Liposome comprising graphene oxide having excellent skin penetration efficacy, and cosmetic composition comprising same

Abstract

The present invention relates to a liposome comprising graphene oxide having excellent skin penetration efficacy, and a cosmetic composition comprising the liposome, which has excellent liposome particle stability and excellent skin penetration efficacy, thereby exhibiting a superb effect on skin improvement.

Description

Liposome containing graphene oxide with excellent skin penetration efficacy and cosmetic composition containing the same

[0001] The present invention relates to a novel liposome utilizing graphene, and more specifically, to a liposome containing graphene oxide having excellent skin penetration efficacy and a cosmetic composition containing the same.

[0002] The skin is largely composed of three layers: the epidermis, dermis, and subcutaneous tissue. Cosmetics are typically applied only to the outermost layer of the epidermis, limiting their ability to deliver beneficial ingredients deep into the skin.

[0003] As consumer awareness has increased, there's a growing trend of expecting dermatologically equivalent results from simply using cosmetics. The cosmetics industry is consistently researching technologies that deliver the functional ingredients of cosmetics to the dermis or even deeper, rather than just the epidermis, to meet these consumer needs.

[0004] Among these technologies, liposomes are a prime example. Liposomes have traditionally been used in the pharmaceutical field as drug delivery vehicles to enhance drug efficacy, reduce toxicity, and target targeting. Recently, research is being conducted to apply this liposome technology to cosmetics, delivering functional ingredients directly to the skin.

[0005] However, unlike the pharmaceutical industry, where active ingredients can easily reach cells directly through oral or injectable methods, in the cosmetics field, ensuring liposomes loaded with active ingredients penetrate the thick stratum corneum, reach skin cells, and deliver functional active ingredients is a technically challenging task. Therefore, the development of liposomes with superior skin penetration and particle stability is essential.

[0006] Accordingly, the inventor of the present invention completed the present invention by developing a novel liposome having excellent particle stability and strong skin penetration by utilizing graphene oxide in liposomes.

[0007] The purpose of the present invention is to provide a novel liposome comprising graphene oxide, which has excellent skin penetration efficacy and can effectively deliver functional ingredients to the skin.

[0008] The technical problems of the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned will be clearly understood by those skilled in the art from the description below.

[0009] According to an embodiment of the present invention, a liposome having excellent skin penetration efficacy is provided, wherein graphene oxide is included on the outer surface of the liposome.

[0010] Liposomes containing graphene oxide according to the present invention have excellent skin penetration efficacy, and thus can effectively deliver functional ingredients to the skin, thereby maximizing their efficacy in the skin.

[0011] The liposomes of the present invention, despite their multilayer structure, possess small particle sizes and excellent stability, enabling them to encapsulate greater amounts of functional ingredients than conventional liposomes. Furthermore, their high penetration power ensures superior skin delivery, resulting in superior skin improvement effects.

[0012] In order to more fully understand the drawings cited in the detailed description of the present invention, a brief description of each drawing is provided.

[0013] Figure 1 is a table showing the particle size distribution of Example 1.

[0014] According to an embodiment of the present invention, a liposome having excellent skin penetration efficacy is provided, wherein graphene oxide is included on the outer surface of the liposome.

[0015] Additionally, the graphene oxide may surround the outer surface of the liposome.

[0016] Additionally, the liposome may further include a phosphatidylcholine-based emulsifier.

[0017] Additionally, the liposome may further include a polyglyceryl emulsifier.

[0018] Additionally, the liposome may include at least one of ceramide, cholesterol, niacinamide, and a functional efficacy ingredient.

[0019] According to an embodiment of the present invention, a cosmetic composition comprising the liposome is provided.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains. In general, the nomenclature used herein is well known and commonly used in the art. In addition, when describing embodiments of the present invention, if a detailed description of a related known structure or function is judged to hinder the understanding of the embodiments of the present invention, a detailed description thereof will be omitted. In addition, although embodiments of the present invention will be described below, the technical idea of ​​the present invention is not limited or restricted thereto, and can be modified and implemented in various ways by those skilled in the art.

[0021] When a part in this specification is said to include a certain component, this does not exclude other components, unless otherwise specifically stated, but rather means that other components may be included. In this specification, the term "and / or" includes a combination of multiple related items or any one of multiple related items.

[0022]

[0023] The present invention relates to a novel liposome utilizing graphene, and relates to a novel type of liposome in which an oxidized form of graphene material is applied to the liposome, thereby improving skin penetration and maximizing the efficacy of functional ingredients in the skin.

[0024] Graphene is a carbon allotrope, a structure consisting of a flat layer of carbon atoms arranged in a hexagonal honeycomb pattern. Due to its structural characteristics, consisting of a single layer of carbon atoms, graphene can exist in various shapes, including tubular and spherical. Graphene oxide, the oxidized form of graphene, possesses hydrophilic functional groups (hydroxyl, carboxyl, epoxy, and ketone groups) that make it more soluble in water and alcohol than graphene. In particular, the high electron density of the carboxyl groups is expected to have antioxidant properties and positive effects on the human body.

[0025] Liposomes are small spherical vesicles with at least one lipid bilayer. Liposomes are composed of amphiphilic molecules with hydrophilic and hydrophobic groups, and the interaction between these amphiphilic molecules spontaneously combines to form an ordered structure in which the outer part of the bilayer is hydrophilic and the inner part is hydrophobic. Liposomes are classified into small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs), and multilamellar vesicles (MLVs) based on their size and lamellarity. SUVs have particle sizes ranging from 20 to 100 nm, LUVs exceeding 100 nm, and MLVs typically have particle sizes ranging from 1 to 5 μm and have multiple lipid bilayers. In general, liposomes have the advantage of being able to efficiently transport both hydrophilic and hydrophobic substances into cells due to their structure.

[0026] The liposome according to the present invention, since it contains graphene oxide (graphene oxide), has excellent skin penetration ability and can effectively deliver functional ingredients to the skin.

[0027] According to an embodiment, the liposome of the present invention may include graphene oxide on the outer surface of the liposome.

[0028] By including the above graphene oxide on the outer surface of the liposome, the stability of the liposome particle increases, and its hydrophilicity increases, facilitating water dispersion. Therefore, the liposome can be utilized as a component of a cosmetic composition.

[0029] In some embodiments, graphene oxide may surround the outer surface of the liposome. Specifically, the outer surface of the liposome may be structured such that graphene wraps around it in a spherical shape. When graphene oxide surrounds the outer surface of the liposome, the graphene oxide surface can significantly contribute to protecting the liposome particles from external forces, allowing them to reach the skin stably. Furthermore, the hydrophilicity of the surface can be further increased, facilitating water dispersion.

[0030] In an embodiment, graphene oxide may be included in an amount of 0.000005 to 1.4 wt%, specifically 0.000007 to 1.2 wt%, and more specifically 0.00001 to 1 wt%, based on the total weight of the liposome. If the graphene oxide is included in an amount of less than 0.000005 wt%, interaction with lecithin may be significantly reduced, resulting in the formation of a large amount of liposomes without graphene oxide on the outer surface. If the graphene oxide is included in an amount of more than 1.4 wt%, the formulation stability of the liposome may be poor, resulting in changes in particle size.

[0031]

[0032] In an embodiment, the liposome may include a phosphatidylcholine emulsifier as the main emulsifying component that forms the particle.

[0033] In an embodiment, a phosphatidylcholine emulsifier may be a main component forming a liposome and may interact with graphene oxide to position the graphene oxide on the outer surface of the liposome.

[0034]

[0035] In an embodiment, the phosphatidylcholine emulsifier may include at least one of hydrogenated phosphatidylcholine, hydrogenated lysophosphatidylcholine, phosphatidylcholine, lecithin, lysolecithin, hydroxylated lecithin, hydrogenated lysolecithin, and hydrogenated lecithin, and may specifically include hydrogenated lecithin, but is not limited thereto.

[0036] In an embodiment, the phosphatidylcholine-based emulsifier may be included in an amount of 0.005 to 10 wt%, specifically 0.01 to 10 wt%, and more specifically 0.05 to 10 wt%, based on the total weight of the liposome. If the phosphatidylcholine-based emulsifier is included in an amount of less than 0.005 wt%, unstable liposomes may be formed, and if the phosphatidylcholine-based emulsifier is included in an amount of more than 10 wt%, the solubility of the phosphatidylcholine-based emulsifier may decrease or the stability of the liposome formulation may be poor.

[0037] In an embodiment, a liposome in which graphene oxide is incorporated into the outer surface of the liposome may further comprise a lipid. In an embodiment, the lipid may comprise at least one selected from the group consisting of fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sphingophospholipids, sterol lipids, prenol lipids, and polyketide lipids, and specifically may comprise at least one of ceramide and cholesterol. However, the present invention is not limited thereto.

[0038] In an embodiment, when a lipid is further included, the lipid may be included in an amount of 0.0001 to 1 wt% based on the total weight of the liposome, specifically 0.0005 to 0.9 wt%, and more specifically 0.001 to 0.8 wt%.

[0039]

[0040] In embodiments, the liposomes may further comprise a polyglyceryl emulsifier.

[0041] In an embodiment, a polyglyceryl emulsifier can further enhance skin penetration function by imparting elasticity to liposomes in which graphene oxide is included on the outer surface of the liposomes.

[0042] In an embodiment, the polyglycerin-based emulsifier may include at least one of polyglyceryl-10 distearate, polyglyceryl-10 myristate, polyglyceryl-10 stearate, polyglyceryl-10 behenate / eicosadiyate, polyglyceryl-10 pentastearate, polyglyceryl-10 pentaoleate, polyglyceryl-2 diisostearate, polyglyceryl-2 dipolyhydroxystearate, polyglyceryl-2 sesquiisostearate, polyglyceryl-2 isostearate, polyglyceryl-2 tetraisostearate, polyglyceryl-2 triisostearate, polyglyceryl-3 diisostearate, polyglyceryl-4 stearate, polyglyceryl-4 isostearate, and polyglyceryl-3 methylglucose distearate, and specifically May contain, but is not limited to, polyglyceryl-3 methyl glucose distearate.

[0043] In an embodiment, the polyglycerin-based emulsifier may be included in an amount of 0.00001 to 1 wt% based on the total weight of the liposome, specifically 0.00005 to 0.9 wt%, and more specifically 0.0001 to 0.8 wt%. When the polyglycerin-based emulsifier is included in the above-described appropriate amount, it can provide excellent elasticity to the liposome, thereby improving skin penetration efficacy and particle stability.

[0044]

[0045] In some embodiments, the liposome may further include a functional ingredient. The functional ingredient is encapsulated within the liposome and delivered to the skin after the liposome penetrates the skin, thereby exerting the effects of each ingredient in the skin.

[0046] In the embodiment, the functional efficacy ingredient may be added by mixing various ingredients depending on the purpose of the cosmetic composition, and may include, for example, an anti-wrinkle agent, a UV protection ingredient, a whitening agent, a pigmentation functional ingredient, a skin soothing functional ingredient, vitamins and their derivatives, and a sebum or pore management functional ingredient, but is not limited thereto.

[0047] Examples of the above whitening agent include hydroquinone glycosides such as niacinamide, arbutin, and α-arbutin and their esters; ascorbic acid phosphate salts such as ascorbic acid, ascorbic acid phosphate ester sodium salt, and ascorbic acid phosphate ester magnesium salt; ascorbic acid fatty acid esters such as ascorbic acid tetraisopalmitic acid ester; ascorbic acid alkyl ethers such as ascorbic acid ethyl ether; ascorbic acid glucosides such as ascorbic acid-2-glucoside and their fatty acid esters; ascorbic acid derivatives such as ascorbic acid sulfate and tocopheryl ascorbyl phosphate; Plant extracts such as kojic acid, ellagic acid, tranexamic acid and its derivatives, ferulic acid and its derivatives, placenta extract, glutathione, oryzanol, butylresorcinol, soluble chamomile extract, soluble licorice extract, licorice root extract, and saxifrage extract may be included, but are not limited thereto.

[0048] Examples of the above vitamins and derivatives thereof include vitamin A such as retinol, retinol acetate, and retinol palmitate; vitamin B group such as thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinic acid such as nicotinamide / benzyl nicotinate, and choline; vitamin C such as ascorbic acid and its sodium salt; vitamin D; vitamin E such as α, β, γ, δ-tocopherol; other vitamins such as pantothenic acid and biotin; Ascorbic acid phosphate salts such as ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt, ascorbic acid fatty acid esters such as ascorbic acid tetraisopalmitate / ascorbyl stearate / ascorbyl palmitate / ascorbyl dipalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucosides and their fatty acid esters such as ascorbic acid-2-glucoside, ascorbic acid derivatives such as tocopheryl phosphate ascorbyl, vitamin derivatives such as tocopherol derivatives such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulate, tocopherol phosphate ester, tocotrienol, and other various vitamin derivatives; etc. may be included, but are not limited thereto.

[0049] In an embodiment, the functional efficacy component may be included in an amount of 0.0001 to 10 wt% based on the total weight of the liposome, specifically 0.0001 to 5 wt%, and more specifically 0.0001 to 3 wt%.

[0050]

[0051] In embodiments, the liposomes may further comprise a preservative.

[0052] In an embodiment, the preservative may include at least one of, but is not limited to, hydroxyacetophenone, salicylic acid, sodium benzoate, phenoxyethanol, 1,2-diols such as 1,2-pentanediol, 1,2-hexanediol; isopropylphenol, sodium phenylphenol.

[0053] When a preservative is included, for example, hydroxyacetophenone may be included in an amount of 0.01 to 0.5 wt%.

[0054]

[0055] In an embodiment, the liposome may comprise a particle size of 40 to 500 nm, specifically 50 to 400 nm, and more specifically 60 to 350 nm. If the particle size is less than 40 nm, the stability of the liposome may be significantly reduced, and if the particle size is greater than 500 nm, the skin penetration efficacy may be reduced.

[0056] In an embodiment, the liposome may be a multilamellar liposome having multiple lipid bilayers. The multilamellar liposome has the advantage of being able to encapsulate a greater amount of active ingredient than a typical liposome.

[0057]

[0058] According to an embodiment of the present invention, a cosmetic composition comprising a liposome according to the present invention is provided.

[0059] In an embodiment, a cosmetic composition comprising liposomes having graphene oxide on the outer surface may be provided in a formulation conventionally manufactured in the art. For example, it may be formulated as an aqueous dispersion formulation, an oil-in-water (O / W), water-in-oil (W / O), water-in-oil-in-water (W / O / W), and oil-in-water-in-oil (O / W / O) type emulsion formulation, a solubilized formulation, etc. However, the present invention is not limited thereto, and the cosmetic composition may also be provided in various formulations such as a solution, suspension, emulsion, solid, gel, oil, powder, paste or foam aerosol, mist, etc.

[0060] According to an embodiment, a cosmetic composition comprising a liposome in which graphene oxide is incorporated into the outer surface of the liposome may additionally include, in addition to the above components, components included in a general cosmetic composition, such as oils, moisturizers, ion sequestrants, bactericides, pH adjusters, antioxidants, alcohols, plant extracts, fragrances, etc. The blending amount of the above components is not particularly limited, and can be easily selected by those skilled in the art within a range that does not impair the purpose and effects of the present invention.

[0061] The mixing amount of the above-described components is not particularly limited, and can be easily selected by a person skilled in the art within a range that does not impair the purpose and effect of the present invention.

[0062]

[0063] Hereinafter, examples and experimental examples are presented to explain the present invention more specifically, but the present invention is not limited thereto.

[0064]

[0065] Experimental Example 1. Comparative Experiment According to the Content of Phosphatidylcholine Emulsifier

[0066] (1) Manufacturing of examples and comparative examples

[0067] In order to confirm the formation and efficacy of liposomes according to the content of phosphatidylcholine-based emulsifiers, liposomes of examples and comparative examples were prepared using the components listed in Table 1 below. Specifically, hydrogenated lecithin was used as a phosphatidylcholine-based emulsifier, polyglyceryl-3 methylglucose distearate was used as a polyglyceryl-based emulsifier, ceramide and cholesterol were used as lipids, niacinamide was used as a functional efficacy ingredient, and hydroxyacetophenone was used as a preservative. The unit of the content of ingredients in Table 1 is weight %.

[0068]

[0069]

[0070] The specific manufacturing methods of the examples and comparative examples are as follows.

[0071] All components including graphene oxide were heated to 60°C, emulsified using a homogenizer at 6000 rpm for 5 minutes, and then further emulsified at 1000 bar for 5 minutes using a high-pressure microemulsifier to complete the examples and comparative examples.

[0072]

[0073] (2) Liposome stability evaluation and physical property measurement

[0074] The stability of the liposome particles in the above examples and comparative examples was evaluated, and particle size, elasticity, and skin permeability were measured. The specific evaluation and measurement methods are as follows.

[0075] Stability was assessed by storing manufactured examples and comparative examples at high temperature (40°C), low temperature (5°C), and room temperature (25°C) for one week to determine whether the liposomes maintained particle size for more than one week without change. As a result, liposomes with maintained particle size were considered to have excellent stability.

[0076] Particle size was measured using an ELAZneo instrument that can measure particle size through the zeta potential of liposome particles dispersed in a solution.

[0077] A variable formation experiment was performed to measure the elasticity. The extent to which liposomes pass through an artificial permeation barrier was measured using a mini extruder. Specifically, after applying a pressure of 0.2 MPa to the liposomes for 1 minute and 30 seconds, the amount of liposome complexes that passed through a polycarbonate membrane with pores of 0.08 μm in size was measured, and the particle size of the liposomes that passed through the polycarbonate membrane was measured, and the elasticity of the liposomes was calculated according to the following equation.

[0078] Deformability Index = J(Flux) ⅹ (R v / R p ) 2

[0079] J(Flux): The amount of liposomes that passed through the membrane

[0080] R v : Particle size of liposomes after extrusion

[0081] R p : Pore size of the membrane

[0082] For skin permeability measurement, a percutaneous absorption and diffusion experiment (Franz diffusion cell) was performed. First, the skin (area: 0.6362 cm) on which the examples and comparative examples were deposited was 2 ) was cut with scissors, 5 mL of 100% methanol was added, and the solution was crushed for 5 minutes using an ultrasonic crusher. The niacinamide content of the solution filtered through a 0.45 μm filter was measured using HPLC. The skin penetration rate (%) was then calculated using the following formula.

[0083] (Skin penetration rate, %) = (Niacinamide content measured in the skin / Niacinamide content contained in the deposited cream) x 100 (%)

[0084] The measurement results by the above evaluation and measurement methods are shown in Table 2. In addition, a graph showing the average particle size and its dispersion of Example 1 is shown in Fig. 1.

[0085]

[0086]

[0087] As shown in Table 2 above, Examples 1 to 4, which were manufactured using an appropriate amount of phosphatidylcholine-based emulsifier, all showed excellent liposome particle stability, whereas Comparative Example 1, which used an excessive amount of phosphatidylcholine-based emulsifier, showed low solubility, and it was confirmed that excessive addition affected particle stability.

[0088] In addition, Examples 1 to 4 were confirmed to have excellent skin penetration efficacy because they had small particle sizes and low polydispersity indexes (PDI), so that small-sized liposomes were evenly formed and had sufficient elasticity. In particular, Examples 1 to 3, in which a polyglyceryl-based emulsifier was used, were confirmed to have better skin penetration efficacy than Example 4, in which a polyglyceryl-based emulsifier was not used. On the other hand, in the case of Comparative Example 1, the formulation itself was not formed due to the excessive hydrogenated lecithin content, so the particles were unstable, making it impossible to measure the particle size and also impossible to measure the skin permeability.

[0089] Therefore, it was confirmed that the appropriate content of the phosphatidylcholine emulsifier is an important component in the formation of liposomes in which the graphene oxide of the present invention is included on the outer surface.

[0090]

[0091] Experimental Example 2. Comparative Experiment According to Graphene Oxide Content

[0092] (1) Manufacturing of examples and comparative examples

[0093] In order to confirm the formation and efficacy of liposomes according to the content of graphene oxide, liposomes of Examples and Comparative Examples were prepared by varying the content of graphene oxide based on Example 1. The unit of the content of components in Table 3 is weight %, and the preparation method is the same as Experimental Example 1.

[0094]

[0095]

[0096] (2) Liposome stability evaluation and physical property measurement

[0097] For the above examples and comparative examples, the stability of liposome particles was evaluated as in Experimental Example 1, and particle size, elasticity, and skin permeability were measured.

[0098] The measurement results using the above evaluation and measurement methods are shown in Table 4.

[0099]

[0100]

[0101] As shown in Table 4 above, Examples 1 and 5 to 7, which were manufactured using an appropriate amount of graphene oxide, all showed excellent liposome particle stability, whereas in the case of Comparative Example 3, the formulation itself was not formed due to an excessive amount of graphene oxide, showing poor particle stability. Through this, it was found that when graphene oxide was mixed in excessive amounts, the particle stability was affected due to insufficient solubility. On the other hand, in the case of Comparative Example 2, which used a small amount of graphene oxide, the stability of the liposome particles was good, but it was confirmed that general liposomes were formed in which graphene oxide was not included on the outer surface of the liposome due to a decrease in the interaction between graphene oxide and the phosphatidylcholine-based emulsifier.

[0102] In addition, Examples 1 and 5 to 7 were confirmed to have excellent skin penetration efficacy because they had small particle sizes and low polydispersity indexes (PDI), so that small-sized liposomes were evenly formed and had sufficient elasticity. On the other hand, Comparative Example 2, in which general liposomes without graphene oxide on the outer surface were formed, showed a significantly lower skin permeation rate than the Examples, so that the skin penetration efficacy was very poor. In the case of Comparative Example 3, the particles were unstable, making it impossible to measure the particle size, and the solubility of graphene oxide prevented the formulation from being implemented, making it impossible to measure the skin permeation rate.

[0103]

[0104] Therefore, it was confirmed that the appropriate content of graphene oxide is an important component in the formation of liposomes in which graphene oxide of the present invention is included on the outer surface.

[0105]

[0106] In conclusion, as confirmed in the experimental examples above, liposomes containing graphene oxide on their outer surfaces exhibited small, evenly distributed particles, excellent particle stability, and superior skin penetration efficacy. Furthermore, when a polyglyceryl-based emulsifier was added, the liposomes exhibited superior elasticity and even better skin penetration efficacy.

[0107]

[0108] While specific aspects of the present invention have been described in detail above, it will be apparent to those skilled in the art that these specific descriptions merely represent preferred embodiments and are not intended to limit the scope of the present invention. Therefore, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. In liposomes with excellent skin penetration efficacy, A liposome in which graphene oxide is incorporated into the outer surface of the liposome.

2. In paragraph 1, The above graphene oxide surrounds the outer surface of the liposome.

3. In paragraph 1, A liposome in which the graphene oxide is contained in an amount of 0.000005 to 1.4 wt% based on the total weight of the liposome.

4. In paragraph 1, A liposome having a particle size of 40 to 500 nm.

5. In paragraph 1, The above liposome is a liposome further comprising a phosphatidylcholine emulsifier.

6. In paragraph 5, A liposome, wherein the phosphatidylcholine emulsifier is included in an amount of 0.005 to 10 wt% based on the total weight of the liposome.

7. In paragraph 1, The above liposome is a liposome further comprising a polyglyceryl emulsifier.

8. In paragraph 7, A liposome, wherein the polyglyceryl emulsifier is contained in an amount of 0.00001 to 1 wt% based on the total weight of the liposome.

9. In paragraph 1, The above liposome is a liposome that further contains lipid.

10. In paragraph 1, The above liposome is a liposome that further contains a functional efficacy ingredient.

11. A cosmetic composition comprising a liposome according to any one of claims 1 to 10.

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