Composition with whitening and moisturizing effects as well as preparation method and application thereof

Abstract

The invention provides a composition with whitening and moisturizing effects. The composition is prepared from the following raw materials in parts by weight: 1 to 3 parts of myrcene, 80 to 90 parts of D-limonene, 6 to 14 parts of gamma-terpinene and 1 to 3 parts of methyl 2-methylaminobenzoate. The invention also provides a preparation method and application of the composition. The composition disclosed by the invention has remarkable whitening and moisturizing effects, and the components also have a remarkable synergistic interaction effect. The composition breaks through the efficacy bottleneck of a traditional single component or simple compounding, achieves remarkable and balanced whitening and moisturizing dual effects at a lower concentration, and also has good biocompatibility, mildness and formula friendliness. The invention provides important technical support for developing a new generation of efficient, safe and multi-effect medicinal and cosmetic functional raw materials, and has remarkable market competitiveness and application prospect.

Description

Technical Field

[0001] The invention relates to a composition with whitening and moisturizing effects. Background Art

[0002] In the field of functional cosmetic ingredients, whitening and moisturizing remain core consumer concerns and drive continuous technological innovation. Despite the diverse range of mainstream active ingredients currently available, the market still faces numerous challenges, including efficacy bottlenecks: single whitening ingredients (such as arbutin, vitamin C derivatives, niacinamide, and certain peptides) often act on a single target, making it difficult to fully address the complex pathways of melanin production, transport, and metabolism. While moisturizing ingredients (such as hyaluronic acid, glycerin, and ceramides) can increase stratum corneum water content, their synergistic effects for deep, long-lasting moisturization and improving the skin's barrier function are often insufficient. Lack of synergy: Simple physical compounding of multiple active ingredients is a common strategy, but without a deep understanding of the biochemical interactions between ingredients and optimal design, true synergy is difficult to achieve and may even be compromised due to antagonism or stability issues. Safety and tolerability: Some highly effective whitening ingredients (such as high-concentration hydroquinone and certain potent acids) pose potential skin irritation, photosensitivity, or long-term safety concerns. Developing solutions that combine high efficacy with gentleness is an urgent industry need. Consumers' pursuit of "natural" and "multi-functional": The market increasingly favors ingredients derived from nature or with high biocompatibility, while demand for formulas with multiple functions (such as whitening + moisturizing + antioxidant) is surging.

[0003] It is a hotspot to find whitening and moisturizing ingredients from natural plants in the field of cosmetics and external use of drugs. For example, Xiao Xinsheng, et al. Comparative Study on the Composition, Antioxidant and Antibacterial Activity of Essential Oils from Different Varieties of Pomelo Peel, Natural Product Research and Development, 2024, 36:218-226, 2, in which 35 chemical components such as D-limonene, β-myrcene, α-pinene, α-phellandrene, linalool, etc. are identified in essential oils from different varieties of pomelo peel. DPPH free radical scavenging experiment shows that the antioxidant capacity of pomelo peel essential oil is positively correlated with the concentration of essential oil. The analysis results show that the components with significant antioxidant and antibacterial effects are D-limonene, citral, linalool, and caryophyllene, myrcenol, and α-phellandrene also have certain antioxidant and antibacterial capacity. Usually, the amount of components contained in plants is small, and most of them are studied as index components. CN202410185315.1, Invention Name: A Compound Essential Oil for Improving Skin Color and Its Preparation Method, discloses a compound essential oil for improving skin color and darkness, which comprises the following components: oleic acid, linoleic acid, palmitic acid, stearic acid, limonene, α-pinene, linalool, palmitoleic acid, eicosanoic acid, squalene, α-copaene, cis-11-eicosenoic acid, β-pinene, trans-caryophyllene, 3-thujaene, camphene, docosanoic acid, myristic acid, p-cymene, (+)-δ-cadinene, menthol, linolenic acid, octanoic acid, menthone, decanoic acid, sabinene, myrcene. The compound essential oil of the invention has excellent skin whitening, brightening and moisturizing effects. The document discloses a complex formula raw material, and the active ingredients are not clear. SUMMARY

[0004] The present application provides a composition with whitening and moisturizing effects.

[0005] The present application provides a composition with whitening and moisturizing effects, which is composed of the following raw materials in the following weight ratio:

[0006] Myrcene 1-3 parts, D-limonene 80-90 parts, γ-terpinene 6-14 parts, and methyl 2-methylaminobenzoate 1-3 parts.

[0007] Preferably, it is composed of the following raw materials in the following weight ratio:

[0008] Myrcene 3 parts, D-limonene 85 parts, γ-terpinene 10 parts, and methyl 2-methylaminobenzoate 2 parts.

[0009] The composition of the present application is prepared by adding pharmaceutically or cosmetically acceptable excipients or auxiliary ingredients to the active ingredients.

[0010] The external preparation is a solution, emulsion, cream, gel, ointment, patch, film, and aerosol.

[0011] The present invention also provides a method for preparing the composition having whitening and moisturizing effects, which comprises the following steps:

[0012] a. Weigh the raw materials of each weight ratio;

[0013] b. Mix well, and add excipients or auxiliary ingredients commonly used in pharmacy or cosmetics to prepare an external preparation commonly used in the field of pharmacy or cosmetics.

[0014] The present invention also provides use of the composition in preparing medicines or cosmetics with whitening effects.

[0015] The present invention also provides use of the composition in preparing medicines or cosmetics with moisturizing effects.

[0016] The present invention also provides a cosmetic additive containing the composition.

[0017] This invention develops an innovative combination of specific plant-derived small molecule compounds. This composition consists of four compounds: myrcene, D-limonene, γ-terpinene, and dimethyl anthranilate (DMA), formulated in a specific ratio. Myrcene has excellent skin penetration-enhancing properties, effectively carrying other active ingredients deep into their target sites. Studies have shown that it can modulate signaling pathways related to the skin barrier and inflammation, such as NF-κB, indirectly improving uneven skin tone and the skin microenvironment. Both D-limonene and γ-terpinene, as monoterpenes, have been shown to possess significant antioxidant capacity (scavenging ROS / RNS), effectively mitigating oxidative stress-induced melanocyte activation. D-limonene has been reported to inhibit tyrosinase activity and the expression of microphthalmia-associated transcription factor (MITF). γ-terpinene is also believed to have anti-inflammatory properties and potential to inhibit melanin production. The structural similarities between the two compounds may lead to complementary or potentiating effects. Methyl 2-methylaminobenzoate (DMA): Not only is it a safe photostabilizer (UV absorber), recent studies have revealed that it can effectively inhibit the production of key inflammatory factors (such as IL-1α and TNF-α), which are important factors in pigmentation and impaired barrier function. DMA also shows potential to directly inhibit tyrosinase activity. Its unique structure may stabilize and enhance the activity of other terpene components.

[0018] Experimental verification demonstrates that the composition obtained by the present invention exhibits significant whitening and moisturizing efficacy, with significant synergistic effects between the ingredients. This composition overcomes the performance bottleneck of traditional single-ingredient or simple compound formulations, achieving significant and balanced dual whitening and moisturizing efficacy at lower concentrations while also exhibiting good biocompatibility, mildness, and formulation-friendliness. This invention provides important technical support for the development of a new generation of highly effective, safe, and multi-functional pharmaceutical and cosmetic ingredients, demonstrating significant market competitiveness and application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Effects of Tangerine Peel Volatile Oil on Zebrafish Tail Length Contraction DETAILED DESCRIPTION

[0020] The raw material compounds of the present invention are all commercially available, and the CAS numbers of the compounds are:

[0021] Myrcene: 123-35-3; D-Limonene: 5989-27-5; γ-Terpinene: 99-85-4; Methyl 2-methylaminobenzoate: 85-91-6.

[0022] Embodiment 1:

[0023] Take 3 mg of myrcene, 85 mg of D-limonene, 10 mg of γ-terpinene, and 2 mg of methyl 2-methylaminobenzoate, mix well, place in a brown glass bottle, and refrigerate.

[0024] Example 2:

[0025] Take 5 mg of myrcene, 80 mg of D-limonene, 14 mg of γ-terpinene, and 1 mg of methyl 2-methylaminobenzoate, mix well, place in a brown glass bottle, and refrigerate.

[0026] Example 3:

[0027] Take 1 mg of myrcene, 90 mg of D-limonene, 6 mg of γ-terpinene, and 3 mg of methyl 2-methylaminobenzoate, mix well, place in a brown glass bottle, and refrigerate.

[0028] Embodiment 4:

[0029] Take 0.05 g of the composition of Example 1 of the present invention, add 5 ml of glycerol to dissolve it, slowly add 90 ml of deionized water, stirring continuously, add 1 g of vitamin C derivative (APPS), 0.5 g of tranexamic acid (tranexamic acid), 0.3 g of dipotassium glycyrrhizate, and 0.5 ml of phenoxyethanol in sequence, add dropwise 10% citric acid aqueous solution to pH 5.5-6.0, then add deionized water to 100 ml, stir well, and obtain whitening and moisturizing water.

[0030] Example 5:

[0031] Take 0.05 g of the composition of Example 1 of the present application, add 5 g of glycerol, 3 g of butanediol, stir to dissolve, slowly add 80 g of deionized water, continuously stir, and sequentially add 2 g of vitamin C derivative (AA2G), 0.5 g of citric acid (transaminic acid), 0.1 g of hyaluronic acid, 0.2 g of glycyrrhizic acid dipotassium, 0.8 g of phenoxyethanol + hexanediol, 0.05 g of disodium EDTA, stir to dissolve, filter through a 0.22 m microporous filter, add deionized water to 100 g to the filtrate, and stir to homogeneity. This is the essence of a facial mask. Take a facial mask packaging bag, place a sterilized silk facial mask in it, and pour 20 ml of the essence into each bag. Seal the bag, and this is a whitening and moisturizing facial mask.

[0032] The beneficial effects of the present application are demonstrated by the following pharmacodynamic test.

[0033] Test Example 1 Whitening efficacy test of the composition of the present application

[0034] 1. Test materials

[0035] 1.1 Test fish The zebrafish used in this test were wild type AB line zebrafish.

[0036] 1.2 Main instruments and reagents

[0037] (1) Main test instruments: Z-A-D5 five-layer single-row independent breeding unit (Shanghai Haisheng Biological Experimental Equipment Co., Ltd.), SZ680 continuous zoom body microscope (Chongqing Aote Optical Instrument Co., Ltd.), ZXSD-A1090 biochemical incubator (Shanghai Zhicheng Analytical Instrument Manufacturing Co., Ltd.), SQP one-millionth electronic scale (Sartorius Scientific Instruments (Beijing) Co., Ltd.), Multiskan GO enzyme label instrument (Thermo Fisher Scientific (China) Co., Ltd.), ultrasonic oscillator (Kunshan Ultrasonic Instrument Co., Ltd.), centrifuge (Hunan Xiangyi Laboratory Instrument Development Co., Ltd.). TM

[0038] (2) Main test reagents: levodopa (98%) (Mcclin), sodium deoxycholate (99%, biotechnology grade) (Mcclin), sodium hydroxide (analytical pure, Tianjin Chuyuan Chemical Reagent Co., Ltd.).

[0039] 2. Test method

[0040] 2.1 Grouping and control

[0041] ​Product Dosage Grouping: Dissolve the composition of Example 1 in purified water and dilute to 0.0015% (0.015 mg / ml), 0.003% (0.03 mg / ml), and 0.006% (0.06 mg / ml) solutions. Dissolve the composition of Example 2 and Example 3 in purified water and dilute to 0.003% (0.03 mg / ml) solutions.

[0042] Control information: Blank control group: purified water.

[0043] 2.2 Main Operational Procedures (1) Collection of Experimental Fish and Fertilized Eggs Sexually mature zebrafish of different sexes were housed in separate tanks in a zebrafish culture unit. Water temperature: 26 ± 2°C; pH: 7.2; conductivity: 520 μs / cm; light / dark cycle: 14 h:10 h. One day before the exposure experiment, sexually mature zebrafish were paired in a 1:2 ratio of male to female, mated naturally, and spawned, and embryos were collected.

[0044] (2) The melanin production detection experiment set up a blank control group and sample groups of different concentrations. Under a stereomicroscope, wild-type AB zebrafish embryos with normal development of 6 to 8 hpf were selected and placed in a 6-well cell culture plate, with 30 embryos placed in each well. Each group had 5 replicate wells in parallel, and 5 mL of the corresponding solution was added to each well. Purified water was added to the blank control group, and the sample group was added with the sample solution of the corresponding concentration. The zebrafish embryos were then placed in an incubator and incubated until 72 hpf, and the melanin production in the zebrafish was detected at 72 hpf. After incubation to 72 hpf, the zebrafish embryos were transferred to an EP tube, lysis buffer (5 mg / mL sodium deoxycholate) was added, homogenized, centrifuged, the precipitate was taken, 1 M sodium hydroxide solution was added, and the assay was performed under an enzyme-linked microplate reader. The formula for calculating the melanin production inhibition rate is as follows:

[0045]

[0046] (3) Tyrosinase activity detection experiment set up a blank control group and sample groups with different concentrations. Under a stereomicroscope, wild-type AB zebrafish embryos with normal development of 6-8 hpf were selected and placed in a 6-well cell culture plate, with 30 embryos placed in each well. Each group had 5 replicate wells in parallel, and 5 mL of the corresponding solution was added to each well. Purified water was added to the blank control group, and the sample group was added with the sample solution of the corresponding concentration. The zebrafish embryos were then placed in an incubator and incubated until 72 hpf, and the tyrosinase activity in the zebrafish was detected at 72 hpf. After incubation to 72 hpf, the zebrafish embryos were transferred to an EP tube, lysis buffer (5 mg / mL sodium deoxycholate) was added, homogenized, centrifuged, the supernatant was taken, 5 mM levodopa solution was added, incubated at 37 ° C for 1 hour, and then detected under a microplate reader. The calculation formula for the tyrosinase activity inhibition rate is as follows:

[0047]

[0048] 3. Test data processing and results

[0049] The data were statistically processed by GraphPad Prism 8.0 software, and the experimental data were expressed by mean ± SEM. The data were statistically analyzed by T test and one-way analysis of variance. The determination results are shown in Table 1.

[0050] Table 1 Whitening efficacy experimental results of the formulation of the present application

[0051]

[0052] Note: *p < 0.05, **p < 0.01, ***p < 0.001, sample group compared with blank control group.

[0053] According to the experimental results, after the zebrafish treated by each formula group of the present application to 72hpf, compared with the blank control group, the melanin production inhibition rate and the tyrosinase activity inhibition rate were significantly increased, and had very significant effect (p < 0.001). Among them, the effect of 0.003% of example 1 complex was the best, the melanin production inhibition rate was 43.71 ± 0.48%, and the tyrosinase activity inhibition rate was 31.25 ± 0.57%. In summary, the composition of the present application has significant whitening effect under this experimental condition.

[0054] Test example 2 Moisturizing efficacy experiment of the composition of the present application

[0055] 1. Test materials

[0056] 1.1 Fish used for test The zebrafish used in this test is wild type AB strain zebrafish.

[0057] 1.2 Main instruments and reagents

[0058] (1) Main test instruments: Z-A-D5 five-layer single-row independent breeding unit (Shanghai Haisheng Biological Experiment Equipment Co., Ltd.), SZ680 continuous zoom body visual microscope (Chongqing Aote Optical Instrument Co., Ltd.), ZXSD-A1090 biochemical incubator (Shanghai Zhicheng Analytical Instrument Manufacturing Co., Ltd.), SQP one-millionth electronic scale (Sartorius Scientific Instruments (Beijing) Co., Ltd.).

[0059] (2) Main test reagents: sodium chloride, sodium hyaluronate.

[0060] 2. Test method

[0061] 2.1 Grouping and control

[0062] Sample dose grouping: Take the composition of Example 1, dissolve and dilute into 0.0015% (0.015 mg / ml), 0.003% (0.03 mg / ml) and 0.006% (0.06 mg / ml) solutions with 2.0% sodium chloride aqueous solution. Take the composition of Example 2, the composition of Example 3, dissolve and dilute into 0.003% (0.03 mg / ml) solutions with 2.0% sodium chloride aqueous solution.

[0063] Control information: ① Blank control group: purified water. ② Model control group: 2.0% sodium chloride solution.

[0064] 2.2 Main operation steps

[0065] Randomly select 72 hpf (72 hours after fertilization) wild type zebrafish with normal development, set up blank control group, model control group and sample group, 10 fish in each group. First, place the zebrafish in each group on a glass slide to lie down, then take pictures under a body microscope. Then transfer the zebrafish in each group to a 96-well cell culture plate, 1 fish per well, and add 200 μL of corresponding solution in each well after sucking dry the water in the well, and place it in a 28°C constant temperature incubator for 20 min. After incubation for 20 min, place the zebrafish in each group on a glass slide to lie down again, and take pictures under a body microscope. Then measure the tail length of zebrafish (the end of yolk sac and the end of tail vertebra) with Image J and calculate the tail length shrinkage rate (%) of each group of zebrafish.

[0066] The tail length shrinkage rate (%) of zebrafish refers to the percentage of the difference in tail length of zebrafish before and after the test substance dehydrates to the tail length before dehydration, and the calculation formula is as follows:

[0067]

[0068] Zebrafish embryos will undergo dehydration and shrinkage under the stimulation of high osmotic pressure (such as 2% NaCl), resulting in a decrease in tail length. By measuring the tail length shrinkage rate (i.e. the degree of reduction in tail area or length), it can be determined whether the test ingredient can reduce dehydration and maintain moisture, thereby indirectly reflecting its moisturizing ability.

[0069] 2.3 Data statistics and determination results

[0070] The data were statistically processed by GraphPad Prism 8.0 software, and the experimental data were expressed by mean ± SEM. The data were statistically analyzed by T test and one-way analysis of variance. The determination results are shown in Table 2, Figure 1 .

[0071] Table 2 Moisturizing efficacy experimental results of the formula of the present application

[0072]

[0073] Note: Comparison between model control group and blank control group: #p<0.05, ##p<0.01, ###p<0.001; comparison between sample group and model control group: *p<0.05, **p<0.01, ***p<0.001.

[0074] The experimental results show that after treating zebrafish with each formulation of the present invention, the tail length shrinkage rate was significantly reduced compared to the model control group, with the exception of Example 1 at 0.006%, which showed a highly significant effect (p < 0.01, p < 0.001). The 0.003% formulation of Example 1 had the best effect, with a tail length shrinkage rate of 5.59 ± 1.05%, a 5.60% reduction compared to the model control. In summary, the present composition has significant moisturizing efficacy under these experimental conditions.

[0075] Test Example 3 Synergistic Effect Test of Raw Material Compatibility of the Composition of the Present Invention

[0076] 1. Whitening efficacy test

[0077] Prepare the compounds according to the ratios listed in Table 3, mix thoroughly, and dissolve in purified water to dilute to a 0.003% sample solution (mass concentration: 0.03 mg / ml). The whitening efficacy of the different compositions was determined using the test method in Section 2.1. Data were analyzed using a T-test with a Holm-Bonferroni correction. The results are shown in Table 3.

[0078] Table 3 The percentage of effective ingredients in Example 1 and the comparative example and the whitening efficacy results after use of the corresponding products

[0079]

[0080]

[0081] Note 1: % refers to the mass percentage of each compound in the formula.

[0082] Note 2: Comparison between the control group and the experimental group: #p<0.05, ##p<0.01, ###p<0.001.

[0083] The results show that the four compounds in the formula of the present invention have a synergistic effect and can significantly enhance the whitening effect after being combined.

[0084] 2. Moisturizing efficacy test

[0085] Prepare the compounds according to the ratios listed in Table 4, mix thoroughly, and dissolve in purified water to dilute to a 0.003% sample solution (mass concentration: 0.03 mg / ml). Determine the moisturizing efficacy of the different compositions using the test method in Section 2.2. Data were analyzed using a Student's T-test with a Holm-Bonferroni correction. The results are shown in Table 3.

[0086] Table 4 The percentage of effective ingredients in Example 1 and the comparative example and the moisturizing effect results of the corresponding products after use

[0087]

[0088]

[0089] Note 1: % refers to the mass percentage of each compound in the formula.

[0090] Note 2: Comparison between the control group and the experimental group: #p<0.05, ##p<0.01, ###p<0.001.

[0091] The results show that the four compounds in the formula of the present invention have a synergistic effect and can significantly enhance the moisturizing effect after being combined.

Claims

1. A composition with whitening and moisturizing effects, characterized in that: It is composed of the following raw materials in the following weight ratios: 1-3 parts of myrcene, 80-90 parts of D-limonene, 6-14 parts of γ-terpinene, and 1-3 parts of methyl 2-methylaminobenzoate.

2. The composition with whitening and moisturizing effects according to claim 1, characterized in that: It is composed of the following raw materials in the following weight ratios: 3 parts of myrcene, 85 parts of D-limonene, 10 parts of γ-terpinene, and 2 parts of methyl 2-methylaminobenzoate.

3. The composition with whitening and moisturizing effects according to claim 1 or 2, characterized in that: The raw material is used as an active ingredient, and auxiliary materials or auxiliary ingredients commonly used in pharmacy or cosmetics are added to prepare an external preparation commonly used in the field of pharmacy or cosmetics.

4. The composition with whitening and moisturizing effects according to claim 3, characterized in that: The external preparation is a solution, emulsion, cream, gel, ointment, patch, film, or aerosol.

5. The method for preparing the composition with whitening and moisturizing effects according to any one of claims 1 to 4, characterized in that: It includes the following steps: a. Weigh the raw materials of each weight ratio; b. Mix well, and add excipients or auxiliary ingredients commonly used in pharmacy or cosmetics to prepare an external preparation commonly used in the field of pharmacy or cosmetics.

6. Use of the composition according to any one of claims 1 to 4 in the preparation of medicines or cosmetics with whitening effects.

7. Use of the composition according to any one of claims 1 to 4 in the preparation of a medicine or cosmetic having a moisturizing effect.

8. A cosmetic additive, characterized in that: It contains the composition according to any one of claims 1 to 4.

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