Glabridin composition with high skin penetration rate and preparation method and application thereof

Abstract

To provide a glabridin composition having a high skin permeation rate, and to provide a preparation method and an application thereof.SOLUTION: The present invention provides a glabridin composition with high skin penetration rate and preparation method and application thereof, which belongs to the field of cosmetics. The glabridin composition is prepared from S1 phase, S2 phase and S3 phase, wherein the S1 phase is composed of oil and fat and glabridin, the S2 phase is prepared from 3-O-ethylascorbic acid, anionic surfactants, nonionic surfactants, polyhydric alcohols and water, and the S3 phase is water. The glabridin composition is prepared by using common emulsification equipment, the preparation cost is low, the operation technology is simple, the composition has good skin permeability, good state stability under high and low temperature conditions, good content stability, good pH stability, and high mildness, and has unexpected technical effects.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to the field of cosmetics, particularly to a glabridin composition with high skin penetration rate and its preparation method and application. [Background technology]

[0002] Glabridin, commonly known as "whitening gold," effectively inhibits tyrosinase activity, inhibits the conversion of dopa pigments, inhibits DHICA oxidase activity, and inhibits the activity of pigment cytochrome P450 3A4 enzyme (abbreviated as CYP3A4), achieving the goal of efficient and environmentally friendly whitening and age spot removal. However, glabridin's insolubility in water and low penetration rate limit its use in formulations.

[0003] Glabridin is a fat-soluble active ingredient, soluble in polyhydric alcohols, slightly soluble in oils and fats, and insoluble in water. Therefore, to improve the skin penetration ability of glabridin, not only the solubility problem of glabridin is solved, but also carrier technologies such as microencapsulation, liposomes, and nanoemulsions are used to encapsulate the active ingredient and carry glabridin to penetrate the stratum corneum, thereby improving its penetration. However, conventional manufacturing methods and formulations have technical problems such as low skin penetration rate, low solubility of glabridin, poor stability, high irritation, high preparation costs, and complex operations.

[0004] Previous technologies have provided methods for encapsulating glabridin with cyclodextrin, such as precipitation, grinding, freeze-drying, and spray-drying, to produce cyclodextrin inclusion complexes. However, these techniques require conventional equipment for non-cosmetic production, and the relatively large molecular weight and hydrophilic exterior of cyclodextrin significantly reduce the ability of active ingredients to directly penetrate the hydrophobic stratum corneum. Furthermore, cyclodextrin inclusion systems have two drawbacks when formulating skin care products. First, cyclodextrin itself is highly viscous on the skin, leaving consumers with an unpleasant sticky feeling during use. Second, cyclodextrin inclusion systems are prone to crystallization during formulation. According to literature, polyhydric alcohols such as pentanediol and hexanediol affect the inclusion stability of cyclodextrin, presenting formulators with difficulties when developing cosmetic formulations.

[0005] Conventional technologies also provide methods for encapsulating glabridin in phospholipids, which are prepared by techniques such as thin film condensation, reverse phase evaporation, injection, and microfluidics, which also require commonly used equipment for non-cosmetic production. Furthermore, liposomes may aggregate, leak, or undergo structural changes during storage, resulting in loss or premature release of active substances. In addition, phospholipases in the body can degrade liposomes, directly affecting the drug delivery efficiency and controlled release properties.

[0006] Therefore, there is an urgent need for a glabridin composition that has a high transdermal absorption rate, good solubility, good stability, a pleasant feel on the skin, little irritation, low production costs, and simple operation techniques. Summary of the Invention [Problem to be solved by the invention]

[0007] In order to provide a glabridin composition that has a high transdermal absorption rate, good solubility, strong stability during storage without crystallization, good content stability, good pH stability, mildness, pleasant texture to the skin, low production cost, and simple operation technology, the present invention provides the following technical solutions: [Means for solving the problem]

[0008] In a first aspect, the present invention provides a glabridin composition, wherein the glabridin is prepared from an S1 phase, an S2 phase, and an S3 phase, wherein the S1 phase is composed of an oil and glabridin, the S2 phase is prepared from 3-O-ethyl ascorbic acid, an anionic surfactant, a nonionic surfactant, a polyhydric alcohol, and water, and the S3 phase is water. The nonionic surfactant is oleth-20 and polyglyceryl-10 oleate. The anionic surfactant is sodium stearoyl glutamate. The fat is caprylic / capric triglyceride. The polyhydric alcohol is 1,3-butanediol. Calculated based on the total mass of the glabridin composition, the glabridin content is 0.10 wt% to 4.00 wt%, the 3-O-ethyl ascorbic acid content is 0.10 wt% to 4.00 wt%, the total content of the nonionic surfactants is 0.70 wt% to 10.00 wt%, the oil content is 1.00 wt% to 40.00 wt%, the polyhydric alcohol content is 0.60 wt% to 6.00 wt%, the anionic surfactant content is 0.10 wt% to 1.00 wt%, the water content in the S2 phase is 0.30 wt% to 3.00 wt%, and the remainder is the S3 phase. Furthermore, the present invention further provides a method for preparing said glabridin composition.

[0009] The technical solution of the present invention is advantageous in improving the skin permeability and solubility of the glabridin composition, and is also advantageous in improving the state stability, content stability, pH stability and mildness under high and low temperature conditions, and has unexpected technical effects.

[0010] The preparation method provided by the present invention does not require the use of equipment commonly used in non-cosmetics production, and can be produced using simple technical operations, which is advantageous in improving the skin permeability and solubility of the glabridin composition, as well as improving the state stability, content stability, pH stability, and mildness under high and low temperature conditions.

[0011] In a second aspect, the present invention provides the use of the glabridin composition of the first aspect in the manufacture of cosmetics.

[0012] In a third aspect, the present invention provides a cosmetic product, which comprises the glabridin composition of the first aspect. DETAILED DESCRIPTION OF THE INVENTION

[0013] [Detailed Description of the Invention] To solve the above technical problems, the present invention provides a glabridin composition and a method for preparing the same. In a first aspect, the present invention provides a glabridin composition. A glabridin composition, wherein the glabridin is prepared from an S1 phase, an S2 phase, and an S3 phase, the S1 phase being composed of an oil and glabridin, the S2 phase being prepared from 3-O-ethyl ascorbic acid, an anionic surfactant, a nonionic surfactant, a polyhydric alcohol, and water, and the S3 phase being water. The nonionic surfactants are oleth-20 and polyglyceryl-10 oleate. The anionic surfactant is sodium stearoyl glutamate. The oil is caprylic / capric triglyceride. The polyhydric alcohol is 1,3-butanediol.

[0014] Calculated based on the total mass of the glabridin composition, the content of the glabridin is 0.10 wt% to 4.00 wt%, the content of the 3-O-ethyl ascorbic acid is 0.10 wt% to 4.00 wt%, the total content of the nonionic surfactants is 0.70 wt% to 10.00 wt%, the content of the oils and fats is 1.00 wt% to 40.00 wt%, the content of the polyhydric alcohol is 0.60 wt% to 6.00 wt%, the content of the anionic surfactant is 0.10 wt% to 1.00 wt%, the content of water in the S2 phase is 0.30 wt% to 3.00 wt%, and the remainder is the S3 phase.

[0015] The method for preparing the glabridin composition includes the following steps: (1) Glabridin and fat are mixed, heated to dissolve, and mixed uniformly to obtain the S1 phase. (2) 3-O-ethyl ascorbic acid, anionic surfactant, nonionic surfactant, polyhydric alcohol and water are mixed, heated to dissolve, and mixed uniformly to obtain the S2 phase. (3) Under conditions where the S2 phase is stirred, the S1 phase obtained in step (1) is added to the S2 phase obtained in step (2) and mixed to form a gel. (4) The gel obtained in step (3) is further mixed with S3 to obtain the glabridin composition.

[0016] In some embodiments, the content of the oleth-20 is 0.10 wt% to 4.00 wt%, and the content of the polyglyceryl-10 oleate is 0.60 wt% to 6.00 wt%, calculated based on the total mass of the glabridin composition.

[0017] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt% to 4.00 wt%, the content of the 3-O-ethyl ascorbic acid is 1.00 wt% to 4.00 wt%, the content of the oleth-20 is 0.50 wt% to 4.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil or fat is 10.00 wt% to 40.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

[0018] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 0.10 wt%, the content of the 3-O-ethyl ascorbic acid is 0.10 wt%, the content of the oleth-20 is 0.10 wt%, the content of the polyglyceryl-10 oleate is 0.60 wt%, the content of the oil / fat is 1.00 wt%, the content of the polyhydric alcohol is 0.60 wt%, the content of the anionic surfactant is 0.10 wt%, the content of water in the S2 phase is 0.30 wt%, and the remainder is the S3 phase.

[0019] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt%, the content of the 3-O-ethyl ascorbic acid is 1.00 wt%, the content of the oleth-20 is 0.50 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 10.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

[0020] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt%, the content of the 3-O-ethyl ascorbic acid is 1.00 wt%, the content of the oleth-20 is 1.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil or fat is 10.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

[0021] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt%, the content of the 3-O-ethyl ascorbic acid is 2.00 wt%, the content of the oleth-20 is 0.50 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 10.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

[0022] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 2.00 wt%, the content of the 3-O-ethyl ascorbic acid is 2.00 wt%, the content of the oleth-20 is 2.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 20.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

[0023] In some embodiments, calculated based on the total mass of the glabridin composition, the content of the glabridin is 4.00 wt%, the content of the 3-O-ethyl ascorbic acid is 4.00 wt%, the content of the oleth-20 is 4.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 40.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

[0024] In some embodiments, the dissolving by heating in the step (1) is performed by heating to 60 to 80° C. In some embodiments, the dissolving by heating in the step (1) is performed by heating to 60° C., 65° C., 70° C., 75° C., or 80° C.

[0025] In some embodiments, the heating and dissolving in step (2) is performed by heating to 60° C. to 70° C. In some embodiments, the heating and dissolving in step (2) is performed by heating to 60° C., 65° C., or 70° C.

[0026] In some embodiments, the dissolving by heating in the step (1) is performed by heating to 70°C. The dissolving by heating in the step (2) is performed by heating to 60°C.

[0027] In some embodiments, the weight ratio of water to polyhydric alcohol in step (2) is 1:1 to 1:2.

[0028] In a second aspect, the present invention provides applications of the glabridin composition of the first aspect. The first aspect is the application of the glabridin composition to the production of cosmetics.

[0029] In a third aspect, the present invention provides a cosmetic product. A cosmetic product comprising the glabridin composition of the first aspect.

[0030] In some embodiments, the cosmetic product is in the form of an essence. In some embodiments, the cosmetic product is in the form of an essence and includes phases A, B, C, D, E, and F. Phase A includes water, disodium EDTA, and carbomer. Phase B includes p-hydroxyacetophenone, 1,2-pentanediol, and 1,2-hexanediol. Phase C includes water and arginine. Phase D includes hydrogenated lecithin, ethoxydiglycol, palmitoyl tripeptide-8, and α-tocopherol. Phase E includes glutathione and an aqueous plant extract solution. Phase F is the glabridin composition of the first embodiment.

[0031] In some embodiments, the aqueous plant extract solution is peony water.

[0032] In some embodiments, calculated based on the total mass of the cosmetic product, the content of the F phase is 1.000 wt% to 2.000 wt%, the content of glutathione in the E phase is 0.001 wt% to 0.050 wt%, the content of peony water in the E phase is 0.050 wt% to 0.500 wt%, the content of hydrogenated lecithin in the D phase is 0.040 wt% to 0.100 wt%, the content of ethoxydiglycol in the D phase is 0.010 wt% to 0.100 wt%, the content of palmitoyl tripeptide-8 in the D phase is 0.001 wt% to 0.005 wt%, and the content of α-tocopherol in the D phase is 0.005 wt% to 0.010 wt%. The water content of the phase C is 1.000 wt% to 2.000 wt%, the arginine content of the phase C is 0.100 wt% to 0.500 wt%, the p-hydroxyacetophenone content of the phase B is 0.050 wt% to 0.300 wt%, the 1,2-pentanediol content of the phase B is 1.000 wt% to 5.000 wt%, the 1,2-hexanediol content of the phase B is 0.500 wt% to 1.000 wt%, the EDTA disodium content of the phase A is 0.020 wt% to 0.100 wt%, the carbomer content of the phase A is 0.100 wt% to 0.500 wt%, and the balance is water of the phase A.

[0033] In some embodiments, calculated based on the total mass of the cosmetic product, the content of the F phase is 1.000 wt%, the content of glutathione in the E phase is 0.010 wt%, the content of peony water in the E phase is 0.100 wt%, the content of hydrogenated lecithin in the D phase is 0.060 wt%, the content of ethoxydiglycol in the D phase is 0.020 wt%, the content of palmitoyl tripeptide-8 in the D phase is 0.002 wt%, and the content of α-tocopherol in the D phase is 0.005 wt%. The water content of the phase C was 1.000 wt%, the arginine content of the phase C was 0.200 wt%, the p-hydroxyacetophenone content of the phase B was 0.100 wt%, the 1,2-pentanediol content of the phase B was 3.000 wt%, the 1,2-hexanediol content of the phase B was 0.500 wt%, the EDTA disodium content of the phase A was 0.050 wt%, the carbomer content of the phase A was 0.200 wt%, and the balance was water of the phase A.

[0034] In some embodiments, calculated based on the total weight of the cosmetic product, the content of the F phase is 2.000 wt%, the content of glutathione in the E phase is 0.050 wt%, the content of peony water in the E phase is 0.500 wt%, the content of hydrogenated lecithin in the D phase is 0.100 wt%, the content of ethoxydiglycol in the D phase is 0.100 wt%, the content of palmitoyl tripeptide-8 in the D phase is 0.005 wt%, and the content of α-tocopherol in the D phase is 0.010 wt%. The water content of Phase C was 2.000 wt%, the arginine content of Phase C was 0.500 wt%, the p-hydroxyacetophenone content of Phase B was 0.300 wt%, the 1,2-pentanediol content of Phase B was 5.000 wt%, the 1,2-hexanediol content of Phase B was 1.000 wt%, the EDTA disodium content of Phase A was 0.100 wt%, the carbomer content of Phase A was 0.500 wt%, and the balance was water of Phase A.

[0035] In some embodiments, calculated based on the total mass of the cosmetic product, the content of Phase F is 1.000 wt%, the content of glutathione in Phase E is 0.001 wt%, the content of peony water in Phase E is 0.050 wt%, the content of hydrogenated lecithin in Phase D is 0.040 wt%, the content of ethoxydiglycol in Phase D is 0.010 wt%, the content of palmitoyl tripeptide-8 in Phase D is 0.001 wt%, and the content of α-tocopherol in Phase D is 0.005 wt%. The water content of the phase C was 1.000 wt%, the arginine content of the phase C was 0.100 wt%, the p-hydroxyacetophenone content of the phase B was 0.050 wt%, the 1,2-pentanediol content of the phase B was 1.000 wt%, the 1,2-hexanediol content of the phase B was 0.500 wt%, the EDTA disodium content of the phase A was 0.020 wt%, the carbomer content of the phase A was 0.100 wt%, and the balance was water of the phase A.

[0036] In some embodiments, the cosmetic product is in an essence form, and the method for producing the cosmetic product includes: (i) The components in phase A are mixed, heated to dissolve, and then the temperature is lowered to 40°C to 50°C to obtain phase A. (ii) The components of phase B are mixed, heated to dissolve, and then cooled to room temperature to obtain phase B. (iii) The components in phase C are stirred until completely dissolved to obtain phase C. (iv) The components in phase D are mixed and stirred, heated to 65°C to 75°C, and homogenized to obtain phase D. (v) While stirring phase A, phases B, C, D, E, and F are added to phase A obtained in step (i) and mixed to obtain the cosmetic product.

[0037] In some embodiments, the dissolution by heating in step (i) is performed by heating to 75°C-85°C, maintaining the temperature for 5-40 minutes, and stirring until complete dissolution. In some embodiments, the dissolution by heating in step (i) is performed by heating to 75°C, 80°C, or 85°C, maintaining the temperature for 5, 10, 15, 20, 25, 30, 35, or 40 minutes, and stirring until complete dissolution.

[0038] In some embodiments, the temperature reduction in step (i) is to 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, or 50°C.

[0039] In some embodiments, the heating and dissolving in step (ii) involves heating to 60°C to 70°C and stirring until complete dissolution. In some embodiments, the heating and dissolving in step (ii) involves heating to 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, or 70°C and stirring until complete dissolution.

[0040] In some embodiments, the room temperature in step (ii) is 20° C. to 35° C. In some embodiments, the room temperature in step (ii) is 25° C. to 30° C.

[0041] In some embodiments, the heating to 65°C to 75°C in step (iv) is heating to 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, or 75°C.

[0042] In some embodiments, the homogenization speed in step (iv) is 1500 rpm-2500 rpm, 1500 rpm, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, or 2500 rpm.

[0043] In some embodiments, the homogenization time in step (iv) is 5 minutes to 30 minutes, hi some embodiments, the homogenization time in step (iv) is 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, or 30 minutes.

[0044] [Effects of the invention] Compared with the prior art, the technical solution provided by the present invention has at least one of the following beneficial technical effects: (1) Compared with formulations lacking any of 3-O-ethyl ascorbic acid, polyhydric alcohol, nonionic surfactant, and anionic surfactant, the glabridin composition of the formulation provided by the present invention is more advantageous in improving the permeability of an essence dosage form, and has an unexpected technical effect. (2) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), the glabridin composition obtained by adopting the preparation technique provided by the present invention is more advantageous in improving the permeability of the essence formulation, and has an unexpected technical effect. (3) Compared with cyclodextrin inclusion and liposome inclusion, the glabridin composition obtained by adopting the preparation technique provided by the present invention is more advantageous in improving the permeability of essence dosage forms, and has unexpected technical effects. (4) Compared with other nonionic surfactants, the glabridin composition of the present invention, which uses oleth-20 and polyglyceryl-10 oleate as nonionic surfactants, is more advantageous in improving the permeability of essence formulations, and has an unexpected technical effect. (5) Compared with other polyhydric alcohols, the glabridin composition obtained in the present invention using 1,3-butanediol as the polyhydric alcohol is more advantageous in improving the permeability of the essence formulation, and has an unexpected technical effect. (6) Compared with other fats and oils, the present invention employs caprylic / capric triglyceride as a fat and oil, which is more advantageous in improving the permeability of essence formulations, and has an unexpected technical effect. (7) Compared with the case where 3-O-ethyl ascorbic acid is not added, the glabridin composition formulated according to the present invention is more advantageous in improving the speed and effectiveness of clinical whitening and spot removal effects in the form of an essence, and has an unexpected technical effect. (8) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), the glabridin composition obtained by adopting the preparation technique provided by the present invention is more advantageous in improving the speed and effectiveness of clinical whitening and spot removal effects in essence formulation, and has unexpected technical effects. (9) Compared with cyclodextrin inclusion and liposome inclusion, the glabridin composition obtained by adopting the preparation technology provided by the present invention is more advantageous in improving the speed and effectiveness of clinical whitening and spot removal effects in essence formulation, and has unexpected technical effects. (10) Compared with the use of a formulation lacking any of 3-O-ethyl ascorbic acid, polyhydric alcohol, nonionic surfactant, and anionic surfactant, the use of the formulation provided by the present invention is more advantageous in improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (11) Compared with the use of other nonionic surfactants, the use of oleth-20 and polyglyceryl-10 oleate in the present invention is more advantageous in improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (12) Compared with the use of other polyhydric alcohols, the use of 1,3-butanediol in the present invention is more advantageous in improving the state stability and content stability of the glabridin composition under high temperature conditions. (13) Compared with the use of other fats and oils, the use of caprylic / capric triglyceride in the present invention is more advantageous in improving the state stability and content stability of the glabridin composition under high temperature conditions. (14) Compared with the use of other anionic surfactants, the use of sodium stearoyl glutamate in the present invention is more advantageous in improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (15) Compared with other preparation methods (such as changing the order of adding 3-O-ethyl ascorbic acid or water), the preparation technique provided by the present invention is more advantageous in improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (16) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), the preparation technique provided by the present invention is more advantageous in improving the pH stability of the glabridin composition under high and low temperature conditions. (17) Compared with not adding 3-O-ethyl ascorbic acid, the formulation provided by the present invention is more advantageous in improving the safety of the glabridin composition and has unexpected technical effects. (18) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), the preparation technique provided by the present invention is more advantageous in improving the safety of the glabridin composition. (19) The method for preparing the glabridin composition provided by the present invention is simple, and the required equipment is simple and is standard equipment in the cosmetics field. There is no need to adopt standard equipment for non-cosmetics production, which is advantageous in reducing production costs.

[0045] [Terminology] In the present invention, regardless of whether terms such as "approximately" or "about" are used, all numerical values ​​disclosed herein are approximate values. Based on the disclosed numerical values, the numerical values ​​of each numerical value may vary by ±10% or less, or by a difference that a person skilled in the art would consider reasonable, such as ±1%, ±2%, ±3%, ±4%, or ±5%.

[0046] The term "room temperature" means an indoor ambient temperature of 20°C to 35°C or 25°C to 30°C.

[0047] The term "and / or" should be understood to mean either of any alternatives or any combination of two or more.

[0048] The term "wt%" stands for percent by weight.

[0049] In the description herein, references to the terms "one embodiment," "some embodiments," "exemplary," "specific example," or "some examples" mean that the particular feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In the description herein, the use of the terms "exemplary" does not necessarily refer to the same embodiment or example. Particular features, structures, materials, or characteristics in the description herein may be combined in any suitable manner in any one or more embodiments or examples. Different embodiments or examples in the description herein, and features of different embodiments or examples, may be combined without being mutually inconsistent. [Example]

[0050] [Mode for Carrying Out the Invention] In order to make those skilled in the art better understand the technical solutions herein, some non-limiting examples are further disclosed below to further describe the present invention.

[0051] The reagents used in the present invention can be purchased from the market or prepared by the methods described in the present invention.

[0052] 1. Glabridin content testing and detection method The test method for glabridin content is based on Q / FZR 0101-2023 "Glabridin, a raw material for cosmetics," and the chromatographic conditions are as follows: a) Column: ZORBAX StableBond C18, 4.6 x 250 mm, 5 μm b) Flow rate: 1.0 mL / min c) Mobile phase: acetonitrile:water = 80:20, filtered through a membrane filtration device at 0.22 pm d) Injection volume: 10μL e) Column temperature: 25°C f) Wavelength: 280nm.

[0053] 2. Reagents Origin of Peony Water: Product name: FangYe5031 Peony Pure Dew, purchased from Shandong FangYe Biotechnology Co., Ltd., lot number: 20231231B5031; INCI: Peony (Paeonia Suffruticosa) Flower Water, p-hydroxyacetophenone, 1,2-hexanediol; Here, the content of each ingredient is as follows: Peony (Paeonia Suffruticosa) Flower Water 99%, p-hydroxyacetophenone 0.5%, 1,2-hexanediol 0.5%.

[0054] Examples 1 to 6: Preparation of Glabridin Compositions Formulation: See Table 1.

[0055] [Table 1]

[0056] Preparation method: (1) Glabridin and fat are mixed, heated to 70°C to dissolve, and mixed uniformly to obtain the S1 phase. (2) 3-O-ethyl ascorbic acid, anionic surfactant, nonionic surfactant, polyhydric alcohol and water are mixed, heated to 60°C to dissolve, and mixed uniformly to obtain S2 phase. (3) Adding the S1 phase obtained in step (1) to the S2 phase obtained in step (2) under stirring conditions to form a gel; (4) The gel obtained in step (3) is further mixed with S3 to obtain the glabridin composition.

[0057] Examples 7 to 11: Essence dosage form Formulation: See Table 2.

[0058] [Table 2]

[0059] Preparation method: (1) Mix the ingredients of Phase A, heat to 80°C, keep warm for 30 minutes, stir until completely dissolved, and then reduce the temperature to 45°C to obtain Phase A. (2) Mix the ingredients of Phase B, heat to 65°C, stir until completely dissolved, and then cool to room temperature to obtain Phase B. (3) Stir the components of phase C until they are completely dissolved to obtain phase C. (4) Mix and stir the ingredients of Phase D, heat to 70°C, and homogenize at 2000 rpm for 10 minutes to obtain Phase D. (5) While stirring phase A, phases B, C, D, E, and F are added to and mixed with phase A obtained in step (1) to obtain the essence-type cosmetic product.

[0060] Comparative Examples 1 to 5: Glabridin Compositions Formulation: See Table 3.

[0061] [Table 3]

[0062] Preparation method: The preparation was carried out with reference to the preparation method of Example 1, except that no components with a content of 0 were added, and other components were added according to the content of the corresponding component in each comparative example.

[0063] Comparative Examples 6 to 11: Consideration of nonionic surfactants Formulation: See Table 4.

[0064] [Table 4]

[0065] Preparation method: The preparation was carried out with reference to the preparation method of Example 1, except that no components with a content of 0 were added, and other components were added according to the content of the corresponding component in each comparative example.

[0066] Comparative Examples 12 to 14: Consideration of anionic surfactants Formulation: See Table 5.

[0067] [Table 5]

[0068] Preparation method: It was prepared according to the preparation method of Example 1, except that a different anionic surfactant was used.

[0069] Comparative Examples 15 to 18: Consideration of oils and fats Formulation: See Table 6.

[0070] [Table 6]

[0071] Preparation method: The preparation was carried out in accordance with the preparation method of Example 1, except that a different oil was used.

[0072] Comparative Examples 19 to 21: Consideration of polyhydric alcohols Formulation: See Table 7.

[0073] [Table 7]

[0074] Preparation method: This was prepared in accordance with the preparation method of Example 1, except that a different polyhydric alcohol was used.

[0075] Comparative Example 22: Consideration regarding preparation method The formulation of this comparative example is shown in Table 8.

[0076] [Table 8]

[0077] Preparation method: This comparative example differs from Example 1 in that 3-O-ethyl ascorbic acid in the S1 phase of the preparation method is added in step (4), and the detailed steps are as follows: (1) Glabridin and fat are mixed, heated to 70°C to dissolve, and mixed uniformly to obtain the S1 phase. (2) A nonionic surfactant, anionic surfactant, polyhydric alcohol and water are mixed, heated to 60°C to dissolve, and mixed uniformly to obtain an S2 phase. (3) Under conditions where the S2 phase is stirred, the S1 phase obtained in step (1) is added to the S2 phase obtained in step (2) and mixed to form a gel. (4) The gel obtained in step (3) is further mixed with water and 3-O-ethyl ascorbic acid in the S3 phase to obtain the glabridin composition.

[0078] Comparative Example 23: Consideration of preparation method The formulation of this comparative example is shown in Table 9.

[0079] [Table 9]

[0080] Preparation method: The preparation method of this comparative example differs from the preparation method of Example 1 in the order in which the components are added. The specific steps are as follows: (1) Glabridin and fat are mixed, heated to 70°C to dissolve, and mixed uniformly to obtain the S1 phase. (2) A nonionic surfactant, anionic surfactant, polyhydric alcohol and water are mixed, heated to 60°C to dissolve, and mixed uniformly to obtain an S2 phase. (3) Under conditions where the S2 phase is stirred, the S1 phase obtained in step (1) is added to the S2 phase obtained in step (2) and mixed to obtain a mixture (note: a gel is not formed). (4) The mixture obtained in step (3) is further mixed with 3-O-ethyl ascorbic acid to obtain the glabridin composition.

[0081] Comparative Example 24: Consideration of Cyclodextrin Dosage Form

[0082] [Table 10]

[0083] Preparation method: The S1 phase was stirred at room temperature until completely dissolved, and the S2 phase was stirred at room temperature until completely dissolved. The S1 and S2 phases were mixed and oscillated at 200 r / min for 24 hours to obtain a clear, transparent solution. The ethanol was then removed using a rotary evaporator at 45°C, and the solution was then frozen in a -20°C refrigerator for 12 hours and lyophilized in a freeze dryer to obtain the glabridin composition (cyclodextrin formulation) of Comparative Example 24.

[0084] Comparative Example 25: Consideration of liposome formulation

[0085] [Table 11]

[0086] Preparation method: The S1 phase is heated to 80°C and stirred to dissolve completely, and the S2 phase is heated to 80°C and stirred to dissolve completely. The S1 phase is added dropwise to the S2 phase, and under constant stirring, the mixture is sheared and emulsified at a high speed of 10,000 rpm for 1 minute to produce a micron-sized dispersion. The mixture is then circulated five times under a high pressure of 1,500 bar to obtain the glabridin composition (liposome formulation) of Comparative Example 25.

[0087] Comparative Examples 26 to 50: Essence Form Table 12 shows the formulations in which Comparative Examples 1 to 25 were added to essence formulations.

[0088] [Table 12]

[0089] Preparation method: The preparations were made with reference to the preparation methods of Examples 7 to 11, with the difference being that phase F was replaced with the glabridin compositions obtained in Comparative Examples 1 to 25, and the components were added according to the content in Table 12.

[0090] Test example 1: Penetration performance test Measurement method: (1) Using the essence formulations of Examples 7 to 9 and Comparative Examples 26, 47, 49, and 50, respectively, the penetration behavior of the samples was studied for 2 hours (h), 4 hours, 8 hours, 12 hours, and 24 hours based on the pigskin-Franz cell system in accordance with "GB-T27818-2011 'In vitro test method for skin absorption of chemicals'" and "Q / FZR 0101-2023 'Glabridin, a raw material for cosmetics'", with reference to Table 13. (2) The essence formulations obtained in Comparative Examples 27 to 46 and 48 were used to study the permeation behavior of the samples for 24 hours based on the pigskin-Franz cell system, and the results are shown in Table 14. This test was conducted in three parallel sets, and the average value was calculated. The test results are shown in Tables 13 and 14.

[0091] [Table 13]

[0092] [Table 14]

[0093] Conclusion: (1) Compared with a formulation lacking any of 3-O-ethyl ascorbic acid, polyhydric alcohol, nonionic surfactant, and anionic surfactant, the glabridin composition of the formulation provided by the present invention is more advantageous in improving the permeability of an essence dosage form, and has an unexpected technical effect. (2) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), the glabridin composition obtained by adopting the preparation technique provided by the present invention is more advantageous in improving the permeability of the essence formulation, and has unexpected technical effects. (3) Compared with cyclodextrin inclusion and liposome inclusion, the glabridin composition obtained by adopting the preparation technique provided by the present invention is more advantageous in improving the permeability of the essence dosage form, and has an unexpected technical effect. (4) Compared with the use of other nonionic surfactants, the present invention employs oleth-20 and polyglyceryl-10 oleate as nonionic surfactants to obtain a glabridin composition, which is advantageous in further improving the permeability of essence formulations, and has an unexpected technical effect. (5) Compared with the use of other polyhydric alcohols, the present invention uses 1,3-butanediol as the polyhydric alcohol to obtain a glabridin composition, which is advantageous in further improving the permeability of the essence formulation, and has an unexpected technical effect. (6) Compared with the use of other fats and oils, the glabridin composition obtained in the present invention by using caprylic / capric triglyceride as a fat and oil is advantageous in further improving the permeability of the essence dosage form, and has an unexpected technical effect.

[0094] Test Example 2: Clinical whitening effect verification Testing method: The essence formulations of Examples 7 to 9 and Comparative Examples 26, 47, 49, and 50 were used, respectively, and the skin color visual assessment difference, ITA° difference, or MI difference was measured at any time point before and after application of the test product according to "Method 1: UV-induced Human Skin Darkening Model Whitening Effect Measurement Method." A significant improvement was observed compared with the negative control (P<0.05), otherwise the test product was deemed to have no blemish removal or whitening effect. The test results are shown in Table 15.

[0095] [Table 15]

[0096] Conclusion: (1) Compared with the absence of 3-O-ethyl ascorbic acid, the glabridin composition formulated according to the present invention is more advantageous in increasing the speed and effectiveness of clinical whitening and spot removal effects in essence formulation, and has an unexpected technical effect. (2) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), the glabridin composition obtained by adopting the preparation technology provided by the present invention is more advantageous in increasing the speed and effectiveness of the clinical whitening and blemish removal effects of the essence formulation, and has unexpected technical effects. (3) Compared with cyclodextrin inclusion and liposome inclusion, the glabridin composition obtained by adopting the preparation technology provided by the present invention is more advantageous in increasing the speed and effectiveness of the clinical whitening and blemish removal effects of the essence formulation, and has unexpected technical effects.

[0097] Test Example 3: Consideration of state stability and content stability Testing method: In accordance with ISO / TR18811-2018 Guidelines for Cosmetics and Toiletries Stability Testing and Q / FZR 0101-2023, Glabridin, a cosmetic raw material, the glabridin compositions obtained in the above examples and comparative examples were stored at 45±2°C and -15±2°C, respectively, and their stability was observed for six months. The glabridin content (here, the content is calculated by multiplying the ratio of the measured glabridin concentration in the product to the theoretical concentration by 100%) after six months was measured (at sampling inspections on days 0, 7, 14, 1 month, 3 months, and 6 months). The results are shown in Tables 16, 17, and 18. (Note: 1. If precipitation or layer separation occurs, observation should be discontinued immediately. " / " indicates that stability was not observed. 2. Do not test the content of samples in which crystalline precipitation is observed with the naked eye.)

[0098] [Table 16] TIFF2026025815000017.tif249161TIFF2026025815000018.tif174161

[0099] [Table 17] TIFF2026025815000020.tif239161TIFF2026025815000021.tif31161

[0100] [Table 18]

[0101] Conclusion: (1) Compared with adopting a formulation lacking any of 3-O-ethyl ascorbic acid, polyhydric alcohol, nonionic surfactant, and anionic surfactant, adopting the formulation provided by the present invention is advantageous in further improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (2) Compared with the use of other nonionic surfactants, the use of oleth-20 and polyglyceryl-10 oleate in the present invention is advantageous in further improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (3) Compared with the use of other polyhydric alcohols, the present invention employs 1,3-butanediol, which is advantageous in further improving the state stability and content stability of the glabridin composition under high temperature conditions. (4) Compared with the use of other fats and oils, the present invention employs caprylic / capric triglyceride, which is advantageous in further improving the state stability and content stability of the glabridin composition under high temperature conditions. (5) Compared with the use of other anionic surfactants, the present invention employs sodium stearoyl glutamate, which is advantageous in further improving the state stability and content stability of the glabridin composition under high and low temperature conditions. (6) Compared with other preparation methods (e.g., different orders of adding 3-O-ethyl ascorbic acid or water), the preparation technique provided by the present invention is advantageous in further improving the state stability and content stability of the glabridin composition under high and low temperature conditions.

[0102] Test Example 4: pH Stability Testing method: In accordance with GB / T 13531.1-2008 "General Test Method for Cosmetics: Determination of pH Value," the highly percutaneous penetration-promoting water-soluble glabridin compositions obtained in Examples 1 to 6, Comparative Example 1, and Comparative Example 22 were taken, and the pH at each stability standing time (the stability standing conditions and time are shown in Test Example 3) was measured to determine the pH stability of the samples. The results are shown in Table 19.

[0103] [Table 19]

[0104] Conclusion: From Examples 1 to 6 and Comparative Example 22, compared with other preparation methods (for example, a different order of adding 3-o-ethyl ascorbic acid), adopting the preparation technique provided by the present invention is advantageous in improving the pH stability of the glabridin composition under high and low temperature conditions.

[0105] Test Example 5: Patch test Testing method: The glabridin compositions of Examples 1-6 and Comparative Examples 1 and 22 in Test Example 1 were taken and subjected to a closed skin patch test in accordance with the "Cosmetics Safety Technical Standards (Version 2015) Human Skin Patch Test" (wherein the test samples were samples aged 0 days, 6 months at 45°C, and 6 months at -15°C, respectively). Test scoring criteria: See Table 20. Test results: See Table 21.

[0106] [Table 20]

[0107] [Table 21]

[0108] Conclusion: (1) Compared with the case where 3-O-ethyl ascorbic acid is not added, the formulation provided by the present invention is further advantageous in improving the safety of the glabridin composition, and has an unexpected technical effect; (2) Compared with other preparation methods (e.g., adding 3-O-ethyl ascorbic acid in a different order), adopting the preparation technique provided by the present invention is advantageous in further improving the safety of the glabridin composition.

[0109] Although the method of the present invention has been described in terms of preferred embodiments, those skilled in the art can obviously modify the methods and applications described herein or make appropriate modifications and combinations within the content, spirit and scope of the present invention to realize and apply the technology of the present invention. Those skilled in the art can achieve this by taking into account the content of this specification and appropriately improving the process parameters. It should be particularly noted that all similar substitutions and modifications are apparent to those skilled in the art, and they are all deemed to be included in the present invention.

Claims

1. A glabridin composition, the glabridin composition being prepared from an S1 phase, an S2 phase, and an S3 phase, the S1 phase being composed of an oil and a fat and glabridin, the S2 phase being prepared from 3-O-ethyl ascorbic acid, an anionic surfactant, a nonionic surfactant, a polyhydric alcohol, and water, and the S3 phase being water; the nonionic surfactant is oleth-20 and polyglyceryl-10 oleate; the anionic surfactant is sodium stearoyl glutamate; the fat is caprylic / capric triglyceride; the polyhydric alcohol is 1,3-butanediol; Calculated based on the total mass of the glabridin composition, the content of the glabridin is 0.10 wt% to 4.00 wt%, the content of the 3-O-ethyl ascorbic acid is 0.10 wt% to 4.00 wt%, the total content of the nonionic surfactants is 0.70 wt% to 10.00 wt%, the content of the oils and fats is 1.00 wt% to 40.00 wt%, the content of the polyhydric alcohol is 0.60 wt% to 6.00 wt%, the content of the anionic surfactant is 0.10 wt% to 1.00 wt%, the content of water in the S2 phase is 0.30 wt% to 3.00 wt%, and the remainder is the S3 phase, The method for preparing the glabridin composition comprises the following steps: (1) Glabridin and fats and oils are mixed, heated to dissolve, and mixed uniformly to obtain an S1 phase; (2) 3-O-ethyl ascorbic acid, an anionic surfactant, a nonionic surfactant, a polyhydric alcohol, and water are mixed, heated to dissolve, and mixed uniformly to obtain an S2 phase; (3) Adding the S1 phase obtained in step (1) to the S2 phase obtained in step (2) under stirring conditions of the S2 phase, and mixing to form a gel; (4) A glabridin composition, characterized in that the gel obtained in step (3) is further mixed with an S3 phase to obtain the glabridin composition.

2. The glabridin composition according to claim 1, characterized in that the content of the oleth-20 is 0.10 wt% to 4.00 wt%, and the content of the polyglyceryl-10 oleate ester is 0.60 wt% to 6.00 wt%, calculated based on the total mass of the glabridin composition.

3. Calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt% to 4.00 wt%, the content of the 3-O-ethyl ascorbic acid is 1.00 wt% to 4.00 wt%, the content of the oleth-20 is 0.50 wt% to 4.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil or fat is 10.00 wt% to 40.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase, or The glabridin composition according to claim 1, characterized in that, calculated based on the total mass of the glabridin composition, the content of the glabridin is 0.10 wt%, the content of the 3-O-ethyl ascorbic acid is 0.10 wt%, the content of the oleth-20 is 0.10 wt%, the content of the polyglyceryl-10 oleate is 0.60 wt%, the content of the oil / fat is 1.00 wt%, the content of the polyhydric alcohol is 0.60 wt%, the content of the anionic surfactant is 0.10 wt%, the content of water in the S2 phase is 0.30 wt%, and the remainder is the S3 phase.

4. Calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt%, the content of the 3-O-ethyl ascorbic acid is 1.00 wt%, the content of the oleth-20 is 0.50 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 10.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase; or Calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt%, the content of the 3-O-ethyl ascorbic acid is 1.00 wt%, the content of the oleth-20 is 1.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil or fat is 10.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase; or Calculated based on the total mass of the glabridin composition, the content of the glabridin is 1.00 wt%, the content of the 3-O-ethyl ascorbic acid is 2.00 wt%, the content of the oleth-20 is 0.50 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 10.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase. Calculated based on the total mass of the glabridin composition, the content of the glabridin is 2.00 wt%, the content of the 3-O-ethyl ascorbic acid is 2.00 wt%, the content of the oleth-20 is 2.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil or fat is 20.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase; or The glabridin composition according to claim 1, characterized in that, calculated based on the total mass of the glabridin composition, the content of the glabridin is 4.00 wt%, the content of the 3-O-ethyl ascorbic acid is 4.00 wt%, the content of the oleth-20 is 4.00 wt%, the content of the polyglyceryl-10 oleate is 6.00 wt%, the content of the oil / fat is 40.00 wt%, the content of the polyhydric alcohol is 6.00 wt%, the content of the anionic surfactant is 1.00 wt%, the content of water in the S2 phase is 3.00 wt%, and the remainder is the S3 phase.

5. The glabridin composition according to claim 1, characterized in that the heating and dissolving in the step (1) is carried out by heating to 60°C to 80°C.

6. The glabridin composition according to claim 1, characterized in that the heating and dissolving in the step (2) is carried out by heating to 60°C to 70°C.

7. The glabridin composition according to claim 1, characterized in that the heating and dissolving in the step (1) is performed by heating up to 70°C, and the heating and dissolving in the step (2) is performed by heating up to 60°C.

8. The glabridin composition according to claim 1, characterized in that the mass ratio of water to polyhydric alcohol added in step (2) is 1:1 to 1:

2.

9. 9. The application of the glabridin composition according to any one of claims 1 to 8 in the manufacture of cosmetics.

10. A cosmetic comprising the glabridin composition according to any one of claims 1 to 8.

Images