Long-acting whitening and non-reverting black composition containing glabridin and pterostilbene and its application

Abstract

The present invention relates to a long-acting whitening and non-reverting black composition containing glabridin and pterostilbene and its application, belonging to the technical field of whitening cosmetics. The composition provided by the present invention comprises the following components in parts by weight: 0.005-0.1 part of glabridin, 0.03-0.4 part of pterostilbene, 0.02-0.2 part of Centella asiatica extract, 0.0005-0.005 part of palmitoyl tripeptide-8, and 0.01-0.1 part of sodium hyaluronate; the application of the composition provided by the present invention is as follows: (1) preparing a phase A containing inclusion vesicles; (2) dissolving glabridin, pterostilbene, and palmitoyl tripeptide-8 to obtain a phase B; dissolving Centella asiatica extract and sodium hyaluronate to obtain a phase C; (3) adding phase A and phase C to phase B and mixing evenly to obtain an inclusion phase; (4) compounding the inclusion phase with a cosmetic base material. The composition provided by the present invention combines melanin regulation and skin barrier repair, enhances the whitening effect and prolongs the time of reverting black through targeted delivery and inclusion vesicle sustained release, and has good application prospects in the whitening cosmetics industry.

Description

Technical Field

[0001] The present invention relates to the technical field of whitening cosmetics, and particularly to a long-acting whitening and non-reverting-to-dark composition containing glabridin and pterostilbene and its application. Background Art

[0002] Whitening products usually achieve whitening effects by inhibiting melanin synthesis, such as phenethyl resorcinol, arbutin, 4-butyl resorcinol, etc. After discontinuation, rapid re-darkening may occur. The main reasons are as follows: First, after discontinuation, melanocytes may overreact in a short time to produce excessive melanin, or after the inhibition of skin melanin synthesis, the production of melanin will increase to restore balance, resulting in re-darkening after discontinuation. Second, in seasons or regions with strong sunlight, the skin is not properly protected and is more vulnerable to ultraviolet damage, which stimulates melanin production and accelerates pigmentation, deepening the skin color. Third, potent whitening ingredients may damage the skin barrier. After discontinuation, the skin is more vulnerable to external stimulus damage, causing pigmentation, or leading to water loss. Dry skin is more likely to produce pigment deposition. Fourth, after discontinuation, the enzymes related to melanin regain their activity and melanin production increases. According to age differences, the normal skin metabolism cycle is about 21 - 40 days. After the discontinuation time exceeds the metabolism cycle, the production of melanin gradually returns to normal and the skin becomes dull again.

[0003] Regarding the phenomenon of rapid re-darkening after whitening, although the existing market has abandoned strong side-effect whitening ingredients such as hydroquinone, the current strong whitening ingredients still pose risks, especially for people with sensitive skin. For example, phenethyl resorcinol achieves whitening by inhibiting melanin synthesis, accompanied by damaged skin barrier. After discontinuation, melanocytes may "rebound" to cause excessive melanin production. In addition, the skin's resistance to the external environment decreases, making it vulnerable to ultraviolet rays and other stimuli, resulting in skin re-darkening. Niacinamide reduces pigmentation by inhibiting the transport of melanin. After discontinuation, a large amount of already-produced melanin quickly transfers to epidermal cells, showing the phenomenon of re-darkening. And delaying re-darkening through multi-pathway compounding often fails to achieve the effect due to imperfect compounding pathways or overly complex ingredients: only blocking or alleviating two or three of these pathways cannot completely solve the problem of melanin deposition. When discontinuing products with incomplete pathways, other melanin-promoting pathways are still active, which may lead to rapid skin stress re-darkening. Some products aim for all-round whitening and add sufficient ingredients to different pathways. High-concentration use or the superposition of multiple potent ingredients may cause skin adverse reactions, indirectly affecting the health of the skin barrier. Thus, the skin becomes significantly sensitive after discontinuing the product, accelerating skin re-darkening.

[0004] Therefore, developing a product and application strategy with mild action, not damaging the skin barrier, and capable of improving the long-acting whitening and non-reverting-to-dark effect can solve the industry pain point of easy re-darkening after whitening and promote the sustainable development of the cosmetics industry, with high application value. Summary of the Invention

[0005] The object of the present invention is to overcome the deficiencies of the prior art and provide a long-acting whitening and non-reverting blackening composition containing glabridin and pterostilbene and its application. The specific composition provided by the present invention forms an inclusion body, simultaneously realizes effects such as melanin regulation, soothing and anti-inflammatory, and skin barrier repair, can extend the time of reverting black, achieve long-acting whitening, and has high application value.

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

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

[0008] The present invention provides a composition with long-acting whitening and non-reverting blackening, and its components include glabridin, pterostilbene (also known as extract of Ormosia henryi Prain bark), Centella asiatica extract (the main components include asiaticoside), palmitoyl tripeptide-8, and sodium hyaluronate.

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

[0010] The present invention makes a scientific ratio according to the interaction of the above specific components and skin absorbability, improves the overall effect, and ensures that each component exerts its maximum efficacy; under a specific ratio, it can better combine multiple mechanisms, comprehensively solve the problem of pigment deposition, enable each component to play a synergistic effect, improve the persistence of the whitening effect, and significantly improve the problem of reverting black after stopping using the product. Each component plays a role in a specific ratio combination, and the effect is significantly better than that of each component acting alone; replacing any component with other components cannot achieve the best effect; changing the ratio between components significantly affects the anti-inflammatory and soothing, melanin inhibition, and reverting black extension effects of the composition.

[0011] The long-acting whitening and non-reverting black composition containing glabridin and pterostilbene provided by the present invention can be further formed into inclusion bodies and compounded for use in cosmetics, which can down-regulate macrophage inflammatory factors TNF-α, IL-1β and PGE2, and has excellent anti-inflammatory and soothing effects. At the same time, after medication and then stopping for a period of time, the inhibition rate of melanin is still relatively high. Clinically applied to the skin, it can significantly improve the whitening effect, achieve long-acting non-reverting black for at least 32 weeks, solve the industry pain point of easy black reversion after whitening, and has extremely high application value.

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

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

[0014] (1) Heat and mix the inclusion body shell raw materials, and then homogenize under a pressure of 400 - 800 bar to obtain phase A; the inclusion body shell raw materials include polyols, phospholipids, co-emulsifiers, oils and fats, and water;

[0015] (2) Heat and dissolve glabridin, pterostilbene, and palmitoyl tripeptide-8 in polyols to obtain phase B; dissolve centella asiatica extract and sodium hyaluronate in water to obtain phase C;

[0016] (3) Add phase A to phase B and mix well, and then continue to add phase C and mix well to obtain the inclusion body phase;

[0017] (4) Compound the inclusion body phase with a cosmetic base material to form a cosmetic formulation, thereby realizing the application of the long-acting whitening and non-reverting black composition containing glabridin and pterostilbene.

[0018] The application solution of the composition provided by the present invention first improves the mildness of the product through the technology of forming inclusion bodies, avoids the irritation or discomfort that may be caused by a large amount of high-concentration active substances contacting the skin in a short time, and protects the health of the skin barrier; at the same time, the inclusion bodies can improve the penetration rate of the active ingredients, ensure the effective utilization rate, reduce losses, and improve the overall whitening effect; due to the strong lipophilicity of palmitoyl tripeptide-8, it can be embedded between the phospholipid bilayers of the inclusion bodies and serve as a specific ligand for surface modification of the nanocarrier, so that the whitening composition binds to the melanocyte receptor MCR1 in a competitive manner, thereby anchoring on the melanocytes and enriching around the melanocytes, increasing the local concentration, and making the active ingredients of the composition not easily lost due to skin metabolism; the inclusion bodies may also continue to play a role through slow release. After being compounded with the cosmetic base material and used, even after the formula is discontinued, there is still a certain level of active ingredients in the user's skin, which helps to continuously consolidate the whitening effect and extend the time of skin darkening.

[0019] It should be noted that the key to the implementation of the preparation process of the inclusion bodies in the above application is to prepare a nanoscale inclusion body composition with a signal peptide embedded on the surface. 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 bodies is not limited to the above scheme, and those skilled in the art can adjust or equivalently replace according to actual needs to prepare a nanoscale inclusion body with a signal peptide embedded on the surface.

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

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

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

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

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

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

[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 alkyl benzoate, polydimethylsiloxane, and olive oil.

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

[0029] More preferably, the preservative is at least one of p-hydroxyacetophenone, phenoxyethanol, sodium benzoate, octanoyl hydroxamic 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 beneficial effects of the present invention are as follows:

[0031] Through strict selection of ingredients, scientific proportioning, and scientific verification, the present invention provides a long-acting whitening and non-reverting blackening composition containing glabridin and pterostilbene, which integrates melanin regulation and skin barrier repair; the composition can further anchor the active components of the composition on melanocytes and enrich them around melanocytes by preparing inclusion bodies with targeted delivery and inclusion body sustained-release technology, increase the local concentration, and continuously exert its effect with the assistance of the sustained-release technology, significantly enhancing the whitening effect and prolonging the time of reverting blackening. The long-acting whitening and non-reverting blackening composition containing glabridin and pterostilbene provided by the present invention solves the industry pain point of easy reverting blackening after using whitening products, has high application value, and promotes the sustainable development of the cosmetics industry. Description of the Drawings

[0032] Figure 1 It is a transmission electron microscope observation image of the inclusion body in the application formula of Example 2.

[0033] Figure 2 It is a transmission electron microscope observation image of the inclusion body in the application formula of Comparative Example 13.

[0034] Figure 3 It is a particle size light intensity distribution diagram of the inclusion body in the application formula of Example 2.

[0035] Figure 4 It is a particle size light intensity distribution diagram of the inclusion body in the application formula of Comparative Example 13. Detailed Description of the Embodiments

[0036] To better illustrate the purpose, technical solution and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. Unless otherwise specified, the test methods used in the following embodiments are all conventional methods; the materials, reagents, etc. used, unless otherwise specified, are reagents and materials that can be obtained from commercial channels.

[0037] Examples 1 - 5

[0038] Examples 1 - 5 are examples of the long - acting whitening and non - returning - black composition containing glabridin and pterostilbene of the present invention and its applications, and the ratios of each component are shown in Table 1.

[0039] In Examples 1 - 5, the applications of the long - acting whitening and non - returning - black composition containing glabridin and pterostilbene include the following steps:

[0040] (1) Preparation of the empty shell of the composition inclusion: Premix all the raw materials of the empty shell of the inclusion, heat to 60 - 70 °C, and obtain the primary emulsion through stirring and homogenization. Then, homogenize 4 - 6 times under a pressure of 400 - 800 bar to obtain the A - phase of the empty shell of the inclusion with a phospholipid bilayer structure; Calculated by 100 parts by weight, the raw materials of the empty shell of the inclusion include the following components: 60 parts of 1,3 - butanediol, 8 parts of lecithin, 4 parts of polyglyceryl - 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, and then add the A - phase empty shell of the inclusion and stir evenly.

[0042] (3) Pre - dissolve the components of phase C, add them to the solution obtained in step (2), and stir for 30 - 60 min to obtain the inclusion phase of the composition with good inclusion.

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

[0044] Table 1 Application formula of the long - acting whitening and non - returning - black composition containing glabridin and pterostilbene in Examples 1 - 5

[0045]

[0046] Comparative Examples 1 - 7

[0047] The differences between Comparative Examples 1 - 7 and Example 2 are that the formula of the long - acting whitening and non - returning - black composition containing glabridin and pterostilbene or the ratio of the application formula is changed, as shown in Table 2 specifically.

[0048] Table 2 Application formula of the composition in Comparative Examples 1 - 7

[0049]

[0050]

[0051] Comparative Examples 8 - 12

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

[0053] Table 3 Application formula of the composition of Comparative Examples 8 - 12

[0054]

[0055] Comparative Example 13

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

[0057] The transmission electron microscope observation results of the inclusions in the application formulas of Example 2 and Comparative Example 13 are respectively as Figure 1 , Figure 2 ; the particle size distribution results of the inclusions in the application formulas of Example 2 and Comparative Example 13 are respectively as Figure 3 , 4 . From Figures 1-4 it can be seen that the inclusions in the application formula prepared in Example 2 have a phospholipid bilayer structure, and the average particle size is about 28.74 nm; the inclusions in the application formula prepared in Comparative Example 13 are multi - layer vesicle structures, and the average particle size is about 174.5 nm.

[0058] Effect Example 1

[0059] To explore the anti - inflammatory and soothing effect of the long - acting whitening and non - blackening composition containing glabridin and pterostilbene of the present invention, the application formulas prepared in the examples and comparative examples were detected by ELISA method for their effect of down - regulating LPS - induced macrophage inflammation. The specific steps are as follows:

[0060] Test method: The cells used in this test were macrophages (RAW264.7). On the premise of meeting the safe cell concentration, a mass concentration of 0.1% was selected as the test concentration for all examples 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 had 3 replicate wells, and LPS stimulation was carried out immediately after drug administration. The detection of the contents of inflammatory factors TNF-α, IL-1β, and PGE2 was carried out according to the operation manuals of the Mouse TNF-α ELISA kit, the Mouse IL-1β ELISA kit, and the Mouse PGE2 ELISA kit respectively. In order to minimize the cytotoxicity of the sample to the greatest extent, the "cosmetic base material" part in the application formula of the examples and comparative examples was completely replaced with water during the cell experiment.

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

[0062] (1) Using the ELISA method to detect the effect of the application formula of the composition provided by the present invention in 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) In the compositions of Comparative Examples 1-5, only high-concentration single components were retained, and the contents of each anti-inflammatory factor were relatively high, and the anti-inflammatory and soothing effects were significantly worse; in Comparative Examples 6-7, the dosage ratios of the composition components were inappropriate and exceeded the defined range of the present invention. After treatment with the application formula of the composition, the contents of anti-inflammatory factors were relatively high and the anti-inflammatory and soothing effects were significantly worse. This comprehensively shows that: the composition ratio defined by the present invention has a synergistic effect of anti-inflammatory and soothing, and within the defined range of the formula, the combined effect is significantly better than the effect of each component at a single high concentration.

[0064] (3) In Comparative Examples 8-12, pterostilbene, glabridin, palmitoyl tripeptide-8, centella asiatica extract, and sodium hyaluronate in Example 2 were respectively replaced with other antioxidant, whitening agent, signal peptide, anti-inflammatory and soothing agent, and moisturizing agent components. Compared with Example 2, the anti-inflammatory and soothing effect of the composition formula was significantly worse. This shows that: through the interaction of the composition components defined by the present invention, there is also a synergistic effect of antioxidant and soothing. If other similar functional components are used for replacement, the same effect of down-regulating inflammatory factors and anti-inflammatory and soothing cannot be achieved.

[0065] Table 4 Contents of 3 inflammatory factors in macrophages treated with the application formula of the examples and comparative examples

[0066]

[0067] Effect Example 2

[0068] To investigate the melanin inhibition effect of the long-acting whitening and non-reverting black composition containing glabridin and pterostilbene of the present invention, the prepared application formulations in the examples and comparative examples were subjected to an inhibition experiment on melanin formation using a 3D reconstituted melanin-containing skin model. The specific steps are as follows:

[0069] Test method: The model used in this test is a 3D reconstituted melanin-containing skin model. On the premise of meeting the safe concentration of the model, 2 groups were set up for each sample, and 3 replicate wells were set in each group. Starting from the day when the model was received (Day0), the negative control, positive control (kojic acid, 500 μg / mL), and the sample group were irradiated with UVB every day (50 mJ / cm 2 ), and the blank control group was not irradiated with UVB, and only the culture medium was changed every day. The positive control group and the sample group were administered twice on Day 3 and Day 5 respectively. The administration method was topical administration, and the administration dose was 2 mg / cm 2 . After culturing for 7 days, the liquid was collected from the first group, and the whitening efficacy of the sample to be tested was evaluated by detecting the melanin content of the model. After culturing for 7 days in the second group, the culture was continued for 5 days. During this period, only the culture medium was changed, and no other treatments were performed. Sampling was carried out on the 13th day for testing. By detecting the melanin content of the model, the test data of the first and second groups were compared to evaluate the reversion of the sample after stopping the drug.

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

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

[0072] Inhibition rate difference before and after stopping the drug (%) = inhibition rate after stopping the drug - inhibition rate before stopping the drug;

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

[0074] (1) Before drug withdrawal, compared with the negative control group, the melanin inhibition rates of Examples 1-5 and Comparative Examples 2, 7, and 13 were significantly increased. However, after drug withdrawal, the rates of melanin recurrence showed differences. 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 after drug withdrawal, the order of melanin inhibition effects 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 rates 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 continuously exert their active effects by means of the targeting, sustained release, and penetration enhancement technologies of the inclusion bodies. With the addition of specific compositions and specific ratios, the anti-inflammatory, moisturizing, antioxidant, anti-aging, and whitening effects of the components complement each other, which can effectively delay the generation of melanin after drug withdrawal, and even promote the degradation, differentiation, or autophagy of some melanin, resulting in a continuous decrease in melanin concentration. After drug withdrawal, the long-term effects of the formulations of Examples 1 and 2 are better.

[0075] (2) Comparing Example 2 and Comparative Example 13, although the components of the applied formulations are exactly the same, the particles formed in Comparative Example 13 are of a multi-layer vesicle structure with significantly larger particle sizes. Due to the existence of the multi-layer structure, the drug may be distributed between each layer, resulting in a decrease in the loading efficiency. Although surface modification can also be carried out, due to the complex structure, the modification is difficult, and the uniformity is not as good as that of the bilayer inclusion body, which will lead to a decrease in targeting. As shown in Table 5, the performance of inhibiting melanin before and after drug withdrawal in Comparative Example 13 was significantly worse than that in Example 2. It can be seen that the particle size, targeting, sustained release, and penetration enhancement effects of the inclusion body carrier formed in the application scheme of the present invention are also very important for the composition to play a role in prolonging the melanin recurrence time.

[0076] (3) In Comparative Examples 1, 3-6, due to the low dosage of glabridin and the lack of specific components with co-action, the whitening effects of the prepared whitening compositions before and after drug withdrawal were poor, and the values were close to those of the NC group. In Comparative Examples 2 and 7, since glabridin was added to an effective amount, there was a certain whitening effect before drug withdrawal. However, due to the lack of interaction of the compound components or the component dosages not being within the scope defined in the present invention, the prepared whitening compositions could still play an anti-melanin role within a certain period of time after drug withdrawal, but the effects were slightly worse than those of the examples. Generally speaking, the long-acting whitening and non-melanin recurrence composition containing glabridin and pterostilbene with a specific ratio provided by the present invention has a certain synergistic effect in inhibiting melanin recurrence and promoting the degradation, differentiation, or autophagy of melanin.

[0077] (4) The melanin inhibition effect before drug withdrawal in Comparative Examples 8-12 was significantly worse than that in the Examples; in Comparative Example 9, glabridin, the whitening component of the present invention, was replaced, and the melanin inhibition effect before and after drug withdrawal became significantly worse; especially obvious signs of melanin rebound appeared after drug withdrawal. In Comparative Examples 8, 10-12, the specific antioxidant, small molecule polypeptide, anti-inflammatory and soothing agent, and moisturizing agent components of the present invention were replaced respectively. After drug withdrawal, the prepared composition could still play a continuous melanin inhibition role within a certain period of time, but the difference in the melanin inhibition rate before and after drug withdrawal was less than that in Examples 1-5, and the concentration difference before and after drug withdrawal was positive. Its effect of inhibiting melanin rebound and promoting melanin degradation, differentiation or autophagy was worse than that in Examples 1-5. It can be seen that glabridin, pterostilbene, palmitoyl tripeptide-8, centella asiatica extract and sodium hyaluronate in the composition selected by the present invention can play a synergistic role in the composition to achieve the effects of inhibiting melanin and prolonging the time of melanin rebound, and have irreplaceability.

[0078] Table 5 Results of melanin inhibition experiments of the application formulas of Examples and Comparative Examples

[0079]

[0080]

[0081] Effect Example 3

[0082] To explore the clinical effect of the long-acting whitening and non-melanin-rebound 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 a human skin melanization model induced by ultraviolet rays was used for the experiment. The specific steps are as follows:

[0083] A positive control group (7% ascorbic acid vitamin C), a negative control group, an Example 2 group and a Comparative Example 7 group were set up in the experiment. Referring to "The First Method for Freckle Removal and Whitening: The Method of Inducing Human Skin Melanization Model by Ultraviolet Rays", 33 eligible volunteer subjects were recruited into the combination according to the requirements. The eligible subjects entered the stage of establishing a human skin melanization model. First, determine the minimal erythema dose (MED) of the test site of each subject, that is, the lowest dose of ultraviolet irradiation (Jm required to cause clearly visible erythema on the skin, and its range reaches most of the irradiated area 2) or the shortest time (s). Then, after selecting the test area at the test site, use an ultraviolet sunlight simulator to irradiate once a day at the same irradiation point at a dose of 0.75 times the MED for 4 consecutive days; the 4 days after the irradiation end are the skin darkening period without any treatment. On the 5th day after the irradiation end, visually evaluate the skin color of each test area and detect it with a skin color instrument. Exclude the test areas with poor consistency (the areas where the ITA° value differs from the average value of all test areas by more than 5), and start applying the corresponding test substance to each darkening test area according to the random table on the same day. The smearing area is 3×3 cm, the interval between each test area is greater than 1.0 cm, and the smearing amount is 2.00±0.05 mg / cm 2 , apply it twice a day with an interval of no less than 4 hours between the two applications, and continuously apply the test substance for 4 weeks.

[0084] At 2 weeks and 4 weeks after the application, detect and record the skin color with an instrument. After the treatment at the 4th week ends, stop using the sample, and continuously detect the skin color with a skin color instrument and visually evaluate it. The detection periods are 8 weeks, 16 weeks, and 32 weeks. Evaluate the difference in visual skin color score, the difference in skin color ITA°, or the difference in MI at any time point before and after the application of the test product. The larger the absolute value of the difference, the more significant and lasting the whitening and freckle-removing effect of the sample is; or use the difference at different time nodes and the difference of the negative control at the same time point for T-test analysis. The smaller the P value, the greater the significant difference, which proves that the sample has a more significant and lasting whitening and freckle-removing effect.

[0085] Among them: 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: Analyze the "difference between different times and before use" and the "difference between the negative control and before use at the same node" by the T-test method.

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

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

[0091] (2) In the positive control group and Comparative Example 7, at the 4th week of sample use, the MI value (melanin index) decreased significantly, and the ITA° value (skin chromaticity index) increased, indicating a reduction in melanin content and a lighter skin color. After stopping the use of the sample, at the 8th week, the skin color of the positive control group remained basically stable without obvious darkening back. In the Comparative Example 7 group, due to the adoption of the encapsulation technology, which had a certain targeting and sustained-release effect, the melanin content also decreased and the skin color became lighter. However, at the 16th - 32nd week, both groups showed the phenomenon of darkening back, and a longer-lasting whitening effect without darkening back could not be achieved.

[0092] (3) In the Example 2 group at the 4th week, all the whitening indicators of this group were better than those of other groups, and a better whitening effect could be exerted. At the 4th week of using the sample, the whitening effect of each indicator was better than that of other groups. After stopping the use of the sample, from the 8th to the 32nd week, the Example 2 group could still continuously maintain a long-lasting whitening effect. Although the whitening agent component used in the formulation of Example 2 was significantly lower than that of Comparative Example 7, through the scientific formulation of each component in Example 2, the darkening-back time was significantly prolonged and a better long-lasting whitening effect was achieved instead.

[0093] This result further confirms that the long-lasting whitening and non-darkening-back composition containing glabridin and pterostilbene provided by the present invention and its application scheme have excellent long-lasting whitening and anti-darkening-back capabilities. Under specific composition components and ratios of the composition and by adopting a suitable application scheme, an excellent long-lasting whitening effect can also be exerted in clinical trials, and it has high application value.

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

[0095]

[0096]

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

Claims

1. A long-acting whitening and anti-darkening composition containing glabridin and pterostilbene, characterized in that: It includes an inclusion body consisting of an inclusion body shell and an active ingredient; The active ingredient 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; Based on 100 parts by weight, the raw materials for preparing the empty shell of the inclusion body include the following components: 40-70 parts of polyol, 2-10 parts of phospholipids, 0.5-10 parts of auxiliary emulsifiers, 0.5-5 parts of oils and fats, and the rest is water.

2. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 1, characterized in that: The following steps are involved: (1) The inclusion shell raw materials are heated and mixed, and then homogenized at a pressure of 400-800 bar to obtain phase A; (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.

3. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 2, 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).

4. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 2, characterized in that: The heating temperature is 60-70° C., and the homogenization is performed 4-6 times.

5. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 2, characterized in that: The polyol is at least one of glycerol, 1,3-butylene glycol, dipropylene glycol, sorbitol, 1,3-propylene glycol, and diglycerol.

6. The use of the long-acting whitening and non-darkening composition containing glabridin and pterostilbene as claimed in claim 2, characterized in that: The phospholipid is at least one of hydrogenated lecithin, lecithin, phosphatidylcholine, soybean lecithin and lysolecithin.

7. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 2, 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.

8. The use of the long-acting whitening and anti-darkening composition containing glabridin and pterostilbene as claimed in claim 2, characterized in that: The oil is at least one of squalane, caprylic / capric triglyceride, C12-15 alcohol benzoate, polydimethylsiloxane, and olive oil.

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