Preparation method and application of blue copper peptide-PDRN composite freeze-drying efficacy core sphere steady-state delivery system

Abstract

The invention relates to a preparation method and application of a blue copper peptide-PDRN composite freeze-dried efficacy core sphere steady-state delivery system, and belongs to the technical field of cosmetics. The invention provides a composite freeze-dried functional core sphere steady-state delivery system of a combination of blue copper peptide, PDRN and macromolecular active ingredients, an ordered and stable nano-assembly steady-state structural system is formed through multiple interaction among blue copper peptide, PDRN and macromolecules, and the problems of stability and compatibility of blue copper peptide are solved; secondly, a composite freeze-dried functional core ball based on a copper-blue peptide liposome inclusion compound is developed, and the transdermal absorption rate of copper-blue peptide is improved; thirdly, the blue copper peptide functional core ball based on excellent transdermal absorption rate is developed; finally, a processing technology for producing a blue copper peptide composite freeze-drying efficacy core sphere steady-state delivery system at low temperature in a whole process based on liquid nitrogen quick freezing is developed.

Description

Technical Field

[0001] The present invention relates to a preparation method and application of a blue copper peptide-PDRN (PDRN: polydeoxyribonucleotide, also known as DNA sodium, the same below) composite freeze-dried efficacy core ball steady-state delivery system, belonging to the technical field of cosmetics. Background Art

[0002] Functional active ingredients are widely used in industries such as cosmetics and health foods. However, many active ingredients suffer from issues such as instability, odor, poor compatibility, and low bioavailability, severely restricting their application in cosmetics and food. In water-based formulations, such as face creams, eye creams, serums, and beverages, the stability, compatibility, and bioavailability of active ingredients face even greater challenges, particularly regarding bioactivity decay during shelf life. Many active ingredients virtually lose their activity within a shelf life of 1-3 years. Therefore, advanced stabilized delivery technologies and innovative product designs are needed to address these pain points and promote product upgrades and innovative development in cosmetics and health foods.

[0003] Copper peptides are currently a popular active ingredient in the cosmetics industry, boasting powerful skin-repairing, firming, and anti-aging benefits. However, copper peptides suffer from poor stability and compatibility, reacting with many active ingredients and base formula components, such as retinol, acids, and chelating agents. This severely limits their use in cosmetic formulations. Therefore, it is necessary to improve the stability of copper peptides to accommodate compatibility with a wider range of active ingredients and base formula components. Summary of the Invention

[0004] In order to overcome the above technical defects, the present invention uses blue copper peptide as the representative of hydrophilic active raw materials to develop a blue copper peptide-PDRN composite freeze-dried efficacy core ball steady-state delivery system, which successfully solves the application pain points of blue copper peptide. First, we innovatively developed a type of composite freeze-dried efficacy core balls consisting of "blue copper peptide (with or without a combination of small molecule active ingredients), PDRN and a combination of large molecule active ingredients". The blue copper peptide, PDRN, large molecule active substances and active small molecules form an ordered and stable nano-assembly steady-state structure system through multiple intermolecular interactions. With its excellent spherical appearance, smooth spherical surface, good mechanical strength and outstanding solubility and dispersibility, it solves the stability and compatibility problems of the blue copper peptide. Secondly, we developed composite freeze-dried efficacy core balls based on blue copper peptide liposome inclusion complexes, which not only solved the stability and compatibility problems of the blue copper peptide, but also improved the transdermal absorption rate of the blue copper peptide. Thirdly, by combining active ingredients such as phloretin and cyclodextrin, which are both active ingredients and penetration enhancers, we developed blue copper peptide efficacy core balls with excellent transdermal absorption rate. Finally, we developed a full-process low-temperature production and processing technology based on liquid nitrogen quick freezing to ensure that the activity of the blue copper peptide is not affected by the process and to ensure the high-quality production of efficacy core balls.

[0005] The first purpose of the present invention is to provide a blue copper peptide-PDRN composite freeze-dried efficacy core ball steady-state delivery system, including: blue copper peptide, PDRN and macromolecular active ingredients.

[0006] Furthermore, in the above technical solution, the PDRN is selected from polydeoxyribonucleotides extracted from salmon or polydeoxyribonucleotides synthesized by biological fermentation, and its molecular weight range is 1000-2000000.

[0007] Furthermore, in the above technical solution, the macromolecular active ingredient is a water-soluble macromolecular active raw material used in cosmetic products.

[0008] Furthermore, in the above technical solution, the macromolecular active ingredients include but are not limited to one or more natural or fermented macromolecular active ingredients such as sodium hyaluronate, tremella polysaccharide, silk fibroin, recombinant humanized type III collagen, β-glucan, dendrobium polysaccharide, aloe polysaccharide, etc.

[0009] Furthermore, in the above technical solution, the molecular weight range of the macromolecular active ingredient is 1000-2000000, a more suitable molecular weight range is 3000-1200000, and an even more suitable molecular weight range is 10000-800000.

[0010] The second purpose of the present invention is to provide a blue copper peptide composite freeze-dried functional core ball steady-state delivery system containing a small molecule active ingredient. That is, based on the above functional core ball, it also contains a small molecule active ingredient.

[0011] Furthermore, in the above technical solution, the small molecule active ingredient is a small molecule active raw material used in cosmetic products.

[0012] Furthermore, in the above technical scheme, the small molecule active ingredients include but are not limited to one or more active ingredients such as ectoine, theanine, trehalose, bosaicin, madecassoside, Vc glucoside, γ-cyclodextrin, mannitol, hydroxypropyl-β-cyclodextrin, cono-like peptides, snake venom-like peptides, acetyl hexapeptide-8, etc.

[0013] Furthermore, in the above technical solution, the blue copper peptide composite freeze-dried functional core ball, wherein: the weight content of blue copper peptide is 0.1-70%, the more suitable weight content range is 1-30%, and the more suitable weight content range is 5-20%; the mass ratio of blue copper peptide or blue copper peptide containing small molecule active ingredients to macromolecular active ingredients (including PDRN) is 10: 1 to 1: 10, the more suitable ratio range is 5: 1 to 1: 5, and the more suitable ratio range is 2: 1 to 1: 2.

[0014] The third purpose of the present invention is to improve the transdermal absorption rate of blue copper peptide. Active substances (both active ingredients and penetration enhancers, such as phloretin, cyclodextrin, hydrolyzed sponge, etc.) are added to the blue copper peptide efficacy core ball steady-state delivery system.

[0015] Furthermore, in the above technical solution, the active substance includes active substance molecules or raw materials with penetration-enhancing effects such as phloretin hydrolyzed sponge.

[0016] Furthermore, in the above technical solution, the mass ratio of the active substance to the blue copper peptide is 100: 1 to 1: 100, more preferably in the ratio range of 10: 1 to 1: 10, and more preferably in the ratio range of 2: 1 to 1: 2.

[0017] The fourth purpose of the present invention is to provide a blue copper peptide liposome composite freeze-dried efficacy core ball steady-state delivery system, that is, blue copper peptide liposomes are used to replace blue copper peptide, wherein: the hydrophilic blue copper peptide is mainly present in the inner cavity or vesicles of the liposome.

[0018] Furthermore, in the above technical solution, the blue copper peptide liposomes are composed of, but not limited to, at least one of soy lecithin, egg yolk lecithin, hydrogenated soy lecithin, cholesterol, and PEGylated phospholipids. The addition of cholesterol, PEGylated phospholipids, and other special lipid components enhances liposome stability.

[0019] Furthermore, in the above technical solution, in the blue copper peptide liposomes, the mass ratio of liposomes to blue copper peptide is 1000: 1 to 1: 2, more preferably in the ratio range of 100: 1 to 1: 1, and more preferably in the ratio range of 50: 1 to 5: 1.

[0020] Furthermore, in the above technical solution, the preparation process of the blue copper peptide liposome includes but is not limited to a thin film dispersion method, a solvent (ethanol, acetone, tetrahydrofuran, etc.) injection method, an ultrasonic dispersion method, a homogenization method, an extrusion method, etc.

[0021] Furthermore, in the above technical solution, the method for removing the organic solvent from the blue copper peptide liposome includes but is not limited to rotary evaporation, vacuum drying, stirring volatilization and other processes.

[0022] Furthermore, in the above technical solution, the particle size of the functional core ball ranges from 0.1 mm to 15 mm, more preferably from 0.5 mm to 8 mm; and even more preferably from 1 mm to 5 mm.

[0023] The fifth purpose of the present invention is to ensure that the activity of blue copper peptide is not affected by the process and to ensure the high-quality production of functional core balls. Based on the full-process low-temperature production and processing technology of liquid nitrogen quick freezing, a processing technology for a blue copper peptide composite freeze-dried functional core ball steady-state delivery system is provided, which includes the following steps: A. Evenly mix blue copper peptide or blue copper peptide liposome and other active ingredients; B. Add purified water or deionized water, heat and stir until the active ingredient is completely dissolved; C. Add the obtained solution dropwise into a heat-insulated liquid nitrogen bucket; D. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry them to obtain a blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system.

[0024] Furthermore, in the above technical solution, the other active ingredients are selected from at least one of small molecule active ingredients, macromolecular active ingredients, and active substances that are both active ingredients and penetration enhancers.

[0025] Furthermore, in the above technical solution, the dropping device includes but is not limited to a peristaltic pump, a syringe pump, a flow pump, and the like, which can control the speed and droplet size.

[0026] Furthermore, in the above technical solution, the functional core balls are packaged into different packaging containers as needed, including but not limited to vials, plastic bottles, glass bottles and various customized packaging materials. Advantageous Effects of the Invention

[0027] This invention proposes for the first time a preparation method for a blue copper peptide-PDRN composite freeze-dried efficacy core ball steady-state delivery system, namely, the "blue copper peptide, PDRN, a combination of small molecule active ingredients, and a combination of large molecule active ingredients" composite freeze-dried efficacy core ball, which has an excellent spherical appearance, a smooth spherical surface, good mechanical strength and outstanding solubility and dispersibility, solving the stability and compatibility problems of blue copper peptide.

[0028] This invention is the first to introduce liposomes into the freeze-dried functional core ball steady-state delivery system, that is, the composite freeze-dried functional core ball steady-state delivery system containing blue copper peptide liposomes, which not only solves the stability and compatibility problems of blue copper peptide, but also improves the transdermal absorption rate of blue copper peptide.

[0029] This invention is the first to introduce a penetration enhancer (which is also an active ingredient) into the freeze-dried functional core ball, which not only promotes the transdermal absorption rate of blue copper peptide, but also enhances the skin care effect of the core ball.

[0030] In the present invention, in the presence of phospholipid complex liposomes or liposome stability enhancers, the delivery carrier achieves the expected high stability and transdermal absorption effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is an appearance morphology of the blue copper peptide-PDRN functional core ball steady-state delivery system; B1 to B15 are blue copper peptide functional core ball samples of Examples 1-15; Figure 2 This is a scanning electron micrograph of a cross-section of the blue copper peptide-PDRN efficacy core ball steady-state delivery system; B4, B8, and B10 are the blue copper peptide efficacy core ball samples of Examples 4, 8, and 10, respectively; Figure 3 This is a flow chart of the preparation process of the blue copper peptide-PDRN freeze-dried efficacy core ball steady-state delivery system. DETAILED DESCRIPTION Example 1 Preparation of Blue Copper Peptide No. 1 Composite Efficacy Core Ball Steady-State Delivery System

[0032] 1. Weigh 0.36g of blue copper peptide, 0.3g of ectoine, 0.78g of trehalose, 0.75g of theanine and 0.75g of mannitol respectively, put them into a beaker and mix them evenly; 2. Add 27.06g of purified water and stir until the active ingredient is completely dissolved; 3. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 4. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide functional core ball steady-state delivery system, which is recorded as B1. The cold trap temperature of the freeze dryer is controlled at around -70°C (with a deviation of 3°C, the same below), and the final temperature of the drying chamber is controlled at around 30°C.

[0033] 5. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Example 2 Preparation of Blue Copper Peptide II Composite Efficacy Core Ball Steady-State Delivery System

[0034] 1. Weigh 0.36g of blue copper peptide, 0.3g of ectoine, 0.6g of trehalose, 0.3g of theanine, 0.75g of mannitol, 0.48g of silk fibroin and 0.15g of Tremella polysaccharide respectively, put them into a beaker and mix them evenly; 2. Add 27.06g of purified water and stir until the active ingredient is completely dissolved; 3. Use a syringe pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 4. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide functional core ball steady-state delivery system, which is recorded as B2. The cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C.

[0035] 5. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Example 3 Preparation of a Blue Copper Peptide-PDRN III Composite Efficacy Core Ball Steady-State Delivery System

[0036] 1. Weigh 0.36g of blue copper peptide and 0.45g of PDRN (salmon extract) separately, put them into a beaker and mix them evenly; then add 12.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.3 g of ectoine, 0.6 g of trehalose, 0.3 g of theanine, and 0.75 g of mannitol separately, put them into a beaker and mix evenly; then add 15.06 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix solution I and solution II evenly to obtain the target solution; 4. Use a syringe pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain a blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, denoted as B3; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0037] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Example 4 Preparation of a Blue Copper Peptide-PDRN IV Composite Efficacy Core Ball Steady-State Delivery System

[0038] 1. Weigh 0.36g of blue copper peptide and 0.3g of PDRN (salmon extract) separately, put them into a beaker and mix evenly; then add 12.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.3 g of ectoine, 0.6 g of trehalose, 0.3 g of theanine, 0.63 g of mannitol, 0.36 g of fibroin, and 0.15 g of Tremella fuciformis polysaccharide respectively, put them into a beaker and mix evenly; then add 15.06 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix solution I and solution II evenly to obtain the target solution; 4. Use a syringe pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B4; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0039] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Example 5 Preparation of Blue Copper Peptide No. V Composite Efficacy Core Ball Steady-State Delivery System

[0040] 1. Weigh 0.18g of blue copper peptide, 0.24g of aloe polysaccharide, 0.3g of bosaicin, 0.48g of silk fibroin, 0.2g of madecassoside, 0.36g of Vc glucoside and 0.63g of β-glucan respectively, put them into a beaker and mix well; 2. Add 27.21g of purified water and stir until the active ingredient is completely dissolved; 3. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 4. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide functional core ball steady-state delivery system, which is recorded as B5. The cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C.

[0041] 5. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0042] Example 6 Preparation of Blue Copper Peptide-PDRN No. VI Composite Efficacy Core Ball Steady-State Delivery System 1. Weigh 0.18g of blue copper peptide and 0.3g of PDRN (salmon extract) separately, put them into a beaker and mix evenly; then add 12.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed to obtain Solution I; 2. Weigh 0.24 g of aloe polysaccharide, 0.3 g of bosaicin, 0.48 g of fibroin, 0.2 g of madecassoside, 0.36 g of Vc glucoside, and 0.63 g of β-glucan separately, place them in a beaker and mix well; then add 15.21 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix solution I and solution II evenly to obtain the target solution; 4. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B6; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0043] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Example 7 Preparation of a Blue Copper Peptide-PDRN No. VII Composite Efficacy Core Ball Steady-State Delivery System

[0044] 1. Weigh 0.45g of blue copper peptide and 0.36g of PDRN (salmon extract) separately, put them into a beaker and mix evenly; then add 14.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.36g sodium hyaluronate, 0.48g acetyl hexapeptide-8, 0.36g ectoine, 0.3g recombinant type III collagen, 0.15g dendrobium polysaccharide, and 0.48g β-glucan separately, place in a beaker and mix well; then add 14.56g purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix solution I and solution II evenly to obtain the target solution; 4. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B7; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0045] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0046] Example 8 Preparation of Blue Copper Peptide-PDRN VIII Composite Efficacy Core Ball Steady-State Delivery System 1. Preparation of blue copper peptide-PDRN liposomes: Weigh 0.45 g of egg yolk lecithin PC90 and 0.05 g of cholesterol respectively, dissolve them in 5 mL of anhydrous ethanol to prepare a lipid ethanol solution; weigh 0.36 g of blue copper peptide and 0.3 g of PDRN (salmon extract) in a 50 mL round-bottom flask, add 15 mL of deionized water to dissolve, and prepare a blue copper peptide-PDRN aqueous solution; under stirring in a 50 °C oil bath, slowly add the lipid ethanol solution dropwise to the blue copper peptide-PDRN aqueous solution. After the addition is complete, continue stirring for 15 minutes to obtain a mixed solution; the mixed solution is rotary evaporated at 60 °C to remove ethanol and part of the water, and finally obtain about 10.0 g of liposome solution I for standby use.

[0047] 2. Weigh 0.3 g of ectoine, 0.3 g of trehalose, 0.3 g of theanine, 0.63 g of mannitol, 0.36 g of fibroin, and 0.15 g of Tremella polysaccharide respectively, put them into a beaker and mix evenly; then add 17.23 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix liposome solution I and solution II evenly to obtain the target solution; 4. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B8; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0048] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0049] Example 9 Preparation of a Blue Copper Peptide-PDRN IX Composite Efficacy Core Ball Steady-State Delivery System 1. Preparation of blue copper peptide-PDRN liposomes: Weigh 0.72 g of soybean lecithin PC90 and 0.05 g of cholesterol respectively, dissolve them in 5 mL of anhydrous ethanol to prepare a lipid ethanol solution; weigh 0.18 g of blue copper peptide and 0.3 g of PDRN (salmon extract) in a 50 mL round-bottom flask, add 15 mL of deionized water to dissolve, and prepare a blue copper peptide-PDRN aqueous solution; under stirring in a 50 °C oil bath, slowly add the lipid ethanol solution dropwise to the blue copper peptide-PDRN aqueous solution. After the addition is complete, continue stirring for 15 minutes to obtain a mixed solution; the mixed solution is rotary evaporated at 60 °C to remove ethanol and part of the water, and finally obtain about 10.0 g of liposome solution I for standby use.

[0050] 2. Weigh 0.24 g of aloe polysaccharide, 0.3 g of bosaicin, 0.48 g of fibroin, 0.2 g of madecassoside, 0.36 g of Vc glucoside, and 0.63 g of β-glucan separately, place them in a beaker and mix well; then add 17.21 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix liposome solution I and solution II evenly to obtain the target solution; 4. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B9; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0051] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0052] Example 10 Preparation of a Blue Copper Peptide-PDRN X Composite Efficacy Core Ball Steady-State Delivery System 1. Weigh 0.45g of blue copper peptide and 0.36g of PDRN (salmon extract) separately, put them into a beaker and mix evenly; then add 10.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.48 g of β-glucan, 0.48 g of hydroxypropyl β-cyclodextrin, 0.06 g of phloretin, and 0.06 g of raspberry ketone respectively, place them in a beaker and mix well; then add 8.0 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Weigh 0.36g sodium hyaluronate, 0.18g acetyl hexapeptide-8, 0.36g ectoine, 0.3g recombinant type III collagen, and 0.15g dendrobium polysaccharide respectively, put them into a beaker and mix them evenly; then add 10.56g purified water and stir until the active ingredients are completely dissolved to obtain solution III; 4. Mix solution I, solution II and solution III to obtain the target solution; 5. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 6. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B10; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0053] 7. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Example 11 Preparation of a Blue Copper Peptide-PDRN No. XI Composite Efficacy Core Ball Steady-State Delivery System

[0054] 1. Weigh 0.3g of blue copper peptide and 0.15g of PDRN (biofermentation) separately, put them into a beaker and mix evenly; then add 8.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.6 g of β-glucan, 0.48 g of hydroxypropyl β-cyclodextrin, and 0.09 g of phloretin separately, place them in a beaker and mix well; then add 8.0 g of purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Weigh 0.66g of silk fibroin, 0.15g of sodium hyaluronate, and 0.18g of ectoine separately, place them in a beaker and mix evenly; then add 12.84g of purified water, heat and stir until the active ingredients are completely dissolved, then add 0.27g of hydrolyzed sponge, stir and disperse evenly to obtain Solution III;

[0055] 4. Mix solution I, solution II and solution III evenly to obtain the target dispersion; 5. Use a peristaltic pump to add the above dispersion dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 6. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain a blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, denoted as B11; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0056] 7. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0057] Example 12 Preparation of a Blue Copper Peptide-PDRN XII Composite Efficacy Core Ball Steady-State Delivery System 1. Preparation of blue copper peptide-PDRN liposomes: Weigh 0.45g soybean lecithin PC90, 0.03g cholesterol, and 0.06g phloretin respectively, and dissolve them in 5mL of anhydrous ethanol to prepare a lipid ethanol solution; weigh 0.36g blue copper peptide and 0.21g PDRN (biological fermentation) in a 50mL round-bottom flask, add 15mL of deionized water to dissolve, and prepare a blue copper peptide-PDRN aqueous solution; under stirring in a 50℃ oil bath, slowly add the lipid ethanol solution dropwise to the blue copper peptide-PDRN aqueous solution. After the addition is completed, continue stirring for 15min to obtain a mixed solution; the mixed solution is rotary evaporated at 60℃ to remove ethanol and part of the water, and finally about 10.0g of liposome solution I is obtained for standby use.

[0058] 2. Weigh 0.48g of silk fibroin, 0.15g of Tremella polysaccharide, 0.24g of ectoine, and 0.3g of methyl β-cyclodextrin respectively, put them into a beaker and mix evenly; then add 18.29g of purified water, heat and stir until completely dissolved, to obtain active ingredient solution No. II; 3. Evenly mix the No. I blue copper peptide liposome solution and the No. II active ingredient solution to obtain the target blue copper peptide efficacy complex solution; 4. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, recorded as B12; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0059] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0060] Example 13 Preparation of a Blue Copper Peptide-PDRN XIII Composite Efficacy Core Ball Steady-State Delivery System

[0061] 1. Weigh 0.27g of blue copper peptide and 0.3g of PDRN (biofermentation) separately, put them into a beaker and mix evenly; then add 12.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed to obtain Solution I; 2. Weigh 0.1g propylene glycol, 0.06g phloretin, 0.36g sodium hyaluronate, 0.78g theanine, 0.36g ectoine, and 0.3g recombinant humanized type III collagen respectively, place them in a beaker and mix well; then add 16.20g purified water and stir until the active ingredients are completely dissolved to obtain Solution II; 3. Mix solution I and solution II evenly to obtain the target solution; 4. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 40 mg. Quickly freeze to obtain small ice balls. 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B13; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 35°C;

[0062] 6. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0063] Example 14 Preparation of a Blue Copper Peptide-PDRN XIV Composite Efficacy Core Ball Steady-State Delivery System 1. Weigh 0.36g of blue copper peptide and 0.24g of PDRN (biofermentation) separately, put them into a beaker and mix evenly; then add 8.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.66 g of silk fibroin, 0.48 g of methyl β-cyclodextrin, and 0.03 g of phloretin separately, put them into a beaker and mix them evenly; then add 8.0 g of purified water and stir until completely dissolved to obtain Solution II; 3. Weigh 0.6 g of β-glucan, 0.15 g of sodium hyaluronate, and 0.18 g of ectoine separately, place them in a beaker and mix well; then add 10.57 g of purified water and stir until completely dissolved to obtain Solution III; 4. Mix solution I, solution II and solution III to obtain the target solution; 5. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 25 mg. Quickly freeze to obtain small ice balls. 6. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B14; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0064] 7. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed.

[0065] Example 15 Preparation of a Blue Copper Peptide-PDRN XV Composite Efficacy Core Ball Steady-State Delivery System 1. Weigh 0.3g of blue copper peptide and 0.45g of PDRN (biofermentation) separately, put them into a beaker and mix evenly; then add 10.0g of purified water and stir until the active ingredients are completely dissolved, ensuring that the blue copper peptide and PDRN are evenly distributed, to obtain Solution I; 2. Weigh 0.3g recombinant type III collagen, 0.72g hydroxypropyl β-cyclodextrin, and 0.09g phloretin separately and mix thoroughly in a beaker. Then add 10.0g purified water and stir until completely dissolved to obtain Solution II. 3. Weigh 0.36g sodium hyaluronate, 0.48g theanine, and 0.36g ectoine separately, place in a beaker and mix evenly; then add 8.97g purified water, heat and stir until the active ingredients are completely dissolved to obtain Solution III;

[0066] 4. Mix solution I, solution II and solution III to obtain the target solution; 5. Use a peristaltic pump to add the above solution dropwise into a liquid nitrogen bucket. The droplet size is about 65 mg. Quickly freeze to obtain small ice balls. 6. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 40 hours to obtain the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system, which is recorded as B15; the cold trap temperature of the freeze dryer is controlled at around -70°C, and the final temperature of the drying chamber is controlled at around 30°C;

[0067] 7. The freeze-dried functional core ball steady-state delivery system is packaged into plastic bottles, which can then be packaged into various packaging containers such as vials and glass bottles as needed. Test Example 1: Appearance of the Blue Copper Peptide-PDRN Composite Efficacy Core Ball Steady-State Delivery System

[0068] Figure 1 : Use a camera to take pictures, characterize the appearance of the blue copper peptide efficacy core ball steady-state delivery system, and conduct comparative analysis.

[0069] from Figure 1 As can be seen, after freeze-drying, all Examples 1-15 produced light blue or blue balls, also known as Meixin balls. The vast majority of the balls were well-shaped and had a relatively smooth surface. A few cracks on the surface of the balls were primarily caused by uneven internal stress during freezing and did not affect subsequent use.

[0070] Sample B1, primarily composed of small-molecule active ingredients and copper peptides, was prone to surface powdering and even cracking due to collisions between the pellets when placed in a storage container, resulting in relatively poor stability. Other copper peptide-PDRN composite core-sphere stable delivery systems containing PDRN and macromolecular active ingredients (such as Tremella fuciformis polysaccharides, silk fibroin, sodium hyaluronate, and beta-glucan) were more robust, exhibited little powdering, and had a smoother surface.

[0071] Samples B5, B6, and B9 have lower levels of blue copper peptide, resulting in a lighter blue color. Samples B7 and B10 have higher levels of blue copper peptide, resulting in a bluer color than other functional core balls.

[0072] Samples 4 and 8, samples 6 and 9, and samples 7 and 10 are three pairs of Meixinqiu steady-state delivery system samples. Their formulas are basically the same, with penetration enhancers added to samples 8, 9, and 10, and the component contents slightly adjusted accordingly to increase the transdermal absorption rate of the blue copper peptide. Figure 1 It can be seen that after adding the penetration enhancer, a relatively perfect spherical shape can still be obtained, and the color of the balls changes slightly.

[0073] Figure 1 The diameter of the core ball of the samples is generally around 4.0mm, except for samples B14 and 15. The diameter of the core ball of sample B14 is the smallest, about 3.5mm; the diameter of the core ball of B15 is the largest, about 5.2mm. Figure 1 It can be seen that the smaller the diameter of the ball, the more perfect the spherical shape, the fewer cracks, and the smoother the surface. This is mainly because the smaller the ball, the faster the liquid nitrogen freezes, and the less internal and external stress. Test Example 2: Blue Copper Peptide-PDRN Composite Efficacy Core Ball Steady-State Delivery System Scanning Electron Microscopy

[0074] Figure 2The following are scanning electron micrographs of samples B4, B8, and B10. The active core spheres were gently broken apart and observed using a scanning electron microscope. The images show a uniform layered structure within the spheres, with evenly distributed micron-scale channels between the layers. During rapid freezing with liquid nitrogen, the active ingredient dissolved in water rapidly precipitates, forming tiny crystals. Then, during freeze-drying, as the ice crystals sublime, water vapor forms micron-scale water vapor channels, connecting the tiny active ingredient crystals together to form a layered structure. Because liquid nitrogen freezes so quickly, the microstructure of the entire sphere is remarkably uniform. The active ingredient layer is extremely thin, typically less than 1 micron, ensuring rapid dissolution when water is added back in. It was also found that as the solid content of the active ingredient in the B4, B8, and B10 solutions increases, the water channels in the electron micrographs gradually decrease in size, as predicted. Test Example 3: Stability of the Blue Copper Peptide-PDRN Composite Efficacy Core Ball Steady-State Delivery System

[0075] Copper peptides have poor stability and are easily affected by chelating ingredients in the formulation, such as acids and chelating agents. Even when these ingredients are excluded, copper peptides exhibit poor stability in aqueous solutions and are susceptible to oxidation. Based on the stability evaluation of cosmetics, the stability of the copper peptide active core ball steady-state delivery system was evaluated through an accelerated 45°C test. The stability of the solution was then analyzed after dilution with a copper peptide control serum (copper peptide concentration approximately 5 mg / mL). Accelerated testing was performed on the copper peptide-PDRN composite active core ball steady-state delivery system, followed by analysis of the solution at various concentrations. With the initial copper peptide concentration set at 100%, the retained copper peptide concentration was measured as a percentage of the initial concentration at various aging times.

[0076] As shown in the table below, after 90 days of accelerated testing, the copper peptide content or concentration in the control serum decreased by approximately 47%, with a retention rate of only around 53%. However, the copper peptide content in the freeze-dried spheres showed minimal change, significantly outperforming the control serum, with retention rates exceeding 98%. Furthermore, the copper peptide retention rates in the spheres containing PDRN remained essentially unchanged, exceeding 99%. This is primarily due to the fact that the copper peptide in the freeze-dried spheres is minimally affected by external factors such as oxygen and moisture.

[0077]

[0078] Stability analysis of the Copper Peptide series of active ingredients. Samples B1, B2, B3, and B4 are from the same series, with essentially the same formula. Sample B1, consisting primarily of freeze-dried copper peptides composed primarily of small molecules, showed a 1.24% decrease in copper peptide content after 28 days of accelerated testing. Sample B2, based on B1, added larger molecules of silk fibroin and Tremella fuciformis polysaccharide. The copper peptide content decreased by 0.98%, demonstrating improved stability compared to Sample B1, demonstrating that the larger molecules further enhance copper peptide stability. Sample B3, based on B1, added PDRN (sodium DNA). The copper peptide content decreased by 0.15%, a reduction of approximately 1 / 8 that of Sample B1, 1 / 6 that of Sample B2, and 1 / 60 that of the control serum. The significantly improved copper peptide stability in Sample B3 suggests a strong interaction between PDRN and the copper peptide, forming a stable nanostructure through weak interactions such as electrostatic and van der Waals forces, which significantly enhances the copper peptide's stability. Sample B4 is based on B1, with the addition of PDRN, silk fibroin and Tremella polysaccharide. The content of blue copper peptide decreased by 0.13%, which is basically the same as sample B3. Similarly, the formulas of samples B5 and B6 are basically the same, except that PDRN is added to sample B6. The reduction in blue copper peptide in sample B5 is 0.87%, and the reduction in sample B6 is 0.07%, which is about 1 / 12 of sample B5. In the remaining samples B7-13, we also found that the content of blue copper peptide in the blue copper peptide functional core ball with PDRN added has almost no change and is very stable. The above series of experiments show that PDRN plays the most critical role in improving the stability of blue copper peptide. Test Example 4: Transdermal Absorption

[0079] For the application cases, a systematic transdermal efficacy evaluation and comparison was conducted, using the "In Vitro Test Method for Skin Absorption of Chemicals." For ease of comparison, a normal saline solution formulation was selected.

[0080]

[0081] As can be seen from the table above, the 24-hour transdermal dose of the control essence water (Application Example 1) is 0.028 mg / cm 2 , Blue Copper Peptide-PDRN Meixin Ball Essence IV (Application Example 2) 24h transdermal dose is 0.048mg / cm 2 , increased by about 70%, which shows that the blue copper peptide functional core ball steady-state delivery system with nano-assembly structure can improve the skin penetration rate of blue copper peptide. Blue copper peptide-PDRN core ball essence VIII (application example 3) compared with IV, only adds liposomes to enhance penetration, and its 24h skin penetration rate is 0.097mg / cm 2, approximately double that of the Beauty Core Ball Essence IV and 246% higher than the control water essence, demonstrating that the penetration-enhancing ingredient significantly improves the transdermal absorption of the copper peptide. Similar results were observed in the following two sets of Beauty Core Ball Essences, VI / IX and VII / X, with the copper peptide in the functional core balls significantly exceeding the control water essence. The copper peptide penetration rates of the functional core balls IX and X, which contained a transdermal penetration enhancer, were significantly higher than those of the non-functional core balls VI and VII, with IX achieving approximately double that of VI and X approximately double that of VII. These results demonstrate that the nano-assembled structure of the composite freeze-dried functional core balls promotes transdermal absorption of the copper peptide, and that the addition of a penetration enhancer further enhances the transdermal absorption of the copper peptide. Test Example 5: Clinical Efficacy Evaluation in Humans

[0082] In order to further verify the skin care efficacy of blue copper peptide, blue copper peptide efficacy core ball sample B10 was selected for a systematic human clinical efficacy evaluation.

[0083]

[0084] Refer to the cosmetic efficacy evaluation method, T / CAB 0152-2022 Cosmetic Anti-wrinkle, Firming, Moisturizing, Oil Control, Repair, Nourishing, Soothing Seven Efficacy Test Methods, T / GDCA 009-2022 Cosmetic Repair Efficacy Human Evaluation Method, T / GDCDC021-2022 Cosmetic Soothing Efficacy Test Method, T / SHRH 018-2021 Cosmetic Improvement of Canthus Wrinkle Efficacy Clinical Evaluation Method, T / TDCA 003-2021 Cosmetic Firming Efficacy Test Method.

[0085] The human clinical efficacy evaluation report shows that after continuous use of Blue Copper Peptide Repair Beauty Core Ball Essence for 28 days, the skin stratum corneum moisture content, skin transepidermal water loss value, VISIA-CR skin redness a* value, VISIA-CR skin red area ratio, VISIA-CR eye corner wrinkle area ratio, VISIA-CR under-eye wrinkle area ratio, skin elasticity R2, skin firmness F4, and skin gloss parameters have been significantly improved compared with the baseline values. Therefore, it is believed that this product has moisturizing, repairing, soothing, anti-wrinkle, firming and nourishing effects. Application Example 1: Blue Copper Peptide Comparison Essence Water

[0086] (1) Preparation: Weigh a certain amount of blue copper peptide, add a certain amount of 0.9% saline, and dissolve to obtain a blue copper peptide aqueous solution for subsequent evaluation. Application Example 2: Blue Copper Peptide-PDRN Beauty Core Ball Essence IV

[0087] (1) Take 60 mg of sample B4 of the Meixin Ball (i.e., the blue copper peptide-PDRN composite efficacy core ball steady-state delivery system, the same below) and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will give the Blue Copper Peptide-PDRN Meixinqiu Essence IV for subsequent evaluation. Application Example 3: Blue Copper Peptide-PDRN Beauty Core Ball Essence VIII

[0088] (1) Take 60 mg of the Meixin Ball sample B8 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will yield the Blue Copper Peptide-PDRN Meixinqiu Essence VIII for subsequent evaluation. Application Example 4: Blue Copper Peptide-PDRN Beauty Core Ball Essence VI

[0089] (1) Take 60 mg of the Meixin Ball sample B6 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will give the Blue Copper Peptide-PDRN Meixinqiu Essence VI for subsequent evaluation. Application Example 5: Blue Copper Peptide-PDRN Beauty Core Ball Essence IX

[0090] (1) Take 60 mg of the Meixin Ball sample B9 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will yield the Blue Copper Peptide-PDRN Meixinqiu Essence IX for subsequent evaluation. Application Example 6: Blue Copper Peptide-PDRN Beauty Core Ball Essence VII

[0091] (1) Take 60 mg of the Meixin Ball sample B7 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will yield the Blue Copper Peptide-PDRN Meixinqiu Essence VII for subsequent evaluation. Application Example 7: Blue Copper Peptide-PDRN Beauty Core Ball Essence X

[0092] (1) Take 60 mg of the Meixin Ball sample B10 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will give the Blue Copper Peptide-PDRN Meixinqiu Essence X for subsequent evaluation. Application Example 8 Blue Copper Peptide-PDRN Beauty Core Ball Essence XI

[0093] (1) Take 60 mg of the Meixinqiu sample B11 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will yield the Blue Copper Peptide-PDRN Meixinqiu Essence XI for subsequent evaluation. Application Example 9: Blue Copper Peptide-PDRN Beauty Core Ball Essence XII

[0094] (1) Take 60 mg of the Meixinqiu sample B12 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will yield the Blue Copper Peptide-PDRN Meixinqiu Essence XII for subsequent evaluation. Application Example 10: Blue Copper Peptide-PDRN Beauty Core Ball Essence XIII

[0095] (1) Take 60 mg of the Meixinqiu sample B13 and place it in a vial; (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette; (3) Pour 3 mL of normal saline into the Meixinqiu vial and shake gently to dissolve evenly. This will yield the Blue Copper Peptide-PDRN Meixinqiu Essence XIII for subsequent evaluation.

[0096] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. The blue copper peptide compound freeze-dried efficacy core ball steady-state delivery system is characterized by: include: Blue copper peptides, polydeoxyribonucleotides, macromolecular active ingredients, small molecule active ingredients, and active substances that are both active ingredients and penetration enhancers.

2. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 1, characterized in that: The polydeoxyribonucleotide is selected from polydeoxyribonucleotides extracted from salmon or polydeoxyribonucleotides synthesized by biological fermentation, and its molecular weight range is 1000-2000000; the macromolecular active ingredient is a water-soluble macromolecular active raw material used in cosmetic products; Its molecular weight range is 1000-2000000; the macromolecular active ingredients include but are not limited to one or more natural or fermented macromolecular active ingredients such as sodium hyaluronate, tremella polysaccharide, silk fibroin, recombinant type III humanized collagen, β-glucan, dendrobium polysaccharide, and aloe polysaccharide.

3. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 1, characterized in that: The small molecule active ingredients include but are not limited to one or more of ectoine, theanine, trehalose, bosaicin, madecassoside, Vc glucoside, γ-cyclodextrin, mannitol, hydroxypropyl-β-cyclodextrin, acetyl hexapeptide-8, cono-like peptides, snake venom-like peptides, and raspberry ketone active ingredients.

4. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 1, characterized in that: The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system has a blue copper peptide weight content of 0.1-70%, and a mass ratio of blue copper peptide to macromolecular active ingredients containing polydeoxyribonucleotides is 10:1 to 1:

10.

5. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 1, characterized in that: The active ingredients include phloretin, cyclodextrin, and hydrolyzed sponge; the mass ratio of the active ingredients to blue copper peptide is 100:1 to 1:

100.

6. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 1, characterized in that: The blue copper peptide is a blue copper peptide liposome, wherein: the hydrophilic blue copper peptide is mainly present in the lumen or vesicles of the liposome.

7. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 6, characterized in that: The composition of the blue copper peptide liposome includes but is not limited to: at least one of soy lecithin, egg yolk lecithin, hydrogenated soy lecithin, cholesterol or PEGylated phospholipids; in the blue copper peptide liposome, the mass ratio of liposome to blue copper peptide is 1000:1 to 1:

2.

8. The blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to claim 1, characterized in that: The particle size of the functional core ball ranges from 0.1 to 15 mm.

9. The processing technology of the blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system according to any one of claims 1 to 8, characterized in that: The steps include: A. combining blue copper peptide or blue copper peptide liposomes with at least one of a small molecule active ingredient, a macromolecular active ingredient, and an active ingredient that is both an active ingredient and a penetration enhancer; B. Add purified water or deionized water, heat and stir until the active ingredient is completely dissolved; C. Add the obtained solution dropwise into a heat-insulated liquid nitrogen barrel; D. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer for freeze drying to obtain a blue copper peptide composite freeze-dried efficacy core ball steady-state delivery system.

Images