Application of a penetration-promoting composition of phenethylresorcinol

Abstract

The present invention discloses an application of a penetration-promoting composition of phenethyl resorcinol, and relates to the technical field of cosmetics. The present invention specifically discloses an application of a penetration-promoting composition comprising wild soybean seed extract, glycerol, sorbitol, and urea in any one of promoting the percutaneous permeation absorption of phenethyl resorcinol, improving the stability of phenethyl resorcinol, and reducing the irritation of phenethyl resorcinol. By comprehensively considering the hydration mechanism, the similar miscibility mechanism, and the structural change mechanism, urea and sorbitol are prepared as a low eutectic solvent and compounded with glycerol and wild soybean seed extract, which significantly improves the percutaneous permeability, stability, and bioavailability of phenethyl resorcinol, and significantly reduces the irritation of phenethyl resorcinol.

Description

Technical Field

[0001] The invention relates to the technical field of cosmetics, in particular to application of a penetration-enhancing composition of phenethylresorcinol. Background Art

[0002] The human skin is composed of three parts: epidermis, dermis and subcutaneous tissue. The top layer of the epidermis is the stratum corneum, which is composed of inanimate keratinocytes and intercellular lipids arranged in layers. The keratinocytes contain keratin and filamentous protein, and the lipids contain ceramide, cholesterol and free fatty acids distributed around the cells in the form of bilayers. The lower layer of the epidermis is the active dermis composed of living cells, which has a high water content. The stratum corneum is the main barrier that hinders the percutaneous penetration of active ingredients.

[0003] Phenylethyl resorcinol has excellent tyrosinase inhibition ability and can effectively inhibit melanin production in skin cells, but its transdermal delivery effect is poor, resulting in low bioavailability. In the related art, chemical penetration enhancers such as aminoketones and surfactants are added to improve the transdermal effect of phenethyl resorcinol, but this is prone to irritation or sensitization. Therefore, it is very important to provide a composition that can effectively and gently improve the transdermal effect of phenethyl resorcinol. Summary of the invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides an application of a penetration-enhancing composition in promoting the percutaneous permeation absorption of phenethyl resorcinol, improving the stability of phenethyl resorcinol, and reducing the irritation of phenethyl resorcinol.

[0005] The present invention also provides a composition.

[0006] The invention also provides a method for promoting the percutaneous permeation absorption of phenethyl resorcinol, improving the stability of phenethyl resorcinol or reducing the irritation of phenethyl resorcinol.

[0007] The present invention also provides application of the composition in preparing cosmetics.

[0008] The invention also provides a cosmetic.

[0009] According to the first aspect of the present invention, a penetration-enhancing composition is used in any one of A1) to A3), wherein the penetration-enhancing composition comprises: wild soybean seed extract, glycerol, sorbitol, and urea;

[0010] The preparation method of the penetration-enhancing composition comprises the following steps:

[0011] After preparing a low eutectic solvent comprising sorbitol and urea, preparing a mixture comprising the low eutectic solvent, wild soybean seed extract, and glycerol to obtain the penetration-enhancing composition;

[0012] A1) Promote the percutaneous absorption of phenethyl resorcinol;

[0013] A2) improving the stability of phenethyl resorcinol;

[0014] A3) Reduce the irritation of phenethyl resorcinol.

[0015] According to some embodiments of the present invention, the penetration enhancing composition comprises, by weight:

[0016]

[0017] According to some embodiments of the present invention, the penetration enhancing composition comprises, by weight:

[0018]

[0019] According to some embodiments of the present invention, the penetration enhancing composition comprises, by weight:

[0020]

[0021] According to some embodiments of the present invention, the penetration enhancing composition comprises, by weight:

[0022]

[0023] According to some embodiments of the present invention, the mass ratio of the wild soybean seed extract, glycerol, sorbitol and urea is (1-6.5):(4-20):(2.5-3.5):1.

[0024] According to some embodiments of the present invention, the mass ratio of the wild soybean seed extract, glycerol, sorbitol and urea is (1.2-4.5):(4.2-13):(2.8-3.2):1.

[0025] According to some embodiments of the present invention, the mass ratio of the wild soybean seed extract, glycerol, sorbitol and urea is (1.2-1.7):(4.2-4.7):(2.8-3.2):1.

[0026] According to some embodiments of the present invention, in the preparation method, preparing a low eutectic solvent comprising sorbitol and urea comprises the following steps: stirring a mixture comprising sorbitol and urea at 80°C to 100°C to obtain the low eutectic solvent. The low eutectic solvent is a transparent liquid. For example, the temperature may be 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C or 100°C.

[0027] According to some embodiments of the present invention, the stability described in A2) includes the stability of phenethyl resorcinol at -15°C to 48°C. For example, it can be the stability at -15°C, -12°C, -10°C, -8°C, -6°C, -4°C, -2°C, 0°C, 2°C, 4°C, 6°C, 8°C, 10°C, 12°C, 14°C, 16°C, 18°C, 20°C, 22°C, 24°C, 26°C, 28°C, 30°C, 32°C, 34°C, 36°C, 38°C, 40°C, 42°C, 44°C, 46°C or 48°C.

[0028] According to some embodiments of the present invention, the stability in A2) refers to the stability of phenethyl resorcinol in a solution. The solution is an aqueous solution.

[0029] A composition according to a second embodiment of the present invention comprises the penetration-enhancing composition described in the first embodiment and phenethyl resorcinol.

[0030] According to some embodiments of the present invention, the composition comprises 0.1% to 50% of the penetration enhancing composition by mass percentage. For example, it can be 0.1%, 0.2%, 0.4%, 0.6%, 0.8%, 1%, 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5% or 50%.

[0031] According to some embodiments of the present invention, the composition includes 0.01% to 5% phenylethyl resorcinol by mass percentage, for example, 0.01%, 0.05%, 0.1%, 0.2%, 0.4%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5% or 5%.

[0032] According to some embodiments of the present invention, the composition further comprises water. If present, the composition comprises 45% to 99.89% water by mass. For example, it may be 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99.89%.

[0033] According to some embodiments of the present invention, the method for preparing the composition comprises the following steps:

[0034] The composition is obtained by mixing the components.

[0035] A method for promoting the percutaneous permeation and absorption of phenethyl resorcinol, improving the stability of phenethyl resorcinol or reducing the irritation of phenethyl resorcinol according to a third aspect of the present invention comprises the following steps:

[0036] A mixture comprising the penetration enhancing composition described in the first embodiment and phenethylresorcinol is prepared.

[0037] Use of the composition described in the second aspect embodiment of the fourth aspect embodiment of the present invention in the preparation of cosmetics.

[0038] According to a fifth aspect of the present invention, a cosmetic comprises the composition described in the second aspect of the present invention.

[0039] According to some embodiments of the present invention, the cosmetic comprises 0.1% to 50% of the composition by mass percentage, for example, 0.1%, 0.5%, 1%, 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5% or 50%.

[0040] According to some embodiments of the present invention, the dosage form of the cosmetic is a cream, emulsion, lotion, gel, mask or lotion.

[0041] According to some embodiments of the present invention, the cosmetic further comprises cosmetically acceptable excipients.

[0042] The present invention has at least the following beneficial effects:

[0043] The penetration-enhancing composition of the embodiment combines the hydration mechanism, the similar dissolution mechanism and the structural change mechanism, and prepares urea and sorbitol as a low eutectic solvent and then compounding with glycerol and wild soybean seed extract, which can significantly improve the transdermal permeability, stability and bioavailability of phenethyl resorcinol, and significantly reduce the irritation of phenethyl resorcinol.

[0044] Other features and advantages of the present invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the present invention. DETAILED DESCRIPTION

[0045] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0046] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. If the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0047] When a numerical range is disclosed herein, the above range is considered to be continuous and includes the minimum and maximum values ​​of the range, as well as every value between such minimum and maximum values. Further, when a range refers to an integer, every integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be combined. In other words, unless otherwise indicated, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0048] "Parts by mass" refers to the basic unit of measurement for expressing the mass ratio of multiple components. 1 part can represent any unit mass, such as 1g or 2.689g. If we say that the mass of component A is a parts and the mass of component B is b parts, it means the ratio of the mass of component A to the mass of component B is a:b. Alternatively, it means that the mass of component A is aK and the mass of component B is bK (K is an arbitrary number, indicating a multiple factor). It should not be misunderstood that the sum of the mass of all components is not limited to 100 parts.

[0049] The promotion of transdermal penetration of active ingredients mainly includes hydration mechanism, similar solubility mechanism and structural change mechanism.

[0050] Hydration mechanism: After the hydration capacity of nitrogen-containing substances in stratum corneum cells increases, the stratum corneum cells will absorb water and swell. The compactness of the originally densely arranged cells changes, which increases the space between cells, thereby helping to increase the permeability of water-soluble active ingredients and polar active ingredients.

[0051] Similar dissolves in water mechanism: mainly using ester solvents similar to the skin to improve the transdermal absorption efficiency of active ingredients. However, since the active layer below the stratum corneum of the skin is a water-soluble channel, if the active substance can only be dissolved in oil, it is not conducive to the further transmission of the active ingredient to the basal layer. Therefore, the water-oil partition coefficient of the active substance must be within a certain range in order to penetrate into the deep layer of the epidermis.

[0052] Mechanism of structural change: By changing the order of lipid arrangement in the stratum corneum, lipids can be fluidized, thereby increasing the permeability of active ingredients.

[0053] By preparing sorbitol and urea into a low eutectic solvent, and then adding wild soybean seed extract and glycerin for compounding, combining the hydration mechanism, similar miscibility mechanism and structural change mechanism, the transdermal permeability of phenylethyl resorcinol is improved from multiple dimensions.

[0054] Urea is a nitrogen-containing substance that can increase the space between skin cells through hydration to promote the penetration of active ingredients; the low eutectic solvent prepared from sorbitol and urea can interact with keratin in keratinocytes, destroy the regular and tight arrangement of keratinocytes, change the skin structure, and then promote the transdermal penetration of phenethyl resorcinol through structural changes, and can also bind to phenethyl resorcinol through weak interaction forces such as non-covalent bonds to improve its stability and biocompatibility; at the same time, the addition of glycerol can further increase the solubility of phenethyl resorcinol and better play the role of similar dissolving in the same way; the low eutectic solvent and the fat-soluble wild soybean seed extract can disturb the tightly arranged lipid bilayer of the epidermis and promote the transdermal penetration of phenethyl resorcinol.

[0055] If not otherwise specified, sorbitol was purchased from Roquette (China) Nutrition Food Co., Ltd.; urea was purchased from Xilong Science Co., Ltd.; and soybean seed extract was purchased from Lysofix of International Flavors (China) Co., Ltd. TM Liquid.

[0056] Unless otherwise specified, room temperature refers to (25±5)℃.

[0057] Example 1

[0058] This example provides a penetration-enhancing composition, which is composed of the following components by weight:

[0059]

[0060] This example also provides a method for preparing the penetration-enhancing composition, the steps are as follows:

[0061] Urea and sorbitol were mixed and stirred in a 90°C water bath until they became a transparent liquid to obtain a low eutectic solvent. Soybean seed extract and glycerol were added to the low eutectic solvent and stirred at room temperature to mix uniformly to obtain a penetration-enhancing composition.

[0062] Example 2

[0063] This example provides a penetration-enhancing composition, which is composed of the following components by weight:

[0064]

[0065]

[0066] This example also provides a method for preparing the penetration-enhancing composition, the steps are as follows:

[0067] Urea and sorbitol were mixed and stirred in a 90°C water bath until they became a transparent liquid to obtain a low eutectic solvent. Soybean seed extract and glycerol were added to the low eutectic solvent and stirred at room temperature to mix uniformly to obtain a penetration-enhancing composition.

[0068] Example 3

[0069] This example provides a penetration-enhancing composition, which is composed of the following components by weight:

[0070]

[0071] This example also provides a method for preparing the penetration-enhancing composition, the steps are as follows:

[0072] Urea and sorbitol were mixed and stirred in a 90°C water bath until they became a transparent liquid to obtain a low eutectic solvent. Soybean seed extract and glycerol were added to the low eutectic solvent and stirred at room temperature to mix uniformly to obtain a penetration-enhancing composition.

[0073] Comparative Example 1

[0074] This example provides a penetration-enhancing composition, which is glycerol.

[0075] Comparative Example 2

[0076] This example provides a penetration-enhancing composition, which is 1,3-propylene glycol.

[0077] Comparative Example 3

[0078] This example provides a penetration-enhancing composition, the composition of which is the same as that of Example 1, except that the preparation method is different.

[0079] The preparation method of the penetration-enhancing composition comprises the following steps:

[0080] After weighing each component, directly mix them evenly at room temperature to obtain a penetration-enhancing composition.

[0081] Comparative Example 4

[0082] This example provides a penetration-enhancing composition, which is basically the same as Example 1, except that the wild soybean seed extract is replaced with an equal mass portion of polyquaternium-10.

[0083] This example also provides a method for preparing the penetration-enhancing composition, the steps are as follows:

[0084] Urea and sorbitol were mixed and stirred in a 90°C water bath until they became a transparent liquid to obtain a low eutectic solvent. Polyquaternium-10 and glycerol were added to the low eutectic solvent and stirred at room temperature to mix uniformly to obtain a penetration-enhancing composition.

[0085] Comparative Example 5

[0086] This example provides a penetration-enhancing composition, which is basically the same as Example 1, except that urea and sorbitol are replaced by an equal amount of 1,3-propylene glycol.

[0087] The preparation method of the penetration-enhancing composition comprises the following steps:

[0088] After weighing each component, directly mix them evenly at room temperature to obtain a penetration-enhancing composition.

[0089] Application Examples

[0090] This example provides three compositions (Application Example 1 to Application Example 3), and the composition ratio of each composition is shown in Table 1 in terms of mass percentage.

[0091] Table 1

[0092]

[0093] This example also provides a method for preparing the composition of Application Example 1 to Application Example 3, and the steps are as follows:

[0094] The active ingredient, the penetration-enhancing composition and deionized water are mixed to obtain the composition.

[0095] Application Example 4

[0096] This example provides a whitening essence cream, the specific ingredients of which are shown in Table 2.

[0097] Table 2

[0098]

[0099]

[0100] This example also provides a method for preparing the whitening essence cream of Application Example 4, the steps are as follows:

[0101] Heat the phase A raw material and the phase B raw material to 80℃-85℃ respectively, then add the phase A raw material to the phase B raw material, maintain 80℃-85℃, homogenize and emulsify for 3min-5min, cool to 60℃-65℃, add the pre-dissolved phase C raw material, stir evenly, cool to 40℃-45℃, add the pre-dissolved phase D raw material, stir until the paste is uniform and fine, and the whitening essence cream is obtained.

[0102] Application comparison

[0103] This example provides 11 compositions (Application Comparative Example 1 to Application Comparative Example 11), and the composition ratio of each composition is shown in Table 3 in terms of mass percentage.

[0104] Table 3

[0105]

[0106]

[0107] This example also provides a method for preparing the composition of Comparative Example 1 to Comparative Example 11, and the steps are as follows:

[0108] The active ingredient, the penetration-enhancing composition and deionized water are mixed to obtain the composition.

[0109] Application Comparative Example 12

[0110] This example provides a whitening essence cream, the specific ingredients and preparation method of which are basically the same as those of Application Example 4, the only difference being that the composition of Application Example 1 is replaced with an equal amount of the composition of Application Comparative Example 1.

[0111] Experimental Example 1

[0112] The permeation experiment was carried out using a Franz vertical double-chamber permeation diffusion cell with an effective permeation area of ​​1.77 cm 2 , the volume of the receiving tank is 12mL, and a PBS buffered saline solution containing 20% ​​(v / v) ethanol is prepared as the receiving solution. Cut the ex vivo pig skin to a suitable size, place the skin stratum corneum upward between the diffusion chamber and the two half-cells of the receiving chamber of the Franz vertical diffusion cell, and fix it with a clip. Fill the receiving chamber with the receiving solution so that the liquid surface just contacts the skin, ensure that there are no bubbles between the receiving solution and the pig skin, and add a magnetic stirring rotor to the receiving tank. Accurately weigh 0.1g of each composition of application examples 1 to 3 and application comparison examples 1 to 11 and place them in the diffusion chamber, then place the receiving tank in a (32±0.5)℃ constant temperature water bath for heating. Turn on the magnetic stirrer and stir at 300rpm. Draw 1mL of the receiving solution at 2, 4, 6, 8, and 12h, respectively. After each sampling, immediately add 1mL of blank receiving solution at the same temperature. The HLPC-DAD method is used to determine the concentration of the component to be tested in the receiving solution at different time periods. The data is processed according to the following formula to calculate the cumulative penetration amount Q and cumulative transmittance.

[0113] Q=[C n ×V+∑C i ×V0] / S(i=1···n-1);

[0114] Q: Cumulative permeation (μg / cm 2); V: volume of receiving liquid in the receiving chamber (12 mL); V0: volume of each sampling (1 mL); C i : Drug concentration in the receiving solution from the first sampling to the last sampling (μg / mL); C n : sample concentration measured at the nth sampling point (μg / mL); S: effective penetration area (1.77cm 2 ).

[0115] Cumulative transmittance = Q × S / M × 100%;

[0116] Q: Cumulative permeation (μg / cm 2 ); S: effective penetration area (1.77cm 2 ); M: amount of sample added (μg).

[0117] The detection conditions are: Agilent 1260 high performance liquid chromatograph, Agilent Zorbox EC-C18 column (4.6×150 mm, 2.7 μm); UV spectrophotometric detector; injection volume 10 μL, flow rate 1 mL / min, detection wavelength 360 nm. The mobile phase is 0.1% (v / v) acetic acid aqueous solution (solution A) and acetonitrile (solution B). The isocratic elution conditions are: 0-10 min (B 60%).

[0118] The experimental results are shown in Table 4.

[0119] Table 4

[0120]

[0121]

[0122] The phenethyl resorcinol in the compositions of application examples 1 to 3 has a very high transdermal permeability. The compositions of application examples 1-2 use glycerol as the penetration enhancing composition, and the transdermal effect of phenethyl resorcinol is not good. Application example 3 directly mixes the components of the penetration enhancing composition without preparing the low eutectic solvent of urea and sorbitol in advance, the penetration enhancing composition in application example 4 replaces the wild soybean seed extract with an equal mass portion of polyquaternium-10, and the penetration enhancing composition in application example 5 replaces the low eutectic solvent prepared by urea and sorbitol with an equal mass portion of 1,3-propylene glycol, and the transdermal permeability of phenethyl resorcinol is significantly reduced. The active ingredients of Comparative Examples 6 and 7 are polydatin, the active ingredients of Comparative Examples 8 and 9 are resveratrol, and the active ingredients of Comparative Examples 10 and 11 are glabridin. Only polydatin has a trace amount of penetration after 6 hours under the promotion of 1,3-propylene glycol. It can be seen that the penetration-promoting composition of Example 3 and Comparative Example 2 has basically no penetration-promoting effect on polydatin, resveratrol, and glabridin. This shows that wild soybean seed extract, glycerol, sorbitol, and urea combined with a specific preparation method can synergistically promote the transdermal absorption of phenylethylresorcinol efficiently and specifically.

[0123] Experimental Example 2

[0124] The compositions of Application Examples 1 to 3 and Comparative Examples 1 to 11 were placed at -15°C, room temperature (25°C), and 48°C for 30 days, respectively. After the samples were taken out and returned to room temperature, the states of the samples under various conditions before and after storage were checked.

[0125] The results are shown in Table 5.

[0126] Table 5

[0127] Group -15℃ normal temperature 48℃ Application Example 1 clarify clarify clarify Application Example 2 clarify clarify clarify Application Example 3 clarify clarify clarify Application Comparative Example 1 Precipitation clarify clarify Application Comparative Example 2 clarify clarify clarify Application Comparative Example 3 clarify clarify clarify Application Comparative Example 4 clarify clarify clarify Application Comparative Example 5 clarify clarify clarify Application Comparative Example 6 Precipitation clarify clarify Application Comparative Example 7 Precipitation clarify clarify Application Comparative Example 8 Precipitation clarify Precipitation Application Comparative Example 9 Precipitation Precipitation Precipitation Application Comparative Example 10 Precipitation Precipitation Precipitation Application Comparative Example 11 Precipitation Precipitation Precipitation

[0128] The compositions of application examples 1 to 3 and application comparative examples 2 to 5 have good stability at different temperatures. Application comparative examples 1 and application comparative examples 6 to 11 all have precipitation at a low temperature of -15°C, and application comparative example 8 also has precipitation at a high temperature of 48°C. Application comparative examples 9 to 11 also have precipitation at a normal temperature of 25°C and a high temperature of 48°C, and the stability is poor. This shows that wild soybean seed extract, glycerol, sorbitol, and urea can synergistically improve the stability of phenethyl resorcinol at different temperatures.

[0129] Experimental Example 3

[0130] The irritation of the compositions of application examples 1 to 3 and application comparative examples 1 to 5 to the chorioallantoic sac of chicken embryos was tested by the chicken embryo chorioallantoic membrane experiment for eye irritation / corrosivity. A 9-day-old chicken embryo with a mass of 50 g to 60 g was selected, the air chamber position was marked on the eggshell surface, the eggshell part was peeled off, the white egg membrane was exposed, and the egg membrane was moistened with 0.9% saline and removed with tweezers. 0.3 mL of sample was taken and directly applied to the chorioallantoic membrane (CAM), ensuring that the coverage area reached at least 50%. Immediately observe the CAM reaction until 5 minutes, record the observation results and make a judgment, repeat 3 times for each sample, and use saline as a negative control. The irritation score (IS) was calculated with reference to "SNT 2329-2009 Chicken embryo chorioallantoic membrane test for eye irritation / corrosivity of cosmetics". Judgment criteria: IS < 1 is non-irritating, 1 ≤ IS < 5 is mildly irritating, and 5 ≤ IS < 10 is moderately irritating.

[0131] The experimental results are shown in Table 6.

[0132] Table 6

[0133] Group IS Value Application Example 1 0 Application Example 2 0.2 Application Example 3 0.47 Application Comparative Example 1 1.53 Application Comparative Example 2 0.91 Application Comparative Example 3 1.72 Application Comparative Example 4 2.33 Application Comparative Example 5 1.56

[0134] The compositions of application examples 1 to 3 and application comparative example 2 are non-irritating, and the irritation of the compositions of application examples 1 to 3 is less than that of application comparative example 2; application comparative example 1 and comparative application examples 3 to 5 are mildly irritating. This indicates that wild soybean seed extract, glycerin, sorbitol, and urea combined with a specific preparation method can synergistically reduce the irritation of phenethyl resorcinol.

[0135] Experimental Example 4

[0136] A total of 31 volunteers were selected, including 7 males and 24 females, aged 20 to 60. The ultraviolet melanin model was established in accordance with the specific requirements of the first method of the test method for the anti-freckle and whitening efficacy of cosmetics in the "Technical Specifications for Safety of Cosmetics" (2015 edition).

[0137] Establishment of UV melanin model: Test the minimum erythema dose (MED) on the back of volunteers, and then select 3 areas with an area of ​​no less than 6cm in the test area. 2 The test areas are divided into the test product area and the negative control area. The interval between each test area is not less than 1.0 cm, and the selected area in each test area is not less than 0.5 cm 2 The blackened test area was irradiated once a day with an ultraviolet sunlight simulator at a dose of 0.75 times the MED for 4 consecutive days.

[0138] After the modeling was completed, the whitening cream prepared in Example 4 and Comparative Example 12 was applied to the blackened part of the back skin of the volunteers (blackened test area) for 4 consecutive weeks (twice a day, with an interval of not less than 4 hours between each application, 2 mg / cm each time). 2 ), and no product was applied to the negative control area. Visual evaluation of skin color and skin colorimeter test were performed on each melanized test area before and 1 / 2 / 3 / 4 weeks after product use. The ITA° value was calculated based on the L*a*b* color space value of the skin colorimeter test.

[0139]

[0140] Among them, L* represents brightness and b* represents yellowness. The larger the ITA° value, the lighter the skin color, and vice versa, the darker the skin color.

[0141] The difference in visual skin color evaluation before and after use [median (minimum value, maximum value)] is shown in Table 7, the regression coefficient of visual skin color evaluation (slope k value (mean ± standard deviation)) is shown in Table 8, the difference in skin ITA° before and after use (mean ± standard deviation) is shown in Table 9, and the analysis results of skin ITA° value regression coefficient (slope k value) (mean ± standard deviation) are shown in Table 10. In Tables 7 to 10, * indicates that there is a significant difference compared with the application comparison group 12 (P<0.05).

[0142] Table 7

[0143] Group 1 week 2 weeks 3 weeks 4 weeks Application Example 4 0.0(-0.5,0.2) 0.0(-0.5,0.3) -0.5(-1.0,0.3) -0.5(-1.5,0.4)* Application Comparative Example 12 0.0(-0.5,0.2) 0.0(-0.5,0.3) -0.5(-0.5,0.3) -0.5(-0.5,0.3)

[0144] Table 8

[0145] Group Slope k value Application Example 4 <![CDATA[-0.14±0.09 * ]]> Application Comparative Example 12 -0.08±0.07

[0146] Table 9

[0147] Group 1 week 2 weeks 3 weeks 4 weeks Application Example 4 0.40±2.03 2.04±3.15 4.53±3.23* 5.68±2.71* Application Comparative Example 12 0.22±2.80 1.33±3.50 2.72±3.39 3.87±3.10

[0148] Table 10

[0149] Group Slope k value Application Example 4 <![CDATA[1.55±0.77 * ]]> Application Comparative Example 12 1.02±0.72

[0150] Compared with the corresponding product of Example 12, after using the product of Example 4 for 4 weeks, the difference in skin color visual score before and after use was significantly improved (P < 0.05); after using the product of Example 4 for 3 and 4 weeks, the difference in skin ITA° before and after use was significantly improved (P < 0.05). The regression coefficient analysis showed that the ITA° and skin color visual score showed that the skin melanization was significantly improved when the product of Example 4 was used compared with the product of Example 12 (P < 0.05). This shows that the product of Example 4 has a good freckle removal and whitening effect. When the concentration of phenethyl resorcinol is low, the permeation-enhancing composition prepared by the present invention can effectively promote the transdermal absorption of phenethyl resorcinol, thereby exerting a better whitening effect.

[0151] The embodiments of the present invention are described in detail above in conjunction with the embodiments, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge scope of ordinary technicians in the relevant technical field without departing from the purpose of the present invention.

Claims

1. Use of a penetration-enhancing composition in any one of A1) to A3), characterized in that: The penetration-enhancing composition comprises: wild soybean seed extract, glycerol, sorbitol and urea; The preparation method of the penetration-enhancing composition comprises the following steps: After preparing a low eutectic solvent comprising sorbitol and urea, preparing a mixture comprising the low eutectic solvent, wild soybean seed extract, and glycerol to obtain the penetration-enhancing composition; A1) Promote the percutaneous absorption of phenethyl resorcinol; A2) improving the stability of phenethyl resorcinol; A3) Reduce the irritation of phenethyl resorcinol.

2. The use according to claim 1, characterized in that: The penetration-enhancing composition comprises, by mass:

3. The use according to claim 1, characterized in that: The penetration-enhancing composition comprises, by mass: Preferably, the penetration-enhancing composition comprises, by weight:

4. The use according to claim 1, characterized in that: The stability described in A2) includes the stability of phenethylresorcinol at -15°C to 48°C.

5. A composition, characterized in that The invention comprises the penetration enhancing composition as described in any one of claims 1 to 3.

6. The composition according to claim 5, characterized in that Calculated by mass percentage, the composition comprises 0.1% to 50% of the penetration-enhancing composition and 0.01% to 5% of phenethyl resorcinol.

7. A method for promoting the percutaneous permeation and absorption of phenethyl resorcinol, improving the stability of phenethyl resorcinol or reducing the irritation of phenethyl resorcinol, characterized in that: The following steps are involved: A mixture comprising the penetration enhancing composition according to any one of claims 1 to 3 and phenethylresorcinol is prepared.

8. Use of the composition according to claim 5 or 6 in the preparation of cosmetics.

9. A cosmetic, characterized in that: Comprising the composition of claim 5 or 6.

10. The cosmetic according to claim 9, characterized in that: The dosage form of the cosmetic is cream, emulsion, water, gel, facial mask or lotion.

Images