KR101303963B1 - Anti-allergy composition comprising (1R,2R,3R)-3-aminocyclopentane-1,2-diol - Google Patents

Abstract

The present invention relates to an antiallergic composition comprising (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol, wherein (1R, 2R, 3R) -3-aminocyclopentane-1,2 -Diol inhibits the expression of COX-2, TNF-α, IL-4, and IL-10 genes and inhibits the activity of AKT-, ERK-, JNK-, and p38-signaling pathways, It can be usefully used for the prevention or treatment of various diseases.

Description

Anti-allergy composition comprising (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol} (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol

The present invention relates to compositions having anti-allergic activity comprising (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol and uses thereof.

More than 5% of allergy-related patients, which were less than 1% in 1980 due to environmental pollution, dietary changes, and stress caused by the development of industry and civilization, are currently increasing every year.

Allergy is a biochemical phenomenon that shows a specific and modified reaction to a foreign substance. During the allergic reaction, various cytokines are released, causing symptoms specific to the allergic reaction. At this time, the allergen is called an allergen. The cause of allergy is a pathological process of the living body that results from an antigen-antibody reaction, and is generally classified into types 1 to 4 according to the time required to cause the response and the type of complement-mediated. Immediate anaphylaxis, which causes bronchial asthma, allergic rhinitis, hay fever and atopic dermatitis, is a type 1 reaction. Immediate hypersensitivity and allergic reactions are due to a variety of changes that occur in mast cells, etc. (Ann. Allergy 56, 464, 1986; Eur. J. Pharmacol., 96, 227, 1983; J. Pharm. Sci., 84, 223 , 1995; Biol. Pharm. Bull., 18, 683, 1995).

During an allergic reaction, IgE is produced in B-cells by helper T-cells activated by foreign antigens presented by macrophage, and the generated IgE binds to the high-affinity IgE antibody receptor (FcRIa) of the mast cell membrane. Done. When antigens such as ticks and pollen bind to a plurality of bound IgE antibodies to form crosslinks, receptors aggregate and the mast cells are activated by such crosslinking and aggregation. Activated mast cells and increase the calcium ions (Ca ^{2 +)} concentration, such as in the cytoplasm, so that the degranulation (degranulation) caused by.

Increasing calcium ion concentration acts on various cellular regulators such as cholesterol of the cell membrane and cytoskeletal system to move granules to the cell membrane, and at the same time degranulates through phobia of granules, fusion of granules and fusion of granules and cell membranes. Cause symptoms. In addition, an increase in calcium ion concentration is caused by phospholipase enzymes as enzymes that act on phospholipids of cell membranes. At the time of degranulation, the chemical transfer material is released from mast cells such as histamine and newly synthesized prostaglandin and leukotriene are also secreted. Chemotransmitters liberated by degranulation include NCFs that act as chemotactic factors for inflammatory cells such as eosinophils or neutrophils, in addition to histamine, serotonin, and leukotriene, which have the effects of vasodilation, vascular permeability, and contraction or secretion of bronchial smooth muscle. (neutrophil chemotactic factor), ECF (eosinophil chemotactic factor), and PAF (platelet activating factor), and the like, these chemical transfer substances are caused by Type 1 allergic reactions.

When secreted histamine binds to vascular endothelial cells, vascular cell contraction occurs, and the plasma in the blood is extravasated into the tissue, and endothelial cells release prostacyclin, which relaxes vascular muscle cells. And induce synthesis of substances such as nitric oxide to induce vasodilation. By this mechanism, the histamine is secreted, and the secreted histamine causes reactions such as swelling, flare, and itching.

Agents for treating or preventing allergies can be broadly divided into steroidal anti-inflammatory drugs or nonsteroidal anti-inflammatory drugs and antihistamines or anti-leukotrienes. Since the former has a strong immunosuppressive action in most cases, it may have a temporary sedative effect in a short period of time, but there are many problems with long-term use, since it has mild side effects such as nausea and serious side effects such as growth inhibition or osteoporosis. The latter may show a temporary relief, but there are side effects such as drowsiness and dizziness, which limits its use. Therefore, researches on compounds that can be applied more safely as well as efficacy and effect are being actively made.

Against this background, the present inventors have made diligent efforts to find compounds that can prevent allergies. As a result, (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol is COX-2, TNF-α, IL- 4, and found to have the effect of inhibiting the expression of the IL-10 gene and inhibiting the activity of AKT, ERK, JNK, p38, and COX-2, and confirmed that it can be used for the prevention or treatment of allergy By this, the present invention was completed.

An object of the present invention to provide an anti-allergic composition that can be used for the treatment of allergic diseases by using a compound that inhibits allergic factors.

Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of allergies.

Another object of the present invention is to provide a food composition for the prevention or improvement of allergies.

Another object of the present invention is to provide a quasi-drug composition for the prevention or improvement of allergies.

Another object of the present invention to provide a cosmetic composition for the prevention or improvement of allergies.

It is still another object of the present invention to provide a method for treating allergy, comprising administering to a subject having, or possibly causing, allergy in a pharmaceutically effective amount of the pharmaceutical composition for preventing or treating the allergy.

As one aspect of the present invention for achieving the above object, there is provided an anti-allergic composition comprising a compound represented by the following formula (1) as an active ingredient.

[Formula 1]

According to another aspect of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of allergy comprising the above composition as an active ingredient.

According to another aspect of the present invention, there is provided a food composition for preventing or improving allergy comprising the above-mentioned composition as an active ingredient.

According to another aspect of the present invention, there is provided a quasi-drug composition for the prevention or improvement of allergy comprising the above composition as an active ingredient.

According to another aspect of the invention, there is provided a cosmetic composition for the prevention or improvement of allergy comprising the above composition as an active ingredient.

According to another aspect of the present invention, there is provided a method for treating allergy, comprising administering a pharmaceutical composition for the prophylaxis or treatment of the allergy described above in a pharmaceutically effective amount to a subject having or is likely to develop the allergy. do.

Hereinafter, the present invention will be described in detail.

According to one aspect of the present invention, the present invention provides a composition for anti-allergy, comprising a compound represented by the following formula (1) as an active ingredient.

[Formula 1]

In the allergy alleviation and prevention composition of the present invention, the allergy alleviation and prevention is characterized in that it is carried out by one or more of the following features. (i) inhibition of expression of COX-2, TNF-α, IL-4, and IL-10 genes, (ii) inhibition of activation of AKT-, ERK-, JNK-, and p38- signaling pathways, (i) NF inhibition of -κB activity, and (iii) inhibition of lipoxygenase activity.

Allergy is a type of hypersensitivity reaction due to imbalance, which is a biochemical phenomenon that shows a specific, modified response to a foreign substance (antigen). Diseases include atopic dermatitis, allergic asthma, rhinitis, and food allergies. 10-40% of the world's population suffers from various allergic diseases. In the normal human immune system, the Th1 response regulates cellular immunity and the Th2 response regulates humoral immunity. In allergic patients, the Th2 response can be over-balanced, leading to a variety of adverse reactions, such as an excessive increase in blood IgE (immunoglobulin E) or excessive release of histamine.

Upon exposure to antigen, it is delivered to T-lymphocytes to release cytokines such as Interleukin (IL) 4, 5, 6 and granulocyte macrophage colony stimulating factor (GM-CSF). Cytokines react with B-lymphocytes in lymph nodes, and B-lymphocytes self-modify plasma cells to secrete IgE antibodies. IgE antibodies are attached to mast cells and basophils, resulting in histamine, serotonin, leukotriene B4, C4, D4, E4, platelet activator, prostaglandin D, interleukin 1, 3, 4, 5, 6, GM-CSF, tumor necrosis factor Releases alpha, bradykinin and the like to mediate the inflammatory response.

In order to treat or prevent allergies, excessive Th2 responses should be suppressed, Th1 responses should be efficiently induced to stabilize the T-immune response, and IgE-mediated inflammatory responses act directly or indirectly on B cells that produce excessive IgE. Should be blocked.

Inflammatory responses induced by allergies include:

Inflammation is an immune response of the human body in response to a wound or disease, and oxidative stress such as ultraviolet rays, free radicals, and free radicals activate inflammatory factors to cause various diseases and aging of the skin. One of the hallmarks of inflammation is the increased oxygenation of arachidonic acid, which is metabolized by the cyclooxygenase (COX) producing prostaglandins and the 5-lipoxygenase pathway producing leukotriene. Prostaglandins and leukotrienes are mediators of inflammation. Thus, therapies designed to inhibit cyclooxygenase and / or lipoxygenase activity are of great interest. There are two forms of cyclooxygenase enzymes, cyclooxygenase-1 and cyclooxygenase-2, which seem to play an important role in the progression of inflammation. Thus, inhibiting cyclooxygenase-2 enzyme may be an effective way to reduce inflammation without the side effects associated with irreversible cyclooxygenase-1 inhibition.

TNF-alpha is an important factor in the inflammatory response and is involved in tissue regeneration (Wajant H. et al. Cell Death and Differentiation 10: 45-65, 2003). In normal conditions, when inflammation occurs, the induction of inflammation caused by these factors is well controlled. That is, in normal conditions, the amount of these factors decreases after inflammation and an immune response.

However, if the amount of factors, such as TNF-alpha, continues to increase without control, it causes chronic inflammation. This chronic inflammation is the cause of diseases such as arthritis, sclerosis, Alzheimer's disease, fibrosis, cancer, diabetes, and inflammatory bowel diseases (Balkwill F) et al. Nature 431: 405-406, 2004; Chen G and David VG Science 296: 1634, 2002).

The principle that the increase of TNF-alpha causes chronic inflammation is as follows.

Intracellular signal transduction pathways of TNF-alpha can be divided into cell survival pathway (NF-kB pathway) and cell death pathway (ROS-JNK-Caspase pathway) (Papa S. et al. Cell Death and Differentiation 13: 712-729, 2006). In this TNF-alpha signaling pathway, free radicals are induced, which are known to be mitochondria, but the mechanism of their formation has not been elucidated (Chandel NS et al. J. Biol. Chem. 276). : 42728-42736, 2001; Hennet T. et al. Cancer Res. 53: 1456-1460, 1993; Hennet T. et al. Biochem. J. 289: 587-592, 1993; Schulze-Osthoff K. et al. J. Biol. Chem. 267: 5317-5323, 1992).

In vivo, an appropriate amount of free radicals play an important role in signal transmission, and there are cases in which free radicals are excessively increased by external stress stimulation in cells. The increased free radicals cause various diseases such as cancer, aging, inflammation, diabetes, arteriosclerosis, and liver fibrosis (Droge W., Physiol. Rev. 82: 47-95, 2002). As such, strategies to block the production of free radicals have been reported as molecular targets for treating inflammatory diseases. Free radicals are known to play an important role in inflammatory pain as well as in acute and chronic inflammation (Salvemini D. et al. Biochem. Soc. Trans. 34: 965-970, 2006).

Free radicals generated in the TNF-alpha signal transduction pathway affect NF-kB activation and TNF-alpha induced cell death, of which TNF-alpha induces chronic free radicals that are excessively increased by an increase in TNF-alpha. Closely related to inflammation (Sulciner DJ et al. Mol. Cell Biol. 16: 7115-7121, 1996; Schulze-Osthoff K. et al. EMBO J. 12: 3095-3104, 1993) (Leist et al. Nat Rev. Mol. Cell Biol. 2: 589-598, 2001).

IL-4 is a 20 kDa cytokine mainly produced in Th2 and mast cells, first known as B-cell growth factor (BCGF), but then cells of almost all tissues, as well as lymphocytes and immune system cells. It has been shown that high affinity IL-4 receptor (IL-4R) is expressed in and various cells respond to it. In addition, IL-4 is an important factor in the development of atopic allergy by increasing Th2 response, inducing potent IgE isomorphism and production and increasing eosinophil mediated inflammatory responses. Known as

IL-10 inhibits the expression of enzymes involved in inflammation such as inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in macrophages. An important mechanism that inhibits the T cell activity of IL-10 is to inhibit MHC II expression by inhibiting MHC exocytosis and recycling in antigen presenting cells such as macrophages, and CD28 T cell activation is inhibited by inhibiting the interaction between CD80 and CD86, and the expression of B7-1, B7-2, and IgE receptors can be effectively inhibited in the expression of allergens in monocytes or dendritic cells. have.

MAPK is well known as a representative signaling pathway for delivering extracellular stimuli from the cell membrane to the intracellular nucleus. MAPK transmits activated signals from receptors such as growth hormone, cytokines, and stress into cells, and is responsible for various functions such as cell proliferation, differentiation, and death. MAPK can be classified into three types: 1) extracellular signal-activated kinases (ERK), 2) c-JUN N-terminal kinase (JNK), and 3) p38 MAPK. ERK (ERK1 / 2) is primarily involved in the signaling of growth hormone and plays a pivotal role in the proliferation and differentiation of cells. On the other hand, p38 MAPK and JNK, which are classified as stress kinases, are activated by stress stimuli external to cells and are known to mediate inflammatory responses and apoptosis.

Two of the most important pathways for inflammation are mediated by the enzymes lipoxygenase (LOX) and cyclooxygenase (COX). These are parallel pathways that produce leukotriene and prostaglandins, respectively, which play an important role in the initiation and progression of the inflammatory response.

Inhibitors showing dual specificity for COX and LOX have a pronounced effect on inhibiting multiple pathways of arachidonic acid metabolism. Such inhibitors block their inflammatory action by limiting the production of prostaglandins (PG) and multiple leukotrienes (LT). This includes the vasodilating, vascular infiltration and chemoattracting actions of PGE2, LTB4, LTD4 and LTE4, which are also known as slow reaction components of anaphalaxis.

NF-κB is a nuclear protein of the Rel gene family. In the cytoplasm, NF-κB exists in an inactive form in combination with inhibitory kappa B (IκB), but such as noxious oxygen, TNF-a and IL-1. IB kinase is activated by various stimuli such as chemokines and LPS and then IκB is released through the phosphorylation process. NF-κB, composed of p50 and p65 heterodimers, is known to promote gene expression that, after being activated, migrates to the nucleus to induce an inflammatory response (Oh GT et al., Artherosclerosis, 159 (1): 17-26, 2001; Epstein FH et al., The New England Journal of Medicine, 336 (15): 1066-1071, 1997; Zhang WJ et al., FASEB J, 15 (130): 2423-2431, 2001; Denk A et al., J. Biol. Chem., 276 (30): 28451-28458, 2001; Sahnoun Z et al., Phsiology, 53 (4): 315-339, 1998; Lindner V Pathobiology, 66 (6 311-320, 1998; Landry DB et al., Am. J. Pathol., 151 (4): 1085-1095, 1997; Gerritsen ME et al., Am. J. Pathol., 147 (2): p278-292, 1995).

The present inventors observed the activation of inflammatory mediators and inflammation-related signaling pathways, and when treated with a compound of the present invention, inflammatory mediators COX-2, TNF-α, IL-4, IL-10, etc. Expression was inhibited (FIG. 2), AKT, ERK-, JNK-, and p38- signaling were inhibited (FIG. 3), and the activity of NF-κB (FIG. 4) and lipoxygenase (Table 2) was also inhibited. It confirmed that it became. This confirmed that the composition of the present invention can be used as an anti-allergic composition.

The compound represented by Chemical Formula 1 can be synthesized by a known method. For example, a high yield of ( 1R , 2R , 3R ) -3-aminocyclopentane-1,2-diol can be obtained through the synthesis procedure shown in Scheme 1 below.

[Reaction Scheme 1]

Reaction reagents and conditions: (a) NaH, DMSO, BnPPh ₃ Cl, THF, 45 ° C .; (b) (i) Dess-Martin periodinane, CH ₂ Cl ₂ , 0 ° C .; (Ii) NaHMDS, MePPh ₃ Br, THF, 0 ° C .; (c) (i) CSI, Na ₂ CO ₃ , toluene, 0 ° C .; (Ii) 25% Na ₂ SO ₃ , rt; (d) 5 mol% (IMesH ₂ ) (PCy ₃ ) (Cl) ₂ Ru = CHPh, toluene, 80 ° C .: (e) 10% Pd / C, H ₂ , 6N HCl, MeOH, rt; (Ii) DOWEX-50wX8 (H ⁺ form, 0.5m NH ₄ OH as an eluent).

In Scheme 1, "Bn" represents a benzyl group, and "Cbz" represents a carboxybenzyl group.

According to another aspect of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of allergy comprising an anti-allergic composition comprising the compound represented by the following formula (1) as an active ingredient as an active ingredient.

[Formula 1]

As used herein, the term "prevention" means any action that inhibits allergy or delays the onset by administration of a composition.

As used herein, the term "treatment" refers to any action in which allergic symptoms are improved or advantageously altered by administration of the composition.

In this case, the compound represented by Chemical Formula 1 of the present invention may be used in the form of a pharmaceutically acceptable salt, and the salt is an acid addition salt formed by a pharmaceutically acceptable free acid. Acid addition salts include inorganic acids and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid. Obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically nontoxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and iodide. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suverate , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, meth Oxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfo Nate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1- Sulfonates, naphthalene-2-sulfonates or mandelate.

The acid addition salt according to the present invention is dissolved in a conventional method, for example, the compound represented by Chemical Formula 1 in an excess of aqueous acid solution, and the salt is water-miscible organic solvent such as methanol, ethanol, acetone or aceto. It can be prepared by precipitation using nitrile.

In addition, the compound represented by Formula 1 of the present invention can be used to make a pharmaceutically acceptable metal salt using a base. An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, as the metal salt, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt. The corresponding silver salt is also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

In addition, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier. The composition comprising a pharmaceutically acceptable carrier may be in a variety of oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may comprise at least one excipient in one or more compounds, for example starch, calcium carbonate, sucrose or lactose, gelatin, etc. Are mixed to prepare. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycero gelatin and the like can be used.

The pharmaceutical composition is any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, liquid solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories. It can have one formulation.

The composition of the present invention is administered in a pharmaceutically effective amount.

As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level refers to the type and severity of the subject, the severity, age, sex and activity of the drug. , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of the drug, and other factors well known in the medical arts. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.

The composition of the present invention may be used alone or in combination with methods for using surgery, hormonal therapy, drug therapy and biological response modifiers for the prevention or treatment of allergies.

On the other hand, according to another aspect of the present invention, the present invention is a method for treating allergy comprising administering the pharmaceutical composition for the prevention or treatment of allergy in a pharmaceutically effective amount to the individual having the onset or potential of allergy To provide.

As used herein, the term "individual" means all animals, including humans, who are already allergic or may be allergic, and by effectively administering to a subject a composition comprising a compound represented by Formula 1 of the present invention, Can be prevented and treated. For example, the compositions of the present invention can treat allergic humans. The composition of the present invention can be administered in parallel with existing allergy treatments.

The route of administration of the composition may be administered via any conventional route so long as it can reach the target tissue. The composition of the present invention may be administered as desired, but is not limited to intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, pulmonary administration, rectal administration. The composition may also be administered by any device capable of transferring the active agent to the target cell.

In addition, according to another aspect of the present invention, the present invention provides a food composition for preventing or improving allergy comprising the above-mentioned anti-allergic composition as an active ingredient.

That is, the anti-allergic composition including the compound represented by Chemical Formula 1 of the present invention may be added to a food composition for preventing or improving allergy. When using an anti-allergic composition comprising the compound represented by Formula 1 of the present invention as a food additive, the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. have. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, in the manufacture of food or beverages, the composition of the present invention is added in an amount of 0.01 to 10% by weight, preferably 0.05 to 1% by weight based on the raw materials. However, in the case of prolonged ingestion for health and hygiene purposes or for health control purposes, the amount may be used below the above range.

There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention. These components can be used independently or in combination.

In addition, the present invention provides a quasi-drug composition for the prevention or improvement of allergy comprising the above-described anti-allergic composition as an active ingredient.

That is, the composition of the present invention may be added to the quasi-drug composition for the purpose of preventing or improving allergy. When the anti-allergic composition containing the compound of Formula 1 of the present invention is used as an quasi-drug additive, the composition may be added as it is or used with other quasi-drug components, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).

Preferably, the quasi-drug composition may be an antiseptic agent, a shower foam, a gagreen, a wet tissue, a detergent soap, a hand wash, a humidifier filler, a mask, an ointment, or a filter filler.

In addition, according to another aspect, the present invention provides a cosmetic composition for the prevention or improvement of allergy comprising the above-described anti-allergic composition as an active ingredient.

That is, the composition of the present invention may be added to the cosmetic composition for the purpose of preventing or improving allergy. When using an anti-allergic composition comprising the compound of Formula 1 of the present invention as a cosmetic additive, the composition may be added as it is or used with other cosmetic ingredients, and may be suitably used according to a conventional method. The mixed amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).

Preferably, the formulation of the cosmetic composition is supple cosmetics, astringent cosmetics, nourishing cosmetics, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body Creams, body oils, body essences, makeup bases, foundations, hair dyes, shampoos, rinses or body cleansers.

Since the composition comprising (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol of the present invention as an active ingredient inhibits an allergic reaction, it is useful for the prevention or treatment of various diseases that may be caused by allergy. It can be useful.

1 is a result of confirming the effect of LKI-24 ((1R, 2R, 3R) -3-aminocyclopentane-1,2-diol) on the degranulation of mast cells through beta- hexosaminidase analysis.
Figure 2 shows the results confirmed by RT-PCR the effect of LKI-24 ((1R, 2R, 3R) -3-aminocyclopentane-1,2-diol) on the expression of inflammatory mediators.
Figure 3 is a result confirmed by Western blot the effect of LKI-24 ((1R, 2R, 3R) -3-aminocyclopentane-1,2-diol) on the inflammatory signaling pathway.
Figure 4 shows the effect of LKI-24 ((1R, 2R, 3R) -3-aminocyclopentane-1,2-diol) on the activity of NF-κB through luciferase analysis.

Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

Manufacturing example  1: (1R, 2R, 3R) -3- Aminocyclopentane -1,2- Diol  Produce

(Step 1) (2R, 3S, 4S) -2,3,4- Tris ( Benzyloxy ) -6- Phenylhex Synthesis of -5-en-1-ol (Formula 2)

To a mixed solution of anhydrous DMSO (3.38 mL, 28.56 mmol) and anhydrous THF (53 mL) was added NaH (1.14 g, 72.16 mmol, 60% in mineral oil) at 0 ° C. and nitrogen-filled conditions, and stirred at room temperature for 1 hour. Then BnPPh ₃ Cl (11.1 g, 28.56 mmol) was added at 0 ° C. and stirred at room temperature for 2 hours. At 0 ° C, (3R, 4R, 5R) -3,4,5-tris (benzyloxy) tetrahydro-2H-pyran-2-ol (4.0 g, 9.52 mmol) was added to the resulting mixture and 45 ° C. Stirred for 2 h. The mixture was then cooled and diluted with EtOAc (50 mL), washed with saturated aqueous NH ₄ Cl and brine, then dried over anhydrous MgSO ₄ and concentrated under reduced pressure. The residue obtained therefrom was subjected to column chromatography (2R, 3R, 4R) -2,3,4-tris (benzyloxy) -6-phenylhex-5-en-1-ol as 80% (Z: E = 3.4: 1).

(2)

R _f = 0.37 (Hexane / EtOAc 3: 1); [a] _D ²⁵ +39.6 ( c 1.0, CHCl ₃ ); Z isomer : ¹ H NMR (500 MHz, CDCl ₃ ) δ 3.68 (t, 1H, J = 5.0 Hz), 3.73 (dd, 1H, J = 12.0, 5.0 Hz), 3.77 (dd, 1H, J = 12.0, 5.0 Hz), 3.94 (t, 1H, J = 5.0 Hz), 4.29 (d, 1H, J = 11.5 Hz), 4.31 (d, 1H, J = 12.0 Hz), 4.48 (d, 1H, J = 12.0 Hz) , 4.56 (d, 1H, J = 11.5 Hz), 4.69 (dd, 1H, J = 10.0, 5.0 Hz), 5.81 (dd, 1H, J = 12.0, 10.0 Hz), 6.90 (d, 1H, J = 12.0 Hz), 7.14-7.40 (m, 20H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 61.42, 70.67, 71.97, 74.19, 74.47, 79.45, 81.17, 126.89, 127.53, 127.78, 127.84, 127.93, 127.98, 128.13, 128.28, 128.51, 128.58, 128.73, 128.99, 136.99. , 138.18, 138.46, 138.52; E isomer : ¹ H NMR (500 MHz, CDCl ₃ ) δ 3.64 (dt, 1H, J = 6.5, 4.0 Hz), 3.82 (d, 2H, J = 4.0), 3.96 (dd, 1H, J = 6.0, 4.0 Hz ), 4.24 (dd, 1H, J = 7.5, 4.0 Hz), 4.45 (d, 1H, J = 12.0 Hz), 4.53 (d, 1H, J = 11.5 Hz), 4.63 (d, 1H, J = 11.5 Hz ), 4.70 (d, 1H, J = 12.0 Hz), 4.76 (d, 1H, J = 11.5 Hz), 4.88 (d, 1H, J = 11.5 Hz), 6.26 (dd, 1H, J = 16.0, 7.5 Hz ), 6.43 (d, 1 H, J = 16.0 Hz), 7.27-7.40 (m, 20 H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 61.31, 70.35, 71.86, 74.19, 74.55, 78.82, 81.01, 126.72, 127.53, 127.83, 127.91, 127.98, 128.06, 128.21, 128.34, 128.58, 128.62, 128.81, 128.99, 134.85, 134.85. , 136.69, 136.81, 138.29, 138.48, 138.63; HRMS (FAB) Calcd for C ₃₃ H ₃₅ O ₄ [M + H ⁺ ] 495.2535, found 495.2547.

(Step 2) (3R, 4S, 5R) -1- Phenylhepta -1,6- Dien -3,4,5-triyl) Tris ( Oxy ) Tris ( Methylene) tribenzene Synthesis of Formula 3

Anhydrous CH ₂ Cl ₂ (18 mL) solution of (2R, 3S, 4S) -2,3,4-tris (benzyloxy) -6-phenylhex-5-en-1-ol (2.28 g, 4.61 mmol) To Dess-Martin periodinane (5.87 g, 13.83 mmol) was added at 0 ° C., stirred at room temperature for 1.5 hours, the reaction mixture was diluted with CH ₂ Cl ₂ and NaHCO ₃ Washed with saturated aqueous solution and brine, dried over anhydrous MgSO ₄ and concentrated under reduced pressure. The obtained aldehyde proceeded to the next reaction without purification. NaHMDS (13.83 mL, 13.83 mmol) was added to anhydrous THF (15 mL) solution of MePPh ₃ Br (4.94 g, 13.83 mmol), stirred at 0 ° C. for 1 hour, and then aldehyde was slowly added at 0 ° C. and 15 minutes at room temperature. Was stirred. The reaction mixture was diluted with EtOAc, washed with H ₂ O and brine, dried over anhydrous MgSO ₄ and concentrated under reduced pressure. The obtained residue was column chromatographed to give 57% (3R, 4S, 5R) -1-phenylhepta-1,6-diene-3,4,5-triyl) tris (oxy) tris (methylene) tribenzene. Z: E = 3.4: 1).

(3)

R f = 0.25 (Hexane / EtOAc 15: 1); [a] _D ²⁵ -73.3 ( c 0.3, CHCl ₃ ); Z isomer : ¹ H NMR (500 MHz, CDCl ₃ ) δ 3.65-3.74 (m, 1H), 4.01 (d, 1H, J = 10.0 Hz), 4.16 (dd, 1H, J = 4.5, 6.0 Hz), 4.25- 4.33 (m, 2H), 4.62-4.48 (m, 3H), 4.89 (dd, 1H, J = 7.5, 10.0 Hz), 5.22-5.39 (m, 2H), 5.78 (dd, 0.7H, J = 10.0, 11.5 Hz), 5.91-5.98 (m, 1H), 6.33 (m, 0.3H), 6.67 (d, 0.3H, J = 16.0 Hz), 6.91 (d, 0.7H, J = 12.0 Hz), 7.09-7.50 (m, 20 H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 70.21, 70.97, 73.67, 75.47, 80.44, 83.68, 118.35, 126.90, 127.41, 127.58, 127.68, 127.71, 127.90, 128.03, 128.22, 128.36, 128.40, 128.47, 128.52, 128.52 , 128.55, 128.58, 128.62, 128.73, 128.82, 129.46, 130.53, 134.95, 136.30, 136.54, 136.92, 138.54, 138.65, 138.94; E isomer : ¹ H NMR (500 MHz, CDCl ₃ ) δ 3.83-3.86 (m, 1H), 4.04 (dd, 1H, J = 6.0, 2.5 Hz), 4.13-4.16 (m, 1H), 4.37 (dd, 2H , J = 11.5, 12.0 Hz), 4.62-4.66 (m, 2H), 4.77-4.84 (m, 2H), 5.25 (d, 1H, J = 17.0 Hz), 5.35 (dd, 1H, J = 11.5, 10.5 Hz), 5.89-5.96 (m, 1H), 6.21-6.26 (m, 1H), 6.51 (d, 1H, J = 16.0 Hz), 7.19-7.48 (m, 20H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 70.54, 74.61, 77.02, 80.82, 81.19, 83.15, 119.59, 126.90, 127.41, 127.66, 127.68, 127.95, 128.38, 128.55, 128.57, 128.58, 128.80, 128.76, 134.53 , 136.91, 138.78,138.84, 138.96; HRMS (FAB) Calcd for C ₃₄ H ₃₄ O ₃ [M + H ⁺ ] 490.2508, found 490.2514.

(Step 3) Synthesis of benzyl (3R, 4R, 5R) -4,5-bis (benzyloxy) -1-phenylhepta-1,6-diene-3-ylcarbamate (Formula 4)

Anhydrous THF of (3R, 4S, 5R) -1-phenylhepta-1,6-diene-3,4,5-triyl) tris (oxy) tris (methylene) tribenzene (3.6 g, 7.34 mmol) (29 ㎖) solution was added CSI (1.95 mL, 21.96 mmol) and Na ₂ CO ₃ (3.5 g, 33.03 mmol) and stirred at 0 ° C. for 24 hours. 25% Na ₂ SO ₃ (10 mL) was added to the reaction mixture, which was stirred for 24 hours at room temperature. Then, the mixture was diluted with EtOAc, washed with H ₂ O and brine, dried over anhydrous MgSO ₄ , and concentrated under reduced pressure. The obtained residue was column chromatographed to give benzyl (3R, 4R, 5R) -4,5-bis (benzyloxy) -1-phenylhepta-1,6-diene-3-ylcarbamate 74% (Z: E =). 2.5: 1, anti: syn = 24: 1).

[Formula 4]

R f = 0.31 (Hexane / EtOAc 5: 1); _{^{[a] D 25 -14.9 (c}} 1.0, CHCl 3); ¹ H NMR (500 MHz, CDCl ₃ ) δ 3.50-3.53 (t, 0.71H, J = 4.5 Hz), 3.60-3.61 (br, 0.29H), 3.91-4.01 (m, 1H), 4.32 (d, 0.29 H, J = 11.5 Hz), 4.33 (d, 0.71H, J = 12.0 Hz), 4.60-4.77 (m, 3.29H), 5.01-5.15 (m, 4.13H), 5.29 (d, 0.29H, J = 17.0 Hz), 5.38 (d, 0.29H, J = 10.0 Hz), 5.53 (t, 0.71H, J = 12.0, 10.0 Hz), 5.70-5.84 (m, 1.71H), 5.90-5.99 (m, 0.29H ), 6.00 (dd, 0.29H, J = 15.5, 7.5 Hz), 6.52 (d, 0.29H, J = 15.5 Hz), 6.53 (d, 0.71H, J = 15.5 Hz), 7.23-7.36 (m, 20H) ); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 49.69, 66.67, 70.64, 73.65, 81.86, 81.94, 119.76, 120.06, 126.80, 127.51, 127.94, 127.99, 128.09, 128.17, 128.40, 128.55, 128.66, 128.69, 132.55, 132.85, 132.85 , 134.88, 135.12, 136.58, 137.05, 138.14, 138.33, 155.99; HRMS (FAB) C ₃₅ H ₃₆ NO ₄ [M + H ⁺ ] 534.2644, found 534.2639.

(Step 4) benzyl (1R, 4R, 5R) -4,5- Bis (benzyloxy) cyclopent -2- Of enylcarbamate (Formula 5)  synthesis

Anhydrous toluene solution of benzyl (3R, 4R, 5R) -4,5-bis (benzyloxy) -1-phenylhepta-1,6-diene-3-ylcarbamate (3.13 g, 5.87 mmol) (59 mL) Grubbs Catalyst (0.24 g, 0.29 mmol) was added thereto, stirred at 80 ° C. for 4 hours, filtered and concentrated through Celite, followed by column chromatography to obtain benzyl (1R, 4R, 5R) -4,5-bis. (Benzyloxy) cyclopent-2-enylcarbamate was obtained in 84% yield.

[Chemical Formula 5]

R f = 0.19 (Hexane / EtOAc 4: 1); [a] _D ²⁵ -32.9 ( c 1.0, CHCl ₃ ); ¹ H NMR (500 MHz, CDCl ₃ ) δ 4.09 (br t, 1H, J = 5.5 Hz), 4.52-4.61 (m, 5H), 4.90-4.93 (br, 1H), 5.12 (s, 2H), 5.19 (d, 1H, J = 7.5 Hz), 5.95 (d, 1H, J = 6.0 Hz), 6.03 (d, 1H, J = 5.5 Hz), 7.27-7.40 (m, 15H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 55.67, 66.99, 71.92, 72.79, 82.56, 86.81, 128.00, 128.09, 128.17, 128.22, 128.34, 128.61, 128.67, 128.72, 128.74, 132.89, 134.65, 136.76, 137.77, 138.37 , 156.37; HRMS (FAB) Calcd for C ₂₇ H ₂₈ NO ₄ [M + H ⁺ ] 430.2018, found 430.2020.

(Step 5) (1R, 2R, 3R) -3- Aminocyclopentane -1,2- Of diol (Formula 6)  synthesis

6N HCl (1.5 mL) was added to MeOH (3 mL) of benzyl (1R, 4R, 5R) -4,5-bis (benzyloxy) cyclopent-2-enylcarbamate (0.1349 g, 0.314 mmol) and 10% After stirring for 24 hours at room temperature under a Pd / C catalyst, hydrogen gas conditions, and filtered through Celite (Celite), and then chromatographed with ion adsorption exchange resin (1R, 2R, 3R) -3-aminocyclo Pentane-1,2-diol was obtained in 94% yield. The (1R, 2R, 3R) -3-aminocyclopentane-1,2-diol prepared in the present invention was named LKI-24 and the experiment was performed.

[Formula 6]

R f = 0.16 (CH ₂ Cl ₂ / MeOH 1: 2); [a] _D ²² -2.3 ( c 1.0, MeOH); ¹ H NMR (500 MHz, D ₂ O) δ 1.43-1.50 (m, 2H), 1.53-1.58 (m, 2H), 2.01-2.14 (m, 1H), 3.50-3.58 (m, 1H), 3.90- 3.93 (m, 1 H), 4.12-4.17 (m, 1 H); ¹³ C NMR (125 MHz, D ₂ O) δ 25.85, 28.93, 51.91, 76.17, 76.54; HRMS (FAB) Calcd for C ₅ H ₁₂ NO ₄ [M + H ⁺ ] 118.0865, found 118.0868.

Example  1: beta- Hexosaminidase  analysis ( beta - hexosaminidase assay )

To determine the effect of LKI-24 ((1R, 2R, 3R) -3-aminocyclopentane-1,2-diol) on the degranulation of mast cells, a beta-hexosaminidase assay was performed. . The beta-hexosaminidase is an inflammatory mediator released due to degranulation of mast cells.

First of all, Rat basophilic The leukemia cell line RBL-2H3 cell line was dispensed in MEM medium containing 15% FBS, 100 units / ml penicillin and streptomycin and 2 × 10 ⁵ cells / well in 24-well plates at 37 ° C., 5% CO ₂ conditions. Then incubated for 24 hours. After removal of the supernatant, MEM medium containing 25 ng / ml of anti-DNP IgE was added and incubated for 4 hours, washed twice with 500 μl of PIPES buffer, 4 mM MgCl ₂ , 5.6 mM glucose, 0.1%. 180 μl of PIPES buffer solution containing BSA was added and incubated for 10 minutes. The cells were pre-cultured and treated with LKI-24 at concentrations of 100, 200, and 300 μΜ for 20 minutes, and then reacted for 20 minutes by adding 50 ng / ml of DNP-BSA. After the cells were left on ice for 10 minutes to terminate the reaction, the supernatant was dispensed in a 25-well plate in a 96-well plate, and 1 mM P-nitrophenyl-acetyl-β-D-glucosaminid was added to each well. After the addition of 25 μl it was reacted for 1 hour at 37 ℃. After the reaction was terminated by adding stop solution (0.1M NaHCO ₃ , 0.1M Na ₂ CO ₃ ), the absorbance was measured using an ELISA reader at 405 nm wavelength.

As a result, it was observed that the degranulation of mast cells was inhibited in proportion to the concentration of LKI-24 (FIG. 1). From these results, the degranulation inhibitory effect of the mast cells of LKI-24 did not reach that of ketotifen, It was confirmed that it can be considered as a new material showing degranulation inhibitory ability.

Example  2: Reverse transcription  Polymerase chain reaction Reverse - Transcriptase Polymerase  Chain Reaction ; RT - PCR )

In order to confirm the activity of inflammatory mediators caused by allergic to LKI-24 at the gene level, reverse transcriptase polymerase chain reaction was performed.

RBL-2H3 cells were dispensed into 6-well plates at 1 × 10 ⁶ cells / well, followed by reaction for 4 hours with the addition of IgE. Each well of the plate was treated with different concentrations of samples, and DNP-BSA was added and reacted at 37 ° C. for 20 minutes. After washing twice with PBS, the cells were lysed by the addition of Trizol (Invitrogen), followed by the addition of chloroform (Sigma) and centrifugation at 13,000 rpm for 15 minutes to obtain a supernatant. RNA was precipitated by the reaction of the obtained supernatant by the addition of isopropanol, and the precipitate was washed once with ethanol to separate RNA. After synthesis of cDNA using 1 μg of the isolated total RNA, using Superscript (Invitrogen) and primers for inflammation-related genes 45 seconds at 94 ℃, 45 seconds at 55 ℃, 1 minute 30 at 72 ℃ RT-PCR was performed by reacting for 35 cycles under the conditions of seconds, and GAPDH was used as a control gene. Each primer is listed in Table 1.

As a result, when LKI-24 was treated at a concentration of 300 μΜ, expression of inflammatory mediators such as COX-2, TNF-α, IL-4, and IL-10 was suppressed, and its effect was higher than that of ketotifen, a positive control. It was observed that the excellent (Fig. 2), from the results confirmed the inhibitory activity against the inflammatory mediators of LKI-24.

Gene name primer SEQ ID NO: rCOX-2 F: 5 'TGT ATG CTA CCA TCT GGC TTC GG 3' One R: 5 'GTT TGG AAC AGT CGC TCG TCA TC 3' 2 rTNF-a F: 5 'CAC CAC GCT CTT CTG TCT ACT GAA C 3' 3 R: 5 'CCG GAC TCC GTG ATG TCT AAG TAC T 3' 4 rIL-4 F: 5 'ACC TTG CTT CAC CCT GTT C 3' 5 R: 5 'TTG TGA GCG TGG ACT CAT TC 3' 6 rIL-10 F: 5 'TAG AAG TGA TGC CCC AGG 3' 7 R: 5 'TCA TCC TCC ACC TGC TCC ACT GC 3' 8 GAPDH F: 5 'GAG TCA ACG GAT TTG GTC GT 3' 9 R: 5 'GAC AAG CTT CCC GTT CTC AG 3' 10

Example  3. Western Blot  analysis ( Western blot assay )

In order to identify the anti-allergic signaling pathway by LKI-24 at the protein level, Western blot analysis was performed.

RBL-2H3 cells were sensitized with IgE, and the cells stimulated with DNP-BSA were washed with PBS, followed by lysis buffer (50 mM Tris-HCl, pH 8.0, 150 mM sodium chloride, 1% NP-40, 0.5% sodium deoxycholate). , 0.1% sodium dodecyl sulfate). Proteins were extracted and quantified by centrifugation at 13,000 rpm for 20 minutes and denatured for 5 minutes at 100 ° C. After quantitative protein electrophoresis using 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), the electrophoretic proteins were transferred to a nitrocellulose membrane, and the nitrocellulose membrane was transferred to 0.1% Tween. Blocked with TBS-T buffer containing 20 and 5% skim dried milk. After reacting the protein of the nitrocellulose membrane with a primary antibody (1: 1,000) and a secondary antibody (1: 10,000) complexed with horseradish peroxidase, an ECL western detection reagent was used. To confirm the desired protein (FIG. 3).

As a result, p-AKT activity was similarly inhibited in the ketotifen treatment group and LKI-24 treatment group, and p-ERK, p-JNK, p-p38, and COX-2 activities were proportional to LKI-24 concentration. Observed inhibition. From the above results, it was confirmed that LKI-24 is effective in the control of inflammatory signaling by allergy.

Example  4. NF -KB Lucifer Reyes  analysis ( NF -KB luciferase assay )

In order to confirm the activity of NF-κB by LKI-24 at the protein level, NF-κB luciferase assay was performed.

After incubating 293T cells in 24-well plates at 5 × 10 ⁴ cells / well, the SV40 plasmid and NF-κB plasmid were transfected into cells using lipofectamine (Invitrogen), and after 24 hours, LKI -24 was treated by concentration. After washing the cells with PBS, 200 웰 of lysis buffer was added to each well to lyse the cells, and luciferase activity was measured using a luciferase assay system (Promega).

As a result, it was observed that the expression of NF-κB was inhibited in proportion to the concentration of LKI-24, which was similar to the effect by ketotifen, a positive control (Fig. 4). From the above results, it was confirmed that LKI-24 can suppress allergic inflammation by controlling the activation of NF-κB.

Example 5. Lipoxygenase Assay

In order to measure the antiallergic function in the allergic inflammatory response of LKI-24, lipoxygenase assay was performed. Lipoxigenase produces many substances from linoleic acid that serve as a variety of chemical mediators involved in in vivo inflammatory and allergic reactions. Therefore, it can be assumed that a substance that inhibits lipoxygenase will be effective for allergy since it will result in suppressing the production of various chemical mediators.

To 20 ml of 0.1 M Tris buffer (pH 8.5), add 20 μl of LKI-24 at 100, 200, 300 μΜ concentration and mix 20 μl of linoleic acid (final concentration 110 μΜ) at room temperature. Pre-reaction for 5 minutes. After 20 μl of soybean lipoxygenase (Type V, 500 UNIT / final concentration) was added to the reaction solution for 5 minutes, the absorbance was measured at 234 nm using a UV-spectrometer (PerkinElmer). . As a positive control, NDGA (nordihydroguaiaretic acid), a phenolic food antioxidant, was used. The IC ₅₀ value of each sample was measured to evaluate lipoxygenase inhibitory activity.

As a result, the concentration of 50% inhibition of lipoxygenase was 150.77 μΜ for LKI-24 and 74.6 μΜ for NDGA, respectively (Table 2). From these results, the effect of LKI-24 did not reach that of NDGA. It was confirmed that it can be considered as an antiallergic substance that inhibits lipoxygenase.

Sample IC ₅₀  (μΜ) LKI-24 150.77 NDGA 74.6

Attach an electronic file to a sequence list

Claims (10)

A composition for anti-allergy, comprising a compound represented by the following formula (1) as an active ingredient, wherein the allergy is by mast cell-mediated composition.
[Formula 1]

The composition of claim 1 having one or more of the following features.
(i) inhibition of expression of COX-2, TNF-α, IL-4, and IL-10 genes; (Ii) inhibition of activation of AKT-, ERK-, JNK-, and p38- signaling pathways; (Iii) inhibit the activity of NF-κB; And (iii) inhibition of the activity of lipoxygenase.
A pharmaceutical composition for preventing or treating mast cell-mediated allergy, comprising the composition of claim 1 or 2 as an active ingredient.
The pharmaceutical composition of claim 3, wherein the pharmaceutical composition is a tablet, pill, powder, granule, capsule, suspension, liquid solution, emulsion, syrup, sterilized aqueous solution, non-aqueous solvent, suspension, emulsion, lyophilized agent and suppository. Pharmaceutical composition for the prevention or treatment of mast cell-mediated allergy, characterized in that it has any one formulation selected from the group consisting of.
A food composition for preventing or improving mast cell-mediated allergy, comprising the composition of claim 1 or 2 as an active ingredient.
The method of claim 5, wherein the food composition is from the group consisting of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes Food composition for the prevention or improvement of mast cell-mediated allergy, characterized in that any one selected.
A quasi-drug composition for preventing or improving mast cell-mediated allergy, comprising the composition of claim 1 or 2 as an active ingredient.
According to claim 7, wherein the quasi-drug composition is used for the production of any one selected from the group consisting of disinfecting detergent, shower foam, gagreen, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment and filter filler. A quasi-drug composition for the prevention or improvement of mast cell-mediated allergies to
A cosmetic composition for preventing or improving mast cell-mediated allergy, comprising the composition of claim 1 or 2 as an active ingredient.
10. The method of claim 9, wherein the formulation of the cosmetic composition is softening longevity, astringent makeup, nourishing longevity, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion , Body cream, body oil, body essence, make-up base, foundation, hair dye, shampoo, rinse and body cleanser for the prevention or improvement of mast cell-mediated allergy, characterized in that it has any one selected from the group consisting of Cosmetic composition.

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