Monosaccharide derivative and use thereof

Abstract

The present invention relates to a novel monosaccharide derivative or a pharmaceutically or cosmetically acceptable salt thereof, wherein the derivative has been confirmed to enhance skin moisturization effects and exhibit excellent skin elasticity and wrinkle improvement effects by inducing skin barrier strengthening through improved skin cell activity. Additionally, as it has been confirmed to exhibit excellent effects in wound healing, the monosaccharide derivative or a pharmaceutically or cosmetically acceptable salt thereof may be provided as a cosmetic composition for skin improvement and a pharmaceutical composition for wound healing.

Description

Technology Field

[0001] The present invention relates to monosaccharide derivatives, and more specifically, to a technology for providing a composition for skin improvement and wound healing containing a novel monosaccharide derivative having high water solubility as an active ingredient. Background Technology

[0002] The skin is the organ with the largest surface area in our body. Directly exposed to the external environment, the skin is responsible for protecting our body from various harmful factors. However, as the skin becomes increasingly damaged by increasing age, ultraviolet radiation, external pollutants, and stress, and its protective function against these factors weakens, its ability to protect and proliferate cells declines. In this case, the body initiates a skin regeneration process for the damaged skin. The process of healing a damaged area involves cell division and migration, through which the wound heals. Therefore, wound healing measurements that analyze cell division and migration are associated with skin regeneration (Gerontology (2013) 59 (2): 159-164. Age-Related Aspects of Cutaneous Wound Healing: A Mini-Review) (Pharmaceuticals 2023, 16(2), 235, Skin Wound Healing and Anti-Wrinkle-Promoting In Vitro Biological Activities of Caragana sinica Flower Absolute and Its Chemical Composition). Furthermore, for cells to divide, their functions and activities must operate normally. Therefore, analyzing relative cell numbers is associated with cell activity. (Aging Clin Exp Res1, 3-15 (1989). Cell proliferation, cell death and aging)

[0003] Human skin is composed of the epidermis and dermis. Fibroblasts exist in the dermis of the skin and produce collagen, a major component of the extracellular matrix. Collagen is an important protein that accounts for approximately 30% of the total body protein weight and possesses a robust triple helix structure. This collagen functions to support the mechanical rigidity and intercellular adhesion of the skin; however, it decreases due to natural aging or photoaging caused by ultraviolet radiation, and this is known to be directly related to the formation of wrinkles.

[0004] UV promotes collagen degradation by stimulating the expression of MMP-1, one of the collagen-degrading enzymes. The reduction of collagen caused by MMP-1 decreases skin elasticity and promotes wrinkle formation. Therefore, demonstrating efficacy in reducing MMP-1 expression is associated with wrinkle improvement (Photochemistry and Photobiology, 2003, 78(1): 43-48, Matrix Metalloproteinase-1 is the Major Collagenolytic Enzyme Responsible for Collagen Damage in UV-irradiated Human Skin).

[0005] The epidermis is located at the outermost layer of the skin and performs a defense against various external physical and chemical stimuli, as well as a protective function that prevents the excessive loss of moisture from the body. These defense and protective functions are made possible by the normal formation and maintenance of the stratum corneum, which is composed of keratinocytes. Keratinocytes are cells formed through a gradual process of change as they migrate from the lowest layer of the epidermis to the stratum corneum after continuous proliferation.

[0006] These keratinocytes undergo repeated processes of differentiation or keratinization. Through this process, old keratinocytes are shed from the skin, and new keratinocytes rising from the lowest layer of the skin take over their function. During these processes, keratinocytes form moisturizing factors and intercellular lipids, enabling the stratum corneum to function as a barrier protecting the skin from the outside.

[0007] Tight junctions (TJs) play a crucial role in this function as a barrier. Tight junctions are intercellular contact structures that seal the spaces between individual cells of epithelial sheets or interstratifying epithelia, such as the epidermis, enabling the collective separation of tissue compartments. Representative molecules constituting tight junctions include Claudin and Occludin, which bind to actin filaments on the outer walls of skin cells and act as connection points between cells, thereby strengthening the binding force of the skin barrier. This enhanced binding force prevents the invasion of pathogens from the outside of the skin and reduces moisture loss from within. (Ther Deliv. 2012 Nov;3(11):1297-327. Tight junctions in skin: new perspectives) (Journal of Investigative Dermatology (2014) 135, e29. Assessing the In Vivo Epidermal Barrier in Mice: Dye Penetration Assays)

[0008] Hyaluronic acid, produced by keratinocytes, is a moisturizing agent classified as a type of glycosaminoglycan. It is a high-molecular-weight polysaccharide consisting of repeating chains of glucuronic acid and N-acetylglucosamine residues. As a major component of the extracellular matrix, hyaluronic acid is closely related to skin moisture content. It has the property of gelling by binding with large amounts of water and is functionally associated with moisture retention and the maintenance of skin elasticity. Hyaluronic acid synthase is a hyaluronic acid synthesis enzyme present in cells, such as HAS1, HAS2, and HAS3, and hyaluronic acid of different lengths is formed depending on the type. Hyaluronic acid produced by cells acts as a humectant, attracting moisture to increase the moisture content within the skin. (Curr Med Chem. 2009;16(14):1718-45. Role, metabolism, chemical modifications and applications of hyaluronan) Furthermore, aquaporins act as transport pumps for water and glycerol expressed in skin cells, playing a role in increasing moisture levels through even delivery to the skin layers. (Journal of Investigative Dermatology (2008) 128, 2145-2151; Roles of Aquaporin-3 in the Epidermis) Prior art literature

[0009] Korean Patent Publication No. 10-2024-0147890 (Published on October 10, 2024) The problem to be solved

[0010] The present invention aims to provide a novel monosaccharide derivative or a pharmaceutically or cosmetically acceptable salt thereof.

[0011] In addition, the present invention aims to provide a pharmaceutical composition for wound treatment comprising a monosaccharide derivative or a pharmaceutically acceptable salt thereof.

[0012] In addition, the present invention provides a cosmetic composition for improving skin comprising a derivative or a cosmetically acceptable salt thereof. means of solving the problem

[0013] The present invention provides a monosaccharide derivative represented by the following chemical formula 1, or a pharmaceutically or cosmetically acceptable salt thereof.

[0014] [Chemical Formula 1]

[0015]

[0016] In the above chemical formula 1,

[0017] R1 is -(CH2) n -R6 or -(CH)m-(R7)2 and,

[0018] The above R6 is a hydroxyl group, a carboxyl group, an amide group, an amine group, an ester group, a nitrile group, or acetylmorpholine, and

[0019] R7 is -COOH or -COO - M + And,

[0020] M is Na, K, or Li, and

[0021] R2, R3, and R4 are each independently a hydroxyl group, an acetoxy group, or acetamide, and

[0022] R5 is -O-R8, and

[0023] R8 is hydrogen or an acetyl group, and

[0024] n and m are each independently integers from 1 to 8.

[0025] The present invention provides a pharmaceutical composition for wound treatment comprising the monosaccharide derivative or a pharmaceutically acceptable salt thereof.

[0026] The present invention provides a cosmetic composition for improving skin elasticity or wrinkles comprising a monosaccharide derivative or a cosmetically acceptable salt thereof.

[0027] In addition, the present invention provides a cosmetic composition for skin barrier strengthening or skin moisturizing comprising a monosaccharide derivative or a cosmetically acceptable salt thereof. Effects of the invention

[0028] The present invention relates to a novel monosaccharide derivative or a pharmaceutically or cosmetically acceptable salt thereof, wherein the derivative has been confirmed to enhance skin moisturization effects and exhibit excellent skin elasticity and wrinkle improvement effects by inducing skin barrier strengthening through improved skin cell activity. Additionally, as it has been confirmed to exhibit excellent effects in wound healing, the monosaccharide derivative or a pharmaceutically or cosmetically acceptable salt thereof may be provided as a cosmetic composition for skin improvement and a pharmaceutical composition for wound healing. Brief explanation of the drawing

[0029] Figure 1 shows the structure and NMR data of a representative compound among the monosaccharide derivatives according to the present invention. Figure 2 is a monosaccharide derivative that can be prepared according to the present invention. Specific details for implementing the invention

[0030] The present invention will be described in more detail below.

[0031] The inventors have confirmed that a novel monosaccharide derivative or a pharmaceutically or cosmetically acceptable salt thereof enhances skin cell activity and induces skin barrier strengthening, thereby improving skin moisturization effects and exhibiting excellent skin elasticity and wrinkle improvement effects, and have also confirmed that it exhibits excellent effects in wound healing, thus completing the present invention.

[0032] Accordingly, the present invention provides a monosaccharide derivative represented by the following chemical formula 1, or a pharmaceutically or cosmetically acceptable salt thereof.

[0033] [Chemical Formula 1]

[0034]

[0035] In the above chemical formula 1,

[0036] R1 is -(CH2) n -R6 or -(CH) m -(R7)2 and,

[0037] The above R6 is a hydroxyl group, a carboxyl group, an amide group, an amine group, an ester group, a nitrile group, or acetylmorpholine, and

[0038] R7 is -COOH or -COO - M + And,

[0039] M is Na, K, or Li, and

[0040] R2, R3, and R4 are each independently a hydroxyl group, an acetoxy group, or acetamide, and

[0041] R5 is -O-R8, and

[0042] R8 is hydrogen or an acetyl group, and

[0043] n and m are each independently integers from 1 to 8.

[0044] In the present invention, “the pharmaceutically or cosmetically acceptable salts thereof” may include salts prepared by adding a base to a monosaccharide derivative. The addition salts available for preparing the pharmaceutically or cosmetically acceptable salts include, but are not limited to, one or more salts selected from the group consisting of sodium, potassium, calcium, ammonium, magnesium, and organic aminos.

[0045] In the present invention, the monosaccharide derivative represented by Formula 1 may be one of the compounds represented by Formulas 2 to 8 below.

[0046] [Chemical Formula 2]

[0047]

[0048] [Chemical Formula 3]

[0049]

[0050] [Chemical Formula 4]

[0051]

[0052] [Chemical Formula 5]

[0053]

[0054] [Chemical Formula 6]

[0055]

[0056] [Chemical Formula 7]

[0057]

[0058] [Chemical Formula 8]

[0059]

[0060] The present invention provides a pharmaceutical composition for wound treatment comprising the monosaccharide derivative or a pharmaceutically acceptable salt thereof.

[0062] The monosaccharide derivative according to the present invention, or a pharmaceutically acceptable salt thereof, may be included in an amount of 0.00001 wt% to 10 wt%, 0.0001 wt% to 10 wt%, 0.001 wt% to 10 wt%, 0.005 wt% to 10 wt%, 0.01 wt% to 10 wt%, 0.05 wt% to 10 wt%, or 0.1 wt% to 10 wt% based on 100 parts by weight of the total composition. More specifically, it may be included in an amount of 0.001 to 5 wt%, 0.01 to 5 wt%, 0.1 to 5 wt%, 0.1 to 4 wt%, 0.1 to 3 wt%, 0.1 to 2 wt%, or 0.1 to 1 wt% based on 100 parts by weight of the composition. If monosaccharide derivatives or pharmaceutically acceptable salts thereof are included in an amount below the above-mentioned range, cell activity induction at the wound site may be reduced, resulting in no wound healing effect or a slow healing speed; if included in an amount above the above-mentioned range, a problem may arise in that it may cause skin irritation.

[0063] For example, in a wound healing assay analysis in which the monosaccharide derivative of the present invention was administered within the above content range, it was confirmed that the monosaccharide derivative exhibited an enhanced wound healing effect through significantly improved growth activity of skin fibroblasts.

[0064] In this invention, the term “wound” encompasses all damage to a living organism and refers to a state of damage to a living organism; it is also referred to as a wound.

[0065] The "wound healing" process is divided into the acute, repair, and scarring phases. The acute phase, also known as the exudative phase, is a stage where a series of reactions occur to remove tissue destruction or foreign substances from the damaged area; this is accompanied by inflammatory and blood coagulation responses. The repair phase, also known as the proliferative phase, is a stage where new blood vessels are formed and the damaged area expands to facilitate recovery. During this phase, active cell proliferation or the active synthesis of collagen and proteoglycans—intercellular substances found in granulation tissue, a type of connective tissue—occurs, allowing epidermal cells to gain mobility and proliferate through cell division to regenerate epidermal tissue. The scarring phase is a stage where active cell proliferation slows down, and the physical strength of the damaged area increases as collagen fibers cross-link. Ultimately, the vascular system atrophies, and tissue distinct from the surrounding normal tissue takes its place at the damaged site. Wound healing occurs through the repetition of these stages.

[0066] In one embodiment, the wound may be a wound in which the epidermis; dermis; epidermis and dermis; or the epidermis, dermis and subcutaneous fat layer of the skin is damaged. Additionally, the wound may include cuts, incisions (e.g., surgical incisions), abrasions, lacerations or lacerations, fractures, contusions, burns, or amputations.

[0067] The above wound may be selected from a group consisting of chronic wounds, acute wounds, surgical wounds, orthopedic wounds, traumatic wounds, combat wounds, and combinations thereof, or may be a wound caused by other diseases. In this case, the disease may be selected from fibrosis, diabetes mellitus, diabetic ulcers, autoimmune skin diseases, abrasions, lacerations, incisions, contusions, bruises, punctures, excisions, burns, ulcers, pressure sores, or combinations thereof.

[0068] The above pharmaceutical composition may further include a suitable carrier, excipient, or diluent commonly used in the manufacture of pharmaceutical compositions.

[0069] Examples of carriers, excipients, or diluents usable in the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.

[0070] The pharmaceutical composition according to the present invention can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external formulations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.

[0071] When formulating, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules, and these solid dosage forms may be prepared by mixing the above compound with at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc.

[0072] In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral administration include suspensions, oral liquids, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as humectants, sweeteners, flavorings, and preservatives, may be included.

[0073] Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As bases for suppositories, Witepsol, Macrogol, Tween 61, cocoa paste, laurin paste, glycerogelatin, etc. may be used.

[0074] The amount of monosaccharide derivative, which is the active ingredient of the pharmaceutical composition according to the present invention, may vary depending on the patient's age, gender, weight, and disease, but may be administered in an amount of 0.001 to 100 mg / kg, preferably 0.01 to 10 mg / kg, once or several times a day.

[0075] Furthermore, the dosage of the pharmaceutical composition according to the present invention may be increased or decreased depending on the route of administration, the severity of the disease, gender, body weight, age, etc. Accordingly, the above dosage does not limit the scope of the present invention in any way.

[0076] The above pharmaceutical composition may be administered to mammals, such as rats, mice, livestock, and humans, via various routes. Any mode of administration is expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, bronchial inhalation, intradural, or intracerebroventricular injection.

[0077] In the present invention, "quasi-drug" refers to articles used for the purpose of diagnosing, treating, improving, alleviating, managing, or preventing diseases in humans or animals, and which have a milder effect than pharmaceuticals. For example, according to the Pharmaceutical Affairs Act, quasi-drugs are defined as products excluding those used for pharmaceutical purposes, and may be products used for the treatment or prevention of diseases in humans or animals, or products that have a mild effect on the human body or do not act directly on it. For example, they may be selected from the group consisting of disinfectants, detergents, kitchen detergents, cleaning detergents, wet wipes, detergents, soaps, hand washes, hair detergents, hair softeners, and ointments, but are not limited thereto.

[0078] The present invention provides a cosmetic composition for improving skin elasticity or wrinkles comprising the monosaccharide derivative or a cosmetically acceptable salt thereof.

[0079] In the present invention, the term "skin elasticity improvement effect" refers to preventing, suppressing, or inhibiting the decline in skin elasticity, or improving skin elasticity that has already declined, and the term "wrinkle improvement effect" refers to preventing, suppressing, or inhibiting the formation of wrinkles on the skin, or alleviating wrinkles that have already formed.

[0080] In addition, the present invention provides a cosmetic composition for skin barrier strengthening or skin moisturizing comprising a monosaccharide derivative or a cosmetically acceptable salt thereof.

[0081] "Skin barrier strengthening" of the present invention refers to restoring the function of the epidermis of the stratum corneum, which is located on the outermost part of the skin. The cosmetic composition of the present invention has a skin barrier improvement effect by increasing the skin permeability of the monosaccharite derivative, thereby aiding the absorption of the monosaccharite derivative.

[0082] The term “skin moisturization” in the present invention refers to increasing moisture in the skin and maintaining a moist state. The skin moisturizing effect may also help improve wrinkles and increase skin elasticity.

[0083] The above monosaccharide derivative, or a cosmetically acceptable salt thereof, may be included in an amount of 0.00001 wt% to 10 wt%, 0.0001 wt% to 10 wt%, 0.001 wt% to 10 wt%, 0.005 wt% to 10 wt%, 0.01 wt% to 10 wt%, 0.05 wt% to 10 wt%, or 0.1 wt% to 10 wt% based on 100 parts by weight of the total composition. More specifically, it may be included in an amount of 0.001 to 5 wt%, 0.01 to 5 wt%, 0.1 to 5 wt%, 0.1 to 4 wt%, 0.1 to 3 wt%, 0.1 to 2 wt%, or 0.1 to 1 wt% based on 100 parts by weight of the composition. If monosaccharide derivatives, or pharmaceutically or cosmetically acceptable salts thereof, are included in an amount below the above-mentioned range, the rate of cell activation induction at the wound site may be reduced, resulting in no skin barrier strengthening effect or a slow rate of improvement; if included in an amount above the above-mentioned range, a problem may arise in that it may cause skin irritation.

[0084] In the present invention, it was confirmed that a monosaccharide derivative inhibits the expression of the gene MMP1, which is involved in the collagen degradation process in the dermis of the skin, thereby exhibiting the effect of enhancing skin elasticity and inhibiting wrinkle formation, and can also exhibit the effect of enhancing the expression of the HAS3 (Hyaluronic acid Synthase 3) gene, which induces the enhancement of hyaluronic acid synthesis, thereby showing skin elasticity and moisturization enhancement effects.

[0085] The "cosmetic" or "cosmetic composition" of the invention may be in the form of a general emulsion formulation and a solubilizing formulation. The cosmetic composition may be prepared in the form of a general emulsion formulation and a solubilizing formulation. For example, it may have a formulation of a lotion such as a softening lotion or a nourishing lotion; a fluid such as a facial lotion or a body lotion; a cream such as a nourishing cream, a moisturizing cream or an eye cream; an essence; a cosmetic ointment; a spray; a gel; a pack; a sunscreen; a makeup base; a foundation such as a liquid type, a solid type or a spray type; a powder; a makeup remover such as a cleansing cream, a cleansing lotion or a cleansing oil; or a cleansing agent such as a cleansing foam, a soap or a body wash.

[0086] In addition, the cosmetic composition may additionally contain fatty substances, organic solvents, solvents, thickeners and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, metal ion chelating agents and chelating agents, preservatives, vitamins, blockers, humectants, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles, or ingredients commonly used in cosmetics.

[0088] Hereinafter, the present invention will be described in detail with reference to examples to aid in understanding. However, the following examples are merely illustrative of the content of the present invention and the scope of the present invention is not limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to those with average knowledge in the art.

[0090] Preparation Example 1: Synthesis of Monosaccharide Derivative

[0091] 1-1. Acetobromo-α-D-glucose (1 g) was dissolved in anhydrous 1,4-dioxane (6 mL) and ethylene glycol (1.6 mL), and silver carbonate (0.8 g) was added. The reaction mixture was stirred at room temperature for 3 hours. Afterward, it was diluted with ethyl acetate (20 mL), filtered through a celite pad, washed with ethyl acetate (10 mL), and the filtrate was evaporated.

[0092] A purified intermediate was obtained by performing column chromatography (Hx / EA=3:1, v / v). The intermediate was dissolved in 10 mL of sodium methoxide (NaOMe) solution (5 mol / L in MeOH) and reacted by stirring at room temperature for 30 minutes. Next, the solution was neutralized with Amberlite IRA-120 resin, filtered, and the solvent removed under vacuum to obtain Compound 1.

[0094] 1-2. Galactosamine hydrochloride (1 g) was dissolved in pyridine anhydride (5 mL). Subsequently, acetic anhydride (Ac2O, 4.5 mL) was added, and the reaction mixture was stirred overnight. Afterward, the mixture was cooled in an ice bath, and ice-cold water (25 mL) was added. The white solid precipitate was collected by vacuum filtration to obtain the product as a white powder (A). Compound A was added to dichloroethane (DCE, 30 mL) and TMSOTf (Trimethylsilyl Trifluoromethanesulfonate, After adding 500 μL, the mixture was heated in an aluminum reaction block for 1 hour.

[0095] Afterwards, cool the residue and triethylamine (NEt 3,400 μL) was added and treated for 10 minutes. The residue was passed through a separating funnel and diluted by adding dichloromethane (DCM, 30 mL). The organic phase was washed with an aqueous solution of saturated sodium bicarbonate (NaHCO3), the solvent was removed under vacuum, and the filtrate was purified by silica gel column chromatography to obtain Compound B. After adding 4 Å molecular sieve (0.5 g), Compound B (1 g), and DCE (30 mL), benzyl 4-hydroxybutanoate (0.7 g) added to DCE (5 mL) was added. The mixture was stirred in an aluminum reaction block at 50°C for 30 minutes, then TMSOTf (300 μL) was added dropwise, and the solution was reacted at 50°C for 2 hours. Next, the solution was cooled, filtered through a sieve, transferred to a separating funnel, and DCM (30 mL) and an aqueous solution of saturated NaHCO3 (40 mL) were added. After separating the two phases, the aqueous solution was extracted with DCM (2 × 30 mL) until the organic layer became colorless.

[0096] The bound organic layer was collected, dried with anhydrous magnesium sulfate (MgSO4), and filtered to remove the solvent under vacuum. The organic extract was further purified by silica gel column chromatography, followed by the addition of anhydrous methanol (MeOH, 15 mL) through a diaphragm, and the removal of argon by fluting with two balloons filled with H2 for 2 hours (at room temperature) (direct bubbling into the solution).

[0097] Subsequently, a new balloon containing H2 was inserted, and the mixture was further stirred at room temperature for 3 hours. Afterward, the mixture was filtered through a Celite plug while washing with MeOH (2 × 10 mL). After removing the solvent under vacuum, Compound 2 was obtained.

[0098] NMR data of the representative compound was confirmed as shown in Fig. 1, and seven types of novel monosaccharide compounds were synthesized as shown in Fig. 2.

[0100] Experimental Example 1: Confirmation of skin regeneration effect by monosaccharide derivative

[0101] To confirm the skin regeneration effect following treatment with monosaccharide derivatives, a wound healing assay was performed.

[0102] First, human dermal fibroblasts (CRL-1635) were purchased from ATCC and used. The human dermal fibroblasts were cultured in DMEM (Dulbecco Modified Eagle Medium-GIBCO) medium containing 10% FBS (fetal bovine serum) and 1% Penicillin / Streptomycin at 37°C in a 5% CO2 incubator.

[0103] Next, transfer 2 × 10⁶ cells to a 24-well plate. 4 Cells were seeded per well and cultured for one day in a 37°C, 5% CO2 incubator. Subsequently, small wounds 1 mm wide were created using an SPLScar™ scratcher (SPL, 201925), and compounds 1 and 2 were added to the medium at a concentration of 2000 ppm, respectively. As a control, the same concentration of rhamnose was added to the medium and cultured. After 24 hours of culture, the wound area was measured to confirm the wound healing effect.

[0104] As a result, as shown in Table 1, it was confirmed that the wound healing effect of compound 1 increased by 38% compared to rhamnose, and that of compound 2 increased by 4%.

[0105] group Wound recovery rate (%) Increase (%) compared to Rhamnose Unprocessed 100.0 - Ramnos 111.955 - Compound 1 154.395 37.91 Compound 2 116.147 3.74

[0107] Experimental Example 2: Confirmation of Reduction in Wrinkle-Associated Gene Expression by Monosaccharide Derivatives

[0108] It was confirmed whether compounds 1 and 2 prepared as in the preparation example affect the expression of the gene MMP1, which is involved in the collagen degradation process in the dermis of the skin.

[0109] Human skin fibroblasts CRL-1635 were cultured in DMEM medium containing 10% FBS and 1% Penicillin / Streptomycin at 37°C in a 5% CO2 incubator.

[0110] Next, transfer the cells to a 6-well plate at a rate of 3 x 10 5 Cells were seeded per well and cultured for one day in a 37°C, 5% CO2 incubator. After replacing the medium with PBS, the setting was 20 mJ / cm². 2 After treating with UVB at a certain intensity, compounds 1 and 2 according to the present invention and rhamnose, a control, were added to the medium at the concentrations specified in Table 2. Subsequently, the culture was carried out for one day under the same conditions as before. Then, total RNA was obtained using the AccuPrep Universal RNA Extraction Kit (Bionia, K-3140), and cDNA was synthesized using a cDNA synthesis kit (Philekorea). The gene expression levels were analyzed by performing qPCR using the synthesized cDNA.

[0111] The results are shown in Table 2.

[0112] group Gene expression (%) Unprocessed 100 Rhamnose 1000 ppm 97 Rhamnose 2000 ppm 95 Compound 1 1000 ppm 82 Compound 1 2000 ppm 85 Compound 2 1000 ppm 79 Compound 2 2000 ppm 90

[0114] As shown in the table above, it was confirmed that compounds 1 and 2 had an effect of inhibiting the expression of MMP1, a collagen-degrading gene, and the effect of reducing MMP1 expression was particularly excellent in cells treated at low concentrations.

[0116] Experimental Example 3: Confirmation of Cell Activity Effects of Monosaccharide Derivatives

[0117] To determine whether monosaccharide derivatives affect cell activity, cell activity was assessed by measuring the relative number of cells using the CCK-8 assay. Human dermal fibroblasts CRL-1635 were cultured in DMEM medium containing 10% FBS and 1% Penicillin / Streptomycin at 37°C in a 5% CO2 incubator.

[0118] Next, transfer 1 × 10⁶ cells to a 96-well plate. 4 Cells were seeded per well and incubated for one day at 37°C in a 5% CO2 incubator. After replacing the medium with PBS, the setting was 20 mJ / cm². 2 After treating with UVB at a certain intensity, compounds 1 and 2 according to the present invention and rhamnose, a control, were added to the medium at the concentrations according to Table 3. Then, the culture was carried out for one day under the same conditions as before. Subsequently, the relative number of cells was measured using the Cell Counting Kit-8 cell proliferation assay kit (Dojindo Molecular Technologies Inc.).

[0119] The results are shown in Table 3.

[0120] group Relative number of cells (%) Unprocessed 100 Rhamnose 500 ppm 119 Rhamnose 1000 ppm 117 Compound 1 500 ppm 125 Compound 1 1000 ppm 117 Compound 2 500 ppm 101 Compound 2 1000 ppm 101

[0122] As shown in Table 3, Compound 1 exhibited a superior cell proliferation effect compared to rhamnose, the positive control, and Compound 2 was found to exhibit a cell proliferation effect similar to that of the untreated control. Thus, Compounds 1 and 2, which are monosaccharide derivatives, showed high safety, and in particular, Compound 1 was found to exhibit a superior cell activity effect.

[0124] Experimental Example 4: Confirmation of skin barrier strengthening efficacy by monosaccharide derivatives

[0125] To determine whether monosaccharide derivatives affect cell activity, the skin barrier strengthening efficacy was confirmed by measuring the tight junction gene (Occludin, Claudin4), a marker responsible for the binding between epidermal cells. Human keratinocytes (HaCaT, Cytion 300493) were purchased from Cytion and used. The human keratinocytes were cultured in DMEM medium containing 10% FBS and 1% Penicillin / Streptomycin at 37°C in a 5% CO2 incubator.

[0126] Next, transfer the cells to a 6-well plate at a rate of 2 x 10 5 Cells were dispensed into wells and cultured for one day in a 37°C, 5% CO2 incubator. Compounds 1 and 2 according to the present invention and rhamnose as a control were added to the medium at the concentrations specified in Tables 4 and 5. Subsequently, the culture was carried out for one day under the same conditions as before. Then, total RNA was obtained using the AccuPrep Universal RNA Extraction Kit (Bionia, K-3140), and cDNA was synthesized using a cDNA synthesis kit. The gene expression levels were analyzed by performing qPCR using the synthesized cDNA.

[0127] The analysis results are shown in Table 4 and Table 5, respectively.

[0128] gene group Relative expression level (%) Claudin4 Unprocessed 100 Rhamnose 2000ppm 169 Compound 1 2000ppm 679

[0129] gene group Relative expression level (%) Occludin Unprocessed 100 Rhamnose 200ppm 86 Compound 2 200 ppm 148

[0131] As a result, as shown in Tables 4 and 5, it was confirmed that compound 1 significantly increased Claudin4 expression and compound 2 increased Occludin expression.

[0132] From the above results, it was confirmed that compounds 1 and 2 affect the expression of genes that induce skin barrier strengthening.

[0134] Experimental Example 5: Confirmation of moisturizing-enhancing efficacy of monosaccharide derivatives

[0135] To determine whether monosaccharide derivatives affect cell activity, moisturizing-enhancing efficacy was confirmed by measuring hyaluronic acid synthesis and intercellular water transport genes (HAS3, Aquaporin3).

[0136] Human keratinocyte Cytion 300493 was cultured in DMEM medium containing 10% FBS and 1% Penicillin / Streptomycin at 37°C in a 5% CO2 incubator.

[0137] Next, transfer the cells to a 6-well plate at a rate of 2 x 10 5 Cells were dispensed into wells and cultured for one day in a 37°C, 5% CO2 incubator. Compounds 1 and 2 according to the present invention and rhamnose, a control, were added to the medium at concentrations according to Tables 6 and 7. Subsequently, the cultures were incubated for one day under the same conditions. Then, total RNA was obtained using the AccuPrep Universal RNA Extraction Kit, and cDNA was synthesized using a cDNA synthesis kit. The gene expression levels were analyzed by performing qPCR using the synthesized cDNA.

[0138] The analysis results are shown in Tables 6 and 7.

[0139] gene group Relative expression level (%) Hyaluronic acid Synthase 3 Unprocessed 100 Rhamnose 2000ppm 130 Compound 1 2000ppm 368

[0140] gene group Relative expression level (%) Aquaporin3 Unprocessed 100 Rhamnose 200ppm 113 Compound 2 200 ppm 339

[0142] As shown in Tables 6 and 7, Compound 1 according to the present invention increased the expression level of the gene HAS3, which induces hyaluronic acid synthesis, to about 3 times compared to rhamnose, and Compound 2 increased the expression level of the water transport gene Aquaporin3 to about 2.5 times compared to rhamnose.

[0143] From the above results, it was confirmed that compounds 1 and 2 can exhibit an effect of improving skin moisturization.

[0145] Foregoing, specific parts of the present invention have been described in detail. It will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the invention. Accordingly, the actual scope of the invention is defined by the appended claims and their equivalents.

Claims

Claim 1 Monosaccharide derivatives represented by the following Chemical Formula 1, or pharmaceutically or cosmetically acceptable salts thereof: [Chemical Formula 1] In the above chemical formula 1, R1 is -(CH2) n -R6 or -(CH) m -(R7)2, wherein R6 is a hydroxyl group, carboxyl group, amide group, amine group, ester group, nitrile group, or acetylmorpholine, and R7 is -COOH or -COO - M + And, M is Na, K or Li, R2, R3 and R4 are each independently a hydroxyl group, an acetoxy group or acetamide, R5 is -O-R8, R8 is hydrogen or an acetyl group, and n and m are each independently integers from 1 to 8. Claim 2 In claim 1, the monosaccharide derivative represented by Chemical Formula 1 is a monosaccharide derivative that is a compound of Chemical Formulas 2 to 8 below, or a pharmaceutically or cosmetically acceptable salt thereof: [Chemical Formula 2] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] Claim 3 A pharmaceutical composition for wound treatment comprising a monosaccharide derivative according to claim 1, or a pharmaceutically acceptable salt thereof. Claim 4 A pharmaceutical composition according to claim 3, wherein the monosaccharide derivative or a pharmaceutically acceptable salt thereof is included in an amount of 0.01 to 10 parts by weight per 100 parts by weight of the total composition. Claim 5 A cosmetic composition for improving skin elasticity or wrinkles comprising a monosaccharide derivative according to claim 1, or a cosmetically acceptable salt thereof. Claim 6 A cosmetic composition for skin barrier strengthening or skin moisturizing comprising a monosaccharide derivative according to claim 1, or a cosmetically acceptable salt thereof. Claim 7 A cosmetic composition according to claim 5 or 6, wherein the monosaccharide derivative or a pharmaceutically acceptable salt thereof is included in an amount of 0.01 to 10 parts by weight per 100 parts by weight of the total composition.

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