Composition for increasing leukocytes and / or basophils

Abstract

The purpose of the present invention is to provide: a composition for increasing leukocytes and / or basophils; a composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase; a composition for activating innate immunity; a method for increasing leukocytes and / or basophils; a method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase; and a method for activating innate immunity. The present invention relates to a composition for increasing leukocytes and / or basophils, the composition containing L-ergothioneine or a salt thereof as an active ingredient.

Description

[Technical Field]

[0001] The present invention relates to a composition for increasing leukocytes and / or basophils. The present invention also relates to a composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase and a composition for activating innate immunity. The present invention further relates to a method for increasing leukocytes and / or basophils, a method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, a method for activating innate immunity, etc. [Background technology]

[0002] White blood cells are generally classified into five types: monocytes (macrophages), lymphocytes, neutrophils, basophils, and eosinophils, which are immune cells involved in the body's defenses. These cells are derived from hematopoietic stem cells and play a role in eliminating foreign substances such as bacteria and viruses that enter the body from the outside, as well as tumor cells and cells that have outlived their usefulness. It is known that the immune function of these immune cells declines with age, and the main reason for this is thought to be that the thymus, which is responsible for producing T cells, and the spleen, which contains a large amount of lymphocytes, shrink more rapidly with age than other organs.

[0003] The epidermal growth factor receptor (hereinafter also referred to as "EGFR") is a tyrosine kinase receptor that activates kinases in the cell membrane and transmits signals when ligands such as epidermal growth factor (hereinafter also referred to as "EGF") bind to it. EGFR is known to be mutated or amplified in cancer tissues, contributing to the oncogenesis of cells, as well as cancer proliferation, invasion, and metastasis. However, it is also expressed in normal tissues, and is known to prevent viral invasion into cells by inhibiting the function of existing EGFR.

[0004] Ergothioneine is an amino acid found in mushrooms etc., and naturally exists in the L-form. Patent Document 1 describes that mice orally administered with ergothioneine showed a decrease in peritestrical fat weight and a decrease in plasma triglyceride (neutral fat) levels compared to mice not orally administered with ergothioneine.

[0005] Patent Document 2 discloses an immune response-activating cytokine production promoter containing ergothioneine and a Toll-like receptor ligand selected from lipopolysaccharide (LPS), Pam2CSK4, synthetic triacylated lipoprotein, and imidanoquinoline compounds as active ingredients. However, in the absence of a TLR ligand, IL-6, IL-12p40, IL-1β, and IL-10 were not detected in samples containing 0 or 10 mM ergothioneine. In other words, the disclosure discloses that, without TLR stimulation, IL-6, IL-12p40, IL-1β, and IL-10 were not detected, regardless of the presence or absence of ergothioneine (Claim 1, etc., and paragraph

[0068] ). Thus, an immune response-activating cytokine production promoter containing ergothioneine and a specific Toll-like receptor ligand as active ingredients is known. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-102286 [Patent Document 2] Patent No. 6121597 Summary of the Invention [Problem to be solved by the invention]

[0007] However, it has not been known until now that L-ergothioneine or a salt thereof has an effect of increasing leukocytes and / or basophils, or an effect of inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase.

[0008] An object of the present invention is to provide a composition for increasing leukocytes and / or basophils. Another object of the present invention is to provide a composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. Another object of the present invention is to provide a composition for activating innate immunity. Another object of the present invention is to provide a method for increasing leukocytes and / or basophils, a method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, and a method for activating innate immunity. [Means for solving the problem]

[0009] As a result of intensive research conducted by the present inventors to solve the above-mentioned problems, they discovered that L-ergothioneine has the effect of increasing leukocytes and / or basophils, and has the effect of inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase.

[0010] That is, although not limited thereto, the present invention relates to the following compositions for increasing leukocytes and / or basophils. [1] A composition for increasing leukocytes and / or basophils, comprising L-ergothioneine or a salt thereof as an active ingredient. [2] A composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, comprising L-ergothioneine or a salt thereof as an active ingredient. [3] A composition for activating natural immunity, comprising the composition described in [1] or [2] above. [4] The composition according to any one of [1] to [3] above, which is an oral composition. [5] The composition according to any one of [1] to [4] above, which is a food or drink. [6] The composition according to any one of [1] to [5] above, wherein the content of L-ergothioneine or a salt thereof is 2 to 50 mg in terms of L-ergothioneine per daily intake for an adult. [7] A method for increasing leukocytes and / or basophils, comprising administering L-ergothioneine or a salt thereof. [8] A method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, which comprises administering L-ergothioneine or a salt thereof. [9] A method for activating innate immunity, comprising administering L-ergothioneine or a salt thereof.

[10] Use of L-ergothioneine or a salt thereof for increasing leukocytes and / or basophils.

[11] Use of L-ergothioneine or a salt thereof for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase.

[12] Use of L-ergothioneine or a salt thereof for activating innate immunity. [Effects of the Invention]

[0011] According to the present invention, a composition for increasing leukocytes and / or basophils can be provided. Furthermore, according to the present invention, a composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase can be provided. According to the present invention, a composition for activating innate immunity, a method for increasing leukocytes and / or basophils, a method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, and a method for activating innate immunity can be provided. [Brief explanation of the drawings]

[0012] [Figure 1] Figure 1 is a graph showing the change in blood white blood cell counts in the test food group and the control food group at the pre-test and the 4-week test. [Figure 2] Figure 2 is a graph showing the change in blood basophil counts in the test food group and the control food group at the pre-test and the 4-week test. [Figure 3] FIG. 3 is a graph showing the inhibitory activity of L-ergothioneine on the substrate binding of epidermal growth factor receptor (EGFR) tyrosine kinase. DETAILED DESCRIPTION OF THE INVENTION

[0013] The composition for increasing leukocytes and / or basophils of the present invention contains L-ergothioneine or a salt thereof as an active ingredient. Hereinafter, the composition for increasing leukocytes and / or basophils of the present invention may also be referred to as the composition of the first aspect of the present invention.

[0014] The composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase of the present invention contains L-ergothioneine or a salt thereof as an active ingredient. Hereinafter, the composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase of the present invention may also be referred to as a composition of the second aspect of the present invention.

[0015] L-ergothioneine is a type of amino acid. The salt of L-ergothioneine is not particularly limited as long as it is a pharmacologically acceptable salt or a salt acceptable for use in foods and beverages, and may be either an acidic salt or a basic salt. Examples of acidic salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, and phosphate; and organic acid salts such as acetate, citrate, maleate, malate, oxalate, lactate, succinate, fumarate, and propionate. Examples of basic salts include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt and magnesium salt.

[0016] L-ergothioneine or its salts may be chemically synthesized or extracted and purified from natural sources. L-ergothioneine is found in large amounts in the Golden / Yellow Oyster mushroom (scientific name: Pleurotus cornucopiae var. citrinopileatus), a mushroom of the Pleurotus genus in the family Pleurocystis. L-ergothioneine is also found in mushrooms such as white button mushrooms, crimini mushrooms, and portabella mushrooms (Agaricus bisporus), grey oyster mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinula edodes), maitake mushrooms (Grifola Frondosa), reishi mushrooms (Ganoderma lucidum), Yamabushitake mushrooms (Hericium erinaceus), willow matsutake mushrooms (Agrocybe aegerita), chanterelles (Cantharellus cibarius), porcini mushrooms (Boletus edulis), and morels (Morchella esculenta). When obtaining L-ergothioneine from a natural product, it is preferable to extract it from Pleurotus cornucopiae. L-ergothioneine or a salt thereof can also be produced by microbial fermentation. An extract containing L-ergothioneine or a salt thereof produced by microbial fermentation, or a product purified from such an extract, may be used. Extraction and purification from natural products can be carried out by known methods. L-ergothioneine or a salt thereof may be isolated.

[0017] L-ergothioneine or its salts are compounds that are found in natural products and foods and beverages and are consumed as food. Therefore, from a safety perspective, L-ergothioneine or its salts are thought to pose few problems, even when taken over a long period of time.

[0018] As shown in the Examples below, when L-ergothioneine was taken, the number of white blood cells and the number of basophils in the blood were significantly increased compared to when L-ergothioneine was not taken. Therefore, L-ergothioneine can be used as an active ingredient for promoting an increase in blood leukocytes and / or basophils. The numbers of blood leukocytes and basophils can be measured by known methods. In this specification, blood leukocytes are of five types: monocytes (macrophages), lymphocytes, neutrophils, basophils, and eosinophils, and the number of blood leukocytes is the total number of these.

[0019] L-ergothioneine or its salts have the effect of increasing the number of white blood cells and basophils in the blood, and therefore have the effect of activating the natural immune system. The effect of increasing white blood cells in the blood may be due to any of the following: reducing or suppressing a decrease in white blood cell count, promoting the recovery of white blood cell count, etc., and refers to the effect of increasing white blood cells in the blood by taking L-ergothioneine or a salt thereof. Furthermore, the effect of increasing blood basophils may be achieved by reducing or suppressing a decrease in the number of basophils, promoting the recovery of the number of basophils, or the like, and means that the intake of L-ergothioneine or a salt thereof can have the effect of increasing the number of basophils in the blood.

[0020] Furthermore, as shown in the Examples below, L-ergothioneine has epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. Therefore, L-ergothioneine can be used as an active ingredient for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity can be measured by known methods, for example, using an assay system using insect cells, as shown in the Examples below.

[0021] L-ergothioneine or its salts have an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory effect and therefore have an innate immune activation effect. L-ergothioneine or its salts can be used as an active ingredient for innate immune activation. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity includes the ability to selectively bind to EGFR and not exhibit any effect (activate) even when bound to EGFR.

[0022] The composition according to the first aspect of the present invention and / or the composition according to the second aspect of the present invention can be used in a composition for activating innate immunity. Thus, a composition for activating innate immunity containing the composition according to the first aspect of the present invention and / or the composition according to the second aspect of the present invention also constitutes one aspect of the present invention. In one aspect, the composition according to the first aspect of the present invention can be used for activating innate immunity. The composition according to the second aspect of the present invention can be used for activating innate immunity. The composition of the first aspect of the present invention, the composition of the second aspect, and the composition for activating innate immunity (also referred to as the composition of the third aspect of the present invention) have an innate immunity activating effect and can be used to prevent or ameliorate conditions or diseases caused by a decrease in innate immunity. Preventing a condition or disease includes preventing the onset, delaying the onset, reducing the incidence, reducing the risk of onset, etc. Ameliorating a condition or disease includes recovering a subject from the condition or disease, alleviating the symptoms of the condition or disease, ameliorating the symptoms of the condition or disease, delaying or preventing the progression of the condition or disease, etc.

[0023] Conditions or diseases caused by a decrease in natural immunity include infectious diseases caused by microorganisms such as viruses and bacteria, for example, infectious enteritis caused by oral infections such as Vibrio cholerae, enterotoxigenic Escherichia coli, Shigella, Salmonella, and viruses, influenza and cold syndrome caused by respiratory tract infection, stomatitis and periodontal disease caused by oral infection, and various malignant tumors, for example, epithelial malignant tumors occurring in solid organs such as the digestive tract, respiratory mucosa, liver, and kidney, and non-epithelial malignant tumors occurring in the musculoskeletal system and soft tissues. Infectious diseases also include symptoms caused by viruses that have been latent in the subject after previous infection, such as herpes viruses.

[0024] Hereinafter, in this specification, the composition for increasing leukocytes and / or basophils, the composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, and the composition for activating innate immunity of the present invention may be collectively referred to simply as the composition of the present invention. It is preferable that the composition of the present invention does not contain a Toll-like receptor ligand.

[0025] The compositions of the present invention can be used for either therapeutic (medical) or non-therapeutic (non-medical) purposes, the latter being a concept that does not include medical procedures, i.e., human surgery, treatment, or diagnosis. The composition of the present invention can be provided in the form of an agent, for example, but is not limited to this form. The agent can be provided as a composition as is, or as a composition containing the agent. In one aspect, the composition of the present invention for increasing leukocytes and / or basophils can also be referred to as an agent for increasing leukocytes and / or basophils. In another aspect, the composition of the present invention for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase can also be referred to as an agent for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. In another aspect, the composition of the present invention for activating innate immunity can also be referred to as an agent for activating innate immunity. From the viewpoint of fully achieving the effects of the present invention, the composition of the present invention is preferably an oral composition. Examples of oral compositions include foods and beverages, oral medicines, quasi-drugs, and feeds, and are preferably foods and beverages or oral medicines, and more preferably foods and beverages.

[0026] The composition of the present invention may contain any additives and ingredients in addition to L-ergothioneine or a salt thereof, as long as the effects of the present invention are not impaired. These additives and ingredients can be selected depending on the form of the composition, and those that can generally be used in foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. can be used. However, it is preferable that the composition of the present invention does not contain a Toll-like receptor ligand. When the composition of the present invention is used as a food or beverage, pharmaceutical, quasi-drug, feed, etc., its production method is not particularly limited, and it can be produced by a general method.

[0027] For example, when the composition of the present invention is made into a food or beverage, various foods and beverages can be prepared by blending L-ergothioneine or a salt thereof with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as needed, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health drinks, functional foods, foods for specified health uses, health supplements, foods and beverages for patients, etc. The health foods, functional foods, foods for specified health uses, health supplements, etc. can be made into various dosage forms, such as fine granules, tablets, granules, powders, capsules, chewable tablets, syrups, liquids, and liquid diets.

[0028] When the composition of the present invention is used as a pharmaceutical or quasi-drug, for example, L-ergothioneine or a salt thereof can be blended with a pharmacologically acceptable carrier and, if necessary, additives to produce a pharmaceutical or quasi-drug in various dosage forms. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in pharmaceuticals or quasi-drugs, and may include, for example, one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. The pharmaceutical or quasi-drug may be administered orally or parenterally, with oral administration being preferred from the viewpoint of more fully achieving the effects of the present invention. When the composition of the present invention is used as a pharmaceutical or quasi-drug, it is preferably an oral pharmaceutical or quasi-drug. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. Dosage forms for parenteral administration include injections and infusions. Pharmaceuticals and quasi-drugs may also be used for non-human animals.

[0029] When the composition of the present invention is used as a feed, L-ergothioneine or a salt thereof may be blended into the feed. Feed also includes feed additives. Examples of feed include livestock feed for cows, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; and pet food for dogs, cats, small birds, etc.

[0030] The content of L-ergothioneine or a salt thereof in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The content of L-ergothioneine or a salt thereof in the composition of the present invention is, for example, preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and preferably 90% by weight or less, more preferably 50% by weight or less, calculated as L-ergothioneine. In one aspect, the content of L-ergothioneine or a salt thereof in the composition is preferably 0.0001 to 90% by weight, more preferably 0.001 to 50% by weight, calculated as L-ergothioneine. In one aspect, when the composition of the present invention is used in foods and beverages, pharmaceuticals, quasi-drugs, feeds, etc., the content of L-ergothioneine or a salt thereof is preferably within the above-mentioned range. The amount converted to L-ergothioneine or similar expressions means, in the case of L-ergothioneine, the amount, or, in the case of a salt of L-ergothioneine, the value obtained by multiplying the number of moles of the salt by the molecular weight of L-ergothioneine.

[0031] The composition of the present invention can be ingested or administered in an appropriate manner depending on its form. From the viewpoint of more fully obtaining the effects of the present invention, the composition of the present invention is preferably ingested orally (administered orally). The intake amount (which can also be called the administration amount) of the composition of the present invention is not particularly limited, and may be an amount that provides an effect of increasing leukocytes and / or basophils, an amount that provides an effect of inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, or an amount that provides an effect of activating natural immunity, and may be appropriately determined depending on the administration form, administration method, subject's body weight, etc.

[0032] In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult) subject, the daily intake of L-ergothioneine or a salt thereof is preferably 2 mg or more, more preferably 5 mg or more, even more preferably 10 mg or more, and preferably 50 mg or less, more preferably 25 mg or less, and even more preferably 20 mg or less, in terms of L-ergothioneine. In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult) subject, the daily intake of L-ergothioneine or a salt thereof is preferably 2 to 50 mg, more preferably 5 to 25 mg, even more preferably 5 to 20 mg, and particularly preferably 10 to 20 mg, in terms of L-ergothioneine. The above amount is preferably ingested or administered once or more times a day, for example, once a day or in divided doses (e.g., 2 to 3 times a day). In one embodiment of the present invention, the composition of the present invention may be an oral composition for ingesting or administering the above amount of L-ergothioneine or a salt thereof per 60 kg body weight per day to a human. In one aspect, when the composition of the present invention is parenterally administered to a human (adult), the dosage of L-ergothioneine or a salt thereof is, for example, preferably 2 to 50 mg, more preferably 5 to 25 mg, even more preferably 5 to 20 mg, and particularly preferably 10 to 20 mg, per day in terms of L-ergothioneine. In one embodiment, for humans (adults), it is preferable to have the subject ingest or administer the above amount of L-ergothioneine or a salt thereof per 60 kg of body weight per day.

[0033] In one aspect, the composition of the present invention preferably contains 2 to 50 mg of L-ergothioneine or a salt thereof per daily intake for an adult, more preferably 5 to 25 mg, even more preferably 5 to 20 mg, and particularly preferably 10 to 20 mg of L-ergothioneine per daily intake for an adult.

[0034] Continuous ingestion or administration of L-ergothioneine or a salt thereof is expected to exhibit a more effective effect of increasing leukocytes and / or basophils. Continuous ingestion or administration of L-ergothioneine or a salt thereof is also expected to exhibit a more effective effect of inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. Continuous ingestion or administration of L-ergothioneine or a salt thereof is also expected to exhibit a more effective effect of activating innate immunity. Therefore, in a preferred embodiment, the composition of the present invention is ingested or administered continuously, preferably for one week or more, more preferably for two weeks or more.

[0035] The subject to which the composition of the present invention is ingested or administered (also referred to as the administration subject) is not particularly limited. The subject is preferably a human or a non-human mammal, more preferably a human. Subjects to whom the compositions of the present invention are administered or ingested include subjects who require or desire an increase in leukocytes and / or basophils, subjects who require or desire epidermal growth factor receptor (EGFR) tyrosine kinase inhibition, and subjects who require or desire innate immune activation. In one embodiment, subjects to whom the compositions of the present invention are administered include subjects with reduced innate immunity and patients with conditions or diseases caused by the aforementioned reduced innate immunity. In one embodiment, subjects to whom the compositions of the present invention are administered may be healthy individuals. Furthermore, subjects to whom the compositions of the present invention are administered may be healthy individuals whose immune function via immunocompetent cells is reduced with age.

[0036] The composition of the present invention may be labeled with an indication of a function exerted by an increase in leukocytes and / or basophils, a function exerted by epidermal growth factor receptor (EGFR) tyrosine kinase inhibition, or a function exerted by activation of innate immunity. The composition of the present invention may be labeled with one or more of the following functions, for example, "increase in leukocytes," "increase in basophils," "inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase," "activation of innate immunity," etc. In one aspect of the present invention, the composition of the present invention is preferably a food or drink to which the above-mentioned label is attached. The above-mentioned label may also be a label indicating that the composition is used to obtain the above-mentioned function. The above-mentioned label may be attached to the composition itself, or to a container or packaging of the composition.

[0037] The present invention also encompasses the following methods and uses. A method for increasing leukocytes and / or basophils, comprising ingesting or administering L-ergothioneine or a salt thereof. A method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, comprising ingesting or administering L-ergothioneine or a salt thereof. A method for activating innate immunity, comprising ingesting or administering L-ergothioneine or a salt thereof. Use of L-ergothioneine or a salt thereof for increasing white blood cells and / or basophils. Use of L-ergothioneine or a salt thereof for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. Use of L-ergothioneine or a salt thereof for activating innate immunity. When L-ergothioneine or a salt thereof is ingested or administered to a subject, it can increase the number of white blood cells and / or basophils and inhibit epidermal growth factor receptor (EGFR) tyrosine kinase, thereby achieving effects of activating natural immunity, etc. Preferably, L-ergothioneine or a salt thereof is orally ingested or administered. The method may be a therapeutic method or a non-therapeutic method. The use may be a therapeutic use or a non-therapeutic use.

[0038] In the above-described methods and uses, L-ergothioneine or a salt thereof, and preferred embodiments thereof, are the same as those of the composition of the present invention described above. In the above-described methods and uses, L-ergothioneine or a salt thereof is preferably ingested or administered to a subject at least once a day, for example, once to several times a day (e.g., two to three times a day). The above-described uses are preferably used in humans or non-human mammals, more preferably in humans. In one embodiment, L-ergothioneine or a salt thereof can be used to achieve an innate immune activation effect by increasing leukocytes and / or basophils, or by inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. In one embodiment, the method for increasing leukocytes and / or basophils can be used for innate immune activation. In one embodiment, the method for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase can be used for innate immune activation.

[0039] In the above-mentioned methods and uses, L-ergothioneine or a salt thereof may be used in an amount that can achieve the effect of increasing leukocytes and / or basophils (this amount may also be referred to as an effective amount). Furthermore, in the above-mentioned methods and uses, L-ergothioneine or a salt thereof may be used in an amount sufficient to obtain an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory effect (which may also be referred to as an effective amount). Furthermore, in the above-mentioned methods and uses, L-ergothioneine or a salt thereof may be used in an amount sufficient to obtain the effect of activating natural immunity (which may also be referred to as an effective amount). The preferred dosage and administration target of L-ergothioneine or a salt thereof are the same as those of the composition of the present invention described above. L-ergothioneine or a salt thereof may be ingested or administered as is, or as a composition containing it. For example, the composition of the present invention may be ingested or administered.

[0040] L-ergothioneine or a salt thereof can be used to produce foods and drinks, pharmaceuticals, quasi-drugs, feed, etc. that are used to increase white blood cells and / or basophils. In one aspect, the present invention also encompasses the use of L-ergothioneine or a salt thereof to produce a composition for increasing white blood cells and / or basophils. The present invention also encompasses L-ergothioneine or a salt thereof, which is used for increasing leukocytosis and / or basophilia. Furthermore, L-ergothioneine or a salt thereof can be used for producing foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. that are used for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. In one aspect, the present invention also encompasses the use of L-ergothioneine or a salt thereof for producing a composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. The present invention also encompasses L-ergothioneine or a salt thereof, which is used for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. Furthermore, L-ergothioneine or a salt thereof can be used for producing foods and drinks, pharmaceuticals, quasi-drugs, feed, etc. that are used to activate innate immunity. In one aspect, the present invention also encompasses the use of L-ergothioneine or a salt thereof for producing a composition for activating innate immunity. The present invention also encompasses L-ergothioneine or a salt thereof used for innate immune activation. [Example]

[0041] The present invention will be described in more detail below with reference to examples, but the scope of the present invention is not limited to these examples.

[0042] Example 1 (Test to evaluate blood white blood cell and basophil counts in humans) To evaluate the effects of an ergothioneine-containing supplement on human blood white blood cell and basophil counts, a placebo-controlled, randomized, double-blind, parallel-group comparative study was conducted on adult men and women (46 in the test food group, 46 in the control food group, a total of 92 subjects) who took one capsule per day for four weeks containing 20 mg of ergothioneine (test food) or one capsule without ergothioneine (control food). Prior to the start of the study (before starting to take the test food or control food), the subjects' blood white blood cell and basophil counts were measured as a pre-test. After taking the test food or control food for four weeks, the subjects' blood white blood cell and basophil counts were measured again (week 4 test).

[0043] (Food for evaluation) Two types of food were used for evaluation, and they were indistinguishable in appearance, flavor, etc. Test food: Capsules containing the test substance (L-ergothioneine 20 mg) Control food: Capsules containing no test substance In addition to the test substance, the ingredients of each evaluation food product included dextrin, hydroxypropyl cellulose, carrageenan, potassium chloride, and titanium oxide. The control food was manufactured using the same ingredients as the test foods, except that it did not contain the test substance (L-ergothioneine).

[0044] Figures 1 and 2 show the changes in blood white blood cell and basophil counts in the test food group and the control food group. In Figures 1 and 2, ■ (black square) represents the test food group, and □ (white square) represents the control food group.

[0045] Figure 1 shows the change in blood white blood cell count (Δ white blood cells (cells / μL)) between the pre-test and the 4-week test for the test food group and the control food group. The change in blood white blood cell count (cells / μL) shown in Figure 1 is the change from the measured value at the pre-test. Specifically, the change at the 4-week test for the test food group was calculated by subtracting the blood white blood cell count (average value) at the pre-test from the blood white blood cell count (average value) at the 4-week test for the test food group. Similarly, for the control food group, the change at the 4-week test was calculated by subtracting the blood white blood cell count (average value) at the pre-test from the blood white blood cell count (average value) at the 4-week test. The change at the pre-test was set to 0. As a result, blood white blood cells increased in the test food group compared to the control food group.

[0046] Figure 2 shows the change in blood basophil count (Δbasophils (%)) between the pre-test and the 4-week test for the test food group and the control food group. Δbasophils (%) was calculated for each group from the blood basophil count (mean value) using the following formula: Δ Basophils (%) = 100 × (blood basophil count at the 4th week test - blood basophil count at the pre-test) / blood basophil count at the pre-test As a result, blood basophils increased in the test food group compared to the control food group.

[0047] <Example 2> (Evaluation of substrate binding inhibitory activity of epidermal growth factor receptor (EGFR) tyrosine kinase) The test was conducted by Eurofins Panlabs. Human recombinant epidermal growth factor receptor (EGFR) tyrosine kinase expressed in insect cells was used. First, epidermal growth factor receptor (EGFR) tyrosine kinase (0.34 μg / mL) was incubated with 100 or 1000 μM L-ergothioneine in HEPES buffer (pH 7.4) at 37°C for 15 minutes. Next, 0.2 mg / mL Poly(Glu:Tyr), 10 μM ATP, 0.25 μCi [γ 32The enzymatic reaction was initiated by adding [P]ATP. After 30 min of incubation at 37 °C, the reaction was stopped by adding 3% H3PO4. Finally, the [ 32 The substrate binding inhibitory activity of ergothioneine was evaluated using the amount of [P]Poly(Glu:Tyr) as an index.

[0048] Figure 3 shows the results of evaluating the substrate binding inhibitory activity of L-ergothioneine against epidermal growth factor receptor (EGFR) tyrosine kinase. The concentration (μM) on the horizontal axis represents the concentration of L-ergothioneine. L-ergothioneine exhibited concentration-dependent activity and demonstrated substrate binding inhibitory activity against epidermal growth factor receptor (EGFR) tyrosine kinase. L-ergothioneine was found to have epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity.

Claims

1. A composition for increasing basophils, comprising L-ergothioneine or a salt thereof as an active ingredient.

2. A composition for inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase, comprising L-ergothioneine or a salt thereof as an active ingredient.

3. The composition according to claim 1 or 2, which is an oral composition.

4. The composition according to any one of claims 1 to 3, which is a food or drink.

5. 5. The composition according to claim 1, wherein the content of L-ergothioneine or a salt thereof is 2 to 50 mg in terms of L-ergothioneine per daily intake for an adult.

Images