Composition for prevention, improvement or treatment of inflammatory diseases, allergic diseases, or sepsis comprising glucopyranoside derivative

Abstract

The present invention relates to a composition for the prevention, improvement, or treatment of inflammatory diseases, allergic diseases, or sepsis. A composition according to one aspect inhibits the expression or activity of pro-inflammatory cytokines IL-8 or TNF-α, inhibits the degranulation of mast cells, and has an effect of improving symptoms of sepsis, and can be usefully used for the prevention, improvement, or treatment of inflammatory diseases, allergic diseases, or sepsis.

Description

Technology Field

[0001] This relates to a composition for the prevention, improvement, or treatment of inflammatory diseases, allergic diseases, or sepsis. Background Technology

[0002] Inflammatory response is a biological defense mechanism triggered by various factors, such as infection by pathogens or tissue damage, and performs an initial protective function to confine damage to the site of infection or injury. Generally, acute inflammatory responses proceed rapidly and last for a short period, accompanied by a systemic reaction known as the acute phase response. Meanwhile, chronic inflammation can be induced as a result of sustained immune activation associated with certain diseases, such as infections or autoimmune disorders, and the accumulation and activation of macrophages lead to an increase in chronic inflammatory responses. However, persistent chronic inflammation can cause severe damage to host cells or tissues.

[0003] Cytokines produced by lipopolysaccharide (LPS) act on the manifestation of inflammation or host defense mechanisms. However, the excessive production of cytokines beyond what is necessary is known to cause inflammatory diseases such as arthritis, autoimmune diseases, immune diseases such as type 1 diabetes, and the death of nerve cells. In this regard, materials that inhibit the production of cytokines can be used as therapeutic agents for various inflammatory diseases in the human body.

[0004] Allergic diseases develop through the interaction of genetic and environmental factors and are representative intractable chronic diseases that are generally difficult to cure. Allergic diseases include rhinitis, asthma, atopic dermatitis, and allergic conjunctivitis; despite the fact that the number of cases is gradually increasing due to worsening environmental pollution, there is currently no treatment available that can completely eliminate the underlying causes.

[0005] Sepsis is caused when lipopolysaccharides (LPS), a component of the cell wall, act as toxins due to infection by pathogenic Gram-negative bacteria, leading to the excessive activation of the body's immune system. This can cause systemic infection or, in severe cases, be accompanied by shock. Sepsis is a major cause of death for patients admitted to intensive care units and is a very serious disease with a mortality rate typically exceeding 30%. Despite advancements in medical technology, sepsis still frequently occurs worldwide as a result of infection following surgery, and it often progresses to sepsis when infected in individuals with weakened immune systems, such as newborns and the elderly. Notably, neonatal sepsis is known to occur in approximately 3 out of every 1,000 full-term infants, while the incidence rate is reported to increase three to four times in premature infants.

[0006] Accordingly, while searching for a compound that can be used for the treatment or improvement of inflammatory diseases, allergic diseases, or septic diseases, the inventors confirmed the preventive, improvement, or therapeutic effects of (3R)-1-octan-3-yl-3-O-beta-D-glucopyranoside on inflammatory diseases, allergic diseases, and sepsis, thereby completing the present invention. Prior art literature

[0007] Korean Patent Publication 10-2021-0131799 The problem to be solved

[0008] One aspect is to provide a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof:

[0009] [Chemical Formula 1]

[0010] .

[0011] Another aspect is to provide a pharmaceutical composition for the prevention or treatment of inflammatory diseases comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0012] Another aspect is to provide a pharmaceutical composition for the prevention or treatment of allergic diseases comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0013] Another aspect is to provide a pharmaceutical composition for the prevention or treatment of sepsis comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0014] Another aspect is to provide a health functional food composition for the prevention or improvement of inflammatory diseases comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0015] Another aspect is to provide a health functional food composition for the prevention or improvement of allergic diseases comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0016] Another aspect is to provide a health functional food composition for the prevention or improvement of sepsis comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0017] Another aspect is to provide a cosmetic composition comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof. means of solving the problem

[0018] One aspect provides a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof:

[0019] [Chemical Formula 1]

[0020] .

[0021] In this specification, the compound represented by the above chemical formula 1 (hereinafter, compound 1) is used interchangeably with the term “3R)-1-octane-3-yl-3-O-beta-D-glucopyranoside” or the term “E3D”.

[0022] In this specification, the term "pharmaceuticalally acceptable" means physiologically acceptable and, when administered to humans, does not typically cause allergic reactions such as gastrointestinal disturbances or dizziness, or similar reactions.

[0023] In this specification, the term “pharmaceuticalally acceptable salt” means a salt according to one aspect of the present invention that is pharmaceutically acceptable and has the desirable pharmacological activity of a parent compound. A salt of a parent compound may be synthesized from a parent compound containing a basic or acidic moiety by conventional chemical methods. Generally, such salts may be prepared by reacting the free acid form of these compounds with a stoichiometric amount of a suitable base, e.g., sodium, calcium, magnesium, or potassium, or by reacting the free base form of these compounds with a stoichiometric amount of a suitable acid. Such reactions are typically carried out in water, in an organic solvent, or in a mixture of both. Generally, where feasible, a non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile may be used. The pharmaceutically acceptable salt comprises both the addition salt of an acid or base and its stereochemical isomer forms, and may be, for example, an addition salt of an organic acid or an inorganic acid. The above salt includes any salt that maintains the activity of the parent compound in the subject of administration and does not cause undesirable effects, and is not particularly limited.

[0024] These salts include inorganic and organic salts, for example, acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzenesulfonic acid, benzoic acid, stearic acid, lactic acid, non-carboxylic acid, non-sulfuric acid, non-tartaric acid, oxalic acid, butyric acid, calcium idete, carbonic acid, chlorobenzoic acid, citric acid, idetic acid, toluenesulfonic acid, fumaric acid, gluteptic acid, esylic acid, pamoic acid, gluconic acid, methylnitric acid, malonic acid, hydrochloric acid, hydroiodoic acid, hydroxynaphtholic acid, isethionic acid, lactobionic acid, mandelic acid, mucinous acid, It may be napsylic acid, muconic acid, p-nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogenated phosphate, dihydrogenated phosphate, salicylic acid, sulfamic acid, sulfanilic acid, or methanesulfonic acid.

[0025] In addition, the forms of the salt include salts of alkali and alkaline earth metals such as ammonium salts, lithium salts, sodium salts, potassium salts, magnesium salts, and calcium salts; salts having organic bases such as benzathine, N-methyl-D-glucarmine, and hydrabamin salts; and salts having amino acids such as arginine and lysine. Additionally, the forms of the salt may be converted into a free form by treatment with a suitable base or acid.

[0027] Another aspect provides a pharmaceutical composition for the prevention or treatment of inflammatory diseases comprising the above compound 1 or a pharmaceutically acceptable salt thereof.

[0028] In this specification, the term "inflammation" refers to a reaction intended to protect the body against harmful agents, comprising a series of processes in which immune cells, blood vessels, and inflammatory mediators are involved to suppress cell damage, remove damaged tissues and necrotic cells, and regenerate tissues. Additionally, in this specification, the term "inflammatory disease" or "inflammatory disease" collectively refers to diseases in which inflammation is the primary lesion, and such inflammatory diseases may include inflammation of the digestive system (gastrointestinal tract, etc.), inflammation of the eye, inflammation of the oral cavity, inflammation of the respiratory system including the lungs, inflammation of the skin, inflammation of the cardiovascular system, inflammation of the brain, inflammation of the ear, etc.

[0029] According to one embodiment, the inflammatory disease is inflammatory bowel disease (IBD), irritable bowel syndrome, Behcet's disease, enteritis, Crohn's disease, ulcerative colitis, vasculitis, mucositis, stomatitis, peri-implantitis, periodontitis, pulpitis, gingivitis, pneumonia, dermatitis, mouth ulcers, uveitis, pharyngitis, tonsillitis, otitis including otitis media, psoriatic arthritis, synovitis, meningitis, encephalitis, and Bickerstaff's encephalitis. It may be any one selected from the group consisting of encephalitis, encephalomyelitis, spondylitis, osteomyelitis, Guillain-Barré syndrome, neuromyelitis optica, cystitis, nephritis, and glomerulonephritis.The above dermatitis may be one or more selected from the group consisting of atopic dermatitis, contact dermatitis, seborrheic dermatitis, dermatitis herpetiformis, neurodermatitis, dermatomyositis, and psoriasis.

[0030] More specifically, the above compound 1 or a pharmaceutically acceptable salt thereof may prevent, improve, or treat inflammatory diseases by inhibiting the expression or activity of inflammatory cytokines such as Interleukin-8 (IL-8) or Tumor necrosis factor-α (TNF-α). Additionally, the above IL-8 may be produced from keratinocytes, for example, HaCaT cells. Thus, the above compound 1 or a pharmaceutically acceptable salt thereof may prevent or treat skin inflammation by inhibiting the production of IL-8 by keratinocytes.

[0031] In this specification, the term "prevention" collectively refers to partially or completely delaying or preventing the onset or recurrence of a disease, disorder, or its associated symptoms, preventing the acquisition or reacquisition of a disease or disorder, or reducing the risk of acquiring a disease or disorder. Such prevention refers to any act of suppressing or delaying the occurrence of inflammation or inflammation-related diseases, disorders, or symptoms through the administration of a composition according to the present invention.

[0032] In this specification, the term "treatment" refers to any act that improves or beneficially alters a disease, disorder, or its associated symptoms.

[0033] In one embodiment, the compound 1 or a pharmaceutically acceptable salt thereof is present in an amount of 0.0001 wt% to 99.0 wt% based on the total weight of the pharmaceutical composition, for example, 0.001 wt% to 99 wt%, 0.001 wt% to 90 wt%, 0.001 wt% to 80 wt%, 0.001 wt% to 60 wt%, 0.001 wt% to 40 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 5 wt%, 0.002 wt% to 99.0 wt%, 0.002 wt% to 90 wt%, 0.002 wt% to 80 wt%, 0.002 wt% to 60 wt%, 0.002 wt% to 40 wt%. 0.002 wt% to 20 wt%, 0.002 wt% to 10 wt%, 0.002 wt% to 5 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 1 wt% to 50 wt%, 1 wt% to 40 wt%, 2 wt% to 40 wt%, 3 wt% to 30 wt%, 4 wt% to 30 wt%, It may be included in an amount of 5% to 30% by weight, 5% to 20% by weight, 5% to 18% by weight, 6% to 15% by weight, 8% to 15% by weight, or 7% to 10% by weight. However, in the case of long-term consumption for the purpose of health and hygiene or health control, it may be below the above range, and since there is no problem in terms of safety, the active ingredient may also be used in an amount greater than the above range.

[0034] In one embodiment, the pharmaceutical composition may be formulated into a preparation selected from the group consisting of tablets, soft or hard capsules, pills, powders, suspensions, syrups, injections, and granules.

[0035] In one embodiment, the pharmaceutical composition may be for oral or parenteral administration.

[0036] The above pharmaceutical composition may include conventional fillers, extenders, binders, disintegrants, anticoagulants, lubricants, wetting agents, pH adjusters, nutrients, vitamins, electrolytes, alginic acid and its salts, pectic acid and its salts, protective colloids, glycerin, flavorings, emulsifiers, or preservatives.

[0037] The above pharmaceutical composition may include a pharmaceutically acceptable carrier, examples of which may be one or more selected from the group consisting of 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 and mineral oil, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin and physiological saline.

[0038] The formulation of the above pharmaceutical composition may vary depending on the method of use and may be formulated using methods well known in the art to which the present invention belongs so as to provide rapid, sustained, or delayed release of the active ingredient after administration to mammals.

[0039] Preparations for oral administration include tablets, soft or hard capsules, pills, powders, suspensions, syrups, injections, and granules, and these preparations may be prepared by mixing one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients. Preparations for parenteral administration may be creams, lotions, ointments, ointments, liquids, aerosols, fluid extracts, elixirs, infusions, sachets, patches, or injections.

[0040] The above method is applicable to any animal, and the animal may include humans and primates, as well as livestock such as cattle, pigs, sheep, horses, dogs, and cats.

[0041] The dosage of the above composition for treatment, prevention, or improvement can be determined by considering the method of administration, the age and gender of the user, the severity and condition of the patient, the absorption and inactivation rate of the active ingredient in the body, and concomitant drugs, and may be administered as 0.1 mg / kg (body weight) to 500 mg / kg (body weight), 0.1 mg / kg (body weight) to 400 mg / kg (body weight), or 1 mg / kg (body weight) to 300 mg / kg (body weight) based on the daily active ingredient, and may be administered once or in multiple doses, but is not limited thereto.

[0043] Another aspect provides a pharmaceutical composition for the prevention or treatment of allergic diseases comprising the above compound 1 or a pharmaceutically acceptable salt thereof.

[0044] The above compound 1 is as described above.

[0045] In this specification, the term "allergic disease" refers to a disease caused by an allergy, which is an antigen-antibody reaction that occurs when an individual is exposed to a certain type of substance, such as an antigen or allergen, and antibodies are produced against it, and subsequently the same substance, the antigen, is exposed again.

[0046] The above allergic disease may be one or more selected from the group consisting of allergic rhinitis, allergic conjunctivitis, allergic asthma, allergic dermatitis, anaphylactic shock, food allergy, hay fever, drug allergy, plant allergy, urticaria, and eczema.

[0047] In one embodiment, the compound 1 may inhibit the degranulation of mast cells. By inhibiting the degranulation of mast cells, it may prevent, improve, or treat an allergic disease. Accordingly, the allergic disease may be a mast cell-mediated allergic disease.

[0049] Another aspect provides a pharmaceutical composition for the prevention or treatment of sepsis comprising the above compound 1 or a pharmaceutically acceptable salt thereof.

[0050] The above compound 1 is as described above.

[0051] In this specification, the term "sepsis" refers to systemic inflammatory response syndrome (SIRS) that occurs when the blood is infected by bacteria that have invaded the human body, or when an inflammatory response and the production of inflammatory substances occur in a part of the body. The sepsis may be severe sepsis or septic shock.

[0052] The main causative bacterium of the above sepsis is Acinetobacter baumannii ( Acinetobacter baumannii ), Esquerikia Colai ( Escherichia coli ), Klebsiella pneumonia ( Klebsiella pneumoniae ), Pseudomonas eruginosa( Pseudomonas aeruginosa ), Sigela Soine( Shigella sonnei ), Staphilococcus aureus( Staphylococcus aureus ), Streptococcus pyogenes( Streptococcus pyogenes ), Bacillus cereus( Bacillus cereus ), Clostridium perfringens( Clostridium perfringens ), Enterococcus faecalis( Enterococcus faecalis ), Salmonella enteratidis( Salmonella enteritidis ) and Campylobacter jejuni( Campylobacter jejuni It may be one or more selected from a group consisting of ).

[0053] According to one embodiment, the sepsis may be induced by LPS.

[0055] Another aspect provides a health food composition for preventing or improving inflammatory diseases comprising compound 1 or a pharmaceutically acceptable salt thereof.

[0056] The above compound 1 and inflammatory disease are as described above.

[0057] In this specification, the term "improvement" refers to any action that at least reduces parameters related to the condition being treated, such as the degree of symptoms.

[0058] In this specification, the term "health functional food" refers to a food manufactured or processed for the purpose of health supplementation using specific ingredients as raw materials or by methods such as extraction, concentration, purification, or mixing of specific ingredients contained in food raw materials, and refers to a food designed and processed to fully exert bio-regulatory functions on the body, such as biological defense, regulation of biological rhythms, and prevention and recovery from disease, through said ingredients. The above-mentioned health functional food composition can perform functions related to the prevention and improvement of skin damage caused by fine dust.

[0059] There are no specific restrictions on the types of the above-mentioned foods. Examples of foods to which the above-mentioned extract may be added include formulations selected from the group consisting of powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, infusions, gum, candies, and health drinks, and include all health foods in the conventional sense.

[0060] The above health drink composition may include various sweeteners, flavorings, or natural carbohydrates as additional ingredients, as in ordinary beverages. The sweetener may be a natural sweetener or a synthetic sweetener. The natural sweetener may be taumatin or stevia extract, and the synthetic sweetener may be saccharin or aspartame.

[0061] The above natural carbohydrate may be monosaccharide, disaccharide, polysaccharide, xylitol, sorbitol, or erythritol. The above monosaccharide may be glucose or fructose, and the disaccharide may be maltose or sucrose. The polysaccharide may be dextrin or cyclodextrin. The proportion of the above natural carbohydrate may generally be about 0.01 to 10 g, for example, about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

[0062] The above-mentioned health functional food may include food-grade acceptable food additives and may include a suitable carrier commonly used in the manufacture of health functional foods.

[0063] In addition to the above, the health food composition of the present invention may include various nutritional supplements, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Furthermore, the composition of the present invention may include fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health food composition of the present invention.

[0065] Another aspect provides a health functional food composition for the prevention or improvement of allergic diseases comprising compound 1 or a pharmaceutically acceptable salt thereof.

[0066] The above compound 1 and allergic disease are as described above.

[0068] Another aspect provides a health food composition for the prevention or improvement of sepsis comprising compound 1 or a pharmaceutically acceptable salt thereof.

[0069] The above compound 1 and sepsis are as described above.

[0071] Another aspect provides a cosmetic composition comprising compound 1 or a pharmaceutically acceptable salt thereof.

[0072] The above compound 1 is as described above.

[0073] According to one embodiment, the cosmetic composition may be for anti-inflammatory purposes, and the inflammation may be skin inflammation.

[0074] The above skin inflammation may be one or more selected from the group consisting of atopic dermatitis, contact dermatitis, seborrheic dermatitis, herpetic dermatitis, neurodermatitis, dermatomyositis, and psoriatic dermatitis.

[0075] The above cosmetic composition may be prepared in any formulation conventionally manufactured in the technical field to which the present invention belongs. For example, it may be formulated into softening lotions, nourishing lotions, emulsions, lotions, creams, pastes, gels, solutions, suspensions, oils, waxes, packs, powders, foundations, sprays, surfactant-containing cleansers, etc., but is not limited thereto. More specifically, it may be prepared in the form of skin lotion, skin softener, skin toner, nourishing cream, massage cream, milk lotion, powder, essence, eye cream, sun lotion, sun cream, makeup primer, makeup base, BB cream, powder foundation, emulsion foundation, cleansing cream, cleansing foam, cleansing water, soap, pack, stick-type product, balm-type product, spray, or powder formulation.

[0076] The above cosmetic composition may further include any conventional cosmetic ingredient selected from additional ingredients commonly used in cosmetics, such as thickeners, dispersants, fragrances, fillers, preservatives, antiseptics, neutralizing agents, sweeteners, vitamins, free-radical scavengers, metal ion chelating agents, functional ingredients, and mixtures thereof. A person skilled in the art may select any additional ingredient and / or the amount thereof so that the advantageous properties of the composition according to this specification are not adversely affected or are substantially affected by the expected addition.

[0077] In the case where the above cosmetic composition is a surfactant-containing cleansing formulation, it may further include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolin derivative, or ethoxylated glycerol fatty acid ester, etc., as a carrier component.

[0078] In the case where the cosmetic composition according to the present invention is in the form of a cream or gel, it may further include animal oil, vegetable oil, wax, paraffin, starch, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide as a carrier component.

[0079] In the case where the above cosmetic composition is in the form of a solution or emulsion, it may further include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, propylene glycol, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan as a solvent, solvating agent, or emulsifying agent.

[0080] In the case where the above cosmetic composition is in the form of a suspension, it may further include, as a carrier component, a liquid diluent such as water, ethanol, or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanth.

[0081] In the case where the above cosmetic composition is in the form of a powder or spray, it may further include lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder as a carrier component, and in particular, in the case of a spray formulation, it may further include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0082] The above cosmetic composition may be used by applying it alone or in combination, or by applying it in combination with other cosmetic compositions other than the present invention. In addition, the cosmetic composition according to the present invention may be used according to conventional methods of use, and the frequency of use may be varied depending on the user's skin condition or preference. Effects of the invention

[0083] A composition according to one aspect inhibits the expression or activity of pro-inflammatory cytokines IL-8 or TNF-α, inhibits the degranulation of mast cells, and has an effect of improving symptoms caused by sepsis, so it can be usefully used for the prevention, improvement, or treatment of inflammatory diseases, allergic diseases, or sepsis. Brief explanation of the drawing

[0084] Figure 1 is the NMR spectrum graph of compound 1: Figure 1a is of compound 1 1 This is the H NMR spectrum graph, and Fig. 1b is of compound 1. 13 This is a C NMR spectrum graph. Figure 2 is a mass spectrometry spectrum graph of compound 1. Figure 3 is a graph showing the TNF-α expression inhibitory activity of Compound 1 in macrophages RAW 264.7: Figure 3a is a graph showing the concentration of TNF-α mRNA, and Figure 3b is a graph showing the concentration of expressed TNF-α. Figure 4 is a graph showing the IL-1β expression inhibitory activity of Compound 1 in macrophages RAW 264.7: Figure 4a is a graph showing the concentration of IL-1β mRNA, and Figure 4b is a graph showing the concentration of expressed IL-1β. Figure 5 is a graph showing the level of expression of the pro-inflammatory cytokine IL-8 in HaCaT cells, which are keratinocytes, following treatment with compound 1. Figure 6 is a graph showing the degree of degranulation of LUVA according to treatment with Compound 1: E3D: Compound 1, Dexa: Dexamethasone. Figure 7 is a graph showing the concentration of TNF-α in the serum of septic mice following the administration of Compound 1 to an LPS-induced septic mouse model; E3D: Compound 1, Dexa: Dexamethasone. Specific details for implementing the invention

[0085] The following examples will be explained in more detail. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

[0087] Reference Example 1. Statistical Analysis

[0088] In the following experimental examples, the significance of differences between individual groups was calculated using nonparametric one-way analysis of variance (Kruskal-Wallis test) and confirmed by Bonferroni correction in post-hoc analysis. P < 0.05 was considered statistically significant.

[0090] Example 1. (3R)-1-octane-3-yl-3-O-beta-D-glucopyranoside

[0091] Nuclear magnetic resonance spectral analysis of the structure of (3R)-1-octane-3-yl-3-O-beta-D-glucopyranoside (Compound 1) ( 1 H NMR and 13 It was determined using 3C NMR and mass spectrometry, and is shown in Figures 1 and 2.

[0092] HPLC-ESI-MS experiments were performed using a high-performance liquid chromatography mass spectrometer (LC-ESI-MS; 8040 Series, Shimadzu).

[0094] Figure 1 is the NMR spectrum graph of compound 1:

[0095] Figure 1a is of compound 1 1 This is the H NMR spectrum graph, and Fig. 1b is of compound 1. 13 This is a C NMR spectrum graph.

[0096] Figure 2 is a mass spectrometry spectrum graph of compound 1.

[0098] Experimental Example 1. Analysis of Anti-inflammatory Activity

[0099] To analyze the anti-inflammatory activity of compound 1, the inhibitory activity of the expression of pro-inflammatory cytokines TNF-α and IL-1β was measured.

[0100] Specifically, RAW 264.7 mouse macrophages 1 x 10 5 The cells were seeded into 96-well plates containing DMEM culture medium prepared at cell / well concentrations. Subsequently, the RAW 267.4 cells were pretreated with Compound 1 at each concentration (0, 6.25, 12.5, 25, 50, or 100 μM each) for 1 hour in a 37°C incubator, and then the cells were stimulated with an LPS solution at a final concentration of 1 μg / mL for 6 hours at 37°C. The supernatant samples were then collected by centrifugation and stored at -70°C, after which the expression of pro-inflammatory cytokines TNF-α and IL-1β was measured, and the results are shown in Figures 3 and 4. Dexamethasone (Dexa) was used as a control.

[0102] Figure 3 is a graph showing the TNF-α expression inhibitory activity of Compound 1 in macrophages RAW 264.7:

[0103] Figure 3a is a graph showing the concentration of TNF-α mRNA, and Figure 3b is a graph showing the concentration of expressed TNF-α.

[0104] Figure 4 is a graph showing the IL-1β expression inhibitory activity of Compound 1 in macrophages RAW 264.7:

[0105] Figure 4a is a graph showing the concentration of IL-1β mRNA, and Figure 4b is a graph showing the concentration of expressed IL-1β.

[0107] As shown in Figures 3 and 4, it was confirmed that the expression inhibitory effect of pro-inflammatory cytokines TNF-α and IL-1β was observed in proportion to the concentration of compound 1.

[0109] Experimental Example 2. Analysis of Skin Inflammation Inhibitory Activity

[0110] To confirm the skin inflammation inhibitory activity of compound 1, the expression level of the pro-inflammatory cytokine IL-8 was measured using HaCaT cells, which are keratinocytes.

[0111] Specifically, HaCaT cells were seeded into a 96-well plate and treated with Compound 1 (0 μM, 0.78 μM, 1.56 μM, 3.125 μM, 6.25 μM, 12.5 μM, 25 μM, and 50 μM, respectively) for 30 minutes in an incubator at 37 °C. Subsequently, the HaCaT cells were stimulated with IFN-γ (10 μg / ml) for 24 hours. The next day, the supernatant samples were collected and centrifuged to remove cell debris. The supernatant samples were then stored at -80 °C, and the expression level of IL-8 was measured via ELISA analysis. The results are shown in Figure 5.

[0113] Figure 5 is a graph showing the level of expression of the pro-inflammatory cytokine IL-8 in HaCaT cells, which are keratinocytes, following treatment with compound 1.

[0114] As shown in Figure 5, it was confirmed that the expression of the pro-inflammatory cytokine IL-8 in keratinocytes was effectively inhibited in proportion to the concentration of compound 1.

[0115] More specifically, Compound 1 has an IC for IL-8 at 1.337±0.04 μM. 50 It was confirmed that it has a value. In particular, it was confirmed that IL-8 is not expressed when treated with compound 1 at a concentration of 50 μM.

[0117] The above results indicate that compound 1 is effective in inhibiting skin inflammation.

[0119] Experimental Example 3. Measurement of Inhibitory Efficacy Against Allergic Diseases in Human Mast Cells (LUVA Cells) via β-Hexosaminidasea assay

[0120] To confirm the inhibitory activity of compound 1 on allergic diseases, a β-hexosaminidase assay was performed using a LUVA cell.

[0121] Specifically, LUVA cells in a 96-well plate at a final concentration of 1 x 10 5Cells were seeded into wells. After 1 hour, the LUVA cells were treated with Compound 1 at different concentrations (0, 6.25, 12.5, 25, or 50 μM, respectively) and then stimulated overnight at 37 °C with 1 μg / ml human IgE. Subsequently, the cells were washed and dispensed onto the bottom of a plate containing 60 μl of Tyrode buffer. Then, the cells were treated again with Compound 1 at the same concentration as before and stimulated for 2 hours with a mixture of A23187 (2 μM) diluted in Tyrode buffer and anti-human IgE. The degree of degranulation of mast cells LUVA was measured by determining the release of β-hexosaminidase in the supernatant and lysate using enzymatic colorimetric analysis with p-nitrophenyl N-acetyl-bD-glucosamine. Dexamethasone was used as a control, and the results are shown in Figure 6.

[0123] Figure 6 is a graph showing the degree of degranulation of LUVA according to treatment with Compound 1: E3D: Compound 1, Dexa: Dexamethasone.

[0124] As shown in Figure 6, it was confirmed that compound 1 exhibits a degranulation inhibitory effect in proportion to its concentration.

[0125] More specifically, it was confirmed that treatment with 6.25 μM of compound 1 resulted in an inhibitory effect of approximately 50% or more on β-hexosaminidase release compared to the untreated control group. This implies that allergic diseases can be effectively alleviated through compound 1.

[0127] Experimental Example 4. Confirmation of the TNF-α inhibitory efficacy of Compound 1 in an LPS-induced sepsis mouse model

[0128] In vivo To confirm the inhibitory effect of compound 1 on TNF-α expression, experiments were conducted using male mice (BALB / C, 8 weeks).

[0129] Specifically, 20 mg / kg of compound 1 suspended in saline was orally administered to the male mice. Then, 3 days later, 5 μg / kg of LPS was injected intraperitoneally (ip) into the mice to induce sepsis. Two hours after the administration of LPS, blood samples were collected from the mice. The blood samples were centrifuged to collect serum, and the concentration of TNF in the serum was measured by measuring the absorbance at a wavelength of 450 nm using a mouse TNF ELISA kit.

[0130] As a result, among LPS-induced sepsis mouse models, the serum TNF-α concentration in mice not pretreated with Compound 1 was found to be approximately 300 pg / ml. In contrast, the serum TNF-α concentration in mice pretreated with Compound 1 among LPS-induced sepsis mouse models was approximately 30 pg / ml, confirming an inhibitory effect of about 90% on TNF-α expression compared to mice not treated with Compound 1. Dexamethasone was used as a control, and the results are shown in Figure 7.

[0132] Figure 7 is a graph showing the concentration of TNF-α in the serum of septic mice following the administration of Compound 1 to an LPS-induced septic mouse model; E3D: Compound 1, Dexa: Dexamethasone.

[0133] As shown in Figure 7, treatment with Compound 1 resulted in approximately 90% inhibition of TNF-α expression in LPS-induced sepsis mice compared to the control group not treated with Compound 1. This indicates that Compound 1 has a significant therapeutic or improvement effect on sepsis.

Claims

Claim 1 A pharmaceutical composition for the prevention or treatment of inflammatory diseases comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof, wherein the inflammatory disease is any one selected from the group consisting of inflammatory bowel diseases (IBD), Behcet's disease, Crohn's disease, ulcerative colitis, vasculitis, uveitis, and psoriatic arthritis: [Chemical Formula 1] . Claim 2 A health functional food composition for preventing or improving inflammatory diseases comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof, wherein the inflammatory disease is any one selected from the group consisting of inflammatory bowel diseases (IBD), Behcet's disease, Crohn's disease, ulcerative colitis, vasculitis, uveitis, and psoriatic arthritis: [Chemical Formula 1] . Claim 3 Cosmetic composition for improving psoriasis comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] .

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