Whitening nanocomposition, method for producing the same, and use

Abstract

The present invention relates to a skin-whitening nanocomposition, its manufacturing method, and its use, and belongs to the technical field of cosmetics or similar cosmetic preparations. The skin-whitening nanocomposition of the present invention comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with and / or adsorbed onto the nanocarrier, and the active ingredient comprises 1 to 15 parts by weight of α-arbutin, 1 to 15 parts by weight of nicotinamide, 1 to 10 parts by weight of 3-O-ethyl ascorbic acid, 0.1 to 1 part by weight of Centella asiatica extract, and 1 to 5 parts by weight of retinyl palmitate, and the nanocarrier comprises 5 to 10 parts by weight of emulsifier, 5 to 20 parts by weight of polyhydric alcohol, 0.1 to 5 parts by weight of phospholipid, and 40 to 60 parts by weight of water. The skin-whitening nanocomposition of the present invention has good skin penetration and retention properties, accumulates at high concentrations in target tissue, remains there for a long time, and is released slowly and controlledly, thereby enabling effective uptake by target cells, thereby increasing bioavailability and enhancing the skin-whitening effect. [Summary Diagram] Figure 4

Description

[Technical Field]

[0001] The present invention relates to the technical field of cosmetics or similar cosmetic preparations, and more particularly to whitening nanocompositions and methods for producing and using the same. [Background technology]

[0002] Human skin contains mainly dark brown melanin, red hemoglobin, and yellow carotenoids, with melanin being the primary factor determining skin color. External factors such as ultraviolet radiation and environmental pollution, as well as internal factors such as hormones and inflammation levels, interact with the skin and influence melanin production in melanocytes through various mechanisms and means. Current skin-whitening active ingredients achieve their whitening effect mainly by reducing the amount of melanin in the skin through various means. Specific methods include inhibiting tyrosinase activity, promoting the metabolism of keratinocytes with pigmentation, and reducing stimulation of melanocytes by ultraviolet radiation or free radicals.

[0003] However, despite the wide variety of whitening products available on the market, most products fail to achieve the whitening effect that satisfies consumers. The main reasons are as follows: (1) Conventional whitening products have a single mechanism of action and are somewhat irritating. For example, some products have strong tyrosinase inhibitory or exfoliating effects, but they lack active ingredients with skin repair properties, causing damage to the skin barrier. (2) The stability of active ingredients with whitening properties is low, and when used directly in cosmetics, they are prone to oxidative modification and inactivation, making it difficult for them to exert their whitening effect. (3) Due to the skin's natural barrier function, it is difficult for whitening active ingredients to pass through the stratum corneum and reach the dermis, and it is especially difficult for them to accumulate to an effective concentration range in the target area of ​​the skin, resulting in low actual whitening care effectiveness. [Overview of the project] [Problems that the invention aims to solve]

[0004] The object of the present invention is to overcome the shortcomings of the prior art and to provide a skin-whitening nanocomposition, a method for producing the same, and a method for using the same. [Means for solving the problem]

[0005] To achieve the above objective, the present invention employs the following technical approach.

[0006] In a first aspect, the present invention comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The active ingredients include 1 to 15 parts by weight of α-arbutin, 1 to 15 parts by weight of nicotinamide, 1 to 10 parts by weight of 3-O-ethyl ascorbic acid, 0.1 to 1 part by weight of Centella asiatica extract, and 1 to 5 parts by weight of retinyl palmitate. The nanocarrier provides a skin-whitening nanocomposition comprising 5 to 10 parts by weight of emulsifier, 5 to 20 parts by weight of polyhydric alcohol, 0.1 to 5 parts by weight of phospholipid, and 40 to 60 parts by weight of water.

[0007] The present invention provides a whitening nanocomposition primarily composed of α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, centella asiatica extract, and retinyl palmitate as whitening active ingredients. By combining these whitening active ingredients with a nanocarrier of a specific composition, the water dispersibility of the whitening nanocomposition is improved, effectively enhancing the solubility of the whitening active ingredients. Furthermore, the stability of the whitening nanocomposition is increased, preventing unwanted degradation or inactivation of the whitening active ingredients during storage or before use, and increasing the concentration of the whitening active ingredients in the whitening product. In addition, by combining the whitening active ingredients with a nanocarrier of a specific composition, the irritancy of the whitening active ingredients can be reduced, allowing them to be incorporated into the product at a sufficient concentration to exert the corresponding functional effects. Moreover, due to the action of the nanocarrier, the whitening active ingredients in the whitening nanocomposition can efficiently penetrate the skin barrier and rapidly reach the basal layer and the dermis deep within the skin where melanocytes are distributed. As a result, they accumulate at high concentrations in the target tissue, remain there for a long time, and are effectively taken up by target cells through sustained and controlled release. As a result, the bioavailability of the whitening active ingredient is improved and its duration of action is extended, significantly enhancing the whitening effect.

[0008] The above-mentioned α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, centella asiatica extract, and retinyl palmitate exhibit a multifunctional and multitarget synergistic effect. Of these, α-arbutin contains highly hydrophilic glucose residues, providing excellent moisturizing effects to the skin and easily penetrating the skin surface. Furthermore, the phenol group of α-arbutin effectively inhibits the biological activity of tyrosinase, thereby reducing melanin production within cells. Nicotinamide not only inhibits the formation of melanin granules but also effectively inhibits the migration of melanin to keratinocytes. Even if some melanin inevitably reaches the epidermis, nicotinamide can accelerate skin cell turnover, promoting the shedding of melanin-containing cells. In addition, nicotinamide inhibits tyrosinase activity, preventing melanin from moving to the stratum corneum and promoting the metabolism of melanin-containing cells. Furthermore, nicotinamide possesses antioxidant properties and can significantly reduce blemishes, brighten skin tone, and improve skin whiteness by decreasing the amount of reactive oxygen species (ROS) in the skin.

[0009] 3-O-ethyl ascorbic acid not only protects the skin from free radical damage and slows down the skin aging process, but it can also suppress tyrosinase activity to reduce melanin production and inhibit tyrosine from producing DHI (dihydroxyindole)-melanin and DHICA (dihydroxyindolecarboxylic acid)-melanin.

[0010] Centella asiatica extract contains a wealth of components, including polysaccharides, vitamins, and flavonoids. These substances have diverse pharmacological effects, such as free radical scavenging, reduction of skin pigmentation, and antibacterial, anti-inflammatory, and fibroblast regeneration promotion. Furthermore, these substances not only improve scarring by promoting the proliferation of human fibroblasts and collagen synthesis, but also exert anti-inflammatory and reparative effects by suppressing oxidative stress.

[0011] The main components of the Centella asiatica extract described above are pentacyclic triterpenoids, including asiaticoside, madecassoside and their aglycones, asiatic acid, and madecassic acid. These compounds can be purchased commercially or prepared by existing manufacturing methods.

[0012] Retinyl palmitate possesses antioxidant properties, can accelerate the turnover of deep skin cells, and promote the metabolism of growth factors, thereby improving skin metabolism, generating more epidermal proteins, and increasing skin elasticity. Furthermore, retinyl palmitate not only exfoliates already formed keratinized cells along with melanin at an early stage, but also has the ability to suppress melanin production, thus exhibiting excellent whitening and skin tone-up effects.

[0013] Optionally, among the above active ingredients, α-arbutin may be in amounts of 2 parts by weight, 4 parts by weight, 6 parts by weight, 8 parts by weight, 10 parts by weight, 12 parts by weight, or 14 parts by weight; nicotinamide may be in amounts of 2 parts by weight, 4 parts by weight, 6 parts by weight, 8 parts by weight, 10 parts by weight, 12 parts by weight, or 14 parts by weight; 3-O-ethyl ascorbic acid may be in amounts of 3 parts by weight, 5 parts by weight, 7 parts by weight, or 9 parts by weight; centella asiatica extract may be in amounts of 0.3 parts by weight, 0.5 parts by weight, 0.7 parts by weight, or 0.9 parts by weight; and retinyl palmitate may be in amounts of 1.5 parts by weight, 2.5 parts by weight, 3.5 parts by weight, or 4.5 parts by weight.

[0014] Optionally, among the above nanocarriers, the emulsifier may be 5.5 parts by weight, 6.5 parts by weight, 7.5 parts by weight, 8.5 parts by weight, or 9.5 parts by weight; the polyhydric alcohol may be 7 parts by weight, 9 parts by weight, 11 parts by weight, 13 parts by weight, 15 parts by weight, 17 parts by weight, or 19 parts by weight; the phospholipid may be 0.5 parts by weight, 1 part by weight, 1.5 parts by weight, 2 parts by weight, 2.5 parts by weight, 3 parts by weight, 3.5 parts by weight, 4 parts by weight, or 4.5 parts by weight; and the water may be 43 parts by weight, 45 parts by weight, 47 parts by weight, 49 parts by weight, 51 parts by weight, 53 parts by weight, 55 parts by weight, 57 parts by weight, or 59 parts by weight.

[0015] The whitening nano-composition described above has an average particle diameter of 20 to 40 nm, which can be measured by a particle diameter analyzer.

[0016] As a preferred embodiment of the whitening nano-composition according to the present invention, the α-arbutin is 8 to 10 parts by weight, nicotinamide is 5 to 10 parts by weight, 3-O-ethylascorbic acid is 3 to 5 parts by weight, centella asiatica extract is 0.1 to 1 part by weight, and retinyl palmitate is 1 to 3 parts by weight.

[0017] As a preferred embodiment of the whitening nano-composition according to the present invention, the emulsifier is 5 to 10 parts by weight, the polyhydric alcohol is 9 to 18 parts by weight, the phospholipid is 0.5 to 1 part by weight, and water is 46 to 55 parts by weight.

[0018] As a preferred embodiment of the whitening nano-composition according to the present invention, the mass ratio of the active ingredient to the nanocarrier is (15 to 30):(65 to 80), preferably (19.1 to 28.5):(69 to 78.5).

[0019] Optionally, the active ingredient may be 20 parts by weight, 21 parts by weight, 22 parts by weight, 23 parts by weight, 24 parts by weight, 25 parts by weight, 26 parts by weight, 27 parts by weight, 28 parts by weight, and the nanocarrier may be 70 parts by weight, 72 parts by weight, 74 parts by weight, 76 parts by weight, 78 parts by weight.

[0020] As a preferred embodiment of the whitening nano-composition according to the present invention, the emulsifier comprises at least one selected from polyoxyethylene castor oil-based emulsifiers, polyoxyethylene hydrogenated castor oil-based emulsifiers, polyglycerin-based emulsifiers, poloxamers, and coconut oil alkyl glucosides.

[0021] Optionally, the polyoxyethylene castor oil-based emulsifier may be at least one of polysorbate-20, polysorbate-60, and polysorbate-80; the polyoxyethylene hydrogenated castor oil-based emulsifier may be at least one of PEG-40 hydrogenated castor oil and PEG-60 hydrogenated castor oil; and the polyglycerin-based emulsifier may be at least one of polyglyceryl fatty acid ester and polyglyceryl-10 stearate.

[0022] As a preferred embodiment of the whitening nano-composition according to the present invention, the polyhydric alcohol includes at least one of glycerin, propylene glycol, butylene glycol, 1,3-propylene glycol, 1,2-pentylene glycol, 1,2-hexylene glycol, dipropylene glycol, isopropanol, polyethylene glycol-200, PPG-10 sorbitol, and octyldodecanol.

[0023] As a preferred embodiment of the whitening nano-composition according to the present invention, the phospholipid includes at least one of hydrogenated lecithin, lecithin, and soybean lecithin.

[0024] In a second aspect, the present invention provides a method for producing the above whitening nano-composition, comprising: Step S1: uniformly mixing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid and centella asiatica extract with phospholipids, water and part of the polyhydric alcohol to obtain a mixed solution I; Step S2: uniformly mixing retinyl palmitate, the emulsifier, and the remaining polyhydric alcohol to obtain a mixed solution II; Step S3: uniformly mixing the mixed solution I obtained in step S1 and the mixed solution II obtained in step S2, then homogenizing the mixture to obtain the whitening nano-composition; the production method comprises the above steps.

[0025] In the above step S3, the homogenization may be performed by a high-pressure homogenizer, and the pressure of the high-pressure homogenizer may be 800 to 1000 bar.

[0026] In a preferred embodiment of the method for producing the whitening nanocomposition according to the present invention, step S1 specifically involves stirring α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and centella asiatica extract with phospholipids, water, and some polyhydric alcohols at 40-65°C and 150-200 rpm for 10-30 minutes to obtain a mixture I.

[0027] In a preferred embodiment of the method for producing the whitening nanocomposition according to the present invention, step S2 specifically involves stirring retinyl palmitate, an emulsifier, and the remaining polyhydric alcohol at 40-65°C and 150-200 rpm for 10-30 minutes to obtain mixture II.

[0028] In a preferred embodiment of the method for producing a whitening nanocomposition according to the present invention, step S3 specifically involves stirring the mixed liquid I from step S1 and the mixed liquid II from step S2 at 40-65°C and 200-270 rpm for 10-30 minutes to homogenize them and obtain a whitening nanocomposition.

[0029] In a third aspect, the present invention provides the use of the above-mentioned whitening nanocomposition in the manufacture of skincare products or cosmetics.

[0030] In a fourth aspect, the present invention provides a whitening skincare product or whitening cosmetic product comprising the above-mentioned whitening nanocomposition.

[0031] In a preferred embodiment of the whitening skincare product or whitening cosmetic according to the present invention, the mass fraction of the whitening nanocomposition in the whitening skincare product or whitening cosmetic is 0.1% to 30%.

[0032] Optionally, the mass fraction of the whitening nanocomposition in the whitening skincare product or whitening cosmetic may be 0.5%, 5%, 10%, 15%, 20%, or 25%, and the form of the whitening skincare product or whitening cosmetic may include, but is not limited to, lotions, creams, emulsions, serums, and gels. [Effects of the Invention]

[0033] Compared to the conventional technology, the beneficial effects of the present invention are as follows: The present invention provides a whitening nanocomposition primarily composed of α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, centella asiatica extract, and retinyl palmitate as whitening active ingredients. By combining these whitening active ingredients with a nanocarrier of a specific composition, the solubility of the whitening active ingredients can be effectively improved, the stability of the whitening nanocomposition can be enhanced, and the irritancy of the whitening active ingredients can be reduced, thereby achieving a sufficient concentration in the product and exhibiting the corresponding functional effects. Furthermore, the whitening active ingredients in the whitening nanocomposition can efficiently penetrate the skin barrier and rapidly reach the basal layer and the dermis deep within the skin where melanocytes are distributed. As a result, they accumulate at high concentrations in the target tissue, remain there for a long time, and are effectively taken up by target cells through sustained and controlled release. Consequently, the bioavailability of the whitening active ingredients is improved, the duration of action is extended, and the whitening effect is enhanced. [Brief explanation of the drawing]

[0034] [Figure 1] This figure shows the results of the chicken embryo allanine irritation test after diluting each of the whitening nanocompositions in Examples 1 to 5 with water 10 times. [Figure 2] This figure shows the cumulative skin penetration amounts of the whitening nanocomposition in Example 1 and the whitening free composition in Comparative Example 8. [Figure 3] This figure shows the amount of skin retention of the whitening nanocomposition in Example 1 and the whitening free composition in Comparative Example 8 (in comparison with the free composition, "**" indicates P<0.01). [Figure 4] This figure shows the time-dependent fluorescence penetration depth of free RhoB and RhoB nanocarriers corresponding to the whitening free composition in Comparative Example 8 and the whitening nanocomposition in Example 1 of the present invention. [Figure 5] This figure shows the relative fluorescence intensity over time of free RhoB and RhoB nanocarriers corresponding to the whitening free composition in Comparative Example 8 and the whitening nanocomposition in Example 1 of the present invention. [Figure 6] This figure shows the relative tyrosinase activity of B16F10 cells corresponding to the blank control group, model group, and experimental group samples of the present invention (in comparison with the model group, "*" represents P<0.05 and "**" represents P<0.01. In comparison with Comparative Example 6, "&&" represents P<0.01. In comparison with Comparative Example 8, "##" represents P<0.01). [Figure 7] This figure shows the intracellular relative melanin content of B16F10 cells corresponding to the blank control group, model group, and experimental group samples of the present invention (in comparison with the model group, "*" represents P<0.05 and "**" represents P<0.01. In comparison with Comparative Example 6, "&&" represents P<0.01. In comparison with Comparative Example 8, "##" represents P<0.01). [Figure 8] This chart compares facial skin color and facial pigmentation / blemishes on days 0, 14, and 28 of Volunteer 1's use of the experimental group's sample. [Figure 9] This chart compares facial skin color and facial pigmentation / blemishes on days 0, 14, and 28 of Volunteer 2's use of the experimental group's sample. [Modes for carrying out the invention]

[0035] The present invention will be described in more detail below with reference to specific examples in order to better explain its objectives, technical proposals, and advantages.

[0036] Unless otherwise specified, all other materials, reagents, etc. used in the examples are commercially available.

[0037] Example 1 In one embodiment of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this embodiment comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The aforementioned active ingredient is It contains 10 parts by weight of α-arbutin, 10 parts by weight of nicotinamide, 5 parts by weight of 3-O-ethyl ascorbic acid, 0.5 parts by weight of Centella asiatica extract, and 3 parts by weight of retinyl palmitate. The aforementioned nanocarrier is It contains 10 parts by weight of an emulsifier (PEG-40 hydrogenated castor oil), 15 parts by weight of a polyhydric alcohol (10 parts by weight of glycerin + 5 parts by weight of octyldodecanol), 0.5 parts by weight of a phospholipid (lecithin), and 46 parts by weight of water.

[0038] The method for producing the whitening nanocomposition according to this embodiment includes the following steps S1 to S3. Step S1: 10 parts by weight of α-arbutin, 10 parts by weight of nicotinamide, 5 parts by weight of 3-O-ethyl ascorbic acid, and 0.5 parts by weight of Centella asiatica extract were stirred with 0.5 parts by weight of lecithin, 10 parts by weight of glycerin, and 46 parts by weight of water at 45°C and 150-200 rpm for 15 minutes to form a homogeneous and transparent liquid A.

[0039] Step S2: 10 parts by weight of PEG-40 hydrogenated castor oil, 5 parts by weight of octyldodecanol, and 3 parts by weight of retinyl palmitate were stirred at 45°C and 150-200 rpm for 15 minutes to form a homogeneous and transparent liquid B.

[0040] Step S3: Liquid A was added to liquid B and stirred for 15 minutes at 200-270 rpm to form a homogenized liquid C. Then, liquid C was homogenized twice using a high-pressure homogenizer at 800 bar to obtain a whitening nanocomposition.

[0041] Example 2 In one embodiment of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this embodiment comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The aforementioned active ingredient is It contains 8 parts by weight of α-arbutin, 6 parts by weight of nicotinamide, 4 parts by weight of 3-O-ethyl ascorbic acid, 0.1 parts by weight of Centella asiatica extract, and 1 part by weight of retinyl palmitate. The aforementioned nanocarrier is It contains 5 parts by weight of an emulsifier (PEG-40 hydrogenated castor oil), 18 parts by weight of a polyhydric alcohol (15 parts by weight of glycerin + 3 parts by weight of octyldodecanol), 0.5 parts by weight of a phospholipid (lecithin), and 55 parts by weight of water.

[0042] The method for producing the whitening nanocomposition according to this example was the same as in Example 1, except that the amount of each component used was different.

[0043] Example 3 In one embodiment of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this embodiment comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The aforementioned active ingredient is It contains 8 parts by weight of α-arbutin, 8 parts by weight of nicotinamide, 3 parts by weight of 3-O-ethyl ascorbic acid, 1 part by weight of Centella asiatica extract, and 1 part by weight of retinyl palmitate. The aforementioned nanocarrier is It contains 6 parts by weight of an emulsifier (PEG-40 hydrogenated castor oil), 9 parts by weight of a polyhydric alcohol (8 parts by weight of glycerin + 1 part by weight of octyldodecanol), 1 part by weight of a phospholipid (lecithin), and 53 parts by weight of water.

[0044] The method for producing the whitening nanocomposition according to this example was the same as in Example 1, except that the amount of each component used was different.

[0045] Example 4 In one embodiment of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this embodiment comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The aforementioned active ingredient is It contains 8 parts by weight of α-arbutin, 5 parts by weight of nicotinamide, 3 parts by weight of 3-O-ethyl ascorbic acid, 0.5 parts by weight of Centella asiatica extract, and 3 parts by weight of retinyl palmitate. The aforementioned nanocarrier is It contains 8 parts by weight of emulsifier (PEG-40 hydrogenated castor oil), 13 parts by weight of polyhydric alcohol (8 parts by weight of glycerin + 5 parts by weight of octyldodecanol), 0.5 parts by weight of phospholipid (lecithin), and 55 parts by weight of water.

[0046] The method for producing the whitening nanocomposition according to this example was the same as in Example 1, except that the amount of each component used was different.

[0047] Example 5 In one embodiment of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this embodiment comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The aforementioned active ingredient is It contains 10 parts by weight of α-arbutin, 8 parts by weight of nicotinamide, 5 parts by weight of 3-O-ethyl ascorbic acid, 0.5 parts by weight of Centella asiatica extract, and 3 parts by weight of retinyl palmitate. The aforementioned nanocarrier is It contains 10 parts by weight of an emulsifier (PEG-40 hydrogenated castor oil), 20 parts by weight of polyhydric alcohol (15 parts by weight of glycerin + 5 parts by weight of octyldodecanol), 0.5 parts by weight of phospholipid (lecithin), and 50 parts by weight of water.

[0048] The method for producing the whitening nanocomposition according to this example was the same as in Example 1, except that the amount of each component used was different.

[0049] Example 6 In one embodiment of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this embodiment is substantially the same as that of Example 1, but differs in that the emulsifier in the nanocarrier is polysorbate-80, the polyhydric alcohol is glycerin, and the phospholipid is soy lecithin.

[0050] The method for producing the whitening nanocomposition according to this example was the same as in Example 1, except that the nanocarrier was different.

[0051] Comparative Example 1 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this comparative example was substantially the same as that of Example 1, but differed in that the active ingredient was α-arbutin (28.5 parts by weight).

[0052] The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0053] Comparative Example 2 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition in this comparative example was substantially the same as that in Example 1, except that the active ingredient was nicotinamide (28.5 parts by weight).

[0054] The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0055] Comparative Example 3 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition in this comparative example was substantially the same as that in Example 1, except that the active ingredient was 3-O-ethyl ascorbic acid (28.5 parts by weight).

[0056] The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0057] Comparative Example 4 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition in this comparative example was substantially the same as that in Example 1, except that the active ingredient was Centella asiatica extract (28.5 parts by weight).

[0058] The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0059] Comparative Example 5 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition in this comparative example was substantially the same as that in Example 1, but differed in that the active ingredient was retinyl palmitate (28.5 parts by weight).

[0060] The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0061] Comparative Example 6 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition according to this comparative example is substantially the same as that of Example 1, but the active ingredient is It differed in that it contained 10 parts by weight of α-arbutin, 10 parts by weight of nicotinamide, 5 parts by weight of 3-O-ethyl ascorbic acid, and 0.5 parts by weight of Centella asiatica extract. The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0062] Comparative Example 7 In one comparative example of the whitening nanocomposition of the present invention, the whitening nanocomposition in this comparative example was substantially the same as that in Example 1, but differed in that the active ingredient was 3 parts by weight of retinyl palmitate.

[0063] The method for producing the whitening nanocomposition according to this comparative example was the same as in Example 1, except that the active ingredient was different.

[0064] Comparative Example 8 In one comparative example of the whitening free composition of the present invention, the whitening free composition according to this comparative example is It contains 10 parts by weight of α-arbutin, 10 parts by weight of nicotinamide, 5 parts by weight of 3-O-ethyl ascorbic acid, 0.5 parts by weight of Centella asiatica extract, 3 parts by weight of retinyl palmitate, and 71.5 parts by weight of solvent (dimethyl sulfoxide and water mixed in a mass ratio of 1:9).

[0065] The method for producing the whitening free composition using this comparative example is as follows. α-Arbutin, nicotinamide, 3-O-ethyl ascorbic acid, Centella asiatica extract, retinyl palmitate, and a solvent were stirred at 45°C and 150-200 rpm for 15 minutes to obtain a whitening free composition.

[0066] Table 1. Parts by weight of each component in the whitening nanocompositions of Examples 1-6 [Table 1] Note: The average particle size in Table 1 above refers to the average value after measuring the sample three times using a particle size analyzer.

[0067] Performance testing 1. Stability Test The whitening nanocompositions in Examples 1-6 were randomly divided into groups A, B, C, and D. Group A was left at -20°C for 3 months, Group B at room temperature for 3 months, Group C at 4°C for 3 months, and Group D at 45°C for 3 months. After these periods, the presence or absence of layer separation or precipitation was observed. The experimental results showed that no layer separation or precipitation occurred in the whitening nanocompositions of each example, even under different temperature conditions. Simultaneously, when comparing the particle size of the whitening nanocompositions of each example before and after testing, no significant change was observed in the average particle size after being left for 3 months under different temperature conditions compared to before the test, fully demonstrating that the whitening nanocompositions of the present invention have excellent storage stability.

[0068] 2. Chicken embryo chorionic allanal membrane irritation test The whitening nanocompositions in Examples 1-5 were each diluted 10-fold with water, and 200 μL of each was dropped onto the surface of the chicken embryo chorionic villi. After 300 seconds, vascular changes were observed and data recorded, and the irritation score (IS) was calculated. As shown in Figure 1, after the 10-fold diluted whitening nanocompositions were in contact with the chicken embryo chorionic villi for 300 seconds, no capillary bleeding, vasolysis, or coagulation phenomena were observed, and the irritation score for Examples 1-5 was 0.07 for all of them. This indicates that the whitening nanocompositions of the present invention are highly safe and non-irritating.

[0069] 3. Patch test Thirty subjects were randomly divided into six groups (five subjects per group). A blank serum (2.0% by weight glycerin, 0.3% by weight carbomer, 0.1% by weight xanthan gum, 0.5% by weight phenoxyethanol, purified water, remainder) was used as the blank control group. A mixture of each of the whitening nanocompositions from Examples 1-5 and the blank serum was used as the experimental group (the mass fraction of the whitening nanocomposition relative to the blank serum was 10%). Subsequently, the experimental group and the blank control group were applied to the inner forearm of the subjects (continued for 24 hours), and skin reactions were observed after the indentation disappeared. The test results showed that none of the 30 subjects exhibited symptoms such as mild erythema, erythema, edematous erythema, severe redness, infiltration, papules, or symptoms accompanied by papules or blisters, confirming that the whitening nanocompositions of the present invention are not irritating to human skin.

[0070] 4. Cumulative permeation and skin retention test A blank serum consisting of 2.0% by weight glycerin, 0.3% by weight carbomer, 0.1% by weight xanthan gum, 0.5% by weight phenoxyethanol, and the remainder purified water was used to prepare a whitening nanocomposition serum (blank serum + whitening nanocomposition of Example 1 at a mass fraction of 5% relative to the blank serum) and a whitening free composition serum (blank serum + whitening free composition of Comparative Example 8 at a mass fraction of 5% relative to the blank serum). Next, a skin permeability test was performed on detached pigskin using the Franz diffusion cell method, and phosphate buffer PBS (pH=7.4) was used as the receptor solution, which was stirred and diffused at 32°C. 0.5 mL of the receptor solution was collected after 4, 8, 12, and 24 hours, and the same amount of fresh receptor solution at constant temperature was immediately replenished. High-performance liquid chromatography (HPLC) analysis was performed to calculate the cumulative permeation of α-arbutin per unit area in the receptor solution from the aforementioned whitening nanocomposition serum and whitening free composition serum at each time point. After 24 hours, the skin was removed, washed, sheared, and polished to obtain a homogeneous solution. An appropriate amount of solvent was added, and the solution was centrifuged. The supernatant was analyzed by HPLC to calculate the amount of α-arbutin retained in the skin per unit area.

[0071] (1)Cumulative skin permeation amount The cumulative skin penetration amount Q of α-arbutin at different sampling times is calculated according to the following formula. Q=Q n / S Here, S is the area of the diffusion cell (2.27 cm 2 ), and Q n is calculated by the following formula.

Mathematical Formula

[0072] (2) Skin retention According to the following formula, the skin retention amount Q m of α-arbutin at different sampling time points is calculated. Q m =C m ×V m / S Here, S is the area of the diffusion cell (2.27 cm 2 ), C m is the drug concentration measured in the homogenized skin solution, and V m is the volume of the homogenized skin solution.

[0073] The test results of cumulative skin permeation amount are shown in Figure 2. From Figure 2, after 12 hours, the cumulative skin permeation amount of α-arbutin per unit area in the whitening free composition serum and the whitening nano-composition serum are 8.16 μg / cm 2 and 29.47 μg / cm 2 respectively; after 24 hours, the cumulative skin permeation amount of α-arbutin per unit area are 24.68 μg / cm 2 and 98.42 μg / cm 2The results were as follows: Compared to the whitening free composition serum, the cumulative skin penetration of α-arbutin per unit area after 12 hours in the whitening nano composition serum improved by 261.2%, and the cumulative skin penetration per unit area after 24 hours improved by 298.8%. The test results for skin retention are shown in Figure 3. From Figure 3, the skin retention amounts of α-arbutin in the whitening free composition serum and the whitening nano composition serum were 43.57 μg / cm³, respectively. 2 and 287.35 μg / cm³ 2 As a result, it was found that the amount of α-arbutin retained in the skin in the whitening nano-composition serum improved by 261.2% compared to the whitening free composition serum. From the above, it was confirmed that the whitening nano-composition of the present invention effectively promotes the skin permeability of α-arbutin and retains it in the skin, thereby effectively improving its dermal bioavailability.

[0074] 5. Observation of skin penetration behavior using laser scanning confocal microscopy. After labeling the samples tested in "4. Cumulative Permeation and Skin Retention Test" above with rhodamine B (RhoB), frozen sections were prepared, and the permeation behavior of free RhoB (sample corresponding to the whitening free composition serum) and RhoB nanocarrier (sample corresponding to the whitening nanocomposition serum) within skin tissue at different time points was observed using a laser scanning confocal microscope. The test results are shown in Figures 4 and 5.

[0075] Figures 4 and 5 show that the fluorescence penetration depth in the skin increased over time. At 4 hours, the penetration depth of free RhoB into the skin was 63.9 μm, while the penetration depth of the RhoB nanocarrier reached 305.6 μm, indicating that the whitening nanocomposition serum can penetrate to the deep tissues of the skin. At the same time (4 hours), the relative fluorescence intensity of free RhoB was 3.8, while the relative fluorescence intensity of the RhoB nanocarrier reached 47.6, showing an improvement of 11.53 times compared to free RhoB. In other words, the fluorescence intensity of the RhoB nanocarrier in the skin is clearly stronger than that of free RhoB, further demonstrating that the nanocarrier promotes the transdermal absorption of the active ingredient and delivers it to the target site in the skin, thereby improving the skin bioavailability of the whitening nanocomposition.

[0076] 6. Intracellular tyrosinase activity Intracellular tyrosinase activity was measured using the L-Dopa oxidation method. The specific procedure is as follows: 5.0 × 10⁶ B16F10 cells in the logarithmic growth phase 4 Cells were seeded at a density of cells / well into 24-well plates and cultured for 24 hours. After that, the cells were divided into a blank control group (added only to DMEM complete medium), a model group (added to DMEM complete medium containing 100 nmol / L α-melanocyte-stimulating hormone (α-MSH)), and an experimental group (added to DMEM complete medium containing 100 nmol / L α-MSH + 2000-fold diluted whitening nanocompositions of Comparative Examples 1-7, the whitening free composition of Comparative Example 8, and the whitening nanocomposition of Example 1). Three double pores were created in each group.

[0077] After continuing incubation for 48 hours, 200 μL of cell lysis buffer containing 1% (v / v) polyethylene glycol octylphenyl ether (Triton X-100) was added to each well, and the mixture was frozen and thawed at -80°C for 30 minutes. The cell lysis mixture was then collected and centrifuged, and 100 μL of the supernatant was transferred to a 96-well plate. 100 μL of 0.1% (w / v) L-DOPA solution was added, and after incubation at 37°C for 2 hours, the absorbance (A) of the sample in each well was measured at a wavelength of 495 nm using a microplate reader. The test results are shown in Figure 6.

[0078] As can be seen from Figure 6, compared to the model group, the whitening nanocompositions of Comparative Examples 1, 2, 3, 4, and 6, the whitening free composition of Comparative Example 8, and the whitening nanocomposition of Example 1 all significantly reduced tyrosinase activity (P<0.05 or P<0.01), while the whitening nanocompositions of Comparative Examples 5 and 7 did not show a significant effect on reducing tyrosinase activity (P>0.05). This suggests that retinyl palmitate is not very effective in suppressing tyrosinase activity.

[0079] Compared to Comparative Example 6, the inhibitory effect of the whitening nanocomposition of Example 1 on the tyrosinase activity of B16F10 cells was more pronounced (P<0.01). Specifically, the inhibition rate of tyrosinase activity in B16F10 cells was 32.3% for the whitening nanocomposition containing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and Centella asiatica extract (Comparative Example 6), while the inhibition rate of tyrosinase activity in B16F10 cells was 64.7% for the whitening nanocomposition containing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, Centella asiatica extract, and retinyl palmitate (Example 1), representing a 100.3% improvement in tyrosinase activity inhibition. From this, it was confirmed that retinyl palmitate has a synergistic effect with α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and Centella asiatica extract, and can significantly suppress intracellular tyrosinase activity.

[0080] Compared to Comparative Example 8 (tyrosinase activity inhibition rate of 34.4%), the whitening nanocomposition of Example 1 showed a more significant reduction in the tyrosinase activity of B16F10 cells (P<0.01), and the tyrosinase activity inhibition rate improved by 88.1%. This fully demonstrates that the nanocarrier can enhance the tyrosinase activity inhibition rate of the active ingredient, significantly improving the whitening effect of the whitening nanocomposition.

[0081] 7. Measurement of cellular melanin content and observation of melanin production status. Intracellular melanin content was measured using the NaOH lysis method. The specific procedure is as follows: 5.0 × 10⁶ B16F10 cells in the logarithmic growth phase 4 Cells were seeded at a density of cells / well into 24-well plates and cultured for 24 hours. After that, the cells were divided into a control group (added only to DMEM complete medium), a model group (added to DMEM complete medium containing 100 nmol / L α-MSH), and an experimental group (added to DMEM complete medium containing 100 nmol / L α-MSH + 2000-fold diluted whitening nanocompositions of Comparative Examples 1-7, the whitening free composition of Comparative Example 8, and the whitening nanocomposition of Example 1). Three double pores were placed in each group.

[0082] After culturing for another 48 hours, the cells from each well were separated and collected in centrifuge tubes. 200 μL of a 1 mol / L NaOH solution containing 10% DMSO was added to each centrifuge tube. Next, the EP (Eppendorf) tubes were heated in an 80°C constant temperature water bath for 1 hour to lyse the cells and dissolve the melanin. The cells were then centrifuged and the supernatant was transferred to a 96-well plate. The absorbance (A) of the sample in each well was measured at a wavelength of 405 nm using a microplate reader. The test results are shown in Figure 7.

[0083] As can be seen from Figure 7, compared to the model group, the whitening nanocompositions of Comparative Examples 1, 2, 3, 4, and 6, the whitening free composition of Comparative Example 8, and the whitening nanocomposition of Example 1 were all able to significantly reduce the intracellular melanin content (P<0.05 or P<0.01), while the whitening nanocompositions of Comparative Examples 5 and 7 did not show a significant effect on reducing the intracellular melanin content (P>0.05). This indicates that retinyl palmitate is not very effective in suppressing intracellular melanin production.

[0084] Compared to Comparative Example 6, the reduction effect of the whitening nanocomposition of Example 1 on the intracellular melanin content of B16F10 cells was more significant (P<0.01). Specifically, the reduction rate of intracellular melanin content in B16F10 cells was 24.6% for the whitening nanocomposition containing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and centella asiatica extract (Comparative Example 6), while the reduction rate of intracellular melanin content in the whitening nanocomposition containing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, centella asiatica extract, and retinyl palmitate (Example 1) was 56.8%, an improvement of 130.9%. From this, it was confirmed that retinyl palmitate has a synergistic effect with α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and centella asiatica extract, and can significantly reduce intracellular melanin content. Furthermore, compared to Comparative Example 8, the intracellular melanin content suppression rate in Example 1 improved by 111.2%. This fully demonstrated that retinyl palmitate has a synergistic effect with α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and centella asiatica extract, significantly promoting the effects of the whitening active ingredients, and that the nanocarrier can further enhance the effects of the whitening active ingredients.

[0085] 8. Human efficacy evaluation test A blank serum was prepared consisting of 2.0% by weight glycerin, 0.3% by weight carbomer, 0.1% by weight xanthan gum, 0.5% by weight phenoxyethanol, and the remainder purified water.

[0086] Control group 1: Blank serum, Control group 2: Blank serum + whitening nanocomposition of Comparative Example 1 in a mass fraction of 5% relative to the blank serum. Control group 3: Blank serum + whitening nanocomposition of Comparative Example 2 in a mass fraction of 5% relative to the blank serum. Control group 4: Blank serum + whitening nanocomposition of Comparative Example 3 in a mass fraction of 5% relative to the blank serum. Control group 5: Blank serum + whitening nanocomposition of Comparative Example 4 in a mass fraction of 5% relative to the blank serum. Control group 6: Blank serum + whitening nanocomposition of Comparative Example 5 in a mass fraction of 5% relative to the blank serum. Control group 7: Blank serum + whitening nanocomposition of Comparative Example 6 in a mass fraction of 5% relative to the blank serum. Control group 8: Blank serum + whitening nanocomposition of Comparative Example 7 in a mass fraction of 5% relative to the blank serum. Control group 9: Blank serum + whitening free composition of Comparative Example 8 in a mass fraction of 5% relative to the blank serum. Experimental group: Blank serum + whitening nanocomposition of Example 1 in a mass fraction of 5% relative to the blank serum.

[0087] Thirty volunteers (ages 20-60, good health, no skin conditions, not pregnant or lactating, no allergies to product ingredients) were recruited. After explaining the evaluation process, expected effects, risks, and precautions, and obtaining informed consent regarding the efficacy evaluation, the volunteers were randomly divided into 10 groups (3 volunteers per group), and efficacy evaluation tests were conducted for each of the control and experimental groups. Specifically, the sample was applied to the face twice a day at the prescribed times as instructed, and the use of other products or medications that could affect skin condition was prohibited during the test period. Participants were required to truthfully and accurately record and report their skin condition and sensation after use. After 4 weeks (28 days) of sample use, each efficacy indicator of the volunteers was observed and compared. Using the Shanghai Skin Huan Vplus (registered trademark) smart skin analysis system and the German CK MX18 skin melanin analyzer, we measured facial skin color and uniformity (individual typological angle (ITA° value) of skin color), skin glossiness (L* value (brightness) in the CIE Lab* color space), total area of ​​melanin and blemishes, and melanin index (MI value) of melanin and blemishes. We calculated the changes in each indicator parameter after sample use and determined the average value.

[0088] Table 2. Percentage changes in various skin indicators before and after sample use in volunteers. [Table 2]

[0089] According to the data in Table 2, after volunteers used the control group 1 sample (blank serum) for 4 weeks, measurements showed that the ITA° value increased by 0.31%, the skin L* value increased by 0.22%, the MI value decreased by 0.54%, and the melanin / spot area decreased by 0.15%. In other words, none of the above indicators showed significant changes, indicating that the blank serum had no effect on improving skin tone and uniformity, or the condition of melanin and spots.

[0090] Compared to control group 1, control groups 2-7, control group 9, and the volunteers in the experimental group showed a clear improvement in skin ITA° and L* values, and a significant decrease in MI values ​​and total melanin / spot area after using the sample for 4 weeks. Control group 8 showed limited improvement in whitening effect due to its low retinyl palmitate content. Among these, the effect of the sample in control group 7 (a whitening nanocomposition containing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and centella asiatica extract) was significantly improved, with the corresponding volunteer's skin ITA° value increasing by 6.58%, L* value increasing by 5.16%, MI value decreasing by 8.47%, and total melanin / spot area decreasing by 10.28%. On the other hand, the experimental group's sample (a whitening nano-composition combining α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, centella asiatica extract, and retinyl palmitate + blank serum) showed even greater efficacy. After the corresponding volunteers used the sample, their skin ITA° value increased by 11.08%, L* value increased by 11.43%, MI value decreased by 18.67%, and the total area of ​​melanin and blemishes decreased by 21.42%, fully demonstrating a synergistic whitening effect between α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, centella asiatica extract, and retinyl palmitate.

[0091] Furthermore, after using the control group 9 sample (whitening free composition of Comparative Example 8 + blank serum), the corresponding volunteers' skin ITA° values ​​increased by 6.86%, L* values ​​increased by 5.96%, MI values ​​decreased by 9.15%, and the total area of ​​melanin and blemishes decreased by 10.76%, indicating that its whitening effect was inferior to that of the experimental group. This demonstrates that only by combining the whitening active ingredient with a nanocarrier can the effects on skin tone and uniformity, as well as melanin and blemishes, be effectively improved.

[0092] Figures 8 and 9 show comparison charts of facial skin tone (Figures 8A and 9A) and facial pigment / spot comparison charts (Figures 8B and 9B) on days 0, 14, and 28 of different volunteers (Volunteers 1 and 2) using the experimental group's sample, all collected using a Vplus instrument. From Figures 8 and 9, it was confirmed that after using a serum containing 5% of the whitening nanocomposition in Example 1 for 28 days, a reduction in the number and average area of ​​melanin and spots, as well as a clear improvement in skin tone uniformity and glossiness, were observed on the volunteers' faces, demonstrating an excellent whitening effect.

[0093] The above embodiments are for illustrative purposes only and do not limit the scope of protection of the present invention. Even if the present invention is described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the proposed technical concept of the present invention without deviating from its substance and scope.

Claims

1. The product comprises an active ingredient and a nanocarrier, wherein the active ingredient is coated with the nanocarrier and / or adsorbed onto the nanocarrier. The active ingredients include 1 to 15 parts by weight of α-arbutin, 1 to 15 parts by weight of nicotinamide, 1 to 10 parts by weight of 3-O-ethyl ascorbic acid, 0.1 to 1 part by weight of Centella asiatica extract, and 1 to 5 parts by weight of retinyl palmitate. The nanocarrier contains 5 to 10 parts by weight of emulsifier, 5 to 20 parts by weight of polyhydric alcohol, 0.1 to 5 parts by weight of phospholipid, and 40 to 60 parts by weight of water. A skin-whitening nanocomposition characterized by the following features.

2. The whitening nanocomposition according to claim 1, characterized in that the mass ratio of the active ingredient to the nanocarrier is (15-30):(65-80).

3. The whitening nanocomposition according to claim 1 or 2, characterized in that the emulsifier comprises at least one of a polyoxyethylene castor oil-based emulsifier, a polyoxyethylene hydrogenated castor oil-based emulsifier, a polyglycerin-based emulsifier, a poloxamer, and a coconut oil alkyl glucoside.

4. The whitening nanocomposition according to claim 1 or 2, characterized in that the polyhydric alcohol comprises at least one of glycerin, propylene glycol, butylene glycol, 1,3-propylene glycol, 1,2-pentylene glycol, 1,2-hexylene glycol, dipropylene glycol, isopropanol, polyethylene glycol-200, PPG-10 sorbitol, and octyldodecanol.

5. The skin-whitening nanocomposition according to claim 1 or 2, characterized in that the phospholipid comprises at least one of hydrogenated lecithin, lecithin, and soy lecithin.

6. A method for producing a skin-whitening nanocomposition according to any one of claims 1 to 5, Step S1 involves uniformly mixing α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid, and Centella asiatica extract with phospholipids, water, and some polyhydric alcohols to obtain a mixture I. Step S2 involves uniformly mixing retinyl palmitate, an emulsifier, and the remaining polyhydric alcohol to obtain mixture II. Step S3 involves uniformly mixing the mixture I in step S1 and the mixture II in step S2, then homogenizing them to obtain a whitening nanocomposition. A manufacturing method characterized by including

7. A method for producing the whitening nanocomposition according to claim 6, characterized in that it satisfies at least one of the following (I) to (III). (I) Specifically, step S1 involves stirring α-arbutin, nicotinamide, 3-O-ethyl ascorbic acid and centella asiatica extract with phospholipids, water and some polyhydric alcohols at 40-65°C and 150-200 rpm for 10-30 minutes to obtain mixture I. (II) Specifically, step S2 involves stirring retinyl palmitate, an emulsifier, and the remaining polyhydric alcohol at 40-65°C and 150-200 rpm for 10-30 minutes to obtain mixture II. (III) Step S3 specifically involves stirring the mixture I in S1 and the mixture II in S2 at 40 to 65°C and 200 to 270 rpm for 10 to 30 minutes to homogenize them and obtain a whitening nanocomposition.

8. Use of the whitening nanocomposition according to any one of claims 1 to 5 in the manufacture of a skincare product or cosmetic.

9. A whitening skincare product or whitening cosmetic comprising the whitening nanocomposition according to any one of claims 1 to 5.

10. The whitening skincare product or whitening cosmetic according to claim 9, characterized in that the mass fraction of the whitening nanocomposition in the whitening skincare product or whitening cosmetic is 0.1% to 30%.

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