Capsule solution of skin-whitening composition, method of preparation and use thereof

Abstract

The present invention discloses a double-layered alveolar capsule that contains phospholipids, polyol, emulsifier and liquid oil in a skin-whitening composition to form a dermoid cell membrane structure. SOLUTION: The capsules are mainly composed of phospholipids, and encapsulate an alcohol-soluble main component, auxiliary components, antioxidant components, and an anti-inflammatory component in a plant extract aqueous solution, and signal molecules are attached to the surface of the capsules, and the composition contains, by mass percentage, 1-3% alcohol-soluble main component, 10-50% polyol, 3-15% phospholipid, 1-3% emulsifying aid, 1-5% liquid oil, 0.01-0.5% signal molecule, 0.01-2% auxiliary components, 0.01-4% antioxidant components, and 17.5-83.97% plant extract aqueous solution. The whitening composition capsule solution of the present application has good whitening efficacy, with each component acting synergistically.

Description

[Technical Field]

[0001] This application claims priority and privilege from Chinese Patent Application No. 202310337523.4, filed with the China Intellectual Property Office on March 31, 2023, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to the field of skin lightening skin care products, and in particular to an encapsulated solution of a skin lightening composition, a method for preparing it and its use. [Background technology]

[0003] Glabridin (flavonoid) is a natural plant extract derived from polyphenols found in wild African licorice. Glabridin has many beneficial effects, including antioxidant, immunomodulatory, anti-inflammatory, and antidepressant properties. Research has shown that glabridin has anti-free radical activity and effectively inhibits cell damage caused by free radicals.

[0004] The target of action of glabridin and other common skin-lightening agents is located in the nucleus of melanocytes. α-MSH signaling molecules bind to the MC1-R receptor on the melanocyte membrane, triggering intracellular reactions such as upregulation of protein kinase A expression, which then activates tyrosinase, catalyzing tyrosine to ultimately form melanin. Inflammation, such as allergies, acne, or sunburn, also induces the binding of α-MSH to the MC1-R receptor, upregulating the expression of inflammatory factors such as IL-1, IL-6, IL-8, and TNF-α, ultimately resulting in pigmentation after the inflammation resolves. Therefore, melanin formation is the result of a complex series of reactions within melanocytes, and achieving effective skin-lightening requires consideration of various aspects in addition to inhibiting tyrosinase activity.

[0005] Prior art technical solutions include: (1) CN108451837A, which combines and encapsulates active ingredients for different whitening mechanisms to achieve multi-target whitening and ease of use of the combined ingredients; (2) CN114796008A, which simultaneously encapsulates glabridin and polypeptides; and (3) CN115778886A, which discloses microencapsulated capsules derived from glabridin plants and a method for producing the same. However, the inventors of the present invention have found that the products obtained by the above prior art technical solutions have problems such as poor stability (e.g., discoloration to pink or yellow after 30 days at room temperature) and poor whitening effect.

[0006] Therefore, there remains a strong demand for a whitening product that is highly stable and has a high whitening effect. Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention has been made in view of the above problems, and aims to provide a capsule solution of a whitening composition having a superior whitening effect, a method for producing the same, and use thereof. [Means for solving the problem]

[0008] To achieve the technical objective, in a first aspect, the present invention provides a method for producing a nanoscale double-layer capsule, the specific steps of which are as follows: In S1, 1 to 3% of the alcohol-soluble main component and 10 to 50% of the polyol are weighed out by mass percentage, and mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. In S2, 3 to 15% of phospholipid, 1 to 3% of emulsifying aid, 1 to 5% of liquid oil, and 0.01 to 0.5% of signal molecule are weighed out by mass percentage, and mixed and stirred in a water bath at 70°C until dissolved to obtain phase B. In step S3, an aqueous solution of plant extracts is prepared, and then 0.01 to 2% of auxiliary ingredients and 0.01 to 4% of antioxidant ingredients are weighed out by mass percentage, dissolved in 17.5 to 83.97% of the aqueous solution of plant extracts, and heated to 65°C to obtain phase C. In S4, phase A and phase B are mixed and stirred uniformly, and then phase C is added and emulsified to obtain a crude emulsion. In S5, the crude emulsion is subjected to high-pressure shear treatment at a temperature of 30 to 40°C to obtain nanoscale capsules, and finally a whitening composition capsule solution is obtained.

[0009] Preferably, the emulsifier in step S4 has an output power of 0.2 kW, a rotation speed of 3000 to 8000 rpm, and a high-speed shear dispersion time of 3 to 10 minutes; The shear pressure is 400 to 1000 bar, and the number of repeated shears is 5 to 10.

[0010] Preferably, the aqueous plant extract solution is an aqueous extract solution of an herbaceous anti-inflammatory plant, and the herbaceous anti-inflammatory plant is one or a combination of peony flower, peony root, rose flower, and purslane.

[0011] Preferably, in step S3, the anti-inflammatory herb is washed, dried, and pulverized to obtain a plant powder, and the plant powder and water are refluxed at 50-80°C in a mass ratio of 1:10-1:20 for 8-24 hours to obtain a stewed solution, which is then filtered and the filtrate is purified by passing it through a macroporous anion exchange resin in a volume ratio of 10-15:1 for a retention time of 15-25 minutes to obtain an aqueous plant extract solution.

[0012] Preferably, the alcohol-soluble main component is glabridin, the auxiliary component is glutathione, and the signal molecule is palmitoyl tripeptide-8.

[0013] Preferably, the polyol is one or a combination of more of glycerol, propylene glycol, butanediol, dipropylene glycol, pentanediol, isopentyl diol; the emulsifying aid is one or a combination of more than one of polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyoxyethylene hydrogenated castor oil, and potassium cetyl phosphate; the liquid oil is one or more combinations of caprylic / capric triglyceride, meadowfoam oil, squalane, olive oil, and peony seed oil; the phospholipid is one or a combination of soy lecithin, hydrogenated lecithin, and soy phosphatidylcholine; The antioxidant component is one or a combination of more of vitamin C, 3-o-ethyl ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, and ascorbic acid polypeptide.

[0014] Preferably, the formulation ratio of the whitening composition capsule solution is, by mass percentage, 1.1±0.1% glabridin, 20±5% polyol, 6±2% phospholipid, 2±0.5% emulsifier, 2±0.5% liquid oil, 0.15±0.05% palmitoyl tripeptide-8, 1±0.2% glutathione, 3±0.5% antioxidant, and 60±15% plant extract aqueous solution.

[0015] In some embodiments, the nanoscale double-layer capsules produced using the above manufacturing methods have a particle size of 20 nm to 110 nm. In some embodiments, the nanoscale double-layer capsules produced using the above manufacturing methods have a particle size of 30 nm to 110 nm. In some embodiments, the nanoscale double-layer capsules produced using the above manufacturing methods have a particle size of 30 nm, 80 nm, or 110 nm.

[0016] In a second aspect, the present invention provides a whitening composition capsule solution obtained by the manufacturing method according to the first aspect.

[0017] The highly transparent and stable whitening composition capsule solution produced using the method for producing nanoscale double-layer capsules described in the first aspect has capsules mainly composed of phospholipids, encapsulating a plant extract containing an alcohol-soluble main ingredient, auxiliary ingredients, antioxidant ingredients, and anti-inflammatory ingredients, and signal molecules are attached to the capsule surface.

[0018] In a third aspect, the present invention provides a use of the whitening composition capsule solution.

[0019] Use of the whitening composition capsule solution according to the second aspect in the field of cosmetics. [Effects of the Invention]

[0020] The beneficial effects of the present invention, which uses an alcohol-soluble main ingredient, are as follows: The components of the whitening composition capsule solution of the present application have excellent synergistic effects, achieving good whitening effects. Furthermore, the whitening composition capsule solution of the present application is a capsule with a double-layered vesicle structure, which is highly stable, can stably encapsulate active ingredients, and is easily absorbed by the skin. While conventional palmitoyl tripeptide-8 is only used as a sedative or anti-allergic polypeptide (and also has α-MSH mimetic activity), the present application uses palmitoyl tripeptide-8 as a targeting peptide, which has amphiphilic properties that allow it to effectively adhere to the capsule surface and form targets. The hydrophilic group of palmitoyl tripeptide-8 can bind to the MC1-R receptor on melanocytes. Furthermore, the combination of glabridin and glutathione creates excellent synergistic effects, effectively reducing eumelanin production and further enhancing whitening effects. The blending ratio of each component in the capsule solution of the whitening composition of the present invention is strictly selected, and it has a significant effect on the performance of whitening effects.

[0021] In a fourth aspect, the present invention provides a skin lightening composition capsule solution.

[0022] A whitening composition capsule solution, the manufacturing method of which comprises: Step (1) of mixing and stirring 1% glabridin and 20% butanediol by mass in a water bath at 65°C until dissolved to obtain phase A; Step (2) of mixing and stirring 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, 5% by mass of soybean lecithin, and 0.15% by mass of palmitoyl tripeptide-8 in a water bath at 70°C until dissolved to obtain phase B; Step (3) of dissolving 1% glutathione and 3% 3-o-ethyl ascorbic acid by mass in a 66.35% aqueous solution of rose flower and heating the solution to 65°C to obtain phase C; The preparation of the rose flower aqueous solution includes the steps of washing, drying and pulverizing the rose flower herbaceous anti-inflammatory plant to obtain plant powder, boiling the plant powder and water at a mass ratio of 1:15 under reflux at 60°C for 8 hours to obtain a boiled solution, filtering the boiled solution, and using macroporous anion exchange resin at a volume ratio of 10:1 for a retention time of 20 minutes to obtain a plant extract aqueous solution; Step (4) of mixing phase A and phase B with stirring, and then adding phase C and emulsifying to obtain a crude emulsion for capsules; and (5) high-pressure shearing of the crude emulsion to nanoscale, controlling the circulating water bath at 30-40°C and repeatedly shearing at a pressure of 800 bar six times to obtain a whitening composition capsule solution.

[0023] In some embodiments, the zeta potential of the skin whitening composition capsule solution is −34 mV.

[0024] In some embodiments, the capsule particle size in the whitening composition capsule solution is 30 nm. DETAILED DESCRIPTION OF THE INVENTION

[0025] The present invention will now be described in more detail with reference to specific examples.

[0026] The specific embodiment described in the present invention is a manufacturing method for preparing a capsule solution of a whitening composition as follows, and the specific steps are as follows: In step S101, glabridin and polyol are mixed and stirred in a water bath at 65°C until dissolved to obtain phase A. In S102, the emulsifier, the liquid oil, the phospholipid, and the palmitoyl tripeptide-8 are mixed and stirred in a water bath at 70°C until dissolved to obtain a phase B. In step S103, a plant extract aqueous solution is prepared by washing, drying, and pulverizing an anti-inflammatory herbaceous plant to obtain a plant powder, stewing the plant powder and water at a mass ratio of 1:10 to 1:20 at 50 to 80°C under reflux for 8 to 24 hours to obtain a stewing solution, filtering the filtrate, and purifying the filtrate with a macroporous anion exchange resin at a volume ratio of 10 to 15:1 for a retention time of 15 to 25 minutes to obtain a plant extract aqueous solution. The plant extract aqueous solution is an extract aqueous solution of an anti-inflammatory herbaceous plant, and the anti-inflammatory herbaceous plant is one or a combination of peony flower, peony root, rose flower, and purslane. In step S104, glutathione and antioxidant components are dissolved in the aqueous solution of rose flower plant extract in the appropriate proportions, and the solution is heated to 65°C to obtain phase C. In S105, firstly, the phase A and the phase B are mixed in a certain ratio and stirred uniformly, and then the phase C is added and emulsified to obtain a crude emulsion; In step S106, the crude emulsion is subjected to high-pressure shearing at a temperature of 30 to 40°C to process it into nanoscale particles, with the emulsifier having an output power of 0.2 kW, a rotation speed of 3000 to 8000 rpm, a high-speed shear dispersion time of 3 to 10 minutes, a shear pressure of 400 to 1000 bar, and repeated shearing times of 5 to 10 times, to finally obtain a highly transparent and stable whitening composition capsule solution.

[0027] When using a whitening composition capsule solution that can be used as a raw material for cosmetics, the whitening composition capsule solution is generally contained in the cosmetic product at a mass rate of 0.5 to 10%, and can be prepared into cosmetics in the form of emulsion, cream, gel, etc.

[0028] The whitening composition capsule solution contains double-layered alveolar capsules with a skin cell membrane structure formed by phospholipids, polyols, emulsifiers, and liquid oils. The capsules contain phospholipids as the main component, glabridin (the main alcohol-soluble component), glutathione (an auxiliary component), antioxidants, and anti-inflammatory components in a plant extract aqueous solution. Palmitoyl tripeptide-8 (a signal molecule) is attached to the capsule surface. By mass percentage, it contains 1-3% glabridin, 10-50% polyol, 3-15% phospholipid, 1-3% emulsifier, 1-5% liquid oil, 0.01-0.5% palmitoyl tripeptide 8, 0.01-2% glutathione, 0.01-4% antioxidant, and 17.5-83.97% aqueous plant extract solution.

[0029] The polyol is one or a combination of glycerol, propylene glycol, butanediol, dipropylene glycol, pentanediol, and isopentyl diol; the emulsifying aid is one or a combination of polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyoxyethylene hydrogenated castor oil, potassium cetyl phosphate, and potassium phosphate; the liquid oil is one or a combination of caprylic / capric triglyceride, meadowfoam oil, squalane, olive oil, and peony seed oil; the phospholipid is one or a combination of soybean lecithin, hydrogenated lecithin, and soybean phosphatidylcholine; and the antioxidant is one or a combination of vitamin C, 3-o-ethyl ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, and ascorbic acid polypeptide.

[0030] Glabridin has a resorcinol structure and is potentially valuable for its whitening effects, but its poor solubility in water and oil makes it difficult to use as a formulating ingredient. Furthermore, glabridin is easily oxidized and discolored by light, so technology is needed to improve its stability.

[0031] The technical principle of this application is as follows: the capsule uses palmitoyl tripeptide-8 as a targeting peptide, and the hydrophilic group exposed in the capsule serves as a signal molecule (the hydrophilic group exposed in the aqueous phase serves as a signal molecule targeting the capsule and binds to the MC1-R receptor), effectively increasing the affinity of the capsule to melanocytes and thereby increasing the efficacy of the composition.

[0032] In addition, the whitening effect of glycyrrhizin can be further improved by adding glutathione. The main whitening mechanism of glycyrrhizin is to inhibit the activity of tyrosinase, thereby inhibiting the melanin production reaction. Regarding glutathione, melanin is classified into eumelanin (black to dark brown), pheomelanin (reddish-brown to yellow), and other less common types. The melanin in human epidermis is mainly eumelanin, with a small amount of pheomelanin. Dopaquinone, which is formed from tyrosine by the catalyst of tyrosinase, partially synthesizes pheomelanin in the presence of glutathione, and the majority of the remainder synthesizes eumelanin. Artificially increasing the concentration of glutathione encourages more dopaquinone to form light-colored pheomelanin, thereby reducing the production of dark-colored eumelanin. Regarding vitamin C or vitamin C derivatives, they act as an antioxidant and reduce the formed melanin to a colorless structure. Regarding plant extract aqueous solutions, they have anti-inflammatory properties.

[0033] By using an emulsifier such as soybean lecithin or hydrogenated lecithin, whose critical bulk parameter is in the range of 1 / 2 to 1, as the main capsule component, a double-layered vesicle with a dermoid cell membrane structure is formed, and the water-soluble active substance is encapsulated in the internal aqueous phase, thereby similarly exhibiting a penetration-enhancing effect.

[0034] [Example 1] (1) 2% glabridin and 50% glycerol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 3% by mass of polyglyceryl-10 stearate, 2% by mass of meadowfoam oil, 10% by mass of hydrogenated lecithin, and 0.05% by mass of palmitoyl tripeptide-8 were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% glutathione and 2% ascorbyl glucoside by mass were dissolved in a 29.95% peony root aqueous solution (prepared in S103 to prepare a plant extract aqueous solution; the anti-inflammatory herb was washed, dried, and crushed to obtain a plant powder; the plant powder and water were simmered at 60°C in a mass ratio of 1:15 for 8 hours to obtain a stewed solution; the stewed solution was filtered; the filtrate was then treated with macroporous anion exchange resin in a volume ratio of 10:1, with a retention time of 20 minutes to obtain a purified plant extract aqueous solution), and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. The shearing was repeated six times at a pressure of 800 bar to obtain a whitening composition capsule solution, with a zeta potential of -28mV and a capsule particle size of 80nm.

[0035] [Example 2] (1) 3% glabridin and 30% dipropylene glycol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 3% by mass of polyglyceryl-10 oleate, 2% by mass of caprylic / capric triglyceride, 8% by mass of soybean lecithin, and 0.1% by mass of palmitoyl tripeptide-8 were mixed and stirred in a water bath at 70°C until dissolved to obtain Phase B. (3) 1.5% by mass of glutathione and 2% by mass of ascorbyl glucoside were dissolved in a 49.4% peony root aqueous solution (prepared in S103, with the same composition as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. The shearing was repeated six times at a pressure of 800 bar to obtain a whitening composition capsule solution, with a zeta potential of -22 mV and a capsule particle size of 110 nm.

[0036] [Example 3] (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, 5% by mass of soybean lecithin, and 0.15% by mass of palmitoyl tripeptide-8 were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 66.35% aqueous rose flower solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. The shearing was repeated six times at a pressure of 800 bar to obtain a whitening composition capsule solution, with a zeta potential of -34mV and a capsule particle size of 30nm. In Example 3, the amount of encapsulated active ingredient was appropriate, and the capsule particle size was appropriate.

[0037] Using the manufacturing methods of Examples 1 to 3, stable whitening composition capsule solutions were obtained. Furthermore, the whitening composition capsule solutions obtained in Examples 1 to 3 maintained high transparency, a bluish appearance, uniformity, and the absence of aggregates even after 30 days of storage. Because Examples 1 and 2 contained a high content of glabridin, the encapsulated main active ingredient, the particle size of the ring-shaped vesicles formed increased with increasing ingredient content. Therefore, the particle size of the whitening composition capsule solution obtained in Example 2 was the largest, while Example 1 had a smaller particle size, and Example 3 had the smallest. Since smaller capsule particle size facilitates transdermal absorption through the intercellular spaces of skin cells, Example 3 was subsequently selected and compared with a comparative example to verify the efficacy of the composition prepared under optimal conditions of the manufacturing method.

[0038] [Comparative Example 1] Palmitoyl tripeptide-8 not added (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, and 5% by mass of soybean lecithin were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 66.5% peony aqueous solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed into nanoscale by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. The shearing was repeated six times at a pressure of 800 bar to obtain a whitening composition capsule solution, with a zeta potential of -34mV and a capsule particle size of 30nm. In Comparative Example 1, palmitoyl tripeptide-8 was not added.

[0039] [Comparative Example 2] No emulsifier added (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 1.5% peony seed oil, 5% soybean lecithin, and 0.15% palmitoyl tripeptide-8 were mixed and stirred in a water bath at 70°C until dissolved to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 68.5% peony aqueous solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. The shearing was repeated six times at a pressure of 800 bar to obtain a whitening composition capsule solution, with a zeta potential of -29 mV and a capsule particle size of 106 nm. In Comparative Example 2, no emulsifier was added, but the capsule particle size increased in this case.

[0040] [Comparative Example 3] High-pressure shear treatment temperature 10 to 15°C (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, 5% by mass of soybean lecithin, and 0.15% by mass of palmitoyl tripeptide-8 were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 66.5% peony aqueous solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled to 10-15°C. Repeated shearing was performed six times at a pressure of 800 bar to obtain a whitening composition capsule solution with a zeta potential of -32 mV and a capsule particle size of 103 nm. In Comparative Example 3, the temperature was low during the high-pressure shearing treatment, reducing the flexibility of the phospholipid bilayer membrane, making it difficult to homogenize the composition into small capsules with uniform particle size. When the capsule particle size distribution in the composition was wide, vesicles with large particle size differences fused by Ostwald ripening, increasing Brownian motion over time and with increasing ambient temperature. As a result of this growth, most of the vesicles eventually aggregated and fused, resulting in a stratified appearance.

[0041] [Comparative Example 4] Palmitoyl tripeptide-8 converted to nonapeptide-1 (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, and 5% by mass of soybean lecithin were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% glutathione, 3% 3-o-ethyl ascorbic acid, and 0.02% nonapeptide-1 were dissolved in a 66.48% peony aqueous solution (prepared in S103, with the same composition as in Example 1) by mass, and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. Repeated shearing at a pressure of 800 bar was performed six times to obtain a whitening composition capsule solution. The zeta potential was -34 mV, and the capsule particle size was 30 nm. In Comparative Example 4, palmitoyl tripeptide-8 was not added, but nonapeptide-1, which does not have amphipathic properties, was used as the signal molecule (however, nonapeptide-1 has α-MSH antagonistic activity).

[0042] [Comparative Example 5] Palmitoyl tripeptide-8 converted to palmitoyl tetrapeptide-7 (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, 5% by mass of soybean lecithin, and 0.06% by mass of palmitoyl tetrapeptide-7 were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 66.44% peony aqueous solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. Repeated shearing at a pressure of 800 bar was performed six times to obtain a whitening composition capsule solution. The zeta potential was -28 mV, and the capsule particle size was 38 nm. In Comparative Example 5, palmitoyl tripeptide-8 was not added, but amphiphilic palmitoyl tetrapeptide-7 was used as a signal molecule (however, palmitoyl tetrapeptide-7 does not have α-MSH antagonistic activity).

[0043] [Comparative Example 6] Palmitoyl tripeptide-8 converted to palmitoyl pentapeptide-4 (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 2% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, 0.06% by mass of palmitoyl pentapeptide-4, and 5% by mass of soybean lecithin were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 66.44% peony aqueous solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. Repeated shearing at a pressure of 800 bar was performed six times to obtain a whitening composition capsule solution. The zeta potential was -25 mV, and the capsule particle size was 34 nm. In Comparative Example 6, palmitoyl tripeptide-8 was not added, but amphiphilic palmitoyl pentapeptide-4 was used as the signal molecule (however, palmitoyl pentapeptide-4 does not have α-MSH antagonistic activity).

[0044] [Comparative Example 7] No phospholipids added (1) 1% glabridin and 20% butanediol were mixed and stirred in a water bath at 65°C until dissolved to obtain Phase A. (2) 6% by mass of polyglyceryl-10 laurate, 1.5% by mass of peony seed oil, and 0.15% by mass of palmitoyl tripeptide-8 were mixed and stirred in a water bath at 70°C until dissolved, to obtain Phase B. (3) 1% by mass of glutathione and 3% by mass of 3-o-ethyl ascorbic acid were dissolved in a 67.35% aqueous rose flower solution (prepared in S103, with the same blending ratio as in Example 1) and heated to 65°C to obtain Phase C. (4) Phases A and B were mixed by stirring, and then phase C was added and emulsified to obtain a crude emulsion for capsules. (5) The crude emulsion was processed to nanoscale size by high-pressure shearing, and the circulating water bath was controlled at 30-40°C. The shearing was repeated six times at a pressure of 800 bar to obtain a whitening composition capsule solution, in which the capsule particle size was 28 nm and the zeta potential was -32 mV. In Comparative Example 7, no phospholipid was added, but no cyclic structure was formed in the whitening composition capsule solution.

[0045] [Comparative Example 8] CN115778886A See Example 7 In S1, 6% licorice extract, 5% apple extract, 2% rice bran extract, 8% ethylhexyl coconut oleate, 3% diglycerin stearate, 2% isopropyl myristate, 4% beheneth-20, 4% sorbeth-30, 2% ethoxydiglycol, and 5% 1,2-hexanediol were heated and mixed at 75°C to obtain an oil phase, and 5% propylene glycol and 5% sorbitol were added to 49% pure water and heated and dissolved in a water bath at 75°C to obtain an aqueous phase. In S2, the aqueous phase is added to the oil phase at a rate of 9 drops / S, and the mixture is stirred and mixed at 75°C and 1000 rpm. After mixing is complete, the mixture is subjected to high-speed shear treatment at a rotation speed of 15000 rpm for 3 minutes to obtain a micron-scale dispersion. In S3, the micron-scale dispersion was subjected to high-pressure homogenization treatment at 75°C and 800 bar pressure six times to obtain microencapsulated capsules derived from the glabridin plant.

[0046] [Comparative Example 9] CN114796008A See Example 1 In an argon atmosphere, 0.1 g of glabridin and 4 g of polyglyceryl-3 methyl glucose distearate were dissolved in an oil phase of 0.5 g of jojoba oil, 0.5 g of meadowfoam oil, and 3 g of dioctyl carbonate. The ingredients of pentanediol, glycerin, trehalose, sodium oleate, and water were weighed and dissolved until the total weight reached 100 g to form an aqueous phase. After both phases were dissolved, the oil phase was gradually added to the aqueous phase at 80°C under shear conditions, and then homogenized six times at 600 bar and 60°C to obtain a supramolecular composition nanosolution.

[0047] [Comparative Examples 10 to 11] Consideration of signal molecules A capsule solution of a whitening composition of Comparative Example 10 was prepared using the same conditions as in Example 3, except that palmitoyl tripeptide-8 in Example 3 was replaced with nonapeptide-1.

[0048] A capsule solution of a whitening composition of Comparative Example 11 was prepared using the same conditions as in Example 3, except that palmitoyl tripeptide-8 in Example 3 was replaced with undecylenoyl phenylalanine.

[0049] [Comparative Example 12] Consideration of auxiliary ingredients A capsule solution of a whitening composition of Comparative Example 12 was prepared using the same conditions as in Example 3, except that the glutathione in Example 3 was replaced with cysteine.

[0050] [Comparative Example 13] Whitening composition capsule solution containing 0% palmitoyl tripeptide-8 and 1.15% glabridin Palmitoyl tripeptide-8 in Example 3 was omitted, the dosage of glabridin in Example 3 was changed to 1.15%, and the other conditions were the same as in Example 3 to obtain a whitening composition capsule solution of Comparative Example 13.

[0051] [Comparative Example 14] Whitening composition capsule solution containing 0% glabridin and 1.15% palmitoyl tripeptide-8 Glabridin was removed from Example 3, the dosage mass percentage of palmitoyl tripeptide-8 in Example 3 was changed to 1.15%, and the other conditions were the same as in Example 3 to obtain a whitening composition capsule solution of Comparative Example 14.

[0052] [Comparative Example 15] Whitening composition capsule solution containing 0% glutathione and 2% glabridin A capsule solution of a whitening composition of Comparative Example 15 was obtained under the same conditions as in Example 3, except that glutathione in Example 3 was omitted and the administration mass percentage of glabridin in Example 3 was changed to 2%.

[0053] [Comparative Example 16] Whitening composition capsule solution containing 0% glabridin and 2% glutathione A capsule solution of a whitening composition of Comparative Example 16 was obtained under the same conditions as in Example 3, except that glabridin in Example 3 was omitted and the administration mass percentage of glutathione in Example 3 was changed to 2%.

[0054] [Test Example 1] Stability test The above Examples and Comparative Examples were left to stand at room temperature for 30 days, after which the particle size, polydispersity coefficient and appearance of the capsule solution of the whitening composition of each Example or Comparative Example were determined. The results are shown in Table 1.

[0055] [Table 1] TIFF0007822581000001.tif142170

[0056] From Table 1, it can be seen that in Comparative Examples 2 and 3, glabridin changes to a powdery color when precipitated, whereas stably encapsulated glabridin does not usually change to a powdery color, and that encapsulation in the other groups stabilizes glabridin.

[0057] From Table 1, it can be seen that Comparative Examples 2 and 3 cannot be stored for a long period of time and are inferior in practicality, and therefore are not relevant to the comparison.

[0058] [Test Example 2] Whitening effect In Observation 1, to compare the whitening effects of the Examples and Comparative Examples, efficacy tests were conducted on the samples using the Demalab Combo and VISIA skin testing devices in accordance with the "Test Method for the Efficacy of Cosmetics for Whitening and Spot Removal" T / ZHCA001-2018 standard. 4% of Example 3, 4% of Comparative Example 1, 4% of Comparative Example 4, 4% of Comparative Example 5, 4% of Comparative Example 6, and 4% of Comparative Example 7 were added to a blank essence, and the MI and ITA° values ​​were compared before and after skin application to 30 volunteers aged 20 to 60.

[0059] In Observation 2, 4% of Example 3 and 4% of each of Comparative Examples 8 to 16 were added to a blank essence, and a test comparison of the MI and ITA° values ​​was conducted on 30 volunteers aged 20 to 60 before and after skin application.

[0060] Here, a lower MI value indicated less skin melanin and whiter skin appearance, while a higher ITA° value indicated whiter and brighter skin.

[0061] [Table 2] TIFF0007822581000002.tif122170

[0062] [Table 3] TIFF0007822581000003.tif122170

[0063] As a result, as shown in Table 2, in Example 3, Comparative Example 1, and Comparative Examples 4 to 16, the MI value (skin pigment) tended to decrease significantly over time of use, and it was confirmed that Example 3 had the most significant effect in reducing skin melanin content (the reduction rate of MI value at 4 weeks reached 43.7%), and was far superior to Comparative Examples 1, 4 to 16.

[0064] As shown in Table 3, in Example 3, Comparative Example 1, and Comparative Examples 4 to 16, ITA° (human skin color) tended to increase significantly over time of use, and it was confirmed that Example 3 had the most significant effect on improving skin color (the increase in ITA° value at week 4 reached 11.0%), and was far superior to Comparative Examples 1, 4 to 16.

[0065] Conventional palmitoyl tripeptide-8 is not used as a targeting peptide, but as a polypeptide with sedative and antiallergic properties. In the present application, palmitoyl tripeptide-8 is primarily used as a targeting peptide, taking into account its antagonistic activity. Comparative Example 4 showed the second-highest reduction in MI (37.1% reduction in MI at 4 weeks, 7.7% increase in ITA°). Compared to Example 3, Comparative Examples 4 and 10 used nonapeptide-1 as the targeting peptide. Although it exhibits good compatibility with the MC1 receptor on melanocytes and antagonizes α-MSH, its lack of amphipathicity makes it less effective as a targeting vector. Comparative Examples 1, 5, and 6 had similar effects. Comparative Examples 5 and 6 used targeting peptides with similar structures to Example 3. However, neither palmitoyl tetrapeptide-7 nor palmitoyl pentapeptide-4 possesses α-MSH antagonistic activity. Therefore, Comparative Examples 5 and 6 exhibited a lower MI reduction effect than Comparative Example 4. Although no target peptide was used in Comparative Example 1, the effect of lowering the MI value and the effect of increasing the ITA° value were superior to those of Comparative Examples 5 and 6. As described above, phospholipid vesicles can encapsulate both water-soluble and oil-soluble active ingredients, and therefore, by cooperating with the target peptide, the whitening effect can be improved.

[0066] The decrease in MI value in Comparative Example 7 was the second largest (the decrease in MI value at 4 weeks was 35.1%, and the increase in ITA° value was 8.9%), and since Comparative Example 7 did not contain phospholipids compared to Example 3, a ring structure (double-layered vesicle) was not formed. From the above, phospholipid vesicles can encapsulate active ingredients, and by cooperating with target peptides, they can improve the whitening effect.

[0067] Furthermore, the results of Example 3 and Comparative Examples 8 to 16 show that when glabridin, palmitoyl tripeptide-8, and glutathione are used simultaneously, they have a synergistic effect, and even if any of the three is changed to another homologous component, it is difficult to achieve a synergistic technical effect, and therefore the synergistic technical effect of the present invention is unexpected.

[0068] To further verify the degree of synergistic and cooperative effects of each component of the whitening composition capsule solution of the present application, the applicant compared the in vitro whitening efficacy of Example 3, Comparative Examples 17 to 19, and Test Examples 1 to 5. The specific procedures are as follows:

[0069] [Comparative Example 17] (1) 0.04% glabridin and 5% butanediol by mass were stirred in a water bath at 65°C until completely dissolved to obtain Phase A. (2) 0.36% by mass of hydroxypropyl β-cyclodextrin was dissolved in 94.6% by mass of water by stirring, and the mixture was heated to 65°C to obtain phase B. (3) While stirring Phase A, slowly add Phase B dropwise and stir at 65°C until no particles are visible to the naked eye, to obtain Phase C. (4) 0.4% by mass of phenoxyethanol was added to Phase C as a preservative and stirred until completely dissolved to obtain water-soluble glycyrrhizin. 4% of the whitening composition of Example 3 was added to simulate the situation where only glabridin was contained in an aqueous skin care product.

[0070] [Comparative Example 18] (1) 0.006% palmitoyl tripeptide-8 and 5% butanediol were stirred at 65°C until completely dissolved to obtain Phase A. (2) 0.04% by mass of glutathione, 0.12% by mass of 3-o-ethyl ascorbic acid, and 2.654% by mass of peony water (prepared in step S103, the blending ratio is the same as in Example 1) were added to 91.78% by mass of water and stirred at room temperature until completely dissolved to obtain phase B. (3) After mixing phase A and phase B, 0.4% phenoxyethanol was added and stirred uniformly, and 4% of the whitening composition of Example 3 was added to simulate the situation where an aqueous skin care product contains other active substances other than glabridin and the corresponding concentrations.

[0071] Comparative Example 19 (1) 0.04% glabridin and 2.5% butanediol by mass were stirred in a water bath at 65°C until completely dissolved to obtain phase A. (2) 0.36% by mass of hydroxypropyl β-cyclodextrin was dissolved in 70% water by stirring, and the mixture was heated to 65°C to obtain phase B. (3) While stirring Phase A, slowly add Phase B dropwise and stir at 65°C until no particles are visible to the naked eye, to obtain Phase C. (4) 0.006% palmitoyl tripeptide-8 and 2.5% butanediol were stirred at 65°C until completely dissolved to obtain Phase D. (5) 0.04% by mass of glutathione, 0.12% by mass of 3-o-ethyl ascorbic acid, and 2.654% by mass of peony water (prepared in step S103, the blending ratio is the same as in Example 1) were added to 21.38% by mass of water and stirred at room temperature until completely dissolved to obtain phase E. (6) Phases D, E, and C were mixed in order, and 0.4% phenoxyethanol was added as a preservative. The mixture was stirred uniformly, and 4% of the whitening composition of Example 3 was added to obtain a simulated aqueous skin care product containing active substances and corresponding concentrations.

[0072] [Test Example 1] Test sample after dilution of Example 1 4% of the capsule solution of the whitening composition of Example 3 was dissolved in 91.4% water by mass, and 4.2% butanediol and 0.4% phenoxyethanol were added and stirred uniformly to obtain a test sample simulating the addition of 4% of the capsule solution of the whitening composition of Example 3 to an aqueous skin care product.

[0073] [Test Example 2] Comparative Example 13 Test sample after dilution 4% of the capsule solution of the whitening composition of Comparative Example 13 was dissolved in 91.4% water by mass, and 4.2% butanediol and 0.4% phenoxyethanol were added and stirred uniformly to obtain a test sample simulating the addition of 4% of the capsule solution of the whitening composition of Comparative Example 13 to an aqueous skin care product.

[0074] [Test Example 3] Comparative Example 14 Test sample after dilution 4% of the capsule solution of the whitening composition of Comparative Example 14 was dissolved in 91.4% water by mass, and 4.2% butanediol and 0.4% phenoxyethanol were added and stirred uniformly to obtain a test sample simulating the addition of 4% of the capsule solution of the whitening composition of Comparative Example 14 to an aqueous skin care product.

[0075] [Test Example 4] Comparative Example 15 Test sample after dilution 4% of the capsule solution of the whitening composition of Comparative Example 15 was dissolved in 91.4% water by mass, and 4.2% butanediol and 0.4% phenoxyethanol were added and stirred uniformly to obtain a test sample simulating the addition of 4% of the capsule solution of the whitening composition of Comparative Example 15 to an aqueous skin care product.

[0076] [Test Example 5] Comparative Example 16 Test sample after dilution 4% of the capsule solution of the whitening composition of Comparative Example 16 was dissolved in 91.4% water by mass, and 4.2% butanediol and 0.4% phenoxyethanol were added and stirred uniformly to obtain a test sample simulating the addition of 4% of the capsule solution of the whitening composition of Comparative Example 16 to an aqueous skin care product.

[0077] [Test Example 3] In vitro whitening efficacy For the negative control, glabridin, palmitoyl tripeptide-8, and glutathione were removed from Example 3, and the mass proportions of the other components were the same as in Example 3. A blank sample was produced using the production method of Example 3, and 4% of the blank sample was dissolved in 91.4% water by mass. 4.2% butanediol and 0.4% phenoxyethanol were added and stirred uniformly to obtain the negative control.

[0078] The test kit was designed to verify synergistic effects using a 3D melanocortical skin model (MelaKutis®) as a test tool. From the day of model shipment (defined as day 0), UVB irradiation treatment (50 mJ / cm2) was performed once a day. 2) was performed, and the sample systems of the positive control, Test Example 1 to Test Example 5, Comparative Example 17 to Comparative Example 19, and negative control were administered to the melanoma model after 3 days of continuous stimulation, and then administered on the 1st day, and the operation was completed after 6 days of continuous stimulation. On the other hand, the blank control (L of the model that has not undergone UVB irradiation treatment and administration operation) * The values ​​and melanin content, incubation time and other incubation conditions were the same as those of the test group, and the brightness (L * The in vitro whitening efficacy of the sample groups was evaluated by the chromatic aberration (α, β) and melanin distribution.

[0079] [Table 4] TIFF0007822581000004.tif104170

[0080] As shown in Table 4, Comparative Example 19 had a higher L than Comparative Examples 17 and 18. * The values ​​and melanin content were both excellent, and a synergistic effect was confirmed by combining glabridin with palmitoyl tripeptide-8, glutathione, vitamin C or a vitamin C derivative, and a plant aqueous solution. Test Example 1 showed better results than Comparative Example 19, and it can be seen that encapsulation using the vector of the present invention also has an excellent penetration-promoting effect.

[0081] The results of Test Example 1 were significantly better than those of Test Examples 2 to 5 (the total active ingredients were the same as those of Test Example 1, but Test Examples 2 to 5 lacked the active ingredients), confirming an unexpected synergistic effect between glabridin, palmitoyl tripeptide-8, and glutathione.

[0082] From the above, the present invention demonstrates an excellent synergistic effect and a high whitening effect by supporting the cooperation of glabridin and glutathione with antioxidant vitamin C or vitamin C derivatives and anti-inflammatory plant extract aqueous solution (see the data in Example 3 and Comparative Examples 1 and 7). Meanwhile, by rigorously selecting the targeting peptide, the targeting effect of the active ingredients (such as glabridin and glutathione) and therefore the whitening effect are further improved, and palmitoyl tripeptide-8 exerts a significant improvement over the whitening composition capsule solution. The cooperation of glabridin, glutathione, and palmitoyl tripeptide-8 produces a remarkable synergistic technical effect.

[0083] The above are merely preferred embodiments of the present invention, and are not intended to limit the present invention. Any minor modifications, equivalent substitutions, and improvements made to the above embodiments based on the technical idea of ​​the present invention should all be included within the protection scope of the technical solutions of the present invention.

Claims

1. A method for preparing nanoscale double-layer capsules, the specific steps of which are as follows: In step S1, 1 to 3% of the alcohol-soluble main component and 10 to 50% of the polyol are weighed out by mass percentage, and mixed and stirred in a water bath at 65°C until dissolved to obtain phase A. In S2, 3 to 15% of phospholipid, 1 to 3% of emulsifying aid, 1 to 5% of liquid oil, and 0.01 to 0.5% of signal molecule are weighed out in mass percentage, and mixed and stirred in a water bath at 70°C until dissolved to obtain phase B, In S3, an aqueous solution of plant extract is prepared, and then 0.01 to 2% of an auxiliary component and 0.01 to 4% of an antioxidant component are weighed out in mass percentages, dissolved in 17.5 to 83.97% of the aqueous solution of plant extract, and heated to 65°C to obtain phase C. In S4, phase A and phase B are mixed and stirred uniformly, and then phase C is added and emulsified to obtain a crude emulsion. In step S5, the crude emulsion is subjected to high-pressure shear treatment at a temperature of 30 to 40°C to obtain nanoscale capsules, and finally a whitening composition capsule solution is obtained. The plant extract aqueous solution is an extract aqueous solution of an herbaceous anti-inflammatory plant, and the herbaceous anti-inflammatory plant is one or a combination of peony flower, peony root, rose flower, and purslane. the alcohol-soluble main component is glabridin, the auxiliary component is glutathione, and the signal molecule is palmitoyl tripeptide-8; the polyol is one or a combination of more of glycerol, propylene glycol, butanediol, dipropylene glycol, pentanediol, isopentyl diol; the emulsifier is one or a combination of more than one of polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyoxyethylene hydrogenated castor oil, and potassium cetyl phosphate; the liquid oil is one or more combinations of caprylic / capric triglyceride, meadowfoam oil, squalane, olive oil, and peony seed oil; the phospholipid is one or a combination of soy lecithin, hydrogenated lecithin, and soy phosphatidylcholine; The method for producing nanoscale double-layered capsules is characterized in that the antioxidant component is one or a combination of several of vitamin C, 3-o-ethyl ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, and ascorbic acid polypeptide.

2. The emulsifier in step S4 has an output power of 0.2 kW, a rotation speed of 3000 to 8000 rpm, and a high-speed shear dispersion time of 3 to 10 minutes, 2. The method for producing nanoscale double-layer capsules according to claim 1, wherein the shear pressure is 400-1000 bar and the number of repeated shearing is 5-10 times.

3. 2. The method for producing nanoscale double-layer capsules according to claim 1, wherein in step S3, the anti-inflammatory herbaceous plant is washed, dried, and pulverized to obtain plant powder, and the plant powder and water are refluxed at 50-80°C at a mass ratio of 1:10-1:20 for 8-24 hours to obtain a stewing solution, and the stewing solution is filtered to obtain a purified plant extract aqueous solution at a volume ratio of filtrate:macroporous anion exchange resin of 10-15:1 and a retention time of 15-25 minutes.

4. The formulation ratio of the whitening composition capsule solution is, by mass percentage, 1.1±0.1% glabridin, 20±5% polyol, 6±2% phospholipid, 2±0.5% emulsifier, 2±0.5% liquid oil, 0.15±0.05% palmitoyl tripeptide-8, 1±0.2% glutathione, 3±0.5% antioxidant, and 60±15% plant extract aqueous solution, and / or 4. The method for producing nanoscale double-layer capsules according to claim 1, wherein the particle size of the nanoscale double-layer capsules is 20 nm to 110 nm.

5. A highly transparent and stable whitening composition capsule solution produced using the method for producing nanoscale double-layer capsules described in claim 4, wherein the capsules are mainly composed of phospholipids, encapsulating a plant extract containing an alcohol-soluble main component, auxiliary components, antioxidant components, and anti-inflammatory components, and signal molecules are attached to the capsule surface.

6. Use of the capsule solution of the whitening composition according to claim 5 in the field of cosmetics.

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