Oral composition

Abstract

To provide an oral composition containing an amino acid and exhibiting excellent muscle-enhancing effect.SOLUTION: The oral composition contains leucine and threonine, and preferably further contains (c) lysine, (d) valine, (e) isoleucine, (f) phenylalanine, (g) methionine, (h) histidine, and (i) tryptophan.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to oral compositions containing leucine and threonine. [Background technology]

[0002] BACKGROUND ART In recent years, with the background of increasing interest in health, various health foods have been developed, for example, health foods containing amino acids.

[0003] Health foods containing such amino acids have been proposed, for example, for enhancing learning and memory abilities, containing amino acids such as alanine, arginine, and leucine (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-184956 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide an oral composition that contains amino acids and exhibits excellent muscle-building effects. [Means for solving the problem]

[0006] As a result of extensive research aimed at solving the above problems, the present inventors have found that an oral composition containing leucine and threonine has an excellent muscle-building effect, and have thus completed the present invention.

[0007] That is, the present invention is as follows. [1] An oral composition comprising (a) leucine and (b) threonine. [2] The oral composition according to [1] above, further comprising (c) lysine, (d) valine, (e) isoleucine, (f) phenylalanine, (g) methionine, (h) histidine, and (i) tryptophan. [3] The oral composition according to [1] or [2] above, which is for muscle building. [4] The oral composition according to any one of [1] to [3] above, wherein the molar composition ratio of the content of the leucine to the total content of essential amino acids in the composition is 0.05 or more and 0.99 or less. [5] The oral composition according to any one of [1] to [4] above, wherein the molar composition ratio of the content of the threonine to the total content of essential amino acids in the composition is 0.01 or more and 0.15 or less. [6] The oral composition according to [2] above, wherein the molar composition ratio of the lysine content to the total content of essential amino acids is 0.03 or more. [7] The oral composition according to any one of [1] to [6] above, wherein the molar composition ratio of the leucine content to the total content of essential amino acids in the composition is 0.35 or more and less than 0.55, and the molar composition ratio of the threonine content to the total content of the essential amino acids in the composition is 0.025 or more and 0.09 or less. [8] The oral composition according to any one of [1] to [6] above, wherein the molar composition ratio of the content of said leucine to the total content of essential amino acids in the composition is 0.6 or less, and the molar composition ratio of said threonine to said leucine is 0.06 or less. [9] The oral composition according to any one of [1] to [6] above, wherein the molar composition ratio of the content of said leucine to the total content of essential amino acids in the composition is 0.5 or less, and the molar composition ratio of said threonine to said leucine is 0.15 or less. [Effects of the Invention]

[0008] The oral composition of the present invention exhibits excellent muscle-building effects. DETAILED DESCRIPTION OF THE INVENTION

[0009] The oral composition of the present invention is characterized by containing (a) leucine and (b) threonine.

[0010] The oral composition of the present invention contains leucine and threonine, which promotes protein production in the body and exhibits excellent muscle-building effects. For example, even with a small amount of intake, muscle-building effects comparable to those of conventional whey protein can be achieved. The oral composition of the present invention can be used for muscle building in athletes and healthy individuals, muscle recovery after illness, and muscle maintenance in the elderly. Furthermore, since the oral composition of the present invention contains leucine and threonine, it has an improved flavor and can be ingested without resistance.

[0011] Each component contained in the oral composition of the present invention will be described below. [(a) Leucine] Leucine is a type of amino acid, a branched-chain amino acid that is one of the essential amino acids for humans, and is abbreviated as Leu or L. Leucine exists in isomers such as L-, D-, and DL-isomers, and all of these can be used in the oral composition of the present invention. The leucine of the present invention refers to leucine that exists as a free amino acid, and does not include leucine that exists as a component of protein. Free amino acids (amino acids that exist independently and separately from proteins) have different chemical properties from amino acids that exist as components of proteins, and the two are clearly distinguished. Note that amino acids such as threonine, which will be described later, are also referred to as free amino acids.

[0012] The content of leucine relative to the total content of essential amino acids in the oral composition of the present invention (the molar composition ratio of leucine content when the total content of essential amino acids is taken as 1) is not particularly limited, but is preferably 0.05 or more and 0.99 or less (essential amino acids:leucine=1:0.05-0.99), and more preferably 0.08 or more and 0.9 or less. From the viewpoint of improving flavor, the blending ratio (molar composition ratio) of leucine relative to the total content of essential amino acids in the oral composition of the present invention is preferably 0.2 or more and 0.99 or less, more preferably 0.65 or more and 0.9 or less, and particularly preferably 0.65 or more and 0.75 or less.

[0013] [(b) Threonine] Threonine, a type of amino acid with a hydroxyethyl group in the side chain, is also called threonine. It is one of the essential amino acids in humans and is abbreviated as Thr or T. Threonine has two optically active centers, and therefore exists as four isomers: L-threonine, D-threonine, L-allothreonine, and D-allothreonine. All of these isomers can be used in the oral composition of the present invention.

[0014] The content (molar composition ratio) of threonine relative to the total content of essential amino acids in the oral composition of the present invention is not particularly limited, but is preferably 0.01 or more and 0.15 or less (essential amino acids:threonine=1:0.01-0.15), and more preferably 0.02 or more and 0.13 or less.

[0015] The content (molar composition ratio) of leucine and threonine in the oral composition of the present invention is preferably a molar composition ratio of threonine to leucine of 0.001 or more and 0.6 or less (leucine:threonine=1:0.001-0.6), more preferably 0.005 or more and 0.55 or less, and even more preferably 0.04 or more and 0.55 or less, in order to further enjoy the effects of the present invention.

[0016] The leucine and threonine of the present invention can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, in order to further enjoy the effects of the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred. The leucine and threonine of the present invention can be commercially available products that are usually available as food ingredients.

[0017] <Other amino acids> The oral composition of the present invention preferably further contains essential amino acids other than leucine and threonine. This allows for a balanced intake of essential amino acids, resulting in more effective muscle building. Specific examples of other essential amino acids include (c) lysine, (d) valine, (e) isoleucine, (f) phenylalanine, (g) methionine, (h) histidine, and (i) tryptophan. The essential amino acids used together with leucine and threonine in the oral composition of the present invention may be one or more, and most preferably all of the essential amino acids (c) to (i).

[0018] [(c) Lysine] Lysine is a basic amino acid. It is one of the essential amino acids for humans and is also called lysine, abbreviated as Lys or K. Lysine exists in the form of isomers, such as L-, D-, and DL-isomers, all of which can be used in the oral composition of the present invention.

[0019] The content of lysine contained in the oral composition of the present invention is preferably 0.03 or more, more preferably 0.03 or more and 0.08 or less, and even more preferably 0.04 or more and 0.08 or less, in terms of molar composition ratio relative to the total content of essential amino acids, in order to better enjoy the effects of the present invention.

[0020] [(d) valine] Valine is a branched-chain amino acid. It is one of the essential amino acids for humans and is also known as 2-aminoisovaleric acid, abbreviated as Val or V. Valine exists as an isomer, such as L-, D-, or DL-isomer, and any of these can be used in the oral composition of the present invention.

[0021] In order to better enjoy the effects of the present invention, the content of valine contained in the oral composition of the present invention is preferably a molar composition ratio of 0.03 or more to the total content of essential amino acids, more preferably 0.03 or more and 0.15 or less, and even more preferably 0.04 or more and 0.13 or less.

[0022] When the oral composition of the present invention contains the essential amino acids (c) to (i), it is preferable to blend them so that (c) lysine and (d) valine are the two amino acids with the highest content ratios (molar composition ratios) among the essential amino acids (c) to (i) (regardless of the content ratios of (c) lysine and (d) valine).

[0023] [(e) Isoleucine] Isoleucine is a branched-chain amino acid. It is one of the essential amino acids for humans and is also known as 2-amino-3-methylpentanoic acid (2-amino-3-methylvaleric acid), abbreviated as Ile or I. Isoleucine exists in the form of L-, D-, and DL-isomers, all of which can be used in the oral composition of the present invention.

[0024] In order to better enjoy the effects of the present invention, the content of isoleucine contained in the oral composition of the present invention is preferably a molar composition ratio of 0.02 or more to the total content of essential amino acids, more preferably 0.02 or more and 0.14 or less, and even more preferably 0.03 or more and 0.12 or less.

[0025] [(f) Phenylalanine] Phenylanine is an aromatic amino acid with a benzyl group in the side chain. It is an essential amino acid in humans and is abbreviated as Phe or F. Phenylanine exists as L-, D-, and DL-isomers, all of which can be used in the oral composition of the present invention.

[0026] The content of phenylalanine contained in the oral composition of the present invention is preferably 0.04 or more in terms of molar composition ratio to the total content of essential amino acids, in order to better enjoy the effects of the present invention, more preferably 0.01 or more and 0.8 or less, and even more preferably 0.05 or more and 0.12 or less.

[0027] When the oral composition of the present invention containing leucine and threonine contains phenylalanine, the content (molar composition ratio) of phenylalanine and threonine is preferably 0.5 or more and 2.0 or less, more preferably 0.7 or more and 1.8 or less, and even more preferably 0.8 or more and 1.5 or less, in terms of the molar composition ratio of phenylalanine to threonine, in order to better enjoy the effects of the present invention.

[0028] [(g) Methionine] Methionine is a hydrophobic amino acid containing sulfur in the side chain. It is one of the essential amino acids for humans and is abbreviated as Met or M. Methionine exists as an isomer, such as L-, D-, or DL-isomer, and any of these can be used in the oral composition of the present invention.

[0029] In order to obtain the effects of the present invention more effectively, the content of methionine contained in the oral composition of the present invention is preferably 0.01 or more in terms of molar composition ratio to the total content of essential amino acids, more preferably 0.01 or more and 0.04 or less, and even more preferably 0.015 or more and 0.04 or less.

[0030] [(h) histidine] Histidine is an aromatic amino acid with a heteroaromatic ring in the side chain. It is an essential amino acid in humans and is abbreviated as His or H. Histidine exists in the form of L-, D-, and DL-isomers, all of which can be used in the oral composition of the present invention.

[0031] In order to further enjoy the effects of the present invention, the content of histidine contained in the oral composition of the present invention is preferably 0.008 or more, more preferably 0.008 or more and 0.03 or less, and even more preferably 0.01 or more and 0.03 or less, in terms of molar composition ratio relative to the total content of essential amino acids.

[0032] [(i) Tryptophan] Tryptophan is an aromatic amino acid with an indole ring in its side chain. It is an essential amino acid in humans and has the systematic name 2-amino-3-(indolyl)propionic acid, abbreviated as Trp or W. Tryptophan exists in the form of L-, D-, and DL-isomers, all of which can be used in the oral composition of the present invention.

[0033] In order to further enjoy the effects of the present invention, the content of tryptophan contained in the oral composition of the present invention is preferably a molar composition ratio of 0.002 or more to the total content of essential amino acids, more preferably 0.002 or more and 0.02 or less, and even more preferably 0.003 or more and 0.02 or less.

[0034] The other essential amino acids of the present invention, like leucine and threonine, can be used not only in the free form but also in the form of a salt, and commercially available products that are usually available as food ingredients can also be used.

[0035] When the oral composition of the present invention contains the amino acids (c) to (i) in addition to (a) leucine and (b) threonine, the (a) leucine and (b) threonine are preferably contained in the following composition ratio, in order to more significantly exhibit the effects of the present invention.

[0036] 1) The molar composition ratio of the content of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.1 or more and less than 0.35, and the molar composition ratio of the content of (b) threonine to the total content of the essential amino acids (a) to (i) is 0.025 or more and 0.13 or less. 2) The molar composition ratio of the content of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.35 or more and less than 0.55, and the molar composition ratio of the content of (b) threonine to the total content of the essential amino acids (a) to (i) is 0.025 or more and 0.09 or less. 3) The molar composition ratio of the content of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.55 or more and less than 0.65, and the molar composition ratio of the content of (b) threonine to the total content of the essential amino acids (a) to (i) is 0.01 or more and 0.04 or less. 4) The molar composition ratio of the content of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.65 or more, and the molar composition ratio of the content of (b) threonine to the total content of the essential amino acids (a) to (i) is 0.01 or more and 0.04 or less. 5) The molar composition ratio of (a) leucine to the total content of essential amino acids (a) to (i) is 0.6 or less, and the molar composition ratio of (b) threonine to (a) leucine is 0.06 or less, preferably 0.05 or less. 6) The molar composition ratio of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.5 or less, and the molar composition ratio of (b) threonine to (a) leucine is 0.15 or less, preferably 0.1 or less, more preferably 0.08 or less. The lower limit of the molar composition ratio of (b) threonine to (a) leucine may be, for example, 0.01 or more, or 0.02 or more. 7) The molar composition ratio of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.4 or less, and the molar composition ratio of (b) threonine to (a) leucine is 0.2 or less, preferably 0.15 or less, more preferably 0.1 or less. The lower limit of the molar composition ratio of (b) threonine to (a) leucine may be, for example, 0.01 or more, or may be 0.02 or more. 8) The molar composition ratio of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.3 or less, and the molar composition ratio of (b) threonine to (a) leucine is 0.4 or less, preferably 0.35 or less. The lower limit of the molar composition ratio of (b) threonine to (a) leucine may be, for example, 0.01 or more, or may be 0.02 or more. 9) The molar composition ratio of (a) leucine to the total content of the essential amino acids (a) to (i) is 0.2 or less, and the molar composition ratio of (b) threonine to (a) leucine is 0.6 or less, preferably 0.5 or less. The lower limit of the molar composition ratio of (b) threonine to (a) leucine may be, for example, 0.01 or more, or may be 0.02 or more.

[0037] The oral composition of the present invention may contain, in addition to the above-mentioned (a) leucine, (b) threonine, and the other essential amino acids (c) to (i), other commonly used substances, such as various excipients, binders, glossing agents, lubricants, stabilizers, diluents, bulking agents, thickeners, emulsifiers, antioxidants, pH adjusters, colorants, flavorings, and additives.

[0038] The intake amount of the oral composition of the present invention is not particularly limited, but from the viewpoint of further enjoying the effects of the present invention, the daily intake of leucine may be 100 mg / day or more, preferably 300 mg / day or more, and more preferably 500 mg / day or more. The upper limit of the intake amount is not particularly limited, but from the viewpoint of further enjoying the effects of the present invention, the daily intake of leucine may be 15,000 mg / day or less, preferably 5,000 mg / day or less, and more preferably 2,500 mg / day or less.

[0039] The oral composition of the present invention is not particularly limited as long as it is in a form that can be taken orally, and may be any of pharmaceuticals (including quasi-drugs), so-called health foods, foods for specified health uses, and foods with functional claims.

[0040] Examples of the form of the oral composition of the present invention include tablets, capsules, powders, granules, liquids, rods, plates, blocks, solids, rounds, pastes, creams, caplets, gels, chewable tablets, and sticks, with tablets, capsules, powders, granules, and liquids being preferred.

[0041] The oral composition of the present invention can be used as an oral composition for muscle building. Such an oral composition for muscle building is not particularly limited as long as it contains leucine and threonine and can be distinguished from other products in that it is used for muscle building. For example, the scope of the present invention includes products that display the muscle building function on the product itself, packaging, instructions, or promotional materials. Functional food claims also include those that claim muscle building as a scientific basis for their functionality.

[0042] Specifically, examples include products that claim to have functions such as inhibiting, maintaining, or increasing muscle mass (muscle weight, muscle cross-sectional area, muscle density), inhibiting, maintaining, or improving muscle quality, inhibiting, maintaining, or increasing muscle strength, etc. More specifically, examples include products that claim to "increase muscle strength," "support muscle-building ability," "suppress muscle breakdown," "macho," "slim-macho," "maintain muscle mass and strength," etc.

[0043] The oral composition for muscle building of the present invention is not limited to those labeled on the product packaging, etc., with the combined components of the present invention (leucine and threonine) as the active ingredient for muscle building. For example, it may be a product in which the active ingredient is not specified. Furthermore, even general foods that are manufactured and sold with suggested functions and uses are included in the scope of the oral composition for muscle building of the present invention. For example, there are products sold with personal testimonials from people who have taken the product posted on their websites, etc., mentioning its functions and uses.

[0044] The subjects who can take the oral composition of the present invention are not particularly limited as long as they are people who need to strengthen their muscles, but preferred examples include people who want to get in shape, athletes, and elderly people with weak legs and hips. [Example]

[0045] The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples.

[0046] <Test 1: Evaluation of cell activation activity> The oral composition of the present invention was used to confirm the cell-activating activity of a mouse myoblast cell line (C2C12). C2C12 is widely used as a model for evaluating muscle mass-increasing effects, and by confirming its cell-activating activity, the muscle-building effect can be confirmed.

[0047] [Test substance] The following substances were used as test substances. Leucine: Reagent for L-leucine Lysine: L-Lysine monohydrochloride reagent Valine: Reagent for L-valine Isoleucine: Reagent for L-isoleucine Threonine: L-threonine reagent Phenylalanine: Reagent for L-phenylalanine Methionine: L-methionine reagent Histidine: L-histidine reagent Tryptophan: L-tryptophan reagent

[0048] (Preparation of test substance) Each test substance was suspended in 10% FBS-amino acid-free DMEM medium to a concentration of 20 mM. The suspension was sterilized through a 0.2 μm filter and diluted to a concentration of 10 μM with the same medium to obtain a test substance preparation solution. Each test substance preparation solution was mixed to achieve the molar composition ratio listed in Table 1 to prepare test substance-containing medium. Regarding the "essential amino acids other than leucine and threonine," a mixture of lysine:valine:isoleucine:phenylalanine:methionine:histidine:tryptophan (molar ratio) of 10.5:11.3:7.8:7.8:5.0:3.3:1 was used.

[0049] [Evaluation test] The specific experimental procedures are as follows. In a 37°C, 5% CO2 incubator, 75 cm 2 C2C12 cells were cultured in a flask with 10% FBS-DMEM. Then, the cells were suspended by trypsinization and placed in each well of a collagen-coated 96-well plate at 8 × 10 3 The cells were seeded at a density of 100 cells / well and pre-cultured for 24 hours in a 5% by volume CO2 incubator at 37°C.

[0050] After removing the medium from each well, the wells were washed once with PBS, and 100 μL / well of medium containing the test substance was added, followed by culturing for 3 hours in a 37° C., 5% by volume CO 2 incubator. The medium used was 10% FBS-amino acid-free DMEM, and the total molar concentration of the test substance in the medium was 10 μM. As a control, 10% FBS-amino acid-free DMEM medium containing no test substance was added. This was designated Comparative Example 1.

[0051] After 3 hours of incubation, the medium was removed, and 150 μL of Cell Counting Kit-8 (Dojindo Laboratories) diluted 20-fold with amino acid-free DMEM was added to each well. The plates were placed in a 37°C, 5% CO2 incubator to allow for adequate color development, and the absorbance at 450 nm of the formazan product, which is proportional to the number of viable cells in each well, was measured.

[0052] The WST-8 color reagent in the Cell Counting Kit-8 is reduced to formazan by the action of dehydrogenase via electron transfer substances. The more viable cells there are, the higher the dehydrogenase activity and the greater the amount of formazan produced. Since formazan has a maximum absorption around 450 nm, the amount of formazan produced was measured based on this absorbance to confirm C2C12 proliferation. Higher formazan absorbance indicates greater C2C12 proliferation, so this absorbance serves as an indicator of myoblast-stimulating activity. As a blank, the absorbance of Cell Counting Kit-8 alone diluted 20-fold with amino acid-free DMEM was measured.

[0053] The difference between the absorbance of each test substance well and the absorbance of the blank was calculated as the cell-activating activity of each test substance well, and the results were evaluated relative to the cell-activating activity of the control well, Comparative Example 1, using the following formula. Table 1 shows the results.

[0054] Cell stimulating activity = (absorbance of each test substance well - absorbance of blank) x 100 / (absorbance of control well - absorbance of blank)

[0055] [Table 1]

[0056] As shown in Table 1, the compositions of Examples 1 to 3 of the present invention containing leucine and threonine exhibited cell-activating activity, as evident from a comparison with a control (Comparative Example 1) containing no leucine or threonine. In particular, at a specific leucine content, high cell-activating activity was observed when the threonine content was within a specific range or when the threonine / leucine molar ratio was within a specific range. Furthermore, high cell-activating activity was observed when the threonine / leucine molar ratio was 0.05 or less. Even when the threonine / leucine molar ratio was slightly above 0.05, a tendency for high cell-activating activity was observed as the ratio of leucine to the total amino acid content decreased.

[0057] As described above, the composition of the present invention contains a well-balanced blend of essential amino acids that are effective in the production of proteins in the body, and can improve the cell-activating activity of C2C12. Therefore, the composition of the present invention can promote muscle building.

[0058] <Test 2: Sensory Test> The oral compositions of the present invention were evaluated for flavor.

[0059] [Preparation of test substance (drink)] The test substances shown in Table 2 were dissolved in pure water to a concentration of 7.5 g / mL to obtain the liquid beverages of Comparative Examples 5 to 6 and Examples 20 to 26. The "essential amino acids other than leucine and threonine" were mixed in a ratio (molar ratio) of lysine:valine:isoleucine:phenylalanine:methionine:histidine:tryptophan = 10.5:11.3:7.8:7.8:5.0:3.3:1.

[0060] [Evaluation method] A sensory evaluation test was conducted on five subjects with knowledge and experience in sensory testing, who consumed the liquid beverage. The evaluation items were the "bitterness characteristic of leucine," "ease of drinking," "taste," and "aftertaste." Each item in the sensory evaluation was scored as follows: Leucine's characteristic bitterness: Strong bitterness 1 ← 3 → 5 Weak bitterness Drinkability: Difficult to drink 1 ← 3 → 5 Easy to drink Taste: Not tasty 1 ← 3 → 5 Delicious Aftertaste: Bad aftertaste 1 ← 3 → 5 Good aftertaste

[0061] [Test Results] The average scores for each item are shown in Table 2. Note that Comparative Example 5 did not contain a mixture of amino acids (mixed ingredients) containing lysine, valine, etc., and therefore was not evaluated for the "bitterness specific to mixed ingredients."

[0062] [Table 2]

[0063] As shown in Table 2, the compositions of Examples 20 to 26 (corresponding to the compositions of Examples 1, 2, 8, 12, 17, 18, and 19, respectively) were excellent in terms of taste in addition to the improved muscle-building effect. In Examples 21 to 26 in which the molar composition ratio of leucine to the total essential amino acid content was 0.2 or more, the "bitterness peculiar to the mixed ingredients" was further improved. Furthermore, in Example 25 in which the molar composition ratio of leucine to the total essential amino acid content was 0.65 or more and threonine was 0.04 or less, this was particularly preferable in terms of both muscle-building effect and compatibility. [Industrial Applicability]

[0064] The oral composition of the present invention can be used as a health food or the like and is therefore industrially useful.

Claims

1. An oral composition comprising (a) leucine and (b) threonine.

2. 2. The oral composition of claim 1, further comprising: (c) lysine; (d) valine; (e) isoleucine; (f) phenylalanine; (g) methionine; (h) histidine; and (i) tryptophan.

3. The oral composition according to claim 1 or 2, which is for muscle building.

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