Oral composition for sodium discharge, and pharmaceutical and food containing the composition

Abstract

To provide an oral composition for sodium discharge based on a novel concept, exhibiting a high discharge effect.SOLUTION: An oral composition for sodium discharge 100 contains a sodium intercalation material 40 as an active ingredient.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an oral composition for excreting sodium, and to a medicine and a food product containing said composition. [Background technology]

[0002] Sodium is an essential component for regulating the amount of water in the body and for regulating muscle stimulation and nerve excitation, but in recent years, excessive sodium intake has become a problem. In particular, excessive intake of salt (NaCl) can cause various diseases, so salt reduction is recommended to promote health. In addition, patients with impaired renal function who require artificial dialysis are imposed with very strict dietary restrictions (reduced salt intake). However, meals with extremely reduced salt content are bland and difficult to fully satisfy. Under these circumstances, techniques have been proposed to promote sodium excretion outside the body (e.g., Patent Documents 1 and 2).

[0003] Patent Document 1 discloses a core-shell composition consisting of a cation-exchangeable core containing a sodium-binding polymer of a specific structure and a semi-permeable shell. When the core-shell composition is orally ingested, the core binds to sodium in the digestive tract. The core-shell composition is excreted as is from the body, thereby allowing sodium to be excreted from the body. Patent Document 2 discloses a food composition for excreting sodium, containing ammonium alginate as an active ingredient. Alginic acid adsorbs sodium in the digestive tract and is excreted as is from the body, allowing sodium to be excreted.

[0004] On the one hand, it is known that many intestinal bacteria inhabit the intestines (small intestine, large intestine) of mammals including humans, and it has been reported that so-called electricity-generating bacteria (current-generating bacteria) exist among these intestinal bacteria (for example, Non-Patent Documents 1 and 2). Here, electricity-generating bacteria (current-generating bacteria) refer to bacteria that have the ability to transfer electrons generated by the decomposition (metabolism) of an electron donor (organic substance) to an electron acceptor outside the cell, that is, the ability to perform extracellular electron transfer (EET: Extracellular Electron Transport) (extracellular electron transfer ability).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] Conventional sodium excretion techniques have not been sufficiently effective, and a new technique with a higher sodium excretion effect has been desired. The present invention solves this problem and provides an oral composition for sodium excretion based on a novel concept that is completely different from the prior art.

Means for Solving the Problems

[0008] As a result of intensive research into achieving the above object, the inventors have found that the above object can be achieved by the following configuration.

[0009] [1] An oral composition for excreting sodium, comprising a sodium intercalation material as an active ingredient. [2] The oral composition for excreting sodium described in [1], wherein the sodium intercalation material is in the form of particles. [3] The oral composition for excreting sodium described in [1] or [2], wherein the sodium intercalation material is a phosphate. [4] The oral composition for excreting sodium described in [3], wherein the phosphate has an olivine structure. [5] The oral composition for excreting sodium described in [3] or [4], wherein the sodium intercalation material is iron phosphate (III). [6] The oral composition for excreting sodium according to any one of [1] to [5], further comprising an electron mediator. [7] The oral composition for excreting sodium described in [6], wherein the electron mediator is at least one selected from the group consisting of flavins and quinones. [8] The oral composition for excreting sodium according to any one of [1] to [7], wherein after oral ingestion, the sodium intercalation material is capable of accepting electrons generated in the intestine by electric-generating bacteria, which are intestinal bacteria. [9] A pharmaceutical comprising an oral composition for excreting sodium according to any one of [1] to [8].

[10] A food comprising an oral composition for excreting sodium according to any one of [1] to [8].

[11] The food product described in

[10] , which is a supplement. Effect of the Invention

[0010] The present invention provides an oral composition for excreting sodium that is highly effective in excreting sodium and is based on a new concept. [Brief description of the drawings]

[0011] [Figure 1] FIG. 2 is a conceptual diagram illustrating the sodium adsorption mechanism of the sodium excretion oral composition of the present embodiment. [Diagram 2] FIG. 1 shows the results of X-ray diffraction (XRD) measurement of iron phosphate (before reaction) and the powder obtained in Experiment 1 (after reaction, with bacteria). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The following description of the components may be based on a representative embodiment of the present invention, but the present invention is not limited to such an embodiment. In this specification, a numerical range expressed using "~" means a range including the numerical values ​​before and after "~" as the lower and upper limits.

[0013] The oral composition for excreting sodium of this embodiment (hereinafter sometimes simply referred to as "oral composition") adsorbs sodium in the intestine and is excreted as is, thereby enabling sodium to be excreted from the body. The present inventors focused on electric-generating bacteria present in the intestine of the living body, and discovered that the adsorption and excretion of sodium can be promoted by utilizing the ability of electric-generating bacteria to perform EET (extracellular electron transfer ability), thereby arriving at the present invention. In that it utilizes EET of intestinal bacteria, the sodium excretion technology of the present invention is an invention based on a completely new concept that has not been seen before. Hereinafter, an embodiment of the present invention will be described in detail.

[0014] [Oral composition for excreting sodium] The sodium excretion oral composition of the present embodiment contains a sodium intercalation material as an active ingredient. In this specification, the term "sodium intercalation material" refers to a material (host, parent) into which sodium ions (guests) can intercalate. Intercalation is a reversible chemical reaction in which another element (sodium ions in this specification) enters the voids of a molecule, molecular group, or crystal (host).

[0015] The type (composition, crystal structure, shape, etc.) of the sodium intercalation material is not particularly limited and may be appropriately selected within the range in which the effects of this embodiment are achieved. For example, the sodium intercalation material may be a compound containing a first transition metal. Examples of the first transition metal include iron (Fe), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), etc., and may be one type or two or more types. Specific examples of the compound include iron phosphate such as FePO4, iron oxide such as Fe3O4, Fe2O3, titanium oxide such as TiO2, manganese oxide such as Mn3O4, Mn2O3, MnO2, MnO3, Mn2O7, vanadium oxide such as V2O5, VO2, and TiS2. Also, edible charcoal (carbon) may be used as the sodium intercalation material.

[0016] In addition, examples of the crystal structure of the sodium intercalation material include layered rock salt type, spinel type, olivine type, etc. As the sodium intercalation material, a phosphate that can have an olivine type structure with high stability and high selectivity for sodium adsorption is preferable, and among them, iron phosphate (III) (FePO4) with low biotoxicity is more preferable. Note that, as long as the effect of this embodiment is exhibited, one type of sodium intercalation material may be used alone, or two or more types may be mixed and used.

[0017] The sodium intercalation material is preferably in the form of particles (powder) from the viewpoint of increasing sodium absorption efficiency. The average particle size of the particles is not particularly limited, and may be, for example, 5 nm to 500 μm, 50 nm to 9000 nm, or 100 nm to 300 nm. The "average particle size" can be determined, for example, by measuring the particle sizes of 100 random particles by observation with an electron microscope and averaging them (arithmetic mean).

[0018] The oral composition of this embodiment may be formed only from the sodium intercalation material, or may contain other ingredients as long as the effects of this embodiment are achieved.

[0019] As other components, the oral composition may contain, for example, an electron mediator. As will be described in detail later, as shown in FIG. - is transferred to an electron acceptor (sodium intercalation material 40) outside the cell via an electron transfer protein 30 present in the cell outer membrane. The electron mediator activates the electron transfer protein 30 and further promotes electron transfer to the sodium intercalation material 40. As a result, sodium absorption efficiency can be improved. Examples of electron mediators include flavins and quinones. Flavins are a general term for derivatives of 7,8-dimethylisoalloxazine having a substituent at the 10th position, and include riboflavin (vitamin B2), FAD, FMN, and the like. Quinones are aromatic organic compounds having a cyclic diketone structure with a double bond and containing six carbon atoms, and examples of these include p-benzoquinone, o-quinone, anthraquinone, and the like. These electron mediators may be used alone or in combination of two or more types within the scope of the effect of this embodiment.

[0020] As other components, the oral composition may contain an electron donor (electron donor) that can be decomposed by the electric-power generating bacteria. Since the electric-power generating bacteria generate electrons by decomposing (metabolizing) organic matter (electron donor), it is expected that the adsorption efficiency of sodium can be improved. The electron donor (electron donor) is not particularly limited as long as it is an organic matter that can be decomposed (metabolized) by the electric-power generating bacteria in the intestine. For example, lactate salts such as sodium lactate, acetate salts such as sodium acetate, etc. are included. It is preferable to appropriately select an electron donor that increases the power generation efficiency based on the type of electric-power generating bacteria. The electron donor may be used alone or in a mixture of two or more types within the range in which the effect of this embodiment is achieved. In addition, since organic matter that serves as an electron donor is already present in the intestine of a living body, the oral composition does not need to contain an electron donor.

[0021] Furthermore, as other components, general-purpose additives (for example, food additives, etc.) may be contained.

[0022] The ratio (proportion) of each component in the oral composition of this embodiment is not particularly limited, and can be appropriately adjusted within the range in which the effects of this embodiment are exhibited and according to the use of the oral composition described later. The content of the sodium intercalation material in the oral composition may be 100% by mass, and the lower limit may be, for example, 1% by mass or more, 10% by mass or more, 30% by mass or more, 50% by mass or more, 70% by mass or more, 90% by mass or more, or 99% by mass or more, and the upper limit may be 99% by mass or less, 90% by mass or less, 70% by mass or less, 50% by mass or less, 30% by mass or less, or 10% by mass or less.

[0023] [Mechanism of sodium excretion] The mechanism by which the oral composition of this embodiment excretes sodium from the body will be described. As shown in FIG. 1, the intestines of a living body contain electric-power-generating bacteria 10, which are intestinal bacteria. The intestines also contain a large amount of organic matter that can serve as electron donors (electron donors) 20 that can be decomposed by the electric-power-generating bacteria. First, the electron donors 20 are decomposed (metabolized) within the electric-power-generating bacteria 10, and electrons e - The generated electron e - is transferred to the sodium intercalation material 40, which is an extracellular electron acceptor, via the electron transfer protein 30 present in the cell outer membrane of the electricity-generating bacterium 10 (EET, extracellular electron transfer ability). The action of this electric bacterium 10 promotes electrochemical intercalation, in which sodium ions contained in digestive matter in the intestine are taken up by the sodium intercalation material 40. Since the sodium intercalation material 40 is not digested or absorbed, it is excreted into the body with sodium adsorbed. In this way, the oral composition 100 can excrete sodium outside the body. The mechanism described above is merely speculation and does not affect the scope of the present invention.

[0024] The electric-generating bacteria that are enterobacteria are not particularly limited, and examples thereof include the electric-generating bacteria described in Non-Patent Documents 1 and 2, the contents of which are incorporated herein by reference.

[0025] In an in vitro experiment, it was confirmed that the particles of the sodium intercalation material form aggregates due to the components derived from the electricity-generating bacteria when sodium is adsorbed in the oral composition of this embodiment. It is presumed that the same phenomenon occurs in the intestines of the living body, which improves the electrical conductivity and adhesiveness between particles and further increases the sodium adsorption efficiency.

[0026] When iron(III) phosphate is used as the sodium intercalation material, iron(III) phosphate (FePO4) adsorbs sodium ions to form an iron(III) phosphate sodium intercalation compound (e.g., Na x FePO4, x=0.4-2.0). At least a part of the iron phosphate (III) is reduced by electrons transferred from the electricity-generating bacteria. The average oxidation number of iron (Fe) in the sodium iron phosphate (III) insertion compound is not particularly limited, but is, for example, +3-+4. The sodium ions incorporated in the sodium intercalation material are not reduced.

[0027] [Uses and embodiments of oral compositions] The oral composition of the present embodiment can promote sodium excretion and adjust (reduce) the sodium concentration in the living body. Therefore, it can be used as a medicine (including quasi-drugs), food, etc. for treating and / or preventing various diseases and symptoms in mammals including humans. Examples of foods include so-called health foods or supplements such as functional foods whose efficacy has been approved by a designated organization, such as foods for specified health uses, foods with nutritional functions, and foods with functional claims, general foods, food additives, feed, etc.

[0028] Diseases and symptoms that can be treated or prevented by the oral composition of this embodiment include, for example, high blood pressure, osteoporosis, kidney disease, heart disease, nervousness, insomnia, blood circulation disorders, skin aging, and the like.

[0029] Examples of the form of pharmaceuticals and foods containing the oral composition of this embodiment include tablets, capsules, powders, granules, liquids, particles, rods, plates, blocks, solids, rounds, pastes, creams, caplets, gels, jelly, chewable tablets, sticks, and the like.

[0030] The pharmaceutical and food of this embodiment may consist of only the oral composition described above, or may contain other ingredients as necessary. The pharmaceutical and food of this embodiment can be manufactured into a desired form by a known method. EXAMPLES

[0031] The present invention will be described in more detail below based on examples. The materials, amounts, ratios, processing contents, processing procedures, etc. shown in the following examples can be appropriately changed without departing from the spirit of the present invention. Therefore, the scope of the present invention should not be interpreted as being limited by the following examples.

[0032] In the experiments described below, we used Shewanella oneidensis MR-1, a typical electricity-generating bacterium. Shewanella is not an intestinal bacterium. However, we speculate that even if intestinal bacteria are used, if the bacteria have extracellular electron transfer (EET), the same results as the following experimental results will be obtained.

[0033] [Experiment 1] The media, bacteria, and intercalation materials described below were prepared. <Culture medium: Phosphate-buffered saline (PBS)> The medium was prepared by dissolving NaCl (8 g / L), KCl (0.2 g / L), Na2HPO4 (1.42 g / L), and KH2PO4 (0.24 g / L) in 1 L of ultrapure water (pH 7.4). The prepared medium (PBS) was sterilized by autoclaving before use. <Bacteria: Shewanella oneidensis MR-1> The bacteria were cultured overnight by shaking at 160 rpm under aerobic conditions at 30 °C in LB broth medium. <Intercalation material: FePO4> Lithium was removed from LiFePO4 (Hohsen Corp.) according to the following procedure to obtain FePO4. At room temperature, LiFePO4 was stirred in K2S2O8 for 24 hours (molar ratio K2S2O8:LiFePO4 = 1:2). Then, it was filtered, washed with ultrapure water, and vacuum dried at 80 °C for 24 hours to obtain FePO4 (powder).

[0034] <Na adsorption test> According to the following procedure, the intercalation material and the medium were contacted in the presence of bacteria in a culture vial. (1) 50 mg of FePO4 was weighed and placed in an autoclaved glass culture vial. The culture vial was irradiated with UV for 5 minutes to sterilize FePO4. (2) A sodium lactate PBS solution (100 mL of PBS containing 50 mM sodium lactate) was prepared in an autoclaved Erlenmeyer flask. (3) 49 mL of the medium was injected into the culture vial through a 0.22 μm filter. (4) The culture vial was closed with an autoclaved rubber cap and sealed with an aluminum cap. (5) The contents of the culture vial were flushed with N2 gas for at least 20 minutes. (6) During step (5), the bacteria were washed three times by centrifugation (6 minutes, 25 °C, 6000 rpm) using the sodium lactate PBS solution (step (2)) filtered through a 0.22 μm filter. (7) 1 mL of the washed bacterial solution (OD 600nm = 15) obtained in step (6) was injected into the N2-flushed culture vial. The final OD of the bacteria in the culture vial 600nm was 0.3. (8) The contents of the culture vial were flushed with N2 for 10 minutes. (9) The culture vial was then incubated in the dark at 30° C. with shaking at 160 rpm for 24 hours.

[0035] [Experiment 1-1] To confirm reproducibility, an experiment similar to Experiment 1 was conducted again.

[0036] [Experiment 2] The experiment was carried out in the same manner as in Experiment 1, except that neither bacteria nor sodium lactate was used. [Experiment 3] The experiment was carried out in the same manner as in Experiment 1, except that no bacteria were used.

[0037] [X-ray diffraction (XRD) measurement] The solid matter was collected from the incubated culture vials (step (9)) of Experiments 1 to 3 and 1-1 by centrifugation (7000 rpm, 10 min, 25°C) in the glove box chamber and washed five times with N2-flushed ultrapure water. It was then vacuum dried at 80°C for 18 hours to obtain a sample for XRD measurement. XRD measurement was performed using a Rigaku SmartLab model under the following measurement conditions: Soller slit: 2.5°, step: 0.01°, speed: 4°, data acquisition mode: 1D, data analysis software: Rigaku PDXL 2.8 version 2.8.4.0.

[0038] Figure 2 shows the X-ray diffraction (XRD) measurement results for Experiment 1 as "Experiment 1 (after reaction)". For comparison, the profile of FePO4 is also shown in Figure 2 as "FePO4 (before reaction)". In Experiment 1 (after reaction), a peak belonging to NaFePO4 was confirmed that was not present in FePO4 (before reaction) (indicated by an arrow in Figure 2). Analysis showed that the powder obtained in Experiment 1 (after reaction) had a composition of NaFePO4: 93.2 mol%, FePO4 (unreacted): 2.5 mol%, and potassium iron hydroxide phosphate hydrate: 4.3 mol%. The X-ray diffraction (XRD) measurement results of Experiment 1-1 also showed a diffraction pattern similar to that of Experiment 1 (not shown), confirming reproducibility. On the other hand, the results of X-ray diffraction (XRD) measurements in Experiment 2 and Experiment 3, which did not use bacteria, were similar to the profile of FePO4 (not shown), and the production of NaFePO4 could not be confirmed (FePO4: 100 mol %). From these results, it was confirmed that the presence of bacteria promotes the adsorption of sodium contained in the medium (derived from NaCl, Na2HPO4, and sodium lactate) to FePO4. [Industrial Applicability]

[0039] The oral composition of the present invention can be used in medicines and foods, and can treat or prevent various diseases and / or symptoms by reducing the sodium concentration in the body. [Explanation of symbols]

[0040] 10 Electricity-generating bacteria 20 Electron donor 30 Electron Transfer Proteins 40 Sodium intercalation materials 100 Sodium excretion oral composition

Claims

1. An oral composition for sodium excretion, containing a sodium intercalation material as an active ingredient.

2. The oral composition for sodium excretion according to claim 1, wherein the sodium intercalation material is particles.

3. The oral composition for sodium excretion according to claim 1, wherein the sodium intercalation material is a phosphate.

4. The oral composition for sodium excretion according to claim 3, wherein the phosphate has an olivine-type structure.

5. The oral composition for sodium excretion according to claim 3, wherein the sodium intercalation material is iron(III) phosphate.

6. The oral composition for sodium excretion according to claim 1, further comprising an electronic mediator.

7. The oral composition for sodium excretion according to claim 6, wherein the electron mediator is at least one selected from the group consisting of flavins and quinones.

8. The sodium excretion oral composition according to claim 1, wherein, after oral ingestion, the sodium intercalation material is capable of receiving electrons generated by intestinal bacteria, which are power-generating bacteria, in the intestines.

9. A pharmaceutical product comprising an oral composition for sodium excretion according to any one of claims 1 to 8.

10. A food comprising the oral composition for sodium excretion according to any one of claims 1 to 8.

11. The food according to claim 10, which is a supplement.

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