KR20180096158A - Composition for treating or preventing aging comprising maresin 1 and use thereof - Google Patents

Abstract

A composition for treating or preventing skin aging comprising Maresin 1 (MaR1) as an active ingredient, and uses thereof are provided.

Description

[0001] The present invention relates to a composition for preventing or treating skin aging comprising maresin 1 as an active ingredient and a use thereof.

The present invention relates to a composition for preventing or treating skin aging comprising maresin 1 and its use.

Skin aging processes, including skin wrinkle formation, are usually caused by intrinsic aging and photoaging. Over time, endogenous aging is accompanied by a decrease in the secretion of various hormones that regulate metabolism, decreased function of immune cells and activity of cells, resulting in decreased biosynthesis of immune proteins and biocompatible proteins necessary for the living body. The extrinsic aging increases the content of ultraviolet rays reaching the surface of the sunlight due to destruction of the ozone layer and the environmental pollution is further intensified, so that the thickness of the skin decreases, the wrinkles increase, the elasticity decreases, Freckles and black blotches are also increasing.

The skin consists of the epidermis, the epidermis dermis boundary, the dermis, and the subcutaneous fat layer in order. The epidermis is divided into the epidermis, the granule, the superficial layer and the basal layer in order from the outside. Intercellular lipids act as a mortar and constitute a skin barrier. In addition, a healthy human epidermal cell has a high concentration of natural moisturizing factor (NMF) to help maintain moisture in the skin. For example, substances such as amino acids are water-soluble, Thereby suppressing drying.

However, as it is nowadays, there is a tendency to adjust the temperature of the air / heating due to the change of environment or life pattern, the stress caused by various stresses and environmental pollution in the social life, frequent washing according to make- Due to various causes such as aging of the skin, moisture of the skin layer is reduced, the skin becomes dry, the surface becomes rough, and the skin loses its moisture and appears to be vigorous. Therefore, the need for a skin moisturizing agent is increasing. Excessive physical and chemical stimuli from the outside, ultraviolet rays, stress and nutritional deficiencies lower the normal functions of the skin and promote skin aging phenomena such as loss of elasticity, epidermalization and wrinkle formation. Especially, The dermis border and the dermis are severely damaged.

The dermis is a fibroblast that produces proteins such as collagen and elastin and a variety of mucopolysaccharides to form an extracellular matrix (ECM). Through proper decomposition, the dermis absorbs and reforms the tissue This happens. Matrix metalloproteinases (MMPs) are mainly responsible for cellular degradation of the dermis. MMP is a zinc-dependent endopeptidase, and TIMP (Tissue Inhibitor of Matrix Metalloproteinases) is an endogenous inhibitor. MMPs are classified into collagenases (MMP-1, MMP-8, MMP-13), gelatinase (MMP-2, MMP-9), stromelysins, (MMP-3, MMP-10, MMP-11), matrilysin (MMP-6, MMP-26), enamelysin (MMP-20), metalloelastase MMP-12), membrane type MMP (MMP-14 ~ 17, MMP-24, MMP-25). Tumor Necrosis Factor (TNF), Extracellular Metrix Metalloproteinase Inducer (EMFRIN), and Transcription Factor 20 (TCF20). If the expression and activity of MMP is inappropriately controlled by endogenous aging or photoaging, the extracellular matrix in the dermis is damaged and destroyed due to a decrease in physiological function, resulting in loss of elasticity and elasticity, resulting in wrinkles of the skin. .

In addition, skin aging can be triggered by secondary reactions via reactive oxygen species (ROS) that occur when ultraviolet light is absorbed into the skin (Lee, Hee-kyung, 2012; Afaq & Mukhtar, 2006; Bowden, 2004). At this time, ROS causes wrinkle formation by chain cleavage and abnormal cross-linking such as collagen, which is a connective tissue component, and increases collagen synthesis by increasing the activity of MMP-1, thereby accelerating aging (Kwon, Fisher et al., 2002; Rhee, 1999; Torres et al., 2003).

Therefore, it can be said that it is important to find a substance capable of suppressing and controlling overexpression of MMP by ultraviolet rays and internal and external factors, and suppressing skin aging by ROS.

One aspect provides a pharmaceutical composition for preventing or treating skin aging comprising maresin 1 as an active ingredient.

Another aspect provides a cosmetic composition for preventing or improving skin aging comprising marecin 1 as an active ingredient.

Another aspect provides a health functional food for preventing or improving skin aging comprising marecin 1 as an active ingredient.

Another aspect provides a method for inhibiting skin aging of an individual comprising administering to the subject the composition described above.

One aspect provides a pharmaceutical composition for preventing or treating skin aging comprising maresin 1 as an active ingredient.

Maresin 1 (MaR1) is a lipoxygenase (LOX) metabolite derived from omega-3 fatty acid, docosahexaenoic acid (DHA), and is a specialized pro- -resolving mediator: SPM). The above maresin 1 may be 7R, 14S-dihydroxy-4Z, 8E, 10E, 12Z, 16Z, 19Z-docosahexaenoic acid having the structure of the following formula 1.

(Equation 1)

The maresin 1 may be in the form of a pharmaceutically acceptable salt thereof. Such salts may be used in the pharmaceutical field, for example, conventional acid addition salts used in external preparations for skin such as salts derived from inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid, sulfamic acid, phosphoric acid or nitric acid and salts derived from organic acids such as acetic acid, And organic acids such as glycolic acid, stearic acid, citric acid, maleic acid, malonic acid, methanesulfonic acid, tartaric acid, malic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, 2- acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, oxalic acid or trifluoroacetic acid ≪ / RTI > The salt may be a base addition salt such as ammonium, dimethylamine, monomethylamine, monoethylamine or diethylamine. In addition, the salt may be in the form of a conventional metal salt, for example, a salt derived from a metal such as sodium, potassium, lithium, magnesium, or calcium. The acid addition salt, the base addition salt or the metal salt may be produced by a conventional method. For example, a base addition salt or a metal salt can be prepared by reacting the ionic form of maresin 1, that is, 7R, 14S-dihydroxy-4Z, 8E, 10E, 12Z, 16Z, 19Z-docosahexaenoic acid with an appropriate base or metal ion Or the like.

The pharmaceutically acceptable salt of maresin 1 may have the structure of Formula 2 below.

(Equation 2)

In Formula 2, M represents sodium, potassium, lithium, magnesium, or calcium.

The pharmaceutically acceptable salt of maresin 1 is sodium 7R, 14S-dihydroxy-4Z, 8E, 10E, 12Z, 16Z, 19Z-docosahexaenoic acid or potassium 7R, 14S-dihydroxy- , 10E, 12Z, 16Z, 19Z-docohexaenoic acid.

The maresin 1 may also be in the form of a solvate thereof.

"Solvate" means a complex or aggregate formed by one or more solute molecules, i.e., marecine 1 or a pharmaceutically acceptable salt thereof, and one or more solvent molecules. The solvate may be, for example, a complex or aggregate formed with water, methanol, ethanol, isopropanol or acetic acid.

The maresin 1 may also be in the form of its stereoisomer. The stereoisomers include all stereoisomers such as enantiomers and diastereomers. The compound may be a stereoisomerically pure form or a mixture of one or more stereoisomers, for example, a racemic mixture. The separation of certain stereoisomers can be carried out by any of the conventional methods known in the art.

 "Active ingredient" is intended to carry out the function referred to in the composition and excludes those that do not fulfill the function as they are included in minor amounts as impurities.

The maresin 1 can be chemically synthesized or commercially available.

The composition may be one for inhibiting, delaying or improving skin wrinkles. The composition may be one for increasing skin elasticity. The composition may be one for suppressing, delaying or improving skin photoaging, stinging, or freckles.

The composition may be one that inhibits collagen degradation in cells. The composition may inhibit collagen degradation by inhibiting the expression or activity of matrix metalloproteinase (MMP). The composition may, for example, suppress the extracellular matrix degradation by inhibiting the expression or activity of MMP-9 and / or MMP2 which degrade gelatin, type 4 collagen or fibronectin.

The composition may be one that increases the antioxidant activity. The composition may be one that increases the antioxidant activity by inhibiting the production of reactive oxygen species (ROS).

The composition may be one that inhibits apoptosis or increases cell viability. The composition may be one that inhibits the apoptosis of the epidermal cells or increases its survival rate.

The composition may comprise a "therapeutically effective amount" of the maresin 1 or a pharmaceutically acceptable salt, solvate, or combination thereof. In this composition, "therapeutically effective amount" means an amount sufficient to exhibit a therapeutic effect when administered to a subject or a cell in need thereof. "Treatment" means treating a disease or medical condition in a mammal, including a human, including an individual, which includes: (a) preventing the occurrence of the disease or medical condition, cure; (b) relieving the disease or medical condition, i. e., eliminating or ameliorating the disease or medical condition in the patient; (c) inhibiting the disease or medical condition, i.e. slowing or stopping the progression of the disease or medical condition in the individual; Or (d) relieving the disease or medical condition in the subject.

The composition may be present in an amount of from 0.001% to 80%, such as from 0.01% to 60%, from 0.01% to 40%, from 0.01% to 30%, from 0.01% to 20% %, 0.01% to 10%, 0.01% to 5%, 0.05% to 60%, 0.05% to 40%, 0.05% to 30%, 0.05% to 20% From 0.05% to 10%, from 0.05% to 5%, from 0.1% to 60%, from 0.1% to 40%, from 0.1% to 30%, from 0.1% to 20% % To 10% by weight, or 0.1% to 5% by weight of maresin 1.

The composition may comprise a pharmaceutically acceptable carrier. In this composition, "acceptable carrier" refers to a substance, generally an inert substance, used in combination with the active ingredient to aid in the application of the active ingredient. The carrier may be an excipient, a disintegrant, a binder, a lubricant, a diluent, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low substituted hydroxy cellulose, or a combination thereof. The disintegrant may be sodium starch glycolate, calcium monohydrogen phosphate anhydrous, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or combinations thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.

The composition may be formulated into parenteral or oral dosage forms. The parenteral dosage form may be an injection or an external preparation for skin. The external skin preparation may be a cream, a gel, an ointment, a skin emulsifier, a skin suspension, a transdermal patch, a drug-containing bandage, a lotion, or a combination thereof. The external preparation for skin is usually used as a component used in external skin preparations such as cosmetics or medicines such as an aqueous component, an oily component, a powder component, an alcohol, a moisturizer, a thickener, an ultraviolet absorber, a whitening agent, an antiseptic, , Coloring agents, various skin nutrients, and the like can be appropriately blended as needed. The external preparation for skin may be a metal blocker such as sodium edetate, sodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate or gluconic acid, caffeine, tannin, bellapamil, licorice extract, glabridine, Vitamin C, ascorbic acid magnesium phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, fructose, fructose and other herbal medicines, various herbal medicines, tocopherol acetate, glycyrrhizic acid, Sugars such as trehalose and the like can also be appropriately compounded. Oral dosage forms may be tablets, capsules, aqueous solutions or suspensions. In the case of tablets, excipients such as lactose and corn starch, and lubricants such as magnesium stearate may be usually added. In the case of capsules, lactose and / or dried corn starch may be used as a diluent. When a suspending agent is required, the active ingredient may be combined with an emulsifying agent and / or a suspending agent. If desired, certain sweetening and / or flavoring agents may be added.

Another aspect provides a cosmetic composition for preventing or improving skin aging comprising marecin 1 as an active ingredient. The above-mentioned "cosmetic composition" means that the effect on the human body is slight as it is an article used in the human body for cleansing and beautifying the human body, adding charm, brightly changing appearance, or maintaining or promoting the health of skin and hair. The cosmetic composition may be a functional cosmetic having an effect of preventing or improving skin aging.

The composition may comprise a cosmetically acceptable carrier. The cosmetic composition may contain a component that can be used in a conventional cosmetic composition, for example, a moisturizer, a powder component, an ultraviolet absorber, an antioxidant, a cosmetic ingredient, a glycolipid, a plant extract , A preservative, a flavoring agent, a pH adjusting agent, a coloring matter, a viscosity adjusting agent or a gelling agent. The cosmetic composition may be at least one selected from the group consisting of lotion, skin, lotion, nutrition lotion, nutritional cream, massage cream, essence, pack, skin lotion, skin softener, skin toner, astringent, milk lotion, moisturizing lotion, , Shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder or eye shadow.

Marecin 1, skin aging and carrier are as described above.

Another aspect provides a health functional food for preventing or improving skin aging comprising marecin 1 as an active ingredient. The "health functional food" means a food prepared and processed in the form of tablets, capsules, powders, granules, liquids, and rings using raw materials and components having useful functions in the human body. The health functional food may be a functional food having an effect of preventing or improving skin aging.

The composition may comprise a pharmaceutically acceptable carrier. The health functional food may contain a food-acceptable food-aid additive in addition to the active ingredient. The above-mentioned "food-aid additive " refers to a component which can be added to foods in a supplementary manner, and is added to produce a health functional food, and can be appropriately selected and used by an ordinary person skilled in the art. The health functional food may be, for example, a nutrient, a vitamin, a mineral (electrolyte), a flavor such as a synthetic flavor and a natural flavor, a colorant and a filler, a pectic acid and its salt, an alginic acid and its salt, A thickener, a pH adjuster, a stabilizer, a preservative, a glycerin, an alcohol, and a carbonating agent used in a carbonated beverage. Unlike the pharmaceutical composition, the health functional food can be manufactured in various forms, and it is advantageous that there is no side effect that may occur when a medicine is taken for a long time by using a food as a raw material. Or as an adjuvant for improving the improvement effect.

Marecin 1, skin aging and carrier are as described above.

Another aspect provides a method of improving, delaying, or inhibiting skin aging of an individual comprising administering the composition to a subject. The composition is the same as described above.

Administration can be by any method known in the art. Administration may be by any means directly administered to a subject, such as by intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration, . The administration can be systemically or locally administered. The administration may be topical administration to a site where skin aging is present. The administration may be by application, for example. The application refers to any method of contacting the composition to the skin of a subject in any suitable manner, thereby allowing the composition to be absorbed into the skin.

The subject may be a mammal, such as a person, a cow, a horse, a pig, a dog, a sheep, a goat, or a cat. The subject may be an individual in need of improving, delaying, or inhibiting skin aging. The subject may be an individual in need of inhibiting cell death, inhibiting collagen degradation or increasing antioxidant activity.

Such administration may comprise administering to a mammal in need of such treatment a therapeutically effective amount of marecine 1 in an amount of 0.01 mg to 10,000 mg, 0.1 mg to 1000 mg, such as 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg. Or the administration comprises administering to the mammal an effective amount of at least one selected from the group consisting of 0.01 to 25 μM, 0.05 to 5 μM, 0.075 to 3.75 μM, 0.1 to 2.5 μM, 0.15 to 2 μM, 0.25 to 1.5 μM, 0.4 to 1.25 μM, 0.5 to 1.2 μM, or 0.75 to 1.15 μM To serve as a working concentration.

According to a pharmaceutical composition, a cosmetic composition, and a health functional food for preventing or treating skin aging according to one aspect, the skin aging of an individual can be suppressed, delayed, or improved.

According to a method of improving skin aging of an individual according to another aspect, skin aging of an individual can be effectively suppressed, retarded, or improved.

FIG. 1 shows the results of cell viability and production of reactive oxygen species after administration of maresin 1 to Hacat cells and irradiation with ultraviolet light.
FIG. 2 shows the results of the expression of MMP-2 and MMP-9 after administration of maresin 1 to Hacat cells and irradiation of ultraviolet light.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  One: Maresin  Identification of the skin aging inhibitory effect of 1

One. Maresin  1 cell survival rate

In this example, maresin 1 was commercially available (Cayman Chemical, Ann Arbor, MI, USA). Maresin 1 was dissolved in ethanol at a concentration of 1 mM and stored at -70 ° C.

The effect of maresin 1 on cell survival in Hacat cells (ATCC, Rockville, MD, USA), a human keratinocyte cell line, was measured using MTT assay. MTT analysis utilizes the principle of reducing MTT, a tetrazolium dye, due to the enzymatic activity of living cells to spontaneous insoluble formazan.

Hacat cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum, 100 U / ml penicillin, and 100 ug / ml streptomycin (Invitrogen, Carlsbad, Calif. (Hyclone; Logan, UT, USA).

The Hacat cells in 96-well (well) microtiter plates (microplate) 5 x 10 ⁴ The concentration of the cells / well was divided and cultured in an incubator at 37 ° C, 5% CO ₂ condition for about 24 hours. Thereafter, each medium containing 0.25, 0.5, and 1 μM of maresin 1 was replaced and cultured for 12 hours. Subsequently, the cells were irradiated with ultraviolet B (70 mJ / cm ² ) and cultured for 24 hours.

MTT solutions were prepared using commercially available (Sigma, St. Louis, Mo., USA) and dissolved in phosphate buffered saline at a concentration of 1 mg / ml. 50 占 퐇 of the prepared MTT solution was added to each well where cells were present. Then, the cells, in the air and complete humidity of about 37 ℃, 5% of CO _2, 95%, and incubated for approximately 3 hours. After 3 hours of incubation, the MTT solution was removed and 200 μl of dimethyl sulfoxide (DMSO) was added. The plates were then further incubated for approximately 5 minutes at room temperature to allow for well mixed DMSO. Optical density (OD) of each well was measured using a plate reader. At this time, the plate reader was set to 570 nm for the test wavelength and 630 nm for the reference wavelength. Fig. 1 shows the results of a change in cell viability after administration of maresin 1 to Hacat cells and ultraviolet irradiation. Referring to FIG. 1A, when the marecin 1 was administered, cell death by ultraviolet irradiation was inhibited in a concentration-dependent manner.

2. Maresin  1 Antioxidant Efficacy Measurements

The effect of maresin 1 on the production of reactive oxygen species (ROS) in Hacat cells was measured using an ROS detection kit (Abcam) containing carboxy-H 2 DCFDA. DCFH-DA is readily hydrolyzed into DCFH which has penetrated the cell membrane and diffuses into the cell, which lost fluorescence by the esterase in the cell, and then rapidly oxidized to DCF with high fluorescence in the presence of ROS. Therefore, the fluorescence intensity of DCF is proportional to the amount of ROS in the cells.

Hacat cells were seeded at a density of 25,000 cells / well in a 96 well microplate in a dark environment and bottomed and incubated for about 24 hours in an incubator at 37 ° C, 5% CO ₂ Respectively. Thereafter, each medium containing 0.25, 0.5, 1 μM of maresin 1 was replaced and cultured for 12 hours. Subsequently, the cells were irradiated with ultraviolet B (70 mJ / cm ² ) and cultured for 24 hours. The medium was removed from each well, 100 쨉 l of 1x dilution buffer was added to each well, and reacted for 30 minutes. Then, 1x dilution buffer was removed from each well, and 100 쨉 l of diluted DCFDA solution was added to each well to stain the cells. The staining was performed by reacting Hacat cells with a diluted DCFDA solution in a cancer environment at about 37 DEG C for about 45 minutes. Then, the DCFDA solution was removed from each well and 100 占 퐇 of 1x dilution buffer or 1x phosphate buffered saline was added to each well. Fluorescence on the plate was then measured using a plate reader. At this time, the plate reader was set to the end point mode, with a wavelength of 485 nm for this and 535 nm for emission.

Fig. 1B shows the results of the production of intracellular ROS after administration of maresin 1 to Hacat cells and ultraviolet irradiation. Referring to FIG. 1B, in the case of administration of maresin 1, intracellular ROS production by ultraviolet irradiation was decreased in a concentration-dependent manner.

3. Maresin  1 of MMP -2 and MMP - 9

The effect of maresin 1 on the expression of genes related to skin elasticity and elasticity in Hacat cells was determined by quantitative real-time PCR (qPCR).

The Hacat cells were subcultured in a 96-well microplate at a concentration of 5 x 10 ⁴ cells / well and incubated in an incubator at 37 ° C and 5% CO ₂ for about 24 hours. Then, each medium containing 0.25, 0.5, 1 μM of maresin 1 was replaced and cultured for 12 hours. Subsequently, the cells were irradiated with ultraviolet B (70 mJ / cm ² ) and cultured for 24 hours.

The degree of gene expression of the cDNA was analyzed by qPCR on an Applied Biosystems 700 sequence detection system (Foster City, CA, USA) using fluorescent TaqMan 5 nuclease assay. At this time, synthesized cDNA, MMP-2 and MMP-9 specific primer set, 2 x TaqMan master mixture and 20 x premade TaqMan gene expression analysis (Applied Biosystems) kit were used. qPCR conditions were as follows: 10 min at 95 캜, 15 sec at 95 캜, and 1 min at 60 캜, 40 times. A set of primers specific for MMP-2, MMP-9 and beta-actin was used for each of the commercially available primers (Hs01548727_m1, # 4331182 for MMP-2, Hs00957562_m1 and # 4331182 for MMP-9, Hs01060665_g1, # 4331182, ThermoFisher; Fremont, CA, USA).

FIGS. 2A and 2B show the expression levels of MMP-2 and MMP-9 after administration of maresin 1 to Hacat cells and ultraviolet irradiation. Referring to FIGS. 2A and 2B, when marecin 1 was administered, the expression of MMP-2 and MMP-9 by UV irradiation decreased in a concentration-dependent manner.

The composition of the present invention can be applied to various formulations as described below, but the present invention is not limited thereto.

[Formulation Example 1] External ointment for skin Composition weight% Maresh 1 0.5 Diethyl sebacate 8 Nonsense 5 Polyoxyethylene oleyl ether phosphate 6 Sodium benzoate One vaseline Suitable amount

[Formulation Example 2] Cream Composition weight% Maresh 1 0.3 Stearic acid 15.0 ethanol 1.0 Potassium hydroxide 0.7 glycerin 5.0 Propylene glycol 3.0 antiseptic Suitable amount incense Suitable amount Purified water Remaining amount (to 100)

[Formulation Example 3] Essence Composition weight% Maresh 1 0.2 Propylene glycol 10.0 glycerin 10.0 Sodium hyaluronate (1% aqueous solution) 5.0 ethanol 5.0 Polyoxyethylene hardened castor oil 1.0 Para-oxybenzoic acid 0.1 incense Suitable amount Purified water Remaining amount (to 100)

[Formulation Example 4] Pack Composition weight% Maresh 1 0.3 Polyvinyl alcohol 13.00 L-ascorbic acid-2-phosphate magnesium salt 1.00 Lauroylhydroxyproline 1.00 Water soluble collagen (1% aqueous solution) 2.00 1,3-butylene glycol 3.00 ethanol 6.00 Purified water Remaining amount (to 100)

[Formulation Example 5] Composition weight% Maresh 1 100 mg glucose 10g Red ginseng extract 50 mg Citric acid 2g Purified water 187.7 g (to 200 ml)

Claims (14)

A pharmaceutical composition for preventing or treating skin aging comprising Maresin 1 (MaR1) as an active ingredient. The pharmaceutical composition according to claim 1, wherein the skin aging is photoaging, scum, or freckles or wrinkles due to ultraviolet rays. The pharmaceutical composition according to claim 1, wherein the maresin 1 is 7R, 14S-dihydroxy-4Z, 8E, 10E, 12Z, 16Z, 19Z-docosahexaenoic acid. The pharmaceutical composition according to claim 1, wherein the maresin 1 inhibits collagen degradation in cells. The pharmaceutical composition according to claim 1, wherein the maresin 1 inhibits the expression or activity of matrix metalloproteinase (MMP). The pharmaceutical composition according to claim 1, wherein the maresin 1 has an antioxidative activity. A cosmetic composition for preventing or improving skin aging comprising Maresin 1 (MaR1) as an active ingredient. [Claim 7] The cosmetic composition according to claim 7, wherein the skin aging is photo-aging caused by ultraviolet rays, stain, freckles, or wrinkles. The cosmetic composition according to claim 7, wherein the maresin 1 is 7R, 14S-dihydroxy-4Z, 8E, 10E, 12Z, 16Z, 19Z-docosahexaenoic acid. The cosmetic composition according to claim 7, which is a formulation of lotion, skin, lotion, nutrition lotion, nutritional cream, massage cream, essence, pack. A health functional food for preventing or improving skin aging comprising Maresin 1 (MaR1) as an active ingredient. [Claim 12] The health functional food according to claim 11, wherein the skin aging is photoaging by sunlight, stain, or freckles or wrinkles. The health functional food according to claim 11, wherein the maresin 1 is 7R, 14S-dihydroxy-4Z, 8E, 10E, 12Z, 16Z, 19Z-docosahexaenoic acid. A method for improving skin aging of an comprising subject comprising administering to the subject a composition according to any one of claims 1 to 6.

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