0095] Dissolve the retinol complex of corn germ extract in sweet almond oil and stir until completely dissolved to obtain a mixed solution I with a concentration of 30%; mix glycerol and butanediol in a mass ratio of 2:1, stir, add the traditional Chinese medicine extract, and stir until completely dissolved to obtain a mixed solution II with a concentration of 25%;

[0096] Add 1000 g of water to the stirring pot, slowly add 3.5 g of carbomer, and continuously stir for 20 min until the carbomer is fully swollen to form a uniform colloidal solution. Slowly pour 40 g of the mixed solution II into the stirring pot and stir for 15 min until evenly dispersed. Then slowly pour 10 g of the mixed solution I into the stirring pot and stir for 10 min. Dropwise add 1 g of triethanolamine to the pot to adjust the pH to 5.5 - 6.5. Add 0.4 g of palmitoyl pentapeptide-4 and 0.4 g of hyaluronic acid, and stir for 10 min until completely dissolved. Add 5 g of phenoxyethanol and stir for 5 min to obtain the product.

[0097] <Comparative Example 3>

[0098] A preparation method of an externally applied repair and anti-wrinkle composition, the preparation method comprising:

[0099] (1) Prepare the retinol complex of corn germ extract, and the method is the same as that in Example 1.

[0100] (2) Prepare the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid, and the method is the same as that in Example 1.

[0101] (3) Prepare the composition:

[0102] Dissolve the retinol complex of corn germ extract in sweet almond oil and stir until completely dissolved to obtain a mixed solution with a concentration of 30%;

[0103] Add 1000 g of water to the stirring pot, slowly add 3.5 g of carbomer, and continuously stir 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. Dropwise add 1 g of triethanolamine to the pot to adjust the pH to 5.5 - 6.5. Add 0.8 g of the conjugate of palmitoyl pentapeptide-4 and hyaluronic acid, and stir for 10 min until completely dissolved. Add 5 g of phenoxyethanol and stir for 5 min to obtain the product.

[0104] <Cell Proliferation Assay>

[0105] The human skin fibroblast cell line HSF was cultured in high-glucose DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin, and placed in an incubator at 37°C and 5% CO2. The cells were passaged every 2-3 days.

[0106] Human skin fibroblasts HSF in the logarithmic growth phase were seeded into 96-well plates at a density of 5×10³ cells / well, with 6 replicates in each group. After the cells adhered to the wall (about 24 h), the following treatments were performed: The blank control group was added with an equal volume of medium without drugs, and Examples 1-4 and Comparative Examples 1-3 were added with a final concentration of 50 μg / mL diluted with medium. After culturing for 48 h, subsequent detections were carried out. The MTT method was used to detect cell proliferation. 20 μL of MTT solution (5 mg / mL) was added to each well, and the cells were cultured for another 4 h. The supernatant was aspirated, 150 μL of DMSO was added to each well, and the mixture was shaken for 10 min to fully dissolve the crystals. The absorbance (OD value) of each well was measured at a wavelength of 570 nm using an enzyme-linked immunosorbent assay (ELISA) reader. The OD value was used to reflect the cell proliferation activity, and the cell proliferation rate (%) was calculated. The test results are shown in Table 1.

[0107] Table 1

[0108] 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

[0109] Human skin fibroblasts are key cells for synthesizing collagen and elastic fibers. An 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, it provides support for skin repair at the cellular level. Specifically, the first active ingredient contains corn germ extract and retinol. Tocopherol in the corn germ extract can stabilize retinol. In the second active ingredient, extracts of Ligusticum chuanxiong, Panax notoginseng, Cornus officinalis, and Artemisia capillaris are mixed in a specific ratio and contain various active ingredients such as ferulic acid, ginsenosides, flavonoids, and chlorogenic acid, which work together to resist wrinkles from multiple aspects such as scavenging free radicals and enhancing skin metabolism. The third active ingredient is a conjugate of palmitoyl pentapeptide-4 and hyaluronic acid, and the conjugate structure has a synergistic effect in the skin. Hyaluronic acid can be filled between the newly formed collagen fibers to maintain the fullness of the skin.

[0110] <Safety Evaluation Test>

[0111] Select 40 volunteers aged between 18 and 60 years old, without a history of skin allergies (especially allergies to cosmetic ingredients), and who have not used glucocorticoids, immunosuppressants and other drugs that may affect skin reactions within the past month. Randomly divide them into 4 groups, with 10 people in each group, and conduct safety tests on the products prepared in Examples 1-4 respectively. Apply a patch tester coated with 0.02-0.03 mL of the sample to the test site (both sides of the spine on the back, one side is the test area and the other side is the blank control area), and gently fix it with medical tape to ensure that the patch tester fits tightly against the skin without air bubbles or wrinkles. After application, observe the test site at three time points: 24 h, 48 h and 72 h. The skin reaction grading criteria are as follows: Grade 0: No reaction; Grade 1: Mild erythema, possibly accompanied by slight itching; Grade 2: Moderate erythema, infiltration, occasional papules, and obvious itching; Grade 3: Severe erythema, infiltration, papules, small blisters may appear, and severe itching; Grade 4: Large blisters, erosion, ulcers, accompanied by pain. The experimental results show that no skin irritation reactions such as erythema, itching, papules, and pain occurred in the subjects of each group within 72 h after using the products of Examples 1-4 of the present invention, indicating that the present invention has no irritation to human skin and has good safety.

[0112] <Repair and Anti-Wrinkle Effect Test>

[0113] Select 70 volunteers aged between 45 and 60 years old with obvious wrinkles (such as crow's feet, glabellar lines, nasolabial folds, etc.) on the face. Randomly divide them into 7 groups, with 10 people in each group. Divide them into experimental groups and blank control groups, and conduct repair and anti-wrinkle effect tests on the products prepared in Examples 1-4, Comparative Examples 1-2, and a commercially available ordinary moisturizing lotion (without the above special active ingredients) respectively. All volunteers need to stop using any anti-wrinkle skin care products for 1 week before the start of the experiment, and only use mild cleansing products and the blank control ordinary moisturizing lotion for basic cleaning and moisturizing to restore the skin condition to the natural baseline level. After cleansing the face in the morning and evening every day, each group of volunteers take an appropriate amount of the product and apply it evenly on the face, gently massage until completely absorbed, and the usage amount is controlled at 1 mL each time to ensure that the product can cover the entire face, and continuously use the product for 8 weeks.

[0114] Use an MPA580 multi-functional skin tester to measure the wrinkle depth, wrinkle area, skin moisture content, skin elasticity and other indicators of each volunteer's face at the 0th week, 4th week and 8th week of using the product. The optical three-dimensional imaging technology of the skin tester is used to measure the wrinkle depth and wrinkle area; the capacitance method is used to measure the skin moisture content; the skin elasticity is measured by measuring the mechanical changes during the stretching and retraction process of the skin, and is represented by the R2 value. The higher the R2 value, the better the skin elasticity. The experimental results are shown in Table 2-3.

[0115] Table 2

[0116] 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

[0117] Table 3

[0118] 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

[0119] As can be seen from Table 2-3, Examples 1-4 are superior to the blank control group in terms of wrinkle improvement, skin moisturization, and elasticity enhancement.

[0120] The effect of Example 1 is better than that of Comparative Example 1. This is probably because when extracting the oil part from corn germ using an organic solvent and obtaining a corn germ extract mainly composed of γ-tocopherol 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, reacting with free radicals preferentially, protecting retinol from the attack of free radicals, improving the stability of retinol to a certain extent, playing a role in stabilizing the structure of retinol, preventing retinol from being oxidized, avoiding the isomerization reaction of retinol, giving full play to the anti-wrinkle effect of retinol, promoting cell renewal, and reducing wrinkles.

[0121] The effect of Example 1 is better than that of Comparative Example 2. This is probably because palmitoyl pentapeptide-4 and hyaluronic acid form a conjugate through chemical linkage to jointly promote the anti-wrinkle effect. Palmitoyl pentapeptide-4 can mimic signal molecules in the skin and stimulate fibroblasts to produce collagen and elastic fibers. Hyaluronic acid can be filled between the newly formed collagen fibers, maintaining the fullness of the skin, making the skin more firm, and reducing the generation of wrinkles. At the same time, the moisturizing effect of hyaluronic acid can provide a good environment for skin cells, which is beneficial for palmitoyl pentapeptide-4 to better exert its function of stimulating cell activity and promoting the synthesis of extracellular matrix components.

[0122] <Skin Irritation Test>

[0123] Thirty healthy adult white rabbits, 15 males and 15 females, with a body weight between 2.0 - 2.5 kg, were selected. Before the experiment, the animals were adaptively raised in the laboratory for 3 days. The breeding environment maintained a temperature of (22 ± 2) °C and a relative humidity of (50 ± 5)%. They had free access to food and water. The 30 rabbits were randomly divided into 3 groups, with 10 rabbits in each group, namely the experimental group and the blank control group. Skin irritation tests were conducted on the products prepared in Example 1, Comparative Example 3, and physiological saline respectively. The hair on both sides of the spine of the rabbits was removed, and the hair removal area was about 3 cm × 3 cm. The dosage was controlled at 1 mL each time to ensure that the product could cover the entire hair removal area. It was gently fixed with medical tape and applied once a day for 7 consecutive days.

[0124] Observe the skin reactions of rabbits at 0.5 h, 2 h, 24 h, 48 h, and 72 h after application, including erythema, edema, pruritus, desquamation, etc. Skin reaction scoring grades: 0 points indicates no visible local reaction, no erythema, no edema; 1 point indicates faintly visible erythema, slightly desquamated and slightly edematous; 2 points indicates moderate erythema, desquamation, and moderate edema; 3 points indicates severe erythema, desquamation, and severe edema; 4 points indicates purplish-red erythema accompanied by eschar formation and skin damage. Average score = sum of local irritation scores of all observed animals on the same day ÷ number of observed animals.

[0125] The test results showed that the skin of rabbits in the blank control group did not show obvious irritant reactions such as erythema and edema at each time point, and the scores were all 0, indicating that the test operation and environment did not cause additional irritation to the skin of rabbits.

[0126] In the group of Example 1, at 2 h after applying the product, slight erythema appeared in individual rabbits, and the average score was 0.2 ± 0.1; after 24 h, the erythema gradually subsided, and only a very small number of rabbits showed extremely slight desquamation, and the average score remained at 0.1 ± 0.05; by 72 h, the skin basically returned to normal, without obvious adverse reactions, and the overall skin irritation score was relatively low.

[0127] In the group of Comparative Example 3, at 0.5 h after applying the product, mild erythema appeared in many rabbits, and some were accompanied by slight edema, and the average score reached 1.2 ± 0.3; at 2 h, the erythema and edema worsened, and some rabbits showed pruritus symptoms, and the average score rose to 2.0 ± 0.4; during 4 - 24 h, although the erythema and edema were alleviated to some extent, there were still obvious traces, and the average score was 1.5 ± 0.3; after 48 - 72 h, a small amount of desquamation and slight residual erythema were still visible, and the average score was 0.8 ± 0.2.

[0128] The skin irritation of Example 1 is lower than that of Comparative Example 3. This is probably because the addition of traditional Chinese medicine extracts can not only be used as anti - wrinkle active ingredients but also effectively reduce the adverse effects of irritant components (possibly from retinol, etc.) on the skin, making the composition more safe and suitable for skin care products. The volatile oils in Ligusticum chuanxiong extract and Artemisia capillaris extract can soothe and calm the skin, have certain anti - inflammatory properties, and can inhibit the release of inflammatory mediators to 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 in a moist state. The organic acids in Cornus officinalis extract can regulate the pH value of the skin, maintain it in a weakly acidic environment, and are beneficial to the stability of the skin barrier function.

[0129] The equipment quantities and processing scales described here are used to simplify the description of the present invention. The applications, modifications, and variations of the present invention are obvious to those skilled in the art.

[0130] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and embodiments. It can be fully applied to various fields suitable for the present invention. For those skilled in the art, additional modifications can be easily made. Therefore, without departing from the general concept defined by the claims and their 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; The preparation method of the first active ingredient is: 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 cosolvent, slowly add the oil phase to 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, to obtain the first active ingredient, wherein the mass ratio of corn germ extract, retinol, maltodextrin and glycerol is 2:0.5:10:10; The preparation method of the third active ingredient is: Prepare a phosphate buffer solution of 1 mol / L palmitoyl pentapeptide-4 and a phosphate buffer solution of 2 mol / L hyaluronic acid. Prepare a phosphate buffer solution with a concentration of 0.2% glutaraldehyde, slowly add a phosphate buffer solution of palmitoyl pentapeptide-4, slowly add a phosphate buffer solution of hyaluronic acid, 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 which 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, namely the third active ingredient.

2. 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.

3. A method for preparing the external anti-wrinkle repairing composition according to claim 1 or 2, characterized in that: The preparation method includes 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.

4. A method for preparing the external anti-wrinkle repairing composition according to claim 1 or 2, 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.

5. Use of the external repairing and anti-wrinkle composition according to claim 1 or 2 in the preparation of cosmetics.

6. The use according to claim 5, characterized in that: The application of the external repairing and anti-wrinkle composition in the preparation of repairing and anti-wrinkle cosmetics.