Composition for preventing or improving decline in renal function

Abstract

The purpose of the present invention is to provide a composition for ameliorating or suppressing the decline of kidney functions and a method for ameliorating or suppressing the decline of kidney functions. The present invention pertains to a composition for ameliorating or suppressing the decline of kidney functions that contains L-ergothioneine or a salt thereof as an active ingredient.

Description

[Technical Field]

[0001] The present invention relates to a composition for suppressing or ameliorating decline in renal function. The present invention also relates to a method for suppressing or ameliorating decline in renal function. [Background technology]

[0002] The kidneys are organs that maintain homeostasis of bodily fluids by filtering blood and excreting waste products and water as urine. During health checkups, the state of kidney function is assessed using indicators such as the blood urea nitrogen (BUN) concentration (BUN value). In Japan and other countries, recent dietary trends high in salt and protein have placed a heavy burden on the kidneys, leading to a decline in kidney function. Renal function is also known to decline with age.

[0003] 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. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-102286 Summary of the Invention [Problem to be solved by the invention]

[0005] However, it has not been known that L-ergothioneine or its salts have the effect of inhibiting or improving renal function decline. Renal dysfunction generally does not produce noticeable symptoms and is irreversible. Therefore, there is a demand for ingredients that are effective in inhibiting or improving renal function decline and that can be applied to foods for specified health uses, functional foods, pharmaceuticals, etc.

[0006] An object of the present invention is to provide a composition for suppressing or ameliorating decline in renal function. Another object of the present invention is to provide a method for suppressing or ameliorating decline in renal function. [Means for solving the problem]

[0007] As a result of extensive research aimed at solving the above problems, the present inventors have found that L-ergothioneine has the effect of suppressing or improving the decline in renal function.

[0008] That is, although not limited to the following, the present invention relates to the following compositions for suppressing or improving decline in renal function, methods for suppressing or improving decline in renal function, etc. [1] A composition for suppressing or improving decline in renal function, comprising L-ergothioneine or a salt thereof as an active ingredient. [2] The composition described in [1] above, which has the effect of suppressing or lowering an increase in blood urea nitrogen (BUN) levels. [3] The composition described in [1] or [2] above, which has the effect of suppressing or lowering the increase in uric acid levels in the blood. [4] The composition according to any one of [1] to [3] above, which has an effect of suppressing an increase in or reducing blood creatinine levels. [5] The composition according to any one of [1] to [4] above, which is an oral composition. [6] The composition according to any one of [1] to [5] above, which is a food or drink. [7] The composition according to any one of [1] to [6] 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. [8] A method for suppressing or improving decline in renal function, which comprises administering L-ergothioneine or a salt thereof to a subject. [9] Use of L-ergothioneine or a salt thereof to suppress decline in renal function or improve renal function. [Effects of the Invention]

[0009] According to the present invention, a composition for suppressing or improving a decline in renal function can be provided. According to the present invention, a method for suppressing or improving a decline in renal function can be provided. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a graph showing the change in BUN values ​​(ΔBUN) in the test food group and the control food group. [Figure 2] FIG. 2 is a graph showing the change in blood uric acid levels (Δuric acid) in the test food group and the control food group. [Figure 3] FIG. 3 is a graph showing the change in blood creatinine levels (Δcreatinine) in the test food group and the control food group. DETAILED DESCRIPTION OF THE INVENTION

[0011] The composition for preventing or ameliorating renal function decline of the present invention contains L-ergothioneine or a salt thereof as an active ingredient. Hereinafter, the composition for preventing or ameliorating renal function decline of the present invention may be simply referred to as the composition of the present invention.

[0012] 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.

[0013] 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.

[0014] 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.

[0015] In the present invention, suppressing decline in renal function includes maintaining renal function, slowing the progression of decline in renal function, halting decline in renal function, etc. Improving renal function includes reducing (alleviating) the degree of decline in renal function, restoring declined renal function, improving renal function, etc. Restoring includes at least partial restoration.

[0016] Renal function can be evaluated, for example, by examining at least one (preferably these three) selected from the group consisting of blood urea nitrogen (BUN) level, creatinine level, and uric acid level. Blood BUN level, creatinine level, and uric acid level are used as indicators of renal function. Suppression of an increase or decrease in at least one of these values ​​(preferably BUN level, blood creatinine level, and blood uric acid level) usually indicates that the decline in renal function has been suppressed or that renal function has been improved.

[0017] As shown in the Examples below, taking L-ergothioneine reduced blood urea nitrogen (BUN), creatinine, and uric acid levels compared to not taking it. L-ergothioneine or a salt thereof has the effect of suppressing or reducing increases in BUN levels, blood uric acid levels, and blood creatinine levels, and therefore has the effect of suppressing or improving renal function decline. L-ergothioneine or a salt thereof can be used as an active ingredient for suppressing or improving renal function decline.

[0018] The composition of the present invention preferably has the effect of suppressing an increase in or decreasing at least one value selected from the group consisting of blood urea nitrogen (BUN) levels, blood uric acid levels, and blood creatinine levels, and more preferably has the effect of suppressing an increase in or decreasing blood BUN levels, blood uric acid levels, and blood creatinine levels.

[0019] In one aspect, the composition of the present invention can be preferably used as a composition for suppressing or ameliorating decline in human renal function. The composition of the present invention can be used, for example, to prevent or ameliorate conditions or diseases caused by decline in renal function. Conditions or diseases caused by decline in renal function include, for example, renal dysfunction, renal failure, glomerulonephritis, uremia, gout, and uric acid stones. In one aspect, the composition of the present invention can be used, for example, to prevent or ameliorate renal dysfunction, renal failure, glomerulonephritis, uremia, gout, or uric acid stones. 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.

[0020] 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 for suppressing or ameliorating renal function decline 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 also be provided as a composition as is, or as a composition containing the agent. In one aspect, the composition for suppressing or ameliorating renal function decline of the present invention can also be referred to as an agent for suppressing or ameliorating renal function decline. 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.

[0021] The composition of the present invention can contain any additives and any components in addition to L-ergothioneine or a salt thereof, as long as the effects of the present invention are not impaired. These additives and components can be selected depending on the form of the composition, and those that can generally be used for foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. can be used. When the composition of the present invention is used as a food and beverage, pharmaceutical, quasi-drug, feed, etc., the production method thereof is not particularly limited, and it can be produced by a general method.

[0022] 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.

[0023] 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.

[0024] 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.

[0025] 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.

[0026] The composition of the present invention can be ingested or administered by an appropriate method 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 can achieve the effect of suppressing or improving the decline in renal function, and may be appropriately set depending on the administration form, administration method, body weight of the subject, etc.

[0027] 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.

[0028] 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.

[0029] It is expected that continuous ingestion or administration of L-ergothioneine or a salt thereof will exhibit a more excellent effect of inhibiting or improving decline in renal function. Therefore, in a preferred embodiment, the composition of the present invention is continuously ingested or administered. In one embodiment of the present invention, the composition of the present invention is preferably continuously ingested or administered for one week or more, more preferably two weeks or more.

[0030] 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 composition of the present invention is administered or taken include those who require or desire to inhibit or improve renal function decline. Further, subjects to whom the composition of the present invention is administered include, for example, humans who require or desire to prevent or improve conditions or diseases caused by renal function decline (e.g., renal dysfunction, renal failure, glomerulonephritis, uremia, gout, uric acid stones, etc.). In one embodiment, subjects to whom the composition of the present invention is administered include subjects with conditions or diseases caused by renal function decline. In one embodiment, the subjects to whom the composition of the present invention is administered may be healthy individuals. The composition of the present invention can also be used in healthy individuals, for example, for the purpose of preventing conditions or diseases caused by renal function decline.

[0031] The composition of the present invention may be labeled with an indication of the functions exerted by inhibiting or improving the decline in renal function. For example, the composition of the present invention may be labeled with an indication of one or more functions, such as "prevention of renal dysfunction," "improvement of renal function," or "prevention of renal disease." 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.

[0032] The present invention also encompasses the following methods and uses. A method for inhibiting or improving decline in renal function, comprising administering or having a subject ingest L-ergothioneine or a salt thereof. Use of L-ergothioneine or a salt thereof for suppressing decline in renal function or improving renal function. When L-ergothioneine or a salt thereof is ingested or administered to a subject, it is possible to inhibit decline in renal function or improve renal function. Preferably, L-ergothioneine or a salt thereof is ingested or administered orally. The method may be a therapeutic method or a non-therapeutic method. The use may be a therapeutic use or a non-therapeutic use.

[0033] In the above-mentioned methods and uses, L-ergothioneine or a salt thereof, and preferred embodiments thereof, are the same as those of the composition for suppressing or ameliorating renal function decline of the present invention described above. In the above-mentioned methods and uses, it is preferable that L-ergothioneine or a salt thereof is ingested or administered to a subject at least once a day, for example, once to several times (e.g., 2 to 3 times) a day. The above-mentioned uses are preferably used in humans or non-human mammals, more preferably in humans. In one aspect, L-ergothioneine or a salt thereof can be used to suppress or improve renal function decline, thereby preventing or ameliorating, for example, renal dysfunction, renal failure, glomerulonephritis, uremia, gout, or uric acid stones.

[0034] In the above-mentioned methods and uses, L-ergothioneine or a salt thereof may be used in an amount (which may also be referred to as an effective amount) that is effective in suppressing or improving renal function decline. The preferred dosage and administration targets of L-ergothioneine or a salt thereof are the same as those of the composition for suppressing or improving renal function decline 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.

[0035] L-ergothioneine or a salt thereof can be used for producing foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. that are used to suppress or improve decline in renal function. In one aspect, the present invention also encompasses the use of L-ergothioneine or a salt thereof for producing a composition for suppressing or improving decline in renal function. The present invention also encompasses L-ergothioneine or a salt thereof used for inhibiting or ameliorating decline in renal function. [Example]

[0036] 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.

[0037] Example 1 (Evaluation of blood renal function markers in humans) To evaluate the effects of an ergothioneine-containing supplement on human blood renal function marker levels, a placebo-controlled, randomized, double-blind, parallel-group comparative study was conducted in 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), subjects' blood renal function marker levels were measured as a pre-test. After taking the test food or control food for four weeks, subjects' blood renal function marker levels were measured again (week 4 test). The renal function markers measured were BUN, uric acid, and creatinine.

[0038] (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).

[0039] (BUN) For each subject, the BUN measurement value at the pre-test was subtracted from the BUN measurement value at the 4-week test (measurement value at the 4-week test - measurement value at the pre-test) to calculate the delta value (change in BUN value) (mg / dL). The average value of the above delta values ​​for the subjects in the test food group was used as the change in BUN value (ΔBUN) for the test food group. The average value of the above delta values ​​for the subjects in the control food group was used as the change in BUN value (ΔBUN) for the control food group. The change in BUN value at the pre-test was set to 0. The results are shown in Figure 1.

[0040] Figure 1 is a graph showing the change in BUN values ​​(ΔBUN) for the test food group and the control food group. In Figures 1, 2, and 3, ■ (black squares) represent the test food group, and □ (white squares) represent the control food group. The units on the vertical axis in Figures 1, 2, and 3 are mg / dL. On the horizontal axis, "Pre" represents the time of the pre-test, and "Week 4" represents the time of the 4-week test. As a result, BUN levels were reduced in the test food group compared to the control food group.

[0041] (uric acid level) For each subject, the uric acid measurement value at the pre-test was subtracted from the uric acid measurement value at the 4-week test (measurement value at the 4-week test - measurement value at the pre-test) to calculate the delta value (change in uric acid level) (mg / dL). The average value of the above delta values ​​for the subjects in the test food group was used as the change in uric acid level (delta uric acid) for the test food group. The average value of the above delta values ​​for the subjects in the control food group was used as the change in uric acid level (delta uric acid) for the control food group. The change in uric acid level at the pre-test was set to 0. The results are shown in Figure 2.

[0042] Figure 2 is a graph showing the change in blood uric acid levels (Δuric acid) in the test food group and the control food group. As a result, blood uric acid levels were lower in the test food group than in the control food group.

[0043] (creatinine level) For each subject, the creatinine measurement value at the pre-test was subtracted from the creatinine measurement value at the 4-week test (measurement value at the 4-week test - measurement value at the pre-test) to calculate the delta value (change in creatinine level) (mg / dL). The average value of the above delta values ​​for the subjects in the test food group was used as the change in creatinine levels for the test food group (delta creatinine). The average value of the above delta values ​​for the subjects in the control food group was used as the change in creatinine levels for the control food group (delta creatinine). The change in creatinine levels at the pre-test was set to 0. The results are shown in Figure 3.

[0044] Figure 3 is a graph showing the change in blood creatinine levels (Δcreatinine) in the test food group and the control food group. As a result, the increase in blood creatinine levels was more suppressed in the test food group than in the control food group.

[0045] The above results demonstrate that L-ergothioneine or a salt thereof has the effect of suppressing or improving the decline in renal function.

Claims

1. A composition for suppressing or improving decline in renal function, comprising L-ergothioneine or a salt thereof as an active ingredient.

2. The composition according to claim 1, which has the effect of suppressing or lowering an increase in blood urea nitrogen (BUN) levels.

3. The composition according to claim 1 or 2, which has the effect of suppressing or lowering an increase in uric acid levels in the blood.

4. The composition according to any one of claims 1 to 3, which has an effect of suppressing an increase in or lowering blood creatinine levels.

5. The composition according to any one of claims 1 to 4, which is an oral composition.

6. The composition according to any one of claims 1 to 5, which is a food or drink.

7. 7. 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.

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