Long-acting whitening and blackening-free composition containing glabridin and pterostilbene and application of long-acting whitening and blackening-free composition

Abstract

The invention relates to a long-acting whitening and blackening-free composition containing glabridin and pterostilbene and application of the long-acting whitening and blackening-free composition, and belongs to the technical field of whitening cosmetics. The composition provided by the invention is prepared from the following components in parts by weight: 0.005 to 0.1 part of glabridin, 0.03 to 0.4 part of pterostilbene, 0.02 to 0.2 part of herba centellae extract, 0.0005 to 0.005 part of palmitoyl tripeptide-8 and 0.01 to 0.1 part of sodium hyaluronate. The application of the composition provided by the invention comprises the following steps: (1) preparing a phase A containing an inclusion empty shell; (2) dissolving glabridin, pterostilbene and palmitoyl tripeptide-8 to obtain a phase B; dissolving the centella asiatica extract and sodium hyaluronate to obtain a phase C; (3) adding the phase A and the phase C into the phase B, and uniformly mixing to obtain an inclusion phase; and (4) compounding the inclusion phase with a cosmetic base material. The composition provided by the invention integrates melanin regulation and control and skin barrier repair, enhances the whitening effect through targeted transmission and inclusion slow release, prolongs the blackening time, and has a very good application prospect in the whitening cosmetic industry.

Description

Technical Field

[0001] The invention relates to the technical field of whitening cosmetics, and in particular to a long-acting whitening and anti-darkness composition containing glabridin and pterostilbene and an application thereof. Background Art

[0002] Whitening products usually achieve whitening effects by inhibiting melanin synthesis, such as phenylethylresorcinol, arbutin, 4-butylresorcinol, etc., which may quickly return to black after discontinuation. The main reasons are as follows: First, after discontinuation, melanocytes may overreact and produce excessive melanin in a short period of time, or after the synthesis of melanin in the skin is inhibited, melanin production will increase to restore balance, resulting in darkening after discontinuation. Second, in seasons or areas with strong sunlight, the skin is not properly protected and is more susceptible to damage from ultraviolet rays, stimulating melanin production, accelerating pigmentation, and darkening the skin color. Third, powerful whitening ingredients may cause damage to the skin barrier. After discontinuation, the skin is more susceptible to external stimuli and damage, causing pigmentation, or causing water loss, and dry skin is more prone to pigment deposition. Fourth, after discontinuation, the enzymes related to melanin resume activity, and melanin production increases. According to age differences, the normal metabolic cycle of the skin is about 21-40 days. After the discontinuation time exceeds the metabolic cycle, the production of melanin gradually returns to normal and the skin becomes dark again.

[0003] Regarding the phenomenon of rapid darkening after whitening, although the current market has abandoned whitening ingredients with strong side effects such as hydroquinone, there are still risks in using strong whitening ingredients, especially for people with sensitive skin. For example, phenylethyl resorcinol achieves whitening by inhibiting melanin synthesis, but it is accompanied by barrier damage. After discontinuation of use, melanocytes may "rebound" and cause excessive melanin production. In addition, the skin's resistance to the external environment decreases, making it susceptible to ultraviolet rays and other stimuli, causing the skin to darken. Niacinamide reduces pigmentation by inhibiting the transport of melanin, but after discontinuation of use, a large amount of melanin that has been produced is quickly transferred to epidermal cells, causing darkening. However, delaying the darkening of the skin through multi-pathway compounding is often difficult to achieve the desired effect due to imperfect compounding pathways or too many complex ingredients: blocking or alleviating only two or three of the pathways cannot completely solve the problem of melanin deposition. When products with incomplete pathways are discontinued, other darkening pathways are still active, which may cause the skin to darken rapidly due to stress. Some products are all-round whitening products, and sufficient ingredients are added to different pathways. High concentrations or the superposition of multiple powerful ingredients may cause adverse skin reactions and indirectly affect the health of the skin barrier, making the skin noticeably sensitive after discontinuation of the product, accelerating the darkening of the skin.

[0004] Therefore, developing a product and application strategy that has a mild effect, does not damage the skin barrier, and can improve the long-lasting whitening and non-darkening effect can solve the industry pain point of easy darkening after whitening, and promote the sustainable development of the cosmetics industry, which has high application value. Summary of the invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a long-lasting whitening and anti-darkening composition containing glabridin and pterostilbene and its application. The specific composition provided by the present invention forms inclusions, and simultaneously achieves the effects of melanin regulation, soothing and anti-inflammatory, skin barrier repair, etc., and can prolong the darkening time and achieve long-lasting whitening, and has a high application value.

[0006] To achieve the above object, the technical solution adopted by the present invention is:

[0007] In a first aspect, the present invention provides a long-lasting whitening and anti-darkening composition containing glabridin and pterostilbene, comprising the following components in parts by weight: 0.005-0.1 parts of glabridin, 0.03-0.4 parts of pterostilbene, 0.02-0.2 parts of Centella asiatica extract, 0.0005-0.005 parts of palmitoyl tripeptide-8, and 0.01-0.1 parts of sodium hyaluronate.

[0008] The invention provides a long-lasting whitening composition that does not cause darkening. The composition comprises glycyrrhizin, pterostilbene (also known as palm tree bark extract), Centella asiatica extract (main component comprises madecassoside), palmitoyl tripeptide-8 and sodium hyaluronate.

[0009] Among them, glycyrrhizin is a whitening ingredient that can inhibit melanin synthesis through multiple pathways; pterostilbene can effectively resist free radicals and reduce oxidative damage to the skin; Centella asiatica extract has good anti-inflammatory and wound healing properties, which can help improve pigmentation caused by irritation or inflammation and promote overall skin health; Palmitoyl tripeptide-8 can not only increase the content of collagen and other extracellular matrix, help improve the overall density and texture of the skin, but is also a competitive α-MSH antagonist that can competitively bind to the melanocyte receptor MCR1 by mimicking α-MSH; Sodium hyaluronate has a strong moisturizing effect, and the hydrophobic position in its structure can form a complex with phospholipids, allowing it to penetrate deeper into the skin, thereby achieving a strong moisturizing and water-locking effect that combines the inside and the outside.

[0010] The present invention scientifically proportions the above-mentioned specific ingredients according to their interactions and skin absorbability, improves the overall effect, and ensures that each ingredient exerts its maximum effectiveness; under a specific proportion, it can better combine multiple mechanisms and comprehensively solve the problem of pigmentation, so that each component can play a synergistic role, improve the durability of the whitening effect, and significantly improve the problem of darkening after discontinuation of the product. The components work in combination in a specific proportion, and the effect is significantly better than their individual effects; replacing any of the components with other ingredients cannot achieve the best effect; changing the ratio between the components significantly affects the anti-inflammatory and soothing, melanin inhibition and darkening delay effects of the composition.

[0011] The long-acting whitening and anti-darkening composition containing glabridin and pterostilbene provided by the present invention can be further formed into inclusions and compounded for use in cosmetics, so as to downregulate macrophage inflammatory factors TNF-α, IL-1β and PGE2, and has excellent anti-inflammatory and soothing effects; at the same time, after the medication is discontinued for a period of time, the inhibition rate of melanin is still high. Clinical application to the skin can significantly improve the whitening effect and achieve a long-term anti-darkening effect of as short as 32 weeks, solving the industry pain point of easy darkening after whitening, and has extremely high application value.

[0012] Preferably, the following components are included in parts by weight: 0.005-0.05 parts of glabridin, 0.03-0.1 parts of pterostilbene, 0.05-0.1 parts of Centella asiatica extract, 0.001-0.005 parts of palmitoyl tripeptide-8, and 0.02-0.05 parts of sodium hyaluronate.

[0013] In a second aspect, the present invention provides an application of the above-mentioned long-acting whitening and non-darkening composition containing glabridin and pterostilbene, comprising the following steps:

[0014] (1) heating and mixing the inclusion shell raw materials, and then homogenizing at a pressure of 400-800 bar to obtain phase A; the inclusion shell raw materials include polyols, phospholipids, emulsifiers, oils and water;

[0015] (2) heating and dissolving glabridin, pterostilbene, and palmitoyl tripeptide-8 in a polyol to obtain phase B; dissolving Centella asiatica extract and sodium hyaluronate in water to obtain phase C;

[0016] (3) adding the phase A to the phase B and mixing, and then adding the phase C and mixing, to obtain an inclusion phase;

[0017] (4) Compounding the inclusion phase with a cosmetic base material into a cosmetic formula to achieve the application of the long-lasting whitening and anti-darkening composition containing glabridin and pterostilbene.

[0018] The application scheme of the composition provided by the present invention firstly improves the mildness of the product through the technology of forming an inclusion body, avoids the irritation or discomfort that may be caused by the high-concentration active substance contacting the skin in a large amount for a short time, and protects the health of the skin barrier; at the same time, the inclusion body can improve the permeability of the active ingredient, ensure the effective utilization rate, reduce the loss, and improve the overall whitening effect; because palmitoyl tripeptide-8 has strong lipophilicity, it can be embedded between the phospholipid bilayers of the inclusion body, and serve as a specific ligand for surface modification of the nanocarrier, so that the whitening composition is competitively bound to the melanocyte receptor MCR1, thereby anchoring on the melanocyte, and enriching around the melanocyte, increasing the local concentration, and making the active ingredients of the composition less likely to be lost due to skin metabolism; the inclusion body may also continue to exert its effect through sustained release, and after being compounded with the cosmetic base material, even after the formula is discontinued, the user's skin still has a certain level of active ingredients, which helps to continuously consolidate the whitening effect and prolong the darkening time.

[0019] It should be noted that the key to the implementation of the preparation process of the inclusion in the above application is to prepare a nano-scale inclusion composition with a signal peptide embedded on the surface, and the core components of the composition are still glabridin, pterostilbene, Centella asiatica extract, palmitoyl tripeptide-8 and sodium hyaluronate. Therefore, except for the defined core components, the preparation method of the inclusion is not limited to the above scheme, and those skilled in the art can adjust or replace it according to actual needs to prepare a nano-scale inclusion with a signal peptide embedded on the surface.

[0020] Preferably, in the step (1), based on 100 parts by weight, the inclusion shell raw material comprises the following components: 40-70 parts of polyol, 2-10 parts of phospholipids, 0.5-10 parts of co-emulsifier, 0.5-5 parts of oil, and the rest is water.

[0021] Preferably, in the step (3), the mass ratio of palmitoyl tripeptide-8 in phase B to phase A is (0.0005-0.005):(1-8).

[0022] Preferably, the heating temperature is 60-70° C., and the number of homogenization is 4-6 times.

[0023] Preferably, in step (3), the mixing is performed by stirring for 30-60 minutes.

[0024] Preferably, the polyol is at least one of glycerol, 1,3-butylene glycol, dipropylene glycol, sorbitol, 1,3-propylene glycol, and diglycerol.

[0025] Preferably, the phospholipid is at least one of hydrogenated lecithin, lecithin, phosphatidylcholine, soybean lecithin, and lysolecithin.

[0026] Preferably, the co-emulsifier is at least one of polyglyceryl-10 oleate, polyglyceryl-10 stearate, polyglyceryl-10 myristate, sodium stearoyl glutamate, oleth-20, potassium cetyl phosphate, and polyglyceryl-10 distearate.

[0027] Preferably, the oil is at least one of squalane, caprylic / capric triglyceride, C12-15 alcohol benzoate, polydimethylsiloxane, and olive oil.

[0028] Preferably, the cosmetic base comprises at least one of water, a preservative, a chelating agent and a polyol.

[0029] Further preferably, the preservative is at least one of p-hydroxyacetophenone, phenoxyethanol, sodium benzoate, caprylhydroxamic acid, caprylyl glycol, and glyceryl caprylate; the chelating agent is at least one of EDTA-2Na and EDTA-4Na; and the polyol is at least one of 1,3-butanediol, dipropylene glycol, 1,3-propanediol, sorbitol, hexylene glycol, and 1,2-pentanediol.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The present invention provides a long-acting whitening and non-darkening composition containing glabridin and pterostilbene, which integrates melanin regulation and skin barrier repair, by strictly selecting ingredients and scientifically proportioning, combined with scientific verification and other means; the composition can further prepare inclusions and inclusion sustained-release technology equipped with targeted transmission, anchor the effective components of the composition on melanocytes, enrich around melanocytes, increase local concentration, and continue to play a role with the aid of sustained-release technology, significantly enhance the whitening effect and prolong the time of returning to black. The long-acting whitening and non-darkening composition containing glabridin and pterostilbene provided by the present invention solves the industry pain point that whitening products are easy to return to black after use, has high application value, and promotes the sustainable development of the cosmetics industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a transmission electron microscope observation image of the inclusions in the application formulation of Example 2.

[0033] Figure 2 This is a transmission electron microscope observation image of the inclusions in the application formulation of Comparative Example 13.

[0034] Figure 3 This is the particle size intensity distribution diagram of the inclusions in the application formula of Example 2.

[0035] Figure 4 This is the particle size intensity distribution diagram of the inclusions in the application formula of Comparative Example 13. DETAILED DESCRIPTION

[0036] In order to better illustrate the purpose, technical scheme and advantages of the present invention, the present invention will be further described below in conjunction with specific examples. The test methods used in the following examples are conventional methods unless otherwise specified; the materials and reagents used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0037] Examples 1-5

[0038] Examples 1-5 are examples of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene of the present invention and its application, wherein the proportions of the components are shown in Table 1.

[0039] In Examples 1-5, the application of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene comprises the following steps:

[0040] (1) Preparing the composite inclusion shell: premixing all the inclusion shell raw materials, heating to 60-70° C., stirring and homogenizing to obtain colostrum, and then homogenizing 4-6 times at a pressure of 400-800 bar to obtain an inclusion shell phase A having a phospholipid bilayer structure; based on 100 parts by weight, the inclusion shell raw materials include the following components: 60 parts of 1,3-butylene glycol, 8 parts of lecithin, 4 parts of polyglycerol-10 oleate, 1 part of sodium stearoyl glutamate, 2 parts of squalane, and the rest is water;

[0041] (2) Heat the components of phase B to 60-70°C for pre-dissolution, then add the empty shells of phase A inclusions and stir evenly.

[0042] (3) Pre-dissolve the components of phase C, add them to the solution of step (2), and stir for 30-60 minutes to obtain an inclusion phase of the encapsulated composite.

[0043] (4) adding the inclusion phase of the composition obtained in step (3) into the essence base material and stirring evenly to obtain a cosmetic essence formula of the composition.

[0044] Table 1 Application formula of embodiment 1-5 long-acting whitening and non-darkening composition containing glabridin and pterostilbene

[0045]

[0046] Comparative Examples 1-7

[0047] The difference between Comparative Examples 1-7 and Example 2 is that the formula or application formula ratio of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene is changed, as shown in Table 2.

[0048] Table 2 Application formula of comparative examples 1-7 compositions

[0049]

[0050]

[0051] Comparative Examples 8-12

[0052] The difference between Comparative Examples 8-12 and Example 2 is that the pterostilbene, glabridin, palmitoyl tripeptide-8, Centella asiatica extract and sodium hyaluronate in the long-acting whitening and non-darkening composition containing glabridin and pterostilbene in Example 2 are replaced by other components having antioxidant, whitening, signal peptide, anti-inflammatory, soothing and moisturizing effects, as shown in Table 3.

[0053] Table 3 Application formula of the composition of comparative examples 8-12

[0054]

[0055] Comparative Example 13

[0056] The only difference between Comparative Example 13 and Example 2 is that the high-pressure homogenization step in the application step (1) of the composition is removed, and phase A is directly obtained by stirring and homogenizing.

[0057] The transmission electron microscopy observation results of the inclusions in the application formulas of Example 2 and Comparative Example 13 are as follows: Figure 1 , Figure 2 ; Example 2, Comparative Example 13 application formula inclusions in the particle size distribution results are as follows Figure 3 , 4 .Depend on Figure 1-4 It can be seen that the inclusions in the application formula prepared in Example 2 have a phospholipid bilayer structure with an average particle size of about 28.74 nm; the inclusions in the application formula prepared in Comparative Example 13 are multilayer vesicles with an average particle size of about 174.5 nm.

[0058] Effect Example 1

[0059] In order to explore the anti-inflammatory and soothing effect of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene of the present invention, the application formula prepared in the embodiment and the comparative example was used to detect its effect of down-regulating LPS-induced macrophage inflammation by ELISA method, and the specific steps are as follows:

[0060] Test method: The cells used in this test are macrophages (RAW264.7). Under the premise of meeting the cell safety concentration, a mass concentration of 0.1% is selected as the test concentration for all embodiments and comparative examples. The experiment set up a blank control group BC, a negative control group NC, a positive control group PC (dexamethasone) and a sample group. Each group has 3 replicates, and LPS stimulation is performed immediately after administration. The content of inflammatory factors TNF-α, IL-1β, and PGE2 was detected according to the operating instructions of the Mouse TNF-α ELISA kit, the operating instructions of the Mouse IL-1β ELISA kit, and the operating instructions of the Mouse PGE2 ELISA kit. In order to minimize the cytotoxicity of the sample, the "cosmetic base" part in the formula of the embodiment and comparative example was completely replaced with water during the cell test.

[0061] The anti-inflammatory and soothing test results of the application formula of the embodiment and the comparative example (the base material is replaced by water) are shown in Table 4. It can be seen from Table 4 that:

[0062] (1) The ELISA method was used to detect the effect of the application formula of the composition provided by the present invention on down-regulating TNF-α, IL-1β and PGE2. The composition formulas of Examples 1-5 and Comparative Examples 8, 12, and 13 all showed relatively better anti-inflammatory effects and could significantly down-regulate inflammatory factors; among them, the anti-inflammatory effects of Examples 1-2 and Comparative Example 13 were significantly better.

[0063] (2) The compositions of comparative examples 1-5 only retain a single component at a high concentration, and the content of each anti-inflammatory factor is relatively high, and the anti-inflammatory and soothing effect is significantly deteriorated; the dosage ratio of the composition components in comparative examples 6-7 is not appropriate and exceeds the specified range of the present invention. After the composition is treated with the application formula, the content of anti-inflammatory factors is relatively high and the anti-inflammatory and soothing effect is significantly deteriorated. This comprehensively shows that the composition ratio specified in the present invention has a synergistic effect of anti-inflammatory and soothing. Within the specified range of the formula, the effect of the combined effect is significantly better than the effect of a single high concentration of each component.

[0064] (3) In Comparative Examples 8-12, the pterostilbene, glabridin, palmitoyl tripeptide-8, Centella asiatica extract, and sodium hyaluronate in Example 2 were replaced with other antioxidants, whitening agents, signal peptides, anti-inflammatory soothing agents, and moisturizer components, respectively. Compared with Example 2, the anti-inflammatory and soothing effects of the composition formula were significantly worse. This shows that the composition components defined in the present invention also have a synergistic effect of anti-oxidation and soothing through interaction. If other similar functional ingredients are used for replacement, the same effect of downregulating inflammatory factors and anti-inflammatory and soothing cannot be achieved.

[0065] Table 4 The contents of three inflammatory factors in macrophages treated with the formulas of the embodiments and comparative examples

[0066]

[0067] Effect Example 2

[0068] In order to explore the melanin inhibition effect of the long-lasting whitening and non-darkening composition containing glabridin and pterostilbene of the present invention, a melanin formation inhibition experiment was carried out on the application formula prepared in the embodiment and the comparative example using a 3D reconstructed melanin-containing skin model, and the specific steps are as follows:

[0069] Test method: The model used in this test is a 3D reconstructed melanin-containing skin model. Under the premise of meeting the model safety concentration, each sample is set up in 2 groups, each group has 3 replicates, and from the day the model is received (Day 0), the negative control, positive control (kojic acid, 500ug / mL) and sample group are irradiated with UVB (50mJ / cm 2 ), the blank control group was not irradiated with UVB, and only the culture medium was replaced every day. The positive control group and the sample group were administered twice on Day 3 and Day 5, respectively, with the administration method being surface administration and the dosage being 2 mg / cm 2 The first group was cultured for 7 days and the whitening effect of the samples was evaluated by testing the melanin content of the model. The second group was cultured for 5 days after 7 days, during which only the culture medium was replaced without any other treatment. On the 13th day, samples were collected for testing. The melanin content of the model was tested and the test data of the first and second groups were compared to evaluate the darkening of the samples after stopping the medication.

[0070] Among them, inhibition rate (%) = [(negative control group NC-sample group) / negative control group NC] x 100%;

[0071] Concentration difference before and after drug withdrawal (pg / mL) = average concentration after drug withdrawal - average concentration before drug withdrawal;

[0072] The difference in inhibition rate before and after drug withdrawal (%) = inhibition rate after drug withdrawal - inhibition rate before drug withdrawal;

[0073] The statistical analysis table of the melanin content in the 3D reconstructed melanin-containing skin model of the melanin inhibition test results of the application formulas of the embodiments and comparative examples is shown in Table 5. It can be seen from Table 5 that:

[0074] (1) Before drug withdrawal, the melanin inhibition rates of Examples 1-5 and Comparative Examples 2, 7, and 13 were significantly improved compared with the negative control group, but after drug withdrawal, the rates of melanin reversion were differentiated. The order of melanin inhibition effects before drug withdrawal was: Example 3 > Example 4 > Example 2 > Comparative Example 2 > Example 1 > Example 5 > Comparative Example 7 > Comparative Example 13, but the order of melanin inhibition effects after drug withdrawal was: Example 2 > Example 1 > Example 3 > Example 4 > Comparative Example 2 > Example 5 > Comparative Example 13 > Comparative Example 7. Among them, the absolute value of the difference in inhibition rate before and after drug withdrawal was ranked as: Example 2 > Example 1 > Example 4 > Example 5 > Example 3 > Comparative Example 13 > Comparative Example 2 > Comparative Example 7. This is because the active components continue to exert their active effects with the help of the targeting, sustained-release and penetration-promoting technologies of the inclusion bodies. With the support of a specific composition and a specific proportion, the components' inflammation-suppressing, moisturizing, antioxidant, anti-aging and whitening effects complement each other, and can effectively delay the production of melanin after drug withdrawal, and even promote the degradation, differentiation or autophagy of some melanin, so that the melanin concentration continues to decrease; after drug withdrawal, the long-term effects under the ratios of Examples 1 and 2 are better.

[0075] (2) Comparing Example 2 and Comparative Example 13, although the components of the application formula are exactly the same, the particles formed in Comparative Example 13 are multilayer vesicle structures with significantly larger particle sizes. Due to the presence of the multilayer structure, the drug may be distributed between each layer, resulting in reduced loading efficiency. Although surface modification can also be performed, the modification is difficult due to the complex structure, and the uniformity is not as good as that of the bilayer inclusions, which will lead to reduced targeting. As shown in Table 5, the melanin inhibition performance of Comparative Example 13 before and after drug withdrawal is significantly worse than that of Example 2. It can be seen that the particle size, targeting, sustained release and penetration-promoting effects of the inclusion carrier formed in the application scheme of the present invention are also very important for the composition to play a role in extending the blackening time.

[0076] (3) Comparative Examples 1 and 3-6 have a low dosage of glabridin and lack specific components that work together. The whitening effects of the prepared whitening compositions before and after drug withdrawal are poor, and the values ​​are close to those of the NC group; Comparative Examples 2 and 7 have a certain whitening effect before drug withdrawal due to the addition of glabridin to the effective amount, but lack the interaction of the compound components or the dosage of the components is not within the scope of the present invention. The prepared whitening compositions can still play a role in suppressing melanin within a certain period of time after drug withdrawal, but the effect is slightly worse than that of the embodiment. It can be seen that the long-acting whitening and non-blackening composition containing glabridin and pterostilbene in a specific ratio provided by the present invention has a certain synergistic effect in suppressing the blackening effect and promoting melanin degradation, differentiation or autophagy.

[0077] (4) The melanin inhibition effect of comparative examples 8-12 before drug withdrawal is significantly worse than that of the embodiment; the whitening component glabridin of the present invention is replaced in comparative example 9, and the melanin inhibition effect before and after drug withdrawal is significantly worse; especially after drug withdrawal, obvious blackening is manifested. In comparative examples 8 and 10-12, the specific antioxidant, small molecule polypeptide, anti-inflammatory soothing agent, and moisturizing agent components of the present invention are replaced respectively. After drug withdrawal, the obtained composition can still play a continuous blackening effect within a certain period of time, but the melanin inhibition rate results before and after drug withdrawal are less than those of embodiments 1-5, and the concentration difference before and after drug withdrawal is a positive value, and its blackening inhibition effect and the effect of promoting melanin degradation, differentiation or autophagy are all worse than those of embodiments 1-5. It can be seen that the glabridin, pterostilbene, palmitoyl tripeptide-8, Centella asiatica extract and sodium hyaluronate in the composition selected by the present invention can work together in the composition to inhibit melanin and extend the blackening time effect, and are irreplaceable.

[0078] Table 5 Melanin inhibition test results of the formula used in the examples and comparative examples

[0079]

[0080]

[0081] Effect Example 3

[0082] In order to explore the clinical effect of the long-lasting whitening and non-darkening composition containing glabridin and pterostilbene of the present invention, according to the results in Effect Example 2, the application formulas of Example 2 and Comparative Example 7 were selected, and the ultraviolet-induced human skin melanization model was used for the experiment, and the specific steps were as follows:

[0083] The experiment set up a positive control group (7% ascorbic acid vitamin C), a negative control group, Example 2 group and Comparative Example 7 group, referring to the "First method for removing spots and whitening: ultraviolet induced human skin melanin model method", and recruited 33 qualified volunteers according to the requirements. Qualified subjects entered the stage of establishing the human skin melanin model. First, the minimum erythema dose (MED) of each subject's test site was determined, that is, the minimum dose of ultraviolet radiation required to reach most areas of the irradiation point to cause clearly visible erythema on the skin (Jm 2) or the shortest time (s). Then, after the test area is selected at the test site, a UV sunlight simulator is used to irradiate the same irradiation point once a day at a dose of 0.75 times the MED for 4 consecutive days; the 4 days after the irradiation are the skin melanization period, and no treatment is done. On the 5th day after the irradiation, the skin color of each test area is visually evaluated and instrumentally tested for skin color, and the test areas with poor consistency (areas where the difference between the ITA° value and the mean of all test areas is greater than 5) are eliminated. Starting from the same day, the corresponding test substances are applied to each melanization test area according to the random table. The coating area is 3×3cm, the interval between each test area is greater than 1.0cm, and the coating amount is 2.00±0.05mg / cm 2 , apply twice a day with an interval of not less than 4 hours between the two times, and apply the test substance continuously for 4 weeks.

[0084] Instrumental testing of skin color was performed 2 weeks and 4 weeks after application, and the results were recorded. After the 4th week of treatment, the samples were discontinued, and instrumental testing and visual evaluation of skin color were continued for 8 weeks, 16 weeks, and 32 weeks. The difference in skin color visual score, skin color ITA° difference, or MI difference at any time point before and after application of the test product was evaluated. The larger the absolute value of the difference, the more significant and lasting whitening and anti-freckle effect the sample has; or the difference at different time points was used for T-test analysis with the difference of the negative control at the same time point. The smaller the P value, the greater the significant difference, which proves that the sample has a more significant and lasting whitening and anti-freckle effect.

[0085] Where: ITA° difference = ITA° value at different times - ITA° value before use;

[0086] MI difference = MI value at different times - MI value before use;

[0087] Visual skin color grade difference = visual skin color grade value at different times - visual skin color grade value before use;

[0088] P value statistical method: The difference between "different time and before use" and "the difference between negative control and before use at the same node" were analyzed by T test.

[0089] The statistical analysis results of the ultraviolet-induced human skin melanization model at different time points before and after use of each test group are shown in Table 6. It can be seen from Table 6 that:

[0090] (1) In the skin melanization model, due to the self-repair mechanism of the skin, in the negative control group, in the absence of ultraviolet stimulation, the skin color will gradually and slowly return to a state close to that before modeling.

[0091] (2) In the positive control group and comparative example 7, the MI value (melanin index) decreased significantly and the ITA° value (skin chromaticity index) increased in the 4th week of sample use, indicating that the melanin content decreased and the skin color became lighter. After the samples were discontinued, at the 8th week, the skin color of the positive control group remained basically stable without obvious darkening. Due to the use of encapsulation technology, the comparative example 7 group had a certain targeting and sustained release effect, and the melanin content was also reduced, and the skin color became further lighter. However, in weeks 16-32, both groups experienced darkening, and it was impossible to achieve longer-term whitening without darkening.

[0092] (3) In the 4th week, the whitening indexes of the Example 2 group were better than those of the other groups, and a better whitening effect was achieved. In the 4th week of using the sample, the whitening effect of each index was better than that of the other groups. After stopping the use of the sample, the Example 2 group was still able to maintain a long-lasting whitening effect from week 8 to week 32. Although the whitening agent components used in the Example 2 ratio were significantly lower than those in the Comparative Example 7, the scientific ratio of each component in the Example 2 significantly prolonged the blackening time and achieved better long-lasting whitening.

[0093] This result further confirms that the long-acting whitening and anti-darkening composition containing glycyrrhizin and pterostilbene provided by the present invention and its application scheme have excellent long-acting whitening and anti-darkening capabilities. Under specific composition components and ratios and using appropriate application schemes, they can also exert excellent long-acting whitening effects in clinical trials and have high application value.

[0094] Table 6 Experimental results of ultraviolet-induced human skin melanization model

[0095]

[0096]

[0097] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A long-acting whitening and anti-darkening composition containing glabridin and pterostilbene, characterized in that: The invention comprises the following components in parts by weight: 0.005-0.1 parts of glabridin, 0.03-0.4 parts of pterostilbene, 0.02-0.2 parts of Centella asiatica extract, 0.0005-0.005 parts of palmitoyl tripeptide-8, and 0.01-0.1 parts of sodium hyaluronate.

2. The long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 1, characterized in that: The invention comprises the following components in parts by weight: 0.005-0.05 parts of glabridin, 0.03-0.1 parts of pterostilbene, 0.05-0.1 parts of Centella asiatica extract, 0.001-0.005 parts of palmitoyl tripeptide-8, and 0.02-0.05 parts of sodium hyaluronate.

3. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 1 or 2, characterized in that: The following steps are involved: (1) heating and mixing the inclusion shell raw materials, and then homogenizing at a pressure of 400-800 bar to obtain phase A; the inclusion shell raw materials include polyols, phospholipids, emulsifiers, oils and water; (2) heating and dissolving glabridin, pterostilbene, and palmitoyl tripeptide-8 in a polyol to obtain phase B; dissolving Centella asiatica extract and sodium hyaluronate in water to obtain phase C; (3) adding the phase A to the phase B and mixing, and then adding the phase C and mixing, to obtain an inclusion phase; (4) Compounding the inclusion phase with a cosmetic base material into a cosmetic formula to achieve the application of the long-lasting whitening and anti-darkening composition containing glabridin and pterostilbene.

4. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: In the step (1), based on 100 parts by weight, the inclusion shell raw material includes the following components: 40-70 parts of polyol, 2-10 parts of phospholipids, 0.5-10 parts of co-emulsifier, 0.5-5 parts of oil, and the rest is water.

5. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: In the step (3), the mass ratio of palmitoyl tripeptide-8 in phase B to phase A is (0.0005-0.005):(1-8).

6. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: The heating temperature is 60-70° C., and the homogenization is performed 4-6 times.

7. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: The polyol is at least one of glycerol, 1,3-butylene glycol, dipropylene glycol, sorbitol, 1,3-propylene glycol, and diglycerol.

8. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: The phospholipid is at least one of hydrogenated lecithin, lecithin, phosphatidylcholine, soybean lecithin and lysolecithin.

9. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: The auxiliary emulsifier is at least one of polyglyceryl-10 oleate, polyglyceryl-10 stearate, polyglyceryl-10 myristate, sodium stearoyl glutamate, oleth-20, potassium cetyl phosphate, and polyglyceryl-10 distearate.

10. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 3, characterized in that: The oil is at least one of squalane, caprylic / capric triglyceride, C12-15 alcohol benzoate, polydimethylsiloxane, and olive oil.

Images