Splenomegaly inhibitor containing n-acetylneuraminic acid or its salt or ester

Abstract

To provide effective splenomegaly inhibitors or food allergy reaction inhibitors.SOLUTION: The present invention provides splenomegaly inhibitors or food allergy reaction inhibitors, containing N-acetylneuraminic acid or its salt or ester.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an agent for suppressing spleen hypertrophy, which comprises N-acetylneuraminic acid or a salt or ester thereof. [Background technology]

[0002] Allergies are classified into four types (I to IV) according to the classification method of Gell and Coombs. Of these, type I allergies are immunoglobulin E (IgE)-dependent allergies, and are also called immediate allergies because symptoms appear relatively quickly after an allergen enters the body.

[0003] Type I allergic reactions consist of a sensitization phase reaction in which sensitization is established, and an elicitation phase reaction in which symptoms are induced. In the sensitization phase, IgE specific to the allergen that has entered the body is produced and binds to IgE receptors on the surface of mast cells that are widely present in tissues throughout the body (perivascular, skin, subcutaneous tissue, lungs, digestive tract, liver, spleen, etc.), resulting in sensitization. In the elicitation phase, the allergen that has sensitized enters the body again and binds to the allergen-specific IgE on the mast cells, which causes inflammatory mediators such as histamine and leukotriene to be released from the mast cells, resulting in the elicitation of allergic symptoms.

[0004] Food allergies are generally classified as type I allergies. The allergens in food allergies are mainly proteins, and allergies to various foods such as wheat, soybeans, chicken eggs, milk, shellfish, fruits, buckwheat, fish, and peanuts have been reported. Among food allergies, chicken egg allergy is particularly common, and it is said that more than 50% of food allergy patients under the age of one have chicken egg allergy.

[0005] The number of people with food allergies has been increasing in recent years, and in Japan, it is said that 1-2% of the total population has some kind of food allergy. The prevalence of food allergies is particularly high in infants, at 5-10%, but while food allergies in infants can be cured naturally as they acquire tolerance as they grow, food allergies in adults are difficult to acquire tolerance to and often require continuous elimination of the causative food.

[0006] Symptoms of food allergies appear in the skin, respiratory tract, mucous membranes, digestive tract, or nerves, but anaphylaxis, a condition in which these symptoms appear throughout the body in multiple organs, can be life-threatening.

[0007] Currently, oral immunostimulation therapy and other treatments are being used to treat food allergies, which can be considered a modern disease, but the results are not necessarily satisfactory. In addition, antihistamines and other drugs are used to improve allergic symptoms, but antihistamines have side effects such as drowsiness. Therefore, there is a need for substances that can suppress allergies, including food allergies.

[0008] In addition, allergies such as food allergies may be accompanied by spleen hypertrophy. Spleen hypertrophy may cause symptoms such as loss of appetite, bloating, abdominal pain, and back pain due to pressure on the stomach, but no substance has been found to suppress spleen hypertrophy. Therefore, a substance that suppresses spleen hypertrophy is also needed.

[0009] On the other hand, sialic acid is a general term for derivatives of neuraminic acid (an acidic amino sugar with nine carbon atoms and a carboxyl group in the molecule), and more than 50 types have been identified, including N-acetylneuraminic acid and N-glycolylneuraminic acid. Sialic acid is widely distributed mainly in the animal kingdom. In humans, sialic acid is N-acetylneuraminic acid, which is biosynthesized from glucose in several steps. N-acetylneuraminic acid is present especially in red blood cells, blood vessels, airways, nerves, and external secretions such as breast milk and saliva. N-acetylneuraminic acid is mainly present at the terminals of glycolipids and glycoproteins on cell membranes, and is responsible for functions such as intercellular signaling. The presence of N-acetylneuraminic acid at the terminals of glycolipids and glycoproteins on cell membranes causes the cell membrane to become negatively charged, so N-acetylneuraminic acid also has the effect of preventing red blood cell aggregation.

[0010] N-acetylneuraminic acid is used as a biomarker of inflammation because it is cleaved and released from the sugar chain by a cleavage enzyme when a disorder such as inflammation occurs. Patent Document 1 also describes that N-acetylneuraminic acid can promote the recovery of the viability of respiratory cells damaged after viral or bacterial infection, and can be used to treat respiratory conditions such as cough.

[0011] However, the function of N-acetylneuraminic acid has not yet been fully elucidated. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] Special Publication No. 2012-531445 Summary of the Invention [Problem to be solved by the invention]

[0013] An object of the present invention is to provide an effective agent for suppressing spleen enlargement or food allergic reaction. [Means for solving the problem]

[0014] As a result of intensive research to achieve the above object, the present inventors discovered that N-acetylneuraminic acid inhibits splenic enlargement and the production of allergen-specific IgE associated with allergic reactions, thereby completing the present invention.

[0015] That is, the present invention includes the following. [1] A spleen enlargement inhibitor comprising N-acetylneuraminic acid or a salt or ester thereof for suppressing spleen enlargement associated with an allergic reaction. [2] The spleen hyperplasia inhibitor described in [1], wherein the allergic reaction is a food allergy reaction. [3] The spleen hyperplasia inhibitor described in [2], wherein the food allergy reaction is a food allergy reaction to chicken eggs. [4] A spleen hypertrophy inhibitor according to any one of [1] to [3], for oral administration. [5] A food allergy reaction suppressant containing N-acetylneuraminic acid or a salt or ester thereof for suppressing sensitization to allergens in food allergy reactions. [6] The food allergy reaction suppressant described in [5], wherein the food allergy reaction is a food allergy reaction to chicken eggs. [7] A food allergy reaction suppressant described in [5] or [6] for oral administration. [8] A food allergy reaction suppressant according to any one of [5] to [7] for reducing the risk of developing a food allergy. [9] A food or beverage containing N-acetylneuraminic acid or a salt or ester thereof for suppressing splenomegaly associated with an allergic reaction and / or for suppressing sensitization to allergens in a food allergic reaction.

[10] A feed containing N-acetylneuraminic acid or a salt or ester thereof for suppressing splenomegaly associated with an allergic reaction and / or for suppressing sensitization to allergens in a food allergic reaction.

[11] A medicine containing N-acetylneuraminic acid or its salts or esters for suppressing splenomegaly associated with allergic reactions and / or for suppressing sensitization to allergens in food allergy reactions. Effect of the Invention

[0016] According to the present invention, it is possible to suppress spleen enlargement associated with allergic reactions, or sensitization to allergens in food allergy reactions. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 is a graph showing the spleen weight of mice that were fed a diet containing no N-acetylneuraminic acid (NANA) or a diet containing NANA and then administered saline or OVA. [Diagram 2] FIG. 2 is a graph showing plasma total IgE concentrations in mice fed a diet containing no NANA or a diet containing NANA, when saline or OVA was administered to the mice. [Diagram 3] FIG. 3 is a graph showing plasma OVA-specific IgE concentrations in mice fed with NANA-free or NANA-supplemented feed, when saline or OVA was administered to the mice. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The present invention will be described in detail below.

[0019] The present invention relates to the use of N-acetylneuraminic acid or a salt or ester thereof for suppressing allergic reactions or pathological conditions associated therewith. In particular, the present invention relates to the use of N-acetylneuraminic acid or a salt or ester thereof for suppressing splenomegaly and food allergy reactions.

[0020] (1) Spleen enlargement inhibitors The present invention relates to a spleen hypertrophy inhibitor comprising N-acetylneuraminic acid or a salt or ester thereof (hereinafter also referred to as "the spleen hypertrophy inhibitor of the present invention"). The spleen hypertrophy inhibitor of the present invention can be used to inhibit spleen hypertrophy associated with an allergic reaction in particular.

[0021] As used herein, "N-acetylneuraminic acid" is a type of sialic acid, a substance in which the amino group at position 5 of neuraminic acid is acetylated.

[0022] In this specification, the term "salt" refers to any pharma- ceutically acceptable salt, and is not particularly limited, and examples thereof include metal salts, ammonium salts, and amine salts. Examples of metal salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, aluminum salts, and zinc salts.

[0023] In the present specification, the term "ester" refers to any pharma- ceutically acceptable ester, and is not particularly limited, and examples thereof include phosphate ester, sulfate ester, acetate ester, propionate ester, butyrate ester, succinate ester, palmitate ester, benzoate ester, and the like. An ester of N-acetylneuraminic acid may be, for example, an ester in which a hydrogen atom in a carboxyl group (-COOH) of N-acetylneuraminic acid is replaced with an alkyl group such as a methyl group (-CH) or an ethyl group (-C2H5). An ester of N-acetylneuraminic acid may also be, for example, an ester in which a hydrogen atom in at least one hydroxyl group (-OH) of the five hydroxyl groups of N-acetylneuraminic acid is replaced with an acetyl group (COCH3-), a sulfo group (-SO3H), or a phosphate group (-PO3H2).

[0024] N-acetylneuraminic acid or a salt or ester thereof can be, for example, Formula (I): [ka] [In the formula, R1 is selected from the group consisting of a hydrogen atom and a C1-C5 alkyl group; R2 to R6 are each independently selected from the group consisting of a hydrogen atom, -COR7, a sulfo group (-SO3H), and a phosphate group (-PO3H2); R7 is a C1 to C5 alkyl group. or a salt thereof.

[0025] In the above formula (I), the wavy line indicates that the carbon atom bonded to -COOR1 and -OR2 is in either the S or R configuration, and Ac represents an acetyl group (-COCH3).

[0026] In the present specification, the term "C1-C5 alkyl group" refers to a straight-chain or branched alkyl group having 1 to 5 carbon atoms. Examples of the C1-C5 alkyl group (C1, C2, C3, C4, or C5 alkyl group) include a methyl group (-CH3), an ethyl group (-C2H5), a propyl group (-C3H7), a butyl group (-C4H9), and a pentyl group (-C5H 11 ), but are not limited to these.

[0027] In one embodiment, in the above formula (I), R1 is preferably a hydrogen atom, a methyl group (-CH3), or an ethyl group (-C2H5), more preferably a hydrogen atom. Also, in one embodiment, in the above formula (I), R2 to R6 are preferably a hydrogen atom, an acetyl group (-COCH3), a sulfo group (-SO3H), or a phosphate group (-PO3H2), more preferably a hydrogen atom.

[0028] In one embodiment, the N-acetylneuraminic acid or its salt or ester may be in the form of a solvate, such as a hydrate. In one embodiment, the N-acetylneuraminic acid or its salt or ester may be isolated or purified N-acetylneuraminic acid or its salt or ester. In one embodiment, the N-acetylneuraminic acid or its salt or ester may be in the form of a monomer. In one embodiment, the N-acetylneuraminic acid or its salt or ester may be in the form of a polymer (e.g., a homopolymer).

[0029] N-acetylneuraminic acid can be obtained, for example, by a method of extraction from natural products such as bird's nest. N-acetylneuraminic acid can also be produced by an enzymatic synthesis method using N-acetylglucosamine and pyruvic acid as raw materials. Alternatively, N-acetylneuraminic acid can be produced by a method using a microorganism such as genetically modified Escherichia coli. In these methods of extracting or producing N-acetylneuraminic acid, N-acetylneuraminic acid is obtained mainly as a polymer containing N-acetylneuraminic acid, which can be hydrolyzed with acid or enzyme to obtain a mixture containing N-acetylneuraminic acid monomers. Furthermore, N-acetylneuraminic acid can be purified from this mixture using an adsorption resin, an ion exchange resin, ultrafiltration, or a permeation membrane, and the purified N-acetylneuraminic acid can be solidified by spray drying, freeze drying, or the like.

[0030] N-acetylneuraminic acid is commercially available and can be obtained from, for example, Fujifilm Wako Pure Chemical Industries, Tokyo Chemical Industry, Sigma Aldrich, and the like.

[0031] Salts or esters of N-acetylneuraminic acid can be produced according to a conventional method. For example, sodium N-acetylneuraminic acid, which is a salt of N-acetylneuraminic acid, and ethyl N-acetylneuraminic acid and ethyl 5-acetamido-4,7,8,9-tetra-o-acetyl-neuraminic acid, which are esters of N-acetylneuraminic acid, can be produced as described in JP-T-2012-531445 and the like.

[0032] As shown in the examples below, N-acetylneuraminic acid has an inhibitory effect on spleen hypertrophy, particularly the inhibitory effect on spleen hypertrophy associated with allergic reactions. The salts and esters of N-acetylneuraminic acid, which are analogous compounds of N-acetylneuraminic acid, also have the same effect as N-acetylneuraminic acid. Therefore, N-acetylneuraminic acid or its salts or esters can be used as an active ingredient of spleen hypertrophy inhibitors, particularly for inhibiting spleen hypertrophy associated with allergic reactions.

[0033] Recent studies suggest that when food allergy occurs, differentiation of precursor cells into mast cells and significant proliferation of mast cells occur in the spleen (Shota Toyoshima et al., 2017, International Immunology, Vol. 29, No. 1, pp. 31-45). Therefore, without being bound by theory, it is believed that N-acetylneuraminic acid or a salt or ester thereof exhibits the above-mentioned inhibitory effect on splenic hypertrophy by suppressing proliferation of mast cells in the spleen.

[0034] In this specification, the term "spleen" refers to an organ having functions such as lymphocyte production, destruction and removal of aged red blood cells, storage of blood components such as white blood cells and platelets, and blood cell production during infancy. The spleen is one of the tissues in which antigen-specific T cell responses and antibody production by B cells occur, and it is known that immune responses in the spleen also play an important role in the development of allergies.

[0035] As used herein, "splenomegaly" refers to an increase in spleen weight or volume. Splenomegaly may be splenomegaly associated with an allergic reaction, for example, splenomegaly caused by an allergic reaction. Splenomegaly may be an increase in splenomegaly weight or volume relative to normal (for example, when no allergic reaction is occurring) splenomegaly.

[0036] As used herein, "allergy" refers to a systemic or local disorder caused by an abnormal reaction of the immune system to a specific antigen. As used herein, "allergic reaction" refers to an abnormal reaction of the immune system to a specific antigen.

[0037] In the present specification, the term "allergen" refers to an antigen that causes allergy. The allergen may be an allergen that enters the body via oral, mucosal, respiratory, skin, intravenous, or other routes. The allergen may be a protein. The allergen may be an allergen contained in dust, mold, dust mites, pollen, food, bee venom, or the like, but is preferably an allergen contained in food (i.e., a food allergen). Examples of food allergens include proteins contained in foods such as wheat, soybeans, chicken eggs, milk, crustaceans, fruits, buckwheat, fish, and peanuts, such as prolamins (e.g., gliadin, etc.), glutenin, egg white albumin (e.g., chicken egg white albumin, etc.), ovomucoid, ovotransferrin, lysozyme, casein, β-lactoglobulin, tropomyosin, PR-10 (Pathogenesis-related protein-10), profilin, valvalbumin, and the like.

[0038] In the present specification, the allergic reaction may be, for example, an allergic reaction to a food allergen (food allergy reaction), for example, a food allergy reaction to chicken eggs. The allergic reaction may be, for example, a food allergy reaction to ovalbumin, such as chicken ovalbumin.

[0039] As shown in the Examples below, the spleen hypertrophy suppression effect can be evaluated, for example, using the spleen weight as an index. For example, mice are raised for about 3 weeks on food supplemented with or without a test substance (N-acetylneuraminic acid or its salt or ester, or the spleen hypertrophy suppressant of the present invention), and then physiological saline with or without an allergen (e.g., ovalbumin) is intraperitoneally administered to the mice. After about 2 weeks, the mice are dissected to measure the spleen weight. (Hereinafter, mice that did not ingest the test substance and were not administered an allergen will be referred to as "non-test substance, allergen-administered mice", mice that did not ingest the test substance and were administered an allergen will be referred to as "non-test substance, allergen-administered mice", mice that ingested the test substance and not administered an allergen will be referred to as "test substance, allergen-administered mice", and mice that ingested the test substance and administered an allergen will be referred to as "test substance, allergen-administered mice".) If the statistical analysis by Tukey's multiple comparisons shows that the spleen weight of the allergen-administered mice that did not ingest the test substance was significantly increased compared to the spleen weight of the allergen-administered mice that did not ingest the test substance but not significantly increased compared to the spleen weight of the allergen-administered mice that did not ingest the test substance, the test substance can be determined to have an inhibitory effect on spleen enlargement (particularly the effect of inhibiting spleen enlargement associated with allergic reactions).

[0040] Spleen hypertrophy can cause symptoms such as loss of appetite, bloating, abdominal pain, back pain, etc., due to pressure on the stomach. Therefore, the spleen hypertrophy inhibitor of the present invention can be used, for example, to prevent or reduce the onset of symptoms caused by spleen hypertrophy (loss of appetite, bloating, abdominal pain, back pain, etc., due to pressure on the stomach).

[0041] In addition, as the spleen hypertrophy progresses, the blood supply to the spleen becomes insufficient, and the part that is no longer supplied with sufficient blood may be damaged, causing bleeding or necrosis, which may lead to a decrease in the function of the spleen and, in turn, a decrease in the defense ability against bacterial or viral infections. Therefore, the spleen hypertrophy inhibitor of the present invention may also be used to prevent or reduce the decrease in the function of the spleen caused by splenic hypertrophy.

[0042] The spleen enlargement inhibitor of the present invention may further contain additives (e.g., carriers (such as solid or liquid carriers), excipients, diluents, disintegrants, binders, coating agents, lubricants, glidants, lubricants, flavorings, sweeteners, colorants, emulsifiers, surfactants, solubilizers, suspending agents, preservatives, buffers, pH adjusters), etc. Examples of additives include titanium dioxide, lactose, mannitol, dextrin, dietary fiber, talc, gelatin, starch, cellulose and derivatives thereof, sugar, ascorbic acid, citric acid, polyethylene glycol, glycerin, animal and vegetable oils and fats, etc. The spleen enlargement inhibitor of the present invention may contain, in addition to N-acetylneuraminic acid or a salt or ester thereof, other pharmacological components having pharmacological activity. The spleen enlargement inhibitor of the present invention may be a composition.

[0043] The spleen hypertrophy inhibitor of the present invention may or may not contain bird's nest.

[0044] The spleen hypertrophy inhibitor of the present invention may be administered by any route, for example, orally. In a preferred embodiment, the spleen hypertrophy inhibitor of the present invention may be for oral administration.

[0045] The subject (subject) to which the spleen hypertrophy inhibitor of the present invention is administered may be any mammal, including humans, livestock (horses, cows, sheep, goats, pigs, etc.), pets (dogs, cats, rabbits, etc.), and experimental animals (mice, rats, monkeys, etc.), and is preferably humans. In the present invention, the subject may be a young or adult. The subject may also be male or female. The subject may be a subject at high risk of developing food allergies. Subjects at high risk of developing food allergies include, for example, subjects with a genetic or environmental predisposition to food allergies, subjects with a history of allergies, etc.

[0046] The dosage or intake amount of the spleen hypertrophy inhibitor of the present invention can be appropriately determined taking into consideration various factors such as the administration route, and the age, body weight, and symptoms of the subject.

[0047] The spleen hypertrophy inhibitor of the present invention may contain an effective amount of N-acetylneuraminic acid or a salt or ester thereof. For example, the spleen hypertrophy inhibitor of the present invention may contain N-acetylneuraminic acid or a salt or ester thereof in an amount of 0.01% by weight or more, 0.1% by weight or more, 1% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, or 70% by weight or more, 99.99% by weight or less, 99% by weight or less, or 90% by weight or less. The spleen enlargement inhibitor of the present invention may contain, for example, 20% by weight to 99.99% by weight, 30% by weight to 99.99% by weight, 40% by weight to 99.99% by weight, 50% by weight to 99.99% by weight, 60% by weight to 99.99% by weight, 70% by weight to 99.99% by weight, 20% by weight to 99% by weight, 30% by weight to 99% by weight, 40% by weight to 99% by weight, 50% by weight to 99% by weight, 60% by weight to 99% by weight, 70% by weight to 99% by weight, 20% by weight to 90% by weight, 30% by weight to 90% by weight, 40% by weight to 90% by weight, 50% by weight to 90% by weight, 60% by weight to 90% by weight, or 70% by weight to 90% by weight.

[0048] The spleen hypertrophy suppressant of the present invention may be administered once, or multiple times at intervals of several hours to several months.

[0049] (2) Food allergy reaction suppressants As described above, it is believed that N-acetylneuraminic acid or its salts or esters can suppress the proliferation of mast cells in the spleen associated with allergic reactions. In addition, as shown in the Examples below, N-acetylneuraminic acid can also suppress the production of allergen-specific IgE, and its analogous substances, salts or esters of N-acetylneuraminic acid, have the same effect.

[0050] Such actions of N-acetylneuraminic acid or its salts or esters (inhibition of proliferation of mast cells in the spleen and inhibition of production of allergen-specific IgE) result in inhibition of food allergy reactions, which are IgE-dependent type I allergic reactions involving mast cells, and therefore N-acetylneuraminic acid or its salts or esters can also be used as an active ingredient of a food allergy reaction suppressant. Thus, the present invention also provides a food allergy reaction suppressant comprising N-acetylneuraminic acid or its salts or esters (hereinafter also referred to as the "food allergy reaction suppressant of the present invention").

[0051] In the food allergy reaction suppressant of the present invention, the meanings of the terms "N-acetylneuraminic acid," "salt," "ester," and "food allergy reaction" are as described in "(1) Spleen hypertrophy suppressant." In the food allergy reaction suppressant of the present invention, the food allergy reaction is not particularly limited, and may be, for example, a food allergy reaction to chicken eggs. The food allergy reaction may also be a food allergy reaction to ovalbumin such as chicken ovalbumin. In the food allergy reaction suppressant of the present invention, the food allergy reaction is particularly a type I allergy reaction, i.e., an immediate type food allergy reaction.

[0052] In this specification, "type I allergy" refers to allergy classified as type I according to the classification method of Gell and Coombs. Type I allergy is an IgE-dependent allergy, and is also called immediate-type allergy because symptoms appear relatively shortly (less than 1 hour) after an allergen enters the body. Symptoms of type I allergy can appear in the skin, respiratory tract, mucous membrane, digestive tract, nerves, etc. Symptoms of type I allergy are typically as follows: Skin symptoms: itching, hives, swelling, redness, eczema, etc. Respiratory symptoms: sneezing, runny nose, stuffy nose, coughing, shortness of breath, wheezing, etc. Mucous membrane symptoms: redness or swelling of the eyes, tears, itching, discomfort or swelling in the mouth, lips, or tongue, etc. Digestive symptoms: diarrhea, nausea, vomiting, bloody stools, etc. Neurological symptoms: headache, loss of energy, confusion, etc.

[0053] Type I allergic reactions consist of a sensitization phase reaction in which sensitization is established and an elicitation phase reaction in which symptoms are induced. The sensitization phase reaction includes a series of reactions from the invasion of an allergen into the body to the establishment of sensitization to the allergen, specifically, the uptake of the allergen by dendritic cells and the presentation of the allergen to T cells, the interaction between activated T cells and B cells, the differentiation of B cells into plasma cells, the production of allergen-specific IgE, and the binding of allergen-specific IgE to IgE receptors on the surface of mast cells (i.e., the establishment of sensitization to the allergen). The elicitation phase reaction includes a series of reactions from the invasion of an allergen that has established sensitization into the body to the induction of symptoms, specifically, the binding of the allergen to allergen-specific IgE on mast cells, the release of inflammatory mediators such as histamine and leukotriene from mast cells, and the onset of allergic symptoms.

[0054] The food allergy reaction inhibitor of the present invention, which inhibits the production of allergen-specific IgE, can be used particularly to inhibit sensitization to allergens in food allergy reactions. In the food allergy reaction inhibitor of the present invention, the meaning of the term "allergen" is as described in "(1) Spleen hypertrophy inhibitor." In this specification, "sensitization to allergens in food allergy reactions" refers to a state in which allergen-specific IgE is produced and binds to IgE receptors on the surface of mast cells.

[0055] As used herein, "suppression of food allergic reactions" means suppression of food allergic reactions, and includes suppression of reactions in the sensitization phase and / or elicitation phase of food allergic reactions.

[0056] As shown in the examples below, the food allergy reaction suppressing effect can be determined, for example, using plasma IgE concentration as an index. For example, mice are raised for about 3 weeks on food supplemented with or not supplemented with a test substance (N-acetylneuraminic acid or its salt or ester, or the food allergy reaction suppressor of the present invention), and then physiological saline with or without an allergen (e.g., ovalbumin) is intraperitoneally administered to the mice. After about 2 weeks, the mice are dissected and the plasma allergen-specific IgE concentration is measured. When the results of statistical analysis by t-test show that the plasma allergen-specific IgE concentration of the mice not ingesting the test substance and administered with the allergen is significantly increased compared to the plasma allergen-specific IgE concentration of the mice not ingesting the test substance and administered with the allergen, but the plasma allergen-specific IgE concentration of the mice not ingesting the test substance and administered with the allergen is not significantly increased compared to the plasma allergen-specific IgE concentration of the mice not ingesting the test substance and administered with the allergen, the test substance can be determined to have a food allergy reaction suppressing effect.

[0057] The food allergy reaction suppressant of the present invention can be used to suppress sensitization to allergens in food allergy reactions, for example, by suppressing the proliferation of mast cells in the spleen and / or the production of allergen-specific IgE.

[0058] The food allergy reaction suppressant of the present invention may contain, in addition to N-acetylneuraminic acid or a salt or ester thereof, other pharmacologically active pharmacological components. The food allergy reaction suppressant of the present invention may further contain additives (e.g., carriers (such as solid or liquid carriers), excipients, diluents, disintegrants, binders, coating agents, lubricants, glidants, lubricants, flavorings, sweeteners, colorants, emulsifiers, surfactants, solubilizers, suspending agents, preservatives, buffers, pH adjusters), etc. Examples of additives include titanium dioxide, lactose, mannitol, dextrin, dietary fiber, talc, gelatin, starch, cellulose and its derivatives, sugar, ascorbic acid, citric acid, polyethylene glycol, glycerin, animal and vegetable oils and fats, etc. The food allergy reaction suppressant of the present invention may be a composition.

[0059] The food allergic reaction suppressant of the present invention may or may not contain bird's nest.

[0060] The route of administration, subjects of administration, and dosage or intake amount of the food allergy reaction suppressant of the present invention are the same as those of the spleen hypertrophy suppressant of the present invention. The food allergy reaction suppressant of the present invention may be, for example, for oral administration.

[0061] In the food allergy reaction suppressant of the present invention, N-acetylneuraminic acid or its salt or ester may be isolated or purified N-acetylneuraminic acid or its salt or ester. In the food allergy reaction suppressant of the present invention, N-acetylneuraminic acid or its salt or ester may also be in the form of a monomer.

[0062] The food allergy reaction suppressant of the present invention may contain an effective amount of N-acetylneuraminic acid or a salt or ester thereof. For example, the food allergy reaction suppressant of the present invention may contain N-acetylneuraminic acid or a salt or ester thereof in an amount of 0.01% by weight or more, 0.1% by weight or more, 1% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, or 70% by weight or more, and 99.99% by weight or less, 99% by weight or less, or 90% by weight or less. The food allergic reaction suppressant of the present invention may contain, for example, 20% by weight to 99.99% by weight, 30% by weight to 99.99% by weight, 40% by weight to 99.99% by weight, 50% by weight to 99.99% by weight, 60% by weight to 99.99% by weight, 70% by weight to 99.99% by weight, 20% by weight to 99% by weight, 30% by weight to 99% by weight, 40% by weight to 99% by weight, 50% by weight to 99% by weight, 60% by weight to 99% by weight, 70% by weight to 99% by weight, 20% by weight to 90% by weight, 30% by weight to 90% by weight, 40% by weight to 90% by weight, 50% by weight to 90% by weight, 60% by weight to 90% by weight, or 70% by weight to 90% by weight.

[0063] The food allergic reaction suppressant of the present invention may be administered once, or multiple times at intervals of several hours to several months.

[0064] The food allergy reaction suppressant of the present invention can suppress sensitization to allergens, which is the early stage of food allergy reactions, and can therefore be used to reduce the risk of developing food allergies or prevent the onset of food allergies. For example, the food allergy reaction suppressant of the present invention can be used to reduce the risk of developing food allergies or prevent the onset of food allergies in subjects who do not have food allergies. The food allergy reaction suppressant of the present invention can also be used to reduce the risk of developing food allergies to a certain allergen or prevent the onset of food allergies to another allergen in subjects who have a food allergy to another allergen.

[0065] In one embodiment, the food allergy reaction suppressant of the present invention can be used to suppress a food allergy reaction and suppress splenomegaly. In one embodiment, the food allergy reaction suppressant of the present invention can be used to suppress sensitization to an allergen in a food allergy reaction and suppress splenomegaly associated with an allergic reaction.

[0066] (3) Food and beverages N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention can be added to food and drink. Thus, the present invention also provides food and drink containing N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention for inhibiting spleen enlargement and / or inhibiting food allergic reaction (hereinafter also referred to as "food and drink of the present invention").

[0067] The food and drink of the present invention containing N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergy reaction inhibitor of the present invention can be used for the same purpose as the spleen enlargement inhibitor of the present invention or the food allergy reaction inhibitor of the present invention. The food and drink of the present invention can be, for example, for suppressing spleen enlargement associated with an allergic reaction, and / or for suppressing sensitization to an allergen in a food allergy reaction. In the food and drink of the present invention, the allergic reaction may be a food allergy reaction, for example, a food allergy reaction against chicken eggs. The allergic reaction may also be, for example, a food allergy reaction against ovalbumin such as chicken ovalbumin.

[0068] In the food and drink of the present invention, N-acetylneuraminic acid or its salt or ester may be isolated or purified N-acetylneuraminic acid or its salt or ester. In the food and drink of the present invention, N-acetylneuraminic acid or its salt or ester may also be in the form of a monomer.

[0069] The food and drink of the present invention may contain an effective amount of N-acetylneuraminic acid or a salt or ester thereof. The food and drink of the present invention may contain, for example, 0.01% by weight or more, 0.1% by weight or more, 1% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, or 50% by weight or more, 90% by weight or less, 80% by weight or less, 70% by weight or less, or 60% by weight or less of N-acetylneuraminic acid or a salt or ester thereof. The food and drink of the present invention may, for example, contain 0.01% by weight to 90% by weight, 0.1% by weight to 90% by weight, 1% by weight to 90% by weight, 10% by weight to 90% by weight, 20% by weight to 90% by weight, 30% by weight to 90% by weight, 40% by weight to 90% by weight, 50% by weight to 90% by weight, 0.01% by weight to 80% by weight, 0.1% by weight to 80% by weight, 1% by weight to 80% by weight, 10% by weight to 80% by weight, 20% by weight to 80% by weight, 30% by weight to 80% by weight, 40% by weight to 8 ... It may contain 0% by weight, 50% to 80% by weight, 0.01% to 70% by weight, 0.1% to 70% by weight, 1% to 70% by weight, 10% to 70% by weight, 20% to 70% by weight, 30% to 70% by weight, 40% to 70% by weight, 50% to 70% by weight, 0.01% to 60% by weight, 0.1% to 60% by weight, 1% to 60% by weight, 10% to 60% by weight, 20% to 60% by weight, 30% to 60% by weight, 40% to 60% by weight, or 50% to 60% by weight.

[0070] The food and beverage of the present invention may further contain additives acceptable for the production of foods and beverages (food additives; for example, carriers (such as solid and liquid carriers), excipients, diluents, disintegrants, binders, coating agents, lubricants, gliding agents, glidants, flavoring agents, sweeteners, colorants, emulsifiers, surfactants, solubilizers, suspending agents, preservatives, buffers, pH adjusters), etc.

[0071] The food and drink of the present invention may be in any form such as processed food, side dish, confectionery, seasoning, beverage, etc., for example, jelly, pudding, gummy, chewing gum, candy, fruit juice drink, fermented milk, tea, carbonated drink, etc. The food and drink of the present invention may be preferably a functional food.

[0072] In the present invention, the term "functional food" refers to food that can impart a specific functionality to the living body, and includes all types of health foods, such as foods for specified health uses (including conditional FOSHU [foods for specified health uses]), foods with functional claims, health functional foods including foods with nutrient functions, foods for special dietary uses, dietary supplements, health supplements, supplements (for example, tablets, coated tablets, sugar-coated tablets, capsules, liquids, and other dosage forms), beauty foods (for example, diet foods), etc. In addition, in the present invention, "functional food" includes health foods to which a health claim based on the food standards of Codex Alimentarius (the Joint FAO / WHO Commission on Food Standards) is applied.

[0073] The food and drink of the present invention may be prepared in any form, such as solid, liquid, mixture, suspension, paste, gel, powder, granule, capsule, etc. In addition, the food and drink of the present invention may contain N-acetylneuraminic acid or its salt or ester, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention, by any suitable method available to those skilled in the art. Specifically, the food and drink of the present invention may contain N-acetylneuraminic acid or its salt or ester, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention in a capsule, or may be wrapped in an edible film or edible coating agent, or may be formed into any form, such as a tablet, after mixing (adding) a suitable excipient, etc., with N-acetylneuraminic acid or its salt or ester, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention. The food and drink of the present invention may be produced by processing a composition containing N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergy reaction inhibitor of the present invention, and other food ingredients.The food and drink of the present invention can also be produced, for example, by blending (adding) N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergy reaction inhibitor of the present invention to various foods (drinks, liquid foods, foods for the sick, nutritional foods, frozen foods, processed foods, other commercially available foods, etc.).

[0074] The subjects (subjects) to which the food and beverage of the present invention is administered can be set in the same manner as the subjects (subjects) to which the spleen enlargement inhibitor or food allergy reaction inhibitor of the present invention is administered as described above, but the subjects to which the food and beverage of the present invention is administered are particularly humans.

[0075] (4) Feed N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention can be added to feed. Thus, the present invention also provides a feed containing N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention for inhibiting spleen enlargement and / or inhibiting food allergic reaction (hereinafter also referred to as "the feed of the present invention").

[0076] The feed of the present invention containing N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergy reaction inhibitor of the present invention can be used for the same purpose as the spleen enlargement inhibitor of the present invention or the food allergy reaction inhibitor of the present invention. The feed of the present invention can be, for example, for suppressing spleen enlargement associated with an allergic reaction and / or for suppressing sensitization to an allergen in a food allergy reaction. In the feed of the present invention, the allergic reaction can be a food allergy reaction, for example a food allergy reaction against chicken eggs. The allergic reaction can also be, for example, a food allergy reaction against ovalbumin such as chicken ovalbumin.

[0077] In the feed of the present invention, the N-acetylneuraminic acid or its salt or ester may be isolated or purified N-acetylneuraminic acid or its salt or ester. In the feed of the present invention, the N-acetylneuraminic acid or its salt or ester may also be in the form of a monomer.

[0078] The feed of the present invention may contain an effective amount of N-acetylneuraminic acid or a salt or ester thereof. For example, the feed of the present invention may contain 0.01% by weight or more, 0.1% by weight or more, 1% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, or 50% by weight or more, 90% by weight or less, 80% by weight or less, 70% by weight or less, or 60% by weight or less of N-acetylneuraminic acid or a salt or ester thereof. The feed of the present invention may, for example, contain 0.01% by weight to 90% by weight, 0.1% by weight to 90% by weight, 1% by weight to 90% by weight, 10% by weight to 90% by weight, 20% by weight to 90% by weight, 30% by weight to 90% by weight, 40% by weight to 90% by weight, 50% by weight to 90% by weight, 0.01% by weight to 80% by weight, 0.1% by weight to 80% by weight, 1% by weight to 80% by weight, 10% by weight to 80% by weight, 20% by weight to 80% by weight, 30% by weight to 80% by weight, 40% by weight to 80% by weight, %, 50% to 80% by weight, 0.01% to 70% by weight, 0.1% to 70% by weight, 1% to 70% by weight, 10% to 70% by weight, 20% to 70% by weight, 30% to 70% by weight, 40% to 70% by weight, 50% to 70% by weight, 0.01% to 60% by weight, 0.1% to 60% by weight, 1% to 60% by weight, 10% to 60% by weight, 20% to 60% by weight, 30% to 60% by weight, 40% to 60% by weight, or 50% to 60% by weight.

[0079] The feed of the present invention may further contain additives acceptable for the production of feed (feed additives; for example, carriers (such as solid or liquid carriers), excipients, diluents, disintegrants, binders, coating agents, lubricants, gliding agents, glidants, flavoring agents, sweeteners, colorants, emulsifiers, surfactants, solubilizers, suspending agents, preservatives, buffers, pH adjusters), etc.

[0080] The feed of the present invention may be prepared in any form, such as solid, liquid, mixture, suspension, paste, gel, powder, granule, capsule, etc. The feed of the present invention may contain N-acetylneuraminic acid or a salt or ester thereof, the spleen hypertrophy inhibitor of the present invention, or the food allergy reaction inhibitor of the present invention, by any suitable method available to those skilled in the art. The feed of the present invention may be produced, for example, by a method similar to the method for producing the food and drink of the present invention described above.

[0081] The subject (subject) to which the feed of the present invention is administered may be any non-human mammal, including livestock (horses, cows, sheep, goats, pigs, etc.), pets (dogs, cats, rabbits, etc.), and laboratory animals (mice, rats, monkeys, etc.). In the present invention, the subject may be a young animal or an adult. The subject may also be male or female. The subject may be a subject at high risk of developing food allergies. Subjects at high risk of developing food allergies include, for example, subjects with a genetic or environmental predisposition to food allergies, subjects with a history of allergies, etc.

[0082] (5) Pharmaceuticals N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention can be added to a pharmaceutical product. Thus, the present invention also provides a pharmaceutical product (hereinafter also referred to as "the pharmaceutical product of the present invention") containing N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergic reaction inhibitor of the present invention for inhibiting spleen enlargement and / or inhibiting food allergic reaction.

[0083] The pharmaceutical product of the present invention, which contains N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, or the food allergy reaction inhibitor of the present invention, can be used for the same purpose as the spleen enlargement inhibitor of the present invention or the food allergy reaction inhibitor of the present invention. The pharmaceutical product of the present invention can be, for example, for suppressing spleen enlargement associated with an allergic reaction, and / or for suppressing sensitization to an allergen in a food allergy reaction. In the pharmaceutical product of the present invention, the allergic reaction can be a food allergy reaction, for example, a food allergy reaction to chicken eggs. The allergic reaction can also be, for example, a food allergy reaction to ovalbumin, such as chicken ovalbumin.

[0084] In the pharmaceutical of the present invention, N-acetylneuraminic acid or its salt or ester may be isolated or purified N-acetylneuraminic acid or its salt or ester. In the pharmaceutical of the present invention, N-acetylneuraminic acid or its salt or ester may also be in the form of a monomer.

[0085] The pharmaceutical of the present invention may contain an effective amount of N-acetylneuraminic acid or a salt or ester thereof. For example, the pharmaceutical of the present invention may contain 0.01% by weight or more, 0.1% by weight or more, 1% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, or 50% by weight or more, 90% by weight or less, 80% by weight or less, 70% by weight or less, or 60% by weight or less of N-acetylneuraminic acid or a salt or ester thereof. The pharmaceutical product of the present invention may, for example, contain 0.01% by weight to 90% by weight, 0.1% by weight to 90% by weight, 1% by weight to 90% by weight, 10% by weight to 90% by weight, 20% by weight to 90% by weight, 30% by weight to 90% by weight, 40% by weight to 90% by weight, 50% by weight to 90% by weight, 0.01% by weight to 80% by weight, 0.1% by weight to 80% by weight, 1% by weight to 80% by weight, 10% by weight to 80% by weight, 20% by weight to 80% by weight, 30% by weight to 80% by weight, 40% by weight to 8 ... It may contain 0% by weight, 50% to 80% by weight, 0.01% to 70% by weight, 0.1% to 70% by weight, 1% to 70% by weight, 10% to 70% by weight, 20% to 70% by weight, 30% to 70% by weight, 40% to 70% by weight, 50% to 70% by weight, 0.01% to 60% by weight, 0.1% to 60% by weight, 1% to 60% by weight, 10% to 60% by weight, 20% to 60% by weight, 30% to 60% by weight, 40% to 60% by weight, or 50% to 60% by weight.

[0086] The pharmaceutical of the present invention may further contain pharma- ceutical acceptable additives (pharmaceutical additives; for example, carriers (such as solid or liquid carriers), excipients, diluents, disintegrants, binders, coating agents, lubricants, glidants, glidants, flavorings, sweeteners, colorants, emulsifiers, surfactants, solubilizers, suspending agents, preservatives, buffers, pH adjusters), etc. In this case, the additives, etc. can be appropriately selected depending on the dosage form of the preparation.

[0087] The pharmaceutical of the present invention may be formulated in any dosage form, such as solid preparations such as tablets, granules, powders, pills, and capsules, liquid preparations such as liquids, suspensions, and syrups, gels, and aerosols. When the pharmaceutical is used as a liquid preparation, it can also be formulated as a dry product intended to be reconstituted with, for example, physiological saline just before use. In addition, the pharmaceutical of the present invention can be appropriately formulated with the amount of N-acetylneuraminic acid or a salt or ester thereof, and the amount can be changed depending on the dosage form, additives, the severity of the target disease, and the like. Preferred administration routes of the pharmaceutical of the present invention include, but are not limited to, oral administration. The pharmaceutical of the present invention can be, for example, for oral administration.

[0088] The subjects (subjects) to which the pharmaceutical product of the present invention is administered can be set in the same manner as the subjects (subjects) to which the above-mentioned spleen enlargement inhibitor or food allergic reaction inhibitor of the present invention is administered.

[0089] (6) Method for inhibiting spleen enlargement The present invention also provides a method for suppressing spleen enlargement in a subject, comprising administering to the subject N-acetylneuraminic acid or a salt or ester thereof, the spleen enlargement inhibitor of the present invention, a food or drink, a feed, or a pharmaceutical product (hereinafter also referred to as the "method for suppressing spleen enlargement of the present invention"). The method for suppressing spleen enlargement of the present invention can be, for example, for suppressing spleen enlargement associated with an allergic reaction.

[0090] In the method for suppressing splenomegaly of the present invention, the allergic reaction may be a food allergy reaction, for example, a food allergy reaction to chicken eggs. The allergic reaction may also be a food allergy reaction to ovalbumin, for example, chicken ovalbumin.

[0091] In the method of suppressing spleen hypertrophy of the present invention, the route of administration, the subject of administration, and the dosage of the spleen hypertrophy inhibitor, food, drink, feed, or medicine of the present invention are as described for the spleen hypertrophy inhibitor, food, drink, feed, or medicine of the present invention. In the method of suppressing spleen hypertrophy of the present invention, N-acetylneuraminic acid or a salt or ester thereof, the spleen hypertrophy inhibitor, food, drink, feed, or medicine of the present invention are administered orally, for example.

[0092] In the method for suppressing spleen hypertrophy of the present invention, N-acetylneuraminic acid or a salt or ester thereof, the spleen hypertrophy inhibitor of the present invention, the food, beverage, feed, or pharmaceutical product may be administered once or multiple times at intervals of several hours to several months.

[0093] (7) Method for suppressing food allergy reactions The present invention also provides a method for suppressing a food allergic reaction in a subject (hereinafter also referred to as "the method for suppressing a food allergic reaction of the present invention"), which comprises administering to the subject N-acetylneuraminic acid or a salt or ester thereof, the food allergic reaction suppressor of the present invention, a food or drink, a feed, or a pharmaceutical. The method for suppressing a food allergic reaction of the present invention may be for suppressing, for example, sensitization to an allergen in a food allergic reaction. In the allergic reaction suppressor of the present invention, the food allergic reaction may be, for example, a food allergy reaction to a chicken egg. The food allergy reaction may also be, for example, a food allergy reaction to an ovalbumin such as chicken ovalbumin. The method for suppressing a food allergy reaction of the present invention may be for suppressing sensitization to an allergen in a food allergic reaction by suppressing the production of allergen-specific IgE.

[0094] In the method for suppressing food allergy reaction of the present invention, the route of administration, the subject of administration, and the dosage of N-acetylneuraminic acid or its salt or ester, the food allergy reaction inhibitor, food and drink, feed, or pharmaceutical of the present invention are as described for the food allergy reaction inhibitor, food and drink, feed, or pharmaceutical of the present invention. In the method for suppressing food allergy reaction of the present invention, N-acetylneuraminic acid or its salt or ester, the food allergy reaction inhibitor, food and drink, feed, or pharmaceutical of the present invention are, for example, orally administered.

[0095] In the method for suppressing food allergy reaction of the present invention, N-acetylneuraminic acid or its salt or ester, the food allergy reaction inhibitor, food and drink, feed, or pharmaceutical of the present invention may be administered once, or may be administered multiple times at intervals of several hours to several months.

Example

[0096] Hereinafter, the present invention will be described more specifically using examples. However, the technical scope of the present invention is not limited to these examples.

[0097] <Suppressive effect of N-acetylneuraminic acid on splenomegaly and suppressive effect on allergic reaction> Using ovalbumin allergy model mice, the suppressive effect of N-acetylneuraminic acid on splenomegaly and the suppressive effect on allergic reaction were examined.

[0098] Specifically, after 6-week-old male Balb / c mice (Charles River Japan, Inc.) were pre-fed for 1 week, they were divided into a group fed a diet containing 0.1% by weight of N-acetylneuraminic acid and a group fed a diet not containing N-acetylneuraminic acid, and bred for 3 weeks (n = 12). As the feed, a commercially available solid feed (CRF-1; Oriental Yeast Co., Ltd.) was used. As N-acetylneuraminic acid, N-acetylneuraminic acid (content 99.4%) obtained from Fujifilm Wako Pure Chemical Industries, Ltd. was used. The feed was given by free intake. During the 3-week breeding period, feces for 24 hours were collected once a week, and the IgA concentration in the feces was measured.

[0099] After 3 weeks of feeding, each group was further divided into two groups, one receiving ovalbumin (OVA) (allergen) from chicken eggs and the other receiving saline. The former group was intraperitoneally administered 200μL of saline containing 20μg of OVA, and the latter group was intraperitoneally administered 200μL of saline without OVA (n=6). After 2 weeks, the mice were weighed and then dissected to measure the weight of each organ (liver, spleen, kidney, and white adipose tissue), total IgE concentration in plasma, and OVA-specific IgE concentration. Fecal IgA concentration was also measured immediately before dissection.

[0100] The measurement results of body weight and the weight of each organ are shown in Table 1 below and FIG.

[0101] Tukey's multiple comparisons showed that OVA administration significantly increased spleen weight in mice not given N-acetylneuraminic acid (NANA). In contrast, no significant increase in spleen weight was observed in mice given N-acetylneuraminic acid. These results and Figures 2 and 3 below show that intake of N-acetylneuraminic acid suppresses spleen enlargement associated with allergic reactions.

[0102] Recent studies have suggested that when food allergy occurs, differentiation of precursor cells into mast cells and significant proliferation of mast cells occur in the spleen (Shota Toyoshima et al., 2017, International Immunology, Vol. 29, No. 1, pp. 31-45). Therefore, it is believed that the above-mentioned splenic hypertrophy is due to proliferation of mast cells, and that N-acetylneuraminic acid inhibits the proliferation of such mast cells.

[0103] [Table 1]

[0104] The results of measuring the total IgE concentration in plasma are shown in Figure 2. The plasma total IgE concentration increased after administration of OVA in mice that were not given N-acetylneuraminic acid, but the increase was suppressed in mice that were given N-acetylneuraminic acid (Figure 2).

[0105] The results of measuring the OVA-specific IgE concentration in plasma are shown in Figure 3. The results of the t-test showed that the plasma OVA-specific IgE concentration was significantly increased by OVA administration in mice that were not given N-acetylneuraminic acid, but no significant increase was observed in mice that were given N-acetylneuraminic acid (Figure 3). Furthermore, the plasma OVA-specific IgE concentration in mice that were given N-acetylneuraminic acid and were administered OVA tended to be lower than the plasma OVA-specific IgE concentration in mice that were not given N-acetylneuraminic acid and were administered OVA. These results indicate that ingestion of N-acetylneuraminic acid suppresses sensitization to allergens, which is the initial stage of a food allergic reaction, and reduces the risk of developing a food allergy.

[0106] Regarding food intake and activity, no differences were observed among the four groups.

[0107] Furthermore, there was no significant difference between the groups in fecal IgA concentrations before OVA administration, and no significant difference was observed between the groups in fecal IgA concentrations immediately before dissection.

Claims

1. A spleen enlargement inhibitor comprising N-acetylneuraminic acid or a salt thereof for suppressing spleen enlargement associated with an allergic reaction.

2. The spleen hypertrophy inhibitor according to claim 1, wherein the allergic reaction is a food allergy reaction.

3. The spleen hypertrophy inhibitor according to claim 2, wherein the food allergy reaction is a food allergy reaction to chicken eggs.

4. The spleen hypertrophy inhibitor according to claim 1, which is for oral administration.

5. A food or drink containing N-acetylneuraminic acid or a salt thereof for suppressing splenomegaly associated with an allergic reaction.

6. A feed containing N-acetylneuraminic acid or a salt thereof for suppressing splenomegaly associated with an allergic reaction.

7. A medicine containing N-acetylneuraminic acid or its salt to suppress splenomegaly associated with allergic reactions.

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