Compositions for reducing skin pigmentation and methods of making the same, cosmetics
Patent Information
- Application Number
- CN202610882830.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-06-17
- Publication Date
- 2026-10-09
AI Technical Summary
[0003]由于本身溶解很难，环糊精存在载药量低、成本偏高、易解离析出微晶的问题；脂质体、微囊包裹也因其的难溶，包裹量低，使用性价比低，且存在再次析出的风险
[0013]在本申请的其他实施例中，所述化妆品包括：具有减少皮肤色素沉着的组合物；所述组合物在使用前混合于水剂、凝胶、膏霜或者乳液，混合后再施用。
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Figure CN122874339A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of cosmetics, and more specifically, to a composition that reduces skin pigmentation, a method for preparing the same, and cosmetics. Background Technology
[0002] Amide compounds, highly active tyrosinase inhibitors, are extremely poorly soluble due to their dense molecular lattice and intramolecular hydrogen bonds. They are almost insoluble in pure water and have a solubility of only 0.001%-0.005% in small molecule alcohols such as ethanol, propylene glycol, butylene glycol, hexanediol, and dipropylene glycol. This makes them prone to crystallization in formulations, poor transdermal absorption, and reduced efficacy. While polyol compounding for solubilization is simple and inexpensive, it often requires 50 or more parts of polyol to aid dissolution. Furthermore, it suffers from crystallization at low temperatures, a sticky feel, generates heat, is highly irritating, and has poor system stability. Adding large amounts of surfactant micelles can slightly improve solubility, but high concentrations can easily cause skin irritation, breakouts, and excessive foaming during application.
[0003] Due to their inherent difficulty in dissolving, cyclodextrins suffer from low drug loading, high cost, and a tendency to dissociate and precipitate microcrystals. Liposomes and microencapsulation also suffer from low encapsulation capacity and low cost-effectiveness due to their poor solubility, and there is a risk of re-precipitation. Overall, existing solutions generally suffer from core pain points such as limited upper limit of solubility, contradiction between stability and irritation, poor compatibility with common skin care ingredients, and difficulty in achieving both solubility and transdermal absorption. Summary of the Invention
[0004] The purpose of this application is to provide a composition that reduces skin pigmentation, a method for preparing the same, and a cosmetic.
[0005] In a first aspect, this application provides a composition for reducing skin pigmentation, the composition comprising: at least one emollient and an active substance; The emollient is composed of at least one of the following: hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol. The active substances include amide compounds and at least one other active ingredient, which includes one or a combination of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
[0006] In the above technical solution, at least one of the following is used as a skin moisturizer: hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol. This moisturizer can synergistically enhance the effects of amide compounds and at least one other active ingredient, including niacinamide, bisabolol, acetylglucosamine, ceramide, and oryzanol, or combinations thereof. This improves the solubility of the active ingredient in the entire composition system and enhances its efficacy. It effectively inhibits the crystallization of amide active ingredients. This solubilization of the active ingredient enhances its bioavailability, ensuring uniform distribution of the amide active ingredient in the system, which is beneficial for transdermal absorption, thereby enhancing its effect in reducing skin pigmentation.
[0007] In other embodiments of this application, the amide compound comprises an oxetane ring, wherein the 3-position of the oxetane ring is substituted by a methyl group and an amide group; the nitrogen atom of the amide group is attached to a nitrogen-containing heterocycle; Optionally, the nitrogen-containing heterocycle is further substituted with a 2,4-dihydroxy-substituted phenyl group.
[0008] In other embodiments of this application, the active substance is composed of N(4(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-carboxamide; and one or a combination thereof of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
[0009] Secondly, this application provides a method for preparing a composition that reduces skin pigmentation, the method comprising: The at least one emollient is heated to 75°C~85°C until it dissolves and becomes transparent. The active substance is then added, stirred until homogeneous, and cooled.
[0010] In other embodiments of this application, the amide compound comprises an oxetane ring, wherein the 3-position of the oxetane ring is substituted with a methyl group and an amide group; the nitrogen atom of the amide group is attached to a nitrogen-containing heterocycle.
[0011] In other embodiments of this application, the active substance is composed of N(4(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-formamide; and one or a combination thereof of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
[0012] Thirdly, this application provides a cosmetic product comprising the composition provided in any of the foregoing embodiments for reducing skin pigmentation, the composition being directly applied to the skin.
[0013] In other embodiments of this application, the cosmetic includes: a composition having the function of reducing skin pigmentation; the composition is mixed with an aqueous solution, gel, cream, or lotion before use and then applied. Attached Figure Description
[0014] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.
[0015] Appendix Figure 1-5 Polarized light micrographs of the solubility of the samples from Examples 1-5 are shown in sequence; Appendix Figure 6-9 Polarized light micrographs of the solubility of samples from Comparative Examples 1-4 are shown in sequence.
[0016] Appendix Figure 10-16 Polarizing microscope images of the samples from Examples 1-7 are shown in sequence; Appendix Figure 17 A polarizing microscope image of sample 6 (Comparative Example 6) is shown. Detailed Implementation
[0017] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. Obviously, the described embodiments are some embodiments of this application, but not all embodiments.
[0018] Therefore, the following detailed description of the embodiments of this application is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of the application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.
[0019] Research has revealed that the amide compounds involved in this invention are highly active tyrosinase inhibitors. Due to their dense molecular lattice and the presence of intramolecular hydrogen bonds, they are extremely difficult to dissolve, almost insoluble in pure water. Therefore, it is necessary to first improve their solubility in solution before formulating the formulation to enhance their efficacy.
[0020] Based on the above research, this application provides a composition that reduces skin pigmentation, the composition comprising: at least one emollient and an active substance; The emollient is composed of at least one of the following: hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol. The active substances include amide compounds and at least one other active ingredient, which includes one or a combination of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
[0021] In the above technical solution, at least one of the following is used as a skin moisturizer: hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol. This moisturizer can synergistically enhance the effects of amide compounds and at least one other active ingredient, including niacinamide, bisabolol, acetylglucosamine, ceramide, and oryzanol, or combinations thereof. This improves the solubility of the active ingredient in the entire composition system and enhances its efficacy. It effectively inhibits the crystallization of amide active ingredients. This solubilization of the active ingredient enhances its bioavailability, ensuring uniform distribution of the amide active ingredient in the system, which is beneficial for transdermal absorption, thereby enhancing its effect in reducing skin pigmentation.
[0022] In other embodiments of this application, the amide compound comprises an oxetane ring, wherein the 3-position of the oxetane ring is substituted by a methyl group and an amide group; the nitrogen atom of the amide group is attached to a nitrogen-containing heterocycle.
[0023] In other embodiments of this application, the nitrogen-containing heterocycle is replaced by a 2,4-dihydroxy-substituted phenyl group.
[0024] In other embodiments of this application, the active substance is composed of N(4(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-carboxamide; and one or a combination thereof of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
[0025] Further, alternatively, in other embodiments of this application, other active substances include at least one of nicotinamide, bisabolol, oryzanol, acetyl glucosamine, ceramide, or tranexamic acid.
[0026] For example, in some embodiments of this application, the other active substances are at least one of nicotinamide, bisabolol, oryzanol, acetylglucosamine, ceramide, or tranexamic acid. Alternatively, in some embodiments of this application, the other active substances are a mixture of nicotinamide and bisabolol; or in some embodiments of this application, the other active substances are a mixture of oryzanol, acetylglucosamine, ceramide, and tranexamic acid.
[0027] The above-mentioned technical solution further defines other active substances in the composition that reduces skin pigmentation, which can further achieve multiple synergistic effects and enhance the efficacy of reducing skin pigmentation while maintaining a non-crystallizing and stable state.
[0028] Furthermore, niacinamide can inhibit the transport of melanosomes to keratinocytes; tranexamic acid can inhibit plasmin and prostaglandin synthesis; and acetyl glycosamine can inhibit tyrosinase glycosylation. When combined with core amide compounds, these three can effectively play a synergistic role, forming a multi-pathway blocking effect from melanin synthesis, transport to metabolism, and further enhancing the efficacy of reducing skin pigmentation.
[0029] Furthermore, bisabolol and oryzanol can serve as oil-soluble anti-inflammatory ingredients, while ceramides can enhance skin barrier repair. Combining these active ingredients with N(4(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-carboxamide can further enhance their synergistic effect, achieving whitening while reducing skin irritation and maintaining a healthy skin barrier, thereby improving the product's anti-allergic effect.
[0030] Furthermore, niacinamide, tranexamic acid, and acetylglucosamine are water-soluble active substances, while bisabolol, oryzanol, and ceramides are oil-soluble active substances. These two types of active substances can synergistically interact with the emollients and hydrophilic moisturizers in this application, achieving high loading of active substances while maintaining the stability of the formulation system and preventing crystallization, thus avoiding the precipitation of active substances and enhancing product efficacy.
[0031] Secondly, this application provides a method for preparing a composition that reduces skin pigmentation, the method comprising: The at least one emollient is heated to 75°C~85°C until it dissolves and becomes transparent. The active substance is then added, stirred until homogeneous, and cooled.
[0032] For example, the at least one emollient is heated to 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C or any two of the aforementioned values, and after it dissolves and becomes transparent, the active substance is added, stirred evenly, and then cooled.
[0033] The above-mentioned technical solution, using the above-mentioned emollients, can effectively dissolve amide compounds and enhance the efficacy of active ingredients.
[0034] Further optionally, in some embodiments of this application, the amide compound comprises an oxetane ring, wherein the 3-position of the oxetane ring is substituted by a methyl group and an amide group; the nitrogen atom of the amide group is attached to a nitrogen-containing heterocycle.
[0035] Further optionally, in some embodiments of this application, the active substance is composed of N(4(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-formamide; and one or a combination thereof of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
[0036] In addition to the essential ingredients mentioned above, this invention may selectively include commonly used cosmetic ingredients such as skin conditioning agents, skin feel modifiers, skin moisturizers, thickeners, preservatives, and fragrances.
[0037] Some embodiments of this application provide a cosmetic product comprising a composition provided in any of the foregoing embodiments that reduces skin pigmentation, the composition being applied directly to the skin.
[0038] In other embodiments of this application, the cosmetic includes: a composition having the function of reducing skin pigmentation; the composition is mixed with an aqueous solution, gel, cream, or lotion before use and then applied.
[0039] The features and performance of this application will be further described in detail below with reference to embodiments: Examples 1-5, Comparative Examples 1-4 A composition is provided, and the composition and content of various embodiments and comparative examples are shown in Table 1 (wt%) below.
[0040] Table 1
[0041] Preparation process: Heat component B to 80℃ until it dissolves and becomes transparent, then add component A, stir evenly, and cool down.
[0042] [Solubility Test:] The solutions prepared in each example and comparative example were placed at 4°C and allowed to stand for 7 days. The crystallization status was then observed using a polarizing microscope.
[0043] The test results are shown in Table 2 below.
[0044] Table 2
[0045] As can be seen from the experimental data in Table 2 above, crystals precipitated in all solutions of Comparative Examples 1-4. However, no crystals were observed in the solutions of Examples 1-5. This indicates that the emollients used in Examples 1-5—hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol—effectively improve the solubility of the target active substance, the amide compound, in solution. In contrast, the emollients used in Comparative Examples 1-4—octyldodecanol and C12-15 benzoate—do not effectively improve the solubility of the target active substance, the amide compound, in solution.
[0046] Furthermore, attached Figure 1-5 Polarized light micrographs of the solubility of samples from Examples 1-5 are shown sequentially. As can be seen from the figures, the samples from each example exhibit no crystallization. This demonstrates that the solutions in Examples 1-5 of this application have good solubility and high effective utilization of the active ingredient.
[0047] Appendix Figure 6-9 The polarized light micrographs of the solubility of samples from Comparative Examples 1-4 are shown sequentially. As can be seen from the figures, all samples from the comparative examples exhibit crystal precipitation. This indicates that the comparative examples have poor solubility and low effective utilization of the active ingredient.
[0048] In summary, none of the comparative schemes can improve the solubility of the active material.
[0049] Examples 6-12, Comparative Examples 5-7 A composition is provided, and the composition and content of Examples 6-12 and Comparative Examples 5-7 are shown in Table 1 (wt%) below.
[0050] Table 3
[0051] Preparation process: Mix the raw materials in group A, heat to 80°C, and stir until homogeneous to obtain the first mixture; Mix the raw materials of group B, stir at 200 rpm, heat to 70°C, and slowly add N(4-(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-formamide while stirring. Continue stirring until completely dissolved to form a transparent liquid, thus obtaining the second mixture. Heat water to 70-80℃, add raw materials from group C and stir to disperse evenly; finally add other water-soluble active ingredients from group C and stir until completely dissolved to obtain the third mixture; Mix the other ingredients thoroughly to obtain the fourth mixture.
[0052] Combine the first mixture, the second mixture, the third mixture, and the fourth mixture.
[0053] [Stability Performance Test] The stability properties of the cream samples obtained in Examples 6-12 and Comparative Examples 5-7 were tested: 1. Is there any crystallization? The samples prepared in each embodiment and comparative example were placed at 45°C for 24 hours; at 25°C for 7 days; and at -10°C for 24 hours. The samples were then removed without shaking or stirring and placed against a white background. Two or more observers independently rotated the bottles at a distance of 20 cm from the samples and slowly observed them, recording whether there were any visible grains, debris, flashes, or hazy turbidity.
[0054] Evaluation criteria: No crystallization; no visible crystals or turbidity after storage at any temperature.
[0055] Crystallization: After storage at any temperature, particles, filaments, or obvious turbidity can be visually observed.
[0056] The absence of crystallization indicates good sample stability; the presence of crystallization indicates poor sample stability.
[0057] The test results are shown in Table 4 below.
[0058] Table 4
[0059] The experimental data in Table 4 above show that: Samples from Examples 6-12 showed no crystallization, indicating that the formulations in Examples 6-12 of this application effectively prevented active ingredient crystallization. The formulation system was stable, and the effective utilization rate of the active ingredients was high. Comparative Example 6, however, showed crystallization. Comparative Example 6 completely lacked at least one of the emollients in Group B of the examples in this application: hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecamide, isosorbide dimethyl ether, or ethoxydiethylene glycol, making it difficult to improve the solubility of the active ingredients in the system. Therefore, crystallization occurred. This shows that its formulation system could not avoid active ingredient crystallization. The formulation system was unstable, and the effective utilization rate of the active ingredients was low. Comparative Examples 5 and 7, because they used the same emollients as the examples: hexyldecyl myristoyl methylaminopropionate, lauroyl amino isopropyl ester, dimethyldecamide, isosorbide dimethyl ether, or ethoxydiethylene glycol, also showed no crystallization. However, their improvement in efficacy was limited.
[0060] Furthermore, attached Figure 10-16 Polarizing microscope images of samples from Examples 6-12 are shown sequentially. As can be seen from the images, the samples from each example exhibit no crystallization. This demonstrates that the solutions of the embodiments of this application can effectively prevent the crystallization of the active ingredient. (Appendix) Figure 17 A polarized light microscope image of Comparative Example 6 is shown. As can be seen from the image, Comparative Example 6 exhibits crystallization, indicating that its formulation system cannot avoid active ingredient crystallization.
[0061] 5. Test Item: Human Efficacy Test Test items and conclusions Evaluation Objective: In accordance with the requirements of the 2015 edition of the "Cosmetic Safety Technical Specifications" regarding the test methods for whitening and freckle-removing effects of cosmetics: Method 1, Ultraviolet-Induced Human Skin Melanization Model Whitening and Freckle-Removing Effect Test Method, skin ITA° value and skin MI value were collected to evaluate the whitening and freckle-removing effects of the samples. Number of test participants: 30 Test area: back Testing period: 4 days for mold making + 4 days for blackening + 28 days of product use The positive control group consisted of a 7% vitamin C ointment, while the negative control group consisted of a blank sample containing no vitamin C and no product used.
[0062] The 28-day test data is shown in Table 5: Table 5
[0063] The experimental data in Table 5 above show that: Compared with the comparative examples, the ITA° value and skin MI value of each embodiment of the present invention are superior to those of the comparative examples.
[0064] Therefore, it can be seen that by adopting the solution of the embodiments of this application, skin pigmentation can be effectively reduced.
[0065] Furthermore, Comparative Examples 5 and 7 contained only one active ingredient, and their ITA° and skin MI values were significantly lower than those of Examples 6-12. This demonstrates that the emollients in Examples 5-8 of this application, composed of at least one of the following: hexyldecyl myristoyl methylaminopropionate, lauroyl amino acid isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol, synergistically enhance the skin-lightening and whitening effects by combining with active ingredients including amide compounds and at least one other active ingredient, such as nicotinamide, bisabolol, acetylglucosamine, ceramide, and oryzanol, or combinations thereof.
[0066] In summary, none of the comparative examples simultaneously demonstrated good formulation stability, good solubility, and enhanced skin-whitening and spot-removing effects. However, the example formulation simultaneously exhibited good formulation stability, good solubility, and enhanced skin-whitening and spot-removing effects.
[0067] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A composition for reducing skin pigmentation, characterized in that, The composition for reducing skin pigmentation includes: at least one emollient and an active substance; The emollient is composed of at least one of the following: hexyldecyl myristoyl methyl amino propionate, lauroyl amino isopropyl ester, dimethyldecylamide, isosorbide dimethyl ether, or ethoxydiethylene glycol. The active substance includes: amide compounds and at least one other active ingredient, which includes: nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol or a combination thereof.
2. The composition for reducing skin pigmentation according to claim 1, characterized in that, The amide compound comprises an oxetane ring, wherein the 3-position of the oxetane ring is substituted by a methyl group and an amide group; the nitrogen atom of the amide group is attached to a nitrogen-containing heterocycle.
3. The composition for reducing skin pigmentation according to claim 2, characterized in that, The nitrogen-containing heterocycle is further replaced by a phenyl group substituted with a 2,4-dihydroxy group.
4. The composition for reducing skin pigmentation according to claim 1, characterized in that, The active substance is composed of N(4-(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-carboxamide; and one or a combination thereof of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
5. A method for preparing the composition for reducing skin pigmentation according to any one of claims 1-4, characterized in that, The preparation method includes: The at least one emollient is heated to 75°C~85°C until it dissolves and becomes transparent. The active substance is then added, stirred until homogeneous, and cooled.
6. The method for preparing the composition for reducing skin pigmentation as described in claim 5, characterized in that, The amide compound comprises an oxetane ring, wherein the 3-position of the oxetane ring is substituted by a methyl group and an amide group; the nitrogen atom of the amide group is attached to a nitrogen-containing heterocycle.
7. The method for preparing the composition for reducing skin pigmentation as described in claim 5, characterized in that, The active substance is composed of N(4-(2,4-dihydroxyphenyl)thiazolyl)3-methyloxetane-3-carboxamide; and one or a combination thereof of nicotinamide, bisabolol, acetyl glucosamine, ceramide and oryzanol.
8. A cosmetic product, characterized in that, The cosmetic product includes the composition according to any one of claims 1-4 that reduces skin pigmentation, the composition being applied directly to the skin.
9. The cosmetic product according to claim 8, characterized in that, The cosmetic product includes: a composition that reduces skin pigmentation; the composition is mixed with an aqueous solution, gel, cream, or lotion before application.