Composition for reducing blood uric acid levels

Abstract

Providing technology to reduce blood uric acid levels. [Solution] A composition for reducing blood uric acid levels, comprising a predetermined peptide.

Description

Technical Field

[0001] The present disclosure relates to a composition for reducing blood uric acid levels.

Background Art

[0002] Uric acid is the end product of the metabolism of nucleic acids, ATP which is an energy source in the body, or purine substances derived from food and beverages in humans, and the uric acid, which is the end product generated in the body, is mainly excreted from the kidneys. Various factors act on the pathway from the generation to the excretion of uric acid. When the production of uric acid becomes excessive or the excretion amount decreases, the blood uric acid level increases and hyperuricemia occurs. As these factors, obesity, overeating, drinking alcohol, excessive exercise (anaerobic exercise), stress, etc. are known. Furthermore, when hyperuricemia persists for a long time and uric acid accumulates in joints and crystallizes, gout develops. While repeating gout attacks and remission, the condition deteriorates, and kidney stones or ureteral stones may also occur concomitantly. Due to changes in lifestyle habits such as recent eating habits in Japan, the number of gout patients is on an increasing trend, and furthermore, the number of patients with hyperuricemia, which is regarded as a gout reserve army, is also increasing.

[0003] The treatment of gout is divided into the treatment of gout attacks and the treatment of hyperuricemia. The treatment of gout attacks is drug treatment mainly centered on non-steroidal anti-inflammatory drugs. For the treatment of hyperuricemia, there are improvement of lifestyle habits and drug treatment with uric acid-lowering drugs, and the treatment is carried out according to the degree of hyperuricemia and concomitant conditions. Gout and hyperuricemia often show concomitant conditions such as obesity, hypertension, and abnormal glucose and lipid metabolism (Non-Patent Document 1).

[0004] Current drug treatments for hyperuricemia include two approaches: one that inhibits uric acid production by inhibiting the activity of the enzyme xanthine oxidase, which produces uric acid from xanthine (Non-Patent Literature 2, Non-Patent Literature 3), and another that promotes uric acid excretion by inhibiting uric acid reuptake. These methods use drugs from these approaches to lower blood uric acid levels. Currently used therapeutic agents include uric acid production inhibitors such as allopurinol and febuxostat, and uric acid excretion promoters such as benzbromarone and probenecid. However, since each drug has its own unique side effects in addition to its benefits, there is a need for the development of new treatments, as well as for drugs that can be administered with greater peace of mind. For example, Patent Document 1 discloses a xanthine oxidase inhibitor containing pimenthol isolated from an extract of allspice (the fruit of Pimenta dioica Merrill, a member of the Myrtaceae family) as an active ingredient. Furthermore, Patent Document 2 discloses a serum uric acid lowering agent in which a protein extracted from rice endosperm with alkali and then precipitated with acid and dried is used as the active ingredient. Furthermore, Patent Document 3 discloses a blood uric acid level lowering agent in which a cheese enzyme hydrolysate obtained by treating cheese with lipase and protease is used as the active ingredient. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2011-132173 [Patent Document 2] International Publication No. 2015 / 098474 [Patent Document 3] International Publication No. 2011 / 102310 [Non-patent literature]

[0006] [Non-Patent Document 1] Japanese Society for Gout and Nucleic Acid Metabolism supervised, Treatment Guidelines for Hyperuricemia and Gout, 3rd Edition [2022 Supplement], Shindan to Chiryo Co., Ltd., p. 28, "1. Treatment Goals" section, published March 7, 2022. [Non-Patent Document 2] American Journal of Kidney Diseases, Vol.47, No.1 (January), 2006: pp 51-59 [Non-Patent Document 3] Journal of Ethnopharmacology, 175, pp.14-20 (2015) [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] This disclosure aims to provide a technology for reducing blood uric acid levels. [Means for solving the problem]

[0008] The present inventors have found that a certain peptide can solve the above problem. This disclosure can provide the following:

[0009] <1> A composition for reducing blood uric acid levels, comprising one or more peptides selected from the group consisting of (a) to (m) below. (a) Leu-Asp-Gln-Trp (Sequence ID 1) (b) Asp-Gln-Trp (c)Ala-Leu-Pro-Met(Sequence ID 2) (d) Ile-Lys (e) Lys-Ile-Pro-Ala (Sequence ID 3) (f)Leu-Asp (g)Leu-Lys (h) Pro-Glu-Trp (i) Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 4) (j)Val-Ile (k)Val-Leu (l) Val-Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 5) (m) Trp-Tyr <2> The composition according to <1>, wherein the reduction of blood uric acid level is achieved by inhibiting the activity of xanthine oxidase. <3> A composition for inhibiting xanthine oxidase activity, comprising one or more peptides selected from the group consisting of the following (a) to (m). (a) Leu-Asp-Gln-Trp (SEQ ID NO: 1) (b) Asp-Gln-Trp (c) Ala-Leu-Pro-Met (SEQ ID NO: 2) (d) Ile-Lys (e) Lys-Ile-Pro-Ala (SEQ ID NO: 3) (f) Leu-Asp (g) Leu-Lys (h) Pro-Glu-Trp (i) Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 4) (j) Val-Ile (k) Val-Leu (l) Val-Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 5) (m) Trp-Tyr <4> The composition according to any one of <1> to <3>, which is a food or drink composition. <5> The composition according to any one of <1> to <3>, which is a pharmaceutical composition.

Advantages of the Invention

[0010] According to the present disclosure, a technique for reducing blood uric acid level can be provided.

Modes for Carrying Out the Invention

[0011] Hereinafter, the details of the present disclosure will be described. However, the present disclosure is not limited to the following modes and can be freely changed within the scope of the present disclosure.

[0012] In this disclosure, (a) A peptide consisting of the amino acid sequence represented by Leu-Asp-Gln-Trp (SEQ ID NO: 1) is sometimes referred to as "LDQW". (b) A peptide consisting of the amino acid sequence represented by Asp-Gln-Trp is sometimes written as "DQW". (c) The peptide consisting of the amino acid sequence represented by Ala-Leu-Pro-Met (SEQ ID NO: 2) is sometimes referred to as "ALPM". (d) A peptide consisting of an amino acid sequence represented by Ile-Lys is sometimes referred to as "IK". (e) A peptide consisting of the amino acid sequence represented by Lys-Ile-Pro-Ala (SEQ ID NO: 3) is sometimes referred to as "KIPA". (f) Peptides consisting of amino acid sequences represented by Leu-Asp are sometimes referred to as "LD". (g) A peptide consisting of an amino acid sequence represented by Leu-Lys is sometimes written as "LK". (h) A peptide consisting of an amino acid sequence represented by Pro-Glu-Trp is sometimes referred to as "PEW". (i) A peptide consisting of the amino acid sequence represented by Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 4) is sometimes referred to as "SLPEW". (j) A peptide consisting of an amino acid sequence represented by Val-Ile is sometimes referred to as "VI". (k) A peptide consisting of an amino acid sequence represented by Val-Leu is sometimes written as "VL". (l) A peptide consisting of the amino acid sequence represented by Val-Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 5) is sometimes referred to as "VSLPEW". Peptides consisting of the amino acid sequence represented by (m)Trp-Tyr are sometimes denoted as "WY".

[0013] In this disclosure, percentages are expressed in terms of mass unless otherwise specified. In this disclosure, words such as "ingestion," "ingestion," and "ingested" can be replaced with words such as "administration," "being administered," and "administered," respectively. In this disclosure, "X~Y" indicating a range means "X or greater and Y or less". Furthermore, when numerical ranges expressed as "X~Y" or "X or greater and Y or less" are listed in stages (for example, in preferred order), the upper and lower limits of each numerical range can be any combination. In this disclosure, any phrase such as "one or more selected from the group consisting of X, Y, and Z" means any of X, Y, Z, a combination of X and Y, a combination of X and Z, a combination of Y and Z, or a combination of X, Y, and Z. In this disclosure, any mention of "X such as x1, x2, and x3" is merely an example of X, and does not imply that X is limited to x1, x2, and x3.

[0014] <Composition for reducing blood uric acid levels> One aspect of this disclosure is, This is a composition for reducing blood uric acid levels, comprising one or more peptides selected from the group consisting of (a) to (m) below. Hereinafter, it may be referred to as "the composition of this embodiment." (a) Leu-Asp-Gln-Trp (Sequence ID 1) (b) Asp-Gln-Trp (c)Ala-Leu-Pro-Met(Sequence ID 2) (d) Ile-Lys (e) Lys-Ile-Pro-Ala (Sequence ID 3) (f)Leu-Asp (g)Leu-Lys (h) Pro-Glu-Trp (i) Ser-Leu-Pro-Glu-Trp (SEQ ID NO: 4) (j)Val-Ile (k)Val-Leu (l) Val-Ser-Leu-Pro-Glu-Trp (Sequence ID 5) (m)Trp-Tyr

[0015] The composition of this embodiment may contain one or more peptides selected from the group consisting of (a) to (m) above as an active ingredient. Furthermore, the composition of this embodiment may consist of one or more peptides selected from the group consisting of (a) to (m). Furthermore, the composition of this embodiment may consist of one or more peptides selected from the group consisting of (a) to (m) above as an active ingredient.

[0016] The peptide in this embodiment may be a physiologically acceptable salt or solvate thereof. That is, the composition in this embodiment may contain the peptide in this embodiment, or a physiologically acceptable salt or solvate thereof, and may contain one or more of these. The term "physiologically acceptable salt" is not particularly limited as long as it is physiologically acceptable. Examples include alkali metal salts (such as sodium salts and potassium salts) and alkaline earth metal salts (such as calcium salts and magnesium salts). The term "physiologically acceptable solvate" is not particularly limited as long as it is physiologically acceptable. Examples include solvates of water, alcohol-based solvents (such as ethanol), etc. The solvate is preferably low in toxicity and water-soluble. The solvate also includes the solvate of the "physiologically acceptable salt" mentioned above.

[0017] The peptide in this embodiment is, for example, (1) A method (chemical synthesis method) in which the peptide in this embodiment is synthesized by a peptide synthesis method, and then the peptide in this embodiment is separated and purified from the obtained crude product. (2) A method for producing or modifying the peptides in this embodiment, extracting them from plants, animals, or microorganisms, and separating and purifying the resulting extracts (biosynthesis method), It can be obtained by the following means.

[0018] The chemical synthesis of peptides can be carried out by liquid-phase or solid-phase methods commonly used for peptide synthesis. The synthesized peptides can be deprotected as needed to remove unreacted reagents and by-products, allowing for the isolation of the peptides in this embodiment. Such peptide synthesis can be carried out using commercially available peptide synthesizers. Peptide biosynthesis can be carried out by conventional methods, such as introducing a peptide expression vector into a host organism to induce its production and secretion. Furthermore, for peptides in this embodiment produced by chemical synthesis or biosynthesis, known separation Purification may be carried out as appropriate. For example, molecular weight fractionation may be performed to obtain a fraction corresponding to the molecular weight of the peptide in this embodiment. Methods for molecular weight fractionation include, for example, ultrafiltration and gel filtration, which can improve the removal rate of unwanted peptides and free amino acids. In the case of ultrafiltration, a desired ultrafiltration membrane can be used, and in the case of gel filtration, a gel filter medium used in exclusion chromatography of the desired size can be used. Furthermore, known separation and purification methods may be used to remove salts, impurities, and increase purity. Examples include various types of chromatography such as ion exchange chromatography, adsorption chromatography, reversed-phase chromatography, and partition chromatography, as well as solvent precipitation, salting out, and partitioning between two liquid phases. The separated and purified peptide fraction can be identified by mass spectrometry or other methods to confirm whether it contains the peptide described in this embodiment.

[0019] The target of ingesting the composition of this embodiment is a person who needs to reduce their blood uric acid levels. The target may be a human or a mammal other than a human. Examples of mammals other than humans include cattle, goats, sheep, pigs, monkeys, dogs, cats, rats, mice, hamsters, guinea pigs, etc. In this disclosure, the word "person" is sometimes used, such as "healthy person," assuming the target is a human, but if the target is not a human, it may be replaced with a word equivalent to "person."

[0020] As described in the background technology section, in the drug treatment of hyperuricemia, there is a system that suppresses uric acid production by inhibiting the activity of the enzyme xanthine oxidase, which produces uric acid from xanthine. This reduces blood uric acid levels. As demonstrated in the examples described later, the peptide in this embodiment inhibits the activity of xanthine oxidase. Therefore, the peptide in this embodiment is expected to have the effect of reducing blood uric acid levels. Therefore, it is preferable that the reduction of blood uric acid levels in this embodiment is achieved by inhibiting the activity of xanthine oxidase.

[0021] The inhibition of xanthine oxidase activity by the peptide in this embodiment can be evaluated by conventional methods. For example, as shown in the examples described later, it can be evaluated by quantifying the uric acid produced by xanthine oxidase using xanthine as a substrate. Specifically, a sample containing a xanthine oxidase solution, with a buffer added instead of the peptide in this embodiment, can be used as a control, and the inhibition rate (%) relative to the control can be evaluated. A higher value of the inhibition rate (%) indicates a greater inhibition of xanthine oxidase activity. The inhibition rate (%) is, for example, 20.2% or higher, while the upper limit is preferably high and not particularly limited, but for example, 100% or less, 90.0% or less, 80.0% or less, 70.0% or less, etc. These can be inconsistent combinations. For example, 20.2% to 100%, 20.2% to 90.0%, 20.2% to 80.0%, 20.2% to 70.0%, etc.

[0022] The composition according to this embodiment has the effect of reducing blood uric acid levels. Therefore, the composition according to this embodiment can be used to reduce blood uric acid levels. The composition of this embodiment can be used to prevent or treat diseases, signs, symptoms, or disorders (in this disclosure, "diseases, signs, symptoms, or disorders" may be referred to as "diseases, etc.") that can be prevented or treated by reducing blood uric acid levels. The diseases in question may be those caused by high levels of uric acid in the blood. Examples include hyperuricemia and gout.

[0023] The composition of this embodiment may be used for non-therapeutic purposes or for therapeutic purposes. "Non-therapeutic purposes" refer to purposes that do not involve medical procedures. In other words, purposes that do not involve treatment or intervention on the subject. Examples include purposes for maintaining or promoting health.

[0024] When the composition of this embodiment is used for non-therapeutic purposes, it can be used on healthy individuals. "Healthy person" means a person who, at the time of ingesting the composition of this embodiment, does not have a disease or other condition that can be prevented or treated by reducing blood uric acid levels (for example, a person who is not a patient with a disease or other condition that can be prevented or treated by reducing blood uric acid levels), and may include a person who is concerned about such a disease or other condition, or a person who is prone to such a disease or other condition. When the composition of this embodiment is used for non-therapeutic purposes, it may reduce blood uric acid levels in healthy individuals. It may also help prevent diseases in healthy individuals.

[0025] When the composition of this embodiment is used for therapeutic purposes, it may be used on non-healthy individuals. "Non-healthy person" may refer to a person who, at the time of ingesting the composition of this embodiment, is suffering from a disease that can be treated by reducing blood uric acid levels (for example, a patient with a disease that can be treated by reducing blood uric acid levels). When the composition of this embodiment is used for therapeutic purposes, it may reduce blood uric acid levels in non-healthy individuals. Furthermore, it may be used to treat diseases or other conditions in non-healthy individuals.

[0026] Furthermore, symptoms resulting from high uric acid levels in the blood may be classified into "symptoms caused by diseases, etc." and "symptoms caused by factors other than diseases, etc." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be intended for "symptoms caused by factors other than diseases, etc." and may be targeted at healthy individuals.

[0027] Furthermore, symptoms that appear in diseases that can be prevented or treated by reducing blood uric acid levels may be classified into "symptoms caused by diseases, etc." and "symptoms caused by factors other than diseases, etc." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be for "symptoms caused by factors other than diseases, etc." and may be targeted at healthy individuals. To illustrate with specific examples, the symptoms that appear in hyperuricemia can be divided into "symptoms that appear in hyperuricemia caused by diseases, etc." and "symptoms that appear in hyperuricemia caused by factors other than diseases, etc." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be intended for "symptoms that appear in hyperuricemia caused by factors other than diseases, etc." and may be targeted at healthy individuals.

[0028] This disclosure can provide the use of one or more peptides selected from the group consisting of (a) to (m) above for producing a composition for reducing blood uric acid levels in healthy individuals (which may be a food or beverage composition, for example, a health food or beverage). Furthermore, this disclosure can provide the use of one or more peptides selected from the group consisting of (a) to (m) above for producing food and beverage compositions (e.g., health foods and beverages) that prevent or improve symptoms caused by high uric acid levels in the blood of healthy individuals. Furthermore, this disclosure can provide the use of one or more peptides selected from the group consisting of (a) to (m) above for producing food and beverage compositions (e.g., health foods and beverages) that prevent or improve symptoms appearing in diseases that can be prevented or treated by reducing blood uric acid levels in healthy individuals.

[0029] When the composition of this embodiment is used for non-therapeutic purposes, it may prevent or improve symptoms that appear in diseases, etc., that can be prevented or treated by reducing blood uric acid levels in healthy individuals.

[0030] The content of the peptide in the composition of this embodiment is set appropriately depending on the embodiment of the composition, but in total, in order of increasing preference, is 0.000001% or more, 0.000005% or more, 0.00001% or more, 0.0001% or more, and 0.001% or more. The percentages, in increasing order of preference, are 100% or less, 20% or less, and 10% or less. Non-contradictory combinations of these are also acceptable. For example, 0.000001% to 100%, 0.000005% to 20%, 0.00001% to 10%, 0.0001% to 10%, 0.001% to 10%, etc.

[0031] The intake amount (effective amount) of the composition in this embodiment is appropriately set depending on the form of the composition, method of use, target, age, sex of the target, and other conditions, but is not particularly limited as long as the effect of reducing blood uric acid levels is exerted in the target who ingests it. The total amount of peptide in this embodiment is preferably 0.001 mg or more, more preferably 0.005 mg or more, and even more preferably 0.01 mg or more per day and per 60 kg of body weight, while preferably 5 g or less, more preferably 1 g or less, and even more preferably 0.5 g or less. Non-contradictory combinations of these are also acceptable. For example, 0.001 mg to 5 g, 0.005 mg to 1 g, 0.01 mg to 0.5 g, etc.

[0032] The composition according to this embodiment can be taken once a day or in divided doses. It may also be taken once every few days or weeks, but it is preferable to take it daily.

[0033] The composition of this embodiment can be taken orally, but is not limited to this. For example, it may be taken nasally, or by gastrostomy or jejunostomy. For example, it may be taken to a subject via a nasogastric feeding tube or the like.

[0034] The composition according to this embodiment can be used, for example, as a food or beverage composition or a pharmaceutical composition. For example, it can be provided as a food or beverage composition for reducing blood uric acid levels, containing the peptide according to this embodiment. Hereinafter, this may be referred to as "the food or beverage composition according to this embodiment." Furthermore, the peptide according to this embodiment can be provided as a pharmaceutical composition for reducing blood uric acid levels. Hereinafter, this may be referred to as "the pharmaceutical composition according to this embodiment."

[0035] The food and beverage composition of this embodiment is not particularly limited as long as it contains the peptide of this embodiment. The food and beverage composition may be food or beverage in any form, such as liquid, paste, gel-like solid, or powder, and may include tablets, liquid foods, etc., as well as wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken batter, breadcrumbs; instant foods such as instant noodles, cup noodles, retort / prepared foods, canned prepared foods, microwaveable foods, instant soups / stews, instant miso soup / clear soup, canned soups, freeze-dried foods, and other instant foods; canned agricultural products, canned fruits Processed agricultural products such as jams and marmalades, pickles, boiled beans, dried agricultural products, and cereals (grain processed products); processed marine products such as canned seafood, fish ham and sausages, processed seafood products, seafood delicacies, and tsukudani (simmered seafood); processed livestock products such as canned and paste products, and meat ham and sausages; processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheeses, ice creams, powdered milk, cream, and other dairy products; fats and oils such as butter, margarine, and vegetable oils; soy sauce, miso, and sausages. Basic seasonings such as vinegars, tomato-based seasonings, mirin, and vinegars; compound seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soup bases, spices, and other compound seasonings; frozen foods such as raw frozen foods, semi-cooked frozen foods, and cooked frozen foods; and confectionery such as caramel, candy, gummy candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, dessert sweets, jelly, and other sweets. Examples of beverages include: carbonated drinks, natural fruit juices, fruit juice beverages, fruit juice-containing soft drinks, fruit pulp beverages, fruit juices with fruit pulp, vegetable beverages, soy milk, soy milk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages, sports drinks, nutritional beverages, alcoholic beverages, and other beverages for enjoyment; baby food, furikake (rice seasoning), nori (rice seasoning for ochazuke), and other commercially available foods; infant formula; enteral nutrition; foods for special dietary uses; foods with health claims (foods for specified health uses, foods with nutritional function claims, foods with functional claims); and nutritional supplements. Furthermore, the food and beverage composition of this embodiment may be a supplement, for example, in tablet form. It may also be in the form of a supplement. If it is a supplement, the peptide in this embodiment can be ingested without being affected by other foods in terms of the amount of food consumed and calories taken per day.

[0036] The food and beverage composition according to this embodiment can be manufactured by adding the peptide according to this embodiment to the raw materials of ordinary food and beverages, and can be manufactured in the same manner as ordinary food and beverages, except for the addition of the peptide according to this embodiment. The addition of the peptide according to this embodiment may be carried out at any stage in the manufacturing process of the food and beverage composition.

[0037] The food and beverage composition in this embodiment also includes raw materials for manufacturing the food and beverage composition, and food additives, etc., that are added to the food and beverage composition during or after the manufacturing process.

[0038] Furthermore, the food and beverage composition of this embodiment may use known or future-discovered prebiotic components or components that support prebiotic effects (hereinafter referred to as "prebiotics"), as long as they do not impair the effects of this embodiment. For example, the food and beverage composition of this embodiment can be manufactured by combining prebiotics such as various proteins or mixtures thereof, or hydrolysates, such as whey protein, casein protein, soy protein, or pea protein; amino acids such as leucine, valine, isoleucine, or glutamine; vitamins such as vitamin B6 or vitamin C; creatine; citric acid; fish oil; or oligosaccharides such as isomaltoligosaccharide, xylooligosaccharide, soy oligosaccharide, fructooligosaccharide, or lactulose, with the peptide of this embodiment.

[0039] The content of the peptide in the food and beverage composition of this embodiment is set appropriately depending on the embodiment of the food and beverage composition, but in terms of total amount, in order of increasing preference, it is 0.000001% or more, 0.000005% or more, 0.00001% or more, 0.0001% or more, and 0.001% or more, while in order of increasing preference, it is 100% or less, 20% or less, and 10% or less. Non-contradictory combinations of these are also acceptable. For example, 0.000001% to 100%, 0.000005% to 20%, 0.00001% to 10%, 0.0001% to 10%, 0.001% to 10%, etc.

[0040] The intake amount (effective amount) of the food and beverage composition in this embodiment is appropriately set according to the form of the food and beverage composition, method of use, target, target age, sex, and other conditions, but is not particularly limited as long as the effect of reducing blood uric acid levels is exerted in the target who ingests it. In this embodiment, the total amount of peptide is preferably 0.001 mg or more, more preferably 0.005 mg or more, and even more preferably 0.01 mg or more per day and per 60 kg of body weight, while preferably 5 g or less, more preferably 1 g or less, and even more preferably 0.5 g or less. Non-contradictory combinations of these are also acceptable. For example, 0.001 mg to 5 g, 0.005 mg to 1 g, 0.01 mg to 0.5 g, etc.

[0041] The food and beverage composition of this embodiment can be consumed once or multiple times a day. It may also be consumed once every few days or weeks, but daily consumption is preferable.

[0042] The food and beverage composition according to this embodiment can be sold as a food or beverage composition or food product labeled with the use of reducing blood uric acid levels, etc. Furthermore, it goes without saying that any other wording that describes a secondary effect resulting from the above use can also be used.

[0043] The aforementioned "display" means all actions taken to inform consumers of the above-mentioned use, and any display that can evoke or infer the above-mentioned use falls under the definition of "display" in this embodiment, regardless of the purpose of the display, the content of the display, the object and medium to which it is displayed, etc. However, It is preferable to display the information in a way that allows consumers to directly recognize the above-mentioned uses. Specifically, examples include the act of describing the above-mentioned use on food and beverage compositions or products related to food and beverages according to this embodiment, or on the packaging of such products; the act of transferring, delivering, displaying for transfer or delivery, or importing products or products on which the above-mentioned use is described; describing the above-mentioned use on advertisements, price lists, or transaction documents relating to the products and displaying or distributing them; or describing the above-mentioned use on information containing such materials and providing it by electromagnetic means (such as the Internet). In particular, it is preferable to describe the use on promotional materials at sales sites such as packaging, containers, catalogs, brochures, POP displays, and other documents.

[0044] Furthermore, it is preferable that the labeling be permitted by the government or other administrative bodies (for example, labeling that is approved based on various systems established by the government and carried out in accordance with such approval). For example, examples include labeling as health functional foods, more specifically, health foods, functional foods, enteral nutrition foods, foods for special dietary uses, nutrient function foods, quasi-drugs, etc., and other labels approved by the Consumer Affairs Agency, such as Foods for Specified Health Uses, nutrient function foods, foods with functional claims, and labels approved under similar systems. Examples of the latter include labeling as Foods for Specified Health Uses, labeling as Foods for Specified Health Uses with Conditions, labeling that indicates an effect on the structure or function of the body, labeling that reduces disease risk, labeling that indicates scientifically based functionality, etc. More specifically, examples include labeling as Foods for Specified Health Uses as defined in the Cabinet Office Ordinance concerning the permission of special purpose labeling, etc., as stipulated in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009) (especially labeling for health purposes), and similar labels.

[0045] Examples of such labels include: "For those concerned about uric acid levels," "For those with elevated uric acid levels," "To lower uric acid levels," "To suppress the rise in uric acid levels," and "For those concerned about purines."

[0046] The food and beverage composition of this embodiment can be used for any subject, including healthy and unhealthy individuals. However, if the food or beverage is labeled with a specific use or function, it may be used for the non-therapeutic purposes described above.

[0047] The pharmaceutical composition of this embodiment is not particularly limited as long as it contains the peptide of this embodiment. The pharmaceutical composition of this embodiment may use the peptide of this embodiment as is, or it may be formulated by incorporating a physiologically acceptable liquid or solid pharmaceutical carrier.

[0048] The dosage form of the pharmaceutical composition in this embodiment is not particularly limited, and specific examples include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, ointments, patches, eye drops, and nasal drops. Furthermore, in formulation, additives such as excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, surfactants, or solvents for injections, which are commonly used as formulation carriers, can be used.

[0049] Furthermore, various organic or inorganic carriers can be used as the formulation carrier, depending on the dosage form. Examples of carriers in the case of solid formulations include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, and odor-masking agents.

[0050] Excipients include, for example, sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, and calcium carboxymethylcellulose; gum arabic; dextran; pullulan; and silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate. Examples include: phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate.

[0051] Examples of binders include, in addition to the above-mentioned excipients, gelatin, polyvinylpyrrolidone, macrogol, and the like.

[0052] Examples of disintegrants include, in addition to the above-mentioned excipients, chemically modified starches or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and cross-linked polyvinylpyrrolidone.

[0053] Examples of lubricants include talc; stearic acid; metal stearate salts such as calcium stearate and magnesium stearate; colloidal silica; beegum; waxes such as gayl wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylate salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as anhydrous silicic acid and silicic acid hydrate; and starch derivatives.

[0054] Examples of stabilizers include para-hydroxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; and sorbic acid.

[0055] Examples of flavoring and odor-modifying agents include sweeteners, acidulants, and flavorings. In the case of liquid formulations for oral administration, examples of carriers used include solvents such as water, and flavoring and odor-masking agents.

[0056] The content of the peptide in the pharmaceutical composition of this embodiment is set appropriately depending on the embodiment of the pharmaceutical composition, but in terms of total amount, in order of increasing preference, it is 0.000001% or more, 0.000005% or more, 0.00001% or more, 0.0001% or more, and 0.001% or more, while in order of increasing preference, it is 100% or less, 20% or less, and 10% or less. Non-contradictory combinations of these are also acceptable. For example, 0.000001% to 100%, 0.000005% to 20%, 0.00001% to 10%, 0.0001% to 10%, 0.001% to 10%, etc.

[0057] The dosage (effective dose) of the pharmaceutical composition in this embodiment is appropriately set according to the form of the pharmaceutical composition, method of use, target, age, sex of the target, and other conditions, but is not particularly limited as long as the effect of reducing blood uric acid levels is exerted in the target to whom it is administered. The total amount of the peptide in this embodiment is preferably 0.001 mg or more, more preferably 0.005 mg or more, and even more preferably 0.01 mg or more per day and per 60 kg of body weight, while preferably 5 g or less, more preferably 1 g or less, and even more preferably 0.5 g or less. Non-contradictory combinations of these are also acceptable. For example, 0.001 mg to 5 g, 0.005 mg to 1 g, 0.01 mg to 0.5 g, etc.

[0058] The pharmaceutical composition of this embodiment can be administered once a day or in divided doses. It may also be administered once every few days or weeks, but daily administration is preferred.

[0059] The pharmaceutical composition of this embodiment may be administered to non-healthy individuals for the therapeutic purpose of treating diseases that can be prevented or treated by reducing the blood uric acid level. Furthermore, the pharmaceutical composition according to this embodiment may be administered to healthy individuals for the non-therapeutic purpose of preventing diseases that can be prevented or treated by reducing blood uric acid levels.

[0060] <Composition for inhibiting xanthine oxidase activity> As previously stated, the reduction of blood uric acid levels in this embodiment is preferably achieved by inhibiting the activity of xanthine oxidase. Accordingly, in another aspect, the present disclosure can provide a composition for inhibiting xanthine oxidase activity comprising one or more peptides selected from the group consisting of (a) to (m). In this case, the composition may contain one or more peptides selected from the group consisting of (a) to (m) above as an active ingredient. Furthermore, the composition may consist of one or more peptides selected from the group consisting of (a) to (m) above. Furthermore, the composition may consist of one or more peptides selected from the group consisting of (a) to (m) above as an active ingredient. For further details, please refer to the previously stated explanation of the manner.

[0061] <Composition for suppressing the rise in blood uric acid levels> As previously mentioned, in the drug treatment of hyperuricemia, there is a system that suppresses uric acid production by inhibiting the activity of the enzyme xanthine oxidase, which produces uric acid from xanthine. This also suppresses the rise in blood uric acid levels. As demonstrated in the examples described later, the peptide in this embodiment inhibits the activity of xanthine oxidase. Therefore, the peptide in this embodiment is expected to have the effect of suppressing the rise in blood uric acid levels. Therefore, in another aspect, this disclosure is: A composition for suppressing the rise in blood uric acid levels can be provided, comprising one or more peptides selected from the group consisting of (a) to (m) above. In this case, the composition may contain one or more peptides selected from the group consisting of (a) to (m) above as an active ingredient. Furthermore, the composition may consist of one or more peptides selected from the group consisting of (a) to (m) above. Furthermore, the composition may consist of one or more peptides selected from the group consisting of (a) to (m) above as an active ingredient. For further details, please refer to the previously stated explanation of the manner.

[0062] As previously mentioned, the suppression of the increase in blood uric acid levels is preferably achieved by inhibiting the activity of xanthine oxidase.

[0063] In addition to the embodiments described herein, this disclosure may also provide, for example, the following embodiments: The use of one or more peptides selected from the group consisting of (a) to (m) above for the production of a composition for reducing blood uric acid levels. The use of one or more peptides selected from the group consisting of (a) to (m) above to reduce blood uric acid levels. Use of a composition containing one or more peptides selected from the group consisting of (a) to (m) above for reducing blood uric acid levels. Non-therapeutic use of one or more peptides selected from the group consisting of (a) to (m) above for the purpose of reducing blood uric acid levels. Non-therapeutic use of a composition containing one or more peptides selected from the group consisting of (a) to (m) above for the purpose of reducing blood uric acid levels. One or more peptides selected from the group consisting of (a) to (m) above, for use in reducing blood uric acid levels. A composition containing one or more peptides selected from the group consisting of (a) to (m) above, for use in reducing blood uric acid levels. A method for reducing blood uric acid levels, comprising administering an effective amount of one or more peptides selected from the group consisting of (a) to (m) above to a subject who requires reduction of blood uric acid levels. A method for reducing blood uric acid levels, comprising administering an effective amount of a composition containing one or more peptides selected from the group consisting of (a) to (m) to a subject who requires a reduction in blood uric acid levels.

[0064] In addition to the embodiments described herein, this disclosure may also provide, for example, the following embodiments: Use of one or more peptides selected from the group consisting of (a) to (m) above for producing a composition for inhibiting xanthine oxidase activity. The use of one or more peptides selected from the group consisting of (a) to (m) above to inhibit the activity of xanthine oxidase. Use of a composition containing one or more peptides selected from the group consisting of (a) to (m) above for inhibiting the activity of xanthine oxidase. Non-therapeutic use of one or more peptides selected from the group consisting of (a) to (m) above to inhibit the activity of xanthine oxidase. Non-therapeutic use of a composition containing one or more peptides selected from the group consisting of (a) to (m) above for inhibiting the activity of xanthine oxidase. One or more peptides selected from the group consisting of (a) to (m) above for use in inhibiting xanthine oxidase activity. A composition containing one or more peptides selected from the group consisting of (a) to (m) above, for use in inhibiting xanthine oxidase activity. A method for inhibiting xanthine oxidase activity, comprising administering an effective amount of one or more peptides selected from the group consisting of (a) to (m) above to a subject requiring xanthine oxidase activity inhibition. A method for inhibiting xanthine oxidase activity, comprising administering an effective amount of a composition containing one or more peptides selected from the group consisting of (a) to (m) above to a subject requiring xanthine oxidase activity inhibition.

[0065] In addition to the embodiments described herein, this disclosure may also provide, for example, the following embodiments: The use of one or more peptides selected from the group consisting of (a) to (m) above for producing a composition for suppressing the increase in blood uric acid levels. The use of one or more peptides selected from the group consisting of (a) to (m) above to suppress the increase in blood uric acid levels. Use of a composition containing one or more peptides selected from the group consisting of (a) to (m) above, for the purpose of suppressing an increase in blood uric acid levels. Non-therapeutic use of one or more peptides selected from the group consisting of (a) to (m) above to suppress an increase in blood uric acid levels. Non-therapeutic use of a composition containing one or more peptides selected from the group consisting of (a) to (m) above, for the purpose of suppressing an increase in blood uric acid levels. One or more peptides selected from the group consisting of (a) to (m) above, for use in suppressing the increase in blood uric acid levels. A composition containing one or more peptides selected from the group consisting of (a) to (m) above, for use in suppressing the increase in blood uric acid levels. A method for suppressing an increase in blood uric acid levels, comprising administering an effective amount of one or more peptides selected from the group consisting of (a) to (m) above to a subject who needs to have an increase in blood uric acid levels suppressed. A method for suppressing an increase in blood uric acid levels, comprising administering an effective amount of a composition containing one or more peptides selected from the group consisting of (a) to (m) above to a subject who needs to have an increase in blood uric acid levels suppressed. [Examples]

[0066] The present disclosure will be further described below using examples, but the present disclosure is not limited to these examples.

[0067] [Test Example 1] (Preparation of peptide samples) The peptide samples listed in Table 2 were prepared as follows. One mg of various synthetic peptides (manufactured by BEX) was dissolved in 0.1 M phosphate buffer (pH 7.2) (manufactured by Fujifilm Corporation) (hereinafter referred to as "buffer") with sodium chloride (final concentration 0.1 M) to a concentration of 20 mM, and sonicated for 10 minutes. These were then subjected to peptide saturation. It was used as a sample in the test.

[0068] (Preparation of xanthine oxidase solution) Milk-derived xanthine oxidase (Sigma-Aldrich) was dissolved in buffer to a concentration of 40 U / L or 100 U / L and used as the xanthine oxidase solution for the enzymatic reaction in the test.

[0069] (Preparation of xanthine solution) Xanthine powder (manufactured by Sigma-Aldrich) was weighed, and a 0.5 M sodium hydroxide solution was added to a concentration of 16.8 mM. The mixture was then sonicated for 10 minutes to completely dissolve it. Subsequently, the xanthine solution (1.68 mM) obtained by diluting it 10-fold with buffer was used in the enzymatic reaction. It was used in the test as a xanthine solution.

[0070] (Enzyme reaction) The peptide sample was added to the prepared xanthine oxidase solution. Then, the xanthine solution was added, and the enzymatic reaction was carried out at room temperature for 30 minutes. In this case, samples with buffer added instead of peptide samples were used as controls (controls in Tables 2 and 3). Each sample consisted of three evaluation samples (i.e., n=3 for each sample). After the enzymatic reaction for 30 minutes, immediately add HCl solution to stop the enzymatic reaction, and then add 0.2% (v / v) solution. Analytical samples were obtained by diluting the formic acid solution 50 or 100 times. The analytical samples were then subjected to liquid chromatography. Uric acid metabolized from xanthine by xanthine oxidase was quantitatively analyzed using a tograph-mass spectrometer (LC-MS / MS).

[0071] (Preparation of analytical samples for calibration curves) Weigh the uric acid powder (manufactured by Tokyo Chemical Industry Co., Ltd.) and add 0.5 M hydroxyl to achieve a concentration of 10 mg / mL. Sodium phosphate solution was added, and the mixture was sonicated for 10 minutes to completely dissolve it. Then, serial dilutions were performed with 0.1% formic acid solution to prepare analytical samples for calibration.

[0072] (LC-MS / MS) For high-performance liquid chromatography (HPLC), we used a Vanquish UHPLC (Thermo Fisher Scientific), for mass spectrometry, a Q Exactive Focus (Thermo Fisher Scientific), and for the column, an XBridge Peptide BEH C18 Column (2.1 mm x 250 mm, 3.5 μm, id) (Waters Corporation). For the mobile phase, 0.1% (v / v) aqueous formic acid and 0.1% (v / v) methanol formate were used under the conditions shown in Table 1. The column temperature was set to 40°C and the autosampler tray temperature to 10°C to quantify uric acid in the analytical sample. The uric acid in the analysis sample had a precursor ion / product ion ratio of m / z: 169.03525 / 96.0196, as monitored by parallel reaction monitoring, and retention The area value of the peak detected around 4.3 minutes into the signal time was quantitatively analyzed using the absolute calibration curve method with Thermo Scientific Xcalibur.

[0073] [Table 1]

[0074] Table 2 shows the evaluation results of the xanthine oxidase activity inhibitory effect. The values ​​in the table represent the inhibition rate (%) compared to the control. From the results in Table 2, (a) LDQW, (c) ALPM, (d) IK, (e) KIPA, (f) LD, (g) LK, (h) PEW Significant xanthine oxidase was found in (i) SLPEW, (j) VI, (k) VL, (l) VSLPEW, and (m) WY. An inhibitory effect on activity was observed.

[0075] [Table 2]

[0076] Table 3 shows the evaluation results of the xanthine oxidase activity inhibitory effect. The values ​​in the table represent the inhibition rate (%) compared to the control. From the results in Table 3, (b) DQW showed a significant xanthine oxidase activity inhibitory effect. Ta.

[0077] [Table 3]

Claims

1. A composition for reducing blood uric acid levels, comprising one or more peptides selected from the group consisting of (a) to (m) below. (a) Leu-Asp-Gln-Trp (Sequence ID 1) (b) Asp-Gln-Trp (c) Ala-Leu-Pro-Met (SEQ ID NO: 2) (d) Ile-Lys (e) Lys-Ile-Pro-Ala (SEQ ID NO: 3) (f) Leu-Asp (g) Leu-Lys (h) Pro-Glu-Trp (i) Ser-Leu-Pro-Glu-Trp (Sequence ID 4) (j) Val-Ile (k) Val-Leu (l) Val-Ser-Leu-Pro-Glu-Trp (Sequence ID 5) (m) Trp-Tyr

2. The composition according to claim 1, wherein the reduction in blood uric acid levels is due to inhibiting the activity of xanthine oxidase.

3. A composition for inhibiting xanthine oxidase activity, comprising one or more peptides selected from the group consisting of (a) to (m) below. (a) Leu-Asp-Gln-Trp (Sequence ID 1) (b) Asp-Gln-Trp (c) Ala-Leu-Pro-Met (SEQ ID NO: 2) (d) Ile-Lys (e) Lys-Ile-Pro-Ala (SEQ ID NO: 3) (f) Leu-Asp (g) Leu-Lys (h) Pro-Glu-Trp (i) Ser-Leu-Pro-Glu-Trp (Sequence ID 4) (j) Val-Ile (k) Val-Leu (l) Val-Ser-Leu-Pro-Glu-Trp (Sequence ID 5) (m) Trp-Tyr

4. A food and beverage composition according to any one of claims 1 to 3.

5. A pharmaceutical composition, as described in any one of claims 1 to 3.

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