Novel sphingolipid and external preparation composition for skin containing same

Abstract

Provided are: a novel sphingolipid which has a low melting point, is in a liquid phase at room temperature, and is readily mixed with a variety of vegetable and / or animal oils; and a composition for an external preparation for the skin, which contains the novel sphingolipid.

Description

[0001] This application is a divisional application of Chinese patent application No. 202080103740.1 (PCT / KR2020 / 018733), filed on December 21, 2020, and entitled “Novel sphingolipids and skin topical compositions containing the same”. Technical Field

[0002] The present invention relates to a novel sphingolipid having a low melting point, existing in a liquid state at room temperature, and being soluble in various oils; and a composition for external use on the skin containing the same, specifically a pharmaceutical composition, a cosmetic composition, or a quasi-drug composition. Background Art

[0003] The stratum corneum is present in the outermost layer of the skin and is composed of dead keratin cells that play a role like bricks and the intercellular lipid components that surround dead keratin cells like cement. In the dead cells that constitute such a stratum corneum, there is a high concentration of natural moisturizing factor (Natural moisturizing factor) as a water-soluble component, which can not only play the role of making the skin present flexibility, but also can maintain appropriate moisture. That is, in order to maintain appropriate moisture in the stratum corneum, the appropriate shedding of the natural moisturizing factor, sebum, intercellular lipid components of the keratinocytes, and keratinocytes as the product of the epidermal differentiation process plays a role as an important factor. If the balance between these factors is broken or missing, then xerosis can be brought out. Various studies have been carried out on the correlation between ceramide as the main constituent of the above-mentioned intercellular lipid components and xerosis, and it has been found that ceramide content decreases and fatty acid length shortens in the skin suffering from xerosis.

[0004] Ceramides are a type of sphingolipid with a structure consisting of fatty acids linked to sphingosine or 4-hydroxydihydrosphingosine via an amide bond. Ceramides account for over 40% of the intercellular lipids that make up the stratum corneum of the skin and are essential for forming the structure and function of the stratum corneum. Furthermore, ceramides act as a lipid barrier, inhibiting water evaporation and maintaining the regular structure of the stratum corneum. While these ceramides offer excellent moisturizing properties, their poor solubility limits their use. For example, when ceramides are added to an aqueous or oily phase to produce a skin application formulation, very high temperatures are required to dissolve them. Furthermore, at lower temperatures, ceramide precipitation occurs. In recent years, the use of ceramides has been boosted by the development of technologies that increase their solubility through liposomes and encapsulation, but the reality is that large amounts of emulsifiers are still required, or only very small amounts of ceramide are used. Summary of the Invention

[0005] Technical issues

[0006] Meanwhile, the present inventors discovered a novel sphingolipid obtained by acylation of natural ceramides derived from plants or animals. This substance not only exhibits the original effects of ceramide, but also has a low melting point, exists in a liquid state at room temperature, and has excellent solubility in various oils. This led to the completion of the present invention.

[0007] Therefore, a technical object of the present invention is to provide the aforementioned novel sphingolipid.

[0008] In addition, another technical problem of the present invention is to provide a skin external application composition for anti-inflammatory, moisturizing, skin protection against ultraviolet (UV) rays, or skin barrier improvement, comprising the above-mentioned sphingolipid as an active ingredient, specifically to provide a skin external application pharmaceutical composition, cosmetic composition, or quasi-drug composition.

[0009] Other objects and advantages of the present invention will be more clearly illustrated by the following detailed description of the invention and the scope of the claims.

[0010] Technical solutions

[0011] In order to achieve the above technical problems, the present invention provides a novel sphingolipid represented by the following Chemical Formula 1.

[0012] [Chemical Formula 1]

[0013]

[0014] In the above formula,

[0015] R1 is CH2-CH2, CH=CH or C(H)R4-CH2,

[0016] R2 is a saturated or unsaturated aliphatic hydrocarbon group having 12 to 28 carbon atoms,

[0017] R3 is a saturated or unsaturated aliphatic hydrocarbon group having 12 to 28 carbon atoms, which may be substituted or unsubstituted by a hydroxyl group,

[0018] Multiple R4 are the same or different and are each independently an aliphatic acyl group having 1 to 6 carbon atoms or a hydroxyl group (OH),

[0019] At least one of the plurality of R4 groups contains an aliphatic acyl group having 1 to 6 carbon atoms.

[0020] According to one embodiment of the present invention, at least one of the multiple R4 groups of the sphingolipid represented by Chemical Formula 1 may include an acetyl group (CH3CO-).

[0021] According to one embodiment of the present invention, in the above Chemical Formula 1, R3 can be obtained using oil or fat derived from at least one natural supply source selected from sea buckthorn, palm, sunflower, rapeseed, rapeseed, olive, coconut, soybean, horse, cattle, sheep, bee, fish, crustacean, and human as a raw material.

[0022] According to one embodiment of the present invention, the sphingolipid may have a melting point (mp) of 40° C. or less.

[0023] According to one embodiment of the present invention, the sphingolipid may be a substance that is soluble in at least one of vegetable oils, animal oils, fractionated oils, and synthetic oils.

[0024] According to one embodiment of the present invention, in thin layer chromatography (TLC) using a predetermined developing solvent [chloroform:methanol:formic acid=190:15:1 (volume ratio)], the Rf value of the sphingolipid can be higher than the Rf value of non-acylated ceramide.

[0025] According to one embodiment of the present invention, the acidity (pH) of the sphingolipid may be 3 to 7.

[0026] Furthermore, the present invention provides a composition for external use on the skin comprising the aforementioned novel sphingolipid, or a pharmaceutically acceptable salt or solvate thereof as an active ingredient.

[0027] According to one embodiment of the present invention, the above-mentioned skin external application composition can be used for anti-inflammation, moisturizing improvement, or skin barrier improvement.

[0028] According to one embodiment of the present invention, the above-mentioned skin external application composition can be used to repair skin damage or relieve skin irritation caused by ultraviolet (UV) rays.

[0029] According to one embodiment of the present invention, the skin external application composition may be a composition for preventing hair damage, moisturizing hair, moisturizing lips, or protecting lips.

[0030] According to one embodiment of the present invention, the content of the novel sphingolipid may be in the range of 0.00001 to 50 wt % based on the total weight of the composition.

[0031] According to one embodiment of the present invention, the skin external application composition may further include at least one of 4-hydroxydihydrosphingosine, sphingosine, and dihydrosphingosine.

[0032] According to one embodiment of the present invention, the above-mentioned skin topical composition may further include at least one of ceramide 1 (EOS), ceramide 2 (NS), ceramide 3 (NP), ceramide 4 (EOH), ceramide 5 (AS), ceramide 6 (NH), ceramide 7 (AP), ceramide 8 (AH) and ceramide 9 (EOP).

[0033] According to one embodiment of the present invention, the skin external application composition may be an oily preparation without an emulsifier.

[0034] Furthermore, the present invention provides a pharmaceutical composition comprising the above-mentioned composition for external use on skin.

[0035] Furthermore, the present invention provides a cosmetic composition comprising the above-mentioned skin external application composition.

[0036] Furthermore, the present invention provides a quasi-drug composition comprising the above-mentioned external skin preparation composition.

[0037] The present invention also provides a method for producing a cosmetic composition, comprising: (i) dissolving a novel sphingolipid represented by Chemical Formula 1, cholesterol, fatty acids, and phospholipids in oil to produce a lipid portion; (ii) mixing a mixture of the sphingolipid and an organic acid with water to produce an aqueous phase portion; and (iii) heating and mixing the lipid portion from step (i) and the aqueous phase from step (ii), and then adding a preservative.

[0038] Effects of the Invention

[0039] According to one embodiment of the present invention, the novel sphingolipid represented by Chemical Formula 1 has a low melting point, is liquid at room temperature, and has excellent solubility and miscibility with various oils. Therefore, it can be easily formulated into various dosage forms without the use of a separate emulsifier or high temperatures. It also exhibits excellent moisturizing and skin barrier enhancement properties, and can be used in all topical skin preparations for all applications of conventional ceramides or sphingolipids.

[0040] Therefore, in the present invention, the novel sphingolipids can be effectively used as active ingredients in pharmaceuticals, cosmetics, quasi-drugs, and other compositions for anti-inflammation, moisturizing improvement, or skin barrier improvement; repair of skin damage or relief of skin irritation caused by ultraviolet (UV) rays; and lip moisturizing or lip protection.

[0041] The effects of the present invention are not limited to the above-exemplified contents, and this specification includes more diverse effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is a graph showing the results of high performance liquid chromatography (HPLC) analysis of a novel sphingolipid according to one embodiment of the present invention.

[0043] Figure 2 This is a photograph showing the results of thin layer chromatography analysis of a novel sphingolipid according to an embodiment of the present invention.

[0044] Figure 3 These are photographs showing the oil solubility of the novel sphingolipid of the present invention.

[0045] Figure 4 This is a graph showing the water content results obtained by clinical application of the cream of the present invention.

[0046] Figure 5 This is a graph showing the results of preventing transepidermal water loss obtained by clinical application of the cream of the present invention.

[0047] Figure 6 The figure shows the changes in lip moisture retention and lip texture obtained by clinical application of the lip balm dosage form of the present invention.

[0048] Figure 7 This is a graph showing the change rate of the minimum erythema dose (MED) obtained by clinical application of the cream of the present invention. DETAILED DESCRIPTION

[0049] Hereinafter, the present invention will be described in detail.

[0050] Unless otherwise defined, all terms (including technical and scientific terms) used in this specification may be used according to the meaning commonly understood by those skilled in the art to which the present invention belongs. In addition, terms defined in commonly used dictionaries should not be interpreted in an ideal or excessive manner unless otherwise explicitly defined.

[0051] Throughout this specification, when a portion is referred to as "comprising" a certain component, unless otherwise specified, the implication is that the portion may further comprise other components, not that the portion is excluded. Furthermore, throughout this specification, "on" includes not only being above or below the portion but also including other portions therebetween, and does not necessarily mean being above based on the direction of gravity.

[0052] The present invention relates to a novel sphingolipid having a normal temperature liquid phase and fat solubility and its use.

[0053] In this specification, normal temperature refers to a normal temperature commonly known in the art (room temperature), for example, 10 to 40°C, specifically 10 to 30°C, and specifically 20±5°C.

[0054] Specifically, the novel sphingolipids of the present invention, unlike conventional ceramides or sphingolipids, have a structure containing at least one acyl group (O-acyl group) within their molecular structure. These novel sphingolipids have a low melting point of below 40°C, allowing them to exist in a liquid form at room temperature. Furthermore, they are soluble in a variety of oils (e.g., vegetable oils, animal oils, fractionated oils, and synthetic oils), allowing for easy dispersion and mixing. Consequently, the novel sphingolipids of the present invention can be easily formulated into various dosage forms without the need for a separate emulsifier, making them particularly effective in hair and / or cosmetic products using oil-based formulations.

[0055] Furthermore, the novel sphingolipids retain the excellent moisturizing properties and skin barrier function-enhancing abilities of conventional ceramides and sphingolipids, and thus can be applied to skin topical compositions whose primary functions are to increase skin moisturizing properties, prevent skin dryness, reduce transepidermal water loss, and / or strengthen the underlying skin. Specifically, they can be applied to pharmaceutical compositions, cosmetic compositions, and / or quasi-drug compositions, etc.

[0056] <New sphingolipids>

[0057] One embodiment of the present invention relates to a sphingolipid represented by the following Chemical Formula 1, and its derivatives, and pharmaceutically acceptable salts or solvates thereof.

[0058] [Chemical Formula 1]

[0059]

[0060] In the above formula,

[0061] R1 is CH2-CH2, CH=CH or C(H)R4-CH2,

[0062] R2 is a saturated or unsaturated aliphatic hydrocarbon group having 12 to 28 carbon atoms,

[0063] R3 is a saturated or unsaturated aliphatic hydrocarbon group having 12 to 28 carbon atoms, which may be substituted or unsubstituted by a hydroxyl group,

[0064] Multiple R4 are the same or different and are each independently an aliphatic acyl group having 1 to 6 carbon atoms or a hydroxyl group (OH),

[0065] At least one of the plurality of R4 groups contains an aliphatic acyl group having 1 to 6 carbon atoms.

[0066] As a specific example of the above chemical formula 1, R2 is a common aliphatic hydrocarbon group known in the art, and specifically can be a linear or branched alkyl, alkenyl or alkynyl group having 12 to 20 carbon atoms.

[0067] Furthermore, R3 is a common aliphatic hydrocarbon group known in the art, specifically a linear or branched alkyl, alkenyl, or alkynyl group having 12 to 24 carbon atoms, which may or may not contain a hydroxyl group (OH). Such R3 can be obtained using as a raw material an oil or fat derived from at least one natural source selected from sea buckthorn, palm, sunflower, rapeseed, rapeseed, olive, coconut, soybean, horse, cattle, sheep, bee, fish, crustaceans, and humans.

[0068] In addition, multiple R4 are the same or different and can be aliphatic acyl or hydroxyl groups. Specifically, multiple R4 can be acetyl (CH3CO-) or hydroxyl groups. More specifically, it is preferred that at least one of the two R4 included in R1 is acetyl (CH3CO-, Ethanoyl).

[0069] As a preferred example of the present invention, the compound of the above Chemical Formula 1 can be further embodied as at least one of the following Chemical Formulas 2 to 7. However, the present invention is not limited thereto.

[0070] [Chemical Formula 2]

[0071]

[0072] [Chemical Formula 3]

[0073]

[0074] [Chemical Formula 4]

[0075]

[0076] [Chemical Formula 5]

[0077]

[0078] [Chemical Formula 6]

[0079]

[0080] [Chemical Formula 7]

[0081]

[0082] In the above chemical formulas 2 to 7,

[0083] R1 to R3 are each the same as defined in Chemical Formula 1.

[0084] Conventionally, ceramides generally have a high melting point (mp) of 90°C or higher, requiring either high temperatures or the use of emulsifiers to formulate them. Consequently, conventional ceramide formulations often result in complex processes and increased costs.

[0085] In contrast, the novel sphingolipid represented by the above chemical formula 1 has a melting point (mp) of 40°C or less and exists in a liquid form at room temperature. In addition, since it contains at least one acetyl group in its chemical structure, it can be easily mixed and dissolved in common oils known in the art at room temperature (see the following). Figure 3 The novel sphingolipids of the present invention, which are oil-soluble at room temperature, can be easily formed into various dosage forms without the use of high temperatures or emulsifiers. Furthermore, they can fully utilize the inherent moisturizing and skin barrier function-enhancing abilities of ceramides.

[0086] As a specific example, the novel sphingolipid may have a melting point (mp) of 40°C or less, for example, 10 to 40°C, specifically 10 to 30°C, and more specifically 10 to 25°C.

[0087] As another specific example, the novel sphingolipid may be a substance soluble in at least one of vegetable oils and fats, animal oils and fats, fractionated oils, and synthetic oils.

[0088] As another specific example, in thin layer chromatography (TLC) using a predetermined developing solvent [chloroform:methanol:formic acid = 190:15:1 (volume ratio)], the Rf value of the sphingolipid can be higher than the Rf value of the non-acylated ceramide. Specifically, the Rf value of the sphingolipid can be 0.8 to 0.9, and the Rf value of the non-acylated ceramide can be 0.4 to 0.5.

[0089] As another specific example, the acidity (pH) of the novel sphingolipid may be 3 to 7.

[0090] In addition, the present invention provides a salt of the novel sphingolipid represented by Chemical Formula 1, preferably a pharmaceutically acceptable salt.

[0091] As used herein, "pharmaceutically acceptable salts" are salts that, within the scope of purely medical judgment, do not cause excessive toxicity, irritation, allergic reactions, etc., and are suitable for use in contact with the tissues of humans and lower animals. Such pharmaceutically acceptable salts are well known in the art and are described in detail, for example, in the literature (SM Berge et al., J. Parmaceutical Sciences, 66, 1, 1977). Salts can be prepared during the final isolation and purification of the compounds of the present invention in the same reaction system or by reacting them separately with an inorganic base or an organic base. Preferred examples of base addition salts include alkali salts such as ammonium salts, salts of lithium, sodium, potassium, magnesium, calcium, and the like, and alkaline earth metal salts; salts with organic bases, for example, aliphatic and aromatic primary, secondary, and tertiary amines, for example, methylamine, ethylamine, propylamine, isopropylamine, the four butylamine isomers, dimethylamine, diethylamine, diethanolamine, dipropylamine, diisopropylamine, di-n-butylamine, pyrrolidine, piperidine, morpholine, trimethylamine, triethylamine, tripropylamine, quinuclidine, pyridine, quinoline and isoquinoline, benzathine, N-methyl-D-glucamine, 2-amino-2-(hydroxymethyl)-1,3-propanediol, hydrabamine salts; and salts with amino acids such as arginine and lysine.

[0092] In addition, the present invention may include hydrates or solvates of the novel sphingolipid represented by the above Chemical Formula 1, and their derivatives. In the above solvates, the solvent is not particularly limited, and may include any common solvent known in the art.

[0093] The novel sphingolipid represented by Chemical Formula 1 of the present invention can be isolated and purified from natural substances, and produced through a predetermined treatment (acylation) or according to a chemical synthesis method known in the art.

[0094] As a specific example, the novel sphingolipid represented by Chemical Formula 1 can be obtained by separating and refining fatty acid oils and fats derived from natural substances, such as natural plants (e.g., sea buckthorn, palm, sunflower, rapeseed, rapeseed, olive, coconut, soybean, etc.) and animals (e.g., horses, cattle, sheep, bees, fish, crustaceans, humans, etc.), thereby isolating ceramide, and then subjecting the isolated ceramide to an acylation treatment according to conventional methods known in the art.

[0095] In addition, the target novel sphingolipid can be further separated and / or purified by processes such as fractionation, and the fractionation solvent used at this time can use the above-mentioned extraction solvent without limitation. It can also be purified by a purification method known to those skilled in the art to which the present invention belongs. As an example of such a purification method, it can be separated and purified by implementing each concentration gradient chromatography of a supplementary purification method consisting of reverse phase partition chromatography, normal phase adsorption chromatography, ion exchange chromatography, size exclusion chromatography, or a combination of one or more thereof. As the above-mentioned chromatography, column chromatography (column chromatography) filled with various synthetic resins such as silica gel or activated alumina and high-speed liquid chromatography (HPLC) can be used alone or in combination. However, the extraction and separation purification method of the compound is not necessarily limited to the above-mentioned method.

[0096] The novel sphingolipid represented by the above chemical formula 1, its isomers, and its pharmaceutically acceptable salts or solvates are not only easily soluble and dispersible in various oils at room temperature, but also possess the excellent moisturizing effect and skin barrier function-enhancing effect inherent to ceramides. Therefore, it can be effectively used in all fields where ceramides or sphingolipids are used.

[0097] <Skin external use composition>

[0098] Another embodiment of the present invention relates to a composition for external use on skin comprising the novel sphingolipid represented by the above Chemical Formula 1, its derivatives, or pharmaceutically acceptable salts or solvates thereof as an active ingredient.

[0099] In this specification, the term "active ingredient" refers to an ingredient that can exhibit the desired activity alone or together with a carrier that has no activity itself.

[0100] In addition, in this specification, "external agent" is a preparation provided for external use, and the skin external agent composition can be formulated by adding a medium or base available in cosmetics, pharmacy or dermatology. This includes all dosage forms suitable for local application. As a specific example, it can be provided in the following forms: a solution, a gel, a solid, a soft mass anhydrous product, an emulsion, a suspension, a microemulsion, a microcapsule, a microsphere or an ionic (liposome) and non-ionic vesicle dispersion obtained by dispersing an oil phase in an aqueous phase; or a cream, a toner, a lotion, a powder, an ointment, a spray, a facial mask or a concealer stick. It can also be used in the form of a foam or an aerosol composition further containing a compressed propellant, but is not limited thereto. These compositions can be manufactured according to the usual methods in the art.

[0101] The skin external application composition of the present invention containing the novel sphingolipid can be used in all fields in which ceramides or sphingolipids have been conventionally used.

[0102] Specific examples include compositions for external use on the skin for anti-inflammatory, moisturizing, or skin barrier improvement purposes; for repairing skin damage or relieving skin irritation caused by ultraviolet (UV) rays; or for preventing hair damage, moisturizing hair, moisturizing lips, or protecting lips. More specifically, compositions for external use on the skin include pharmaceutical compositions, cosmetic compositions, and / or quasi-drug compositions, but are not particularly limited thereto.

[0103] The content of the novel sphingolipid is not particularly limited and can be appropriately adjusted within a typical content range that exhibits the aforementioned efficacy. For example, based on the total weight of the composition (e.g., 100% by weight), the content of the novel sphingolipid can be in the range of 0.00001 to 50% by weight, specifically 0.0001 to 40% by weight, and more specifically 0.001 to 30% by weight.

[0104] In addition, the skin topical composition of the present invention may further contain common ingredients known in the art in addition to the above-mentioned ingredients. For example, it may contain ceramide, cholesterol, fatty acids, 4-hydroxydihydrosphingosine, phospholipids, or mixtures thereof. Among them, ceramide, cholesterol, fatty acids, and 4-hydroxydihydrosphingosine are the main components of intercellular lipids, and phospholipids are the main substances that constitute cell walls. They can effectively prevent water evaporation from the skin epidermis through a structure and composition similar to that of intercellular lipids, thereby maximizing water retention in the skin.

[0105] As a specific example, the above-mentioned skin external preparation composition may further contain at least one of 4-hydroxydihydrosphingosine, sphingosine, and dihydrosphingosine. In this case, the content of the above-mentioned components is not particularly limited and can be appropriately adjusted within the content range known in the art.

[0106] In addition, ceramide is one of the intercellular lipid components that make up the stratum corneum of the skin, constituting more than 40% of the skin lipids. It plays a role in maintaining and restoring the skin barrier, so it is necessary to maintain and replenish ceramide in order to maintain skin elasticity. Thus, there are 9 types of ceramides that make up the skin. Non-limiting examples of usable ceramides include ceramide 1 (EOS), ceramide 2 (NS), ceramide 3 (NP), ceramide 4 (EOH), ceramide 5 (AS), ceramide 6 (NH), ceramide 7 (AP), ceramide 8 (AH), ceramide 9 (EOP), or mixtures thereof. In this case, the content of ceramide is not particularly limited and can be appropriately adjusted within the content range known in the art.

[0107] In the present invention, the above-mentioned external skin preparation composition may be a pharmaceutical composition, a cosmetic composition, or a quasi-drug composition that can be applied to the skin, but is not particularly limited thereto.

[0108] As a specific example, the above-mentioned skin external application composition may be an oil composition that does not contain an emulsifier. Such an emulsifier is not particularly limited and may be a common component known in the art.

[0109] <Pharmaceutical Composition>

[0110] Another embodiment of the present invention relates to a pharmaceutical composition comprising the above-mentioned composition for external use on skin, specifically a pharmaceutical composition for external use on skin. As a specific example, the pharmaceutical composition comprises the novel sphingolipid represented by Chemical Formula 1, or a pharmaceutically acceptable salt or solvate thereof as an active ingredient.

[0111] The pharmaceutical composition is preferably used for anti-inflammatory, moisturizing or skin barrier improvement purposes; repairing skin damage caused by ultraviolet (UV) rays or relieving skin irritation purposes; or preventing hair damage, moisturizing hair, moisturizing lips or protecting lips, but is not particularly limited thereto.

[0112] In addition to the sphingolipid of Chemical Formula 1, or a pharmaceutically acceptable salt or solvate thereof, the pharmaceutical composition of the present invention may further comprise pharmaceutically suitable and physiologically acceptable carriers, excipients, and diluents. Representative examples of the pharmaceutically acceptable carriers, excipients, or diluents include lactose, glucose, sucrose, sorbitol, mannitol, xylitol, maltitol, starch, gelatin, glycerol, acacia gum, alginate, calcium phosphate, calcium carbonate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil, injectable esters, Witepsol, Macrogol (polypropylene glycol), Tween 61, cocoa butter, and lauryl esters. For example, the pharmaceutical composition can be formulated by using common excipients, binders, disintegrants, lubricants, solubilizers, suspending agents, preservatives, or extenders known in the art.

[0113] In addition, the pharmaceutical composition can be formulated into any dosage form known in the art, such as cream, gel, patch, spray, ointment, plaster, emulsion, liniment, pasta or cataplasma.

[0114] In the pharmaceutical composition of the present invention, the dosage of the novel sphingolipid of Chemical Formula 1 as an active ingredient can be appropriately adjusted according to the form and purpose of use, the patient's condition, the type and severity of symptoms, etc. For external use, the drug can be administered once a day or divided into multiple doses. However, it is not particularly limited thereto. For example, the preferred dosage of the above-mentioned pharmaceutical composition varies depending on the patient's condition, age, weight, degree of disease progression, drug form, route of administration, and time, and can be appropriately determined by an expert or a person skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at a dosage of 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg per day. For external use, the drug can be administered once a day or divided into multiple doses. However, it is not particularly limited thereto.

[0115] <Cosmetic Composition>

[0116] Another embodiment of the present invention relates to a cosmetic composition comprising the above-mentioned external skin preparation composition. As a specific example, the cosmetic composition comprises the novel sphingolipid represented by the above-mentioned Chemical Formula 1, or a pharmaceutically acceptable salt or solvate thereof as an active ingredient.

[0117] The above-mentioned cosmetic composition is preferably used for anti-inflammatory, moisturizing or skin barrier improvement purposes; for repairing skin damage caused by ultraviolet (UV) rays or relieving skin irritation; or for preventing hair damage, moisturizing hair, moisturizing lips or protecting lips, but is not particularly limited thereto.

[0118] In the cosmetic composition of the present invention, the content of the sphingolipid of Chemical Formula 1 as an active ingredient is not particularly limited and can be appropriately adjusted depending on the form and purpose of use, skin condition, type and severity of symptoms, and the like.

[0119] In addition to the novel sphingolipid of Chemical Formula 1, or a pharmaceutically acceptable salt or solvate thereof, the cosmetic composition of the present invention may further include ingredients commonly used in cosmetic compositions. For example, conventional adjuvants known in the art, such as stabilizers, solubilizers, vitamins, pigments, and fragrances, carriers, and purified water may be included without limitation. Furthermore, to the extent that the objectives of the present invention are not hindered, conventional cosmetic compositions may further include water-soluble vitamins, oil-soluble vitamins, high-molecular-weight peptides, high-molecular-weight polysaccharides, sphingolipids, natural extracts, waxes, oils, detergents, surfactants, colorants, and fixatives.

[0120] Furthermore, the cosmetic composition of the present invention can be formulated into any dosage form commonly manufactured in the art, and can be appropriately selected depending on the intended purpose. For example, it can be in the form of a solution, emulsion, or viscous mixture. More specifically, it can be formulated into a skin softener, astringent, moisturizer, moisturizing essence, moisturizing oil, moisturizing oil, nourishing cream, massage cream, powder, facial mask, powder foundation, emulsion foundation, primer, surfactant-containing cleanser, gel, lotion, wax, spray, beauty serum, hair styling agent, and ointment. However, this is not limiting. For application of ceramide to the skin, dosage forms such as lotion, cream, and essence are preferred.

[0121] In particular, the novel sphingolipids of the present invention are oil-soluble and have excellent miscibility at room temperature, even without the use of an emulsifier alone. Therefore, they can be effectively used in hair care products and / or lip makeup products such as lipsticks that use oil-based formulations.

[0122] As a specific example of the present invention, the cosmetic composition can be used for moisturizing or protecting the lips. Such a lip cosmetic composition can be in the form of at least one selected from the group consisting of lip gloss, lip balm, lip cream, lip balm, and lipstick, but is not particularly limited thereto.

[0123] As another specific example of the present invention, the cosmetic composition can be used to prevent hair damage, moisturize hair, condition hair, or dye hair. Such hair cosmetic compositions have excellent formulation stability and can be formulated into convenient dosage forms. For example, they can be formulated in mist, serum, or leave-on forms. Specifically, they can be formulated into shampoo, hair conditioner, hair treatment, hair tonic, scalp treatment, hair lotion, hair cream, hair nourishing lotion, or general ointment. However, these are not particularly limiting.

[0124] The method for producing the cosmetic composition of the present invention is not particularly limited, and methods known in the art may be used without limitation. The above-described production method is not limited to the following production method, and the steps of each process may be modified or selectively combined as needed.

[0125] As an embodiment of the above-mentioned production method, it may include: (i) a step of dissolving the novel sphingolipid represented by Chemical Formula 1, cholesterol, fatty acids and phospholipids in oil to produce a lipid portion; (ii) a step of mixing the sphingolipid and organic acid mixture with water to produce an aqueous phase portion; and (iii) a step of heating and mixing the lipid portion of the above step (i) and the aqueous phase portion of the above step (ii) and further adding a preservative.

[0126] As the cholesterol used in the present invention, any common cholesterol known in the art can be used without limitation.

[0127] Phospholipids may be any common component known in the art without limitation. Non-limiting examples thereof include hydrogenated lecithin, hydrogenated phosphatidylcholine, phospholipids, hydrogenated lysophosphatidylcholine, hydrogenated lysophosphatidylcholine, hydroxylated lecithin, unsaturated lecithin, or a mixture of at least one of these.

[0128] In addition, the fatty acid may be any common component known in the art without limitation. For example, a linear saturated fatty acid having 12 to 30 carbon atoms, preferably 18 to 26 carbon atoms, may be used. Non-limiting examples of usable fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, branched-chain lauric acid, branched-chain myristic acid, branched-chain palmitic acid, branched-chain stearic acid, branched-chain oleic acid, or a mixture of at least one of these.

[0129] In step (i), the lipid fraction comprising the novel sphingolipid, cholesterol, fatty acids, and phospholipids is preferably added to the oil and then heated to 80-85°C for dissolution. The oil used in this process may be a conventional component known in the art, for example, silicone oils, hydrocarbon oils, higher fatty acid oils, ester oils, glyceride oils, lanolin oils, vegetable oils, or mixtures thereof.

[0130] The sphingolipid used in step (ii) is an essential component of the composition for simulating skin constituents and is different from the novel sphingolipid used in step (i). Such sphingolipids can be any common sphingolipid known in the art, for example, PY, ceramide, and other common sphingolipids.

[0131] The cosmetic composition of the present invention can be produced by heating and mixing the lipid portion and the aqueous phase portion dissolved by heating as described above, and then optionally adding a preservative.

[0132] In this case, the content ratio (mixing ratio) of the lipid portion and the aqueous phase portion is not particularly limited and can be appropriately adjusted within a range known in the art.

[0133] The water phase may be at a temperature of 75 to 80° C. The water phase may be a polyol, water, or a mixture thereof, and preferably a mixture of a polyol and water.

[0134] <Quasi-drug composition>

[0135] Another embodiment of the present invention relates to a quasi-drug composition comprising the above-mentioned external skin preparation composition. As a specific example, the quasi-drug composition comprises the novel sphingolipid represented by the above-mentioned Chemical Formula 1, or a pharmaceutically acceptable salt or solvate thereof.

[0136] The quasi-drug composition is preferably used for anti-inflammatory, moisturizing or skin barrier improvement purposes; for repairing skin damage or relieving skin irritation caused by ultraviolet (UV) rays; or for preventing hair damage, moisturizing hair, moisturizing lips or protecting lips, but is not particularly limited thereto.

[0137] The quasi-drug composition of the present invention may further contain, in addition to the above-mentioned components, a pharmaceutically acceptable carrier, excipient, or diluent, as needed. Such pharmaceutically acceptable carriers, excipients, or diluents may include, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, flavoring agents, and preservatives, as long as they do not impair the effects of the present invention.

[0138] Furthermore, when a composition containing the novel sphingolipid of the present invention as an active ingredient is used as a quasi-drug, it may further contain one or more active ingredients exhibiting the same or similar functions. When adding these additional ingredients, consideration should be given to skin safety, ease of formulation, and stability of the active ingredients, resulting from combined use. The quasi-drug composition may further contain one or more ingredients selected from the group consisting of: tyrosinase inhibitors such as kojic acid and arbutin, hydroquinone, and vitamin C (L-ascorbic acid), which are known whitening ingredients in the art; retinoic acid, TGF-β, animal placenta-derived proteins, betulinic acid, and chlorella extract, which are known ingredients in the art for improving skin elasticity, wrinkles, or moisturizing; and their derivatives and various plant extracts. The content of the additional ingredients is not particularly limited and may range from 0.0001% to 5% by weight relative to the total weight of the composition. This content range can be adjusted appropriately based on factors such as skin safety and ease of use.

[0139] Examples of the quasi-drug compositions of the present invention include disinfecting cleansers, body washes, ointments, wet wipes, and coatings. However, these are not particularly limiting, and the formulation method, volume, method of use, and components of the quasi-drug can be appropriately selected using conventional techniques known in the art.

[0140] Furthermore, the quasi-drug composition containing the novel sphingolipid of the present invention as an active ingredient can be used for anti-inflammatory, moisturizing, or skin barrier improvement purposes, including application to the skin of an individual; for repairing skin damage or alleviating skin irritation caused by ultraviolet (UV) rays; or for preventing hair damage, moisturizing hair, moisturizing lips, or protecting lips. In this case, the individual can include mammals including mice, livestock, and humans, without limitation.

[0141] The following examples are provided to further illustrate the present invention. These examples are only for the purpose of illustrating the present invention in more detail. It is obvious to those skilled in the art that the scope of the present invention is not limited by these examples according to the spirit of the present invention.

[0142] [Example 1: Production of Novel Sphingolipids]

[0143] 1-1. Sea buckthorn fatty acids

[0144] Sea buckthorn oil obtained from sea buckthorn seeds is treated with ethanol and caustic soda to separate the sea buckthorn oleyl alcohol portion and the glycerol portion, and then the carboxylic acid is reduced by treating with hydrochloric acid and fractionated with hexane to obtain the alcohol portion as fatty acid.

[0145] 1-2. Seabuckthorn Ceramide

[0146] The seabuckthorn fatty acid produced in Example 1-1 was dissolved in ethyl acetate, and sodium methoxide and 4-hydroxydihydrosphingosine were added, and the mixture was reacted at 50° C. for 2 hours. The reaction solution was then cooled to 5° C. and filtered to obtain a white filtrate.

[0147] The obtained white filtered product was dried and analyzed by silica thin-layer chromatography (developing conditions: chloroform+methanol+formic acid=190:15:1, 10% sulfuric acid for color development), whereby the presence of seabuckthorn ceramide was confirmed.

[0148] 1-3. Novel sphingolipids

[0149] The seabuckthorn ceramide produced in Example 1-2 was dissolved in ethyl acetate and treated with glacial acetic acid and triethylamine. After reacting at 50°C for 2 hours, a saturated sodium chloride aqueous solution equal in volume to the initial ethyl acetate was added. The mixture was allowed to stand and the lower layer removed. The supernatant was treated with sodium sulfate and concentrated under reduced pressure using excess ethanol. The ethyl acetate residue was removed to obtain a colorless liquid.

[0150] The obtained liquid novel sphingolipid was analyzed by high performance liquid chromatography (mobile phase chloroform:methanol = 96:4, normal phase stationary phase, light scattering detector), and the O-acylated peak represented by Chemical Formula 7 was confirmed (see below). Figure 1 ).

[0151] [Experimental Example 1: Melting Point Evaluation]

[0152] The melting points of the seabuckthorn ceramide produced in Example 1-2 and the novel sphingolipid (O-acylated seabuckthorn ceramide) produced in Example 1-3 were confirmed.

[0153] The experimental results showed that the melting point of the seabuckthorn ceramide of Example 1-2 was as high as 110°C, while the melting point of the novel sphingolipid produced in Example 1-3 was 15°C, thus confirming that it existed in a liquid state at room temperature (see Table 1 below).

[0154] [Table 1]

[0155]

[0156] [Experimental Example 2: Chromatographic Analysis]

[0157] The seabuckthorn ceramide produced in Example 1-2 and the novel sphingolipid (acylated seabuckthorn ceramide) produced in Example 1-3 were developed by silica gel thin layer chromatography in a solvent ratio of chloroform + methanol + formic acid = 190:15:1, and the color was developed in a 10% sulfuric acid solution to confirm a spot. The results are as follows. Figure 2 shown.

[0158] The experimental results showed that the novel sphingolipids of the present invention have an increased Rf value compared to conventional ceramides due to acylation (see the following). Figure 2 ).

[0159] [Experimental Example 3: Evaluation of Oil Miscibility at Normal Temperature]

[0160] The new sphingolipids prepared in the examples were mixed with various oils to evaluate their solubility at room temperature. The results are shown in Tables 2 and 3. Figure 3 shown.

[0161] As shown in Table 2 below, the novel sphingolipids produced in the present invention exhibit excellent solubility and miscibility in a variety of vegetable and animal oils. In particular, their excellent solubility and dispersibility in oils at room temperature make it possible to easily create a variety of dosage forms without the use of conventional emulsifiers or separate high-temperature processes.

[0162] [Table 2]

[0163]

[0164] [ Dosage Form Example 1: Cream Preparation]

[0165] The liquid sphingolipids produced in the Examples were used to produce a cream that can be applied to the human body by a conventional method according to the composition described in the following Table 3. The content of each component in Table 3 is expressed in % by weight.

[0166] [Table 3]

[0167]

[0168]

[0169]

[0170] [ Dosage Form Example 2: Lip Balm Manufacturing]

[0171] A cream that can be applied to the human body by a conventional method was prepared according to the composition described in the following Table 3. The content of each component in Table 3 is expressed in % by weight.

[0172] [Table 4]

[0173]

[0174] [ Experimental Example 4: Evaluation of Skin Moisture Content]

[0175] Regarding the cream of the present invention, changes in skin moisture content were evaluated as follows.

[0176] The cream of Example 2, which contains a novel sphingolipid, was used as a sample, and the cream of Comparative Example 2, which does not contain a sphingolipid, was used as a control. Changes in the electrical conductivity of the epidermal water content were quantified using a corneometer to measure changes in skin moisture before and after application. Specifically, the electrical conductivity of the skin was measured before application of each cream. The creams of Example 2 and Comparative Example 2 were applied twice daily, and the electrical conductivity was measured 4, 7, 10, and 14 days later. The results were expressed as percentages (%).

[0177] Figure 4 The results of a comparative experiment comparing the changes in skin moisture content over time using creams containing the novel sphingolipids of the present invention are shown. Specifically, it was found that the rate of increase in moisture in the cream of Example 2 was significantly higher than that in Comparative Example 2 from the time of application until 14 days had passed.

[0178] This confirmed that the cosmetic composition of the present invention containing the novel sphingolipid has an enhanced moisture-increasing effect and thus has relatively excellent moisturizing effect and anti-drying effect.

[0179] [ Experimental Example 5: Evaluation of Skin Barrier Restoration Ability]

[0180] Regarding the cream of the present invention, changes in skin barrier recovery ability were evaluated as follows.

[0181] As a sample, the cream of Example 2 containing the novel sphingolipid was used, and as a control, the cream of Comparative Example 2 containing no sphingolipid was used. 2 The transepidermal water loss (TEWL) was measured at 4 hrs (15min) and the skin barrier recovery ability after sample application was evaluated.

[0182] Figure 5 These are the results of a comparative experiment comparing the skin barrier recovery ability of sphingolipid-containing creams of the present invention by measuring the transepidermal water loss (TEWL). Specifically, the cream of Example 2 exhibited lower TEWL than that of Comparative Example 2. This demonstrates that the cosmetic composition of the present invention, containing the novel sphingolipid, exhibits excellent skin barrier recovery efficacy.

[0183] [ Experimental Example 6: Evaluation of the Skin Barrier Restoration Ability of Lips

[0184] Regarding the cream of the present invention, the moisturizing effect on lips and the change in lip texture were evaluated as follows.

[0185] The lip balm of Example 3 containing the novel sphingolipid was applied to the lips, and the volume of the concave part in the lip skin was measured using Antera 3D CS (mm 3 ), the measurement results are as follows Figure 6 shown.

[0186] like Figure 6 As shown, the lip balm containing the sphingolipid of the present invention has a volume value lower than that of the control group (0w) in proportion to the application time, and thus it can be seen that it has an excellent effect of improving the skin texture of the lips.

[0187] [ Experimental Example 7: Evaluation of Skin Protection Against Ultraviolet (UV)

[0188] The cream of the present invention was evaluated for skin soothing (redness relief) and protective efficacy against external stimulation (ultraviolet rays, UV) as follows.

[0189] As a sample, the cream of Example 2 containing the novel sphingolipid was used, and as a control group, the cream of Comparative Example 2 not containing the novel sphingolipid was used. Specifically, the inner upper arm of the subject was used as a test site. After cleaning with a cleanser, the skin was kept stable for at least 30 minutes in a place maintained at a constant temperature and humidity (24±1°C, RH50±5%). Then, the test site was repeatedly irradiated with ultraviolet rays (UVB: 2-3 MED, UVA: 60-100 J / cm 2 ) and measured the minimum amount of light that induced erythema, the minimal erythema dose (MED). The results are as follows Figure 7 shown.

[0190] like Figure 7 As shown, the sphingolipid-containing cream of the present invention has a higher MED than the control group. This means that the minimum light intensity that induces skin erythema is increased, indicating that it prevents skin damage caused by ultraviolet rays and exhibits a skin protective effect.

Claims

1. A sphingolipid represented by the following Chemical Formula 1: [Chemical Formula 1] In the formula, R1 is CH2-CH2, CH=CH or C(H)R4-CH2, R2 is a saturated or unsaturated aliphatic hydrocarbon group having 12 to 28 carbon atoms, R3 is a saturated or unsaturated aliphatic hydrocarbon group having 12 to 28 carbon atoms, which may be substituted or unsubstituted by a hydroxyl group, Multiple R4 are the same or different and are each independently an aliphatic acyl group having 1 to 6 carbon atoms or a hydroxyl group (OH), in, At least one of the plurality of R4s contains an aliphatic acyl group having 1 to 6 carbon atoms.

2. The sphingolipid according to claim 1, wherein at least one of the plurality of R4s of the sphingolipid represented by Chemical Formula 1 comprises an acetyl group (CH3CO-).

3. The sphingolipid according to claim 1, which is represented by any one of the following Chemical Formulas 2 to 7: [Chemical Formula 2] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] In the chemical formulas 2 to 7, R1 to R3 are each the same as defined in claim 1.

4. The sphingolipid according to claim 1, wherein R3 in Chemical Formula 1 is obtained using as a raw material an oil or fat derived from at least one source selected from sea buckthorn, palm, sunflower, rapeseed, rapeseed, olive, coconut, soybean, horse, cattle, sheep, bee, fish, crustacean, and human. The sphingolipid according to claim 1 , having a melting point (mp) of 40° C. or lower. The sphingolipid according to claim 1 , which is soluble in at least one of vegetable oils and fats, animal oils and fats, fractionated oils, and synthetic oils. 7 . The sphingolipid according to claim 1 , wherein the Rf value of the sphingolipid is higher than the Rf value of non-acylated ceramide in thin layer chromatography (TLC) using a developing solvent of chloroform:methanol:formic acid=190:15:1 in a volume ratio. The sphingolipid according to claim 1 , which has a pH of 3 to 7. 9 . A composition for external use on the skin comprising the sphingolipid according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof as an active ingredient. 10 . The composition for external use on skin according to claim 9 , which is used for anti-inflammation, improvement of moisturizing, or improvement of skin barrier. The composition for external use on skin according to claim 9, which is used for repairing skin damage or alleviating skin irritation caused by ultraviolet rays (UV).

12. The composition for external use on skin according to claim 9, which is used for preventing hair damage, moisturizing hair, moisturizing lips, or protecting lips. 13 . The composition for external use on skin according to claim 9 , wherein the content of the sphingolipid is in the range of 0.00001 to 50% by weight based on the total weight of the composition. The composition for external use on skin according to claim 9 , further comprising at least one of 4-hydroxysphingosine, sphingosine, and dihydrosphingosine.

15. The skin external application composition according to claim 9, further comprising at least one of ceramide 1 (EOS), ceramide 2 (NS), ceramide 3 (NP), ceramide 4 (EOH), ceramide 5 (AS), ceramide 6 (NH), ceramide 7 (AP), ceramide 8 (AH), and ceramide 9 (EOP). The composition for external use on skin according to claim 9 , which is an oily preparation not containing an emulsifier. A pharmaceutical composition comprising the composition for external skin application according to claim 9. 18 . A cosmetic composition comprising the skin external application composition according to claim 9 . A quasi-drug composition comprising the external skin preparation composition according to claim 9.

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