A topical skin agent composition containing crosslinked hyaluronic acid gel

Abstract

The present invention relates to an oil-in-water type topical skin agent composition which uses a gel of crosslinked hyaluronic acid or its salt, thereby having a special texture and feel like ice cream, and the composition of the present invention contains gel particles and emulsified particles of crosslinked hyaluronic acid or its salt with a D(0.5) of particle size distribution in a specific range in the aqueous phase and the oil phase respectively, so that the composition has a granular feel like ice cream, mashed potatoes or meringue, and also has a soft appearance and texture, can provide a refreshing feel when applied, and is easy to clean because the outer phase is an aqueous phase.

Description

Technical Field

[0001] The present invention relates to an oil-in-water type composition having a special texture and containing a natural polymer hydrogel.

[0002]

Related Applications

[0003] This application claims the priority of a Korean patent application with an application date of January 13, 2022 and an application number of 10-2022-0005472, the entire text of which is incorporated herein by reference. Background Art

[0004] In products applied to the skin, such as cosmetics, in addition to the functionality or efficacy of the product, the usability is also one of the factors that have a decisive impact on consumer satisfaction. In this regard, products with various usability have been developed. Representative special usability in cosmetics is the usability of water bursting or the feeling of moisture, but this kind of usability is limited to being obtained only through dosage forms with a water phase as the discontinuous phase, such as W / O (water-in-oil) or W / S (silicone oil-in-water) emulsions. Since the external phase of these dosage forms is oil or silicone oil, the initial oiliness is serious, or since the water bursting property originates from the phase inversion feeling, that is, the feeling of internal phase water bursting when the internal phase and the external phase are interchanged, it shows discontinuity, so it is easy to have an unsmooth usability when applying. In addition, there is a feeling that the oil component of the external phase remains on the skin while only the water component floats on the surface, and the oil or silicone oil component of the external phase may irritate the skin and remain on the skin, making it difficult to clean. Summary of the Invention

[0005] Technical Problem

[0006] In one aspect, the present invention aims to provide an oil-in-water type composition having a special usability.

[0007] Technical Solution

[0008] To solve the above problems, in one embodiment, the present invention provides an oil-in-water type topical skin agent composition, wherein the aqueous phase of the composition contains gel particles of crosslinked hyaluronic acid or its salt with a D(0.5) of 30 to 150 μm in the particle size distribution, and the oil phase of the composition contains emulsified particles with a D(0.5) of 0.001 to 30 μm in the particle size distribution.

[0009] Advantageous Effects

[0010] This specification discloses an oil-in-water type topical skin agent composition which uses a gel of crosslinked hyaluronic acid or its salt, and thus has a special texture and feel like ice cream. The composition of the present invention contains gel particles and emulsified particles of crosslinked hyaluronic acid or its salt with a D(0.5) of a specific range in the aqueous phase and the oil phase respectively, so that the composition has a granular feel like ice cream, mashed potatoes or meringue, and also has a soft appearance and texture. When the composition of the present invention is applied, it spreads smoothly like melting, and the oily feel when the emulsified particles burst and the moist feel when the gel particles burst can be continuously felt, thus providing a refreshing feel, and it is easy to clean because the outer phase is an aqueous phase. In addition, different from the existing products using crosslinked hyaluronic acid materials which have a sticky feeling due to viscosity, the composition of the present invention can also provide a low sticky feeling after absorption and a long-lasting moist feel even when containing a high content of crosslinked hyaluronic acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 Shows the particle size distribution diagram of Example 1 which is an embodiment of the present invention.

[0012] Figure 2 Shows the particle size distribution diagram of Example 2 which is an embodiment of the present invention.

[0013] Figure 3 Shows the particle size distribution diagram of Comparative Example 1.

[0014] Figure 4 Shows the particle size distribution diagram of Comparative Example 2.

[0015] Figure 5 Shows a photographed picture of the appearance of Example 1 which is an embodiment of the present invention.

[0016] Figure 6 Shows a photographed picture of the appearance of Comparative Example 1.

[0017] Figure 7 Shows a photographed picture of the appearance of Comparative Example 2.

[0018] Figure 8 Shows the measurement results of the water content of Example 1 and Comparative Example 1 changing over time.

[0019] Figure 9 Shows a photographed picture of Example 1 (left hand) and Comparative Example 1 (right hand) before the stickiness evaluation.

[0020] Figure 10 Shows a photographed picture of Example 1 (left hand) and Comparative Example 1 (right hand) after the stickiness evaluation. DETAILED DESCRIPTION OF THE INVENTION

[0021] Hereinafter, embodiments of the present application will be described in more detail with reference to the accompanying drawings. However, the technology disclosed in the present application is not limited to the embodiments described in this specification and can be implemented in other forms. It should be understood that the purpose of providing the following embodiments in this specification is to make the disclosure more thorough and complete and to fully convey the concept of the present application to those skilled in the art. In addition, within the scope not exceeding the technical concept of the present application, those skilled in the art can implement the concept of the present application in various other forms.

[0022] In this specification, singular expressions include plural forms unless the context clearly indicates otherwise. In the present application, terms such as "comprising", "including", or "having" are intended to indicate the presence of the features, numbers, steps, operations, components, or combinations thereof described in the specification, but do not exclude the presence or possibility of addition of one or more other features, numbers, steps, operations, components, or combinations thereof.

[0023] In one embodiment, the present invention provides an oil-in-water skin topical composition, wherein the aqueous phase contains gel particles of crosslinked hyaluronic acid or its salt with D(0.5) in the particle size distribution of 30 to 150 μm, and the oil phase contains emulsified particles with D(0.5) in the particle size distribution of 0.001 to 30 μm.

[0024] In the present invention, the "skin topical composition" is a composition in a dosage form applied to the outside of the skin, which can be directly applied by hand or using various application tools such as a spatula, and can include various dosage forms of cosmetics, pharmaceuticals, quasi-drugs, etc.

[0025] In the present invention, the hyaluronic acid is a linear anionic natural polysaccharide formed by alternating bonding of β-D-N-acetylglucosamine and β-D-glucuronic acid, and exists in the form of a salt. The molecular structure of hyaluronic acid can be represented by the following Chemical Formula 1.

[0026]

Chemical Formula 1

[0027]

[0028] Wherein, n is 200 to 25,000, and the unit of x is mol.

[0029] In one embodiment of the present invention, the salt may be an acid addition salt, a base addition salt or an amino acid salt, but is not particularly limited thereto. For example, the salt may include: inorganic acid salts such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, phosphate, etc.; organic acid salts such as citrate, oxalate, acetate, formate, propionate, benzoate, trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, etc.; inorganic base salts such as sodium salt, potassium salt, calcium salt, magnesium salt, copper salt, zinc salt, aluminum salt, ammonium salt, etc.; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt, diisopropylammonium salt, etc.; amino acid salts such as lysine salt, arginine salt, histidine salt, aspartate salt, glutamate salt. In one embodiment, the salt may be sodium hyaluronate, potassium hyaluronate, hyaluronic acid acetate, ammonium hyaluronate or C12-13 alkyl glyceryl hydrolyzed hyaluronate. In the present invention, the weight average molecular weight of the high molecular weight hyaluronic acid or its salt varies according to the length of the sugar chain. As an example, the weight average molecular weight of the high molecular weight hyaluronic acid or its salt may be 100 to 5,000 kDa. Specifically, the weight average molecular weight of the high molecular weight hyaluronic acid or its salt may be 100 kDa or more, 300 kDa or more, 500 kDa or more, 700 kDa or more, 900 kDa or more, 1,100 kDa or more, 1,300 kDa or more, 1,400 kDa or more, 1,500 kDa or more or 1,600 kDa or more, and 5,000 kDa or less, 4,000 kDa or less, 3,000 kDa or less, 2,700 kDa or less, 2,400 kDa or less, 2,100 kDa or less, 1,800 kDa or less, 1,700 kDa or less, 1,600 kDa or less, 1,500 kDa or less or 1,400 kDa or less. More specifically, the weight average molecular weight of the high molecular weight hyaluronic acid or its salt may be 1,300 to 1,800 kDa.

[0030] Natural hyaluronic acid has the characteristics of poor structural stability and being easily decomposed and removed in the body. Therefore, in one embodiment of the present invention, gel particles containing crosslinked hyaluronic acid or its salt are provided, and the crosslinking of the hyaluronic acid or its salt is not limited to the crosslinking method as long as gel particles having the particle size distribution of the present invention can be prepared.

[0031] In one embodiment, the crosslinked hyaluronic acid or its salt can be chemically crosslinked by a crosslinking agent. Specifically, the crosslinking agent can be at least one selected from sulfone crosslinking agents, epoxy crosslinking agents, and phosphate crosslinking agents, but is not limited thereto. For example, the crosslinking agent can be one or more selected from divinyl sulfone (DVS), 1,4-butanediol diglycidyl ether (BDDE), ethylene glycol diglycidyl ether (EGDGE), 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, polyethylene glycol diglycidyl ether (PEGDE), 1,2-ethylene glycol diglycidyl ether, and sodium trimetaphosphate (STMP).

[0032] In one embodiment, the aqueous phase of the composition may contain gel particles of crosslinked hyaluronic acid or its salt, and D(0.5) in the particle size distribution of the gel particles is 30 to 150 μm. At this time, the particle size distribution represents the percentage of a group of particles in a certain particle size range in the total particle group, and when it is shown graphically, it is a particle size distribution curve. The D(0.5) is also referred to as D50, D(V,0.5), or median particle size. The D(0.5) means the size of the particles distributed in the middle 50% in the particle size distribution graph, and appears as a peak on the distribution graph. In one embodiment, the 30 to 150 μm can be the size of at least 50%, 60%, 70%, 80%, or 90% of the particles contained in the composition, that is, the range can be the value of D(0.5), D(0.6), D(0.7), D(0.8), or D(0.9). In one embodiment, the particle size distribution can be measured by a particle size analyzer Mastersizer 2000 using X-ray diffraction method from Malvern Panalytical. As long as it is a particle size analyzer capable of measuring particle size distribution, it is not limited by its method or type.

[0033] Specifically, in the particle size distribution of the gel particles of the crosslinked hyaluronic acid or its salt, D(0.5) can be 30 μm or more, 40 μm or more, 50 μm or more, 60 μm or more, 70 μm or more, 80 μm or more, 85 μm or more, 90 μm or more, 95 μm or more, 100 μm or more, 105 μm or more, 110 μm or more, 120 μm or more, 130 μm or more, or 140 μm or more, and 150 μm or less, 140 μm or less, 130 μm or less, 120 μm or less, 115 μm or less, 110 μm or less, 105 μm or less, 100 μm or less, 95 μm or less, 90 μm or less, 80 μm or less, 70 μm or less, 60 μm or less, 50 μm or less, or 40 μm or less. When the D(0.5) value in the particle size distribution of the gel particles is less than 30 μm, the refreshing feeling of water bursting during coating may not be obvious. When the D(0.5) value of the gel particles exceeds 150 μm, due to the too large particles, the soft texture like sherbet cannot be exhibited, and a foreign body sensation will be brought, which may lead to a poor use feeling.

[0034] In one embodiment, the method for preparing the gel particles of the crosslinked hyaluronic acid or its salt is not limited as long as the gel of the crosslinked hyaluronic acid or its salt can be prepared into particles in the above size range. For example, after crosslinking hyaluronic acid or its salt to prepare a gel, it can be pulverized by passing through a mesh to prepare the gel particles. At this time, the particle size can be adjusted by the mesh size of the mesh.

[0035] In one embodiment, the oil phase of the composition may comprise emulsion particles, and D(0.5) in the particle size distribution of the emulsion particles is 0.001 to 30 μm. In the present invention, the term "emulsion particles" is distinguished from the "gel particles of crosslinked hyaluronic acid or its salts", and refers to the particles of the oil phase dispersed in the aqueous phase of the composition. In one embodiment, depending on the preparation method of the composition and the types and contents of the components contained in the composition, D(0.5) of the emulsion particles may exhibit a single peak or multiple peaks. Specifically, D(0.5) in the particle size distribution of the emulsion particles may be 0.001 μm or more, 0.01 μm or more, 0.1 μm or more, 0.5 μm or more, 1 μm or more, 2 μm or more, 3 μm or more, 4 μm or more, 5 μm or more, 6 μm or more, 7 μm or more, 8 μm or more, 9 μm or more, 10 μm or more, 11 μm or more, 12 μm or more, 13 μm or more, 14 μm or more, 15 μm or more, 20 μm or more, or 25 μm or more, and 30 μm or less, 29 μm or less, 28 μm or less, 27 μm or less, 25 μm or less, 24 μm or less, 23 μm or less, 22 μm or less, 21 μm or less, 20 μm or less, 19 μm or less, 18 μm or less, 17 μm or less, 16 μm or less, 15 μm or less, 14 μm or less, 13 μm or less, 12 μm or less, 11 μm or less, 10 μm or less, 9 μm or less, 8 μm or less, 7 μm or less, 5 μm or less, 1 μm or less, 0.5 μm or less, 0.1 μm or less, or 0.001 μm or less. In the particle size distribution of the emulsion particles, when the D(0.5) value is less than 0.001 μm, nanoemulsion preparation processes such as high-pressure emulsification are required, so the preparation is difficult. When the D(0.5) value exceeds 30 μm, the stability of the dosage form may be reduced.

[0036] Currently, compositions in dosage forms containing gels of crosslinked hyaluronic acid or its salts often have the problem of greasiness. However, the composition according to one embodiment of the present invention contains particles within a specific particle size distribution range by crushing the gel of crosslinked hyaluronic acid or its salts, so that a composition that is non-greasy and has excellent moisturizing feeling and absorption rate can be provided even at a high content of hyaluronic acid.

[0037] In one embodiment, the type of oil contained in the emulsified particles is not limited as long as it is an oil commonly used in the technical field. In one embodiment, the oil can be an ester oil, a hydrocarbon oil, an oil of natural origin, a silicone oil, etc. Specifically, the oil can be selected from polydecene, hydrogenated polydecene, polybutene, hydrogenated polyisobutene, dicaprylyl carbonate, diisostearyl malate, butylene glycol dicaprylate / dicaprate, cetyl 2-ethyl hexanoate, triethylhexanoin, caprylic / capric triglyceride, dicetearyldimer dilinoleate, diisostearyl malate, dicetearyldimer dilinoleate, hexyl laurate, pentaerythrityl tetraethylhexanoate, pentaerythrityl tetraisostearate, octyldodecylstearoyl stearate, cyclopentasiloxane, cyclohexasiloxane, dimethicone, methyltrimethicone, cyclomethicone, phenyltrimethicone, squalane, tamanu oil, macadamia nut oil, sunflower seed oil, olive oil, evening primrose oil, argan oil, apricot oil, sesame oil, orange oil, rosewood oil, bergamot oil, camellia oil, tea tree oil, and jojobaoil, or at least one of them.

[0038] In one embodiment of the present invention, the composition may have a texture and appearance similar to sherbet. At this time, the "sherbet" may refer to the following state: when the composition is scraped onto a glass plate to confirm the appearance, it has a granular feeling and also has a soft physical property, such as being similar to a light and soft foam (seeFigure 5 )。In one embodiment, the present invention may have the texture and appearance of an ice cream bar, and when in use, it is also applied smoothly like melting ice cream, and the moist feeling when the gel particles burst and the oily feeling when the emulsified particles burst can be continuously felt.

[0039] In one embodiment, based on the total weight of the composition, the content of the gel of hyaluronic acid or its salt may be from 0.01 to 20% by weight. Specifically, based on the total weight of the composition, the content of the gel of hyaluronic acid or its salt may be 0.01% by weight or more, 0.05% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1% by weight or more, 1.5% by weight or more, 2% by weight or more, 2.5% by weight or more, 3% by weight or more, 3.5% by weight or more, 4% by weight or more, 4.5% by weight or more, 5% by weight or more, 6% by weight or more, 7% by weight or more, 8% by weight or more, 9% by weight or more, 10% by weight or more, 11% by weight or more, 12% by weight or more, 13% by weight or more, 14% by weight or more, 15% by weight or more, or 19% by weight or more, and 20% by weight or less, 19% by weight or less, 18% by weight or less, 17% by weight or less, 16% by weight or less, 15% by weight or less, 14% by weight or less, 13% by weight or less, 12% by weight or less, 11% by weight or less, 10% by weight or less, 9% by weight or less, 8% by weight or less, 7% by weight or less, 6% by weight or less, 5% by weight or less, 4% by weight or less, 3% by weight or less, 2% by weight or less, 1% by weight or less, or 0.5% by weight or less. In one embodiment, based on the total weight of the composition, the content of the gel of hyaluronic acid or its salt in dry weight may be from 0.01 to 5% by weight. Specifically, based on the total weight of the composition, the content of the gel of hyaluronic acid or its salt in dry weight may be 0.01% by weight or more, 0.05% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1% by weight or more, 1.1% by weight or more, 1.3% by weight or more, 1.5% by weight or more, 1.7% by weight or more, 2% by weight or more, 2.2% by weight or more, 2.4% by weight or more, 2.6% by weight or more, or 2.8% by weight or more, and 5% by weight or less, 4% by weight or less, 3% by weight or less, 2.5% by weight or less, 2% by weight or less, 1.7% by weight or less, 1.5% by weight or less, 1.3% by weight or less, 1.1% by weight or less, 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, 0.6% by weight or less, or 0.5% by weight or less.If the content exceeds this range, a special appearance and texture like that of ice cream may not appear.

[0040] In one embodiment, the elastic modulus (G') of the composition can be adjusted by adjusting the physical properties of the gel of hyaluronic acid or its salt. For example, the elastic modulus (G') of the composition can be 100 to 9000 Pa. More specifically, the elastic modulus can be 100 Pa or more, 200 Pa or more, 300 Pa or more, 400 Pa or more, 500 Pa or more, 600 Pa or more, 700 Pa or more, 800 Pa or more, 900 Pa or more, 1000 Pa or more, 1100 Pa or more, 1200 Pa or more, 1500 Pa or more, 2000 Pa or more, 3000 Pa or more, 4000 Pa or more, 5000 Pa or more, 6000 Pa or more, 7000 Pa or more, or 8000 Pa or more, and 9000 Pa or less, 8000 Pa or less, 7000 Pa or less, 6000 Pa or less, 5000 Pa or less, 4000 Pa or less, 3000 Pa or less, 2000 Pa or less, 1900 Pa or less, 1800 Pa or less, 1700 Pa or less, 1600 Pa or less, 1500 Pa or less, 1400 Pa or less, 1300 Pa or less, 1200 Pa or less, 1100 Pa or less, or 1000 Pa or less. When the elastic modulus exceeds this range, a dosage form with an appearance like that of ice cream may not appear because it is too hard or close to a liquid.

[0041] In one embodiment, the elastic modulus can be measured using a rheometer (Maven, USA). Specifically, the elastic modulus is measured at 25 °C using a 20 mm cone plate in a frequency range of 0.1 to 10 Hz, a shear stress of 1 Pa, and a gap of 1 mm, and can be the G' value measured at 1 Hz. At this time, the specifications of the sample for measuring the elastic modulus (G') are unified into a disk form with a diameter of 20 mm and a thickness of 1 mm.

[0042] In one embodiment, the composition can be a composition for skin moisturization.

[0043] In another embodiment, the present invention can provide a method for skin moisturization, the method comprising applying an effective dose of an oil-in-water topical composition for skin to the skin of a subject in need thereof, wherein the aqueous phase of the composition comprises gel particles of crosslinked hyaluronic acid or its salt with a D(0.5) of 30 to 150 μm in the particle size distribution, and the oil phase of the composition comprises emulsified particles with a D(0.5) of 0.001 to 30 μm in the particle size distribution. In another embodiment, the present invention can provide the use of an oil-in-water composition in the preparation of a topical composition for skin moisturization, wherein the aqueous phase of the oil-in-water composition comprises gel particles of crosslinked hyaluronic acid or its salt with a D(0.5) of 30 to 150 μm in the particle size distribution, and the oil phase of the oil-in-water composition comprises emulsified particles with a D(0.5) of 0.001 to 30 μm in the particle size distribution. In another embodiment, the present invention can provide the use of an oil-in-water composition in a topical composition for skin moisturization, wherein the aqueous phase of the oil-in-water composition comprises gel particles of crosslinked hyaluronic acid or its salt with a D(0.5) of 30 to 150 μm in the particle size distribution, and the oil phase of the oil-in-water composition comprises emulsified particles with a D(0.5) of 0.001 to 30 μm in the particle size distribution. In another embodiment, the present invention can provide the non-therapeutic cosmetic use of an oil-in-water composition as an active ingredient in skin moisturization, wherein the aqueous phase of the oil-in-water composition comprises gel particles of crosslinked hyaluronic acid or its salt with a D(0.5) of 30 to 150 μm in the particle size distribution, and the oil phase of the oil-in-water composition comprises emulsified particles with a D(0.5) of 0.001 to 30 μm in the particle size distribution.

[0044] In one aspect, the cosmetic composition has an outer form comprising a cosmetically or dermatologically acceptable medium or substrate. It can be in all dosage forms suitable for topical application. For example, it can be prepared in the form of a solution, gel, anhydrous paste, emulsion obtained by dispersing an oil phase in an aqueous phase, suspension, microemulsion, microcapsule, microsphere, or ionic (liposome) and non-ionic vesicle dispersant, or it can be prepared in the form of a cream, emollient lotion, milky emulsion, ointment, etc. These compositions can be prepared according to conventional methods in the art. The cosmetic composition according to an embodiment of the present invention is not particularly limited in its dosage form and can be prepared as a skin care composition, a makeup composition, a composition for caring for or cleansing the body or hair, etc. For example, in one embodiment of the present invention, it can be prepared as ampoules, creams, emollient lotions, astringent lotions, nutritive lotions, nutritive creams, massage creams, serums, eye creams, eye serums, cleansing creams, cleansing foams, cleansing waters, cleansing towels containing the cosmetic composition, face masks, body lotions, body creams, body oils, and body serums, etc. For example, in one embodiment of the present invention, it can be prepared as makeup primers, makeup base lotions, foundations, concealers, lipsticks, lip glosses, lip balms, loose powders, lip liners, eyeliner pencils, mascaras, eyebrow pencils, eyeshadows, blushes, two-way powder compacts, or ultraviolet screening agents, etc. For example, in one embodiment of the present invention, it can be prepared as bath agents, facial cleansers, hand soaps, shampoos, conditioners, hair rinses, hair masks, hair tonics, scalp care agents, scalp and hair dual care agents, hair lotions, hair creams, hair nutritive lotions, or ordinary ointments, etc.

[0045] When the dosage form according to an embodiment of the present invention is a paste, cream or gel, animal fibers, plant fibers, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, polysiloxanes, bentonites, silica, talc or zinc oxide, etc. can be used as carrier components. When the dosage form according to an embodiment of the present invention is a solution or emulsion, solvents, solubilizers or emulsifying agents are used as carrier components, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 - butanediol oil, glycerol fatty acid esters, polyethylene glycol or fatty acid esters of sorbitan. When the dosage form according to an embodiment of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan esters and polyoxyethylene sorbitan anhydride esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, etc. can be used as carrier components. When the dosage form according to an embodiment of the present invention is a cleansing agent containing a surfactant, fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, hydroxyethyl sulfonates, imidazoline derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkyl amide betaines, fatty alcohols, fatty acid glycerol esters, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters, etc. can be used as carrier components.

[0046] The cosmetic composition according to an embodiment of the present invention may further contain functional additives and components contained in ordinary cosmetic compositions. The functional additives may include components selected from water - soluble vitamins, oil - soluble vitamins, high - molecular peptides, high - molecular polysaccharides, sphingolipids and seaweed extracts. In addition, the formulated components included may be oil components, moisturizers, emollients, surfactants, organic pigments and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH regulators, alcohols, pigments, fragrances, blood circulation promoters, coolants, antiperspirants, pure water, etc.

[0047] In one embodiment, the composition may be a pharmaceutical composition.

[0048] When applying the composition according to an embodiment of the present invention to pharmaceuticals, it can be prepared into a parenteral dosage form in semi-solid or liquid form by adding a commonly used inorganic carrier or organic carrier to the active ingredient used in an embodiment of the present invention. The composition according to an embodiment of the present invention can easily formulate the active ingredient according to conventional methods well-known in the art. At this time, surfactants, excipients, coloring agents, fragrances, preservatives, stabilizers, buffers, suspending agents and other commonly used adjuvants can be appropriately used. The dosage of the active ingredient of the pharmaceutical composition according to an embodiment of the present invention will vary depending on the age, sex, weight, pathological condition and its severity, route of administration of the administration object or the judgment of the prescriber. Determining an appropriate dosage based on these factors is within the level of those skilled in the art. The dosage per day, for example, can be 0.1 mg / kg / day to 100 mg / kg / day, and more specifically can be 5 mg / kg / day to 50 mg / kg / day, but is not limited thereto.

[0049] Hereinafter, the present invention will be described more specifically through the following examples. However, the purpose of providing these examples is only to help understand the present invention, and the scope and range of the present invention are not limited by them.

[0050]

Preparation Example

[0051] Example 1

[0052] As an embodiment of the present invention, Example 1 having the composition shown in Table 1 below was prepared according to the following method.

[0053] Specifically, sodium hyaluronate (manufacturer: Hyaluron Co., Ltd.) was mixed with a solution containing a cross-linking agent (PEGDE, manufacturer: Sigma) and NaOH to cross-link the hyaluronate to prepare a gel form. The cross-linked product in the gel form was passed through a sieve to be pulverized, thereby preparing particles with D(0.5) in the particle size distribution being between 30 and 150 μm. According to the conventional method in the art, the pulverized hyaluronate gel particles were mixed into the prepared oil-in-water type composition to prepare Example 1.

[0054] Example 2

[0055] As an embodiment of the present invention, Example 2 was prepared in the same manner as Example 1, except that BDDE (manufacturer: Sigma) was used as the cross-linking agent in Example 2.

[0056] Comparative Example 1

[0057] Comparative Example 1 was prepared in the same manner as Example 1, except that uncrosslinked sodium hyaluronate (manufacturer: Hyaluron D) was used instead of the comminuted hyaluronate gel particles in Comparative Example 1.

[0058] Comparative Example 2

[0059] Comparative Example 2 was prepared in the same manner as Example 1, except that the particle size distribution of the comminuted hyaluronate gel particles in Comparative Example 2 exceeded 150 μm.

[0060]

Table 1

[0061]

[0062]

[0063] (wt%)

[0064]

Experimental Example 1

[0065] In the following experiments, the particle size distributions of Example 1, Comparative Example 1, and Comparative Example 2 prepared above were measured, and the appearance and usability were compared accordingly.

[0066] First, a Mastersizer 2000 from Malvern Panalytical was used to measure the particle size distribution of each composition, and the results are shown in Figures 1 to 4 . Referring to the results, the peaks (D(0.5)) of the emulsified particles in Example 1 and Example 2 and Comparative Example 1 and Comparative Example 2 all appeared in the range of 0.1 to 20 μm, and in addition to Comparative Example 1 containing uncrosslinked hyaluronate, not only the peaks of the emulsified particles but also the peaks of the crosslinked hyaluronate gel particles appeared in Example 1 and Example 2 and Comparative Example 2. Specifically, the D(0.5) values of Example 1 and Example 2 were around 100 μm, and the D(0.5) value of Comparative Example 2 was greater than 150 μm.

[0067] Then, each composition was thinly spread on a glass plate and photographed vertically from top to bottom to confirm the appearance at different particle size distribution values of the crosslinked hyaluronate gel particles. In addition, about 0.3 ml of each composition was placed on the back of the hand and then spread for about 20 seconds under the rolling condition of twice per second, and the overall spreading usability was confirmed at this time.

[0068] The results are as shown in Table 2 below and Figures 5 to 7 shown. In Example 1 ( Figure 5) and in Example 2, the emulsified particles and the crosslinked hyaluronate gel particles are well mixed, thus having a soft appearance and a feeling of water bursting, but in Comparative Example 1 ( Figure 6 ), since there are no gel particles, it shows a smooth surface state and no feeling of water bursting. In Comparative Example 2 ( Figure 7 ), the size of the gel particles is too large, resulting in poor mixing of the emulsified particles and the gel particles, and when coating, the gel particles do not burst naturally to let out water, but shift to the side and frequently deviate from the coating range.

[0069]

Table 2

[0070] Distinguish D(0.5) Explosive water feeling Example 1 108μm Strong Example 2 104μm Strong Comparative Example 1 4μm None Comparative Example 2 520μm Slight

[0071]

Experimental Example 2

[0072] The elasticity of Example 1 and Comparative Example 1 prepared above was measured according to the following method.

[0073] A rheometer (Maven, USA) was used to measure the elastic modulus. At this time, the set conditions were to use a 20 mm cone plate of the plate type at 25 °C, and to measure under an oscillation stress of 1 Pa, a frequency range of 0.1 to 10 Hz, a shear stress of 1 Pa, and a gap of 1 mm.

[0074]

Table 3

[0075] Example 1 Comparative Example 1 Elastic modulus (G', Pa) 1068 89.45

[0076] From this result, it can be seen that in Example 1 according to an embodiment of the present invention, the gel of hyaluronic acid or its salt has a specific particle size distribution, so it contains more than several tens of times its dry weight of water, and thus the elasticity value of this composition is much greater than that of Comparative Example 1 containing uncrosslinked general hyaluronic acid.

[0077]

Experimental Example 3

[0078] An in vitro water evaporation test of the examples and comparative examples was carried out to compare the moisturizing power of Example 1 and Comparative Example 1 prepared above. Specifically, 4 g of each composition was separately filled into a glass container with a diameter of 3 cm and stored under constant temperature (30 °C), constant humidity (50%), and windless conditions for 96 hours. The weight of the composition over time was measured respectively, and from this, the amount of water remaining after evaporation in each composition, that is, the water content (g), was derived.

[0079] The results are as Figure 8As shown, the water evaporation rate of Example 1 is lower than that of Comparative Example 1, and Comparative Example 1 contains almost no moisture after 48 hours. This means that the composition of the present invention can have an excellent moist feeling when applied to the skin and has a longer retention time of moisturizing ability.

[0080]

Experimental Example 4

[0081] For comparison and evaluation with Comparative Example 1 to confirm whether the prepared Example 1 has a non-greasy and refreshing feeling in use. Specifically, three women in their 30s to 40s with normal skin were used as experimental subjects. 0.3 g of Example 1 was applied to the back of the left hand, and 0.3 g of Comparative Example 1 was applied to the back of the right hand, and then patted and absorbed well. Twenty square papers with a diameter of 5 mm (A4 paper of Double A company) were attached to each back of the hand, and then the number of papers still attached when the hand was turned over once was recorded to evaluate the greasiness. When the number of attached papers is 0 to 3, the greasiness level is evaluated as "low greasiness"; when the number of attached papers is 4 to 7, the greasiness level is evaluated as "having greasiness"; when the number of attached papers is 7 or more, the greasiness level is evaluated as "high greasiness".

[0082] The results are as Figure 9 and Figure 10 shown. For Example 1, the number of remaining paper pieces when the hand was turned over was 1, and for Comparative Example 1 it was 4. It can be confirmed that the greasiness of Example 1 is significantly lower and shows a refreshing feeling in use.

[0083] The present invention can provide the following embodiments as an example.

[0084] The first embodiment can provide an oil-in-water type topical skin composition, wherein the aqueous phase contains gel particles of crosslinked hyaluronic acid or its salt with D(0.5) in the particle size distribution being 30 to 150 μm, and the oil phase contains emulsified particles with D(0.5) in the particle size distribution being 0.001 to 30 μm.

[0085] The second embodiment can provide the composition according to the first embodiment, wherein the composition has an ice cream texture.

[0086] The third embodiment can provide the composition according to the first embodiment or the second embodiment, wherein D(0.5) in the particle size distribution of the emulsified particles is 0.1 to 10 μm.

[0087] The fourth embodiment can provide the composition according to any one of the first to third embodiments, wherein the crosslinked hyaluronic acid or its salt is chemically crosslinked by a crosslinking agent, and the crosslinking agent is at least one selected from sulfone crosslinking agents, epoxy crosslinking agents, and phosphate crosslinking agents.

[0088] The fifth embodiment can provide the composition according to any one of the first to fourth embodiments, wherein the crosslinking agent is one or more selected from divinyl sulfone, 1,4-butanediol diglycidyl ether, ethylene glycol diglycidyl ether, 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, polyethylene glycol diglycidyl ether, 1,2-ethylene glycol diglycidyl ether, and sodium trimetaphosphate.

[0089] The sixth embodiment can provide the composition according to any one of the first to fifth embodiments, wherein the weight average molecular weight of the crosslinked hyaluronic acid or its salt is 100 to 5,000 kDa.

[0090] The seventh embodiment can provide the composition according to any one of the first to sixth embodiments, wherein the particle size distribution is measured by Mastersizer 2000 of Malvern Panalytical.

[0091] The eighth embodiment can provide the composition according to any one of the first to seventh embodiments, wherein the composition is for skin moisturization.

[0092] The ninth embodiment can provide the composition according to any one of the first to eighth embodiments, wherein the composition is a cosmetic composition.

[0093] The tenth embodiment can provide the composition according to any one of the first to ninth embodiments, wherein the composition is a pharmaceutical composition.

[0094] The eleventh embodiment can provide the use of the oil-in-water composition according to any one of the first to tenth embodiments in the preparation of an external preparation composition for skin moisturization, wherein the aqueous phase of the oil-in-water composition contains gel particles of crosslinked hyaluronic acid or its salt with D(0.5) of 30 to 150 μm in the particle size distribution, and the oil phase of the oil-in-water composition contains emulsified particles with D(0.5) of 0.001 to 30 μm in the particle size distribution.

Claims

1. An oil-in-water type topical skin agent composition, wherein, the aqueous phase contains gel particles of crosslinked hyaluronic acid or its salt with D(0.5) in the particle size distribution being 30 to 150 μm, the oil phase contains emulsified particles with D(0.5) in the particle size distribution being 0.001 to 30 μm, based on the total weight of the composition, the content of the gel particles of the crosslinked hyaluronic acid or its salt is 0.01 to 1% by weight, and the weight average molecular weight of the crosslinked hyaluronic acid or its salt is 100 to 5,000 kDa, the emulsified particles contain at least one selected from polydecene, hydrogenated polydecene, polybutene, hydrogenated polyisobutene, dicaprylyl carbonate, diisostearyl malate, butanediol dicaprylate / dicaprate, cetearyl octanoate, triisooctanoin, caprylic / capric triglyceride, dicetearyl dimer dilinoleate, hexyl laurate, pentaerythritol tetraethylhexanoate, pentaerythritol tetraisononanoate, octyldodecyl stearoyl stearate, cyclopentasiloxane, cyclohexasiloxane, polydimethylsiloxane, methylpolysiloxane, cyclomethicone, phenylpolysiloxane, squalane, tamanu oil, macadamia oil, sunflower oil, olive oil, evening primrose oil, argan oil, almond oil, sesame oil, orange oil, rosewood oil, bergamot oil, camellia oil, tea tree oil and jojoba oil, the elastic modulus (G') of the composition is 300 to 9,000 Pa, and the composition has an ice cream texture.

2. The composition according to claim 1, wherein, D(0.5) in the particle size distribution of the emulsified particles is 0.1 to 10 μm.

3. The composition according to claim 1, wherein, the crosslinked hyaluronic acid or its salt is chemically crosslinked by a crosslinking agent, and the crosslinking agent is at least one selected from sulfone crosslinking agents, epoxy crosslinking agents and phosphate crosslinking agents.

4. The composition according to claim 3, wherein, the crosslinking agent is at least one selected from divinyl sulfone, 1,4-butanediol diglycidyl ether, ethylene glycol diglycidyl ether, 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, polyethylene glycol diglycidyl ether, 1,2-ethylene glycol diglycidyl ether and sodium trimetaphosphate.

5. The composition according to claim 1, wherein, the particle size distribution is measured by Mastersizer 2000 of Malvern Panalytical.

6. The composition according to claim 1, wherein, the composition is a composition for skin moisturization.

7. The composition according to claim 1, wherein, the composition is a cosmetic composition.

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