Composition for preventing, ameliorating or treating rhinitis comprising brazilin as effective component

Abstract

The present invention relates to a composition for the prevention, improvement, or treatment of rhinitis comprising brazilin as an active ingredient. More specifically, it has been confirmed that the brazilin of the present invention improves sneezing and nasal scratching, which are clinical allergic symptoms of allergic rhinitis, reduces the levels of serum IgE, histamine, and cytokines (IL-4, IL-5) increased by the induction of allergic rhinitis, as well as the thickness of the nasal epithelium and the number of goblet cells, and reduces the levels of cytokines (TNF-α, IL-6, IL-1β) increased by the induction of non-allergic rhinitis. Therefore, it can be usefully used in pharmaceuticals, health functional foods, quasi-pharmaceuticals, etc., for the prevention, improvement, or treatment of rhinitis.

Description

Technology Field

[0001] The present invention relates to a composition for the prevention, improvement, or treatment of rhinitis comprising brazilin as an active ingredient. Background Technology

[0002] Rhinitis refers to an inflammatory disease of the nasal mucosa accompanied by one or more symptoms such as rhinorrhea (runny nose), sneezing, itching, and nasal congestion. However, since it is practically difficult to confirm the inflammatory response within the nasal cavity itself during diagnosis, the diagnosis is typically based on the presence or absence of symptoms such as itching, sneezing, rhinorrhea, and nasal congestion.

[0003] Rhinitis can be broadly classified into allergic rhinitis and non-allergic rhinitis. While most people associate rhinitis with allergies, non-allergic rhinitis is also common. In particular, non-allergic rhinitis is frequently observed in adults and the elderly. When looking at the overall frequency including children, it is reported that allergic rhinitis accounts for 43%, non-allergic rhinitis for 23%, and a mixed type for 34%.

[0004] Allergic rhinitis and non-allergic rhinitis share similar symptoms, such as runny nose and nasal congestion, making it difficult to distinguish them based on symptoms alone. Of course, sneezing, nasal itching, and eye itching tend to be less common in non-allergic rhinitis. If rhinitis symptoms are suspected, a skin prick test or serum-specific IgE test is performed; if positive, the correlation with symptoms is confirmed to diagnose allergic rhinitis. If negative, a nasal cytology test is performed to check the eosinophil count; if elevated, eosinophilic non-allergic rhinitis is considered, while if normal, various types of non-allergic rhinitis, such as vasomotor rhinitis, may be considered. Even in cases of allergic rhinitis, skin prick tests or serum-specific IgE tests may yield negative results; this occurs when specific IgE is produced only in the nasal mucosa rather than systemically, and is diagnosed as localized allergic rhinitis.

[0005] Since non-allergic rhinitis has no identifiable cause, avoidance therapy and immunotherapy are not applicable, and the only option is to attempt to control it through medication. However, medication is known to be not very effective. Due to the scarcity of studies on patients with non-allergic rhinitis and the lack of guidelines for drug treatment, pharmacological treatment of the condition is difficult in clinical practice.

[0006] Regarding prior art related to brazilin, Korean Published Patent No. 2013-0060834 discloses a pharmaceutical composition having an osteoporosis-inhibiting effect containing brazilin or a pharmaceutically acceptable salt thereof as an active ingredient, and Korean Published Patent No. 2023-0143477 discloses a pharmaceutical composition for the prevention or treatment of cancer containing brazilin as an active ingredient. However, there has not yet been any disclosure regarding the 'composition for the prevention, improvement, or treatment of rhinitis containing brazilin as an active ingredient' of the present invention. The problem to be solved

[0007] The present invention was derived from the above-mentioned needs. The present invention provides a composition for the prevention, improvement, or treatment of rhinitis comprising brazilin as an active ingredient. More specifically, the present invention was completed by confirming that the brazilin of the present invention improves sneezing and nasal scratching, which are clinical allergic symptoms of allergic rhinitis; reduces the serum levels of IgE, histamine, and cytokines (IL-4, IL-5) increased by the induction of allergic rhinitis, as well as the thickness of the nasal epithelium and the number of goblet cells; and reduces the levels of cytokines (TNF-α, IL-6, IL-1β) increased by the induction of non-allergic rhinitis. means of solving the problem

[0008] To solve the above problem, the present invention provides a health functional food composition for the prevention or improvement of rhinitis comprising brazilin represented by Chemical Formula 1 or a food-grade acceptable salt thereof as an active ingredient.

[0009] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of rhinitis comprising brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0010] In addition, the present invention provides a quasi-drug for the prevention or improvement of rhinitis comprising brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0011] In addition, the present invention provides a veterinary composition for the prevention or treatment of rhinitis comprising brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0012] In addition, the present invention provides a feed additive for the prevention or improvement of rhinitis comprising brazilin represented by Formula 1 or a food-grade acceptable salt thereof as an active ingredient.

[0013] In addition, the present invention provides a method for preventing or treating rhinitis comprising the step of administering brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof to an individual other than a human. Effects of the invention

[0014] The present invention relates to a composition for the prevention, improvement, or treatment of rhinitis comprising brazilin as an active ingredient. More specifically, the brazilin of the present invention improves sneezing and nasal scratching, which are clinical allergic symptoms of allergic rhinitis; reduces the serum levels of IgE, histamine, and cytokines (IL-4, IL-5) and the thickness of nasal epithelium and the number of goblet cells that are increased by the induction of allergic rhinitis; and reduces the levels of cytokines (TNF-α, IL-6, IL-1β) that are increased by the induction of non-allergic rhinitis. Brief explanation of the drawing

[0015] Figure 1 shows the results of confirming the reduction effect of nasal scratching (A) and sneezing (B) symptoms following the administration of Brazilin of the present invention in an animal model of allergic rhinitis induction. CON is the normal control group, HDM is the allergic rhinitis induction group treated with house dust mites, Brazilin-0.05 is the group administered 0.05 mg / kg of Brazilin, Brazilin-0.1 is the group administered 0.1 mg / kg of Brazilin, Brazilin-0.5 is the group administered 0.5 mg / kg of Brazilin, and DEX is the positive control group administered dexamethasone. *** indicates that the number of nasal scratching and sneezing in the allergic rhinitis induction group increased statistically significantly compared to the normal control group, with p<0.001. ##, ### indicates that the number of nose scratching and sneezing episodes in the brazilin administration group of the present invention or the positive control dexamethasone administration group (DEX) was statistically significantly reduced compared to the allergic rhinitis induction group, where ## is p<0.01 and ### is p<0.001. Figure 2 shows the results confirming the effect of reducing serum total IgE and HDM-specific IgE levels following the administration of the brazilin of the present invention in an animal model of allergic rhinitis induction. CON is the normal control group, HDM is the allergic rhinitis induction group treated with house dust mites, Brazilin-0.05 is the group administered 0.05 mg / kg of brazilin, Brazilin-0.1 is the group administered 0.1 mg / kg of brazilin, Brazilin-0.5 is the group administered 0.5 mg / kg of brazilin, and DEX is the positive control group administered dexamethasone. *** indicates that serum total IgE and HDM-specific IgE levels in the allergic rhinitis induction group increased statistically significantly compared to the normal control group, with p<0.001. ##, ### indicates that the total IgE and HDM-specific IgE levels in the serum of the brazilin administration group of the present invention or the positive control group, dexamethasone administration group, were statistically significantly reduced compared to the allergic rhinitis induction group, with ## being p<0.01 and ### being p<0.001. Figure 3 shows the results confirming the effect of reducing serum histamine content following the administration of the brazilin of the present invention in an animal model of allergic rhinitis induction. CON is the normal control group, HDM is the allergic rhinitis induction group treated with house dust mites, Brazilin-0.05 is the group administered 0.05 mg / kg of brazilin, Brazilin-0.1 is the group administered 0.1 mg / kg of brazilin, Brazilin-0.5 is the group administered 0.5 mg / kg of brazilin, and DEX is the positive control group administered dexamethasone. *** indicates that the serum histamine content of the allergic rhinitis induction group increased statistically significantly compared to the normal control group, with p<0.001. ### indicates that the serum histamine content of the brazilin administration group of the present invention or the positive control group dexamethasone administration group (DEX) was statistically significantly reduced compared to the allergic rhinitis induction group, with p<0.001. Figure 4 shows the results confirming the effect of reducing serum IL-4(A) and IL-5(B) levels following the administration of the brazilin of the present invention in an animal model of allergic rhinitis induction. CON is the normal control group, HDM is the allergic rhinitis induction group treated with house dust mites, Brazilin-0.05 is the group administered 0.05 mg / kg of brazilin, Brazilin-0.1 is the group administered 0.1 mg / kg of brazilin, Brazilin-0.5 is the group administered 0.5 mg / kg of brazilin, and DEX is the positive control group administered dexamethasone. *** indicates that the serum IL-4 and IL-5 levels in the allergic rhinitis induction group increased statistically significantly compared to the normal control group, with p<0.001. ### indicates that the serum IL-4 and IL-5 content of the brazilin administration group of the present invention or the positive control group dexamethasone administration group was statistically significantly reduced compared to the allergic rhinitis induction group, with p<0.001. Figure 5 shows the results of confirming the effect of reducing the thickness of the nasal epithelium following the administration of the brazilin of the present invention in an animal model of allergic rhinitis induction. CON is the normal control group, HDM is the allergic rhinitis induction group treated with house dust mites, Brazilin 0.05 is the group administered 0.05 mg / kg of brazilin, Brazilin 0.1 is the group administered 0.1 mg / kg of brazilin, Brazilin 0.5 is the group administered 0.5 mg / kg of brazilin, and DEX is the positive control group administered 1 mg / kg of dexamethasone. Figure 6 shows the results of confirming the effect of reducing goblet cells associated with mucus production following the administration of the brazilin of the present invention in an animal model of allergic rhinitis induction. CON is the normal control group, HDM is the allergic rhinitis induction group treated with house dust mites, Brazilin 0.05 is the group administered 0.05 mg / kg of brazilin, Brazilin 0.1 is the group administered 0.1 mg / kg of brazilin, Brazilin 0.5 is the group administered 0.5 mg / kg of brazilin, and DEX is the positive control group administered 1 mg / kg of dexamethasone. Figure 7 shows the results confirming the effect of reduced TNF-α (A), IL-6 (B), and IL-1β (C) content following treatment with the brazilin of the present invention in nasal cells induced with non-allergic rhinitis. CON is the normal control group, LPS is the non-allergic rhinitis-induced group treated with 5 μg / ml LPS, Brazilin-1 is the group treated with 1 μg / ml brazilin, Brazilin-5 is the group treated with 5 μg / ml brazilin, and Brazilin-10 is the group treated with 10 μg / ml brazilin. *** indicates that the content of TNF-α, IL-6, and IL-1β in the non-allergic rhinitis-induced group increased statistically significantly compared to the normal control group, with p<0.001. #, ##, and ### indicate that the content of TNF-α, IL-6, and IL-1β in the brazilin-treated group of the present invention was statistically significantly reduced compared to the allergic rhinitis-induced group, where # is p<0.05, ## is p<0.01, and ### is p<0.001. Specific details for implementing the invention

[0016] To achieve the objective of the present invention, the present invention provides a health functional food composition for the prevention or improvement of rhinitis comprising, as an active ingredient, brazilin represented by the following chemical formula 1 or a food-grade acceptable salt thereof.

[0017]

[0018] The above rhinitis may be any one selected from the group consisting of allergic rhinitis, infectious rhinitis, idiopathic rhinitis, vasomotor rhinitis, eosinophilic non-allergic rhinitis syndrome, hormonal rhinitis, drug-induced rhinitis, food-related rhinitis, emotional rhinitis, and atrophic rhinitis, but is not limited thereto.

[0019] The above allergic rhinitis may be rhinitis caused by house dust mites, but is not limited thereto.

[0020] The above "acceptable salts" refer to any salts of the compounds of the present invention that do not exhibit toxicity or are not unsuitable for food or pharmaceutical use while maintaining the biological properties of the compounds of the present invention. Such salts may be derived from, and include, various organic and inorganic counterions known in the art. These salts include organic or inorganic acids, such as hydrochloric acid, hydrobromide, sulfuric acid, nitric acid, phosphoric acid, sulfamic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, glutaric acid, pyruvate, lactic acid, malonic acid, succinic acid, sorbic acid, ascorbic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, chrysanthenic acid, cinnamic acid, mandelic acid, phthalic acid, lauric acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, Camponic acid, camphorsulfonic acid, 4-methylbicyclo [2.2.Acid addition salt formed with [2]-oct-2-en-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, cyclohexylsulfamic acid, quinic acid, or muconic acid, etc.; Or, it may include salts formed when an acidic proton present in the parent compound is substituted with a metal ion (e.g., alkali metal ion, alkaline earth metal ion, or aluminum ion), an alkali metal or alkaline earth metal hydroxide (e.g., sodium, potassium, calcium, magnesium, aluminum, lithium, zinc, and barium hydroxide), or ammonia, or coordinately bonded with an organic base, such as an aliphatic, alicyclic, or aromatic organic amine, such as ammonia, methylamine, dimethylamine, diethylamine, picoline, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylene-diamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, N-methylglucarmine, piperazine, tris(hydroxymethyl)-aminomethane, or tetramethylammonium hydroxide.

[0021] In addition, examples of salts include sodium, potassium, calcium, magnesium, ammonium, or tetraalkylammonium salts, and in cases where the compound contains a basic functional group, salts with non-toxic organic or inorganic acids, such as hydrohalides (e.g., hydrochloride or hydrobromide), sulfates, phosphates, sulfamates, nitrates, acetates, trifluoroacetate, trichloroacetate, propionates, hexanoates, cyclopentylpropionate, glycolates, glutarates, rubates, lactates, malonates, succinates, sorbates, ascorbates, maleates, fumarates, tartarates, citrates, benzoates, 3-(4-hydroxybenzoyl fumarate), tartarates, citrates, benzoates, 3-(4-hydroxybenzoyl)benzoates, picrates, It may include cinnamate, mandelate, phthalate, laurate, methanesulfonate mesylate), ethanesulfonate, 1,2-ethane-disulfonate, 2-hydroxyethanesulfonate, benzenesulfonate (besylate), 4-chlorobenzenesulfonate, 2-naphthalenesulfonate, 4-toluenesulfonate, camphorate, camphorsulfonate, 4-methylbicyclo[2.2.2]-oct-2-en-1-carboxylate, glucoheptonate, 3-phenylpropionate, trimethylacetate, tert-butylacetate, lauryl sulfate, gluconate, benzoate, glutamate, hydroxynaphtoate, salicylate, stearate, cyclohexylsulfamate, quinate or muconate salts, etc.

[0022] The above composition is preferably prepared in any one formulation selected from powder, granules, pills, tablets, capsules, candy, syrup, and beverage, but is not limited thereto.

[0023] When the health functional food composition of the present invention is used as a food additive, the active ingredient may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods. The amount of the active ingredient can be appropriately determined according to its purpose of use (prevention or improvement). Generally, when manufacturing food or beverages, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, relative to the raw material. However, in the case of long-term consumption for the purpose of health and hygiene or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.

[0024] There are no specific restrictions on the types of the above-mentioned foods. Examples of foods to which the above-mentioned active ingredients may be added include meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and include all health functional foods in the conventional sense.

[0025] When the composition of the present invention is used as a health beverage, it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The aforementioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As sweeteners, natural sweeteners such as taumarin and stevia extract, or synthetic sweeteners such as saccharin or aspartame may be used. The proportion of the above natural carbohydrates is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention. The composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain 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, the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

[0026] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of rhinitis comprising brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0027] In the pharmaceutical composition of the present invention, the rhinitis is as described above.

[0028] In the pharmaceutical composition of the present invention, the "acceptable salt" is as described above.

[0029] The composition of the present invention may further include pharmaceutically acceptable carriers, excipients, or diluents in addition to the active ingredient, and may be in various oral or parenteral formulations. When formulating, it is prepared using commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants, and other diluents or excipients. Solid formulations for oral administration include capsules, powders, granules, tablets, pills, etc., and these solid formulations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., with one or more compounds. In addition, lubricants such as magnesium stearate and talc are also used in addition to simple excipients. Liquid formulations for oral administration include suspensions, emulsions, syrups, and aerosols; in addition to commonly used simple diluents such as water and liquid paraffin, they may contain various excipients, such as humectants, sweeteners, flavorings, and preservatives. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized agents, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspension solvents. Witepsol, Macrogol, Tween 61, cocoa dough, laurin dough, and glycerogelatin may be used as bases for suppositories. For parenteral administration, it is preferable to select a method of topical application or injection via the abdominal cavity, rectum, vein, muscle, subcutaneous, intrauterine dura mater, or cerebrovascular system.

[0030] The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the level of the effective amount may be determined according to factors including the type and severity of the patient's disease, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as a single or multiple doses. It is important to administer an amount that obtains maximum effect with a minimum amount without side effects by taking all of the above-mentioned factors into account, and this can be easily determined by a person skilled in the art.

[0031] The dosage of the composition of the present invention varies depending on the patient's body weight, age, gender, health status, diet, time of administration, method of administration, excretion rate, and severity of the disease. The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modulators.

[0032] In addition, the present invention provides a quasi-drug for the prevention or improvement of rhinitis comprising brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0033] The term "quasi-drug" used in the present invention refers to articles used for the purpose of diagnosing, treating, improving, alleviating, managing, or preventing diseases of humans or animals, and which have a milder effect than pharmaceuticals. For example, according to the Pharmaceutical Affairs Act, quasi-drugs are defined as articles excluding those used for pharmaceutical purposes, and include products used for the treatment or prevention of diseases of humans or animals, or products that have a mild effect on the human body or do not act directly on it.

[0034] The quasi-drug of the present invention is used for the purpose of improving rhinitis, and there are no particular limitations on its formulation. In each formulation, other ingredients may be arbitrarily selected and combined according to the formulation or purpose of use of other quasi-drugs. The amount of the active ingredient can be appropriately determined according to the purpose of use (inhibition or alleviation). For example, it may include conventional adjuvants such as thickeners, stabilizers, solubilizers, vitamins, pigments, and fragrances, as well as carriers.

[0035] In addition, the present invention provides a veterinary composition for the prevention or treatment of rhinitis comprising brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0036] A veterinary composition containing the active ingredient of the present invention may further include suitable excipients and diluents according to conventional methods. Examples of excipients and diluents that may be included in a veterinary composition containing the active ingredient of 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, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.

[0037] A veterinary composition containing an active ingredient according to the present invention may further include fillers, anticoagulants, lubricants, humectants, spices, emulsifiers, preservatives, etc., and the veterinary composition according to the present invention may be formulated using methods well known in the art to provide rapid, sustained, or delayed release of the active ingredient after administration to an animal, and the formulation may be in the form of a powder, granule, tablet, capsule, suspension, emulsion, solution, syrup, aerosol, soft or hard gelatin capsule, suppository, sterile injectable solution, sterile topical agent, etc.

[0038] The veterinary composition according to the present invention may be administered once or several times a day, depending on the age, sex, and weight of the animal, and the dosage may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, etc. Accordingly, the above dosage does not limit the scope of the present invention in any way.

[0039] In addition, the present invention provides a feed additive for the prevention or improvement of rhinitis comprising brazilin represented by Formula 1 or a food-grade acceptable salt thereof as an active ingredient.

[0040] The feed additive of the present invention corresponds to an auxiliary feed under the Feed Management Act. In the present invention, the term "feed" may refer to any natural or artificial prescribed food, single meal, etc., or the components of said single meal, intended for or suitable for animals to eat, consume, and digest. The types of said feed are not particularly limited, and feeds commonly used in the relevant technical field may be used. Non-limiting examples of said feed include plant-based feeds such as grains, root vegetables, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal, or grain by-products; and animal-based feeds such as proteins, inorganic substances, oils and fats, minerals, single-cell proteins, zooplankton, or food waste. These may be used individually or in a mixture of two or more types.

[0041] In addition, the present invention provides a method for preventing or treating rhinitis comprising the step of administering brazilin represented by Formula 1 or a pharmaceutically acceptable salt thereof to an individual other than a human.

[0042] The present invention will be described in detail below by way of embodiments. However, the following embodiments are merely illustrative of the present invention, and the scope of the present invention is not limited to the following embodiments.

[0043] Example 1. in vivo Improvement effect on allergic rhinitis

[0044] 1) Allergic rhinitis model and sample administration

[0045] In BALB / c mice, 2 mg of aluminum hydroxide and 25 µg of house dust mite (HDM) were injected into the peritoneal cavity a total of three times (days 0, 7, and 14) over a period of 3 weeks, and then allergic rhinitis was induced by administering 25 µg of HDM intranasally from day 21 to day 27. The number of sneezing and nose rubbing incidents was measured for 15 minutes after the last intranasal HDM exposure, blood was collected on day 28, and mouse heads were separated and intranasal lavage fluid was collected and analyzed.

[0046] In the evaluation of efficacy against allergic rhinitis, the positive control dexamethasone (DEX, 1 mg / kg) and the brazilin of the present invention (0.05 mg / kg, 0.1 mg / kg, 0.5 mg / kg; CAS NO. 474-07-7) were orally administered once a day dissolved in PBS for 7 days from day 21 to day 27 of HDM administration, and 8 to 11 animals were used per group.

[0047] 2) Confirmation of changes in clinical symptoms (nasal scratching and sneezing) following the administration of brazilin in an animal model of allergic rhinitis.

[0048] In an animal model of allergic rhinitis induced by the administration of brazilin according to the present invention, the frequency of nasal rubbing and sneezing, which are representative clinical symptoms of rhinitis, was measured.

[0049] As a result, as disclosed in Figure 1, the number of nose scratching and sneezing in the rhinitis-induced group (HDM) increased significantly compared to the normal control group (CON), whereas the number of nose scratching and sneezing in the group administered the brazilin of the present invention decreased statistically significantly.

[0050] 3) Confirmation of a decrease in serum IgE following the administration of brazilin in an animal model of allergic rhinitis.

[0051] The serum IgE levels of an animal model with allergic rhinitis induced by the administration of brazilin according to the present invention were confirmed.

[0052] As a result, as disclosed in Figure 2, total IgE and HDM-specific IgE levels were significantly increased in the rhinitis-induced group (HDM) compared to the normal control group (CON), and in contrast, total IgE and HDM-specific IgE levels were statistically significantly decreased in the brazilin administration group of the present invention.

[0053] 4) Confirmation of reduction in serum histamine and inflammatory cytokines following administration of brazilin in an animal model of allergic rhinitis

[0054] The serum levels of histamine and inflammatory cytokines (IL-4, IL-5) in an animal model of allergic rhinitis induced by the administration of brazilin according to the present invention were examined.

[0055] As a result, as disclosed in Figure 3, histamine levels were significantly increased in the rhinitis-induced group (HDM) compared to the normal control group (CON), and in contrast, histamine levels were statistically significantly decreased in the brazilin administration group of the present invention.

[0056] In addition, it was confirmed that IL-4 and IL-5 levels increased significantly in the rhinitis-induced group (HMD), whereas IL-4 and IL-5 levels decreased statistically significantly in the group administered the brazilin of the present invention (Fig. 4).

[0057] 5) Confirmation of histological improvement in rhinitis following administration of brazilin in an animal model of allergic rhinitis induced

[0058] H&E staining was performed to confirm histopathological changes in nasal tissues in an animal model of allergic rhinitis induced by the administration of brazilin according to the present invention.

[0059] As a result, as disclosed in Fig. 5, the thickness of the nasal epithelium was significantly increased due to the accumulation of increased inflammatory cells in the rhinitis-induced group (HDM) compared to the normal control group (CON), and in contrast, it was confirmed that the thickness of the nasal epithelium of the brazilin administration group of the present invention was reduced.

[0060] In addition, PAS staining was performed to confirm mucus secretion in the nasal tissue, and it was confirmed that goblet cells associated with mucus production increased in the rhinitis-induced group (HDM) compared to the normal group (CON), whereas goblet cells decreased in a concentration-dependent manner in the brazilin administration group of the present invention (Fig. 6).

[0061] Example 2. in vitro Improvement effect on non-allergic rhinitis

[0062] It is known that Th2-dominated cytokines are important in allergic rhinitis, while Th1-dominated inflammatory cytokines (TNF-α, IL-6, IL-1β) are important in non-allergic rhinitis. Therefore, we aimed to confirm the improvement effect on non-allergic rhinitis by treating nasal epithelial cells (HNEpCs) with inflammation induced by LPS (5 μg / ml) with brazilin at different concentrations (1, 5, and 10 μg / ml) and measuring the changes in the content of TNF-α, IL-6, and IL-1β.

[0063] As a result, as disclosed in Figure 7, the levels of TNF-α, IL-6, and IL-1β were significantly increased in the group treated with LPS alone compared to the normal control group (CON), and the levels of inflammatory cytokines were statistically significantly reduced in a concentration-dependent manner in the group treated with the brazilin of the present invention.

Claims

Claim 1 A health functional food composition for the prevention or improvement of rhinitis comprising, as an active ingredient, brazilin represented by the following chemical formula 1 or a food-grade acceptable salt thereof. [Chemical Formula 1] Claim 2 A health functional food composition for the prevention or improvement of rhinitis according to claim 1, characterized in that the rhinitis is any one of the rhinitis selected from the group consisting of allergic rhinitis, infectious rhinitis, idiopathic rhinitis, vasomotor rhinitis, eosinophilic non-allergic rhinitis syndrome, hormonal rhinitis, drug-induced rhinitis, food-related rhinitis, emotional rhinitis, and atrophic rhinitis. Claim 3 A health functional food composition for the prevention or improvement of rhinitis, characterized in that, in paragraph 2, the allergic rhinitis is rhinitis caused by house dust mites. Claim 4 A health functional food composition for the prevention or improvement of rhinitis according to claim 1, characterized in that the composition is manufactured in any one formulation selected from powder, granules, pills, tablets, capsules, candies, syrups, and beverages. Claim 5 A pharmaceutical composition for the prevention or treatment of rhinitis comprising, as an active ingredient, brazilin represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof. [Chemical Formula 1] Claim 6 A pharmaceutical composition for the prevention or treatment of rhinitis according to claim 5, characterized by further comprising, in addition to the active ingredient, a pharmaceutically acceptable carrier, excipient, or diluent. Claim 7 A quasi-drug for the prevention or improvement of rhinitis comprising, as an active ingredient, brazilin represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof. [Chemical Formula 1] Claim 8 A veterinary composition for the prevention or treatment of rhinitis comprising, as an active ingredient, brazilin represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof. [Chemical Formula 1] Claim 9 A feed additive for the prevention or improvement of rhinitis comprising, as an active ingredient, Brazilin represented by the following Chemical Formula 1 or a food-grade acceptable salt thereof. [Chemical Formula 1] Claim 10 A method for the prevention or treatment of rhinitis comprising the step of administering Brazilin represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof to an individual other than a human. [Chemical Formula 1]

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