Glabridin whitening oil agent with high solubility and high stability and preparation method thereof

Abstract

The invention provides high-solubility and high-stability glabridin whitening oil as well as a preparation method and application thereof, and belongs to the technical field of cosmetics. By introducing the specific natural glycolipid, the solubility and long-term stability of glabridin in various common oils and fats can be remarkably improved, and a uniform oil phase system which is clear and transparent in appearance and light in texture is formed. The composition avoids turbid feeling, sticky skin feeling and safety worries caused by traditional chemical solubilizers or emulsifiers, conforms to the development trend of natural, safe and efficient cosmetics, and provides a core solution for developing high-quality and transparent-appearance skin-nourishing-with-oil whitening effect products. The requirements of the market on high-end skin care oil with excellent efficacy and pleasant sensory experience are met.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a highly soluble and highly stable glycyrrhizin whitening oil and its preparation method. Background Technology

[0002] Glycyrrhizin is a natural flavonoid compound extracted from licorice root. It is widely considered a highly effective skin-brightening active ingredient due to its potent inhibitory effect on tyrosinase, a key enzyme in skin melanin production, and has attracted considerable attention in the cosmetics industry. With the popularization of the "oil-based skincare" concept, oil-based skincare products are increasingly favored due to their good skin affinity, repairing properties, and potential for delivering lipid-soluble active ingredients. However, many highly effective skin-brightening active ingredients, including glycyrrhizin, have extremely low solubility in common oil solvents due to their inherent molecular structure, which severely limits their application in transparent, anhydrous oil-based products.

[0003] Currently, the conventional methods used in the cosmetics industry to improve the dispersion of poorly soluble ingredients in the oil phase mainly include using chemically synthesized solubilizers or forming emulsion systems through emulsification. While using synthetic solubilizers can improve solubility to some extent, it may introduce ingredients that are not skin-friendly, and excessive use can affect the natural claims and skin feel of the formula. On the other hand, emulsion systems will make the product appear opaque and milky white, losing the clear texture that oil products should have, and the system is relatively complex, posing more challenges to stability.

[0004] Therefore, the market urgently needs a new technology that can effectively and stably integrate highly effective but poorly soluble whitening ingredients such as glycyrrhizin into an oil-phase carrier without sacrificing transparency, safety, and skin feel. Summary of the Invention

[0005] The purpose of this invention is to provide a highly soluble and highly stable glycyrrhizin whitening oil and its preparation method, which solves the technical problem that the highly active whitening ingredient glycyrrhizin has poor solubility in the oil phase system, is easy to precipitate, leading to unstable formulations and difficulty in applying it to transparent oil-based cosmetics.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides the application of mannose erythritol ester in improving the solubility of glycyrrhizin in oils.

[0007] The present invention also provides a licorice root-adjusting solvent, wherein the licorice root-adjusting solvent contains mannose erythritol ester.

[0008] The present invention also provides a glycyrrhizin oil composition, comprising, by weight: 80-120 parts of oil, 0.01-20 parts of glycyrrhizin, and 0.5-20 parts of the above glycyrrhizin solubilizer.

[0009] Preferably, the oil is selected from one or more of caprylic / capric triglycerides, squalane, jojoba oil, and almond oil.

[0010] Preferably, the oil is caprylic / capric triglyceride.

[0011] Preferably, the composition further includes other skin-whitening active ingredients other than glycyrrhizin.

[0012] Preferably, the other whitening active ingredients include at least one of pterostilbene, undecylenoyl phenylalanine, arbutin, phenylethyl resorcinol, or plant extracts with whitening activity.

[0013] The present invention also provides a method for preparing the above-mentioned glycyrrhizin oil-preparing composition, characterized by comprising the following steps: premixing glycyrrhizin with a solubilizer and a portion of oil to form a mixed carrier, heating and stirring the mixed carrier, and then adding the remaining oil and mixing to obtain the glycyrrhizin oil-preparing composition; Alternatively, glycyrrhizin, solubilizer, other whitening active ingredients other than glycyrrhizin, and a portion of oil are premixed to form a mixture. The mixture is then heated and stirred, and the remaining oil is added and mixed to obtain a glycyrrhizin oil composition.

[0014] Preferably, the temperature of the heating and stirring treatment is 70°C to 90°C; And / or, the heating and stirring treatment lasts for 20 to 40 minutes; And / or, the weight of the portion of grease accounts for 5% to 30% of the total weight of grease.

[0015] The present invention also provides an oil-based cosmetic, characterized in that it comprises a glycyrrhiza oil-fixing composition as described in any one of claims 3 to 7 or a glycyrrhiza oil-fixing composition prepared by the preparation method described in claim 8 or 9.

[0016] The beneficial effects of this invention are: This invention, by introducing specific natural glycolipids, significantly enhances the solubility and long-term stability of glycyrrhizin in various common oils, forming a clear, transparent, and lightweight homogeneous oil phase system. This composition avoids the turbidity, stickiness, and safety concerns associated with traditional chemical solubilizers or emulsifiers, aligning with the trend towards natural, safe, and effective cosmetics. It provides a core solution for developing high-quality, transparent "oil-based skincare" whitening products, meeting the market demand for high-end skincare oils that combine superior efficacy with a pleasant sensory experience. Attached Figure Description

[0017] Figure 1 Comparison images of the appearance of different samples; Figure 2 Particle size distribution curve of glycyrrhiza oil solution; Figure 3 Microscopic images of nano-dispersions in a solution of glycyrrhizin oil; Figure 4 This is a comparison of the inhibitory effects of different samples on melanin production in B16 cells. Detailed Implementation

[0018] This invention provides the application of mannose erythritol ester in improving the solubility of glycyrrhizin in oils.

[0019] In this invention, mannosylerythritol lipid (MEL) is a naturally derived surfactant prepared through microbial fermentation. It is commonly found in the metabolites of fungi such as Candida and Ustilago maydis, exhibiting excellent biocompatibility, low toxicity, and environmental friendliness, aligning with the green development trend of cosmetic raw materials. In the application of this invention, mannosylerythritol lipid can significantly improve the solubility and dispersion stability of glycyrrhizin in oils, thereby preventing its crystallization in the system and maintaining the transparency and homogeneity of the system.

[0020] The present invention also provides a licorice root-adjusting solvent, wherein the licorice root-adjusting solvent contains mannose erythritol ester.

[0021] The solubilizer for glycyrrhizin refers to a substance or composition that can effectively improve the solubility of glycyrrhizin in the oil phase. In this invention, the solubilizer uses mannose-erythritol ester as the main functional component and can be used alone or in combination with other auxiliary solubilizing components, such as other types of glycolipids (e.g., sophorolipids, rhamnolipids, etc.), nonionic surfactants (e.g., polyglycerol esters, sucrose esters, etc.), or natural emulsifiers (e.g., lecithin, cholesterol, etc.). This solubilizer acts as a molecular bridge in the system, promoting the uniform dispersion and stable existence of glycyrrhizin in the oil phase through specific adjustments.

[0022] The present invention also provides a glycyrrhizin oil-based composition, comprising, by weight: 80-120 parts of oil, 0.01-20 parts of glycyrrhizin, and 0.5-20 parts of the above-mentioned glycyrrhizin solubilizer. More preferably, the oil comprises 85-105 parts by weight, the glycyrrhizin comprises 0.05-15 parts by weight, and the glycyrrhizin solubilizer comprises 1-18 parts by weight. Most preferably, the oil comprises 80-99 parts by weight, the glycyrrhizin comprises 0.1-10 parts by weight, and the glycyrrhizin solubilizer comprises 0.5-15 parts by weight.

[0023] The described glycyrrhizin oil composition is a functional cosmetic raw material or semi-finished product with an oil phase as the base carrier, suitable for preparing various oil-based skin care products. The oil, as the base phase of the system, provides moisturizing, occlusive, and carrier functions; glycyrrhizin, as the core whitening active ingredient, inhibits tyrosinase activity and reduces melanin production; the solubilizer ensures the high solubility of glycyrrhizin in the oil and the stability of the system.

[0024] Preferably, the oil is selected from one or more of caprylic / capric triglyceride, squalane, jojoba oil, and almond oil. Oils are commonly used in cosmetics to provide lubrication, moisturization, and carrier functions. Caprylic / capric triglyceride (GTCC) is a common synthetic ester oil with a refreshing, non-greasy feel, good spreadability, and stability. Squalane is a natural hydrocarbon oil similar to human sebum, possessing excellent affinity, moisturizing properties, and stability. Jojoba oil is a plant-derived liquid wax ester with good permeability, antioxidant properties, and skin-softening effects. Sweet almond oil is rich in unsaturated fatty acids and vitamins, providing moisturizing, soothing, and skin-improving effects. These oils can be used individually or in combination, depending on factors such as product feel, cost, and source.

[0025] Preferably, the oil is caprylic / capric triglyceride. Caprylic / capric triglyceride is widely used in cosmetics. It is colorless, odorless, low viscosity, easy to spread, and has good compatibility with a variety of active ingredients, making it suitable as a carrier oil for light oil-based products such as essential oils and skin care oils.

[0026] Preferably, the composition further includes other whitening active ingredients other than glycyrrhizin. To enhance the whitening effect or achieve multiple skincare benefits, other whitening active ingredients may also be added to the composition of the present invention. These ingredients may include, but are not limited to: pterostilbene (with antioxidant and melanin-inhibiting effects), undecylenoyl phenylalanine (which blocks melanocyte activation signals), arbutin (which inhibits tyrosinase activity), phenylethyl resorcinol (a potent tyrosinase inhibitor), and plant extracts with whitening activity (such as licorice extract, mulberry bark extract, and scutellaria baicalensis extract). These ingredients may be added alone or in combination to synergistically enhance the whitening and spot-fading effects.

[0027] The present invention also provides a method for preparing the above-mentioned glycyrrhizin oil composition, characterized by comprising the following steps: premixing glycyrrhizin with a solubilizer and a portion of oil to form a mixed carrier; heating and stirring the mixed carrier; then adding the remaining oil and mixing to obtain the glycyrrhizin oil composition; or premixing glycyrrhizin, a solubilizer, other whitening active ingredients (excluding glycyrrhizin), and a portion of oil to form a mixture; heating and stirring the mixture; then adding the remaining oil and mixing to obtain the glycyrrhizin oil composition. Preferably, the heating and stirring temperature is 70°C to 90°C; and / or the heating and stirring time is 20 minutes to 40 minutes; and / or the weight of the portion of oil accounts for 5% to 30% of the total weight of the oil.

[0028] The present invention also provides an oil-based cosmetic, characterized in that it comprises the above-described licorice oil-fixing composition or the licorice oil-fixing composition prepared by the above preparation method.

[0029] Oil-based cosmetics refer to cosmetic formulations that use oils as the main matrix or carrier. Common formulations include essential oils, skin care oils, massage oils, bath oils, makeup remover oils, ointments, and creams. These products typically possess excellent moisturizing, occlusive, skin-friendly, and active ingredient delivery capabilities, making them suitable for dry skin, sensitive skin, or consumers who prefer an "oil-based skincare" approach. In addition to active ingredients, oil-based cosmetics can also contain various excipients, such as antioxidants (e.g., vitamin E, BHT), fragrances, pigments, preservatives (e.g., phenoxyethanol, p-hydroxyacetophenone), plant essential oils (e.g., rosehip oil, tea tree oil), and fat-soluble sunscreens (e.g., ethylhexyl methoxycinnamate), to meet the product's stability, sensory characteristics, and functional requirements. The licorice root oil-fixing composition of this invention can be directly used as an active ingredient in the formulation of the aforementioned oil-based cosmetics, imparting highly effective whitening, skin-tone evening, and skin-brightening skincare benefits.

[0030] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0031] Example 1 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder is premixed with 10 parts by weight of glycolipid and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0032] Example 2 A method for preparing a 5% glycyrrhiza oil solution includes the following steps: (1) 5 parts by weight of glycyrrhizin powder, 10 parts by weight of glycolipid and 10 parts by weight of GTCC (caprylic / capric triglyceride) are premixed to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0033] Example 3 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder is premixed with 10 parts by weight of glycolipid and 10 parts by weight of squalane to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, make up to 100 parts by weight with squalane and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0034] Example 4 A method for preparing a 2% whitening combination oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder, 0.5 parts by weight of pterostilbene and 0.5 parts by weight of undecenoyl phenylpropionate powder are premixed with 10 parts by weight of glycolipid and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0035] Example 5 This embodiment provides the application of the glycyrrhiza oil solution from Example 1 in essential oil, and the glycyrrhiza oil solution from Example 1 is used to prepare essential oil.

[0036] Comparative Example 1 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder was premixed with 20 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0037] Comparative Example 2 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder is premixed with 10 parts by weight of polyglycerol-3-isostearate and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0038] Comparative Example 3 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder was premixed with 10 parts by weight of PEG-8 and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0039] Comparative Example 4 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder was premixed with 10 parts by weight of PEG-40 and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0040] Comparative Example 5 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder is premixed with 10 parts by weight of polyglycerol-4 oleate and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0041] Comparative Example 6 A method for preparing a 1% glycyrrhiza oil solution includes the following steps: (1) 1 part by weight of glycyrrhizin powder is premixed with 10 parts by weight of sophorolipid and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the glycyrrhiza oil solution.

[0042] Comparative Example 7 A method for preparing a 1% nicotinamide oil solution includes the following steps: (1) 1 part by weight of nicotinamide powder is premixed with 10 parts by weight of sophorolipid and 10 parts by weight of GTCC (caprylic / capric triglyceride) to form a mixed carrier; (2) Heat the mixture obtained in step (1) in a water bath at 80°C and stir continuously for 30 minutes. After taking it out, use GTCC to make up to 100 parts by weight, and stir until the system is uniform. Cool to obtain the nicotinamide oil solution.

[0043] Experimental Example The products prepared in Examples 1-5 and Comparative Examples 1-7 were compared in appearance, and the results are as follows: Figure 1 As shown in Table 1: Table 1. Appearance Comparison Results

[0044] Stability test Examples 1-4 and Example 5 were stored at 4°C, room temperature, and 40°C for 30 days, respectively. The results of their appearance stability are shown in Table 2. Table 2 Stability Results

[0045] Particle size analysis 0.1 g of the 1% glycyrrhiza oil solution prepared in Example 1 was placed in a 50 ml colorimetric tube, diluted with an appropriate amount of water, and measured using a ZetaView nanoparticle tracking analyzer. The instrument parameters were set as follows: laser wavelength 85 nm, temperature 26.22 °C, frame rate 30 fps, and 11 locations were measured for each sample. The particle size distribution and concentration were calculated by tracking the Brownian motion of the particles. The results are shown in Table 3. Table 3. Particle size analysis results

[0046] Figure 2 This is the particle size distribution curve.

[0047] Figure 3 The images show microscopic observations of the nanoparticle size. Test results indicate that the 1% glycyrrhizin oil solution prepared in this invention forms a uniform and stable nano-dispersion of glycyrrhizin in the oil phase. The average particle size of the system is approximately 148.5 nm, with a concentrated particle size distribution (Span = 1.4). This nano-dispersion effectively ensures the transparency and long-term physical stability of the components, and provides a structural basis for the efficient delivery and improved bioavailability of the active ingredients.

[0048] MTT assay for cytotoxicity 1) Press 1×10 4 Cells were seeded at a density of cells / well into 96-well plates and incubated overnight in an incubator (37°C, 5% CO2).

[0049] 2) Experimental Groups: The experiment included a zeroing group, a control group, a positive control group, and a sample group. In the sample group, each sample had 8 concentration gradients, and each concentration gradient had 3 replicate wells.

[0050] 3) Solution preparation: Prepare test samples at different concentrations using basal culture medium. 4) Drug administration: Drug administration was performed when the cell seeding rate in the 96-well plate reached 40%–60%. For the control group, 200 μL of culture medium containing 10% PBS was added to each well; for the positive control group, 200 μL of culture medium containing 10% DMSO was added to each well; for the sample group, 200 μL of culture medium containing the corresponding concentration of the sample was added to each well; for the zeroing group, no cells were seeded, only 200 μL of cell culture medium was added. After drug administration, the 96-well plate was placed in an incubator (37℃, 5% CO2) for incubation.

[0051] 5) Detection: After culturing cells for 24 hours, discard the supernatant, add MTT working solution (0.5 mg / mL), and incubate at 37°C in the dark for 4 hours. After incubation, discard the supernatant, add 100 µL LDMSO to each well, and read the OD value at 490 nm.

[0052] 6) Cell viability calculation: Calculated according to the formula. Cell viability = (sample well OD - zeroing well OD) / (solvent control well OD - zeroing well OD) * 100% The results are shown in Table 4.

[0053] Table 4. Cell viability test results

[0054] Test on the effect of B16 cell melanin production 1) Collect cells in the logarithmic growth phase, at a cell density of 2 × 10⁻⁶. 5 Cells were seeded per well into 24-well plates and cultured in an incubator (37°C, 5% CO2) for 24 h. Based on the cytotoxicity results, the test sample was added, kojic acid (3 mg / mL) was used as a positive control, and untreated cells were used as a blank control. Three replicates were set up for each group.

[0055] 2) After adding the sample, continue culturing in an incubator (37℃, 5% CO2) for 24 h, discard the supernatant, add 0.5 mL of 1 M NaOH containing 10% DMSO, and incubate in an 80℃ constant temperature oven for 1 h. After returning to room temperature, transfer 200 μL to each well of a 96-well plate, using 1 M NaOH containing 10% DMSO as a blank well, and read the absorbance value at 405 nm. Calculate the relative inhibition rate of melanin in cells according to the following formula.

[0056] Cellular melanin inhibition rate % = (1 - (sample well OD - blank well OD) / (solvent control well OD - blank well OD)) * 100% The results are shown in Table 5 and Figure 4 As shown: Table 5 Results of melanin inhibition in cells

[0057] As can be seen from the above embodiments, the present invention provides a clear, transparent, and long-term stable glycyrrhizin-based composition. This composition maintains a uniform and transparent state without precipitation over a wide temperature range. Glycyrrhizin is uniformly dispersed in the oil phase at the nanoscale. In vitro cell experiments show that this composition has good cell compatibility at the tested concentration and can effectively inhibit melanin production in melanocytes, confirming its potential efficacy in skin whitening products.

[0058] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Mannose erythritol ester is used to improve the solubility of glycyrrhizin in oils.

2. A solvent for increasing the concentration of glycyrrhiza uralensis, characterized in that, The licorice root extract contains mannose erythritol ester.

3. A composition for fixing the oil content of glycyrrhiza uralensis, characterized in that, The product comprises, by weight: 80-120 parts of oil, 0.01-20 parts of glycyrrhizin, and 0.5-20 parts of the solubilizer as described in claim 2.

4. The licorice oil-fixing composition according to claim 3, characterized in that, The oil is selected from one or more of caprylic / capric triglycerides, squalane, jojoba oil, and almond oil.

5. The licorice oil-fixing composition according to claim 4, characterized in that, The oil is caprylic / capric triglyceride.

6. The licorice oil-fixing composition according to claim 3, characterized in that, The composition also includes other skin-whitening active ingredients other than glycyrrhizin.

7. The licorice oil-fixing composition according to claim 6, characterized in that, The other whitening active ingredients include at least one of pterostilbene, undecenoyl phenylalanine, arbutin, phenylethyl resorcinol, or plant extracts with whitening activity.

8. The method for preparing the glycyrrhiza oil-fixing composition according to any one of claims 3 to 7, characterized in that, Includes the following steps: Glycyrrhizin, a solubilizer, and a portion of oil are premixed to form a mixed carrier. The mixed carrier is then heated and stirred. The remaining oil is added and mixed to obtain a glycyrrhizin oil formulation. Alternatively, glycyrrhizin, solubilizer, other whitening active ingredients other than glycyrrhizin, and a portion of oil are premixed to form a mixture. The mixture is then heated and stirred, and the remaining oil is added and mixed to obtain a glycyrrhizin oil composition.

9. The method according to claim 8, characterized in that, The temperature for the heating and stirring process is 70°C to 90°C. And / or, the heating and stirring treatment lasts for 20 to 40 minutes; And / or, the weight of the portion of grease accounts for 5% to 30% of the total weight of grease.

10. An oil-based cosmetic, characterized in that, The composition comprising the glycyrrhiza oil-fixing agent composition as described in any one of claims 3 to 7, or the glycyrrhiza oil-fixing agent composition prepared by the preparation method described in claim 8 or 9.

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