Mixture of amino group-containing compound and organic acid with co-amorphous structure

Abstract

The present invention provides a means that can mask the odd taste of dipeptide sweeteners and the bitterness of amino acids, that increases the dissolution rate of amino acids, that involves less time and effort during production, that has less restrictions regarding the compositional makeup and use application, and that does not use expensive peptides. This mixture is characterized in that an amorphous structure is formed by an organic acid and an amino group-containing compound, and is particularly characterized in that the amino group-containing compound is a peptide or an amino acid.

Description

[Technical Field]

[0001] The present invention relates to a mixture that suppresses (reduces) the bitterness of orally ingestible compositions such as foods, beverages, and oral pharmaceuticals, and a method for producing an orally ingestible composition with suppressed (reduced) bitterness. [Background technology]

[0002] Many organic compounds containing amino groups have excellent functionality and are used in foods, beverages, and oral medicines. However, some of these compounds can have unpleasant tastes such as bitterness, aftertaste, or roughness, so there is a need for technology to reduce these unpleasant tastes.

[0003] Branched chain amino acids (BCAAs) such as valine, leucine, and isoleucine are known to have a bitter taste. As techniques for suppressing the bitterness of foods, beverages, and oral medications containing BCAAs, for example, Patent Document 1 discloses a technique of incorporating γ-glutamyl peptide, and Patent Document 2 discloses a technique of coating with fats and oils. Peptides are more expensive than amino acids, which affects production costs. Furthermore, fat and oil coating is limited to applications that can tolerate fats and oils.

[0004] There is a need for a technology to reduce the off-taste of sweeteners such as dipeptides, such as NL-α-aspartyl-L-phenylalanine 1-methyl, and Patent Document 4 discloses a technology for incorporating peptides. However, peptides have the problem of increasing production costs.

[0005] Furthermore, Patent Document 5 discloses that when a product containing an acidulant was manufactured to suppress the bitterness of amino acids, the product sometimes had poor meltability in the mouth and felt rough. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent Publication No. 2016-171761 [Patent Document 2] WO2017-159708 [Patent Document 3] Patent Publication No. 2011-103799 [Patent Document 4] WO2008-139946 [Patent Document 5] Patent Publication No. 2018-154598 Summary of the Invention [Problem to be solved by the invention]

[0007] The problem to be solved by the present invention is to provide a means for masking the unpleasant taste of foods, beverages, and oral medicines without using expensive peptides, with few limitations on applications and compositions, and with minimal production effort. [Means for solving the problem]

[0008] The present invention was made to solve the above-mentioned problems, and it was found that an amino group-containing compound and an organic acid can form a co-amorphous structure, and that the co-amorphous structure suppresses off-tastes more than a simple mixture. Furthermore, it was surprisingly found that the dissolution rate can be increased, and that the co-amorphous structure has the effect of quickly dissolving poorly soluble substances in the mouth or in water while suppressing off-tastes.

[0009] That is, the present invention provides: (1) A mixture of an amino group-containing compound and an organic acid, characterized in that the amino group-containing compound and the organic acid have a co-amorphous structure. (2) The mixture according to (1), wherein the amino group-containing compound is a peptide or an amino acid. (3) The mixture according to (2), wherein the amino group-containing compound is at least one amino acid selected from the group consisting of leucine, isoleucine, valine, cystine, phenylalanine, tyrosine, tryptophan, arginine, and histidine. (4) The mixture according to (2), wherein the amino group-containing compound is an amino acid, and the amino acid is a branched-chain amino acid. (5) The mixture according to (4), wherein the branched-chain amino acid is leucine, isoleucine, or valine. (6) The mixture according to (2), wherein the amino group-containing compound is an amino acid, and the amino acid is an amino acid that exhibits a bitter taste. (7) The mixture according to (2), wherein the amino group-containing compound is a peptide, and the peptide is a dipeptide. (8) The mixture according to (2), wherein the peptide is NL-α-aspartyl-L-phenylalanine 1-methyl. (9) The mixture according to (1) or (2), wherein the organic acid is citric acid, tartaric acid, malic acid, phthalic acid, fumaric acid, or succinic acid, or a salt or hydrate thereof. (10) The mixture according to (9), wherein the organic acid is ferrous citrate or a salt thereof. (11) The mixture according to (2), wherein the amino group-containing compound is an amino acid selected from the group consisting of leucine, isoleucine, and valine, and the organic acid is citric acid, tartaric acid, and malic acid. (12) The mixture according to (11), wherein the amino acid is leucine and the organic acid is citric acid. (13) The mixture according to (10), wherein the amino acid is tyrosine. This provides:

[0010] The co-amorphous structure mixtures obtained above all have improved water solubility and can be used in beverages, seasonings, sweeteners, and culture media. Therefore, the present invention also provides: (14) A beverage comprising the mixture according to any one of (1) to (13). (15) A seasoning comprising the mixture according to any one of (1) to (13). (16) A sweetener comprising the mixture according to any one of (1) to (13). (17) A culture medium comprising the mixture according to any one of (1) to (13). (18) An oral medicine comprising the mixture according to any one of (1) to (13). It also provides.

[0011] Amino acids have a bitter taste, while NL-α-aspartyl-L-phenylalanine 1-methyl is known as a harmless sweetener, but it has an unpleasant taste, such as a sweetness that lingers longer than sugar. The present inventors have found that the above-mentioned co-amorphous structure mixture has the effect of masking these bitter and / or unpleasant tastes.

[0012] Therefore, the present invention (19) An edible product having a masked bitterness and / or unpleasant taste, characterized by containing the mixture according to any one of (1) to (13). (20) An edible powder product having a masked bitterness and / or unpleasant taste, characterized by containing the mixture according to any one of (1) to (13). (21) An edible product that masks the bitterness of amino acids, characterized in that a mixture containing bitter amino acids and organic acids in a molar ratio of 4:6 to 6:4 has a co-amorphous structure. (22) The edible product according to (21), wherein the molar ratio of the amino acid to the organic acid is 1:1. (23) An edible product that masks the unpleasant taste of NL-α-aspartyl-L-phenylalanine 1-methyl ester, characterized by a co-amorphous structure of a mixture containing NL-α-aspartyl-L-phenylalanine 1-methyl ester and an organic acid in a 1:1 molar ratio. (24) A method for masking the bitterness of an amino acid, characterized in that the bitter amino acid and the organic acid form a co-amorphous structure. (25) A method for masking the unpleasant taste of NL-α-aspartyl-L-phenylalanine 1-methyl ester, characterized in that the mixture is a mixture of NL-α-aspartyl-L-phenylalanine 1-methyl ester and an organic acid in a co-amorphous structure. It also provides:

[0013] The present invention further comprises: (26) A method for producing a mixture of bitter amino acids and organic acids having a co-amorphous structure, the mixture containing bitter amino acids and organic acids, the amino acids and organic acids being in a molar ratio of 1:1, and the method comprising grinding and mixing the amino acids and organic acids in a ball mill. (27) A method for producing a mixture of bitter amino acids and organic acids having a co-amorphous structure, the method comprising mixing an aqueous solution of the amino acid and an aqueous solution of the organic acid in a molar ratio of 1:1 and spray-drying the mixture at a temperature of 130°C or higher. (28) A method for producing a mixture of (A) and (B) having a co-amorphous structure, comprising NL-α-aspartyl-L-phenylalanine 1-methyl (A) and an organic acid (B), the molar ratio of (A) to (B) being 1:1, and the mixture being ground and mixed in a ball mill. (29) A method for producing a mixture of (A) and (B) having a co-amorphous structure, comprising: mixing an aqueous solution of (A) and an aqueous solution of (B) containing NL-α-aspartyl-L-phenylalanine 1-methyl (A) and an organic acid (B) in a molar ratio of 1:1; and spray-drying the mixture at a temperature of 130°C or higher. It also provides:

[0014] In the present invention, the term "off-flavor" refers to an unpleasant taste or flavor that is not felt when ordinary foods or medicines are orally ingested, and specific examples include bitterness, astringency, spiciness, harshness, roughness, etc. The presence or absence and degree of off-flavor can be evaluated by sensory evaluation as shown in the examples below.

[0015] The amino acids and organic acids used in the present invention usually exist as crystals. This is because the amorphous form of these simple substances is unstable and will transition to crystals if left unattended. In crystals, molecules are regularly arranged to form a crystal lattice. On the other hand, amorphous substances do not have the long-range order of a crystal lattice and have very low interactions that stabilize the solid state, such as lattice energy. Therefore, they disperse and hydrate more easily than crystals, and have a faster dissolution rate.

[0016] When amino acid crystals are ground in a ball mill, they are subjected to high impact and shear forces, causing them to become amorphous. It is believed that the presence of an organic acid as a counter substance stabilizes the amorphous structure due to its high affinity with the amino acid. Because the organic acid in the co-amorphous structure of the present invention is highly hydrophilic, it is believed that water penetrates more easily than in a typical amorphous structure of an amino acid alone, resulting in improved dissolution rates and dissolution amounts.

[0017] Incidentally, the present inventors have previously filed a patent application (Japanese Patent Application No. 2019-117131) for a co-amorphous structure formed between amino acids, for example, a co-amorphous structure of tyrosine and arginine. When the structure is dissolved in water, as shown schematically in FIG. 11, the kinetic solubility of the tyrosine in the co-amorphous structure is higher than the thermodynamic solubility of normal crystalline tyrosine, and the tyrosine remains stably dissolved without crystallization, despite the fairly high tyrosine concentration.

[0018] Figure 6 compares the supernatant cystine concentration of a co-amorphous structure containing equimolar amounts of cystine and citric acid with that of a crystalline mixture containing equimolar amounts of cystine and citric acid crystals. The co-amorphous structure has a higher dissolution rate than the crystalline mixture. While the present invention is not bound by any theory, the co-amorphous structure is structurally unstable compared to crystals, and has a lower lattice energy, making it more easily dissolved. This is commonly recognized in the pharmaceutical industry, where the solubility of crystals is called kinetic solubility and the solubility of amorphous structures is called thermodynamic solubility.

[0019] Furthermore, the reason why the co-amorphous structure shown in Figure 6 is stable at a higher supernatant cystine concentration than the crystals is that the co-amorphous structure takes a longer time to precipitate as a crystal than the crystals. When crystals dissolve, they form aggregates that maintain their crystalline structure in water, whereas the co-amorphous structure does not have a crystalline structure and therefore forms completely random aggregates in water. The random aggregates must be transformed into aggregates with a crystalline structure, and this transformation takes a long time.

[0020] Incidentally, solid solutions of three amino acids, such as valine, leucine, and isoleucine, are known (WO 2010 / 050168), and it is also known that the dissolution rates of the valine, leucine, and isoleucine in these solid solutions are improved. However, solid solutions are crystalline, with portions of the crystal lattice substituted with other molecules, or with other molecules intercalated between the crystal lattices. This means that the solid solutions are crystalline and do not have the random structure of amorphous bodies. The dissolution rate of the solid solutions is much slower than that of the co-amorphous structure of the present invention, and the effect of improving bitterness, etc. is also inferior. [Effects of the Invention]

[0021] The mixture of an amino acid-containing compound and an organic acid having a co-amorphous structure of the present invention can significantly increase the dissolution rate of the amino group-containing compound, easily dissolve even poorly soluble compounds, and mask the bitterness of the amino group-containing compound, eliminate aftertaste, or improve the melt-in-the-mouth feel. [Brief explanation of the drawings]

[0022] [Figure 1] FIG. 1 is a powder X-ray diffraction pattern of the mixture of various amino acids and a counter substance obtained in Example 1. [Figure 2] 1 is a graph showing the results of a dissolution test of a Leu-citric acid co-amorphous material and Leu + citric acid crystals. [Figure 3] 1 is a graph showing the results of a dissolution test of a Leu-Arg co-amorphous material and a Leu+Arg crystal. [Figure 4] 1 is a graph showing the results of a dissolution test of Val-citric acid co-amorphous material and Val+citric acid crystals. [Figure 5] 1 is a graph showing the results of a dissolution test of Ile-citric acid co-amorphous material and Ile+citric acid crystals. [Figure 6] 1 is a graph showing the results of a dissolution test of a Cys-citric acid co-amorphous material and a Cys+citric acid crystal. [Figure 7] 1 is a graph showing the results of a dissolution test of a Cys-citric acid co-amorphous material and a Cys+citric acid crystal. [Figure 8] FIG. 1 is a powder X-ray diffraction pattern of the mixture of cystine and various organic acids obtained in Example 3. [Figure 9] FIG. 1 shows powder X-ray diffraction patterns of mixtures of various amino acids and citric acid obtained in Example 4. [Figure 10] FIG. 1 is a powder X-ray diffraction pattern of a mixture of NL-α-aspartyl-L-phenylalanine 1-methyl ester obtained in Example 5 and various organic acids. [Figure 11] 1 is a graph illustrating the dissolution behavior of a crystal and an amorphous substance. DETAILED DESCRIPTION OF THE INVENTION

[0023] The mixture of the present invention is one in which the amino group-containing compound and the organic acid have an amorphous structure.

[0024] The amino group-containing compound is, for example, an amino acid or a peptide.

[0025] The amino acid is represented by R-CH(NH2)COOH, where R contains at least one group selected from the group consisting of a hydrogen group, an alkyl group having 1 to 5 carbon atoms, and a hydroxyl group, an amino group, a carboxyl group, an aromatic ring, a sulfide bond, a disulfide bond, a thiol group, and / or a group containing a cyclic structure.

[0026] An amino acid in which R is a hydrogen group is glycine, and an amino acid in which R is an alkyl group having 1 to 5 carbon atoms may be alanine or a branched-chain amino acid such as valine, leucine, or isoleucine. An amino acid containing a hydroxyl group may be serine, threonine, or the like. An amino acid containing an amino group may be lysine, arginine, ornithine, glutamine, asparagine, or the like. An amino acid containing a carboxyl group may be aspartic acid, glutamic acid, or the like. An amino acid containing an aromatic ring may be phenylalanine, tyrosine, or the like. An amino acid containing a sulfide or disulfide bond may be methionine, cystine, or the like. An amino acid containing a thiol group may be cysteine, or the like. An amino acid containing a cyclic structure may be one containing a heterocycle such as histidine, tryptophan, proline, or hydroxyproline. Imino acids such as proline and hydroxyproline may also be included in the amino acids of the present invention.

[0027] One of the purposes of the present invention is to make it possible to easily dissolve poorly soluble amino acids. Poorly soluble amino acids include those that have low solubility, such as cystine, tyrosine, and tryptophan, and those that have solubility, such as phenylalanine, valine, leucine, and isoleucine, but have low affinity for water even when added to water due to their hydrophobic side chains, making them difficult to dissolve. The co-amorphous structure of the present invention improves the solubility of these amino acids.

[0028] Another object is to mask the bitterness and roughness of these branched-chain amino acids, as well as phenylalanine, tryptophan, arginine, tyrosine, histidine, and the like, and to eliminate the roughness and improve the melt-in-the-mouth feel, since these branched-chain amino acids and amino acids such as phenylalanine, tryptophan, arginine, tyrosine, and histidine are known to have a bitter taste, and cystine and the like are known to have a rough texture when placed in the mouth, similar to the feeling of biting sand.

[0029] Peptides are amino acids linked by peptide bonds, and depending on the number of bonds, they can be classified as dipeptides, tripeptides, etc. Peptides, or peptide ester derivatives in which the terminal carboxyl group of a peptide is converted to a methyl ester, can also be co-formed with organic acids into amorphous structures. Examples of peptides include glycomacropeptides and peptides of branched-chain amino acids such as dileucine and trileucine. For example, the dipeptide NL-α-aspartyl-L-phenylalanine 1-methyl (trade name "aspartame," abbreviated as AP) is known as a non-toxic sweetener, but it has a lingering sweet aftertaste. It has been found that when this is formed into the co-amorphous structure of the present invention, the aftertaste is reduced, resulting in a taste closer to that of sugar.

[0030] There are many types of organic acids, including carboxylic acids other than amino acids, sulfonic acids, and phenols, but carboxylic acids are particularly desirable. These organic acids form a co-amorphous structure with the amino group-containing compound. Examples of carboxylic acids include citric acid, tartaric acid, malic acid, succinic acid, phthalic acid, and fumaric acid. The organic acid may be in the form of a hydrate or a salt such as an iron salt or a sodium salt. For example, sodium ferrous citrate may be used. The combination of the amino group-containing compound and the organic acid may be any combination that can form a co-amorphous structure with both.

[0031] The mixing ratio of the amino group-containing compound to the organic acid in the mixture with the co-amorphous structure of the present invention may be any ratio that can form a co-amorphous structure, for example, a molar ratio of 1:0.1 to 1:10, preferably 1:0.2 to 1:5, preferably 1:0.5 to 1:2, more preferably 1:0.6 to 1:2, even more preferably 6:4 to 4:6, and most preferably 1:1. A molar ratio of 1:1 is usually sufficient, but is not limited thereto and may be any ratio that can form a co-amorphous structure. For example, in the case of leucine and citric acid, the molar ratio may be 6:4.

[0032] The amino group-containing compound and organic acid of the present invention have a co-amorphous structure, which is a structure in which the amino group-containing compound and organic acid interact with each other to maintain an amorphous state, and the two are uniformly dispersed and mixed. If a method of dissolving and solidifying the amino group-containing compound and organic acid, such as spray drying, melt quenching (hot melt), or freeze drying, is used, the two will be in a solidified solution state, that is, a state of being mixed at the molecular level. If a method of mixing and grinding the two in powder form, such as grinding with a ball mill, is used, the two will be in a fine powder state, and will be in a state of being mixed at the molecular level as a solid.

[0033] Whether or not the amino group-containing compound and the organic acid form a co-amorphous structure can be confirmed by known methods, such as X-ray diffraction and Raman spectroscopy.

[0034] The mixture of the present invention is sufficient as long as the amino group-containing compound and the organic acid form a co-amorphous structure, but may also form three or more co-amorphous structures including other amino group-containing compounds and organic acids. Furthermore, the mixture may also contain other amino group-containing compounds or organic acids that do not form a co-amorphous structure with the amino group-containing compound or organic acid, or third components other than the amino group-containing compound or organic acid that may or may not form a co-amorphous structure, their salts, or other components.

[0035] The co-amorphous structure of the amino group-containing compound or organic acid of the present invention can be produced by known methods for producing amorphous bodies of amino group-containing compounds or organic acids, such as a grinding method using a ball mill, a spray drying (spray granulation) method using a spray dryer, a melt quenching method, or a freeze-drying method.

[0036] For example, a Verder Scientific Emax ball mill can be used as a ball mill. This method involves adding an amino group-containing compound and an organic acid in a predetermined mixing ratio, adding a grinding aid if necessary, and grinding and mixing until a co-amorphous structure is achieved. The amino group-containing compound and organic acid may be crystalline or amorphous, but are typically crystalline. A grinding aid is added to prevent caking of the amino group-containing compound and organic acid during grinding. Ethanol or other additives may be added in an amount of approximately 0.1 to 5 mass%, preferably 1 to 3 mass%, based on the total weight of the amino group-containing compound and organic acid. The grinding conditions are such that the amino group-containing compound and organic acid form a co-amorphous structure; typically, a ball mill rotation speed of 200 to 1200 rpm is sufficient for approximately 1 to 12 hours. Because the temperature of the ball mill rises during grinding, it is recommended to cool the ball mill pot to below 15°C, preferably 5 to 15°C. Grinding aids such as ethanol volatilize during grinding and do not remain in the mixture. In addition, a planetary ball mill (Kurimoto Iron Works, Ltd.), an attritor (Nippon Coke and Engineering Co., Ltd.), or a Simoyer (Zoz GmbH) can also be used as the ball mill.

[0037] In the case of production by spray drying, an aqueous solution containing an amino group-containing compound and an organic acid in a predetermined mixing ratio is prepared and spray-dried at a temperature of 130°C or higher, preferably 160°C or higher.

[0038] The co-amorphous structure of an amino group-containing compound and an organic acid of the present invention has the effect of masking the bitterness and off-taste of amino acid-containing compounds, and is therefore useful as a method for masking these. Examples of amino group-containing compounds that have a bitter taste include amino acids such as valine, leucine, isoleucine, phenylalanine, tryptophan, arginine, tyrosine, and histidine.

[0039] Furthermore, cystine has a rough texture when placed in the mouth, similar to the sensation of biting sand. However, when cystine is converted into the co-amorphous structure of the present invention, this rough texture disappears and the mouthfeel improves, making it useful as a method for masking this rough texture. Furthermore, NL-α-aspartyl-L-phenylalanine 1-methyl and the like are known as harmless sweeteners, but they have a long-lasting sweetness and an unpleasant taste. However, when this is converted into the co-amorphous structure of the present invention, the sweetness disappears more quickly, eliminating the unpleasant taste. Therefore, this method is also useful as a method for masking the unpleasant taste of the sweetness of such dipeptides.

[0040] The uses of the present invention are not limited in any way, but mixtures of amino group-containing compounds and organic acids in a co-amorphous structure can be used for new applications or as a substitute for conventionally used amino group-containing compounds, inorganic compounds, or organic acids. Examples of such applications include various beverages, sweeteners, seasonings, beverage powders, health foods, oral medicines, and culture media. Edible products are compositions that are taken orally or used in the oral cavity, including foods, seasonings, medicines, quasi-drugs, and cosmetics. Edible powder products are powders of these, such as products that are dissolved in water to make a beverage (sports drink powders). [Example]

[0041] Example 1 (1) Preparation of Amino Acid-Counter Co-Amorphous Mixture A 125 mL zirconia pot was charged with 4.06 g (0.031 mol) of leucine (Leu) (Ajinomoto Co., Inc.), 5.94 g (0.031 mol) of citric acid (Fujifilm Wako Chemical Co., Ltd.), and 0.4 mL of ethanol as a grinding aid. Fifty 10 mm zirconia balls were placed in the pot and placed in a ball mill (Verder Scientific, Retsch Emax). The mixture was milled and mixed at 1000 rpm for 6 hours at a grinding temperature of approximately 28 °C, with 15 °C cooling water flowing around the periphery of the pot. 9.1 g of powder was obtained.

[0042] Amorphous mixtures were prepared in the same manner except that the amino acids and counter substances were changed to the second and subsequent ones in Table 1, and powders of the mixtures were obtained.

[0043] [Table 1]

[0044] Although the time period used here is 6 hours, some compounds can become co-amorphous in a shorter time period. For example, Leu-citric acid can become co-amorphous in as little as 10 minutes.

[0045] (2) Experiment to confirm amorphization The powder X-ray diffraction patterns of the solids obtained in (1) were obtained using a powder X-ray diffractometer (Malvern Panalytical, Empyrean). The results are shown in Figure 1. As a result, no clear peaks characteristic of crystalline structures were observed for Leu-citric acid, Leu-tartaric acid, Leu-Arg, (Val-citric acid, Ile-citric acid)Val-Arg, or Ile-Arg. This confirmed that the solids of Leu-citric acid, Leu-tartaric acid, Leu-Arg, (Val-citric acid, Ile-citric acid)Val-Arg, and Ile-Arg obtained in (1) were amorphous. On the other hand, clear peaks characteristic of crystalline structures were observed for Leu-malic acid, Leu-Gly, Leu-Ala, and Leu-Ser.

[0046] (3) Dissolution amount confirmation test Each 200 mL polypropylene sample bottle contained 100 mL of 1 mol / L Tris-HCl buffer (pH 7.6), 2.46 g of the solid obtained in (1), and 1 g of Leu crystals (previously ground in a ball mill (Verder Scientific, Retsch Emax) for 1 minute) and 1.46 g of citric acid crystals. Each was placed in a 25°C water bath (Tokyo Rikakikai, NCB-3300) and stirred using a magnetic stirrer (AS ONE Corporation, B-1 Magnetic Stirrer Octopus). After 1 minute, 2 mL of each sample bottle was sampled and filtered through a 0.45 μm filter (GL Sciences, Chromatodisc). The filtered samples were diluted 200-fold and the Leu concentration in the supernatant was quantified using high-performance liquid chromatography (HPLC) (Agilent, 1100 Series).

[0047] The same procedure was repeated after 3, 5, 10, and 20 minutes. The results are shown in Figure 2. This confirms that the solid Leu-citric acid obtained in (1) dissolves more quickly than the crushed crystals.

[0048] Similar dissolution confirmation tests were conducted by changing the amino acid and counter substance from the second one onwards in Table 2, and the results shown in Figures 3 to 5 were obtained. From this, it was confirmed that the solids of Leu-Arg, Val-citric acid, and Ile-citric acid obtained in (1) dissolve faster than the crushed crystals.

[0049] [Table 2]

[0050] (4) Sensory test results The core amorphous Leu-citric acid prepared in (1) was subjected to a sensory test to determine its bitterness-masking ability.

[0051] A panel of 30 people rated the bitterness of two types of Leu-citric acid, core amorphous and crystalline mixture, on a 5-point scale (very bitter (5), bitter (4), slightly bitter (3), not very bitter (2), hardly bitter (1)).

[0052] The results of the evaluation are shown in Table 3. As a result, the core amorphous was evaluated as having less bitterness than the crystalline mixture.

[0053] [Table 3]

[0054] Example 2 Using 5.56 g (0.027 mol) of cystine (Cys2) (manufactured by Ajinomoto Co., Inc.), 4.44 g (0.027 mol) of citric acid (manufactured by Fujifilm Wako Chemical Co., Ltd.), and 0.2 ml of ethanol as a grinding aid, grinding and mixing were carried out in the same manner as in Example 1 (1), and 9.7 g of powder was obtained.

[0055] This solid was subjected to a dissolution confirmation test in the same manner as in (3) of Example 1. The results are shown in Figures 6 and 7.

[0056] Example 3 Cystine (Cys2) (Ajinomoto Co., Inc.), an organic acid shown in Table 4, and 0.2 ml of ethanol as a grinding aid were ground and mixed in the same manner as in Example 1 (1) to obtain a powder. The powder X-ray diffraction patterns of these solids were obtained in the same manner as in (2) of Example 1. The results are shown in Figure 8. No clear peaks characteristic of crystals were observed in any of the powders, confirming that they were amorphous powders. [Table 4]

[0057] Example 4 Using amino acids (manufactured by Ajinomoto Co., Inc.), the organic acids shown in Table 5, and 0.2 ml of ethanol as a grinding aid, grinding and mixing were carried out in the same manner as in Example 1 (1) to obtain powders. Powder X-ray diffraction patterns were obtained for these solids in the same manner as in Example 1(2). The results are shown in Figure 9. No clear peaks characteristic of crystals were observed in any of the powders, confirming that they were amorphous powders. [Table 5]

[0058] Example 5 NL-α-aspartyl-L-phenylalanine 1-methyl (trade name "Aspartame" AP) manufactured by Ajinomoto Co., Inc.), the organic acids shown in Table 6, and 0.2 ml of ethanol as a grinding aid were used to grind and mix in the same manner as in (1) of Example 1 to obtain a powder. A powder X-ray diffraction pattern was obtained for this solid in the same manner as in Example 1(2). The results are shown in Figure 10. The powder obtained by mixing fumaric acid and citric acid with AP did not show any clear peaks typical of crystals, confirming that it was an amorphous powder. Furthermore, the powder obtained by grinding and mixing AP and citric acid had almost no aftertaste, as the off-flavor was masked, and the citric acid provided a refreshing sweetness. On the other hand, the powder obtained by grinding and mixing AP with malic acid, tartaric acid, and succinic acid was not found to be amorphous. [Table 6]

[0059] Example 6 Production by spray drying 4.00 g of leucine and 5.85 g of citric acid were dissolved in 120 g of water and spray-dried at a temperature of 170°C to obtain 4.2 g of a co-amorphous mixture of leucine and citric acid. [Industrial Applicability]

[0060] The co-amorphous structure of the present invention not only exhibits good solubility for its constituent amino group-containing compounds, such as amino acids and peptides, but also has the effect of masking bitterness and other unpleasant tastes, and can be widely used in the fields of food and pharmaceuticals, including beverages, seasonings, sweeteners, and the like, where amino group-containing compounds are used. The co-amorphous structure is particularly effective in applications involving the dissolution of poorly soluble amino acids, amino acids that exhibit a bitter taste, and peptides that have a long-lasting sweet taste.

Claims

1. A mixture of a peptide or amino acid and an organic acid, characterized in that the peptide or amino acid and the organic acid form a co-amorphous structure (excluding a mixture in which arginine and citric acid form a co-amorphous structure).

2. The mixture described in claim 1, characterized in that the amino acid is at least one amino acid selected from the group consisting of leucine, isoleucine, valine, cystine, phenylalanine, tyrosine, tryptophan, arginine, and histidine.

3. The mixture described in claim 1, characterized in that the amino acid is a branched-chain amino acid.

4. 4. The mixture according to claim 3, wherein the branched chain amino acid is leucine, isoleucine or valine.

5. The mixture described in claim 1, characterized in that the amino acid is an amino acid that exhibits a bitter taste.

6. The mixture described in claim 1, characterized in that the peptide is a dipeptide.

7. 2. The mixture of claim 1, wherein the peptide is NL-α-aspartyl-L-phenylalanine 1-methyl.

8. 2. The mixture according to claim 1, wherein the organic acid is citric acid, tartaric acid, malic acid, phthalic acid, fumaric acid or succinic acid, or a salt or hydrate thereof.

9. 9. The mixture of claim 8, wherein the organic acid is ferrous citrate or a salt thereof.

10. The mixture of claim 1, wherein the amino acid is leucine, isoleucine, or valine, and the organic acid is citric acid, tartaric acid, or malic acid.

11. 11. The mixture of claim 10, wherein the amino acid is leucine and the organic acid is citric acid.

12. 10. The mixture of claim 9, wherein the amino acid is tyrosine.

13. 10. The mixture of claim 9, wherein the amino acid is cystine.

14. A beverage comprising the mixture according to any one of claims 1 to 12.

15. A seasoning comprising the mixture according to any one of claims 1 to 12.

16. A sweetener comprising a mixture according to any one of claims 1 to 12.

17. A culture medium comprising the mixture according to any one of claims 1 to 12.

18. An oral pharmaceutical preparation comprising a mixture according to any one of claims 1 to 12.

19. An edible product having a masked bitterness and / or unpleasant taste, comprising the mixture according to any one of claims 1 to 12.

20. An edible powder product having a masked bitterness and / or unpleasant taste, comprising the mixture according to any one of claims 1 to 12.

21. The edible product masks the bitterness of amino acids, characterized in that a mixture containing a bitter amino acid and an organic acid in a molar ratio of 4:6 to 6:4 (excluding a mixture in which arginine and citric acid have a co-amorphous structure) has a co-amorphous structure.

22. 22. The edible product of claim 21, wherein the amino acid and the organic acid are in a molar ratio of 1:

1.

23. An edible product for masking the unpleasant taste of N-L-α-aspartyl-L-phenylalanine 1-methyl, characterized in that a mixture containing N-L-α-aspartyl-L-phenylalanine 1-methyl and an organic acid in a molar ratio of 1:1 has a co-amorphous structure.

24. A method for masking the bitterness of an amino acid, characterized in that the bitter amino acid and an organic acid are mixed in an amorphous structure.

25. A method for masking the unpleasant taste of NL-α-aspartyl-L-phenylalanine 1-methyl, characterized in that the mixture is a mixture of NL-α-aspartyl-L-phenylalanine 1-methyl and an organic acid in a co-amorphous structure.

26. A method for producing a mixture of a bitter amino acid and an organic acid having a co-amorphous structure, the method comprising grinding and mixing the amino acid and the organic acid in a molar ratio of 1:1 using a ball mill (excluding a method for producing a mixture in which arginine and citric acid have a co-amorphous structure).

27. A method for producing a mixture of a bitter amino acid and an organic acid having a co-amorphous structure, the method comprising mixing an aqueous solution of the amino acid and an aqueous solution of the organic acid in a molar ratio of 1:1, and spray-drying the mixture at a temperature of 130°C or higher (excluding a method for producing a mixture in which arginine and citric acid have a co-amorphous structure).

28. A method for producing a mixture of (A) and (B) having a co-amorphous structure, comprising: N-L-α-aspartyl-L-phenylalanine 1-methyl (A) and an organic acid (B), the molar ratio of (A) to (B) being 1:1, and (A) and (B) being milled and mixed in a ball mill.

29. A method for producing a mixture of N-L-α-aspartyl-L-phenylalanine 1-methyl (A) and an organic acid (B) having a co-amorphous structure, the method comprising: mixing an aqueous solution of (A) and an aqueous solution of (B) at a molar ratio of 1:1; and spray-drying the mixture at a temperature of 130°C or higher.

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