Preparation method and application of astaxanthin composite freeze-drying functional core sphere steady-state delivery system

Abstract

The invention relates to a preparation method and application of an astaxanthin composite freeze-dried functional core sphere steady-state delivery system, and belongs to the field of cosmetics. Astaxanthin is used as a fat-soluble active raw material, and a composite freeze-drying functional core sphere steady-state delivery system of astaxanthin, a liposome active component, a micromolecular antioxidant active component and a natural or fermented macromolecular polysaccharide active component is innovatively researched and developed. The astaxanthin, the liposome active component, the micromolecular antioxidant active component and the macromolecular active polysaccharide form an ordered and stable nano-assembly steady-state structure through intermolecular multiple interaction, and the nano-assembly steady-state structure has excellent spherical appearance, smooth spherical surface, good mechanical strength and excellent dissolution dispersibility; the problems of stability, compatibility, absorptivity and the like of the astaxanthin are solved; meanwhile, a whole-process low-temperature production and processing technology based on liquid nitrogen quick freezing and a nitrogen protection dropwise adding technology are further developed, it is guaranteed that the activity of astaxanthin is not affected by the technology, and high-quality production of the functional core balls is guaranteed.

Description

Technical Field

[0001] The invention relates to a preparation method and application of an astaxanthin composite freeze-dried functional core ball steady-state delivery system, belonging to the 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] Astaxanthin has recently garnered significant attention as a skincare and food ingredient. Known as one of the "strongest natural antioxidants on Earth," its antioxidant activity is 1,000 times that of vitamin E, 150 times that of anthocyanins, and 800 times that of coenzyme Q10. Studies have shown that astaxanthin, whether fat-soluble or water-soluble, effectively scavenges free radicals. Astaxanthin, with its multiple benefits and effects, including antioxidants, vision protection, anti-inflammatory properties, cardiovascular disease prevention, immune enhancement, and anti-aging, holds enormous potential for application in health foods, cosmetics, supplements, and biopharmaceuticals.

[0004] However, astaxanthin has poor stability, especially to light and oxygen, and is easily degraded in the presence of these conditions. In particular, when astaxanthin is used in cosmetics and food and beverages, the astaxanthin emulsions or droplets dispersed in the formulations are very susceptible to oxidation and deterioration, thereby losing their biological activity. This has greatly limited the widespread application of astaxanthin. Summary of the Invention

[0005] In order to overcome the above technical defects, the present invention uses astaxanthin as a fat-soluble active raw material to develop a freeze-dried functional core ball steady-state delivery system of astaxanthin liposomes, which successfully solves the pain points of astaxanthin application. First, a type of composite freeze-dried functional core ball steady-state delivery system of "astaxanthin + liposome active ingredient + small molecule antioxidant active ingredient + natural or fermented macromolecular polysaccharide active ingredient" was innovatively developed. Astaxanthin, liposome active ingredient, small molecule antioxidant active ingredient and macromolecular active polysaccharide form an orderly and stable nano-assembly stabilized structure through multiple intermolecular interactions. The specific excellent spherical appearance, smooth spherical surface, good mechanical strength and excellent solubility and dispersibility solve the problems of astaxanthin stability, compatibility, absorbability and so on; secondly, a full-process low-temperature production and processing technology based on liquid nitrogen quick freezing and a nitrogen protection drop-adding process were developed to ensure that the activity of astaxanthin is not affected by the process and the high-quality production of functional core balls.

[0006] 1. The present invention provides a preparation method and application of a steady-state delivery system of composite freeze-dried functional core balls based on astaxanthin. It innovatively develops a type of composite freeze-dried functional core ball steady-state delivery system of "astaxanthin + liposome active ingredient + small molecule antioxidant active ingredient + natural or fermented macromolecular polysaccharide active ingredient". The system has excellent spherical appearance, smooth spherical surface, good mechanical strength and outstanding solubility and dispersibility, which solves the pain points of astaxanthin such as stability, compatibility and absorbability.

[0007] 2. The astaxanthin composite freeze-dried functional core ball stable delivery system includes, in addition to astaxanthin, a lipid-based active ingredient. The lipid-based active ingredient and astaxanthin nanoassembly form liposomes, enhancing the stability and transdermal absorption rate of astaxanthin.

[0008] The astaxanthin liposomes include, but are not limited to, soy lecithin, egg yolk lecithin, hydrogenated soy lecithin, phytosterols, triglycerides, and combinations thereof. The composite liposomes enhance liposome stability by adding special lipid components such as cholesterol and PEGylated phospholipids.

[0009] The astaxanthin is derived from Haematococcus pluvialis astaxanthin oil, Antarctic krill oil, synthetic astaxanthin, and the astaxanthin content ranges from approximately 5% to 90% by weight, with 10%, 50%, and 90% astaxanthin oil being preferred. The astaxanthin is primarily present within the lumen or vesicles of the liposome complex, thereby achieving stable encapsulation and delivery.

[0010] The astaxanthin composite freeze-dried efficacy core ball steady-state delivery system has an astaxanthin content of 0.01-10% by weight, more preferably 0.05-5% by weight, and even more preferably 0.1-1% by weight.

[0011] The astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, wherein the weight ratio of astaxanthin to lipid active ingredient is 1:1-1000, more preferably in the ratio range of 1:1-100, and more preferably in the ratio range of 1:1-10;

[0012] The preparation process of the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system 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.

[0013] The astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, wherein the method for removing the organic solvent includes but is not limited to rotary evaporation, vacuum drying, stirring volatilization and other processes.

[0014] 3. The astaxanthin composite freeze-dried functional core ball steady-state delivery system, in addition to astaxanthin liposomes, also includes small molecule antioxidant active ingredients to reduce or minimize astaxanthin oxidation and further improve the stability of astaxanthin.

[0015] The small molecule antioxidant active ingredients mainly refer to small molecule antioxidants commonly used in cosmetics or foods, including one or more active ingredients such as ergothioneine, vitamin C ethyl ether, ascorbyl glucoside, catechin, phloretin, raspberry ketone, arbutin, etc.

[0016] The weight content of the small molecule antioxidant active ingredient is 5-70%, more preferably 10-50%, and even more preferably 15-30%;

[0017] 4. The astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, in addition to astaxanthin liposomes, also includes natural or fermented macromolecular polysaccharide active ingredients to improve the stability of astaxanthin.

[0018] The natural macromolecular polysaccharide active ingredients mainly refer to water-soluble macromolecular active raw materials used in cosmetic products, including dendrobium polysaccharide, aloe polysaccharide, mushroom polysaccharide, ganoderma lucidum polysaccharide, wolfberry polysaccharide, oat beta-glucan, carboxymethyl cellulose, and methyl cellulose.

[0019] The fermented macromolecular polysaccharide active ingredients include pullulan, yeast polysaccharide, yeast beta-glucan and sodium hyaluronate.

[0020] The macromolecular active ingredient has a molecular weight range of 1,000-2,000,000, more preferably 3,000-1,200,000, and even more preferably 10,000-800,000.

[0021] In the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, the weight content of the macromolecular active ingredient is 5-80%, more preferably 10-60%, and even more preferably 20-40%.

[0022] 5. The astaxanthin composite freeze-dried functional core ball steady-state delivery system also includes other water-soluble small molecule active substances to enhance other health effects of the astaxanthin functional core ball.

[0023] The water-soluble small molecule active substance includes one or more active ingredients such as arginine, madecassoside, theanine, trehalose, cyclodextrin, mannitol, and snake venom peptide.

[0024] The weight content of the small molecule antioxidant active ingredient is 1-50%, more preferably 5-30%.

[0025] 6. The present invention has developed a full-process low-temperature and nitrogen protection production process based on liquid nitrogen quick freezing to ensure that the activity of astaxanthin is not affected by the process and to ensure the high-quality production of functional core balls. The processing technology of the astaxanthin composite freeze-dried functional core ball steady-state delivery system includes the following steps:

[0026] A. dissolving astaxanthin oil and lipid active ingredients in an organic solvent to obtain a lipid solution;

[0027] B. mixing the lipid solution and purified water uniformly, and then evaporating to obtain an astaxanthin liposome dispersion;

[0028] C. Evenly mix the macromolecular polysaccharide active ingredient and the small molecule active ingredient, add purified water, and heat and stir until the active ingredient is completely dissolved to obtain an active ingredient solution;

[0029] D. mixing the astaxanthin liposome dispersion and the active ingredient solution to obtain a target dispersion;

[0030] E. Add the obtained dispersion dropwise into a heat-insulated liquid nitrogen bucket. When adding dropwise, nitrogen protection needs to be introduced into the target dispersion;

[0031] F. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry them to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system.

[0032] Furthermore, in the above technical solution, the dripping equipment includes but is not limited to a peristaltic pump, a syringe pump, and a flow pump.

[0033] 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.

[0034] 7. The astaxanthin composite freeze-dried efficacy core ball steady-state delivery system developed by the present invention has a particle size range of 0.1-15 mm, more preferably 0.5-8 mm; more preferably 1-5 mm.

[0035] In the best case, the astaxanthin liposome composite freeze-dried efficacy core ball steady-state delivery system provided by the present invention is composed of the following:

[0036] Astaxanthin: Mainly comes from Haematococcus pluvialis astaxanthin oil, Antarctic krill oil, synthetic astaxanthin, etc.

[0037] Lipid active ingredients: one or more of soy lecithin, egg yolk lecithin, hydrogenated soy lecithin, phytosterols, triglycerides, cholesterol, PEGylated phospholipids and the like.

[0038] Small molecule antioxidant active ingredients: one or more of ergothioneine, vitamin C ethyl ether, ascorbyl glucoside, catechin, phloretin, raspberry ketone, arbutin and the like.

[0039] Macromolecular polysaccharides: mainly natural polysaccharides and / or fermented polysaccharides. Natural polysaccharides include dendrobium polysaccharide, aloe polysaccharide, mushroom polysaccharide, ganoderma polysaccharide, wolfberry polysaccharide, oat β-glucan, carboxymethyl cellulose, and methyl cellulose; fermented polysaccharides include one or more ingredients such as pullulan, yeast polysaccharide, yeast β-glucan, and sodium hyaluronate.

[0040] Other water-soluble small molecule active ingredients: one or more of arginine, madecassoside, theanine, trehalose, cyclodextrin, mannitol, and snake venom peptide.

[0041] Advantageous Effects of the Invention

[0042] The present invention proposes for the first time a method for preparing an astaxanthin composite freeze-dried functional core ball steady-state delivery system, namely, a composite freeze-dried functional core ball steady-state delivery system with the functional combination of "astaxanthin + liposome active ingredient + small molecule antioxidant active ingredient + large molecule polysaccharide active ingredient". The system has an excellent spherical appearance, a smooth spherical surface, good mechanical strength and outstanding solubility and dispersibility, which solves the stability and compatibility problems of astaxanthin.

[0043] This invention is the first to introduce astaxanthin liposomes into the freeze-dried efficacy core ball steady-state delivery system, which not only solves the stability and compatibility problems of astaxanthin, but also improves the transdermal absorption rate of astaxanthin.

[0044] The present invention is the first to introduce nitrogen protection into the preparation of an astaxanthin composite freeze-dried efficacy core ball steady-state delivery system to ensure the stability of astaxanthin during the processing process. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1This is a physical picture of the astaxanthin efficacy core ball steady-state delivery system; B1, B2, B3 and B4 are samples of the astaxanthin composite efficacy core ball steady-state delivery system of Examples 1-4, respectively.

[0046] Figure 2 This is a physical picture of the astaxanthin efficacy core ball steady-state delivery system; B5, B6, B7 and B8 are samples of the astaxanthin composite efficacy core ball steady-state delivery system of Examples 5-8, respectively.

[0047] Figure 3 This is a scanning electron microscope image of a cross-section of the astaxanthin efficacy core ball steady-state delivery system; B4, B7 and B8 are samples of the astaxanthin composite efficacy core ball steady-state delivery system of Examples 4, 7 and 8, respectively.

[0048] Figure 4 This is a flow chart of the preparation process of the astaxanthin freeze-dried efficacy core ball steady-state delivery system. DETAILED DESCRIPTION

[0049] Example 1 Preparation of Astaxanthin Composite Efficacy Core Ball Steady-State Delivery System No. 1

[0050] 1. Weigh 0.45g astaxanthin oil (10%), 0.54g sodium hyaluronate, 0.36g dendrobium polysaccharide, 0.27g aloe polysaccharide, 0.21g arginine and 0.24g madecassoside respectively, put them into a beaker and mix well;

[0051] 2. Add 27.93g of purified water and stir until the active ingredients are evenly dispersed and dissolved;

[0052] 3. 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.

[0053] 4. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B1. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0054] 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.

[0055] Example 2 Preparation of Astaxanthin Composite Efficacy Core Ball Steady-State Delivery System No. II

[0056] 1. Weigh 0.45 g astaxanthin oil (10%), 0.66 g soy lecithin, and 0.09 g cholesterol separately and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid ethanol solution; slowly add the astaxanthin lipid ethanol solution dropwise to 20 mL of pure water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 50°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0057] 2. Weigh 0.45 g of sodium hyaluronate, 0.36 g of dendrobium polysaccharide, 0.27 g of aloe polysaccharide, 0.21 g of arginine, and 0.24 g of madecassoside respectively, place them in a beaker and mix well; then add 19.0 g of purified water and stir to dissolve evenly to obtain an active ingredient solution;

[0058] 3. Mixing the astaxanthin liposome dispersion and the active ingredient solution to obtain the target dispersion;

[0059] 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.

[0060] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B2. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0061] 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.

[0062] Example 3 Preparation of Astaxanthin Composite Efficacy Core Ball Steady-State Delivery System No. III

[0063] 1. Weigh 0.45 g astaxanthin oil (10%), 0.66 g soy lecithin, and 0.09 g cholesterol separately and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid ethanol solution; slowly add the astaxanthin lipid ethanol solution dropwise to 20 mL of pure water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 50°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0064] 2. Weigh 0.45 g of sodium hyaluronate, 0.36 g of dendrobium polysaccharide, 0.27 g of aloe polysaccharide, 0.21 g of arginine, and 0.24 g of madecassoside respectively, place them in a beaker and mix well; then add 19.0 g of purified water and stir to dissolve evenly to obtain an active ingredient solution;

[0065] 3. Mixing the astaxanthin liposome dispersion and the active ingredient solution to obtain the target dispersion;

[0066] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0067] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B3. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0068] 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.

[0069] Example 4 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. IV

[0070] 1. Weigh 0.45 g astaxanthin oil (10%), 0.66 g soy lecithin, and 0.09 g cholesterol separately and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid ethanol solution; slowly add the astaxanthin lipid ethanol solution dropwise to 20 mL of pure water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 50°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0071] 2. Weigh 0.45 g of sodium hyaluronate, 0.36 g of dendrobium polysaccharide, 0.15 g of aloe polysaccharide, 0.15 g of arginine, 0.24 g of madecassoside, and 0.18 g of ergothioneine respectively, put them into a beaker and mix well; then add 19.0 g of purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0072] 3. Mixing the astaxanthin liposome dispersion and the active ingredient solution to obtain the target dispersion;

[0073] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0074] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B4. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0075] 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.

[0076] Example 5 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. V

[0077] 1. Weigh 0.45 g astaxanthin oil (10%), 0.66 g soy lecithin, and 0.09 g cholesterol separately and dissolve them in 10 mL tetrahydrofuran to prepare a lipid tetrahydrofuran solution; slowly add the astaxanthin lipid tetrahydrofuran solution dropwise to 20 mL of purified water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 40°C to remove tetrahydrofuran and part of the water, and finally obtain about 10.0 g astaxanthin liposome dispersion for use.

[0078] 2. Weigh 0.45 g of sodium hyaluronate, 0.36 g of dendrobium polysaccharide, 0.15 g of aloe polysaccharide, 0.15 g of arginine, 0.24 g of madecassoside, and 0.3 g of catechin respectively, put them into a beaker and mix well; then add 19.0 g of purified water and stir to dissolve evenly to obtain an active ingredient solution;

[0079] 3. Mixing the astaxanthin liposome dispersion and the active ingredient solution to obtain the target dispersion;

[0080] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0081] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B5. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0082] 6. Pack the freeze-dried functional core balls into plastic bottles, and then pack them into various packaging containers such as vials and glass bottles as needed.

[0083] Example 6 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. VI

[0084] 1. Weigh 0.45 g astaxanthin oil (10%), 0.66 g soy lecithin, and 0.09 g cholesterol separately and dissolve them in 10 mL tetrahydrofuran to prepare a lipid tetrahydrofuran solution; slowly add the astaxanthin lipid tetrahydrofuran solution dropwise to 20 mL of purified water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 40°C to remove tetrahydrofuran and part of the water, and finally obtain about 10.0 g astaxanthin liposome dispersion for use.

[0085] 2. Weigh 0.45 g of sodium hyaluronate, 0.36 g of dendrobium polysaccharide, 0.15 g of aloe polysaccharide, 0.15 g of arginine, 0.24 g of madecassoside, and 0.54 g of ascorbyl ether respectively, place them in a beaker and mix well; then add 19.0 g of purified water and stir to dissolve evenly to obtain an active ingredient solution;

[0086] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0087] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0088] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B6. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0089] 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.

[0090] Example 7 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. VII

[0091] 1. Weigh 0.30 g astaxanthin oil (50%), 0.48 g hydrogenated soy lecithin, 0.15 g egg yolk lecithin, and 0.09 g triglyceride and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid anhydrous ethanol solution; slowly add the astaxanthin lipid anhydrous ethanol solution dropwise to 20 mL of pure water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 45°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0092] 2. Weigh 0.24 g Tremella polysaccharide, 0.18 g Mushroom polysaccharide, 0.45 g oat beta glucan, 0.3 g theanine, 0.15 g trehalose, and 0.18 g ergothioneine respectively, put them into a beaker and mix well; then, add 19.0 g purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0093] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0094] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0095] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B7. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0096] 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.

[0097] Example 8 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. VIII 1. Weigh 0.30 g of astaxanthin oil (90%), 0.48 g of hydrogenated soybean lecithin, 0.15 g of egg yolk lecithin, and 0.09 g of triglyceride and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid anhydrous ethanol solution; slowly drop the astaxanthin lipid anhydrous ethanol solution into 20 mL of pure water, and after the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 45°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0098] 2. Weigh 0.24 g Tremella polysaccharide, 0.18 g Mushroom polysaccharide, 0.45 g Oat β-glucan, 0.3 g Theanine, 0.15 g Trehalose and 0.36 g Ascorbyl glucoside respectively, put them into a beaker and mix well; then add 19.0 g purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0099] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0100] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0101] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system; 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.

[0102] 6. Dispense the freeze-dried active ingredient pellets into plastic bottles. Subsequently, dispense into vials, glass bottles, and other packaging containers as needed. This is designated B8.

[0103] Example 9 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. IX

[0104] 1. Weigh 0.30 g astaxanthin oil (50%), 0.6 g hydrogenated soy lecithin, 0.3 g egg yolk lecithin, and 0.09 g triglyceride and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid anhydrous ethanol solution; slowly add the astaxanthin lipid anhydrous ethanol solution dropwise to 20 mL of pure water. After the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 45°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0105] 2. Weigh 0.24 g Tremella polysaccharide, 0.18 g Mushroom polysaccharide, 0.45 g Oat β-glucan, 0.3 g Theanine, 0.15 g Trehalose, 0.03 g Phloretin and 0.21 g Hydroxypropyl β-cyclodextrin respectively, put them into a beaker and mix well; then add 19.0 g purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0106] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0107] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0108] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B9. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0109] 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.

[0110] Example 10 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. X 1. Weigh 0.21 g astaxanthin oil (50%), 0.45 g egg yolk lecithin, 0.3 g phytosterol, and 0.09 g PEGylated phospholipid separately and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid anhydrous ethanol solution; slowly drop the astaxanthin lipid anhydrous ethanol solution into 20 mL of pure water, and after the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 45°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0111] 2. Weigh 0.15g of Ganoderma lucidum polysaccharide, 0.18g of Lycium barbarum polysaccharide, 0.75g of yeast polysaccharide, 0.3g of methylcellulose, 0.15g of mannitol, 0.24g of arbutin, and 0.12g of vitamin C ethyl ether respectively, put them into a beaker and mix them evenly; then add 19.0g of purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0112] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0113] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0114] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B10. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0115] 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.

[0116] Example 11 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. XI 1. Weigh 0.36 g astaxanthin oil (90%), 0.6 g egg yolk lecithin, 0.3 g phytosterol, 0.09 g PEGylated phospholipid, and 0.24 g raspberry ketone respectively, and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid anhydrous ethanol solution; slowly drop the astaxanthin lipid anhydrous ethanol solution into 20 mL of pure water, and after the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 45°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0117] 2. Weigh 0.15g of pullulan, 0.7g of yeast beta glucan, 0.45g of sodium hyaluronate, 0.06g of carboxymethyl cellulose, 0.15g of mannitol, and 0.12g of ergothioneine respectively, put them into a beaker and mix well; then, add 19.0g of purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0118] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0119] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0120] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B11. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0121] 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.

[0122] Example 12 Preparation of Astaxanthin Liposome Composite Efficacy Core Ball Steady-State Delivery System No. XII 1. Weigh 0.36 g astaxanthin oil (90%), 0.45 g egg yolk lecithin, 0.45 g hydrogenated soy lecithin, 0.18 g cholesterol, and 0.18 g phloretin respectively, and dissolve them in 10 mL of anhydrous ethanol to prepare a lipid anhydrous ethanol solution; slowly drop the astaxanthin lipid anhydrous ethanol solution into 20 mL of pure water, and after the addition is complete, continue stirring for 30 minutes to obtain a mixed solution; rotary evaporate the mixed solution at 45°C to remove ethanol and part of the water, and finally obtain about 10.0 g of astaxanthin liposome dispersion for use.

[0123] 2. Weigh 0.24 g pullulan, 0.78 g yeast beta-glucan, 0.48 g sodium hyaluronate, 0.15 g ergothioneine, 0.15 g theanine, and 0.03 g snake venom peptide respectively, put them into a beaker and mix well; then add 19.0 g purified water, stir and dissolve evenly to obtain an active ingredient solution;

[0124] 3. Mixing the astaxanthin liposome dispersion and the small molecule active ingredient solution to obtain the target dispersion;

[0125] 4. Use a peristaltic pump to add the above solution drop by drop into a heat-insulated liquid nitrogen bucket. When adding drop by drop, introduce nitrogen into the target dispersion to prevent astaxanthin from being oxidized and lost. The droplet size is about 40 mg, and small ice balls are obtained by rapid freezing.

[0126] 5. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry for 24-48 hours to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, designated as B12. The freeze dryer's cold trap temperature is controlled at approximately -70°C, and the final drying chamber temperature is controlled at approximately 30°C.

[0127] 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.

[0128] Detection and analysis examples

[0129] Test Example 1 Astaxanthin composite freeze-dried efficacy core ball steady-state delivery system sample sample group 1

[0130] Use a camera to take pictures to characterize the appearance and morphology of the astaxanthin liposome composite freeze-dried efficacy core ball steady-state delivery system and conduct comparative analysis.

[0131] Samples B1, B2, B3 and B4 are from Examples 1-4, respectively. The astaxanthin oil is 10% Haematococcus pluvialis astaxanthin oil, and the formula is basically the same. Figure 1 It can be seen that after freeze-drying, B1, B2, B3 and B4 are all orange astaxanthin freeze-dried efficacy core ball steady-state delivery systems, that is, efficacy core balls, and the balls are all well spherical and have good uniformity in size. The orange astaxanthin distribution of sample B1 efficacy core ball is uneven, which is mainly due to the fact that astaxanthin liposomes are not prepared in advance, and astaxanthin oil and other component aqueous solutions are directly mixed, which is uneven and easily leads to phase separation. Samples B2, B3 and B4 are all first assembled by mixing astaxanthin oil and lipid components to prepare astaxanthin liposomes, and then the liposomes are mixed with other active ingredient aqueous solutions. In this way, the astaxanthin liposomes can be evenly dispersed in the liquid, and the color of the efficacy core balls obtained is relatively more uniform. There are a few cracks on the surface of some small balls, which is mainly due to uneven internal stress during freezing, which does not affect subsequent use.

[0132] Test Example 2 Astaxanthin composite freeze-dried efficacy core ball steady-state delivery system sample sample group 2

[0133] Samples B5, B6, B7 and B8, from Examples 5-8, are orange astaxanthin composite freeze-dried efficacy core ball steady-state delivery system. Figure 2It can be seen that the spheres are all well-spherical and uniform in size. Samples 5 and 6 used 10% astaxanthin oil, Sample 7 used 50% astaxanthin oil, and Sample 8 used 90% astaxanthin oil. In terms of astaxanthin content, Samples 5 and 6 have similar astaxanthin content, while Sample 7 has a higher astaxanthin content, and Sample 8 has the highest astaxanthin content. Therefore, the color of the astaxanthin liposome composite freeze-dried functional core sphere steady-state delivery system is the darkest in Sample 8.

[0134] Scanning electron microscopy of a sample of the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system in test example 3

[0135] Gently break the functional core ball apart and then observe it with a scanning electron microscope. Figure 3 As can be seen in the figure, the interior of the sphere is a uniform layered structure, with evenly distributed micron-sized channels between the layers. Sample B8 contains some small particles, which are a small number of agglomerated liposome nanoparticles. The majority of the liposome nanoparticles are evenly distributed in the active molecule layer. During rapid freezing with liquid nitrogen, the active substance dissolved in the water rapidly precipitates to form extremely small crystals. Then, during freeze-drying, as the ice crystals sublime, water vapor forms micron-sized water vapor channels, connecting the tiny active substance crystals together to form a layered structure. Because liquid nitrogen freezes very quickly, the microstructure of the entire sphere is very uniform. The active substance layer is very thin, generally less than 1 micron, which ensures that the active substance can dissolve extremely quickly when water is added again.

[0136] Test Example 4 Astaxanthin Content in Astaxanthin Composite Freeze-Dried Efficacy Core Ball Steady-State Delivery System Sample

[0137] Table 1 shows the astaxanthin content and astaxanthin retention rate of different astaxanthin composite efficacy core ball steady-state delivery systems. Samples B1-B6 are all systems with 10% astaxanthin oil. Samples B1 and B2 did not have nitrogen protection during the dropwise addition process. The main difference between the two is that sample B1 is astaxanthin oil and sample B2 is astaxanthin liposomes. The astaxanthin retention rate of sample B1 is about 81%, which is mainly due to the oxidation of some astaxanthin during the preparation and dropwise addition process. The astaxanthin retention rate of sample B2 is about 88%, which is significantly higher than that of sample B1, indicating that liposome encapsulation can significantly reduce the oxidation of astaxanthin and improve the stability of astaxanthin.

[0138] Table 1: Astaxanthin content of astaxanthin composite efficacy core ball steady-state delivery system

[0139]

[0140] The formulas of samples B2 and B3 are exactly the same, but the addition process is slightly different. Sample B3 was nitrogen-protected during the addition. It can be seen that the astaxanthin content and retention rate of the two samples are different. The astaxanthin retention rate of sample B3 reaches over 96%, which is significantly higher than that of sample B2. This shows that implementing nitrogen protection during the addition process can significantly reduce the probability of astaxanthin being oxidized, which is especially important in industrial production. Compared with sample B3, sample B4 has basically the same formula, except that thioneine is added to further enhance the stability of astaxanthin. The experimental results also show that after the addition of thioneine, the retention rate of astaxanthin is further improved to over 99%. Samples B5 and B6 have similar formulas to B4, except that antioxidant active ingredients are used. The retention rate of astaxanthin in the samples is also very high, similar to sample B4, reaching over 98%.

[0141] Samples B7-B12 are astaxanthin composite freeze-dried functional pellets with a steady-state delivery system based on 50% astaxanthin oil and 90% astaxanthin. All samples were prepared by first preparing astaxanthin liposomes, then adding them dropwise under nitrogen to form pellets, and then freeze-drying them. As shown in the table, the astaxanthin liposomes and nitrogen protection effectively protected astaxanthin from oxidation, with astaxanthin retention rates exceeding 98% in all samples.

[0142] Test Example 4: Stability

[0143] Astaxanthin is susceptible to oxidation and deterioration. Based on the stability evaluation of cosmetics, the stability of astaxanthin-based core beads was evaluated through a 45°C accelerated test and compared with astaxanthin control dispersion I and astaxanthin control serum I (see Application Examples). The astaxanthin-based core beads were first subjected to an accelerated test, then prepared into solutions of varying concentrations for analysis. Using an initial astaxanthin concentration of 100%, the retained astaxanthin concentration was measured as a percentage of the initial concentration at various aging times.

[0144] As can be seen from Table 2, the astaxanthin content in the astaxanthin control dispersion I (control sample 1) dropped rapidly, decreasing by about 10% after 1 hour, by about 35% after 5 hours, by about 95% after 48 hours, and remaining at zero after 120 hours. The astaxanthin content in the astaxanthin control essence I dropped even faster, dropping by about 15% after 1 hour, by about 55% after 5 hours, and remaining only about 1% after 48 hours. This may be due to the presence of trace metal ions in the essence formula, which accelerate the oxidative degradation of astaxanthin.

[0145] Table 2: Astaxanthin content of the astaxanthin composite efficacy core ball steady-state delivery system

[0146]

[0147] Sample B3 astaxanthin composite efficacy core ball steady-state delivery system is based on liposome-encapsulated astaxanthin. No antioxidant active ingredients are added. The astaxanthin is stable. After 10 days (240h), the astaxanthin retention rate is still about 91%, and after 60 days (60d), the astaxanthin retention rate is about 86%. With the addition of antioxidant active ingredient B4, the stability of astaxanthin is further improved. After 10 days, the astaxanthin retention rate reaches more than 98%, and after 60 days (60d), the astaxanthin retention rate is still more than 95%. For other samples, the astaxanthin content in the astaxanthin composite efficacy core ball does not change much after 240h (10 days), and the retention rate is about 98%. After 60 days (60d), the astaxanthin retention rate is basically more than 95%. This is mainly because the oxidative degradation rate of astaxanthin can be reduced under the liposome coating, and the addition of antioxidant active ingredients further improves the stability of astaxanthin. Moreover, astaxanthin is more stable in a dry state. The results of the analysis and evaluation experiments show that the stability of astaxanthin in the composite freeze-dried functional core ball steady-state delivery system is significantly higher than that in astaxanthin oil or essence, and the content remains stable.

[0148] Test Example 5: Transdermal Absorption

[0149] A systematic transdermal efficacy evaluation and comparison was conducted for the application cases. The evaluation method was based on the “In Vitro Test Method for Skin Absorption of Chemicals”. The evaluation results are shown in Table 3.

[0150] Table 3 Transdermal efficacy evaluation of astaxanthin composite efficacy core ball steady-state delivery system

[0151]

[0152] First, for the convenience of comparison, the astaxanthin control dispersion liquid I, astaxanthin control essence liquid I, astaxanthin efficacy core ball essence-I, astaxanthin efficacy core ball essence-II and astaxanthin efficacy core ball essence-III were diluted with deionized water to an astaxanthin concentration of about 0.05%, and then the transdermal test was carried out. Because astaxanthin is very easy to oxidize, only the transdermal data of 1h and 4h were observed and analyzed to minimize the impact of astaxanthin instability on the test. As can be seen from the above table, the astaxanthin transdermal amount of the astaxanthin composite efficacy core ball essence is significantly higher than that of the astaxanthin control dispersion liquid I and essence liquid I, and the 4h transdermal amount is 3 times that of the astaxanthin control essence liquid I. The results show that astaxanthin liposomes and the nano-assembly structure of the efficacy core ball can not only improve the stability of astaxanthin, but also improve the transdermal absorption rate of astaxanthin.

[0153] Application Example 1 Astaxanthin Control Dispersion I

[0154] (1) Weigh 1.5 g of Tween 80 and dissolve it in 95 g of deionized water to obtain a Tween 80 aqueous solution. Then weigh 5 g of astaxanthin oil (10%). While dispersing with a shearing homogenizer, add 5 g of astaxanthin oil dropwise to the Tween aqueous solution. After complete addition, homogenize for another 2 minutes to obtain astaxanthin control dispersion I. This will be used for subsequent evaluation.

[0155] Application Example 2 Astaxanthin Control Essence I

[0156] The formula of astaxanthin control essence is shown in Table 4. The brief process is as follows:

[0157] (1) Weigh the raw materials of phase A in sequence, heat and stir at 40°C to dissolve evenly;

[0158] (2) After stirring and cooling, add phase B and stir evenly, then discharge the material to obtain the astaxanthin control essence solution for subsequent evaluation.

[0159] Table 4 Astaxanthin control essence formula

[0160]

[0161]

[0162] Application Example 3 Astaxanthin Efficacy Core Ball Essence-I

[0163] (1) Take 500 mg of the functional core ball sample B from Example 4 and place it in a vial;

[0164] (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette;

[0165] (3) Pour 10 mL of normal saline into the vial of the functional core ball and shake gently to dissolve evenly to obtain the astaxanthin functional core ball essence-I.

[0166] Application Example 4 Astaxanthin Effective Core Ball Essence-Ⅱ

[0167] (1) Take 7500 mg of the functional core ball sample B from Example 7 and place it in a vial;

[0168] (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette;

[0169] (3) Pour 10 mL of normal saline into the vial of the Effective Core Ball and shake gently to dissolve evenly to obtain the Astaxanthin Effective Core Ball Essence-II.

[0170] Application Example 5 Astaxanthin Effective Core Ball Essence-Ⅲ

[0171] (1) Take 500 mg of the functional core ball sample B from Example 8 and place it in a vial;

[0172] (2) Prepare some 0.9% saline solution and add 3 mL of saline solution to the vial using a pipette;

[0173] (3) Pour 10 mL of normal saline into the vial of the functional core ball and shake gently to dissolve evenly to obtain the astaxanthin functional core ball essence-III.

[0174] The above embodiments illustrate the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions merely illustrate the principles of the present invention. Various changes and improvements may be made to the present invention without departing from the scope of the present invention, and all such changes and improvements fall within the scope of protection of the present invention.

Claims

1. Astaxanthin composite freeze-dried efficacy core ball steady-state delivery system, characterized by: include: Astaxanthin, liposome active ingredients, small molecule antioxidant active ingredients, natural or fermented macromolecular polysaccharide active ingredients, and other small molecule active ingredients.

2. The astaxanthin composite freeze-dried functional core ball steady-state delivery system according to claim 1, characterized in that: The liposome active ingredient is selected from at least one of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, phytosterols, and triglycerides.

3. The astaxanthin composite freeze-dried functional core ball steady-state delivery system according to claim 1, characterized in that: The small molecule antioxidant active ingredients include one or more of ergothioneine, vitamin C ethyl ether, ascorbyl glucoside, catechin, phloretin, raspberry ketone, and arbutin active ingredients.

4. The astaxanthin composite freeze-dried functional core ball steady-state delivery system according to claim 1, characterized in that: The natural macromolecular polysaccharide active ingredients include dendrobium polysaccharide, aloe polysaccharide, mushroom polysaccharide, ganoderma polysaccharide, wolfberry polysaccharide, oat beta-glucan, carboxymethyl cellulose, and methyl cellulose; the fermented macromolecular polysaccharide active ingredients include pullulan, yeast polysaccharide, yeast beta-glucan, and sodium hyaluronate.

5. The astaxanthin composite freeze-dried functional core ball steady-state delivery system according to claim 1, characterized in that: Other small molecule active ingredients are selected from one or more of arginine, madecassoside, theanine, trehalose, cyclodextrin, mannitol, snake venom peptide and the like.

6. The astaxanthin composite freeze-dried functional core ball steady-state delivery system according to claim 1, characterized in that: The particle size range of the steady-state delivery system is 0.1-15 mm.

7. The processing technology of the astaxanthin composite freeze-dried functional core ball steady-state delivery system according to any one of claims 1 to 6, characterized in that: The steps include: A. dissolving astaxanthin oil and liposome active ingredients in an organic solvent to obtain a lipid solution; B. mixing the lipid solution and purified water uniformly, and then evaporating to obtain an astaxanthin liposome dispersion; C. Evenly mix the macromolecular polysaccharide active ingredient and the small molecule active ingredient, add purified water, and heat and stir until the active ingredient is completely dissolved to obtain an active ingredient solution; D. mixing the astaxanthin liposome dispersion and the active ingredient solution to obtain a target dispersion; E. Add the obtained dispersion dropwise into a heat-insulated liquid nitrogen bucket. When adding dropwise, nitrogen protection needs to be introduced into the target dispersion; F. Transfer the small ice balls formed by freezing with liquid nitrogen to a freeze dryer and freeze-dry them to obtain the astaxanthin composite freeze-dried efficacy core ball steady-state delivery system.

8. The processing technology of the astaxanthin composite freeze-dried functional core ball steady-state delivery system according to claim 7, characterized in that: The drop-adding equipment includes but is not limited to a peristaltic pump, a syringe pump, and a flow pump; 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.

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