Disk-shaped nanoparticles and composition for promoting skin absorption comprising the same

Abstract

The present invention relates to a composition for promoting skin absorption containing nanoparticles, wherein the composition has the advantage of excellent stability by controlling the content of cholesterol and lecithin, as well as the ability to control the number, particle size, and shape of the nanoparticles.

Description

Technology Field

[0001] This relates to a composition for promoting skin absorption. Background Technology

[0002] For functional cosmetics aimed at skin whitening and wrinkle improvement, it is crucial to effectively deliver active ingredients to the skin. This is because no matter how beneficial an ingredient is, it cannot produce proper results if it fails to penetrate skin barriers, such as the stratum corneum, and reach deeper into the skin.

[0003] Transdermal absorption promoters play a role in increasing the skin permeability of active ingredients in cosmetics by lowering the skin's barrier function. These formulations must be intended solely to enhance the permeability of ingredients that are non-toxic and non-irritating. Substances that promote transdermal absorption can be classified according to their characteristics into water-soluble organic solvents that increase skin absorption by enhancing the solubility of lipophilic molecules; formulations that promote absorption by breaking down keratin and moisturizing and softening the stratum corneum; and surfactants and oils that act on the lipids of the stratum corneum to loosen the tight layers of the stratum corneum.

[0004] Meanwhile, polyethylene glycol (PEG) is widely used in cosmetics as a surfactant, detergent, emulsifier, etc. During the manufacturing process, 1,4-dioxane, which is harmful to humans, can be produced as a byproduct due to the dimerization of ethylene oxide.

[0005] Therefore, there is a need to develop a skin delivery system that can promote the absorption of active ingredients into the skin by using a safer surfactant without PEG components. Prior art literature

[65535] Republic of Korea Published Patent Application No. 10-2005-0026778 The problem to be solved

[0006] One aspect provides a nanoparticle composition comprising cholesterol, hydrogenated lecithin and polyglyceryl nonionic surfactant.

[0007] Another aspect is to provide a composition for promoting skin absorption comprising a nanoparticle composition according to one aspect. means of solving the problem

[0008] One aspect provides a nanoparticle composition comprising cholesterol, hydrogenated lecithin, and a polyglyceryl nonionic surfactant.

[0009] In this specification, the term "nanoparticle" refers to a lipid-based skin delivery system that has the effect of promoting the absorption of an active substance into the skin while softening the skin without damaging the skin barrier.

[0010] In one embodiment, it was confirmed that the number, size, and shape of nanoparticles can be controlled by adjusting the content of hydrogenated lecithin. Accordingly, the nanoparticles according to one embodiment may have one or more shapes selected from the group consisting of micelles, disk-shaped, bicells, and multi-layers depending on the content of hydrogenated lecithin. For example, when the content of hydrogenated lecithin is 0.01 wt% or more, micelle-shaped nanoparticles are formed; when it is 0.05 wt% or more, disk-shaped or bicell shapes are produced; and when it is 1 wt% or more, disk-shaped or bicell-shaped particles may decrease and multi-layer particles may increase.

[0011] Since the rate of skin penetration of the composition and the loading capacity of the active substance encapsulated within the nanoparticles can vary depending on the size and shape of the nanoparticles, the development of various particle shapes is necessary for the efficient skin absorption of the active substance of the composition.

[0012] The above nanoparticles may have a particle size of 20 nm to 500 nm. The above nanoparticles may have a size of, for example, 20 nm to 500 nm, 20 nm to 450 nm, 20 nm to 400 nm, 20 nm to 350 nm, 20 nm to 300 nm, 20 nm to 250 nm, 20 nm to 200 nm, 30 nm to 500 nm, 30 nm to 450 nm, 30 nm to 400 nm, 30 nm to 350 nm, 30 nm to 300 nm, 30 nm to 250 nm, 30 nm to 200 nm, 40 nm to 500 nm, 40 nm to 450 nm, 40 nm to 400 nm, 40 nm to 350 nm, 40 nm to 300 nm, 40 nm to 250 nm, or 40 nm to 200 nm. In one embodiment, the nanoparticles may have a particle size of 20 nm to 200 nm. The particle size may refer to the diameter of the nanoparticles. The particle size of the nanoparticles may vary depending on the type of constituent components or active substances.

[0013] The above nanoparticles may have a vesicle wall thickness of 5 nm to 30 nm. The above nanoparticles may have a thickness of, for example, 5 nm to 30 nm, 5 nm to 25 nm, 5 nm to 20 nm, 5 nm to 15 nm, 5 nm to 10 nm, 10 nm to 30 nm, 10 nm to 25 nm, 10 nm to 20 nm, or 5 nm to 15 nm. In one embodiment, disk-shaped or bicell-shaped nanoparticles may have a vesicle wall thickness of 5 nm to 30 nm.

[0014] The cholesterol may be included in an amount of 0.5 to 20 weight% based on the total weight of the composition. The cholesterol may be included, for example, in an amount of 0.5 to 20 weight%, 0.5 to 15 weight%, 0.5 to 10 weight%, 0.5 to 5 weight%, 0.5 to 3 weight%, 0.5 to 2 weight%, or 0.5 to 1 weight%. In one embodiment, the cholesterol may be included in an amount of 0.5 to 2 weight% based on the total weight of the composition. In this case, if the content of the cholesterol falls outside the above range, there is a problem in that the transparency of the nanoparticle composition may decrease and the formulation stability may decrease.

[0015] The above hydrogenated lecithin may be included in an amount of 0.01 to 10% by weight based on the total weight of the composition. The above hydrogenated lecithin may be included, for example, in an amount of 0.01 to 5% by weight, 0.01 to 3% by weight, 0.01 to 2% by weight, or 0.01 to 1% by weight, 0.05 to 10% by weight, 0.05 to 5% by weight, 0.05 to 3% by weight, 0.05 to 2% by weight, or 0.05 to 1% by weight. In one embodiment, the above hydrogenated lecithin may be included in an amount of 0.01 to 1% by weight based on the total weight of the composition. In a specific embodiment, the above hydrogenated lecithin may be included in an amount of 0.05 to 1% by weight based on the total weight of the composition. At this time, if the content of the hydrogenated lecithin falls outside the above range, a sufficient number of the desired nanoparticle shapes may not be formed.

[0016] The above polyglyceryl nonionic surfactant may be one or more selected from the group consisting of polyglyceryl fatty acid esters, polyglyceryl esters, and polyglyceryl ethers.

[0017] In one embodiment, the polyglyceryl nonionic surfactant is polyglyceryl-4 caprylate / caprate, polyglyceryl-5 caprylate / caprate, polyglyceryl-6 caprylate / caprate, polyglyceryl-7 caprylate / caprate, polyglyceryl-8 caprylate / caprate, polyglyceryl-9 caprylate / caprate, polyglyceryl-10 caprylate / caprate, polyglyceryl-4 caprate, polyglyceryl-5 caprate, polyglyceryl-6 caprate, polyglyceryl-7 caprate, polyglyceryl-8 caprate, polyglyceryl-9 caprate, polyglyceryl-10 caprate, polyglyceryl-4 laurate, polyglyceryl-5 laurate, polyglyceryl-6 laurate, polyglyceryl-7 laurate, polyglyceryl-8 Laurate, Polyglyceryl-9 Laurate, Polyglyceryl-10 Laurate, Polyglyceryl-6 Cocoate, Polyglyceryl-7 Cocoate, Polyglyceryl-8 Cocoate, Polyglyceryl-9 Cocoate, Polyglyceryl-10 Cocoate, Polyglyceryl-11 Cocoate, Polyglyceryl-12 Cocoate, Polyglyceryl-6 Myristate, Polyglyceryl-7 Myristate, Polyglyceryl-8 Myristate, Polyglyceryl-9 Myristate, Polyglyceryl-10 Myristate, Polyglyceryl-11 Myristate, Polyglyceryl-12 Myristate, Polyglyceryl-10 Oleate, Polyglyceryl-11 Oleate, Polyglyceryl-12 Oleate, Polyglyceryl-10 Stearate, Polyglyceryl-11 It may be one or more selected from the group consisting of stearate and polyglyceryl-12 stearate. More specifically, the polyglyceryl nonionic surfactant may be polyglyceryl-10 laurate and polyglyceryl-10 myristate.

[0018] In one embodiment, it was confirmed that when two types of polyglyceryl nonionic surfactants were used, the formulation stability was superior compared to when a polyglyceryl surfactant was used alone or a PEG surfactant was used. Therefore, the nanoparticles according to one embodiment can stably form particles of a desired shape when a specific surfactant is used.

[0020] Another aspect provides a composition for promoting skin absorption comprising a nanoparticle composition according to one aspect.

[0021] In one embodiment, the skin absorption-promoting composition may further include a skin active substance. The skin active substance may be, for example, niacinamide, adenosine, Centella Asiatica, oleanolic acid, retinol, ascorbic acid, flavonoid, polyphenol, isoflavone, ceramide, tocopherol, madecassic acid, asiaticoside, hyaluronic acid, collagen, etc. The skin active substance may be for skin whitening, wrinkle improvement, moisturization, skin barrier strengthening, antioxidant, anti-inflammatory, anti-aging, skin elasticity, and skin soothing, but is not limited thereto. Effects of the invention

[0023] A composition according to one aspect not only has excellent stability by controlling the cholesterol and lecithin content, but also has the advantage of being able to control the number, particle size, and shape of nanoparticles. Brief explanation of the drawing

[0024] Figure 1 shows the results of confirming the particle size and shape of the nanoparticle composition according to cholesterol content. Figure 2 shows the results of confirming the particle size and shape of the nanoparticle composition according to the lecithin content. Figure 3 shows the results of observing the structure of disk-particles in a nanoparticle composition according to one embodiment from various angles using a tilting cryo-TEM stage. Figure 4 shows the results of confirming the average thickness and diameter of disk particles in a nanoparticle composition according to one embodiment. Specific details for implementing the invention

[0025] Preferred embodiments are presented below to aid in understanding the present invention. However, the following embodiments are provided merely to facilitate a better understanding of the invention, and the scope of the invention is not limited by the following embodiments.

[0027] [Example]

[0028] Examples 1 to 4. Preparation of nanoparticle compositions

[0029] A nanoparticle composition containing the components and content (weight%) of Table 1 below was prepared. Specifically, the oil phase was heated and dissolved while mixing at 70–80°C, and then slowly added to the aqueous phase while stirring with an agitator for 5 minutes. After the first stirring, high-pressure emulsification was performed under conditions of 1,000 bar and 3 cycles to finally produce nanoparticles.

[0030] Examples 1 to 4 differ in the content of hydrogenated lecithin.

[0032] ingredient Example 1 Example 2 Example 3 Example 4 Awards Division purified water To 100 To 100 To 100 To 100 antiseptic Appropriate amount Appropriate amount Appropriate amount Appropriate amount polyol 5.00 5.00 5.00 5.00 Yoo Sang-bu Hydrogenated lecithin 0.05 0.10 0.50 1.00 cholesterol 1.00 1.00 1.00 1.00 Dipropylene glycol 10.00 10.00 10.00 10.00 Polyglyceryl-10 laurate 2.00 2.00 2.00 2.00 Polyglyceryl-10 myristate 1.75 1.75 1.75 1.75

[0034] [Comparative Example]

[0035] Comparative Examples 1 to 8. Preparation of nanoparticle compositions

[0036] A nanoparticle composition was prepared in the same manner as the above example, except that it contained the components and content (weight%) of Table 2 below.

[0037] Specifically, Comparative Examples 1 to 8 do not contain hydrogenated lecithin, unlike the Examples.

[0038] In addition, Comparative Examples 1 to 3 differ in cholesterol content. Comparative Examples 4 and 5 contain only one of polyglyceryl-10 laurate and polyglyceryl-10 myristate. Comparative Examples 6 to 8 used polyethylene glycol (PEG) surfactants instead of polyglyceryl nonionic surfactants.

[0039] ingredient Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Awards Division purified water To 100 To 100 To 100 To 100 To 100 To 100 To 100 To 100 antiseptic Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount polyol 5.00 5.00 5.00 5.00 5.00 5.00 5.00 5.00 Yoo Sang-bu Hydrogenated lecithin - - - - - - - - cholesterol 0.50 1.00 2.00 1.00 1.00 1.00 1.00 1.00 Dipropylene glycol 10.00 10.00 10.00 10.00 10.00 10.00 10.00 10.00 Polyglyceryl-10 laurate 2.00 2.00 2.00 3.75 - - - - Polyglyceryl-10 myristate 1.75 1.75 1.75 - 3.75 - - - PEG-40 Hydrogenated Castor Oil - - - - -- 3.75 - - Octyldodeces-16 - - - - - - 3.75 - Coles-24 - - - - - - - 3.75

[0041] [Experimental Example]

[0042] Experimental Example 1. Confirmation of particle size, shape, and formulation stability according to cholesterol content

[0043] Particle size, morphology, and formulation stability according to cholesterol content of the nanoparticle composition according to one embodiment were confirmed. Specifically, after preparation, particle size and morphology were observed via Cryo-TEM (Cryogenic transmission electron microscopy) measurements, and visual evaluation was performed to assess long-term stability.

[0044] Figure 1 shows the results of confirming the particle size and shape of the nanoparticle composition according to cholesterol content.

[0045] As a result, as shown in Fig. 1, round vesicles were identified in Comparative Examples 1 to 3, and the particle size tended to decrease as the cholesterol content increased. In particular, when the cholesterol content was 1%, it was confirmed that not only was the particle size uniform, but it also remained stable for more than 60 days without separation, precipitation, or turbidity. When the cholesterol content was less than 1% or 2% or more, the transparent formulation became turbid or turned milky white.

[0046] Therefore, the nanoparticle composition according to one embodiment contains cholesterol in a specific amount, thereby not only forming particles of a constant size and shape but also having excellent formulation stability.

[0048] Experimental Example 2. Confirmation of nanoparticle morphology depending on the presence or absence of lecithin

[0049] Nanoparticles were identified according to the presence or absence of lecithin in a nanoparticle composition according to one embodiment. Specifically, after fixing the cholesterol content at 1%, the size distribution and morphology of the nanoparticle composition according to the presence or absence of lecithin were identified using DLS (Dynamic light scattering) and Cryo-TEM.

[0050] Figure 2 shows the results of confirming the particle size and shape of the nanoparticle composition according to the lecithin content.

[0051] As a result, unlike Comparative Example 2 in Fig. 1, where only circular nanoparticles were observed, disc-shaped nanoparticles were observed in Examples 1 to 4 in Fig. 2, which contain lecithin. Specifically, while the ratio of cholesterol and surfactant was the same, disc-shaped particles were clearly observed in Examples 1 through 4, which contained 0.05% or more lecithin compared to Comparative Example 2, as the lecithin content increased. It was confirmed that the number of disc-shaped particles increased with increasing lecithin content, but as the content exceeded 1%, the number of particles decreased, and multi-layered particles were formed.

[0052] In addition, the structure of the disk particles within the nanoparticle composition was observed using a tilting cryo-TEM (cryogenic-TEM) stage to further confirm the structure.

[0053] Figure 3 shows the results of observing the structure of disk-particles in a nanoparticle composition according to one embodiment from various angles using a tilting cryo-TEM stage.

[0054] As a result, as shown in Figure 3, the nanoparticles, which appeared as cylinders when observed at a stage tilt of 0 degrees, were observed as wide discs when tilted 50 degrees. Through this, it was found that the structure of the particles forming a two-dimensional structure, which represents the side view and top view of the nanoparticles, is a nanodisk.

[0055] Figure 4 shows the results of confirming the average thickness and diameter of disk particles in a nanoparticle composition according to one embodiment.

[0056] In addition, as shown in Figure 4, 300 nanodiscs observed in the cryo-TEM image were selected and their average thickness and diameter were measured, and it was confirmed that they had a thickness of 9.5 nm and a diameter of 45 nm, respectively.

[0057] That is, the nanoparticle composition according to one embodiment can not only form disc-shaped nanoparticles by including lecithin, but also allows for the control of the number, size, and shape of the nanoparticles by adjusting the lecithin content.

[0059] Experimental Example 3. Confirmation of nanoparticle formation depending on the type of surfactant

[0060] The presence or absence of nanoparticle formation was confirmed according to the type of surfactant in the nanoparticle composition according to one embodiment. Specifically, as in Comparative Examples 4 to 8, when a polyglyceryl-based surfactant was used alone or when a polyethylene glycol (PEG) surfactant was used alone, the presence or absence of nanoparticle formation was compared by visual evaluation after being stored for 30 days.

[0061] As a result, it was confirmed that when PEG surfactants were used, crystals precipitated or separated, and when polyglyceryl surfactants were used alone, cloudiness occurred and stability was poor.

[0063] In other words, summarizing the above results, it can be seen that the stable formation of particles with specific shapes, such as disc particles, is observed when cholesterol, lecithin, and a surfactant are in an optimal ratio and a specific surfactant is used.

[0065] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

Claims

Claim 1 A nanoparticle composition in the form of disk-shaped or bicell nanoparticles comprising cholesterol, hydrogenated lecithin, and a polyglyceryl nonionic surfactant, wherein the polyglyceryl nonionic surfactant is polyglyceryl-10 laurate and polyglyceryl-10 myristate. Claim 2 delete Claim 3 A nanoparticle composition according to claim 1, wherein the cholesterol is included in an amount of 0.5 to 2 weight% based on the total weight of the composition. Claim 4 A nanoparticle composition according to claim 1, wherein the hydrogenated lecithin is included in an amount of 0.01 to 1 weight% based on the total weight of the composition. Claim 5 delete Claim 6 delete Claim 7 A nanoparticle composition according to claim 1, wherein the nanoparticles have a size of 20 nm to 500 nm. Claim 8 A nanoparticle composition according to claim 1, wherein the nanoparticles have a thickness (vesicle wall thickness) of 5 nm to 30 nm. Claim 9 A composition for promoting skin absorption comprising the nanoparticle composition of claim 1. Claim 10 A composition for promoting skin absorption according to claim 9, further comprising a skin active substance.

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