Oral composition for hydration

Abstract

Provided is an oral composition for water replenishment in which the amount of glucose, which is a conventionally used carbohydrate, is relatively small, wherein the oral composition is capable of rapidly absorbing water. Specifically, provided is an oral composition for hydration comprising: a sugar alcohol, an organic acid, a vitamin, a specific sugar, or a combination thereof.

Description

Oral composition for hydration

[0001] This disclosure relates to oral compositions for hydration, etc. All references cited herein are incorporated herein by reference.

[0002] For mammals, especially humans, water is essential for survival, so rapid hydration is crucial. In particular, when dehydration occurs due to excessive heat or strenuous exercise, rapid hydration is even more important.

[0003] International Publication No. 2022 / 251624

[0004] Biochim Biophys Acta. 1999;1472(1-2):107-14.

[0005] Oral compositions for hydration (e.g., beverage compositions or gel-like (especially jelly-like) compositions) are preferably composed to contain a certain amount of carbohydrates (e.g., 4-8% by mass) when energy recovery is also considered. Supplementing with carbohydrates is considered particularly important when the oral composition is used for hydration by individuals who have performed heavy labor or sports. However, with recent changes in lifestyle and the growing health consciousness, there is a growing need to reduce sugar intake not only when hydrating in normal daily life, but also when hydrating after heavy labor or sports. Furthermore, there are many individuals with high blood sugar levels or those concerned about the risk of dental caries, and for such individuals, there is a growing demand for compositions that use relatively less glucose, a carbohydrate that has traditionally been used in oral compositions for hydration.

[0006] However, since glucose is an ingredient that not only restores energy but also aids in rapid water absorption, it was not easy to provide an oral composition that uses a relatively small amount of glucose and allows for rapid water absorption.

[0007] Therefore, we conducted research with the aim of providing an oral composition for hydration that uses a relatively small amount (preferably no) amount of glucose, a carbohydrate that has been used conventionally, and that can rapidly absorb water.

[0008] Water absorption primarily occurs in the small intestine (intestinal epithelial cells). Therefore, it is crucial to understand how efficiently the water contained in orally ingested compositions is absorbed by intestinal epithelial cells. However, a system for easily evaluating water absorption in vitro, closely resembling that of a living organism, had not yet been established. Therefore, the present inventors first developed a system using human iPS cell-derived intestinal epithelial cells (F-hiSIEC). ＴＭ Using this system, we investigated and successfully constructed a screening system that has functions similar to those of human organisms (intestinal epithelial cells) and can accurately evaluate whether the water absorption performance changes depending on the components contained in the composition. This makes it possible to more accurately investigate how efficiently water contained in orally ingested compositions is absorbed in actual living organisms. Then, using this screening system, we screened for components that enable efficient water absorption.

[0009] This disclosure includes, for example, the subject matter described in the following sections: Section 1. An oral composition for hydration comprising a sugar alcohol. Section 2. The oral composition according to Section 1, comprising 10 to 250 mM of a sugar alcohol. Section 3. The oral composition according to Section 1 or 2, wherein the sugar alcohol is at least one sugar alcohol selected from the group consisting of xylitol, erythritol, dextrose, mannitol, lactitol, and sorbitol. Section 4. The oral composition according to Section 1 or 2, wherein the sugar alcohol is erythritol. Section 5. An oral composition for hydration comprising an amino acid and / or a salt thereof. Section 6. The oral composition according to Section 5, comprising 10 to 250 mM of an amino acid and / or a salt thereof. Section 7. The oral composition according to Section 5 or 6, wherein the amino acid is at least one amino acid selected from the group consisting of alanine, serine, proline, glycine, methionine, isoleucine, valine, threonine, and tryptophan. Section 8. An oral composition according to claim 5 or 6, wherein the amino acid is at least one amino acid selected from the group consisting of alanine, serine, and proline. Claim 9. An oral composition according to claim 5 or 6, wherein the amino acid is alanine and / or leucine. Claim 10. An oral composition according to any one of claims 7 to 9, further comprising a branched-chain amino acid different from the said amino acid and / or a salt of said branched-chain amino acid. Claim 11. An oral composition for hydration comprising an unbranched-chain amino acid and / or a salt thereof and a branched-chain amino acid and / or a salt thereof. Claim 12. An oral composition according to claim 11, comprising an unbranched-chain amino acid and / or a salt thereof and a branched-chain amino acid and / or a salt thereof in a molar ratio of 1:0.05 to 4. Claim 13. An oral composition according to claim 11 or 12, wherein the unbranched-chain amino acid is alanine. Claim 14. An oral composition according to any one of claims 11 to 13, wherein the branched-chain amino acid is leucine. Claim 15. An oral composition for hydration comprising an organic acid and / or a salt thereof. Item 16. The oral composition according to item 15, wherein the organic acid is an organic acid having a molecular weight of 46 to 300, having no nitrogen atoms and having a carboxyl group and / or a phosphate group.Item 17. The oral composition according to Item 15, wherein the organic acid is at least one selected from the group consisting of carbonic acid, bicarbonate, citric acid, lactic acid, phosphoric acid, gluconic acid, acetic acid, and malic acid. Item 18. The oral composition according to Item 15, wherein the organic acid and / or salt thereof is citric acid and / or a salt thereof. Item 19. The oral composition according to any one of Items 15 to 18, containing 0.05 to 50 mM of an organic acid and / or a salt thereof. Item 20. An oral composition for hydration, comprising allulose. Item 20a. The oral composition according to Item 20, further comprising alanine and / or a salt thereof. Item 21. The oral composition according to Item 20 or 20a, containing 10 to 250 mM of allulose. Item 21a. The oral composition according to Item 20a, containing 10 to 250 mM of allulose and 10 to 250 mM of alanine and / or a salt thereof. Item 22. Oral compositions for hydration, comprising vitamins. Item 23. The oral composition according to Item 22, wherein the vitamin is at least one selected from the group consisting of vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, pantothenic acid, and biotin. Item 24. The oral composition according to Item 22, wherein the vitamin is vitamin B3 and / or vitamin C. Item 25. The oral composition according to any one of Items 22 to 24, containing 0.01 to 50 mM of a vitamin. Item 26. Oral compositions for hydration, comprising sugar alcohols and amino acids and / or salts thereof. Item 27. The oral composition according to Item 26, wherein the amino acid is at least one amino acid selected from the group consisting of alanine, serine, proline, glycine, methionine, isoleucine, valine, threonine, and tryptophan. Item 28. The oral composition according to Item 26, wherein the amino acid is alanine. Item 29. An oral composition according to any one of claims 26 to 28, wherein the sugar alcohol is at least one sugar alcohol selected from the group consisting of xylitol, erythritol, dextrose, mannitol, lactitol, and sorbitol. Claim 30. An oral composition according to any one of claims 26 to 28, wherein the sugar alcohol is erythritol. Claim 31. An oral composition according to any one of claims 26 to 30, comprising 10 to 250 mM of a sugar alcohol.Item 32. An oral composition according to any one of items 26 to 31, comprising 10 to 250 mM of an amino acid and / or a salt thereof. Item 33. An oral composition for hydration comprising a sugar alcohol and an organic acid and / or a salt thereof. Item 34. An oral composition according to item 33, wherein the organic acid is at least one selected from the group consisting of carbonic acid, bicarbonate, citric acid, lactic acid, phosphoric acid, gluconic acid, acetic acid, and malic acid. Item 35. An oral composition according to item 33, wherein the organic acid is citric acid. Item 36. An oral composition according to any one of items 33 to 35, wherein the sugar alcohol is at least one sugar alcohol selected from the group consisting of xylitol, erythritol, dextrose, mannitol, lactitol, and sorbitol. Item 37. An oral composition according to any one of items 33 to 36, wherein the sugar alcohol is erythritol. Item 38. An oral composition according to any one of items 33 to 37, comprising 10 to 250 mM of a sugar alcohol. Item 39. An oral composition according to any one of items 33 to 38, comprising 0.05 to 120 mM of an organic acid and / or a salt thereof. Item 40. An oral composition for hydration comprising a sugar alcohol and a vitamin. Item 41. An oral composition according to item 40, wherein the vitamin is at least one selected from the group consisting of vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, pantothenic acid, and biotin. Item 42. An oral composition according to item 40, wherein the vitamin is vitamin C and / or vitamin B6. Item 43. An oral composition according to any one of items 40 to 42, wherein the sugar alcohol is at least one sugar alcohol selected from the group consisting of xylitol, erythritol, dextrose, mannitol, lactitol, and sorbitol. Item 44. An oral composition according to any one of items 40 to 42, wherein the sugar alcohol is erythritol. Item 45. An oral composition according to any one of claims 40 to 44, comprising 10 to 250 mM of a sugar alcohol. Claim 46. An oral composition according to any one of claims 40 to 45, comprising 0.01 to 50 mM of a vitamin. Claim 47. An oral composition for hydration comprising 10 to 250 mM of erythritol and 10 to 250 mM of alanine and / or a salt thereof.Item 48. An oral composition for hydration comprising 10 to 250 mM erythritol and 0.05 to 50 mM citric acid and / or its salt. Item 49. An oral composition for hydration comprising 10 to 250 mM erythritol and 0.01 to 50 mM vitamin B3 and / or vitamin C.

[0010] The present invention provides an oral composition for hydration that uses a relatively small amount of glucose (preferably no glucose at all) and that allows for efficient (preferably rapid) absorption of water.

[0011] F-hiSIEC ＴＭThis shows an overview of a screening system for evaluating water absorption in intestinal cells, constructed using Fujifilm Wako Pure Chemical Industries, Ltd. Figure 1 shows the screening results (Apical media volume) using various amino acids (all at a concentration of 50 mM) as test substances in the screening system shown. Figure 1 shows the screening results (Apical media volume) using erythritol and alanine (L-isomer and D-isomer) as test substances in the screening system shown. Figure 1 shows the screening results (Apical media volume) using erythritol as a test substance in the screening system shown. Figure 1 shows the screening results (Apical media volume) using erythritol and alanine as test substances in the screening system shown. Figure 1 shows the screening results (Apical media volume) using allulose as a test substance in the screening system shown. Figure 1 shows the screening results (Apical media volume) using allulose and alanine as test substances in the screening system shown. The following screening results (Apical media volume) are shown for the screening system in Figure 1 using alanine 50 mM and leucine 15 mM as test substances. The following screening results (Apical media volume) are shown for the screening system in Figure 1 using alanine 50 mM and leucine 17.5 mM as test substances. The following screening results (Apical media volume) are shown for the screening system in Figure 1 using alanine 50 mM and leucine 20 mM as test substances. The following screening results (Apical media volume) are shown for the screening system in Figure 1 using citric acid as a test substance. The following screening results (Apical media volume) are shown for the screening system in Figure 1 using citric acid 0.5 mM and erythritol 50.0 mM as test substances. The following screening results (Apical media volume) are shown for the screening system in Figure 1 using citric acid 0.5 mM and erythritol 65.5 mM as test substances. The screening results (amount in Apical medium) using vitamin B3 as the test substance in the screening system shown in Figure 1 are presented.In the screening system of FIG. 1, screening results (amount of medium on the apical side) using vitamin C as the test substance are shown. In the screening system of FIG. 1, screening results (amount of medium on the apical side) using erythritol, alanine, and vitamin B6 as the test substances are shown. In the screening system of FIG. 1, screening results (amount of medium on the apical side) using 50 mM of erythritol and 0.1 mM of vitamin C as the test substances are shown. In the screening system of FIG. 1, screening results (amount of medium on the apical side) using 65.5 mM of erythritol and 0.1 mM of vitamin C as the test substances are shown. Results of having a human ingest an electrolyte beverage containing alanine (alanine electrolyte beverage) or an electrolyte beverage not containing alanine (control beverage) and collecting blood over time to examine changes (%) in plasma volume are shown.

[0012] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The present disclosure preferably includes oral compositions for rehydration and the like, but is not limited thereto, and the present disclosure includes all that are disclosed herein and recognizable by those skilled in the art.

[0013] The oral composition for rehydration included in the present disclosure contains specific components. Examples of the specific components include sugar alcohols, organic acids (particularly amino acids) and / or their salts, vitamins, specific sugars, or combinations thereof. Hereinafter, the oral composition for rehydration included in the present disclosure may be referred to as the oral composition of the present disclosure. Also, the specific components may be referred to as the components of the present disclosure. That is, the oral composition of the present disclosure contains the components of the present disclosure.

[0014] As described above, examples of the components of the present disclosure include sugar alcohols, organic acids (particularly amino acids) and / or their salts, vitamins, specific sugars, or combinations thereof. Details will be described below.

[0015] Examples of sugar alcohols include xylitol, erythritol, dextrose, mannitol, lactitol, maltitol, and sorbitol, among which erythritol is preferred. The sugar alcohol can be used alone or in combination of two or more kinds.

[0016] In the oral composition of the present disclosure, the sugar alcohol is preferably contained, for example, in an amount of 10 to 700 mM. The upper or lower limit of this range may be, for example, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, or 690 mM. Any two values among these values and 10 mM and 700 mM can be used as the upper and lower limits of this range. This range may be, for example, 10 to 650 mM. This range is more preferably 10 to 250 mM, still more preferably 20 to 200 mM, and even more preferably 30 to 150 mM.

[0017] As stated above, the oral compositions of this disclosure are particularly preferably in which erythritol is included. If erythritol is included, it is preferably in a concentration of 10 to 650 mM. The upper or lower limits of this range are, for example, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, The values ​​may be 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, or 640 mM. Any two of these values, as well as 10 mM and 650 mM, can be used as the upper and lower limits of the range. The range may be, for example, 20 to 600 mM, more preferably 20 to 200 mM, and even more preferably 30 to 150 mM.

[0018] Examples of preferred organic acids and / or salts thereof include amino acids and / or salts thereof, and organic acids other than amino acids and / or salts thereof.

[0019] Examples of salts of organic acids include alkali metal salts, alkaline earth metal salts, ammonium salts, halide salts (especially hydrochloride salts), and sulfates. Examples of alkali metal salts include sodium salts and potassium salts. Examples of alkaline earth metal salts include magnesium salts and calcium salts.

[0020] As organic acids and / or their salts, as mentioned above, amino acids and / or their salts are preferred. Examples of amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Among these, alanine, serine, proline, glycine, methionine, isoleucine, valine, threonine, and tryptophan are more preferred, alanine, serine, and proline are even more preferred, and alanine is particularly preferred. Branched-chain amino acids are also preferred, and among the specific amino acids mentioned above, branched-chain amino acids are more preferred. The amino acids may be L-forms, D-forms, or DL-forms, with L-forms or DL-forms being preferred. In addition, there are α-amino acids, β-amino acids, γ-amino acids, δ-amino acids, etc., and any of these may be used, with α-amino acids being preferred. For example, as mentioned above, alanine is particularly preferred as the amino acid, but either α-alanine or β-alanine may be used, with α-alanine being more preferred. Furthermore, in the case of alanine (α-alanine), the L-form or DL-form is particularly preferred.

[0021] Amino acids can be used individually or in combination of two or more. When two or more amino acids are used in combination, it is preferable that at least one is a branched-chain amino acid, and more preferably that a non-branched-chain amino acid and a branched-chain amino acid are used in combination. In this case, the non-branched-chain amino acid and / or its salt and the branched-chain amino acid and / or its salt are preferably included in a molar ratio (non-branched-chain amino acid and / or its salt: branched-chain amino acid and / or its salt) of 1:0.05 to 4, more preferably 1:0.1 to 2, and even more preferably 1:0.2 to 1. In combinations of non-branched-chain amino acids and / or its salt and branched-chain amino acids and / or its salt, more specifically, at least one selected from the group consisting of alanine, serine, and proline is preferred as the non-branched-chain amino acid, and at least one selected from the group consisting of valine, leucine, and isoleucine is preferred as the branched-chain amino acid. In particular, it is preferable to use alanine as the unbranched-chain amino acid, and especially preferable to use a combination of alanine as the unbranched-chain amino acid and leucine as the branched-chain amino acid.

[0022] Preferred amino acid salts include alkali metal salts, alkaline earth metal salts, hydrochloride salts, and sulfate salts. Preferred alkali metal salts include sodium salts and potassium salts. Preferred alkaline earth metal salts include calcium salts and magnesium salts. Among these, sodium salts, potassium salts, or hydrochloride salts are preferred. These salts can also be used individually or in combination of two or more.

[0023] In this disclosure, when a product is described as "component X and / or its salt," the amount refers to the total amount of both component X and its salt. For example, when a product is described as "amino acid and / or its salt," the amount refers to the total amount of both the amino acid and its salt.

[0024] In the oral compositions of this disclosure, the amino acids and / or salts thereof are preferably present in an amount of, for example, 10 to 250 mM. The upper or lower limit of this range may be, for example, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, or 240 mM. Any two of these values, as well as 10 mM and 250 mM, can be used as the upper and lower limits of this range. The range is more preferably 20 to 200 mM, and even more preferably 30 to 150 mM.

[0025] As mentioned above, organic acids and / or salts thereof may also preferably include organic acids and / or salts thereof other than amino acids. For example, organic acids that do not contain a nitrogen atom and have a carboxyl group and / or a phosphate group, with a molecular weight of 46 to 300, are preferred. Organic acids that satisfy these conditions may be referred to as specific organic acids in this disclosure. The upper or lower limits of the molecular weight of the specific organic acid in this disclosure may be 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, or 295. Any two of these values, as well as any two values ​​from 46 and 300, may be used as the upper and lower limits of the molecular weight range of the specific organic acid in this disclosure. The molecular weight of the specific organic acid in this disclosure may be, for example, 50 to 150 or 60 to 200. Furthermore, if the specific organic acid in this disclosure has carboxyl groups, it is preferable that it has 1 to 4 (1, 2, 3, or 4) carboxyl groups.

[0026] The specific organic acids in this disclosure include, for example, carbonic acid, bicarbonate, citric acid, lactic acid, phosphoric acid, gluconic acid, acetic acid, malic acid, tartaric acid, malonic acid, succinic acid, fumaric acid, maleic acid, glutaric acid, itaconic acid, etc. Carbonic acid, bicarbonate, citric acid, lactic acid, phosphoric acid, gluconic acid, acetic acid, and malic acid are more preferred, and citric acid is particularly preferred. The specific organic acids in this disclosure can be used individually or in combination of two or more. Although carbonic acid, bicarbonate, and phosphoric acid are sometimes classified as inorganic acids, in this disclosure they are treated as organic acids. Furthermore, in this disclosure, although the -CO-OH in carbonic acid (OH-CO-OH) is not usually understood to be a carboxyl group, since it is structurally the same as a carboxyl group, carbonic acid is treated as having a carboxyl group (-COOH). The same applies to bicarbonate.

[0027] In the oral compositions of the present disclosure, the specific organic acids and / or salts thereof of the present disclosure are preferably present in an amount of, for example, 0.05 to 120 mM. The upper or lower limits of this range may be, for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, or 115 mM. Any two values ​​from these ranges, as well as 0.05 mM and 120 mM, can be used as the upper and lower limits of this range. The range may be, for example, 0.1 to 100 mM, 0.1 to 75 mM, 0.1 to 50 mM, or 0.1 to 40 mM, or it may be 0.2 to 30 mM.

[0028] Preferred salts of the specific organic acids in this disclosure include alkali metal salts, alkaline earth metal salts, and ammonium salts. Preferred alkali metal salts include sodium salts and potassium salts. Preferred alkaline earth metal salts include calcium salts and magnesium salts. Among these, sodium salts, potassium salts, or ammonium salts are preferred. These salts can also be used individually or in combination of two or more.

[0029] Examples of vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B3 (niacin), vitamin B6 (pyridoxine, pyridoxal, pyridoxamine, with pyridoxine being preferred), vitamin B12, vitamin B13 (orotic acid), vitamin C (ascorbic acid or its salts: especially sodium salt and potassium salt), vitamin D, vitamin E, vitamin K, pantothenic acid, biotin, etc. Vitamins can be used individually or in combination of two or more.

[0030] In the oral compositions of this disclosure, the vitamin is preferably contained in an amount of, for example, 0.01 to 50 mM. The upper or lower limit of this range may be, for example, 0.02, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or 45 mM. Any two values ​​from these ranges, as well as 0.01 mM and 50 mM, can be used as the upper and lower limits of this range. The range may be, for example, 0.02 to 40 mM or 0.05 to 30 mM.

[0031] Specific sugars include allulose (also known as psicose). D-allulose is preferred. In the oral compositions of this disclosure, allulose is preferably present in an amount of, for example, 5 to 400 mM. The upper or lower limits of this range may be, for example, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 250, 250, 275, 300, 325, 350, or 375 mM. Any two of these values, as well as 5 mM and 400 mM, can be used as the upper and lower limits of this range. The range is preferably, for example, 10 to 375 mM, more preferably 20 to 200 mM, and even more preferably 30 to 150 mM.

[0032] In the oral compositions of this disclosure, two or more of these components of this disclosure may be used in combination. When used in combination, the content of each component is preferably in the amounts described above. For example, when a sugar alcohol and an amino acid and / or its salt are used in combination, as described above, the sugar alcohol is preferably present in a concentration of 10 to 700 mM, and the amino acid and / or its salt is preferably present in a concentration of 10 to 250 mM.

[0033] The combination of components of this disclosure is not particularly limited, and the components described above can be freely combined and used. For example, at least two (two, three, four, or five) selected from the group consisting of sugar alcohols, amino acids and / or salts thereof, specific organic acids and / or salts thereof as disclosed, vitamins, and specific sugars (allulose) can be used in combination.

[0034] While not particularly limited, preferred combinations include, for example, at least one selected from the group consisting of amino acids and / or their salts, the specific organic acids and / or their salts as disclosed herein, and vitamins, and a sugar alcohol. In this case, the type and content (concentration) of each component are as described above.

[0035] When combining a sugar alcohol with an amino acid and / or its salt, it is particularly preferable that the sugar alcohol contains erythritol (preferably 10 to 650 mM, more preferably as described above), and the amino acid and / or its salt contains alanine and / or its salt, and / or leucine and / or its salt (preferably 10 to 250 mM, more preferably as described above). Furthermore, the combination may also contain the specific organic acids and / or their salts and / or vitamins of this disclosure.

[0036] When combining a sugar alcohol with the specific organic acid and / or salt thereof of this disclosure, it is particularly preferable that the sugar alcohol contains erythritol (preferably 10 to 650 mM, more preferably as described above) and the specific organic acid and / or salt thereof contains citric acid and / or salt thereof (preferably 0.05 to 50 mM, more preferably as described above). In addition, amino acids and / or salts thereof, and / or vitamins may be used in combination with this.

[0037] When combining sugar alcohols and vitamins, it is particularly preferable to include erythritol as the sugar alcohol (preferably 10 to 650 mM, more preferably as described above) and at least one vitamin selected from the group consisting of vitamin B3, vitamin B6, and vitamin C (preferably 0.01 to 50 mM, more preferably as described above). A combination of erythritol and vitamin B3, or a combination of erythritol and vitamin C, is especially preferred.

[0038] The oral compositions of this disclosure may preferably be beverage compositions or oral gel-like (particularly jelly-like) compositions. These forms of composition are preferable for efficient hydration.

[0039] As described above, the oral composition of this disclosure is configured to contain preferred components obtained by screening using a screening system that can accurately evaluate whether the water absorption performance in intestinal epithelial cells changes depending on the components contained in the composition. The screening system is based on human iPS cell-derived intestinal epithelial cells F-hiSIEC ＴＭ This screening system was constructed using F-hiSIEC on top of a cultured cell insert plate (Greiner Bio-One, Kremsmunster, Australia). More specifically, the screening system uses F-hiSIEC on top of a cultured cell insert plate (Greiner Bio-One, Kremsmunster, Australia). ＴＭ Culturing F-hiSIEC ＴＭThis constructs a structure that separates the apical side from the basolateral side. By adding a dye-containing buffer and screening material to the apical side, and utilizing the property that water and compounds move to the basolateral side but dyes have poor permeability, the water absorption performance of various screening materials can be examined by measuring the dye concentration and calculating the amount of culture medium on the apical side. An overview of this screening system is shown in Figure 1.

[0040] The oral composition of this disclosure is particularly suitable for use in hydration by intestinal epithelial cells because it exhibits excellent water absorption performance in these cells. For this reason, it is especially suitable for individuals who require rapid hydration, such as those who have lost water through exercise or those suffering from dehydration. While intravenous infusions are sometimes used for rapid hydration, they require special equipment and formulations, making them inconvenient to administer. The oral composition of this disclosure is advantageous because it can be easily stored and carried by filling it into ordinary beverage containers (e.g., PET bottles or glass bottles) or gel containers (e.g., pouches).

[0041] In addition to the components described above, the oral compositions of this disclosure may contain various components commonly added to oral compositions (e.g., beverage compositions and oral gel compositions) without particular limitation. Examples of other components include fruit juices (grapefruit, apple, orange, lemon, pineapple, banana, pear, etc.), flavorings (vanillin, linalool, natural flavorings, etc.), stabilizers, dietary fiber (guar gum, polydextrose, indigestible dextrin, pectin, cellulose, etc.), and sugars other than allulose (monosaccharides such as glucose and fructose, disaccharides such as sucrose (including white sugar), maltose, and lactose, and oligosaccharides such as fructooligosaccharides, soy oligosaccharides, and galactooligosaccharides, etc.). It is also preferable to refrain from adding glucose. More specifically, for example, a glucose content of 100 mM or less, 80 mM or less, or 70 mM or less is preferred, 65 mM or less or 60 mM or less is more preferred, and 55 mM or less or 50 mM or less is even more preferred.

[0042] Further, the oral composition of the present disclosure preferably contains an electrolyte component, and Na ＋ , K ＋ , Ca ２＋ , Mg ２＋ , or Cl － as an electrolyte component (Na ＋ , K ＋ , Ca ２＋ , Mg ２＋ , or Cl － ) is more preferable, and an electrolyte component that supplies Na ＋ , K ＋ , Ca ２＋ , or Mg ２＋ into the oral composition is even more preferable. The salts of the above-mentioned organic acids are also included in the electrolyte component. As the electrolyte component other than the salts of the above-mentioned organic acids, inorganic acid salts are preferably mentioned, and more specifically, for example, the following components are preferably mentioned. As the inorganic acid salt that supplies Na ＋ , for example, NaCl, Na ２ SO ４ , etc. are mentioned. As the inorganic acid salt that supplies K ＋ , for example, KCl, K ３ PO ４ , K ２ HPO ４ , KH ２ PO ４ , etc. are mentioned. As the inorganic acid salt that supplies Ca ２＋ , for example, CaCl ２ [[ID=५4]], CaSO ４ , CaHPO ４ , etc. are mentioned. As the inorganic acid salt that supplies Mg ２＋ , for example, MgCl ２、 MgCO ３ , etc. are mentioned. As the inorganic acid salt that supplies Cl － , for example, NaCl, KCl, MgCl ２ , CaCl ２ , etc. are mentioned. The electrolyte component may be used alone or in combination of two or more.

[0043] The oral composition of the present disclosure contains Na ＋ , K＋ Ca ２＋ Mg ２＋ , or Cl － Preferably, the composition contains at least one selected from the group consisting of the following, and more preferably, two, three, or four selected from the group. For example, the oral composition of this disclosure is Na ＋ _K ＋ Ca ２＋ , and Mg ２＋ It is preferable that it contains [a certain substance].

[0044] There are no particular limitations, but Na ＋ _K ＋ Ca ２＋ Mg ２＋ , or Cl － When an electrolyte component containing these inorganic ions is used, it is preferable that these inorganic ions are used in the oral composition of this disclosure such that they are within the concentration range described below. Furthermore, it is preferable that the oral composition of this disclosure contains at least one selected from the group consisting of these inorganic ions in the concentration range described below.

[0045] Na ＋ If present, its concentration is preferably 15 to 60 mM. The upper or lower limits of this range may be, for example, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or 55 mM. Any two of these values, as well as 15 mM and 60 mM, can be used as the upper and lower limits of this range. The range may be, for example, 16 to 55 mM.

[0046] K ＋ If present, its concentration is preferably 0.5 to 25 mM. The upper or lower limits of this range may be, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 mM. Any two values ​​from these ranges, as well as 0.5 mM and 25 mM, can be used as the upper and lower limits of this range. The range may be, for example, 1 to 22 mM.

[0047] Ca ２＋If present, its concentration is preferably 75 mM or less. The lower limit of the concentration is not particularly limited, but for example, 0.05 mM is given. The upper or lower limit of the range (0.05 to 75 mM) may be, for example, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 mM. Any two values ​​from these, as well as 0.05 mM and 75 mM, can be used as the upper and lower limits of the range. The range may be, for example, 0.1 to 65 mM.

[0048] Mg ２＋ If it is included, its concentration is preferably 17 mM or less. The lower limit of the concentration is not particularly limited, but for example, 0.05 mM is given. The upper or lower limit of the range (0.05 to 17 mM) may be, for example, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 mM. Any two values ​​from these, as well as 0.05 mM and 17 mM, can be used as the upper and lower limits of the range. The range may be, for example, 0.1 to 16 mM.

[0049] Cl － If present, its concentration is preferably 0.5 to 60 mM. The upper or lower limits of this range may be, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or 55 mM. Any two values ​​from these ranges, as well as 0.5 mM and 60 mM, can be used as the upper and lower limits of this range. The range may be, for example, 1 to 55 mM.

[0050] The oral compositions of this disclosure can be prepared, for example, by adding the components of this disclosure and, if necessary, other components to water (particularly water suitable for drinking). After the preparation of each component, the oral compositions of the present invention may be degassed, sterilized, cooled, and filled into containers, if necessary.

[0051] In this specification, the term "comprising" includes both "consisting essentially of" and "consisting of." Furthermore, this disclosure encompasses all combinations of the constituent elements described herein.

[0052] Furthermore, the various characteristics (properties, structure, function, etc.) described for each embodiment of this disclosure described above may be combined in any way to identify the subject matter covered by this disclosure. In other words, this disclosure covers all subject matter consisting of any combination of the combinable characteristics described herein.

[0053] The embodiments of this disclosure will be described in more detail below with examples, but the embodiments of this disclosure are not limited to the examples below.

[0054] Development of a screening system for evaluating moisture absorption performance: F-hiSIEC ＴＭ (Fujifilm Wako Pure Chemical Corporation) was cultured according to the instruction manual, and a system was constructed to easily evaluate water absorption in vitro in a manner similar to that of living organisms. Using this system, the water absorption performance of compositions containing each test substance in intestinal cells was evaluated. More specifically, the procedure was as follows. Note: F-hiSIEC ＴＭ These are human iPS cell-derived intestinal epithelial cells. Figure 1 shows an overview of the screening system.

[0055] F-hiSIEC ＴＭ Thaw at 37°C and apply 1.0 × 10 to the top of a 24-well cell culture insert (Greiner Bio-One, Kremsmunster, Australia) coated with Matrigel Matrix Growth Factor Reduced (Corning, NY, USA). ５ Sown using cells / well. F-hiSIEC ＴＭCulture Medium was used, with the culture medium changed every two days, and the cells were incubated for 10 days until the assay. To investigate the water-promoting effect, HBSS with pH 6.5 containing 10 mM MES, 4.5 g / L glucose, and 10 mg / L phenol red was used on the apical side, and HBSS with pH 7.4 containing 10 mM HEPES and 4.5 g / L glucose was used on the basolateral side.

[0056] Before the screening assay, the cells in the cell culture insert were equilibrated after washing with the buffer described above. Then, the assay was started by replacing the HBSS on the Apical side (HBSS with pH 6.5 containing 10 mM MES, 4.5 g / L glucose, and 10 mg / L phenol red) with 150 mL of HBSS containing each test substance (HBSS with pH 6.5 containing 10 mM MES, 4.5 g / L glucose, and 10 mg / L phenol red). If the test substance was acidic, it was dissolved in HBSS and then readjusted to pH 6.4 using NaOH before being used in the assay. For the Basolateral side, HBSS with pH 7.4 containing 10 mM HEPES and 4.5 g / L glucose was mixed with NaCl to make it isotonic with the Apical side medium. After standing at 37°C for 4 hours, the Apical side medium was collected. The weight of the medium was measured using an analytical electronic balance. Furthermore, the amount of culture medium (μL) was calculated by measuring the concentration of phenol red. A smaller amount of Apical culture medium indicates higher water absorption performance.

[0057] The phenol red concentration was measured as follows: 100 μL of collected culture medium was mixed with 50 μL of 1N NaOH to create the measurement sample. The absorbance of the measurement sample was measured at 570 nm using a SpectraMax 190 microplate reader (Molecular Devices LLC., San Jose, CA, USA). The volume of the culture medium was calculated from the calculated phenol red concentration.

[0058] As described above, each test substance screened was dissolved in HBSS (HBSS with a pH of 6.5 containing 10 mM MES, 4.5 g / L glucose, and 10 mg / L phenol red). When describing the specific screening results below, the names and concentrations of the test substances used refer to the names and concentrations of the test substances dissolved in the aforementioned HBSS. In the screening results, the control (sometimes referred to as "Con") shows the results when no test substances were added (i.e., the HBSS alone).

[0059] Unless otherwise specified, α-amino acids were used as amino acids. Furthermore, when L- and D-forms of an amino acid exist, the L-form was used unless otherwise specified. For example, when alanine is written, L-alanine is indicated unless otherwise specified. Also, all allulose used in this study was the D-form (D-allulose).

[0060] Screening Results for Various Amino Acids Figure 2 shows the screening results (mean ± standard error (n=3)) using various amino acids (all at a concentration of 50 mM) as test substances. One-way ANOVA was performed for statistical analysis, and Dunnett's test was used for post-hoc testing. * indicates P < 0.05 (vs Con).

[0061] These results show that, among the various amino acids, alanine, serine, glutamine, and proline significantly enhance water absorption performance (particularly increasing water absorption in a short period of time), and that alanine exhibits a particularly high effect in this regard.

[0062] Investigation of changes in water absorption performance with erythritol and alanine In the same manner as the screening assay described above, the water absorption performance was investigated when erythritol, L-alanine, a mixture of L-alanine and D-alanine, or a combination thereof were used as the test substance.

[0063] Study 1: The concentrations of each test substance were adjusted as follows. When using a combination of test substances, the concentrations of each test substance remained as follows: Erythritol: 65.5 mM, Alanine L-isomer: 50 mM, Alanine D / L-isomer: D-isomer 25 mM, L-isomer 25 mM. The results (mean ± standard error (n=2)) are shown in Figure 3a. Since n=2, no statistical test was performed.

[0064] Furthermore, studies evaluating the absorption of L-alanine and D-alanine in rats have reported that the L-isomer:D-isomer is absorbed in a ratio of approximately 1:0.6 (Non-patent document 1: Biochim Biophys Acta. 1999;1472(1-2):107-14). Therefore, it is assumed that if 50 mM of racemic DL-alanine is ingested, 40 mM will be absorbed as alanine.

[0065] Study 2: The concentrations of each test substance were adjusted as follows: Erythritol 10–125 mM. The results (mean ± standard error (n=3)) are shown in Figure 3b. One-way ANOVA was performed for statistical analysis, and Dunnett's method was used for post-hoc testing. * indicates P < 0.05 (vs Con).

[0066] Study 3: The concentrations of each test substance were adjusted as follows: 50 mM erythritol, 50 mM alanine, or 50 mM erythritol and 50 mM alanine. The results (mean ± standard error (n=3)) are shown in Figure 3c. Two-way ANOVA was performed for statistical analysis. * indicates P < 0.05 (vs Con; main effect), and $ indicates P < 0.05 (interaction).

[0067] Investigation of changes in water absorption performance with allulose and alanine: In the same manner as the screening assay described above, the water absorption performance was investigated when allulose and alanine were used as test substances.

[0068] Study 1: The concentrations of each test substance were adjusted as follows: Allulose 0, 5, 15, or 30 mM. The results (mean ± standard error (n=3)) are shown in Figure 4a. One-way ANOVA was performed for statistical analysis, and Dunnett's method was used for post-hoc testing. * indicates P < 0.05 (vs Con).

[0069] Study 2: The concentrations of each test substance were adjusted as follows: alanine 50 mM, allulose 50 mM, or alanine 50 mM and allulose 50 mM. The results (mean ± standard error (n=3)) are shown in Figure 4b. Two-way ANOVA was performed for statistical analysis. * indicates P < 0.05 (vs Con).

[0070] Investigation of changes in water absorption performance with leucine and alanine: In the same manner as the screening assay described above, the water absorption performance was investigated when leucine and alanine were used as test substances.

[0071] The concentrations of each test substance were adjusted as follows: alanine 50 mM, leucine 15 mM, leucine 17.5 mM, leucine 20 mM, alanine 50 mM and leucine 15 mM, alanine 50 mM and leucine 17.5 mM, or alanine 50 mM and leucine 20 mM. The results (mean ± standard error (n=3)) are shown in Figures 5a to 5c. Two-way ANOVA was performed for statistical analysis. * indicates P < 0.05 (vs Con), and $ indicates P < 0.05 (interaction).

[0072] Investigation of changes in water absorption performance with citric acid, erythritol, and alanine: In the same manner as the screening assay described above, the water absorption performance was investigated when citric acid, erythritol, and alanine were used as test substances.

[0073] Study 1: The concentrations of each test substance were adjusted as follows: Citric acid 0, 0.1, 0.5, 1.0, 5.0, or 10.0 mM. The results (mean ± standard error (n=3)) are shown in Figure 6a. One-way ANOVA was performed for statistical analysis, and Dunnett's method was used for post-hoc testing. * indicates P < 0.05 (vs Con).

[0074] Study 2: The concentrations of each test substance were adjusted as follows: 50 mM erythritol, 65.5 mM erythritol, 0.5 mM citric acid, 50 mM erythritol and 0.5 mM citric acid, or 65.5 mM erythritol and 0.5 mM citric acid. The results (mean ± standard error (n=3)) are shown in Figures 6b and 6c. Two-way ANOVA was performed for statistical analysis. * indicates P < 0.05 (vs Con; main effect), and $ indicates P < 0.05 (interaction).

[0075] Investigation of changes in water absorption performance due to vitamins: Similar to the screening assay described above, the water absorption performance was investigated when various vitamins and the components used in the above study were used as test substances. Pyridoxine was used as vitamin B6.

[0076] Study 1: The concentrations of each test substance were adjusted as follows: Vitamin B3 0.05 mM or 0.1 mM. The results (mean ± standard error (n=3)) are shown in Figure 7a. One-way ANOVA was performed for statistical analysis, and Dunnett's method was used for post-hoc testing. * indicates P < 0.05 (vs Con).

[0077] Study 2: The concentrations of each test substance were adjusted as follows: Vitamin C 0.05, 0.1, 0.5, 1.0, or 5.0 mM. The results (mean ± standard error (n=3)) are shown in Figure 7b. One-way ANOVA was performed for statistical analysis, and Dunnett's method was used for post-hoc testing. * indicates P < 0.05 (vs Con).

[0078] Study 3: The concentrations of each test substance were adjusted as follows: alanine 50 mM, erythritol 65.5 mM, vitamin B6 0.16 mM; alanine 50 mM and vitamin B6 0.16 mM; or erythritol 65.5 mM and vitamin B6 0.16 mM. The results (mean ± standard error (n=2)) are shown in Figure 7c. Since n=2, no statistical test was performed.

[0079] Study 4: The concentrations of each test substance were adjusted as follows: erythritol 50 mM, erythritol 65.5 mM, vitamin C 0.1 mM, erythritol 50 mM and vitamin C 0.1 mM, or erythritol 65.5 mM and vitamin C 0.1 mM. The results (mean ± standard error (n=3)) are shown in Figures 7d and 7e. Two-way ANOVA was performed for statistical analysis. * indicates P < 0.05 (vs Con; main effect), and $ indicates P < 0.05 (interaction).

[0080] The effect of alanine on restoring plasma volume after dehydration was investigated. Under the following conditions, humans were given either an electrolyte beverage containing alanine (alanine electrolyte beverage) or an electrolyte beverage without alanine (control beverage), and blood was collected over time to examine the change in plasma volume (%). A higher plasma volume indicates that more water was absorbed into the body.

[0081] [Study Overview] Study Design: Randomized, open-label, crossover comparative study Subjects: 11 males (23 ± 5 years old, weight 67.6 ± 7.2 kg) Dehydration Conditions: Dehydrated by cycling in a hot environment (36°C, 40% RH (relative humidity)) with a dehydration equivalent to 2% of initial body weight Amount Intake: Intake of an amount equivalent to the amount of dehydration in 30 minutes

[0082] [Overview of the test food (beverage), dehydration rate, and intake amount]

[0083]

[0084] The percentage change in plasma volume from the baseline value before ingestion of the test food was calculated. The differences in temporal changes between trial conditions up to 2 hours after ingestion were analyzed using a mixed model ANOVA with baseline values ​​as the covariate, fixed effects as the test food, ingestion order (the beverages consumed in phases I and II were different, and the order of ingestion of those beverages), timing (phases I and II), time point (time points after ingestion), and interaction between the test food and time point, and random effects as the subjects. The results are shown in Figure 8.

[0085] Both the alanine electrolyte beverage group and the control beverage group showed similar rates of dehydration and intake, but the alanine electrolyte beverage group showed a significantly greater increase in plasma volume.

Claims

1. An oral composition for hydration comprising erythritol and alanine and / or a salt thereof.

2. The composition according to claim 1, comprising 10 to 650 mM of erythritol.

3. The oral composition according to claim 2, comprising 10 to 250 mM of alanine and / or a salt thereof.

4. An oral composition for hydration comprising erythritol and citric acid and / or a salt thereof.

5. The oral composition according to claim 4, comprising 10 to 650 mM erythritol.

6. The oral composition according to claim 5, comprising 0.05 to 120 mM of citric acid and / or a salt thereof.

7. An oral composition for hydration, comprising erythritol and vitamin C.

8. The oral composition according to claim 7, comprising 10 to 650 mM of erythritol.

9. The oral composition according to claim 8, comprising 0.05 to 50 mM of vitamin C.

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