Sodium ion scavenger

Abstract

To provide a sodium ion scavenger.SOLUTION: A sodium ion scavenger comprising at least one selected from the group consisting of an α - acid, an iso - α - acid, and a reduced iso - α - acid.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to sodium ion sequestrants. [Background technology]

[0002] The technology for capturing specific ions can reduce the effective concentration of those ions in the body and expel those ions from the body, and therefore may be used to treat diseases caused by high effective concentrations of specific ions in the body, such as heavy atom poisoning, internal radiation exposure, iron overload, and various lifestyle-related diseases.

[0003] In the human body, sodium ions (Na + ) is abundant in extracellular fluid along with chloride ions and plays a role in regulating the osmotic pressure of cells. High sodium ion concentrations in the body can lead to hypernatremia, which can cause nervous system symptoms such as agitation and confusion. It can also increase the burden on the kidneys, which are the organs primarily responsible for excreting salt from the body, and in some cases can cause kidney failure.

[0004] For example, Patent Document 1 discloses a food composition containing alginate as a food composition intended to increase sodium excretion. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 2019-13221 Summary of the Invention [Problem to be solved by the invention]

[0006] Sodium ions are one type of ion whose concentration is important in the body, but there are still few reported examples of techniques for capturing sodium ions, and further development is desired.

[0007] The present disclosure aims to provide a sodium ion sequestering agent. [Means for solving the problem]

[0008] The present disclosure relates, for example, to the following: [1] A sodium ion scavenger containing at least one selected from the group consisting of α acids, iso-α acids, and reduced iso-α acids. [2] The sodium ion scavenger according to [1], which contains at least one selected from the group consisting of hop extract, isomerized hop extract, and reduced product of isomerized hop extract. [3] The sodium ion scavenger according to [1] or [2], which contains at least one selected from the group consisting of iso-α acids, tetrahydroiso-α acids, and hexahydroiso-α acids. [4] The sodium ion scavenger according to any one of [1] to [3], which contains at least one selected from the group consisting of tetrahydroiso-α-acids and hexahydroiso-α-acids. [5] The sodium ion scavenger according to any one of [1] to [4], which is a beverage. [6] A method for capturing sodium ions, comprising contacting at least one selected from the group consisting of α acids, iso-α acids, and reduced iso-α acids with sodium ions. [Effects of the Invention]

[0009] According to the present disclosure, a sodium ion sequestering agent can be provided. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 shows the salt concentration dependence of the amount of sodium ions captured in pure water (pH 6.8) and a solution prepared by adding hydrochloric acid to pure water to adjust the pH to 3.0 under the condition of 0.4 v / v% (854.0 BU) isomerized hop extract in Test Example 3. [Figure 2]FIG. 1 shows the average results at pH 6.8 and pH 3.0 under conditions of 0.4 v / v % (854.0 BU) isomerized hop extract in Test Example 3, and the linear approximation line. [Figure 3] FIG. 1 shows the salt concentration dependence of the amount of sodium ions captured in pure water (pH 6.8) at 0.03 v / v % (64.0 BU) of isomerized hop extract in Test Example 3. [Figure 4] FIG. 1 shows the salt concentration dependence of the amount of sodium ion captured in pure water (pH 6.8), artificial gastric juice from which pectin has been removed, and artificial gastric juice under the condition of 0.4 v / v% (854.0 BU) isomerized hop extract in Test Example 3. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, an embodiment for carrying out the present invention will be described, but the present invention is not limited to the following embodiment.

[0012] The sodium ion scavenger according to one embodiment of the present invention is a sodium ion scavenger. + The term "sequestering agent" refers to a composition that captures sodium ions by physically or chemically adsorbing sodium ions onto a sodium ion-sequestering agent (sodium ion sequestering agent) or by electrostatic interaction, and is preferably a composition that captures sodium ions from a liquid. The sodium ion sequestering agent contains at least one selected from the group consisting of α acids, iso-α acids, and reduced iso-α acids. Hereinafter, at least one selected from the group consisting of α acids, iso-α acids, and reduced iso-α acids is also referred to as "component A." In one embodiment, the sodium ion sequestering agent may contain component A as an active ingredient, or may contain an effective amount of component A.

[0013] <α acid> Alpha acid is a general term for compounds represented by the following general formula (I) (hereinafter also referred to as "compounds of formula (I)"). A sodium ion sequestering agent according to one embodiment may contain one or more compounds of formula (I), and in one aspect may contain multiple compounds of formula (I). In formula (I), R represents a monovalent hydrocarbon group, and in one aspect represents a monovalent aliphatic hydrocarbon group. In a preferred aspect, R represents a monovalent aliphatic hydrocarbon group having from 2 to 5 carbon atoms, and in a more preferred aspect, R represents an alkyl having from 2 to 5 carbon atoms. [ka]

[0014] In a more preferred embodiment, R is ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, [ka] In a further preferred embodiment, R may be isopropyl, isobutyl, sec-butyl, ethyl, or isopentyl. The compound of formula (I) in which R is isopropyl is known as cohumulone. The compound of formula (I) in which R is isobutyl is known as humulone and α-lupulic acid. The compound of formula (I) in which R is sec-butyl is known as adhumulone. The compound of formula (I) in which R is ethyl is known as posthumulone. The compound of formula (I) in which R is isopentyl is known as prehumulone. That is, in a further preferred embodiment, the compound of formula (I) may be cohumulone, humulone, adhumulone, posthumulone, or prehumulone.

[0015] Alpha acids are one of the main components of hop extracts, which will be described later, and are known as a type of bitter component in foods that use hop extracts or processed products thereof, such as beer. Alpha acids contained in hop extracts can be used in the state of the hop extract (contained in the sodium ion scavenger of one embodiment), alpha acids isolated from hop extracts can also be used, and alpha acids artificially synthesized by chemical synthesis and / or enzymatic synthesis can also be used.

[0016] The proportion of α acid in component A may be, for example, 0.01% by mass or more, 0.1% by mass or more, 1.00% by mass or more, 10% by mass or more, 50% by mass or more, 90% by mass or more, 98% by mass or more, or 100% by mass or less, or 99% by mass or less, 95% by mass or less, 80% by mass or less, 40% by mass or less, 5.0% by mass or less, 1.5% by mass or less, 0.5% by mass or less, or 0.05% by mass or less, and these upper and lower limits may be freely combined. Note that sodium ion sequestrants whose main component of component A is an iso-α acid or reduced iso-α acid described below may contain a trace amount of unreacted α acid, and in this case the content of the α acid is usually not more than the above-mentioned upper limit, for example, not more than 1.5% by mass.

[0017] <Hop extract> The hop extract is an extract or concentrate thereof from hop (Humulus lupulus) cones. The hop extract may be liquid or solid. Solid hop extracts can be obtained by substantially removing the solvent from the hop cone extract by concentration and / or drying. Hop extracts can be prepared, for example, by subjecting cones or their compressed material, either directly or after crushing, to an extraction procedure. Examples of extraction methods include extraction with an ethanol solvent and supercritical carbon dioxide extraction, which are used to prepare hop extracts for beer brewing. Other commonly used hop extraction methods can also be used, such as cold or hot immersion of hop cones or their crushed material in a solvent; extraction with heating and stirring followed by filtration to obtain an extract; or percolation. The obtained extract can be filtered or centrifuged to remove solids, if necessary, and then used as is, or after partial concentration and / or drying, depending on the intended use. After concentration and / or drying, the hop extract may be further purified by washing with a non-dissolving solvent, or may be dissolved or suspended in an appropriate solvent for use.Furthermore, the solvent extract obtained as described above may be dried by conventional means such as vacuum drying or freeze-drying to obtain a dried hop extract.

[0018] Examples of solvents (extraction solvents) used in the extraction include water; lower alcohols having 1 to 4 carbon atoms, such as methanol, ethanol, propanol, and butanol; lower alkyl esters, such as ethyl acetate; glycols, such as ethylene glycol, butylene glycol, propylene glycol, and glycerin; polar solvents, such as acetone and acetic acid; hydrocarbons, such as benzene and hexane; and nonpolar solvents, such as ethers, such as ethyl ether and petroleum ether. These solvents may be used alone or in combination of two or more.

[0019] A commercially available hop extract can also be used, such as CO2 Pure Resin Extract (Hopsteiner) which is obtained by extracting mainly humulone compounds and lupulone compounds from crushed hop cones using supercritical carbon dioxide.

[0020] Hop extract contains α acids. The α acids contained in the hop extract are mainly humulone, cohumulone, and adhumulone. The α acid content in the hop extract may be 1.0% by mass or more, 2.0% by mass or more, 3.0% by mass or more, 5.0% by mass or more, 7.0% by mass or more, 10.0% by mass or more, 15.0% by mass or more, or 25.0% by mass or more, based on the total mass of the extract, and may be 80.0% by mass or less, 50.0% by mass or less, 40.0% by mass or less, 35.0% by mass or less, 30.0% by mass or less, 20.0% by mass or less, 12.0% by mass or less, 8.0% by mass or less, 6.0% by mass or less, or 4.0% by mass or less, and these upper and lower limits can be freely combined. For example, the alpha acid content of the hop extract may be 1.0% by mass or more and 80.0% by mass or less, 3.0% by mass or more and 50.0% by mass or less, or 5.0% by mass or more and 35.0% by mass or less, based on the total mass of the extract. The alpha acid content of the hop extract can be measured, for example, by high performance liquid chromatography or ultraviolet spectrophotometry.

[0021] The hop extract may contain other components in addition to α acids, such as at least one selected from the group consisting of β acids (lupulone compounds), extraction solvents, water, tannins, flavonoids, terpenoids, polyphenols, vitamins, minerals, pH adjusters, and buffers.

[0022] <Iso-α acid> Iso-α acids (iso-α acids) are a general term for compounds represented by the following general formula (II) (hereinafter also referred to as "formula (II) compounds"). A sodium ion sequestering agent according to one embodiment may contain one or more types of formula (II) compounds, and in one aspect, may contain multiple types of formula (II) compounds. In formula (II), R is the same as in formula (I). Iso-α acids exist in two stereoisomers, cis and trans, based on the chirality of the quaternary carbon atom indicated by * in formula (II). Iso-α acids according to the present disclosure may be cis or trans, or may be a mixture of cis and trans. [ka]

[0023] The compound of formula (II) where R is isopropyl is known as isocohumulone. The compound of formula (II) where R is isobutyl is known as isohumulone. The compound of formula (II) where R is sec-butyl is known as isoadhumulone. The compound of formula (II) where R is ethyl is known as isoposthumulone. The compound of formula (II) where R is isopentyl is known as isoprehumulone. That is, a further preferred embodiment of the compound of formula (II) may be isocohumulone, isohumulone, isoadhumulone, isoposthumulone, or isoprehumulone.

[0024] Iso-α acids are substances obtained by isomerization of α acids. Because iso-α acids are more water-soluble than α acids, for example, when the sodium ion sequestering agent of this embodiment is a beverage, if Component A contains iso-α acids, a larger amount of Component A can be contained per volume of beverage. Furthermore, because iso-α acids are more stable than α acids, the usable period of the sodium ion sequestering agent tends to be longer when Component A contains iso-α acids.

[0025] The iso-α acids can be those contained in isomerized hop extract, which is an extract obtained by isomerizing α acids contained in hop extract, those isolated from isomerized hop extract, those obtained by isomerizing isolated α acids, or iso-α acids artificially synthesized by chemical synthesis and / or enzymatic synthesis. Isomerized hop extracts sold by suppliers can also be used. Commercially available isomerized hop extracts are available, for example, from Hops Extract Corporation of America.

[0026] Methods for isomerizing α acids are known, and any method may be used. Typically, iso-α acids are isomerized by heating them under weakly alkaline conditions at a pH of 8 to 9 or in the presence of magnesium oxide. α acids are isomerized into iso-α acids by boiling. When isomerizing α acids contained in a hop extract, the hop extract may be subjected to the isomerization treatment directly, or prior to the isomerization treatment, the hop extract may be added to heated alkaline water (pH 8 to 9 after addition of the hop extract), the dissolved α acids may be separated from the insoluble β acids, and the resulting α acid fraction may be subjected to the isomerization treatment.

[0027] The proportion of iso-α acid in component A may be, for example, 0.01% by mass or more, 0.1% by mass or more, 1.00% by mass or more, 10% by mass or more, 50% by mass or more, 90% by mass or more, 98% by mass or more, or 100% by mass or less, or 99% by mass or less, 95% by mass or less, 80% by mass or less, 40% by mass or less, 5.0% by mass or less, 1.5% by mass or less, 0.5% by mass or less, or 0.05% by mass or less, and these upper and lower limits may be freely combined. Note that sodium ion sequestrants whose main component of component A is a reduced iso-α acid described below may contain a small amount of unreacted iso-α acid, and in this case the content of iso-α acid is usually below the above upper limit, for example, 1.5% by mass or less.

[0028] The isomerized hop extract contains iso-α acids. The iso-α acids contained in the isomerized hop extract are mainly cis-isohumulone, cis-isocohumulone, cis-isoadhumulone, trans-isohumulone, trans-isocohumulone, and trans-isoadhumulone. The iso-α acid content in the isomerized hop extract may be 1.0% by mass or more, 2.0% by mass or more, 3.0% by mass or more, 5.0% by mass or more, 7.0% by mass or more, 10.0% by mass or more, 15.0% by mass or more, or 25.0% by mass or more, based on the total mass of the extract, and may be 80.0% by mass or less, 50.0% by mass or less, 40.0% by mass or less, 35.0% by mass or less, 30.0% by mass or less, 20.0% by mass or less, 12.0% by mass or less, 8.0% by mass or less, 6.0% by mass or less, or 4.0% by mass or less, and these upper and lower limits can be freely combined. For example, the iso-α acid content of the isomerized hop extract may be 1.0% by mass or more and 80.0% by mass or less, 3.0% by mass or more and 50.0% by mass or less, or 5.0% by mass or more and 35.0% by mass or less, based on the total mass of the extract. The iso-α acid content of the isomerized hop extract can be measured, for example, by high-performance liquid chromatography or ultraviolet spectrophotometric analysis. In addition to iso-α acids, the isomerized hop extract may contain other components similar to those in hop extracts.

[0029] <Reduced iso-α-acid> Reduced iso-α acids are reduction products of iso-α acids and are a general term for compounds obtained by the reduction of iso-α acids. A sodium ion scavenger according to one embodiment may contain one or more compounds obtained by the reduction of iso-α acids, and in one embodiment, may contain multiple such compounds. In a preferred embodiment, reduced iso-α acids may be compounds obtained by the reduction of iso-α acids using molecular hydrogen as a reducing agent and / or a hydride reducing agent as a reducing agent. That is, in a preferred embodiment, reduced iso-α acids may be compounds obtained by the hydrogenation reaction and / or hydride reduction reaction of iso-α acids. A catalyst used in the hydrogenation reaction of iso-α acids is, for example, a nickel catalyst. A hydride reducing agent used in the hydride reduction of iso-α acids is, for example, sodium borohydride. Reduced iso-α acids exist in the same stereoisomers as those described above for iso-α acids, but the iso-α acids according to the present disclosure may be cis- or trans-isomers, or may be a mixture of cis- and trans-isomers.

[0030] A more preferred embodiment of the reduced iso-α acid includes a compound represented by the following general formula (III) (hereinafter also referred to as "formula (III) compound"), a compound represented by the following general formula (IV) (hereinafter also referred to as "formula (IV) compound"), and a compound represented by the following general formula (V) (hereinafter also referred to as "formula (V) compound"). In formulas (III), (IV), and (V), R is the same as in formula (I). In the formula (III) compound and the formula (V) compound, the stereoisomerism resulting from the chirality of the quaternary carbon atom at the root of the carbonyl reduced to the iso-α acid may be R or S, or a mixture of R and S (meso isomer). [ka] [ka] [ka]

[0031] Compounds of formula (III) are also known collectively as "dihydroiso-α acids" and "rhoiso-α acids." Compounds of formula (IV) are also known collectively as "tetrahydroiso-α acids." Compounds of formula (V) are also known collectively as "hexahydroiso-α acids." In a more preferred embodiment, the reduced iso-α acid may be at least one selected from the group consisting of tetrahydroiso-α acids and hexahydroiso-α acids. When the reduced iso-α acid is at least one selected from the group consisting of tetrahydroiso-α acids and hexahydroiso-α acids, the sodium ion-trapping ability per component A in the sodium ion-trapping agent is increased.

[0032] When component A contains reduced iso-α acids, the sodium ion-sequestering agent tends to have a higher sodium ion-sequestering ability per component A. Because reduced iso-α acids are more water-soluble than α acids, for example, when the sodium ion-sequestering agent of this embodiment is a beverage, if component A contains reduced iso-α acids, a larger amount of component A can be contained per volume of beverage. Furthermore, because reduced iso-α acids are more stable than α acids, the usable period of the sodium ion-sequestering agent tends to be longer when component A contains reduced iso-α acids.

[0033] The reduced iso-α acids can be an extract obtained by reducing iso-α acids contained in isomerized hop extract (reduced product of isomerized hop extract), those isolated from the reduced product of isomerized hop extract, those obtained by reducing the isolated iso-α acids, or reduced iso-α acids artificially synthesized by chemical synthesis and / or enzymatic synthesis. Reduction of iso-α acids can be carried out using the reducing agent described above under reaction conditions typically used by those skilled in the art. Products sold by suppliers can also be used as reduced products of isomerized hop extract. Examples of commercially available reduced products of isomerized hop extract include the Tetra Iso-Extract series (Hopsteiner) and the Hexa Iso-Extract series (Hopsteiner).

[0034] The proportion of reduced iso-α acids in component A may be, for example, 0.01% by mass or more, 0.1% by mass or more, 1.00% by mass or more, 10% by mass or more, 50% by mass or more, 90% by mass or more, 98% by mass or more, or 100% by mass or less, based on the total mass of component A contained in the sodium ion scavenger, or 99% by mass or less, 95% by mass or less, 80% by mass or less, 40% by mass or less, 5.0% by mass or less, 1.5% by mass or less, 0.5% by mass or less, or 0.05% by mass or less, and these upper and lower limits may be freely combined. Furthermore, the proportion of tetrahydroiso-α-acids and / or hexahydroiso-α-acids in component A may be, for example, 0.01% by mass or more, 0.1% by mass or more, 1.00% by mass or more, 10% by mass or more, 50% by mass or more, 90% by mass or more, 98% by mass or more, or 100% by mass or less, based on the total mass of component A contained in the sodium ion scavenger, or may be 99% by mass or less, 95% by mass or less, 80% by mass or less, 40% by mass or less, 5.0% by mass or less, 1.5% by mass or less, 0.5% by mass or less, or 0.05% by mass or less, and these upper and lower limits may be freely combined.

[0035] The reduced product of isomerized hop extract contains reduced iso-α acids. The reduced iso-α acids contained in the reduced product of isomerized hop extract are mainly dihydroiso-α acids (low-iso-α acids), tetrahydroiso-α acids, and hexahydroiso-α acids. The content of reduced iso-α acids in the reduced product of isomerized hop extract may be 1.0% by mass or more, 2.0% by mass or more, 3.0% by mass or more, 5.0% by mass or more, 7.0% by mass or more, 10.0% by mass or more, 15.0% by mass or more, or 25.0% by mass or more, based on the total mass of the extract, and may be 80.0% by mass or less, 50.0% by mass or less, 40.0% by mass or less, 35.0% by mass or less, 30.0% by mass or less, 20.0% by mass or less, 12.0% by mass or less, 8.0% by mass or less, 6.0% by mass or less, or 4.0% by mass or less, and these upper and lower limits can be freely combined. For example, the content of reduced iso-α acids in the reduced product of isomerized hop extract may be 1.0% by mass or more and 80.0% by mass or less, 3.0% by mass or more and 50.0% by mass or less, or 5.0% by mass or more and 35.0% by mass or less, based on the total amount of the extract. The content of reduced iso-α acids in the reduced product of isomerized hop extract can be measured, for example, by high-performance liquid chromatography or ultraviolet spectrophotometric analysis. In addition to reduced iso-α acids, the reduced product of isomerized hop extract may contain other components similar to those in hop extract.

[0036] <Aspects of Component A> Component A may be at least one selected from the group consisting of iso-α acids and reduced iso-α acids, at least one selected from the group consisting of iso-α acids, tetrahydroiso-α acids, and hexahydroiso-α acids, at least one selected from the group consisting of tetrahydroiso-α acids and hexahydroiso-α acids, or tetrahydroiso-α acids or hexahydroiso-α acids. That is, the sodium ion scavenger of one embodiment may contain at least one selected from the group consisting of reduced iso-α acids, at least one selected from the group consisting of iso-α acids, tetrahydroiso-α acids, and hexahydroiso-α acids, at least one selected from the group consisting of tetrahydroiso-α acids and hexahydroiso-α acids, or tetrahydroiso-α acids or hexahydroiso-α acids.

[0037] The form of component A contained in the sodium ion sequestering agent is not particularly limited, and may be component A (compound) or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a mixture thereof. Examples of pharmaceutically acceptable salts include potassium salts, sodium salts, and calcium salts, and preferably potassium salts or sodium salts, more preferably potassium salts. Examples of pharmaceutically acceptable solvates include extract solvates, hydrates, alcohol solvates (e.g., methanol solvates, ethanol solvates), and ether solvates (e.g., diethyl ether solvates).

[0038] The content of component A in the sodium ion scavenger may be, based on BU, 1.0 BU or more, 3.0 BU or more, 6.0 BU or more, 10 BU or more, 15 BU or more, 20 BU or more, 30 BU or more, 40 BU or more, or 50 BU or more, or 1000 BU or less, 300 BU or less, 200 BU or less, 150 BU or less, 120 BU or less, 100 BU or less, 90 BU or less, or 80 BU or less, and these upper and lower limits may be freely combined. For example, the content of component A in the sodium ion scavenger may be, based on BU, 1.0 BU or more and 1000 BU or less, 10 BU or more and 200 BU or less, 30 BU or more and 150 BU or less, or 50 BU or more and 100 BU or less. Such a content of component A can be appropriately selected by those skilled in the art depending on the form of the sodium ion scavenger, etc. Note that BU (Bitterness Units) is an index representing bitterness intensity and the content of bitter substances. The BU may be a value calculated from the measured absorbance according to the following method. First, 20 mL of isooctane and 0.5 mL of 6N hydrochloric acid (6N hydrochloric acid) are added to 10 mL of a sample (e.g., beer, wort, etc.), the mixture is shaken, and the mixture is centrifuged to recover the upper layer (isooctane layer). The absorbance of the isooctane layer at 275 nm is measured, and the obtained measurement value is multiplied by a constant of 50 to obtain the bitterness value (BU).

[0039] Furthermore, as described above, component A may be contained as a hop extract, an isomerized hop extract, or a reduction product of an isomerized hop extract. That is, in one embodiment, the sodium ion scavenger may contain at least one selected from the group consisting of hop extract, an isomerized hop extract, and a reduction product of an isomerized hop extract. In one embodiment when the sodium ion scavenger contains an α acid, the sodium ion scavenger may contain a hop extract, and the α acid may be one contained in the hop extract. In one embodiment when the sodium ion scavenger contains an isomerized hop extract, and the iso-α acid may be one contained in the isomerized hop extract. In one embodiment when the sodium ion scavenger contains a reduced iso-α acid, the sodium ion scavenger may contain a reduction product of an isomerized hop extract, and the reduced iso-α acid may be one contained in the reduction product of the isomerized hop extract.

[0040] <Formulation and additives> The sodium ion scavenger of one embodiment can be administered orally or parenterally, and is preferably administered orally. Oral preparations may be, for example, liquids, granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, or suspensions. Parenteral preparations may be injections (e.g., subcutaneous injections, intravenous injections, intramuscular injections, and intraperitoneal injections) and infusions. When the sodium ion scavenger of one embodiment is an oral preparation, its form may be a food or a pharmaceutical product, or an active ingredient thereof, or an additive therefor, and in one aspect, it may be a food or a food additive. Note that the concept of food in the present disclosure includes beverages.

[0041] A preferred embodiment of the sodium ion scavenger may be a food product, preferably a beverage. The beverage may be an alcoholic or non-alcoholic beverage, more preferably a non-alcoholic beverage. In the present disclosure, an "alcoholic beverage" refers to a beverage having an ethanol concentration of 1% by weight or more. In the present disclosure, a "non-alcoholic beverage" refers to a beverage having an ethanol concentration of less than 1% by weight. The ethanol concentration in a non-alcoholic beverage may be less than 0.5% by weight, less than 0.05% by weight, or less than 0.005% by weight, based on the total amount of the scavenger, or may be 0% by weight (i.e., no ethanol is contained). Examples of non-alcoholic beverages include water, soft drinks (e.g., carbonated water, tea drinks, coffee drinks), fruit juice drinks, dairy drinks, sports drinks, and energy drinks. Examples of foods (excluding beverages) include bread, noodles, rice, tofu, dairy products, soy sauce, miso paste, and confectioneries. In one embodiment, the beverage in the sodium ion sequestering agent may be a beverage other than beer, a beverage other than beer-flavored beverages, or a beverage other than beer and beer-flavored beverages.

[0042] When the sodium ion scavenger is a food, the sodium ion scavenger may be a health food, a food with functional claims, a food with nutrient function claims, a food for specified health uses, or a food for medical patients. Foods with functional claims and foods for specified health uses may be foods that are labeled, for example, as having the function of "increasing the excretion of dietary salt in the feces and lowering high blood pressure" or "having the function of promoting the excretion of dietary salt from the body by adsorbing it and suppressing the absorption of salt ingested from food."

[0043] In one embodiment, the sodium ion sequestering agent may contain pharmaceutically acceptable additives in addition to Component A, or a hop extract, isomerized hop extract, or reduced product of an isomerized hop extract. The additives can be appropriately selected by those skilled in the art depending on the dosage form and shape.

[0044] For example, when the sodium ion sequestering agent of one embodiment is a food product, the additives contained in the sodium ion sequestering agent may include at least one selected from the group consisting of water, buffering agents, coloring agents, stabilizers, sweeteners, acidulants, flavorings, antioxidants, bittering agents, apple fiber, soybean fiber, meat extract, black vinegar extract, gelatin, corn starch, honey, animal and vegetable fats and oils; proteins such as gluten; amino acids; peptides; monosaccharides such as glucose and fructose; disaccharides such as sucrose; polysaccharides such as dextrose and starch; sugar alcohols such as erythritol, xylitol, sorbitol, and mannitol; vitamins such as vitamin C; minerals such as zinc, copper, and magnesium; functional ingredients such as CoQ10, α-lipoic acid, carnitine, capsaicin, and polyphenols; fruit juice; and milk and milk components, or may be at least one selected from the above group. The sodium ion sequestering agent as a food product can be prepared by adding component A, or a hop extract, an isomerized hop extract, or a reduced product of an isomerized hop extract to an intermediate at any stage in the manufacturing process of the food product or to the manufactured food product.

[0045] For example, when the sodium ion scavenger of one embodiment is a pharmaceutical product, the additives contained in the sodium ion scavenger may include at least one selected from the group consisting of excipients, binders, diluents, flavorings, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, and preservatives, or may be at least one selected from the above group. For example, when the sodium ion scavenger is an oral preparation, the pharmaceutical sodium ion scavenger can be produced by adding, for example, an excipient (e.g., lactose, sucrose, starch, mannitol), a disintegrant (e.g., calcium carbonate, carboxymethylcellulose calcium), a binder (e.g., pregelatinized starch, gum arabic, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropyl cellulose), or a lubricant (e.g., talc, magnesium stearate, polyethylene glycol 6000) to component A, a hop extract, an isomerized hop extract, or a reduced product of an isomerized hop extract, followed by compression molding, and then coating, if necessary, for the purposes of taste masking, enteric coating, or sustained release, by a method known per se. Examples of coating agents that can be used include ethyl cellulose, hydroxymethyl cellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, and Eudragit (manufactured by Rohm, Germany, methacrylic acid-acrylic acid copolymer). Furthermore, for example, when the sodium ion scavenger is in the form of an injection, it can be prepared by dissolving, suspending, or emulsifying Component A, or a hop extract, isomerized hop extract, or a reduced product of an isomerized hop extract, together with a dispersant (e.g., Tween 80 (manufactured by Atlas Powder, Inc., USA), HCO60 (manufactured by Nikko Chemicals), polyethylene glycol, carboxymethylcellulose, sodium alginate, etc.), a preservative (e.g., methylparaben, propylparaben, benzyl alcohol, chlorobutanol, phenol), an isotonic agent (e.g., sodium chloride, glycerin, sorbitol, glucose, invert sugar), or the like, in an aqueous solvent (e.g., distilled water, physiological saline, Ringer's solution, etc.) or an oily solvent (e.g., vegetable oils such as olive oil, sesame oil, cottonseed oil, and corn oil, or propylene glycol).

[0046] The sodium scavenger of one embodiment may be one intended for ingestion by or administration to a mammal (e.g., human, mouse, rat, rabbit, dog, cat, cow, horse, pig, monkey, etc.), or one intended for ingestion by or administration to a mammal. The intake or administration amount of the sodium scavenger of one embodiment can be appropriately determined by a person skilled in the art based on the age, body weight, symptoms, intake or administration interval, dosage form, and intake or administration method of the subject. For example, the sodium scavenger of one embodiment may be one intended for ingestion or administration so that the daily dose of the sodium scavenger of one embodiment is 0.10 to 10,000 mg, 1.0 to 1,000 mg, 3.0 to 300 mg, or 10 to 100 mg, calculated as component A, for an adult weighing 60 kg.

[0047] A sodium scavenger according to one embodiment can capture sodium ions, where "capturing" includes adsorption. The ability of a sodium scavenger to capture sodium ions can be evaluated based on, for example, whether the sodium ion concentration in an aqueous solution containing the sodium ion scavenger is reduced after stirring by adding salt or sodium chloride to the aqueous solution and stirring the solution compared to the concentration before stirring. In this case, the sodium ion scavenger may be evaluated as capturing sodium ions when it reduces the sodium ion concentration in the aqueous solution by 5% or more, 10% or more, 15% or more, 20% or more, or 25% or more. In this case, the sodium ion scavenger may be evaluated as capturing sodium ions when it reduces the sodium ion concentration in the aqueous solution by 100 ppm, 300 ppm, 600 ppm, 1000 ppm, 1500 ppm, or 2000 ppm. In this case, the sodium ion scavenger may be evaluated as capturing sodium ions when a positive correlation or linearity is observed in the amount of sodium ions captured when tested at multiple sodium ion concentrations, or when a positive correlation or linearity is observed in the amount of sodium ions captured when tested at multiple sodium ion scavenger concentrations. In the above case, the sodium ion scavenger may be evaluated as scavenging sodium ions when the amount of sodium ions trapped per 1BU of ingredient A when evaluated at a salt concentration of 1 w / v% is 1 ppm or more, 2 ppm or more, 3 ppm or more, 5 ppm or more, 7 ppm or more, 9 ppm or more, 12 ppm or more, 15 ppm or more, or 20 ppm or more.

[0048] When the sodium scavenger according to one embodiment is a beverage, the sodium scavenger may contain a drinkable concentration of component A and may capture sodium. In this case, whether the concentration of component A is within the drinkable concentration range may be evaluated according to a method commonly used by those skilled in the art, for example, by sensory evaluation. An example of a detailed sensory evaluation is the sensory evaluation described in the Examples of the present application. In this case, whether the sodium scavenger captures sodium may be evaluated in the same manner as described above.

[0049] In another aspect, the sodium scavenger of one embodiment may be a method for scavenging sodium ions, comprising contacting component A, or a hop extract, an isomerized hop extract, or a reduced product of an isomerized hop extract, with sodium ions. In another aspect, the sodium scavenger of one embodiment may be use of component A, or a hop extract, an isomerized hop extract, or a reduced product of an isomerized hop extract, in scavenging sodium ions. In another aspect, the sodium scavenger of one embodiment may be use of component A, or a hop extract, an isomerized hop extract, or a reduced product of an isomerized hop extract, for the manufacture of a sodium scavenger. In another aspect, the sodium scavenger of one embodiment may be component A, or a hop extract, an isomerized hop extract, or a reduced product of an isomerized hop extract, for use in scavenging sodium ions. [Example]

[0050] The present invention will be described in more detail below using examples, but the present invention is not limited to the following examples.

[0051] In the following examples, BU (Bitterness Units) was used as an index of the content of component A. BU was calculated according to the following method. First, 20 mL of isooctane and 0.5 mL of 6N hydrochloric acid were added to 10 mL of a sample, and the mixture was shaken and centrifuged, after which the upper layer (isooctane layer) was collected. The absorbance of the isooctane layer at 275 nm was measured, and the obtained measurement value was multiplied by a constant of 50 to obtain the bitterness value (BU).

[0052] The hop extract used in this example was prepared from Saaz hop Type 90 pellets (hop pellets: SAZ (Type 90), EAT) as follows: First, 5.0 g of hop pellets per liter were added to hot water. The resulting mixture was boiled at 100°C for 60 minutes using an autoclave. After boiling, the mixture was filtered using filter paper, and the filtrate was ice-cooled to obtain a hop extract. The theoretical BU value of this hop extract is approximately 78. The BU values ​​in the following tables are calculated from the dilution ratio based on this value.

[0053] The isomerized hop extract used in this example was a commercially available product (hop extract (isomerized hop extract), SS Steiner, Inc.). The iso-α acid content of this isomerized hop extract was 30.0±2.0 w / w%. The α acid and β acid contents of this isomerized hop extract were less than 0.6 w / w% and less than 0.2 w / w%, respectively. The BU of this isomerized hop extract was 276,650. The BU in the following tables is calculated from the dilution ratio based on this value.

[0054] In this example, a commercially available product (Tetrahop Iso Extract, SS Steiner, Inc.) was used as the reduced product of isomerized hop extract containing tetrahydroiso-α acids (hereinafter also referred to as "TETRA extract"). According to the supplier's data sheet, the content of tetrahydroiso-α acids in this TETRA extract was 9.0±0.5 w / w% as measured by HPLC and 10.0±0.5 w / w% as measured by ultraviolet spectrophotometry. Furthermore, the content of α acids and iso-α acids in this TETRA extract was below the detection limit. The BU of this TETRA extract was 63,000. The BU in the following tables is the BU calculated from the dilution ratio based on this value.

[0055] In this example, a commercially available product (Hexa Iso Extract (9:1), SS Steiner, Inc.) was used as the reduced product of isomerized hop extract containing hexahydroiso-α acids (hereinafter also referred to as "HEXA extract"). According to the supplier's data sheet, the hexahydroiso-α acid content of this HEXA extract was 9.0±0.5 w / w% as measured by HPLC. This HEXA extract also contained 1.0±0.5 w / w% tetrahydroiso-α acids, which are unreduced carbonyls, as measured by HPLC. Furthermore, the content of α acids and iso-α acids in this TETRA extract was below the detection limit. The BU of this TETRA extract was 62,000. The BU in the following tables is the BU calculated from the dilution ratio based on this value.

[0056] In this example, as a reference example, a test was also carried out using the alginate salt described in Patent Document 1. As the alginate salt, alginic acid K (manufactured by Kimika Co., Ltd.) and alginic acid NH3 (manufactured by Kimika Co., Ltd.) were used.

[0057] <Test Example 1: Sodium ion capture test in saline solution> The types and concentrations of capture components shown in Tables 1 to 3 were added to pure water (pH 6.8) and a solution prepared by adjusting the pH to 3.0 with hydrochloric acid. 1 w / v% salt was added to the solution, and the mixture was stirred at room temperature for 10 minutes. The sodium ion concentration was measured before and after stirring using a compact sodium ion meter (Na-11, LAQUAtwin, HORIBA) to evaluate the capture rate. The compact sodium ion meter uses a membrane that selectively binds sodium ions, and can measure the sodium ion concentration based on the potential difference (ion electrode method).

[0058] The results are shown in Tables 1 to 3. Table 1 shows the results for isomerized hop extract at pH 3.0. Table 2 shows the results for isomerized hop extract, TETRA extract, and HEXA extract at pH 6.8. Table 3 shows the results for alginate at pH 3.0 and pH 6.8 as a reference example. Tables 1 to 3 show that isomerized hop extract, TETRA extract, and HEXA extract exhibited the ability to capture sodium ions in solutions of pH 3.0 and pH 6.8, similar to the alginate described in Patent Document 1.

[0059] [Table 1] [Table 2] [Table 3]

[0060] <Test Example 2: Sodium ion capture test in artificial gastric juice, artificial intestinal juice, and their continuous conditions> The sodium ion-trapping ability of the trapping components, the types and concentrations of which are shown in Tables 4 to 9, was evaluated under conditions of artificial gastric fluid and artificial intestinal fluid, as well as under conditions of successive exposure from conditions simulating the stomach to conditions simulating the intestine.

[0061] The artificial gastric juice conditions were tested as follows. First, sodium hydroxide was added to a solution composed of 99.5% pure water, 0.3% hydrochloric acid, and 0.2% sodium chloride by mass to adjust the pH to 3.0. The capture component was then added to the solution, followed by 1% salt (w / v) and 0.5% pepsin (w / v), and the mixture was stirred at 37°C for 1 hour. The sodium ion concentration was measured before and after stirring using a compact sodium ion meter (Na-11, LAQUAtwin, HORIBA) to evaluate the capture rate. In the following tables, this condition is shown as pH "3.0." Note that pH 3.0 corresponds to the stomach pH after a meal, and pepsin is the major digestive enzyme present in the stomach.

[0062] The test for the conditions in the artificial intestinal fluid was performed as follows. First, the capture component was added to a solution composed of 99% pure water, 0.7% potassium dihydrogen phosphate, and 0.09% sodium hydroxide, followed by 1% salt (w / v) and 0.5% pancreatin (w / v). The mixture was stirred at 37°C for 1 hour. Before and after stirring, the sodium ion concentration was measured using a compact sodium ion meter (Na-11, LAQUAtwin, HORIBA) to evaluate the capture rate. In the tables that follow, this condition is shown as a pH of 6.8. Note that pH 6.8 corresponds to the pH of the duodenum to small intestine after a meal, and pancreatin is the major digestive enzyme present in the small intestine.

[0063] The test for sequential exposure from simulated gastric conditions to simulated intestinal conditions was conducted as follows. First, the same procedure as in the test for simulated gastric fluid conditions described above was performed, and the sodium ion concentration was measured after 1 hour of stirring. Next, sodium hydroxide was added to the solution to adjust the pH to 6.5-7.0. Then, 0.5 w / v% pancreatin was added to the solution, and the solution was stirred for another 1 hour at 37°C. After stirring, the sodium ion concentration was measured using a compact sodium ion meter (Na-11, LAQUAtwin, HORIBA) to evaluate the retention rate. In the following tables, this condition is shown as "pH 3.0 → 6.8." This evaluation allows us to evaluate the retention of sodium ions during the process of an orally ingested sodium ion sequestering agent first passing through the stomach and then through the intestine.

[0064] The results are shown in Tables 4 to 9. Tables 4 and 5 show the results for isomerized hop extract. Table 6 shows the results for TETRA extract. Table 7 shows the results for HEXA extract. Table 8 shows the results for hop extract. Table 9 shows the results for alginate as a reference example. Tables 4 to 9 show that isomerized hop extract, TETRA extract, HEXA extract, and hop extract exhibited sodium ion-trapping ability similar to the alginate described in Patent Document 1. Furthermore, among these, TETRA extract and HEXA extract exhibited superior sodium ion-trapping ability per BU (i.e., per component A).

[0065] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9]

[0066] <Test Example 3: Test on the Salt Concentration Dependence of Sodium Ion Capture Amount> In a test similar to Test Example 1 or Test Example 2, it was investigated whether the amount of sodium ions captured exhibited salt concentration dependency when tested under conditions of multiple salt concentrations. In the test, the amount of captured sodium ions was evaluated under conditions of multiple salt concentrations from 0.5 w / v% to 2.0 w / v%, similar to Test Example 1 or Test Example 2. The difference in the measured values ​​(ppm) of a compact sodium ion meter before and after stirring was used as an index of the amount of captured sodium ions.

[0067] FIG. 1 shows the salt concentration dependence of the amount of sodium ions captured in pure water (pH 6.8) and in a solution prepared by adding hydrochloric acid to pure water to adjust the pH to 3.0 under conditions of 0.4 v / v% (854.0 BU) isomerized hop extract. The results in FIG. 1 show the averages at pH 6.8 and pH 3.0, as well as the combined average. FIG. 2 shows the averages of the results at pH 6.8 and pH 3.0 under conditions of 0.4 v / v% (854.0 BU) isomerized hop extract, as well as their linear approximation lines. As shown in FIGS. 1 and 2, the amount of sodium ions captured increased linearly with salt concentration under both acidic and neutral conditions. The R of the linear approximation in FIG. 2 2 The value was 0.98, and a strong positive correlation was observed between the amount of sodium ions captured and the salt concentration.

[0068] Figure 3 shows the salt concentration dependence of the amount of sodium ions captured in pure water (pH 6.8) at 0.03 v / v% (64.0 BU) isomerized hop extract. As shown in Figure 3, even at a lower concentration of 0.03 v / v% (64.0 BU) isomerized hop extract, the amount of sodium ions captured increased linearly with respect to the salt concentration. The R of the linear approximation in Figure 3 2 The value was 0.93, and a strong positive correlation was observed between the amount of sodium ions captured and the salt concentration.

[0069] 4 shows the salt concentration dependence of the amount of sodium ions captured in pure water (pH 6.8), artificial gastric juice from which pectin has been removed, and artificial gastric juice at 0.4 v / v% (854.0 BU) isomerized hop extract. As shown in FIG. 4, even when artificial gastric juice was used, the amount of sodium ions captured increased linearly with the salt concentration.

[0070] <Test Example 4: Examination of drinkable concentration> Isomerized hop extract, TETRA extract, or HEXA extract was added to commercially available beverages (Kirin Beverage Co., Ltd., with non-alcoholic beer-flavored beverages also manufactured by Kirin Brewery Co., Ltd.), and three evaluators evaluated the drinkable concentration. In the evaluation, if the intensity and quality of the bitterness were acceptable for the liquid type without masking or other measures, the beverage was rated as drinkable, and the upper limit of the amount of drinkable extract (v / v%) added was determined to be the upper limit of drinkable content of that extract for that beverage.

[0071] As a result, first, the addition rate of isomerized hop extract shown in Table 10 was the upper limit for potable consumption under unmasked conditions.

[0072] [Table 10]

[0073] Furthermore, when TETRA extract and HEXA extract were added to coffee (Fire ONEDAY Black) without masking, the upper limit of their potable contents was 0.05 v / v%, and when added to a non-alcoholic beer-flavored beverage (Kirin Greens Free), the upper limit was 0.05 v / v% and 0.06 v / v%, respectively.

[0074] <Test Example 5: Amount of sodium ions captured when contained in a beverage> The sodium ion-trapping ability was evaluated using solutions containing 0.05 v / v% TETRA extract in beverages: water (ion-exchanged water), carbonated water (gas pressure: 0.5 MPa), commercially available black tea (pH 6.8, Afternoon Tea Delicious Sugar-Free, Kirin Beverage Co., Ltd.), and coffee (pH 5.8, Kirin Fire One Day Black, Kirin Beverage Co., Ltd.), to which 1 w / v% salt was added in the same manner as in Test Example 1. As a comparative example, a similar test was conducted without adding TETRA extract. The results are shown in Table 11. Table 11 demonstrates that the addition of 0.05 v / v% TETRA extract, which is within the drinkable concentration range, can trap sodium ions in each commercially available beverage. This suggests that the sodium ion scavenger can also be used to suitably trap sodium ions in beverages.

[0075] [Table 11]

Claims

1. A sodium ion scavenger containing at least one selected from the group consisting of α acids, iso-α acids, and reduced iso-α acids.

2. The sodium ion scavenger according to claim 1, which contains at least one selected from the group consisting of hop extract, isomerized hop extract, and reduced product of isomerized hop extract.

3. The sodium ion scavenger according to claim 1, comprising at least one selected from the group consisting of iso-α acids, tetrahydroiso-α acids, and hexahydroiso-α acids.

4. The sodium ion scavenger according to claim 1, comprising at least one selected from the group consisting of tetrahydroiso-α-acids and hexahydroiso-α-acids.

5. The sodium ion scavenger according to any one of claims 1 to 4, which is a beverage.

6. A method for capturing sodium ions, comprising contacting at least one selected from the group consisting of α acids, iso-α acids, and reduced iso-α acids with sodium ions.

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